Scolaris Content Display Scolaris Content Display

Reduction in saturated fat intake for cardiovascular disease

This is not the most recent version

view the current version 21 August 2020
Collapse all Expand all

References

References to studies included in this review

Jump to:

Black 1994 {published and unpublished data}

Black HS, Herd JA, Goldberg LH, Wolf JE, Thornby JI, Rosen T, et al. Effect of a low‐fat diet on the incidence of actinic keratosis. New England Journal of Medicine 1994;330(18):1272‐5.
Black HS, Thornby JI, Wolf JE, Goldberg LH, Herd JA, Rosen T, et al. Evidence that a low‐fat diet reduces the occurrence of non‐melanoma skin cancer. International Journal of Cancer 1995;62(2):165‐9.
Jaax S, Scott LW, Wolf JE, Thornby JI, Black HS. General guidelines for a low‐fat diet effective in the management and prevention of nonmelanoma skin cancer. Nutrition and Cancer 1997;27(2):150‐6.

DART 1989 {published and unpublished data}

Burr ML, Fehily AM. Fish and the heart. Lancet 1989;ii:1450‐2.
Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989;2(8666):757‐61.
Burr ML, Fehily AM, Rogers S, Welsby E, King S, Sandham S. Diet and reinfarction trial (DART): design, recruitment, and compliance. European Heart Journal 1989;10(6):558‐67.
Burr ML, Holliday RM, Fehily AM, Whitehead PJ. Haematological prognostic indices after myocardial infarction: evidence from the diet and reinfarction trial (DART). European Heart Journal 1992;13(2):166‐70.
Burr ML, Sweetham PM, Fehily AM. Diet and reinfarction [letter]. European Heart Journal 1994;15(8):1152‐3.
Fehily AM, Vaughan‐Williams E, Shiels K, Williams AH, Horner M, Bingham G, et al. The effect of dietary advice on nutrient intakes: evidence from the diet and reinfarction trial (DART). Journal of Human Nutrition & Dietetics 1989;2(4):225‐5.

Houtsmuller 1979 {published data only}

Houtsmuller AJ, Van Hal‐Ferwerda J, Zahn KJ, Henkes HE. Favourable influences of linoleic acid on the progression of diabetic micro‐ and macroangiopathy. Nutrition and Metabolism 1980;24(Suppl 1):105‐18.
Houtsmuller AJ, Zahn KJ, Henkes HE. Unsaturated fats and progression of diabetic retinopathy. Documenta Ophthalmologia 1979;48(2):363‐71.
Houtsmuller AJ, van Hal‐Ferwerda J, Zahn KJ, Henkes HE. Influence of different diets on the progression of diabetic retinopathy. Progress in Food Nutritition and Science 1980;4(5):41‐6.

Ley 2004 {published and unpublished data}

Ley SJ, Metcalf PA, Scragg RK, Swinburn BA. Long‐term effects of a reduced fat diet intervention on cardiovascular disease risk factors in individuals with glucose intolerance. Diabetes Research and Clinical Practice 2004;63(2):103‐12.
Swinburn BA, Metcalf PA, Ley SJ. Long‐term (5‐year) effects of a reduced‐fat diet intervention in individuals with glucose intolerance. Diabetes Care 2001;24(4):619‐24.
Swinburn BA, Woollard GA, Chang EC, Wilson MR. Effects of reduced‐fat diets consumed ad libitum on intake of nutrients particularly antioxidant vitamins. Journal of the American Dietetic Association 1999;99(11):1400‐5.

Moy 2001 {published and unpublished data}

Moy TF, Yanek LR, Raqueno JV, Bezirdjian PJ, Blumenthal RS, Wilder LB, et al. Dietary counseling for high blood cholesterol in families at risk of coronary disease. Preventive Cardiology 2001;4(4):158‐64.

MRC 1968 {published and unpublished data}

Ederer F, Leren P, Turpeinen O, Frantz ID. Cancer among men on cholesterol lowering diets: experience of five clinical trials. Lancet 1971;2(7717):203‐6.
Heady JA. Are PUFA harmful?. British Medical Journal 1974;1(898):115‐6.
MRC. Controlled trial of soya‐bean oil in myocardial infarction. Lancet 1968;2(570):693‐9.

Oslo Diet‐Heart 1966 {published and unpublished data}

Leren P. Prevention of coronary heart disease, some results from the Oslo secondary and primary intervention studies. Journal of the American College of Nutrition 1989;8(5):407‐10.
Leren P. The Oslo diet‐heart study. Eleven year report. Circulation 1970;42(5):935‐42.
Leren P. The effect of a cholesterol lowering diet in male survivors of myocardial infarction. (A controlled clinical trial) [Virkningen av cholesterolsenkende diett hos menn som har gjennomgatt hjerteinfarkt. Et kontrollert klinisk fors/ok]. Nordisk Medicin 1967;77(21):658‐61.
Leren P. The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Acta Medica Scandinavia. Supplementum 1966;466:1‐92.
Leren P. The effect of plasma‐cholesterol‐lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Bulletin of the New York Academy of Medicine 1968;44(8):1012‐20.

Oxford Retinopathy 1978 {published and unpublished data}

Coppack SW, Doll HA, Pim B, Hockaday TD. Intravenous glucose tolerance and mortality in non‐insulin‐dependant diabetes mellitus. Quarterly Journal of Medicine 1990;75(277):451‐60.
Hillson RM, Hockaday TD, Mann JI, Newton DJ. Hyperinsulinaemia is associated with development of ECG abnormalities in diabetics. Diabetes Research 1984;1(3):143‐9.
Hockaday TD, Hockaday JM, Mann JI, Turner RC. Prospective comparison of modified fat‐high‐carbohydrate with standard low‐carbohydrate dietary advice in the treatment of diabetes: one year follow‐up study. British Journal of Nutrition 1978;39(2):357‐62.
Howard‐Williams J, Patel P, Jelfs R, Carter RD, Awdry P, Bron A, et al. Polyunsaturated fatty acids and diabetic retinopathy. British Journal of Ophthalmology 1985;69(1):15‐8.
Lopez‐Espinoza I, Howard WJ, Mann JI, Carter RD, Hockaday TD. Fatty acid composition of platelet phospholipids in non‐insulin‐dependent diabetics randomized for dietary advice. British Journal of Nutrition 1984;52(1):41‐7.

Rose corn oil 1965 {published data only}

Rose GA, Thomson WB, Williams RT. Corn oil in treatment of ischaemic heart disease. British Medical Journal 1965;1(5449):1531‐3.

Rose olive 1965 {published data only}

Rose GA, Thomson WB, Williams RT. Corn oil in treatment of ischaemic heart disease. British Medical Journal 1965;1(5449):1531‐3.

Simon 1997 {published and unpublished data}

Djuric Z, Heilbrun LK, Reading BA, Boomer A, Valeriote FA, Martino S. Effects of a low fat diet on levels of oxidative damage to DNA in human peripheral nucleated blood cells. Journal of the National Cancer Institute 1991;83(11):766‐9.
Djuric Z, Martino S, Heilbrun LK, Hart RW. Dietary modulation of oxidative DNA damage. Advances In Experimental Medicine and Biology 1994;354:71‐83.
Kasim SE, Martino S, Kim P‐N, Khilnani S, Boomer A, Depper J, et al. Dietary and anthropometric determinants of plasma lipoproteins during a long‐term low‐fat diet in healthy women. American Journal of Clinical Nutrition 1993;57(2):146‐53.
Simon MS, Heilbrun LK, Boomer A, Kresge C, Depper J, Kim PN, et al. A randomised trial of a low‐fat dietary intervention in women at high risk for breast cancer. Nutrition and Cancer 1997;27(2):136‐42.

STARS 1992 {published and unpublished data}

Blann AD, Jackson P, Bath PM, Watts GF. von Willebrand factor, a possible indicator of endothelial cell damage, decreases during long‐term compliance with a lipid‐lowering diet. Journal of Internal Medicine 1995;237(6):557‐61.
Watts GF. Nutritional, metabolic, and genetic determinants of the progression of coronary heart disease. STARS Group. Journal of Cardiovascular Pharmacology 1995;25(Suppl 4):S11‐9.
Watts GF, Brunt JN, Coltart DJ, Lewis B. The St. Thomas Atherosclerosis Regression Study (STARS). Atherosclerosis 1992;97:231.
Watts GF, Jackson P, Burke V, Lewis B. Dietary fatty acids and progression of coronary artery disease in men. American Journal of Clinical Nutrition 1996;64(2):202‐9.
Watts GF, Jackson P, Mandalia S, Brunt JN, Lewis ES, Coltart DJ, et al. Nutrient intake and progression of coronary artery disease. American Journal of Cardiology 1994;73(5):328‐32.
Watts GF, Lewis B, Brunt JN, Lewis ES, Coltart DJ, Smith LD, et al. Effects on coronary artery disease of lipid‐lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS). Lancet 1992;339(8793):563‐9.
Watts GF, Lewis B, Brunt JNH, Swan AV. Coronary Atheroma Regression Trials. Lancet 1992;339(i):1241‐3.
Watts GF, Lewis B, Jackson P, Burke V, Lewis ES, Brunt JN, et al. Relationships between nutrient intake and progression/regression of coronary atherosclerosis as assessed by serial quantitative angiography. Canadian Journal of Cardiology 1995;11(Suppl G):110G‐4G.
Watts GF, Mandalia S, Brunt JN, Slavin BM, Coltart DJ, Lewis B. Independent associations between plasma lipoprotein subfraction levels and the course of coronary artery disease in the St. Thomas' Atherosclerosis Regression Study (STARS). Metabolism: Clinical and Experimental 1993;42(11):1461‐7.
Watts GF, Mandalia S, Slavin BM, Brunt JN, Coltart DJ, Lewis B. Metabolic determinants of the course of coronary artery disease in men. Clinical Chemistry 1994;40(12):2240‐6.

Sydney Diet‐Heart 1978 {published and unpublished data}

Blacket RB, Leelarthaepin B, McGilchrist C, Palmer AJ, Woodhill JM. The synergistic effect of weight loss and changes in dietary lipids on the serum cholesterol of obese men with hypercholesterolaemia: implications for prevention of coronary heart disease. Australian and New Zealand Journal of Medicine 1979;9(5):521‐9.
Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak‐Hong SF, Faurot KR, Suchindran CM, et al. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta‐analysis. BMJ 2013;346:e8707. [DOI: 10.1136/bmj.e8707]
Woodhill JM, Palmer AJ, Leelarthaepin B, McGilchrist C, Blacket RB. Low fat, low cholesterol diet in secondary prevention of coronary heart disease. Advances in Experimental Medicine and Biology 1978;109:317‐30.

Veterans Admin 1969 {published data only}

Dayton S, Hashimoto S, Dixon W, Pearce ML. Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat. Journal of Lipid Research 1966;7(1):103‐11.
Dayton S, Hashimoto S, Pearce ML. Adipose tissue linoleic acid as a criterion of adherence to a modified diet. Journal of Lipid Research 1967;8(5):508‐10.
Dayton S, Hashimoto S, Pearce ML. Influence of a diet high in unsaturated fat upon composition of arterial tissue and atheromata in man. Circulation 1965;32(6):911‐24.
Dayton S, Hashimoto S, Rosenblum D, Pearce M. Vitamin E status of humans during prolonged feeding of unsaturated fats. Journal of Laboratory and Clinical Medicine 1965;65(5):739‐47.
Dayton S, Pearce ML. Diet and atherosclerosis. Lancet 1970;1(644):473‐4.
Dayton S, Pearce ML. Diet and cardiovascular diseases. Lancet 1969;1(584):51‐2.
Dayton S, Pearce ML. Diet high in unsaturated fat: a controlled clinical trial. Minnesota Medicine 1969;52(8):1237‐42.
Dayton S, Pearce ML. Prevention of coronary heart disease and other complications of atherosclerosis by modified diet. American Journal of Medicine 1969;46(5):751‐62.
Dayton S, Pearce ML. Trial of unsaturated‐fat diet. Lancet 1968;2(581):1296‐7.
Dayton S, Pearce ML, Goldman H, Harnish A, Plotkin D, Shickman M, et al. Controlled trial of a diet high in unsaturated fat for prevention of atherosclerotic complications. Lancet 1968;2(577):1060‐2.
Dayton S, Pearce ML, Hashimoto S, Dixon WJ, Tomayasu U. A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis. Circulation 1969;15(1, Suppl 2):II‐1‐63.
Dayton S, Pearce ML, Hashimoto S, Fakler LJ, Hiscock E, Dixon WJ. A controlled clinical trial of a diet high in unsaturated fat. New England Journal of Medicine 1962;266:1017‐23.
Hiscock E, Dayton S, Pearce ML, Hashimoto S. A palatable diet high in unsaturated fat. Journal of the American Dietetic Association 1962;40:427‐31.
Pearce ML, Dayton S. Incidence of cancer in men on a diet high in polyunsaturated fat. Lancet 1971;1(697):464‐7.
Sturdevant RA, Pearce ML, Dayton S. Increased prevalence of cholelithiasis in men ingesting a serum‐cholesterol‐lowering diet. New England Journal of Medicine 1973;288(1):24‐7.
Tompkins MJ, Dayton S, Pearce ML. Effect of long‐term feeding of various fats on whole blood clotting times in men. Journal of Laboratory and Clinical Medicine 1964;64(5):763‐72.

WHI with CVD 2006 {published data only}

Anderson G, Cummings S, Freedman LS, Furberg C, Henderson M, Johnson SR, et al. Design of the Women's Health Initiative clinical trial and observational study. Controlled Clinical Trials 1998;19(1):61‐109.
Carty CL, Kooperberg C, Neuhouser ML, Tinker L, Howard B, Wactawski‐Wende J, et al. Low‐fat dietary pattern and change in body‐composition traits in the Women's Health Initiative Dietary Modification Trial. American Journal of Clinical Nutrition 2011;93(3):516‐24.
Howard BV, Curb JD, Eaton CB, Kooperberg C, Ockene J, Kostis JB, et al. Low‐fat dietary pattern and lipoprotein risk factors: the Women's Health Initiative dietary modification trial. American Journal of Clinical Nutrition 2010;91(4):860‐74.
Howard BV, Van Horn L, Hsia J, Manson JE, Stefanick ML, Wassertheil‐Smoller S, et al. Low‐fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295(6):655‐66.
Robinson JG, Wallace R, Safford MM, Pettinger M, Cochrane B, Ko MG, et al. Another treatment gap: Restarting secondary prevention medications: The Women's Health Initiative. Journal of Clinical Lipidology 2010;4(1):36‐45.
Rossouw JE, Finnegan LP, Harlan WR, Pinn VW, Clifford C, McGowan JA. The evolution of the Women's Health Initiative: perspectives from the NIH. Journal of the American Medical Women's Association 1995;50(2):50‐5.

WHI without CVD 2006 {published data only}

Anderson G, Cummings S, Freedman LS, Furberg C, Henderson M, Johnson SR, et al. Design of the Women's Health Initiative clinical trial and observational study. Controlled Clinical Trials 1998;19(1):61‐109.
Anderson GL, Manson J, Wallace R, Lund B, Hall D, Davis S, et al. Implementation of the Women's Health Initiative study design. Annals of Epidemiology 2003;13(9 Suppl):S5‐17.
Beresford SA, Johnson KC, Ritenbaugh C, Lasser NL, Snetselaar LG, Black HR, et al. Low‐fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295(6):643‐54.
Bowen D, Ehret C, Pedersen M, Snetselaar L, Johnson M, Tinker L, et al. Results of an adjunct dietary intervention program in the Women's Health Initiative. Journal of the American Dietetic Association 2002;102(11):1631‐7.
Carty CL, Kooperberg C, Neuhouser ML, Tinker L, Howard B, Wactawski‐Wende J, et al. Low‐fat dietary pattern and change in body‐composition traits in the Women's Health Initiative Dietary Modification Trial. American Journal of Clinical Nutrition 2011;93(3):516‐24.
Curb JD, McTiernan A, Heckbert SR, Kooperberg C, Stanford J, Nevitt M, et al. Outcomes ascertainment and adjudication methods in the Women's Health Initiative. Annals of Epidemiology 2003;13(9 Suppl):S122‐8.
Hays J, Hunt JR, Hubbell FA, Anderson GL, Limacher M, Allen C, et al. The Women's Health Initiative recruitment methods and results. Annals of Epidemiology 2003;13(9 Suppl):S18‐77.
Hebert JR, Patterson RE, Gorfine M, Ebbeling CB, St Jeor ST, Chlebowski RT, et al. Differences between estimated caloric requirements and self‐reported caloric intake in the women's health initiative. Annals of Epidemiology 2003;13(9):629‐37.
Howard BV. Dietary fat and cardiovascular disease: putting the Women's Health Initiative in perspective. Nutrition Metabolism & Cardiovascular Diseases 2007;17(3):171‐4.
Howard BV, Manson JE, Stefanick ML, Beresford SA, Frank G, Jones B, et al. Low‐fat dietary pattern and weight change over 7 years: the Women's Health Initiative Dietary Modification Trial. JAMA 2006;295(1):39‐49.
Howard BV, Van Horn L, Hsia J, Manson JE, Stefanick ML, Wassertheil‐Smoller S, et al. Low‐fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295(6):655‐66.
Neuhouser ML, Tinker L, Shaw PA, Schoeller D, Bingham SA, Horn LV, et al. Use of recovery biomarkers to calibrate nutrient consumption self‐reports in the Women's Health Initiative. American Journal of Epidemiology 2008;167(10):1247‐59.
Patterson RE, Kristal A, Rodabough R, Caan B, Lillington L, Mossavar‐Rahmani Y, et al. Changes in food sources of dietary fat in response to an intensive low‐fat dietary intervention: early results from the Women's Health Initiative. Journal of the American Dietetic Association 2003;103(4):454‐60.
Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Gurs‐Collins T, et al. Measurement characteristics of the Women's Health Initiative food frequency questionnaire. Annals of Epidemiology 1999;9(3):178‐87.
Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, et al. Low‐fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295(6):629‐42.
Prentice RL, Thomson CA, Caan B, Hubbell FA, Anderson GL, Beresford SA, et al. Low‐fat dietary pattern and cancer incidence in the Women's Health Initiative Dietary Modification Randomized Controlled Trial. Journal of the National Cancer Institute 2007;99(20):1534‐43.
Ritenbaugh C, Patterson RE, Chlebowski RT, Caan B, Fels‐Tinker L, Howard B, et al. The Women's Health Initiative Dietary Modification trial: overview and baseline characteristics of participants. Annals of Epidemiology 2003;13(9 Suppl):S87‐97.
Robinson JG, Wallace R, Safford MM, Pettinger M, Cochrane B, Ko MG, et al. Another treatment gap: Restarting secondary prevention medications: The Women's Health Initiative. Journal of Clinical Lipidology 2010;4(1):36‐45.
Rossouw JE, Finnegan LP, Harlan WR, Pinn VW, Clifford C, McGowan JA. The evolution of the Women's Health Initiative: perspectives from the NIH. Journal of the American Medical Women's Association 1995;50(2):50‐5.
The Women's Health Initiative Study Group. Design of the Women's Health Initiative clinical trial and observational study. Controlled Clinical Trials 1998;19(1):61‐109.
Tinker LF, Bonds DE, Margolis KL, Manson JE, Howard BV, Larson J, et al. Low‐fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: the Women's Health Initiative randomized controlled dietary modification trial. Archives of Internal Medicine 2008;168(14):1500‐11.
Tinker LF, Perri MG, Patterson RE, Bowen DJ, McIntosh M, Parker LM, et al. The effects of physical and emotional status on adherence to a low‐fat dietary pattern in the Women's Health Initiative. Journal of the American Dietetic Association 2002;102(6):789‐800.
Tinker LF, Rosal MC, Young AF, Perri MG, Patterson RE, Van Horn L, et al. Predictors of dietary change and maintenance in the Women's Health Initiative Dietary Modification Trial. Journal of the American Dietetic Association 2007;107(7):1155‐66.
Women's Health Initiative Study Group. Dietary adherence in the Women's Health Initiative Dietary Modification Trial. Journal of the American Dietetic Association 2004;104(4):654‐8.

WINS 2006 {published and unpublished data}

Chlebowski RT, Blackburn GL, Buzzard IM, Rose DP, Martino S, Khandekar JD, et al. Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. The Women's Intervention Nutrition Study. Journal of Clinical Oncology 1993;11(11):2072‐80.
Chlebowski RT, Blackburn GL, Thomson CA, Nixon DW, Shapiro A, Hoy MK, et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the women's intervention nutrition study. JNCI Journal of the National Cancer Institute 2006;98(24):1767‐76.
Chlebowski RT, Rose DP, Buzzard IM, Blackburn GL, York M, Insull W, et al. Dietary fat reduction in adjuvant breast cancer therapy: current rationale and feasibility issues. Adjuvant: The Cancer Journal 1990;6:357‐63.
Hoy MK, Winters BL, Chlebowski RT, Papoutsakis C, Shapiro A, Lubin MP, et al. Implementing a low‐fat eating plan in the Women's Intervention Nutrition Study. Journal of the American Dietetic Association 2009;109(4):688‐96.
Rose DP, Chlebowski RT, Connolly JM, Jones LA, Wynder EL. Effects of tamoxifen adjuvant therapy and a low‐fat diet on serum binding proteins and estradiol bioavailability in postmenopausal breast cancer patients. Cancer Research 1992;52(19):5386‐90.
Rose DP, Connolly JM, Chlebowski RT, Buzzard IM, Wynder EL. The effects of a low‐fat dietary intervention and tamoxifen adjuvant therapy on the serum estrogen and sex hormone‐binding globulin concentrations of postmenopausal breast cancer patients. Breast Cancer Research & Treatment 1993;27(3):253‐62.
Wynder EL, Cohen LA, Winters BL. The challenges of assessing fat intake in cancer research investigations. Journal of the American Dietetic Association 1997;97(7 Suppl):S5‐8.

References to studies excluded from this review

Jump to:

Agewall 2001 {published data only}

Agewall S. Multiple risk intervention trial in high risk hypertensive men: comparison of ultrasound intima‐media thickness and clinical outcome during 6 years of follow‐up. Journal of Internal Medicine 2001;249(4):305‐14.

Ammerman 2003 {published data only}

Ammerman AS, Keyserling TC, Atwood JR, Hosking JD, Zayed H, Krasny C. A randomized controlled trial of a public health nurse directed treatment program for rural patients with high blood cholesterol. Preventive Medicine 2003;36(3):340‐51.

Anderson 1990 {published and unpublished data}

Anderson JW, Garrity TF, Smith BM, Whitis SE. Follow‐up on a clinical trial comparing the effects of two lipid lowering diets. Arteriosclerosis 1990;10(5):882a.
Anderson JW, Garrity TF, Wood CL, Whitis SE, Smith BM, Oeltgen PR. Prospective, randomized, controlled comparison of the effects of low‐fat and low‐fat plus high‐fiber diets on serum lipid concentrations. American Journal of Clinical Nutrition 1992;56(5):887‐94.

Aquilani 2000 {published data only}

Aquilani R, Tramarin R, Pedretti RF, Bertolotti G, Sommaruga M, Mariani P, et al. Can a very‐low‐fat diet achieve cholesterol goals in CAD?. Cardiology Review 2000;17(10):36‐40.

Arntzenius 1985 {published data only}

Arntzenius AC, Kromhout D, Barth JD, Reiber JH, Bruschke AV, Buis B, et al. Diet, lipoprotiens and progression of coronary atherosclerosis: The Leiden Intervention Trial. New England Journal of Medicine 1985;312(13):805‐8.

Aro 1990 {published data only}

Aro A, Ahola I, Jauhiainen M, Mutanen M, Valsta LM. Effects of plasma phospholipid fatty acids of rapeseed oil and sunflower oil diets [Abstract]. Arteriosclerosis 1990;10:877a.

ASSIST 2001 {published data only}

Moher M, Yudkin P, Wright L, Turner R, Fuller A, Schofield T, et al. Cluster randomised controlled trial to compare three methods of promoting secondary prevention of coronary heart disease in primary care. BMJ 2001;322(7298):1338.

Australian Polyp Prev 95 {published and unpublished data}

MacLennan R. Effect of fat, fibre and beta‐carotene on colorectal adenomas after 24 months. Gastroenterology 1991;100:A382.
MacLennan R, Macrae F, Bain C, Battistutta D, Chapuis P, Gratten H, et al. Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas. The Australian Polyp Prevention Project. Journal of the National Cancer Institute 1995;87(23):1760‐6.
Macrae FA, Hughes NR, Bhathal PS, Tay D, Selbie L, MacLennan R. Dietary suppression of rectal epthelial cell proliferation. Gastroenterology 1991;100:A383.

Azadbakht 2007 {published and unpublished data}

Azadbakht L, Mirmiran P, Esmaillzadeh A, Azizi F. Better dietary adherence and weight maintenance achieved by a long‐term moderate fat diet. British Journal of Nutrition 2007;97(2):399‐404.

Bakx 1997 {published data only}

Bakx JC, Stafleu A, Van Staveren WA, Van den Hoogen HJ, Van Weel C. Long‐term effect of nutritional counseling: a study in family medicine. American Journal of Clinical Nutrition 1997;65(6 Suppl):1946S‐50S.

Ball 1965 {published data only}

Ball KP, Hanington E, McAllen PM, Pilkington TR, Richards JM, Sharland DE, et al. Low‐fat diet in myocardial infarction: A controlled trial. Lancet 1965;2(411):501‐4.

Barnard 2009 {published data only}

Barnard ND, Cohen J, Jenkins DJ, Turner‐McGrievy G, Gloede L, Green A, et al. A low‐fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, controlled, 74‐wk clinical trial. American Journal of Clinical Nutrition 2009;89(5):1588S‐96S.

Barndt 1977 {published data only}

Barndt R, Blankenhorn CH, Crawford DW, Brooks SH. Regression and progression of early femoral atherosclerosis in treated hyperlipidaemic patients. Annals of Internal Medicine 1977;86(2):139‐46.

Baron 1990 {published data only}

Baron JA, Gleason R, Crowe B, Mann JI. Preliminary trial of the effect of general practice based nutritional advice. British Journal of General Practice 1990;40(333):137‐41.

Barr 1990 {published data only}

Barr SL, Ramakrishnan R, Holleran S. A 30% fat diet high in polyunsaturates and a 30% fat diet high in monounsaturates both lower total and low density lipoprotein cholesterol levels in normal males [Abstract]. Arteriosclerosis 1990;10:872a.

Barsotti 1991 {published data only}

Barsotti A. Modern trends in the therapy of arteriosclerosis in the light of new physiopathological findings [Moderne tendenze della terapia dell'arteriosclerosi alla luce delle nuove acquisizioni fisiopatologiche]. Cardiologia 1991;36(12, Suppl 1):33‐48.

Baumann 1982 {published data only}

Baumann J, Martschick R. Therapy of hyperlipidemia with xanthinol nicotinate as opposed to low fat diet [Therapie der Hyperlipidämie mit Xantinolnicotinat gegenüber fettarmer Diät]. Die Medizinische Welt 1982;33(4):139‐41.

BDIT Pilot Studies 1996 {published and unpublished data}

Boyd NF, Cousins M, Beaton M, Fishell E, Wright B, Fish E, et al. Clinical trial of low‐fat, high‐carbohydrate diet in subjects with mammographic dysplasia: report of early outcomes. Journal of the National Cancer Institute 1988;80(15):1244‐8.
Boyd NF, Cousins M, Beaton M, Han L, McGuire V. Methodological issues in clinical trials of dietary fat reduction in patients with breast dysplasia. Progress in Clininical and Biological Research 1986;222:117‐24.
Boyd NF, Cousins M, Beaton M, Kriukov V, Lockwood G, Tritchler D. Quantitative changes in dietary fat intake and serum cholesterol in women: results from a randomized, controlled trial. American Journal of Clinical Nutrition 1990;52(3):470‐6.
Boyd NF, Cousins M, Kriukov V. A randomised controlled trial of dietary fat reduction: the retention of subjects and characteristics of drop outs. Journal of Clinical Epidemiology 1992;45(1):31‐8.
Boyd NF, Cousins M, Lockwood G, Tritchler D. Dietary fat and breast cancer risk: the feasibility of a clinical trial of breast cancer prevention. Lipids 1992;27(10):821‐6.
Boyd NF, Cousins M, Lockwood G, Tritchler D. The feasibility of testing experimentally the dietary fat‐breast cancer hypothesis. Progress in Clinical and Biological Research 1990;346:231‐41.
Boyd NF, Martin LJ, Beaton M, Cousins M, Kriukov V. Long‐term effects of participation in a randomized trial of a low‐fat, high‐carbohydrate diet. Cancer Epidemiology, Biomarkers & Prevention 1996;5(3):217‐22.
Lee‐Han H, Cousins M, Beaton M, McGuire V, Kriukov V, Chipman M, et al. Compliance in a randomized clinical trial of dietary fat reduction in patients with breast dysplasia. American Journal of Clinical Nutrition 1988;48(3):575‐86.

Beckmann 1995 {published data only}

Beckmann SL, Os I, Kjeldsen SE, Eide IK, Westheim AS, Hjermann I. Effect of dietary counselling on blood pressure and arterial plasma catecholamines in primary hypertension. American Journal of Hypertension 1995;8(7):704‐11.

beFIT 1997 {published and unpublished data}

Retzlaff BM, Walden CE, McNeney WB, Buck BL, McCann BS, Knopp RH. Nutritional intake of women and men on the NCEP Step I and Step II diets. Journal of the American College of Nutrition 1997;16(1):52‐61.
Walden CE, Retzlaff BM, Buck BL, McCann BS, Knopp RH. Lipoprotein lipid response to the National Cholesterol Education Program Step II diet by hypercholesterolemic and combined hyperlipidemic women and men. Arteriosclerosis, Thrombosis and Vascular Biology 1997;17(2):375‐82.
Walden CE, Retzlaff BM, Buck BL, Wallick S, McCann BS, Knopp RH. Differential effect of National Cholesterol Education Program (NCEP) Step II Diet on HDL cholesterol, its subfractions, and apoprotein A‐1 levels in hypercholesterolemic women and men after 1 year: the beFIT study. Arteriosclerosis, Thrombosis and Vascular Biology 2000;20(6):1580‐7.

Beresford 1992 {published data only}

Beresford SA, Farmer EM, Feingold L, Graves KL, Sumner SK, Baker RM. Evaluation of a self‐help dietary intervention in a primary care setting. American Journal of Public Health 1992;82(1):79‐84.

Bergstrom 1967 {published data only}

Bergstrom G, Svanborg A. Dietary treatment of acute myocardial infarction. Acta Medica Scandinavica 1967;181(6):717‐21.

Bierenbaum 1963 {published data only}

Bierenbaum ML, Fleischman AI, Raichelson RI, Hayton T, Watson P. Ten year experience of modified fat diets on younger men with coronary heart disease. Lancet 1973;1(7817):1404‐7.
Bierenbaum ML, Green DP, Florin A, Fleischman AI, Caldwell AB. Modified‐fat dietary management of the young male with coronary disease. A five‐year report. JAMA 1967;202(13):1119‐23.
Bierenbaum ML, Green DP, Gherman C, Florin A, Caldwell AB. The effects of two low fat dietary patterns on the blood cholesterol levels of young male coronary patients. Journal of Chronic Diseases 1963;16:1073‐83.

Bloemberg 1991 {published and unpublished data}

Bloemberg BP, Kromhout D, Goddijn HE, Jansen A, Obermann‐de Boer GL. The impact for the guidelines for a healthy diet of the Netherlands Nutrition Council on total and high density lipoprotein cholesterol in hypercholesterolemic free living men. American Journal of Epidemiology 1991;134(1):39‐48.

Bloomgarden 1987 {published data only}

Bloomgarden ZT, Karmally W, Metzger MJ, Brothers M, Nechemias C, Bookman J, et al. Randomized, controlled trial of diabetic patient education: improved knowledge without improved metabolic status. Diabetes Care 1987;10(3):263‐72.

Bonk 1975 {published data only}

Bonk S, Hubotter E, Nickel C, Stocksmeier U, Vahey P, Volk I, et al. Myocardial infarct patients with and without intensive nutrition consultation over several years‐‐ comparison of physiological and social variables [Herzinfarktpatienten mit und ohne mehrjährige intensive Ernährungsberatung ‐ Vergleich von physiologischen und sozialen Variablen]. Infusionstherapie und Klinische Ernährung 1975;2(4):290‐6.

Bonnema 1995 {published data only}

Bonnema SJ, Jespersen LT, Marving J, Gregersen G. Supplementation with olive oil rather than fish oil increases small arterial compliance in diabetic patients. Diabetes, Nutrition and Metabolism Clinical and Experimental 1995;8:81‐7.

Bosaeus 1992 {published data only}

Bosaeus I, Belfrage L, Lindgren C, Andersson H. Olive oil instead of butter increases net cholesterol excretion from the small bowel. European Journal of Clinical Nutrition 1992;46(2):111‐5.

Boyd 1988 {published and unpublished data}

Boyd NF, McGuire V, Shannon P, Cousins M, Kriukov V, Mahoney L, et al. Effect of a low‐fat high‐carbohydrate diet on symptoms of cyclical mastopathy. Lancet 1988;2(8603):128‐32.

Brehm 2009 {published data only (unpublished sought but not used)}

Brehm BJ, Lattin BL, Summer SS, Boback JA, Gilchrist GM, Jandacek RJ, et al. One‐year comparison of a high‐monounsaturated fat diet with a high‐carbohydrate diet in type 2 diabetes. Diabetes Care 2009;32(2):215‐20.

Brensike 1982 {published data only}

Brensike JF, Kelsey SF, Passamani ER, Fisher MR, Richardson JM, Loh IK, et al. National Heart, Lung, and Blood Institute type II Coronary Intervention Study: design, methods, and baseline characteristics. Controlled Clinical Trials 1982;3(2):91‐111.

BRIDGES 2001 {published and unpublished data}

Hebert JR, Ebbeling CB, Olendzki BC, Hurley TG, Ma Y, Saal N, et al. Change in women's diet and body mass following intensive intervention for early‐stage breast cancer. Journal of the American Dietetic Association 2001;101(4):421‐31.

Broekmans 2003 {published and unpublished data}

Broekmans WM, Klöpping‐Ketelaars IA, Weststrate JA, Tijburg LB, Van Poppel G, Vink AA, et al. Decreased carotenoid concentrations due to dietary sucrose polyesters do not affect possible markers of disease risk in humans. Journal of Nutrition 2003;133(3):720‐6.

Brown 1984 {published data only}

Brown GD, Whyte L, Gee MI, Crockford PM, Grace M, Oberle K, et al. Effects of two "lipid‐lowering" diets on plasma lipid levels of patients with peripheral vascular disease. Journal of the American Dietetic Association 1984;84(5):546‐50.

Bruce 1994 {published data only}

Bruce SL, Grove SK. The effect of a coronary artery risk evaluation program on serum lipid values and cardiovascular risk levels. Applied Nursing Research 1994;7(2):67‐74.

Bruno 1983 {published data only}

Bruno R, Arnold C, Jacobson L, Winick M, Wynder E. Randomized controlled trial of a nonpharmacologic cholesterol reduction program at the worksite. Preventive Medicine 1983;12(4):523‐32.

Butcher 1990 {published data only}

Butcher LA, O'Dea K, Sinclair AJ, Parkin JD, Smith IL, Blombery P. The effects of very low fat diets enriched with fish or kangaroo meat on cold‐induced vasoconstriction and platelet function. Prostaglandins, Leukotrienes, and Essential Fatty Acids 1990;39(3):221‐6.

Byers 1995 {published data only}

Byers T, Mullis R, Anderson J, Dusenbury L, Gorsky R, Kimber C, et al. The costs and effects of a nutritional education program following work‐site cholesterol screening. American Journal of Public Health 1995;85(5):650‐5.

Caggiula 1996 {published data only}

Caggiula AW, Watson JE, Kuller LH, Olson MB, Milas NC, Berry M, et al. Cholesterol‐lowering intervention program. Effect of the step I diet in community office practices. Archives of Internal Medicine 1996;156(11):1205‐13.

Canadian DBCP 1997 {published data only (unpublished sought but not used)}

Boyd NF, Greenberg C, Lockwood G, Little L, Martin L, Byng J, et al. Effects at two years of a low‐fat, high‐carbohydrate diet on radiologic features of the breast: results from a randomized trial. Journal of the Nationl Cancer Institute 1997;89(7):488‐96.

CARMEN 2000 {published and unpublished data}

Poppitt SD, Keogh GF, Prentice AM, Williams DE, Sonnemans HM, Valk EE, et al. Long‐term effects of ad libitum low‐fat, high‐carbohydrate diets on body weight and serum lipids in overweight subjects with metabolic syndrome. American Journal of Clinical Nutrition 2002;75(1):11‐20.
Raben A, Astrup A, Vasilaras TH, Prentice AM, Zunft H‐JF, Formiguera X, et al. The CARMEN study [CARMEN‐studiet]. Ugeskrift für Laeger 2002;164(5):627‐31.
Saris WH, Astrup A, Prentice AM, Zunft HJ, Formiguera X. CARMEN Project: European multicentre study on the impact of dietary fat/CHO ratio and simple/complex CHO changes on long term weight control in overweight subjects. International Journal of Obesity 1997;21(Suppl 2):S71.
Saris WH, Astrup A, Prentice AM, Zunft HJ, Formiguera X, Verboeket‐van de Venne WP, et al. Randomized controlled trial of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates on body weight and blood lipids: the CARMEN study. International Journal of Obesity 2000;24(10):1310‐8.
Vasilaras TH, Astrup A, Raben A. Micronutrient intake in overweight subjects is not deficient on and ad libitum fat‐reduced, high‐simple carbohydrate diet. European Journal of Clinical Nutrition 2004;58(2):326‐36.

CARMEN sub‐study 2002 {published and unpublished data}

Poppitt SD, Keogh GF, Prentice AM, Williams DEM, Sonnemans HMW, Valk EEJ, et al. Long‐term effects of ad libitum low‐fat, high‐carbohydrate diets on body weight and serum lipids in overweight subjects with metabolic syndrome. American Journal of Clinical Nutrition 2002;75(1):11‐20.

Cerin 1993 {published data only}

Cerin A, Collins A, Landgren BM, Eneroth P. Hormonal and biochemical profiles of premenstrual syndrome. Treatment with essential fatty acids. Acta Obstetricia et Gynecologica Scandinavica 1993;72(5):337‐43.

Chan 1993 {published data only}

Chan JK, McDonald BE, Gerrard JM, Bruce VM, Weaver BJ, Holub BJ. Effect of dietary alpha‐linolenic acid and its ratio to linolenic acid on platelet and plasma fatty acids and thrombogenesis. Lipids 1993;28(9):811‐7.

Chapman 1950 {published data only}

Chapman CB, Gibbons T, Henschel A. The effect of the rice‐fruit diet on the composition of the body. New England Journal of Medicine 1950;243(23):899‐905.

Charbonnier 1975 {published data only}

Charbonnier A, Nepveux P, Fluteau G, Fluteau D. Immediate effects of ingestion of olive oil on the principal lipid constituents of the plasma. Comparison with other edible fats. Médecine & Chirurgie Digestives 1975;4 Suppl 2:73‐9.

Cheng 2004 {published data only}

Cheng C, Graziani C, Diamond JJ. Cholesterol‐lowering effect of the Food for Heart Nutrition Education Program. Journal of the American Dietetic Association 2004;104(12):1868‐72.

Chiostri 1988 {published data only}

Chiostri JE, Kwiterovich PO. Effect of American Heart Association Phase 2 diet versus eater's choice based diet on hypercholesterolaemia. Circulation 1988;78(4):II‐385.

Choudhury 1984 {published data only}

Choudhury S, Jackson P, Katan MB, Marenah CB, Cortese C, Miller NE, et al. A multifactorial diet in the management of hyperlipidaemia. Atherosclerosis 1984;50(1):93‐103.

Clark 1997 {published data only}

Clark M, Ghandour G, Miller NH, Taylor CB, Bandura A, DeBusk RF. Development and evaluation of a computer‐based system for dietary management of hyperlipidemia. Journal of the American Dietetic Association 1997;97(2):146‐50.

Clifton 1992 {published data only}

Clifton PM, Wight MB, Nestel PJ. Is fat restriction needed with HMGCoA reductase inhibitor treatment?. Atherosclerosis 1992;93(1‐2):59‐70.

Cobb 1991 {published data only}

Cobb MM, Teitelbaum HS, Breslow JL. Lovastatin efficacy in reducing low‐density lipoprotein cholesterol levels on high‐ vs low‐fat diets. JAMA 1991;265(8):997‐1001.

Cohen 1991 {published data only}

Cohen MD, D'Amico FJ, Merenstein JH. Weight reduction in obese hypertensive patients. Family Medicine 1991;23(1):25‐8.

Cole 1988 {published data only}

Cole TG, Schmeisser D, Prewitt TE. AHA phase 3 diet reduces cholesterol in moderately hypercholesterolemic premenopausal women [Abstract]. Circulation 1988;78(4):II‐73.

Colquhoun 1990 {published data only}

Colquhoun DM, Moores D, Somerset SM. Comparison of the effects of an avocado enriched and american heart association diets on lipid levels [Abstract]. Arteriosclerosis 1990;10:875a.

Consolazio 1946 {published data only}

Consolazio FC, Forbes WH. The effects of high fat diet in a temperate environment. Journal of Nutrition 1946;32:195‐204.

Cox 1996 {published data only}

Cox RH, Gonzales‐Vigilar MC, Novascone MA, Silva‐Barbeau I. Impact of a cancer intervention on diet‐related cardiovascular disease risks of white and African‐American EFNEP clients. Journal of Nutrition Education 1996;28:209‐18.

Croft 1986 {published data only}

Croft PR, Brigg D, Smith S, Harrison CB, Branthwaite A, Collins MF. How useful is weight reduction in the management of hypertension?. Journal of the Royal College of General Practitioners 1986;36(291):445‐8.

Curzio 1989 {published and unpublished data}

Curzio JL, Kennedy SS, Elliott HL, Farish E, Barnes JF, Howie CA, et al. Hypercholesterolaemia in treated hypertensives: a controlled trial of intensive dietary advice. Journal of Hypertension. Supplement 1989;7(6):S254‐5.

Dalgard 2001 {published data only}

Dalgard C, Thuroe A, Haastrup B, Haghfelt T, Stender S. Saturated fat intake is reduced in patients with ischemic heart disease 1 year after comprehensive counseling but not after brief counseling. Journal of the American Dietetic Association 2001;101(12):1420‐9.

Da Qing IGT 1997 {published data only}

Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997;20(4):537‐44.

DAS 2000 {published data only}

Bovbjerg VE, McCann BS, Brief DJ, Follette WC, Retzlaff BM, Dowdy AA, et al. Spouse support and long‐term adherence to lipid‐lowering diets. American Journal of Epidemiology 1995;141(5):451‐60.
Knopp RH, Retzlaff B, Walden C, Fish B, Buck B, McCann B. One‐year effects of increasingly fat‐restricted, carbohydrate‐enriched diets on lipoprotein levels in free‐living subjects. Proceedings of the Society for Experimental Biology & Medicine 2000;225(3):191‐9.
Knopp RH, Walden CE, McCann BS, Retzlaff B, Dowdy A, Gey G, et al. Serial changes in lipoprotein cholesterol in hypercholesterolemic men treated with alternative diets [abstract]. Arteriosclerosis 1989;9:745A.
Knopp RH, Walden CE, Retzlaff BM, McCann BS, Dowdy AA, Albers JJ, et al. Long‐term cholesterol‐lowering effects of 4 fat‐restricted diets in hypercholesterolaemic and combined hyperlipidaemic men: the Dietary Alternatives Study. JAMA 1997;278(18):1509‐15.
Walden CE, McCann BS, Retzlaff B, Dowdy A, Hanson M, Fish B, et al. Alternative fat‐restricted diets for hypercholesterolemia and combined hyperlipidemia: feasibility, design, subject recruitment, and baseline characteristics of the dietary alternatives study. Journal of the American College of Nutrition 1991;10(5):429‐42.

DASH 1997 {published data only}

Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. New England Journal of Medicine 1997;336(16):1117‐24.
Blackburn GL. Functional foods in the prevention and treatment of disease: significance of the Dietary Approaches to Stop Hypertension Study. American Journal of Clinical Nutrition 1997;66(5):1067‐71.

Davey Smith 2005 {published data only}

Davey Smith G, Bracha Y, Svendsen KH, Neaton JD, Haffner SM, Kuller LH, et al. Incidence of type 2 diabetes in the randomized multiple risk factor intervention trial. Annals of Internal Medicine 2005;142(5):313‐22.

De Boer 1983 {published data only}

De Boer AC, Turek JV, Pannebakker MA, den Ottolander GJ. The effect of diets high in polyunsaturated and high in saturated fatty acids on blood lipids and platelet tests in patients with coronary artery disease (CAD) [abstract]. Thrombosis and Haemostasis 1983;50:96.

De Bont 1981 {published and unpublished data}

De Bont AJ, Baker IA, St Leger AS, Sweetnam PM, Wragg KG, Stephens SM, et al. A randomised controlled trial of the effect of low fat diet advice on dietary response in insulin independent diabetic women. Diabetologia 1981;21(6):529‐33.

DeBusk 1994 {published data only}

DeBusk RF, Miller NH, Superko HR, Dennis CA, Thomas RJ, Lew HT, et al. A case‐management system for coronary risk factor modification after acute myocardial infarction [see comments]. Annals of Internal Medicine 1994;120(9):721‐9.

DEER 1998 {published data only (unpublished sought but not used)}

Stefanick ML, Mackey S, Sheehan RD, Ellsworth N, Haskell WL, Wood PD. Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol. New England Journal of Medicine 1998;339(1):12‐20.

Delahanty 2001 {published data only}

Delahanty LM, Hayden D, Ammerman A, Nathan DM. Medical nutrition therapy for hypercholesterolemia positively affects patient satisfaction and quality of life outcomes. Annals of Behavioral Medicine 2002;24(4):269‐78.
Delahanty LM, Sonnenberg LM, Hayden D, Nathan DM. Clinical and cost outcomes of medical nutrition therapy for hypercholesterolemia: a controlled trial. Journal of the American Dietetic Association 2001;101(9):1012‐23.

Delius 1969 {published data only}

Delius L. Treatment of hypotensive circulatory disorder [Die Behandlung der hypotonen Kreislaufregulationsstörung]. Deutsche Medizinische Wochenschrift 1969;94(42):2172‐3.

Demark 1990 {published data only}

Demark WW, Bowering J, Cohen PS. Reduced serum cholesterol with dietary change using fat‐modified and oat bran supplemented diets. Journal of the American Dietetic Association 1990;90(2):223‐9.

Dengel 1995 {published data only}

Dengel JL, Katzel LI, Goldberg AP. Effect of an American Heart Association diet, with or without weight loss, on lipids in obese middle‐aged and older men. American Journal of Clinical Nutrition 1995;62(4):715‐21.

Denke 1994 {published data only}

Denke MA, Grundy SM. Individual responses to a cholesterol lowering diet in 50 men with moderate hypercholesterolaemia. Archives of Internal Medicine 1994;154(3):17‐25.

Diabetes CCT 1995 {published data only}

The Diabetes Control and Complications Trial (DCCT) Research Group. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. American Journal of Cardiology 1995;75(14):894‐903.

Diet & Hormone Study 2003 {published data only (unpublished sought but not used)}

Gann PH, Chatterton RT, Gapstur SM, Liu K, Garside D, Giovanazzi S, et al. The effects of a low‐fat/high‐fiber diet on sex hormone levels and menstrual cycling in premenopausal women: a 12‐month randomized trial (the Diet and Hormone Study). Cancer 2003;98(9):1870‐9.

DIET 1998 {published data only}

Dornelas EA, Wylie‐Rosett J, Swencionis C. The DIET study: long term outcomes of a cognitive‐behavioural weight control intervention in independent‐living elders. Journal of the American Dietetic Association 1998;98(11):1276‐81.

Ding 1992 {published data only}

Ding Q. Clinical study of qianxining in the treatment of 60 cases of yang hyperactivity due to yin deficiency type of hypertension. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1992;12(7):409‐11, 388‐9.

DIRECT 2009 {published data only (unpublished sought but not used)}

Ben‐Avraham S, Harman‐Boehm I, Schwarzfuchs D, Shai I. Dietary strategies for patients with type 2 diabetes in the era of multi‐approaches; review and results from the Dietary Intervention Randomized Controlled Trial (DIRECT). Diabetes Research and Clinical Practice 2009;86(Suppl 1):S41‐8.
Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, et al. Weight loss with a low‐carbohydrate, Mediterranean, or low‐fat diet. New England Journal of Medicine 2008;359(3):229‐41.

Dobs 1991 {published data only}

Dobs AS, Sarma PS, Wilder L. Lipid‐lowering diets in patients taking pravastatin, a new HMG‐CoA reductase inhibitor: compliance and adequacy. American Journal of Clinical Nutrition 1991;54(4):696‐700.

DO IT 2006 {published and unpublished data}

Berstad P, Seljeflot I, Veierod MB, Hjerkinn EM, Arnesen H, Pedersen JI, et al. Supplementation with fish oil affects the association between very long‐chain n‐3 polyunsaturated fatty acids in serum non‐esterified fatty acids and soluble vascular cell adhesion molecule‐1. Clinical Science 2003;105(1):13‐20.
Ellingsen I, Hjerkinn EM, Seljeflot I, Arnesen H, Tonstad S, Ellingsen I, et al. Consumption of fruit and berries is inversely associated with carotid atherosclerosis in elderly men.[Erratum appears in British Journal of Nutrition 2008;99(3):697]. British Journal of Nutrition 2008;99(3):674‐81.
Ellingsen I, Seljeflot I, Arnesen H, Tonstad S, Ellingsen Ingrid, Seljeflot Ingebjorg, et al. Vitamin C consumption is associated with less progression in carotid intima media thickness in elderly men: A 3‐year intervention study. Nutrition Metabolism & Cardiovascular Diseases 2009;19(1):8‐14.
Furenes EB, Seljeflot I, Solheim S, Hjerkinn EM, Arnesen H. Long‐term influence of diet and/or omega‐3 fatty acids on matrix metalloproteinase‐9 and pregnancy‐associated plasma protein‐A in men at high risk of coronary heart disease. Scandinavian Journal of Clinical & Laboratory Investigation 2008;68(3):177‐84.
Hjerkinn EM, Abdelnoor M, Breivik L, Bergengen L, Ellingsen I, Seljeflot I, et al. Effect of diet or very long chain omega‐3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima‐media thickness and by pulse wave propagation in elderly men with hypercholesterolaemia. European Journal of Cardiovascular Prevention & Rehabilitation 2006;13(3):325‐33.
Hjerkinn EM, Seljeflot I, Ellingsen I, Berstad P, Hjermann I, Sandvik L, et al. Influence of long‐term intervention with dietary counselling, long‐chain n‐3 fatty acid supplements, or both on circulating markers of endothelial activation in men with long‐standing hyperlipidemia. American Journal of Clinical Nutrition 2005;81(3):583‐9.
Lindman AS, Pedersen JI, Hjerkinn EM, Arnesen H, Veierod MB, Ellingsen I, et al. The effects of long‐term diet and omega‐3 fatty acid supplementation on coagulation factor VII and serum phospholipids with special emphasis on the R353Q polymorphism of the FVII gene. Thrombosis & Haemostasis 2004;91(6):1097‐104.
Troseid M, Arnesen H, Hjerkinn EM, Seljeflot I. Serum levels of interleukin‐18 are reduced by diet and n‐3 fatty acid intervention in elderly high‐risk men. Metabolism: Clinical & Experimental 2009;58(11):1543‐9.
Troseid M, Seljeflot I, Hjerkinn EM, Arnesen H. Interleukin‐18 is a strong predictor of cardiovascular events in elderly men with the metabolic syndrome: synergistic effect of inflammation and hyperglycemia. Diabetes Care 2009;32(3):486‐92.

Due 2008 {published and unpublished data}

Bladbjerg EM, Larsen TM, Due A, Jespersen J, Stender S, Astrup A. Postprandial coagulation activation in overweight individuals after weight loss: Acute and long‐term effects of a high‐monounsaturated fat diet and a low‐fat diet. Thrombosis Research 2014;133(3):327‐33.
Due A, Larsen TM, Hermansen K, Stender S, Holst JJ, Toubro S, et al. Comparison of the effects on insulin resistance and glucose tolerance of 6‐mo high‐monounsaturated‐fat, low‐fat, and control diets. American Journal of Clinical Nutrition 2008;87(4):855‐62.
Due A, Larsen TM, Mu H, Hermansen K, Stender S, Astrup A. Comparison of 3 ad libitum diets for weight‐loss maintenance, risk of cardiovascular disease, and diabetes: a 6‐mo randomized, controlled trial. American Journal of Clinical Nutrition 2008;88(5):1232‐41.
Rasmussen LG, Larsen TM, Mortensen PK, Due A, Astrup A. Effect on 24‐h energy expenditure of a moderate‐fat diet high in monounsaturated fatty acids compared with that of a low‐fat, carbohydrate‐rich diet: a 6‐mo controlled dietary intervention trial. American Journal of Clinical Nutrition 2007;85(4):1014‐22.
Sloth B, Due A, Larsen TM, Holst JJ, Heding A, Astrup A, et al. The effect of a high‐MUFA, low‐glycaemic index diet and a low‐fat diet on appetite and glucose metabolism during a 6‐month weight maintenance period. British Journal of Nutrition 2009;101(12):1846‐58.

Duffield 1982 {published data only}

Duffield RG, Lewis B, Miller NE, Jamieson CW, Brunt JN, Colchester AC. Treatment of hyperlipidaemia retards progression of symptomatic femoral atherosclerosis. A randomised controlled trial. Lancet 1983;2(8351):639‐42.
Duffield RG, Miller NE, Jamieson CW, Lewis B. A controlled trial of plasma lipid reduction in peripheral atherosclerosis‐‐an interim report. British Journal of Surgery 1982;69(Suppl):S3‐S5.

Dullaart 1992 {published and unpublished data}

Dullaart RP, Beusekamp BJ, Meijer S, Hoogenberg K, Van Doormaal JJ, Sluiter WJ. Long‐term effects of linoleic‐acid‐enriched diet on albuminuria and lipid levels in type 1 (insulin‐dependent) diabetic patients with elevated urinary albumin excretion. Diabetologia 1992;35(2):165‐72.

Eating Patterns 1997 {published and unpublished data}

Beresford SA, Curry SJ, Kristal AR, Lazovich D, Feng Z, Wagner EH. A dietary intervention in primary care practice: the Eating Patterns Study. American Journal of Public Health 1997;87(4):610‐6.

Ehnholm 1982 {published data only}

Ehnholm C, Huttunen JK, Pietinen P, Leino U, Mutanen M, Kostiainen E, et al. Effect of diet on serum lipoproteins in a population with a high risk of coronary heart disease. New England Journal of Medicine 1982;307(14):850‐5.

Ehnholm 1984 {published data only}

Ehnholm C, Huttunen JK, Pietinen P, Leino U, Mutanen M, Kostiainen E, et al. Effect of a diet low in saturated fatty acids on plasma lipids, lipoproteins, and HDL subfractions. Arteriosclerosis 1984;4(3):265‐9.

Eisenberg 1990 {published data only}

Eisenberg S. The effect of dietary substitution of monounsaturated fatty acids with carbohydrates on lipoprotein levels, structure, and function in a free‐living population [abstract]. Arteriosclerosis 1990;10:872A.

Elder 2000 {published data only}

Elder JP, Candelaria JI, Woodruff SI, Criqui MH, Talavera GA, Rupp JW. Results of language for health: cardiovascular disease nutrition education for Latino English‐as‐a‐second‐language students. Health Education & Behavior 2000;27(1):50‐63.

Ellegard 1991 {published data only}

Ellegard L, Bosaeus I. Sterol and nutrient excretion in ileostomists on prudent diets. European Journal of Clinical Nutrition 1991;45(9):451‐7.

Esposito 2003 {published data only}

Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003;289(14):1799‐804.

Esposito 2004 {published data only}

Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, et al. Effect of a Mediterranean‐style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 2004;292(12):1440‐6.

EUROACTION 2008 {published data only}

Wood DA, Kotseva K, Connolly S, Jennings C, Mead A, Jones J, et al. Nurse‐coordinated multidisciplinary, family‐based cardiovascular disease prevention programme (EUROACTION) for patients with coronary heart disease and asymptomatic individuals at high risk of cardiovascular disease: a paired, cluster‐randomised controlled trial. Lancet 2008;371(9629):1999‐2012.

FARIS 1997 {published data only}

Goble A, Jackson B, Phillips P, Race E, Oliver RG, Worcester MC. The Family Atherosclerosis Risk Intervention Study (FARIS): risk factor profiles of patients and their relatives following an acute cardiac event. Australian and New Zealand Journal of Medicine 1997;27(5):568‐77.

Fasting HGS 1997 {published data only}

Dyson PA, Hammersley MS, Morris RJ, Holman RR, Turner RC. The Fasting Hyperglycaemia Study: II. Randomized controlled trial of reinforced healthy‐living advice in subjects with increased but not diabetic fasting plasma glucose. Metabolism 1997;46(12 Suppl 1):50‐5.

Ferrara 2000 {published data only}

Ferrara LA, Raimondi AS, d'Episcopo L, Guida L, Dello Russo A, Marotta T. Olive oil and reduced need for antihypertensive medications. Archives of Internal Medicine 2000;160(6):837‐42.

Fielding 1995 {published data only}

Fielding CJ, Havel RJ, Todd KM, Yeo KE, Schloetter MC, Weinberg V, et al. Effects of dietary cholesterol and fat saturation on plasma lipoproteins in an ethnically diverse population of healthy young men. Journal of Clinical Investigation 1995;95(2):611‐8.

Finnish Diabet Prev 2000 {published data only}

Uusitupa M, Louheranta A, Lindstrom J, Valle T, Sundvall J, Eriksson J, et al. The Finnish Diabetes Prevention Study. British Journal of Nutrition 2000;83(Suppl 1):S137‐42.

Finnish Mental Hosp 1972 {published data only}

Miettinen M, Turpeinen O, Karvonen MJ, Elosuo R, Paavilainen E. Effect of cholesterol‐lowering diet on mortality from coronary heart‐disease and other causes: a twelve‐year clinical trial in men and women. Lancet 1972;2(782):835‐8.
Miettinen M, Turpeinen O, Karvonen MJ, Pekkarinen M, Paavilainen E, Elosuo R. Dietary prevention of coronary heart disease in women: the Finnish mental hospital study. International Journal of Epidemiology 1983;12(1):17‐25.
Turpeinen O, Miettinen M, Karvonen M, Roine P, Pekkarinen M, Lehtosuo EJ, et al. Dietary prevention of coronary heart disease: long‐term experiment. I. Observations on male subjects. American Journal of Clinical Nutrition 1968;21(4):255‐76.

Fisher 1981 {published data only}

Fisher EA, Breslow JL, Zannis VI, Shen G, Blum CB. Dietary saturated fat, not cholesterol, affects plasma lipids and Apo E. Arteriosclerosis 1981;1(5):364a.

FIT Heart 2011 {published data only}

Mochari‐Greenberger H, Terry MB, Mosca L. Does stage of change modify the effectiveness of an educational intervention to improve diet among family members of hospitalized cardiovascular disease patients?. Journal of the American Dietetic Association 2010;110(7):1027‐35.
Mochari‐Greenberger H, Terry MB, Mosca L. Gender, age and race/ethnicity do not modify the effectiveness of a diet intervention among family members of hospitalized cardiovascular disease patients. Journal of Nutrition Education and Behavior 2011;43(5):366‐73.

Fleming 2002 {published data only}

Fleming RM. The effect of high‐, moderate‐, and low‐fat diets on weight loss and cardiovascular disease risk factors. Preventive Cardiology 2002;5(3):110‐5.

Fortmann 1988 {published data only}

Fortmann SP, Haskell WL, Wood PD. Effects of weight loss on clinic and ambulatory blood pressure in normotensive men. American Journal of Cardiology 1988;62(1):89‐93.

Foster 2003 {published data only}

Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, et al. A randomized trial of a low‐carbohydrate diet for obesity. New England Journal of Medicine 2003;348(21):2082‐90.

Frenkiel 1986 {published data only}

Frenkiel PG, Lee DW, Cohen H, Gilmore CJ, Resser K, Bonorris GG, et al. The effect of diet on bile acid kinetics and biliary lipid secretion in gallstone patients treated with ursodeoxycholic acid. American Journal of Clinical Nutrition 1986;43(2):239‐50.

FRESH START 2007 {published data only}

Denmark‐Wahnefried W, Clipp EC, Lipkus IM, Lobach D, Snyder DC, Sloane R, et al. Main outcomes of the FRESH START trial: a sequentially tailored, diet and exercise mailed print intervention among breast and prostate cancer survivors. Journal of Clinical Oncology 2007;25(19):2709‐18.

Gambera 1995 {published data only}

Gambera PJ, Schneeman BO, Davis PA. Use of the Food Guide Pyramid and US Dietary Guidelines to improve dietary intake and reduce cardiovascular risk in active‐duty Air Force members. Journal of the American Dietetic Association 1995;95(11):1268‐73.

Gaullier 2007 {published data only}

Gaullier J‐M, Halse J, Hoivik HO, Hoye K, Syvertsen C, Nurminiemi M, et al. Six months supplementation with conjugated linoleic acid induces regional‐specific fat mass decreases in overweight and obese. British Journal of Nutrition 2007;97:550‐60.

Ginsberg 1988 {published data only}

Ginsberg H. Both a high monounsaturated fat diet and the step 1 AHA diet significantly reduce plasma cholesterol levels in healthy males [abstract]. Circulation 1988;78:II73.

Gjone 1972 {published data only}

Gjone E, Nordoy A, Blomhoff JP, Wiencke I. The effects of unsaturated and saturated dietary fats on plasma cholesterol, phospholipids and lecithin: cholesterol acyltransferase activity. Acta Medica Scandinavica 1972;191(6):481‐4.

Glatzel 1966 {published data only}

Glatzel H. The relationship between postprandial triglyceridemia and the fat content of the basic diet [Die Abhängigkeit der postcenalen Triglyceridamie vom Fettgehalt der Grundkost]. Klinische Wochenschrift 1966;44(5):283‐4.

Goodpaster 1999 {published data only}

Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL. Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 1999;48(4):839‐47.

Grundy 1986 {published data only}

Grundy SM, Nix D, Whelan MF, Franklin L. Comparison of three cholesterol‐lowering diets in normolipidaemic men. JAMA 1986;256(17):2351‐5.

Hardcastle 2008 {published data only}

Hardcastle S, Taylor A, Bailey M, Castle R. A randomised controlled trial on the effectiveness of a primary health care based counselling intervention on physical activity, diet and CHD risk factors. Patient Education & Counseling 2008;70(1):31‐9.

Harris 1990 {published data only}

Harris WS, Feldman EB. Intensive dietary intervention in hypercholesterolemic patients. Observed versus predicted changes in cholesterol levels [abstract]. Arteriosclerosis 1990;10:853A.

Hartman 1993 {published data only}

Hartman T, McCarthy P, Himes J. Use of eating pattern messages to evaluate changes in eating behaviors in a worksite cholesterol education program. Journal of the American Dietetic Association 1993;93(10):1119‐23.

Hartwell 1986 {published data only}

Hartwell SL, Kaplan RM, Wallace JP. Comparison of behavioral interventions for control of type II diabetes mellitus. Behavior Therapy 1986;17:447‐61.

Hashim 1960 {published data only}

Hashim SA, Arteaga A, Van Itallie TB. Effect of saturated medium‐chain triglyceride on serum‐lipids in man. Lancet 1960;1(7134):1105‐7.

Haufe 2011 {published and unpublished data}

Haufe S, Engeli S, Kast P, Böhnke J, Utz W, Haas V, et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology 2011;53(5):1504‐14.
Haufe S, Utz W, Engeli S, Kast P, Böhnke J, Pofahl M, et al. Left ventricular mass and function with reduced‐fat or reduced‐carbohydrate hypocaloric diets in overweight and obese subjects. Hypertension 2012;59(1):70‐5.

Haynes 1984 {published data only}

Haynes RB, Harper AC, Costley SR, Johnston M, Logan AG, Flanagan PT, et al. Failure of weight reduction to reduce mildly elevated blood pressure: a randomized trial. Journal of Hypertension 1984;2(5):535‐9.

Heber 1991 {published data only}

Heber D, Ashley JM, Leaf DA, Barnard JA. Reduction of serum estradiol in postmenopausal women given free access to low‐fat high carbohydrate diet. Nutrition 1991;7(2):137‐41.

Heine 1989 {published and unpublished data}

Heine RJ, Mulder C, Popp‐Snijders C, Van der Meer J, Van der Veen EA. Linoleic‐acid‐enriched diet: long‐term effects on serum lipoprotein and apolipoprotein concentration and insulin sensitivity in noninsulin‐dependent diabetic patients. American Journal of Clinical Nutrition 1989;49(3):448‐56.

Hellenius 1995 {published and unpublished data}

Hellenius ML, Brismar KE, Berglund BH, De Faire U. Effects on glucose tolerance, insulin secretion, insulin‐like growth factor 1 and its binding protein, IGFBP‐1, in a randomized controlled diet and exercise study in healthy, middle‐aged men. Journal of Internal Medicine 1995;238(2):121‐30.
Hellenius ML, Dahlof C, Aberg H, Krakau I, De Faire U. Quality of life is not negatively affected by diet and exercise intervention in healthy men with cardiovascular risk factors. Quality of Life Research 1995;4(1):13‐20.
Hellenius ML, De Faire U, Berglund B, Hamsten A, Krakau I. Diet and exercise are equally effective in reducing risk for cardiovascular disease. Results of a randomized controlled study in men with slightly to moderately raised cardiovascular risk factors. Atherosclerosis 1993;103(1):81‐91.
Hellenius ML, Krakau I, De Faire U. Favourable long‐term effects from advice on diet and exercise given to healthy men with raised cardiovascular risks. Nutrition, Metabolism and Cardiovascular Diseases 1997;7:293‐300.
Hellenius, ML. Prevention of Cardiovascular Disease: Studies on the Role of Diet and Exercise in the Prevention of Cardiovascular Disease among Middle‐Aged Men [PhD thesis]. Huddinge, Sweden: Karolinska Intitute, 1995.
Naslund GK, Fredrikson M, Hellenius ML, De Faire U. Effect of diet and physical exercise intervention programmes on coronary heart disease risk in smoking and non‐smoking men in Sweden. Journal of Epidemiology and Community Health 1996;50(2):131‐6.

Heller 1993 {published and unpublished data}

Heller RF, Knapp JC, Valenti LA, Dobson AJ. Secondary prevention after acute myocardial infarction. American Journal of Cardiology 1993;72(11):759‐62.
Heller RF, Walker RJ, Boyle CA, O'Connell DL, Rusakaniko S, Dobson AJ. A randomised controlled trial of a dietary advice program for relatives of heart attack victims. Medical Journal of Australia 1994;161(9):529‐31.

Hildreth 1951 {published data only}

Hildreth EA, Mellinkoff SM, Blair GW, Hildreth DM. The effect of vegetable fat ingestion on human serum cholesterol concentration. Circulation 1951;3(5):641‐6.

Holm 1990 {published data only (unpublished sought but not used)}

Holm LE, Nordevang E, Ikkala E, Hallstrom L, Callmer E. Dietary intervention as adjuvant therapy in breast cancer patients‐‐a feasibility study. Breast Cancer Research and Treatment 1990;16(2):103‐9.
Nordevang E, Callmer E, Marmur A, Holm LE. Dietary intervention in breast cancer patients: effects on food choice. European Journal of Clinical Nutrition 1992;46(6):387‐96.
Nordevang E, Ikkala E, Callmer E, Hallstrom L, Holm LE. Dietary intervention in breast cancer patients: effects on dietary habits and nutrient intake. European Journal of Clinical Nutrition 1990;44(9):681‐7.

Horlick 1957 {published data only}

Horlick L, Craig BM. Effect of long‐chain polyunsaturated and saturated fatty acids on the serum‐lipids of man. Lancet 1957;2:566‐9.

Horlick 1960 {published data only}

Horlick L, O'Neil JB. Effect of modified egg‐yolk fats on blood‐cholesterol levels [letter]. Lancet 1960;1:438.

Howard 1977 {published data only}

Howard AN, Marks J. Hypocholesterolaemic effect of milk [letter]. Lancet 1977;2(8031):255‐6.

Hunninghake 1990 {published data only}

Hunninghake DB, Laskarzewski PM. Gender difference in the response to lovastatin administration with and without a cholesterol lowering diet [abstract]. Arteriosclerosis 1990;10:786A.

Hutchison 1983 {published data only}

Hutchison K, Oberle K, Crockford P, Grace M, Whyte L, Gee M, et al. Effects of dietary manipulation on vascular status of patients with peripheral vascular disease. JAMA 1983;249(24):3326‐30.

Hyman 1998 {published and unpublished data}

Hyman DJ, Ho KS, Dunn K, Simons‐Morton D. Dietary intervention for cholesterol reduction in public clinic patients. American Journal of Preventive Medicine 1998;15(2):139‐45.

Iacono 1981 {published data only}

Iacono JM, Judd JT, Marshall MW, Canary JJ, Dougherty RM, Mackin JF, et al. The role of dietary essential fatty acids and prostaglandins in reducing blood pressure. Progress in Lipid Research 1981;20:349‐64.

IMPACT 1995 {published data only}

Fielding JE, Mason T, Kinght K, Klesges R, Pelletier KR. A randomized trial of the IMPACT worksite cholesterol reduction program. American Journal of Preventive Medicine 1995;11(2):120‐3.

Iso 1991 {published data only}

Iso H, Konishi M, Terao A, Kiyama M, Tanigaki M, Baba M, et al. A community‐based education program for serum cholesterol reduction in urban hypercholesterolemic persons: comparison of intensive and usual education groups. Nippon.Koshu.Eisei.Zasshi [Japanese Journal of Public Health] 1991;38(9):751‐61.

Ives 1993 {published data only}

Ives DG, Kuller LH, Traven ND. Use and outcomes of a cholesterol‐lowering intervention for rural elderly subjects. American Journal of Preventive Medicine 1993;9(5):274‐81.

Jalkanen 1991 {published data only}

Jalkanen L. The effect of a weight reduction program on cardiovascular risk factors among overweight hypertensives in primary health care. Scandinavian Journal of Social Medicine 1991;19(1):66‐71.

Jerusalem Nut 1992 {published data only}

Berry EM, Eisenberg S, Friedlander Y, Harats D, Kaufmann NA, Norman Y, et al. Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins: the Jerusalem Nutrition Study. II. Monounsaturated fatty acids vs carbohydrates. American Journal of Clinical Nutrition 1992;56(2):394‐403.

Jula 1990 {published data only}

Jula A, Ronnemaa T, Rastas M, Karvetti RL, Maki J. Long‐term nopharmacological treatment for mild to moderate hypertension. Journal of Internal Medicine 1990;227(6):413‐21.

Junker 2001 {published data only}

Junker R, Pieke B, Schulte H, Nofer R, Neufeld M, Assmann G, et al. Changes in hemostasis during treatment of hypertriglyceridemia with a diet rich in monounsaturated and n‐3 polyunsaturated fatty acids in comparison with a low‐fat diet. Thrombosis Research 2001;101(5):355‐66.

Karmally 1990 {published data only}

Karmally W, Carpentiri C, Viscardi T, Cheverez V, Holleran S, Ramakrishnan R, et al. Replacing monounsaturated by polyunsaturated fatty acids within an AHA step I diet does not affect the plasma levels or metabolism of low density and high density lipoproteins in normal men [abstract]. Arteriosclerosis 1990;10:877A.

Karvetti 1992 {published data only}

Karvetti RL, Hakala P. A seven‐year follow‐up of a weight reduction programme in Finnish primary health care. European Journal of Clinical Nutrition 1992;46(10):743‐52.

Kastarinen 2002 {published data only}

Kastarinen MJ, Puska PM, Korhonen MH, Mustonen JN, Salomaa VV, Sundvall JE, et al. Non‐pharmacological treatment of hypertension in primary health care: A 2‐year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland. Journal of Hypertension 2002;20(12):01.

Kather 1985 {published data only}

Kather H, Wildenberg U, Wieland E. Influence of different dietary conditions in ideal‐weight subjects on serum levels of free fatty acids and of glycerol in vivo and on lipid mobilization in vitro [abstract]. European Journal of Clinical Investigation 1985;15:A.

Katzel 1995 {published data only}

Katzel LI, Bleecker ER, Colman EG, Rogus EM, Sorkin JD, Goldberg AP. Effects of weight loss vs aerobic exercise training on risk factors for coronary disease in healthy, obese, middle‐aged and older men. A randomized controlled trial [see comments]. JAMA 1995;274(24):1915‐21.

Kawamura 1993 {published data only}

Kawamura M, Akasaka T, Kasatsuki T, Nakajima J, Onodera S, Fujiwara T, et al. Blood pressure is reduced by short‐time calorie restriction in overweight hypertensive women with a constant intake of sodium and potassium. Journal of Hypertension. Supplement 1993;11(Suppl 5):S320‐1.

Keidar 1988 {published data only}

Keidar S, Krul ES, Goldberg AC, Bateman J, Schonfield G. Fat‐free diet modulates epitope expression of LDL‐apo [abstract]. Arteriosclerosis 1988;8:565A.

Kempner 1948 {published data only}

Kempner W. Treatment of hypertensive vascular disease with rice diet. American Journal of Medicine 1948;4(4):545‐77.

Keys 1957a {published data only}

Keys A, Anderson JT, Grande F. Serum‐cholesterol response to dietary fat [letter]. Lancet 1957;1:787.

Keys 1957b {published data only}

Keys A, Anderson JT, Grande F. Essential fatty acids, degree of unsaturation, and effect of corn (maize) oil on the serum‐cholesterol level in man. Lancet 1957;1(6959):66‐8.

Keys 1957c {published data only}

Keys A. Prediction of serum‐cholesterol responses of man to changes in fats in the diet. Lancet 1957;2:959‐66.

Khan 2003 {published and unpublished data}

Khan F, Elherik K, Bolton‐Smith C, Barr R, Hill A, Murrie I, et al. The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects. Cardiovascular Research 2003;59(4):955‐62.

King 2000 {published data only}

King S, David S, Newton H, Hevey D, Rafferty F, Horgan JH. The effect of dietary modification on the training outcome and body composition in patients undergoing undergoing a cardiac rehabilitation programme. Coronary Health Care 2000;4(2):76‐81.

Kingsbury 1961 {published data only}

Kingsbury KJ, Morgan DM, Aylott C, Emmerson R. Effects of ethyl arachidonate, cod‐liver oil, and corn oil on the plasma‐cholesterol level: a comparison in normal volunteers. Lancet 1961;1(7180):739‐41.

Koopman 1990 {published data only}

Koopman H, Spreeuwenberg C, Westerman RF, Donker AJ. Dietary treatment of patients with mild to moderate hypertension in a general practice: a pilot intervention study (2). Beyond three months. Journal of Human Hypertension 1990;4(4):372‐4.

Koranyi 1963 {published data only}

Koranyi A. Prophylaxis and treatment of the coronary syndrome. Therapia Hungarica 1963;11:17‐20.

Korhonen 2003 {published data only}

Korhonen M, Kastarinen M, Uusitupa M, Puska P, Nissinen A. The effect of intensified diet counselling on the diet of hypertensive subjects in primary health care: a 2‐year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland. Preventive Medicine 2003;36(1):8‐16.

Kriketos 2001 {published data only}

Kriketos AD, Robertson RM, Sharp TA, Drougas H, Reed GW, Storlien LH, et al. Role of weight loss and polyunsaturated fatty acids in improving metabolic fitness in moderately obese, moderately hypertensive subjects. Journal of Hypertension 2001;19(10):1745‐54.

Kris 1994 {published data only}

Kris EP, Mustad VA. Chocolate feeding studies: a novel approach for evaluating the plasma lipid effects of stearic acid. American Journal of Clinical Nutrition 1994;60(6 Suppl):1029S‐36S.

Kristal 1997 {published data only}

Kristal AR, Shattuck AL, Bowen DJ, Sponzo RW, Nixon DW. Feasibility of using volunteer research staff to deliver and evaluate a low‐fat dietary intervention: the American Cancer Society Breast Cancer Dietary Intervention Project. Cancer Epidemiology, Biomarkers and Prevention 1997;6(6):459‐67.

Kromhout 1987 {published data only}

Kromhout D, Arntzenius AC, Kempen‐Voogd N, Kempen HJ, Barth JD, Van der Voort HA, et al. Long‐term effects of linoleic‐acid enriched diet, changes in body weight and alcohol consumption on serum total and HDL‐cholesterol. Atherosclerosis 1987;66(1‐2):99‐105.

Kummel 2008 {published data only}

Kummel MV. Effects of an intervention on health behaviors of older coronary artery bypass (CAB) patients. Archives of Gerontology and Geriatrics 2008;2(2):227‐44.

Laitinen 1993 {published data only}

Laitinen JH, Ahola IE, Sarkkinen ES, Winberg RL, Harmaakorpi IP, Uusitupa MI. Impact of intensified dietary therapy on energy and nutrient intakes and fatty acid composition of serum lipids in patients with recently diagnosed non‐insulin‐dependent diabetes mellitus. Journal of the American Dietetic Association 1993;93(3):276‐83.

Laitinen 1994 {published data only}

Laitinen J, Uusitupa M, Ahola I, Siitonen O. Metabolic and dietary determinants of serum lipids in obese patients with recently diagnosed non‐insulin‐dependent diabetes. Annals of Medicine 1994;26(2):119‐24.

Lean 1997 {published and unpublished data}

Han TS, Richmond P, Avenell A, Lean ME. Waist circumference reduction and cardiovascular benefits during weight loss in women. International Journal of Obesity and Related Metabolic Disorders 1997;21(2):127‐34.
Lean ME, Han TS, Prvan T, Richmond PR, Avenell A. Weight loss with high and low carbohydrate 1200 kcal diets in free living women. European Journal of Clinical Nutrition 1997;51(4):243‐8.

Leduc 1994 {published data only}

Leduc CP, Cherniak D, Faucher J. Effectiveness of a group dietary intervention on hypercholesterolaemia: a randomised controlled clinical trial [poster abstract]. Atherosclerosis 1994;19:149.

Lewis 1958 {published data only}

Lewis B. Effect of certain dietary oils on bile‐acid secretion and serum‐cholesterol. Lancet 1958;1(7030):1090‐2.

Lewis 1981 {published data only}

Lewis B, Hammett F, Katan M, Kay RM, Merkx I, Nobels A, et al. Towards an improved lipid‐lowering diet: additive effects of changes in nutrient intake. Lancet 1981;2(8259):1310‐3.

Lewis 1985 {published data only}

Lewis B. Randomised controlled trial of the treatment of hyperlipidaemia on progression of atherosclerosis. Acta Medica Scandinavica. Supplement 1985;701:53‐7.

Lichtenstein 2002 {published data only}

Lichtenstein AH, Ausman LM, Jalbert SM, Vilella‐Bach M, Jauhiainen M, McGladdery S, et al. Efficacy of a therapeutic lifestyle change/step 2 diet in moderately hypercholesterolemic middle‐aged and elderly female and male subjects. Journal of Lipid Research 2002;43(2):264‐73.

Lim 2010 {published data only}

Lim SS, Noakes M, Keogh JB, Clifton PM. Long‐term effects of a low carbohydrate, low fat or high unsaturated fat diet compared to a no‐intervention control. Nutrition, Metabolism, and Cardiovascular Diseases 2010;20(8):599‐607.

Linko 1957 {published data only}

Linko E. Vegetable oils and serum cholesterol: short‐term experiments with rapeseed and sunflower oils. Acta Medica Scandinavica 1957;159(6):475‐88.

Lipid Res Clinic 1984 {published data only}

Gordon DJ, Salz KM, Roggenkamp KJ. Dietary determinants of plasma cholesterol change in the recruitment phase of the Lipid Research Clinics Coronary Primary Prevention Trial. Arteriosclerosis 1982;2(6):537‐48.
Lipid Research Clinics. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984;251(3):365‐74.
The Lipid Research Clinics. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251(3):351‐64.

Little 1990 {published data only}

Little P, Girling G, Hasler A, Craven A, Trafford A. The effect of a combination low sodium, low fat, high fibre diet on serum lipids in treated hypertensive patients. European Journal of Clinical Nutrition 1990;44(4):293‐300.

Little 2004 {published data only}

Little P, Kelly J, Barnett J, Dorward M, Margetts B, Warm D, et al. Randomised controlled factorial trial of dietary advice for patients with a single high blood pressure reading in primary care. BMJ 2004;328(7447):1054.

Lottenberg 1996 {published data only}

Lottenberg AM, Nunes VS, Lottenberg SA, Shimabukuro AF, Carrilho AJ, Malagutti S, et al. Plasma cholesteryl ester synthesis, cholesteryl ester transfer protein concentration and activity in hypercholesterolemic women: effects of the degree of saturation of dietary fatty acids in the fasting and postprandial states. Atherosclerosis 1996;126(2):265‐75.

Luszczynska 2007 {published data only}

Luszczynska A, Scholz U, Sutton S. Planning to change diet: a controlled trial of an implementation intentions training intervention to reduce saturated fat intake among patients after myocardial infarction. Journal of Psychosomatic Research 2007;63(5):491‐7.

Lyon Diet Heart 1994 {published data only}

De Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, et al. Mediterranean alpha‐linolenic acid‐rich diet in secondary prevention of coronary heart disease. Lancet 1994;343(8911):1454‐9.
De Lorgeril M, Salen P. Mediterranean diet in secondary prevention of coronary heart disease. Australian Journal of Nutrition and Dietetics 1998;55(Suppl):s16‐s20.
De Lorgeril M, Salen P, Caillat‐Vallet E, Hanauer M‐T, Barthelemy JC, Mamelle N. Control of bias in dietary trial to prevent coronary recurrences: the Lyon Diet Heart study. European Journal of Clinical Nutrition 1997;51(2):116‐22.
De Lorgeril M, Salen P, Martin J‐L, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart study. Circulation 1999;99(6):779‐85.
De Lorgeril M, Salen P, Martin JL, Mamelle N, Monjaud I, Touboul P, et al. Effect of a Mediterranean type of diet on the rate of cardiovascular complications in patients with coronary artery disease. insights into the cardioprotective effect of certain nutriments. Journal of the American College of Cardiology 1996;28(5):1103‐8.
De Lorgeril M, Salen P, Martin JL, Monjaud I, Boucher P, Mamelle N. Mediterranean dietary pattern in a randomised trial. Archives of Internal Medicine 1998;158(11):1181‐7.
Renaud S, De Lorgeril M, Delaye J, Guidollet J, Jacquard F, Mamelle N, et al. Cretan Mediterranean diet for prevention of coronary heart disease. American Journal of Clinical Nutrition 1995;61(6 Suppl):1360S‐7S.

Lysikova 2003 {published data only}

Lysikova SL, Pogozheva AV, Akol'zina SE, Vasil'ev AV, Vorob'eva LS. The study of the clinical potency of antiatherogenic diet containing flavonoids in cardiovascular patients [Russian]. Voprosy Pitaniia 2003;72(3):8‐11.

Macdonald 1972 {published data only}

Macdonald I. Relationship between dietary carbohydrates and fats in their influence on serum lipid concentrations. Clinical Science 1972;43(2):265‐74.

Mansel 1990 {published data only}

Mansel RE, Harrison BJ, Melhuish J, Sheridan W, Pye JK, Pritchard G, et al. A randomized trial of dietary intervention with essential fatty acids in patients with categorized cysts. Annals of the New York Academy of Sciences 1990;586:288‐94.

MARGARIN 2002 {published data only}

Bemelmans WJ, Broer J, Feskens EJ, Smit AJ, Muskiet FA, Lefrandt JD, et al. Effect of an increased intake of alpha‐linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha‐linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. American Journal of Clinical Nutrition 2002;75(2):221‐7.

Marniemi 1990 {published and unpublished data}

Hakala P, Karvetti RL. Weight reduction on lactovegetarian and mixed diets. European Journal of Clinical Nutrition 1989;43(6):421‐30.
Marniemi J, Seppanen A, Hakala P. Long‐term effects on lipid metabolism of weight reduction on lactovegetarian and mixed diet. International Journal of Obesity 1990;14(2):113‐25.

Mattson 1985 {published data only}

Mattson FH, Grundy SM. Comparison of effects of dietary saturated, monounsaturated and polyunsaturated fatty acids on plasma lipids and lipoproteins in man. Journal of Lipid Research 1985;26(2):194‐202.

McAuley 2005 {published and unpublished data}

McAuley KA, Hopkins CM, Smith KJ, McLay RT, Williams SM, Taylor RW, et al. Comparison of a high‐fat and high‐protein diets with a high‐carbohydrate diet in insulin‐resistant obese women. Diabetologia 2005;48:8‐16.
McAuley KA, Smith KJ, Taylor RW, McLay RT, Williams SM, Mann JI. Long‐term effects of popular dietary approaches on weight loss and features of insulin resistance. International Journal of Obesity 2006;30(2):342‐9.

McCarron 1997 {published data only}

McCarron DA, Oparil S, Chait A, Haynes RB, Kris EP, Stern JS, et al. Nutritional management of cardiovascular risk factors. A randomized clinical trial. Archives of Internal Medicine 1997;157(2):169‐77.

McCarron 2001 {published data only}

McCarron DA, Reusser ME. Reducing cardiovascular disease risk with diet. Obesity Research 2001;9(Suppl 4):335S‐40S.

McKeown‐Eyssen 1994 {published and unpublished data}

McKeown‐Eyssen GE, Bright SE, Bruce WR, Jazmaji V. A randomized trial of a low fat high fibre diet in the recurrence of colorectal polyps. Journal of Clinical Epidemiology 1994;47(5):525‐36.

McManus 2001 {published and unpublished data}

McManus K, Antinoro L, Sacks F. Randomized controlled trial of a moderate‐fat low‐energy diet compared with a low fat, low‐energy diet for weight loss in overweight adults. International Journal of Obesity and Related Metabolic Disorders 2001;25(10):1503‐11.

McNamara 1981 {published data only}

McNamara DJ, Kolb R, Parker T, Batwin H, Brown C, Samuel P, et al. Diet and cholesterol homeostasis in men [abstract]. Arteriosclerosis 1981;1:369A.

MeDiet 2002 {published and unpublished data}

Carruba G, Granata OM, Pala V, Campisi I, Agostara B, Cusimano R, et al. A traditional Mediterranean diet decreases endogenous estrogens in healthy postmenopausal women. Nutrition and Cancer 2006;56(2):253‐9.
Castagnetta L, Granata OM, Cusimano R, Ravazzolo B, Liquori M, Polito L, et al. The Mediet Project. Annals of the New York Academy of Science 2002;963:282‐9.
Granata OM, Traina A, Ramirez S, Campisi I, Zarcone M, Amodio R, et al. Dietary enterolactone affects androgen and estrogen levels in healthy postmenopausal women. Annals of the New York Academy of Science 2009;1155:232‐6.

Medi‐RIVAGE 2004 {published and unpublished data}

Borel P, Moussa M, Reboul E, Lyan B, Defoort C, Vincent‐Baudry S, et al. Human fasting plasma concentrations of vitamin E and carotenoids, and their association with genetic variants in apo C‐III, cholesteryl ester transfer protein, hepatic lipase, intestinal fatty acid binding protein and microsomal triacylglycerol transfer protein. British Journal of Nutrition 2009;101(5):680‐7.
Borel P, Moussa M, Reboul E, Lyan B, Defoort C, Vincent‐Baudry S, et al. Human plasma levels of vitamin E and carotenoids are associated with genetic polymorphisms in genes involved in lipid metabolism. Journal of Nutrition 2007;137(12):2653‐9.
Gastaldi M, Diziere S, Defoort C, Portugal H, Lairon D, Darmon M, et al. Sex‐specific association of fatty acid binding protein 2 and microsomal triacylglycerol transfer protein variants with response to dietary lipid changes in the 3‐mo Medi‐RIVAGE primary intervention study. American Journal of Clinical Nutrition 2007;86(6):1633‐41.
Vincent S, Gerber M, Bernard MC, Defoort C, Loundou A, Portugal H, et al. The Medi‐RIVAGE study (Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms): rationale, recruitment, design, dietary intervention and baseline characteristics of participants. Public Health Nutrition 2004;7(4):531‐42.
Vincent‐Baudry S, Defoort C, Gerber M, Bernard MC, Verger P, Helal O, et al. The Medi‐RIVAGE study: reduction of cardiovascular disease risk factors after a 3‐mo intervention with a Mediterranean‐type diet or a low‐fat diet. American Journal of Clinical Nutrition 2005;82(5):964‐71.

Mensink 1987 {published data only}

Mensink RP, Katan MB. Effect of monounsaturated fatty acids versus complex carbohydrates on high‐density lipoproteins in healthy men and women. Lancet 1987;1(8525):122‐5.

Mensink 1989 {published data only}

Mensink RP, Katan MB. Effect of a diet enriched with monounsaturated or polyunsaturated fatty acids on levels of low density and high density lipoprotein cholesterol in healthy women and men. New England Journal of Medicine 1989;321(7):436‐41.

Mensink 1990a {published data only}

Mensink RP, Katan MB. Effect of dietary trans fatty acids on high density and low density lipoprotein cholesterol levels in healthy subjects. New England Journal of Medicine 1990;323(7):439‐45.

Mensink 1990b {published and unpublished data}

Mensink RP. Effect of Monounsaturated Fatty Acids on High‐Density and Low‐Density Lipoprotein Cholesterol Levels and Blood Pressure in Healthy Men and Women. Wageningen, Netherlands: Wageningen University and Research Centre, 1990.

Metroville Health 2003 {published data only (unpublished sought but not used)}

Aziz KU, Dennis B, Davis CE, Sun K, Burke G, Manolio T, et al. Efficacy of CVD risk factor modification in a lower‐middle class community in Pakistan: the Metroville Health Study. Asia Pacific Journal of Public Health 2003;15(1):30‐6.

Michalsen 2006 {published and unpublished data}

Michalsen A, Lehmann N, Pithan C, Knoblauch NT, Moebus S, Kannenberg F, et al. Mediterranean diet has no effect on markers of inflammation and metabolic risk factors in patients with coronary artery disease. European Journal of Clinical Nutrition 2006;60(4):478‐85.

Miettinen 1994 {published data only}

Miettinen TA, Vanhanen H. Dietary sitostanol related to absorption, synthesis and serum level of cholesterol in different apolipoprotein E phenotypes. Atherosclerosis 1994;105(2):217‐26.

Millar 1973 {published data only}

Millar JH, Zilkha KJ, Langman MJ, Payling‐Wright H, Smith AD, Belin J, et al. Double‐blind trial of linoleate supplementation of the diet in multiple sclerosis. BMJ 1973;1(5856):765‐8.

Miller 1998 {published data only}

Miller ER, Appel LJ, Risby TH. Effect of dietary patterns on measures of lipid peroxidation: results from a randomised clinical trial. Circulation 1998;98(22):2390‐5.

Miller 2001 {published and unpublished data}

Miller SL, Reber RJ, Chapman‐Novakofski K. Prevalence of CVD risk factors and impact of a two‐year education program for premenopausal women. Women's Health Issues 2001;11(6):486‐93.

Milne 1994 {published data only}

Milne RM, Mann JI, Chisholm AW, Williams SM. Long‐term comparison of three dietary prescriptions in the treatment of NIDDM. Diabetes Care 1994;17(1):74‐80.

Minnesota Coronary 1989 {published data only}

Brewer ER, Ashman PL, Kuba K. The Minnesota Coronary Survey: composition of diets, adherence and serum lipid response [Abstract]. Circulation 1975;51 and 52(Suppl II):269.
Dawson EA, Gatewood LC. The Minnesota Coronary Survey: methodology and characteristics of the population [Abstract]. Circulation 1975;51 and 52(Suppl II):271.
Frantz ID, Dawson EA, Ashman PL, Gatewood LC, Bartsch GE, Kuba K, et al. Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis 1989;9(1):129‐35.
Frantz ID, Dawson EA, Kuba K, Brewer ER, Gatewood LC, Bartsch GE. The Minnesota Coronary Survey: effect of diet on cardiovascular events and deaths [abstract]. Circulation 1975;51 and 52(Suppl II):4.

Minnesota HHP 1990 {published data only}

Murray DM, Kurth C, Mullis R, Jeffery RW. Cholesterol reduction through low‐intensity interventions: results from the Minnesota Heart Health Program. Preventive Medicine 1990;19(2):181‐9.

Mojonnier 1980 {published data only}

Mojonnier ML, Hall Y, Berkson DM, Robinson E, Wethers B, Pannbacker B, et al. Experience in changing food habits of hyperlipidaemic men and women. Journal of the American Dietetic Association 1980;77(2):140‐8.

Mokuno 1988 {published data only}

Mokuno H, Yamada N, Sugimoto T. Cholesterol free diet in heterozygous familial hypercholesterolaemia: significant lowering effect on plasma cholesterol (abstract). Arteriosclerosis 1988;8(5):590a.

Mortensen 1983 {published data only}

Mortensen JZ, Schmidt EB, Nielsen AH, Dyerberg J. The effect of N‐6 and N‐3 polyunsaturated fatty acids on hemostasis, blood lipids and blood pressure. Thrombosis and Haemostasis 1983;50(2):543‐6.

MRFIT substudy 1986 {published data only}

Daniel GJ, Dolecek TA, Caggiula AW, Van Horn LV, Epley L, Randall BL. Increasing the use of meatless meals: a nutrition intervention substudy in the Multiple Risk Factor Intervention Trial (MRFIT). Journal of the American Dietetic Association 1986;86(6):778‐81.

MSDELTA 1995 {published data only}

Ginsberg HN. New directions in dietary studies and heart disease: the National Heart, Lung and Blood Institute sponsored Multicenter Study of Diet Effects on Lipoproteins and Thrombogenic Activity. Advances In Experimental Medicine and Biology 1995;369:241‐7.

MSFAT 1997 {published and unpublished data}

Van het Hoff K, Weststrate JA, Van den Berg H, Velthuis‐te Wierik EJ, De Graaf C, Zimmermanns NJ, et al. A long‐term study on the effect of spontaneous consumption of reduced fat products as part of a normal diet on indicators of health. International Journal of Food Sciences and Nutrition 1997;48(1):19‐29.
Velthuis‐te Wierik EJ, Van Leeuwen RE, Hendriks HF, Verhagen H, Loft S, Poulsen HE, et al. Short‐term moderate energy restriction does not affect indicators of oxidative stress and genotoxicity in humans. Journal of Nutrition 1995;125(10):2631‐9.
Velthuis‐te Wierik EJ, Van den Berg H, Weststrate JA, Van het Hoff KH, De Graaf C. Consumption of reduced‐fat products: effects on parameters of anti‐oxidative capacity. European Journal of Clinical Nutrition 1996;50(4):214‐9.
Weststrate JA, Van het Hof KH, Van den Berg H, Velthuis‐te Wierik EJ, De Graaf C, Zimmermanns NJ, et al. A comparison of the effect of free access to reduced fat products or their full fat equivalents on food intake, body weight, blood lipids and fat‐soluble antioxidants levels and haemostasis variables. European Journal of Clinical Nutrition 1998;52(6):389‐95.

Mujeres Felices 2003 {published data only}

Fitzgibbon ML, Gapstur SM, Knight SJ. Mujeres felices por ser saludables: a breast cancer risk reduction program for Latino women. Preventive Medicine 2003;36(5):536‐46.
Fitzgibbon ML, Gapstur SM, Knight SJ. Results of Mujeres Felices por ser Saludables: a dietary/breast health randomized clinical trial for Latino women. Annals of Behavioral Medicine 2004;28(2):95‐104.

Mutanen 1997 {published data only}

Mutanen M. Comparison between dietary monounsaturated and polyunsaturated fatty acids as regards diet‐related diseases. Biomedicine and Pharmacotherapy 1997;51(8):314‐7.

Muzio 2007 {published data only}

Muzio F, Mondazzi L, Harris WS, Sommariva D, Branchi A. Effects of moderate variations in the macronutrient content of the diet on cardiovascular disease risk factors in obese patients with the metabolic syndrome. American Journal of Clinical Nutrition 2007;86(4):946‐51.

Naglak 2000 {published data only (unpublished sought but not used)}

Naglak MC, Mitchell DC, Shannon BM, Pearson TA, Harkness WL, Kris‐Etherton PM. Nutrient adequacy of diets of adults with hypercholesterolemia after a cholesterol‐lowering intervention: long term assessment. Journal of the American Dietetic Association 2000;100(11):1385‐91.

NAS 1987 {published data only}

Chlebowski RT, Nixon DW, Blackburn GL, Jochimsen P, Scanlon EF, Insull W, et al. A breast cancer Nutrition Adjuvant Study (NAS): protocol design and initial patient adherence. Breast Cancer Research and Treatment 1987;10(1):21‐9.

National Diet Heart 1968 {published data only}

Baker BM, Frantz ID, Keys A, Kinsell LW, Page IH, Stamler J, et al. The National Diet‐Heart Study: An initial report. JAMA 1963;185:105‐6.
Brown HB. The National Diet Heart Study ‐ implications for dietitians and nutritionists. Journal of the American Dietetic Association 1968;52(4):279‐87.
Page IH, Brown HB. Some observations on the National Diet‐Heart Study. Circulation 1968;37(3):313‐5.
The National Diet‐Heart Study Research Group. The National Diet‐Heart Study. Nutrition Reviews 1968;26(5):133‐6.
The National Diet‐Heart Study Research Group. The National Diet‐Heart Study final report. Circulation 1968;37(II):1‐428.

NCEP weight 1991 {published and unpublished data}

Wood PD, Stefanick ML, Williams PT, Haskell WL. The effects on plasma lipoproteins of a prudent weight‐reducing diet, with or without exercise, in overweight men and women. New England Journal of Medicine 1991;325(7):461‐6.

Neil 1995 {published data only}

Neil HA, Roe L, Godlee RJ, Moore JW, Clark GM, Brown J, et al. Randomised trial of lipid lowering dietary advice in general practice: the effects on serum lipids, lipoproteins, and antioxidants [see comments]. BMJ 1995;310(6979):569‐73.

Neverov 1997 {published data only}

Neverov NI, Kaysen GA, Tareyeva IE. Effect of lipid‐lowering therapy on the progression of renal disease in nondiabetic nephrotic patients. Contributions to Nephrology 1997;120:68‐78.

Next Step 1995 {published and unpublished data}

Tilley BC, Vernon SW, Glanz K, Myers R, Sanders K, Lu M, et al. Worksite cancer screening and nutrition intervention for high‐risk auto workers: design and baseline findings of the Next Step Trial. Preventive Medicine 1997;26(2):227‐35.
Tilley BC, Vernon SW, Myers R, Glanz K, Lu M, Sanders K, et al. Planning the next step. A screening promotion and nutrition intervention trial in the work site. Annals of the New York Academy of Sciences 1995;768:296‐9.

Nordoy 1971 {published data only}

Nordoy A, Rodset JM. The influence of dietary fats on platelets in man. Acta Medica Scandinavica 1971;190(1‐2):27‐34.

Norway Veg Oil 1968 {published data only}

Natvig H, Borchgrevink CF, Dedichen J, Owren PA, Schiotz EH, Westlund K. A controlled trial of the effect of linolenic acid on incidence of coronary heart disease: the Norwegian Vegetable Oil Experiment of 1965‐66. Scandinavian Journal of Clinical and Laboratory Investigation. Supplement 1968;105:1‐20.

Nutrition Breast Health {published and unpublished data}

Djuric Z, Poore KM, Depper JB, Uhley VE, Lababidi S, Covington C, et al. Methods to increase fruit and vegetable intake with and without a decrease in fat intake: compliance and effects on body weight in the Nutrition and Breast Health Study. Nutrition and Cancer 2002;43(2):141‐51.

O'Brien 1976 {published data only}

O'Brien JR, Etherington MD, Jamieson S. Effect of a diet of polyunsaturated fats on some platelet‐function tests. Lancet 1976;2(7993):995‐6.

ODES 2006 {published data only}

Anderssen S, Holme I, Urdal P, Hjermann I. Diet and exercise intervention have favourable effects on blood pressure in mild hypertensives: the Oslo Diet and Exercise Study (ODES). Blood Pressure 1995;4(6):343‐9.
Anderssen SA, Hjermann I, Urdal P, Torjesen PA, Holme I. Improved carbohydrate metabolism after physical training and dietary intervention in individuals with the "atherothrombogenic syndrome". Oslo Diet and Exercise Study (ODES). A randomized trial. Journal of Internal Medicine 1996;240(4):203‐9.
Holme I, Haaheim LL, Tonstad S, Hjermann I, Holme I, Haaheim LL, et al. Effect of dietary and antismoking advice on the incidence of myocardial infarction: a 16‐year follow‐up of the Oslo Diet and Antismoking Study after its close. Nutrition Metabolism & Cardiovascular Diseases 2006;16(5):330‐8.
Rokling‐Andersen MH, Reseland JE, Veierod MB, Anderssen SA, Jacobs DR, Urdal P, et al. Effects of long‐term exercise and diet intervention on plasma adipokine concentrations. American Journal of Clinical Nutrition 2007;86(5):1293‐301.
The ODES Investigators. The Oslo Diet and Exercise Study (ODES): design and objectives. Controlled Clinical Trials 1993;14(3):229‐43.
Torjesen PA, Birkeland KI, Anderssen SA, Hjermann I, Holme I, Urdal P. Lifestyle changes may reverse development of the insulin resistance syndrome. The Oslo Diet and Exercise Study: a randomized trial. Diabetes Care 1997;20(1):26‐31.

Oldroyd 2001 {published data only}

Oldroyd JC. Randomised controlled trial evaluating the effectiveness of behavioural interventions to modify cardiovascular risk factors in men and women with impaired glucose tolerance: Outcomes at 6 months. Diabetes Research and Clinical Practice 2001;52(1):29‐43.
Oldroyd JC, Unwin NC, White M, Mathers JC, Alberti KG. Randomised controlled trial evaluating lifestyle interventions in people with impaired glucose tolerance. Diabetes Research & Clinical Practice 2006;72(2):117‐27.

Ole Study 2002 {published and unpublished data}

Bray GA, Lovejoy JC, Most‐Windhauser M, Smith SR, Volaufova J, Denkins Y, et al. A 9‐mo randomized clinical trial comparing fat‐substituted and fat‐reduced diets in healthy obese men: the Ole Study. American Journal of Clinical Nutrition 2002;76(5):928‐34.
Lovejoy JC, Bray GA, Lefevre M, Smith SR, Most MM, Denkins YM, et al. Consumption of a controlled low‐fat diet containing olestra for 9 months improves health risk factors in conjunction with weight loss in obese men: the Ole Study. International Journal of Obesity and Related Metabolic Disorders 2003;27(10):1242‐9.

OLIVE 1997 {published data only (unpublished sought but not used)}

Colquhoun DM. Rationale and design of the "OLIVE" study (Comparison of an Olive oil enriched to a low fat diet intervention study using vascular endpoints) [Abstract]. 11th International Symposium on Atherosclerosis, Paris. October 1997:326.
Colquhoun DM, Somerset S, Glasziou PP, Richards D, Weyers J. Comparison of an olive oil enriched diet to a low fat diet intervention study using vascular endpoints: assessed by repeat quantitative angiography (OLIVE study). Australian Journal of Nutrition and Dietetics 1998;55(Suppl 4):S24‐9.

ORIGIN 2008 {published data only}

Gerstein H, Yusuf S, Riddle MC, Ryden L, Bosch J. Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention). American Heart Journal 2008;155(1):26‐32.

Oslo Study 2004 {published data only}

Hjerkinn EM, Sandvik L, Hjermann I, Arnesen H. Effect of diet intervention on long‐term mortality in healthy middle‐aged men with combined hyperlipidaemia. Journal of Internal Medicine 2004;255(1):68‐73.
Hjermann I. Intervention of smoking and eating habits in healthy men carrying high risk for coronary heart disease. The Oslo Study. Acta Medica Scandinavica. Supplementum 1981;651:281‐4.
Hjermann I. Smoking and diet intervention in healthy coronary high risk men. Methods and 5‐year follow‐up of risk factors in a randomized trial. The Oslo study. Journal of the Oslo City Hospitals 1980;30(1):3‐17.
Hjermann I, Leren P, Norman N, Helgeland A, Holme I. Serum insulin response to oral glucose load during a dietary intervention trial in healthy coronary high risk men: the Oslo study. Scandinavian Journal of Clinical and Laboratory Investigation 1980;40(1):89‐94.
Hjermann I, Velve BK, Holme I, Leren P. Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo Study Group of a randomised trial in healthy men. Lancet 1981;2(8259):1303‐10.

Pascale 1995 {published data only}

Pascale RW, Wing RR, Butler BA, Mullen M, Bononi P. Effects of a behavioral weight loss program stressing calorie restriction versus calorie plus fat restriction in obese individuals with NIDDM or a family history of diabetes. Diabetes Care 1995;18(9):1241‐8.

PEP 2001 {published data only}

Ohrig E, Geib HC, Haas G‐M, Schwandt P. The prevention education program (PEP) Nuremberg: design and baseline data of a family oriented intervention study. International Journal of Obesity 2001;25(Suppl 1):S89‐92.

PHYLLIS 1993 {published data only}

Bond GM, Crepaldi G, Zanchetti A, Avogaro P, Marubini E, Maseri A, et al. Plaque hypertension lipid‐lowering Italian study (PHYLLIS): A protocol for non‐invasive evaluation of carotid atherosclerosis in hypercholesterolaemic hypertensive subjects. Journal of Hypertension 1993;11(Suppl 5):S314‐5.

Pilkington 1960 {published and unpublished data}

Pilkington TR, Stafford JL, Hankin VS, Simmonds FM, Koerselman HB. Practical diets for lowering serum lipids. British Medical Journal 1960;1(5165):23‐5.

Polyp Prevention 1996 {published and unpublished data}

Lanza E, Schatzkin A, Ballard BR, Clifford DC, Paskett E, Hayes D, et al. The polyp prevention trial II: dietary intervention program and participant baseline dietary characteristics. Cancer Epidemiology, Biomarkers and Prevention 1996;5(5):385‐92.
Schatzkin A, Lanza E, Freedman LS, Tangrea J, Cooper MR, Marshall JR, et al. The polyp prevention trial I: rationale, design, recruitment, and baseline participant characteristics. Cancer Epidemiology, Biomarkers and Prevention 1996;5(5):375‐83.

POUNDS LOST 2009 {published and unpublished data}

Anton SD, Gallagher J, Carey VJ, Laranjo N, Cheng J, Champagne CM, et al. Diet type and changes in food cravings following weight loss: findings from the POUNDS LOST Trial. Eating & Weight Disorders: EWD 2012;17(2):e101‐8.
Anton SD, LeBlanc E, Allen HR, Karabetian C, Sacks F, Bray G, et al. Use of a computerized tracking system to monitor and provide feedback on dietary goals for calorie‐restricted diets: the POUNDS LOST study. Journal of Diabetes Science & Technology 2012;6(5):1216‐25.
Bray GA, Smith SR, DeJonge L, de Souza R, Rood J, Champagne CM, et al. Effect of diet composition on energy expenditure during weight loss: the POUNDS LOST Study. International Journal of Obesity 2012;36(3):448‐55.
De Jonge L, Bray GA, Smith SR, Ryan DH, De Souza RJ, Loria CM, et al. Effect of diet composition and weight loss on resting energy expenditure in the POUNDS LOST study. Obesity 2012;20(12):2384‐9.
De Souza RJ, Bray GA, Carey VJ, Hall KD, LeBoff MS, Loria CM, et al. Effects of 4 weight‐loss diets differing in fat, protein, and carbohydrate on fat mass, lean mass, visceral adipose tissue, and hepatic fat: results from the POUNDS LOST trial. American Journal of Clinical Nutrition 2012;95(3):614‐25.
Mattei J, Qi Q, Hu FB, Sacks FM, Qi L, Mattei Josiemer, et al. TCF7L2 genetic variants modulate the effect of dietary fat intake on changes in body composition during a weight‐loss intervention. American Journal of Clinical Nutrition 2012;96(5):1129‐36.
Mirzaei K, Xu M, Qi Q, De Jonge L, Bray GA, Sacks F, et al. Variants in glucose‐ and circadian rhythm‐related genes affect the response of energy expenditure to weight‐loss diets: the POUNDS LOST Trial. American Journal of Clinical Nutrition 2014;99(2):392‐9.
Nicklas JM, Sacks FM, Smith SR, LeBoff MS, Rood JC, Bray GA, et al. Effect of dietary composition of weight loss diets on high‐sensitivity c‐reactive protein: the Randomized POUNDS LOST trial. Obesity 2013;21(4):681‐9.
Qi Q, Bray GA, Hu FB, Sacks FM, Qi L, Qi Q, et al. Weight‐loss diets modify glucose‐dependent insulinotropic polypeptide receptor rs2287019 genotype effects on changes in body weight, fasting glucose, and insulin resistance: the Preventing Overweight Using Novel Dietary Strategies trial. American Journal of Clinical Nutrition 2012;95(2):506‐13.
Qi Q, Bray GA, Smith SR, Hu FB, Sacks FM, Qi L, et al. Insulin receptor substrate 1 gene variation modifies insulin resistance response to weight‐loss diets in a 2‐year randomized trial: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. Circulation 2011;124(5):563‐71.
Qi Q, Xu M, Wu H, Liang L, Champagne CM, Bray GA, et al. IRS1 genotype modulates metabolic syndrome reversion in response to 2‐year weight‐loss diet intervention: the POUNDS LOST trial. Diabetes Care 2013;36(11):3442‐7.
Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, et al. Comparison of weight‐loss diets with different compositions of fat, protein, and carbohydrates. New England Journal of Medicine 2009;360(9):859‐73.
Williamson DA, Anton SD, Han H, Champagne CM, Allen R, LeBlanc E, et al. Adherence is a multi‐dimensional construct in the POUNDS LOST trial. Journal of Behavioral Medicine 2010;33(1):35‐46.
Williamson DA, Anton SD, Han H, Champagne CM, Allen R, LeBlanc E, et al. Early behavioral adherence predicts short and long‐term weight loss in the POUNDS LOST study. Journal of Behavioral Medicine 2010;33(4):305‐14.
Xu M, Qi Q, Liang J, Bray GA, Hu FB, Sacks FM, et al. Genetic determinant for amino acid metabolites and changes in body weight and insulin resistance in response to weight‐loss diets: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. Circulation 2013;127(12):1283‐9.
Zhang X, Qi Q, Bray GA, Hu FB, Sacks FM, Qi L, et al. APOA5 genotype modulates 2‐y changes in lipid profile in response to weight‐loss diet intervention: the Pounds Lost Trial. American Journal of Clinical Nutrition 2012;96(4):917‐22.
Zhang X, Qi Q, Zhang C, Smith SR, Hu FB, Sacks FM, et al. FTO genotype and 2‐year change in body composition and fat distribution in response to weight‐loss diets: the POUNDS LOST Trial.[Erratum appears in Diabetes. 2013 Feb;62(2):662 Note: Smith, Steven R [added]; Bray, George A [added]]. Diabetes 2012;61(11):3005‐11.

PREDIMED 2008 {published data only (unpublished sought but not used)}

Buil‐Cosiales P, Irimia P, Ros E, Riverol M, Gilabert R, Martinez‐Vila E, et al. Dietary fibre intake is inversely associated with carotid intima‐media thickness: a cross‐sectional assessment in the PREDIMED study. European Journal of Clinical Nutrition 2009;63(10):1213‐9.
Castañer O, Corella D, Covas MI, Sorlí JV, Subirana I, Flores‐Mateo G, et al. In vivo transcriptomic profile after a Mediterranean diet in high‐cardiovascular risk patients: a randomized controlled trial. American Journal of Clinical Nutrition 2013;98(3):845‐53.
Damasceno NRT, Sala‐Vila A, Cofán M, Pérez‐Heras AM, Fitó M, Ruiz‐Gutiérrez V, et al. Mediterranean diet supplemented with nuts reduces waist circumference and shifts lipoprotein subfractions to a less atherogenic pattern in subjects at high cardiovascular risk. Atherosclerosis 2013;230(2):347‐53.
Díaz‐López A, Bulló M, Martínez‐González MÁ, Guasch‐Ferré M, Ros E, Basora J, et al. Effects of mediterranean diets on kidney function: A report from the PREDIMED trial. American Journal of Kidney Diseases 2012;60(3):380‐9.
Estruch R, Martínez‐González MA, Corella D, Salas‐Salvadó J, Ruiz‐Gutiérrez V, Covas MI, et al. Effects of a Mediterranean‐style diet on cardiovascular risk factors: a randomized trial. Annals of Internal Medicine 2006;145(1):1‐11.
Estruch R, Ros E, Salas‐Salvadó J, Corvas M‐I, Corella D, Arós F, et al. PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. New England Journal of Medicine 2013;368(14):1279‐1290. [DOI: 10.1056/NEJMoa1200303]
Fernández‐Real JM, Bulló M, Moreno‐Navarrete JM, Ricart W, Ros E, Estruch R, et al. A Mediterranean diet enriched with olive oil is associated with higher serum total osteocalcin levels in elderly men at high cardiovascular risk. Journal of Clinical Endocrinology & Metabolism 2012;97(10):3792‐8.
Guasch‐Ferré M, Bulló M, Babio N, Martínez‐González MA, Estruch R, Covas MI, et al. Mediterranean diet and risk of hyperuricemia in elderly participants at high cardiovascular risk. Journals of Gerontology Series A‐Biological Sciences & Medical Sciences 2013;68(10):1263‐70.
Hu EA, Toledo E, Diez‐Espino J, Estruch R, Corella D, Salas‐Salvado J, et al. Lifestyles and risk factors associated with adherence to the Mediterranean diet: a baseline assessment of the PREDIMED trial. PloS One 2013;8(4):e60166.
Martínez‐Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas‐Salvadó J, San Julián B, et al. Mediterranean diet improves cognition: The PREDIMED‐NAVARRA randomised trial. Journal of Neurology, Neurosurgery, and Psychiatry 2013;84(12):1318‐25.
Martínez‐Lapiscina EH, Clavero P, Toledo E, San Julián B, Sanchez‐Tainta A, Corella D, et al. Virgin olive oil supplementation and long‐term cognition: The Predimed‐Navarra randomized, trial. Journal of Nutrition, Health and Aging 2013;17(6):544‐52.
Mitjavila MT, Fandos M, Salas‐Salvadó J, Covas MI, Borrego S, Estruch R, et al. The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals. A randomized, controlled, trial. Clinical Nutrition 2013;32(2):172‐8.
Nordmann AJ, Suter‐Zimmermann K, Bucher HC, Shai I, Tuttle KR, Estruch R, et al. Meta‐analysis comparing Mediterranean to low‐fat diets for modification of cardiovascular risk factors. American Journal of Medicine 2011;124(9):841‐51.
Prieto RM, Fiol M, Perello J, Estruch R, Ros E, Sanchis P, et al. Effects of Mediterranean diets with low and high proportions of phytate‐rich foods on the urinary phytate excretion. European Journal of Nutrition 2010;49(6):321‐6.
Razquin C, Martinez JA, Martinez‐Gonzalez MA, Bes‐Rastrollo M, Fernández‐Crehuet J, Marti A. A 3‐year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes. International Journal of Obesity 2010;34(2):266‐72.
Razquin C, Martinez JA, Martinez‐Gonzalez MA, Fernández‐Crehuet J, Santos JM, Marti A. A Mediterranean diet rich in virgin olive oil may reverse the effects of the ‐174G/C IL6 gene variant on 3‐year body weight change. Molecular Nutrition & Food Research 2010;54 Suppl 1:S75‐82.
Razquin C, Martinez JA, Martinez‐Gonzalez MA, Mitjavila MT, Estruch R, Marti A, et al. A 3 years follow‐up of a Mediterranean diet rich in virgin olive oil is associated with high plasma antioxidant capacity and reduced body weight gain. European Journal of Clinical Nutrition 2009;63(12):1387‐93.
Razquin C, Martinez JA, Martinez‐Gonzalez MA, Salas‐Salvado J, Estruch R, Marti A. A 3‐year Mediterranean‐style dietary intervention may modulate the association between adiponectin gene variants and body weight change. European Journal of Nutrition 2010;49:311‐9.
Ruiz‐Canela M, Estruch R, Corella D, Salas‐Salvadó J, Martínez‐González MA. Association of Mediterranean diet with peripheral artery disease: the PREDIMED randomized trial. JAMA 2014;311(4):415‐7.
Sala‐Vila A, Romero‐Mamani ES, Gilabert R, Núñez I, De la Torre R, Corella D, et al. Changes in ultrasound‐assessed carotid intima‐media thickness and plaque with a mediterranean diet: A substudy of the PREDIMED trial. Arteriosclerosis, Thrombosis, and Vascular Biology 2014;34(2):439‐45.
Salas‐Salvado J, Garcia‐Arellano A, Estruch R, Marquez‐Sandoval F, Corella D, Fiol M, et al. Components of the Mediterranean‐type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease. European Journal of Clinical Nutrition 2008;62(5):651‐9.
Salas‐Salvadó J, Bulló M, Babio N, Martínez‐González MÇ, Ibarrola‐Jurado N, Basora J, et al. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED‐Reus nutrition intervention randomized trial. Diabetes Care 2011;34:14‐9.
Salas‐Salvadó J, Bulló M, Estruch R, Ros E, Covas MI, Ibarrola‐Jurado N, et al. Prevention of diabetes with Mediterranean diets: a subgroup analysis of a randomized trial. Annals of Internal Medicine 2014;160(1):1‐10.
Salas‐Salvadó J, Fernandez‐Ballart J, Ros E, Martínez‐González MA, Fito M, Estruch R, et al. Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: one‐year results of the PREDIMED randomized trial. Archives of Internal Medicine 2008;168(22):2449‐58.
Schröder H, De la Torre R, Estruch R, Corella D, Martínez‐González MA, Salas‐Salvadó J, et al. Alcohol consumption is associated with high concentrations of urinary hydroxytyrosol. American Journal of Clinical Nutrition 2009;90(5):1329‐35.
Schröder H, Fitó M, Estruch R, Martínez‐González MA, Corella D, Salas‐Salvadó J, et al. A short screener is valid for assessing Mediterranean diet adherence among older Spanish men and women. Journal of Nutrition 2011;141(6):1140‐5.
Solá R, Fitó M, Estruch R, Salas‐Salvadó J, Corella D, De La Torre R, et al. Effect of a traditional Mediterranean diet on apolipoproteins B, A‐I, and their ratio: A randomized, controlled trial. Atherosclerosis 2011;218(1):174‐80.
Sánchez‐Taínta A, Estruch R, Bulló M, Corella D, Gómez‐Gracia E, Fiol M, et al. Adherence to a Mediterranean‐type diet and reduced prevalence of clustered cardiovascular risk factors in a cohort of 3,204 high‐risk patients. European Journal of Cardiovascular Prevention & Rehabilitation 2008;15(5):589‐93.
Sánchez‐Villegas A, Galbete C, Martínez‐González MA, Martinez JA, Razquin C, Salas‐Salvadó J, et al. The effect of the Mediterranean diet on plasma brain‐derived neurotrophic factor (BDNF) levels: the PREDIMED‐NAVARRA randomized trial. Nutritional Neuroscience 2011;14(5):195‐201.
Sánchez‐Villegas A, Martínez‐González MA, Estruch R, Salas‐Salvadó J, Corella D, Covas MI, et al. Mediterranean dietary pattern and depression: The PREDIMED randomized trial. BMC Medicine 2013;11:208.
Toledo E, Delgado‐Rodríguez M, Estruch R, Salas‐Salvadó J, Corella D, Gomez‐Gracia E, et al. Low‐fat dairy products and blood pressure: follow‐up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study. British Journal of Nutrition 2009;101(1):59‐67.
Toledo E, Hu FB, Estruch R, Buil‐Cosiales P, Corella D, Salas‐Salvadó J, et al. Effect of the Mediterranean diet on blood pressure in the PREDIMED trial: Results from a randomized controlled trial. BMC Medicine 2013;11:207.
Urpi‐Sarda M, Casas R, Chiva‐Blanch G, Romero‐Mamani ES, Valderas‐Martínez P, Arranz S, et al. Virgin olive oil and nuts as key foods of the Mediterranean diet effects on inflammatory biomakers related to atherosclerosis. Pharmacological Research 2012;65(6):577‐83.
Waterhouse AL. Resveratrol metabolites in urine as biomarker of wine intake in free‐living subjects: The PREDIMED Study. Free Radical Biology & Medicine 2009;46(12):1561.
Zamora‐Ros R, Urpi‐Sarda M, Lamuela‐Raventos RM, Estruch R, Martínez‐González MA, Bulló M, et al. Resveratrol metabolites in urine as a biomarker of wine intake in free‐living subjects: The PREDIMED Study. Free Radical Biology & Medicine 2009;46(12):1562‐6.
Zazpe I, Estruch R, Toledo E, Sánchez‐Taínta A, Corella D, Bulló M, et al. Predictors of adherence to a Mediterranean‐type diet in the PREDIMED trial. European Journal of Nutrition 2010;49(2):91‐9.
Zazpe I, Sánchez‐Taínta A, Estruch R, Lamuela‐Raventos RM, Schröder H, Salas‐Salvadó J, et al. A large randomized individual and group intervention conducted by registered dietitians increased adherence to Mediterranean‐type diets: the PREDIMED study. Journal of the American Dietetic Association 2008;108(7):1134‐44.

PREMIER 2003 {published and unpublished data}

Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, et al. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA 2003;289(16):2083‐93.
Elmer PJ, Obarzanek E, Vollmer WM, Simons‐Morton D, Stevens VJ, Young DR, et al. Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18‐month results of a randomized trial. Annals of Internal Medicine 2006;144(7):485‐95.
Ledikwe JH, Rolls BJ, Smiciklas‐Wright H, Mitchell DC, Ard JD, Champagne C, et al. Reductions in dietary energy density are associated with weight loss in overweight and obese participants in the PREMIER trial. American Journal of Clinical Nutrition 2007;85(5):1212‐21.
Lien LF, Brown AJ, Ard JD, Loria C, Erlinger TP, Feldstein AC, et al. Effects of PREMIER lifestyle modifications on participants with and without the metabolic syndrome. Hypertension 2007;50(4):609‐16.
Lin PH, Appel LJ, Funk K, Craddick S, Chen C, Elmer P, et al. The PREMIER intervention helps participants follow the Dietary Approaches to Stop Hypertension dietary pattern and the current Dietary Reference Intakes recommendations. Journal of the American Dietetic Association 2007;107(9):1541‐51.
Lin PH, Miwa S, Li YJ, Wang Y, Levy E, Lastor K, et al. Factors influencing dietary protein sources in the PREMIER trial population. Journal of the American Dietetic Association 2010;110(2):291‐5.
Maruthur NM, Wang NY, Appel LJ. Lifestyle interventions reduce coronary heart disease risk: results from the PREMIER Trial. Circulation 2009;119(15):2026‐31.
McGuire HL, Svetkey LP, Harsha DW, Elmer PJ, Appel LJ, Ard JD. Comprehensive lifestyle modification and blood pressure control: a review of the PREMIER trial. Journal of Clinical Hypertension 2004;6(7):383‐90.
Obarzanek E, Vollmer WM, Lin PH, Cooper LS, Young DR, Ard JD, et al. Effects of individual components of multiple behavior changes: the PREMIER trial. American Journal of Health Behavior 2007;31(5):545‐60.
Svetkey LP, Erlinger TP, Vollmer WM, Feldstein A, Cooper LS, Appel LJ, et al. Effect of lifestyle modifications on blood pressure by race, sex, hypertension status, and age. Journal of Human Hypertension 2005;19(1):21‐31.
Svetkey LP, Harsha DW, Vollmer WM, Stevens VJ, Obarzanek E, Elmer PJ, et al. Premier: a clinical trial of comprehensive lifestyle modification for blood pressure control: rationale, design and baseline characteristics. Annals of Epidemiology 2003;13(6):462‐71.
Young DR, Coughlin J, Jerome GJ, Myers V, Chae SE, Brantley PJ. Effects of the PREMIER interventions on health‐related quality of life. Annals of Behavioral Medicine 2010;40(3):302‐12.

Pritchard 2002 {published data only}

Pritchard JE, Nowson CA, Billington T, Wark JD. Benefits of a year‐long workplace weight loss program on cardiovascular risk factors. Nutrition and Dietetics 2002;59(2):87‐96.

Puget Sound EP 2000 {published and unpublished data}

Kristal AR, Curry SJ, Shattuck AL, Feng Z, Li S. A randomized trial of a tailored, self‐help dietary intervention: the Puget Sound Eating Patterns Study. Preventive Medicine 2000;31(4):380‐9.

Rabast 1979 {published data only}

Rabast U, Schonborn J, Kasper H. Dietetic treatment of obesity with low and high‐carbohydrate diets: comparative studies and clinical results. International Journal of Obesity 1979;3(3):201‐11.

Rabkin 1981 {published data only}

Rabkin SW, Boyko E, Streja DA. Relationship of weight loss and cigarette smoking to changes in high‐density lipoprotein cholesterol. American Journal of Clinical Nutrition 1981;34(9):1764‐8.

Radack 1990 {published data only}

Radack K, Deck C, Huster G. The comparative effects of n‐3 and n‐6 polyunsaturated fatty acids on plasma fibrinogen levels: a controlled clinical trial in hypertriglyceridemic subjects. Journal of the American College of Nutrition 1990;9(4):352‐7.

Rasmussen 1995 {published data only}

Rasmussen OW, Thomsen CH, Hansen KW, Vesterlund M, Winther E, Hermansen K. Favourable effect of olive oil in patients with non‐insulin‐dependent diabetes. The effect on blood pressure, blood glucose and lipid levels of a high‐fat diet rich in monounsaturated fat compared with a carbohydrate‐rich diet [Gunstig virkning af olivenolie hos ikkeinsulinkraevende diabetikere. Virkningen pa blodtryk, blodglukose og lipidniveauer af en dioet med et hojt indhold af monoumoettet fedt sammenlignet med en kulhydratrig dioet]. Ugeskrift for Laeger 1995;157(8):1028‐32.

Reaven 2001 {published data only}

Reaven GM, Abbasi F, Bernhart S, Coulston A, Darnell B, Dashti N, et al. Insulin resistance, dietary cholesterol, and cholesterol concentration in postmenopausal women. Metabolism: Clinical & Experimental 2001;50(5):594‐7.

Reid 2002 {published data only}

Reid R, Fodor G, Lydon‐Hassen K, D'Angelo MS, McCrea J, Bowlby M, et al. Dietary counselling for dyslipidemia in primary care: results of a randomized trial. Canadian Journal of Dietetic Practice & Research 2002;63(4):169‐75.

Renaud 1986 {published data only}

Renaud S, Godsey F, Dumont E, Thevenon C, Ortchanian E, Martin JL. Influence of long‐term diet modification on platelet function and composition in Moselle farmers. American Journal of Clinical Nutrition 1986;43(1):136‐50.

Rivellese 1994 {published and unpublished data}

Rivellese AA, Auletta P, Marotta G, Saldalamacchia G, Giacco A, Mastrilli V, et al. Long term metabolic effects of two dietary methods of treating hyperlipidaemia. BMJ 1994;308(6923):227‐31.

Rivellese 2003 {published data only}

Rivellese AA, Maffettone A, Vessby B, Uusitupa M, Hermansen K, Berglund L, et al. Effects of dietary saturated, monounsaturated and n‐3 fatty acids on fasting lipoproteins, LDL size and post‐prandial lipid metabolism in healthy subjects. Atherosclerosis 2003;167(1):149‐58.

Roderick 1997 {published and unpublished data}

Roderick P, Ruddock V, Hunt P, Miller G. A randomized trial to evaluate the effectiveness of dietary advice by practice nurses in lowering diet‐related coronary heart disease risk. British Journal of General Practice 1997;47(414):7‐12.

Roman CHD prev 1986 {published data only}

Research Group of the Rome Project of Coronary Heart Disease Prevention. Eight‐year follow‐up results from the Rome Project of Coronary Heart Disease Prevention. Research Group of the Rome Project of Coronary Heart Disease Prevention. Preventive Medicine 1986;15(2):176‐91.
Research Group of the Rome Project of Coronary Heart Disease Prevention. The Roman Coronary Disease Prevention Project: effectiveness of intervention and reduction of mortality over a 10‐year period [II Progetto Romano di Prevenzione della Cardiopatia Coronarica: efficacia dell'intervento e riduzione della mortalita in 10 anni]. Giornale Italiano di Cardiologia 1986;16(3):196‐202.

Rose 1987 {published data only}

Rose DP, Boyar AP, Cohen C, Strong LE. Effect of a low fat diet on hormone levels in women with cystic breast disease. I. Serum steroids and gonadotropins. Journal of the National Cancer Institute 1987;78(4):623‐6.

Sarkkinen 1995 {published and unpublished data}

Makinen E, Uusitupa MI, Pietinen P, Aro A, Penttila I. Long term effects of three fat modified diets on serum lipids in free living hypercholesterolaemic subjects (abstract). European Heart Journal 1991;12:162.
Sarkkinen ES, Agren JJ, Ahola I, Ovaskainen ML, Uusitupa MI. Fatty acid composition of serum cholesterol esters, and erythrocyte and platelet membranes as indicators of long‐term adherence to fat‐modified diets. American Journal of Clinical Nutrition 1994;59(2):364‐70.
Sarkkinen ES, Uusitupa MI, Nyyssonen K, Parviainen M, Penttila I, Salonen JT. Effects of two low‐fat diets, high and low in polyunsaturated fatty acids, on plasma lipid peroxides and serum vitamin E levels in free‐living hypercholesterolaemic men. European Journal of Clinical Nutrition 1993;47(9):623‐30.
Sarkkinen ES, Uusitupa MI, Pietinen P, Aro A, Ahola I, Penttila I, et al. Long‐term effects of three fat‐modified diets in hypercholesterolemic subjects. Atherosclerosis 1994;105(1):9‐23.
Sarkkinen, E. Long‐Term Feasibility and Effects of Three Different Fat‐Modified Diets in Free‐Living Hypercholesterolemic Subjects [PhD thesis]. Kuopio, Finland: University of Kuopio, 1995.
Uusitupa MI, Sarkkinen ES, Torpstrom J, Pietinen P, Aro A. Long‐term effects of four fat‐modified diets on blood pressure. Journal of Human Hypertension 1994;8(3):209‐18.

Schaefer 1995a {published data only}

Schaefer EJ, Lichtenstein AH, Lamon‐Fava S, McNamara JR, Schaefer MM, Rasmussen H, et al. Body weight and low density lipoprotein cholesterol changes after consumption of a low fat ad libitum diet. JAMA 1995;274(18):1450‐5.

Schaefer 1995b {published data only}

Schaefer EJ, Lichtenstein AH, Lamon‐Fava S, Contois JH, Li Z, Rasmussen H, et al. Efficacy of a National Cholesterol Education Program Step 2 diet in normolipidaemic and hypercholesterolaemic middle‐aged and elderly men and women. Arteriosclerosis, Thrombosis, and Vascular Biology 1995;15(8):1079‐85.

Schectman 1996 {published data only}

Schectman G, Wolff N, Byrd JC, Hiatt JG, Hartz A. Physician extenders for cost‐effective management of hypercholesterolemia. Journal of General Internal Medicine 1996;11(5):277‐86.

Schlierf 1995 {published data only}

Schlierf G, Schuler G, Hambrecht R, Niebauer J, Hauer K, Vogel G, et al. Treatment of coronary heart disease by diet and exercise. Journal of Cardiovascular Pharmacology 1995;25(Suppl 4):S32‐4.

Seppanen‐Laakso 1992 {published data only}

Seppanen‐Laakso T, Vanhanen H, Laakso I, Kohtamaki H, Viikari J. Replacement of butter on bread by rapeseed oil and rapeseed oil‐containing margarine: effects on plasma fatty acid composition and serum cholesterol. British Journal of Nutrition 1992;68:639‐54.

Seppelt 1996 {published and unpublished data}

Seppelt B, Weststrate JA, Reinert A, Johnson D, Luder W, Zunft HJ. Long‐term effects of nutrition with fat‐reduced foods on energy consumption and body weight [Langzeiteffekte einer Ernährung mit fettreduzierten Lebensmitteln auf die Energieaufnahme und das Körpergewicht]. Zeitschrift für Ernährungswissenschaft 1996;35(4):369‐77.

Singh 1991 {published data only}

Singh RB, Rastogi SS, Sircar AR. Dietary strategies for risk‐factor modification to prevent cardiovascular diseases. Nutrition 1991;7(3):210‐4.

Singh 1992 {published data only}

Singh RB, Niaz MA, Agarwal P, Begom R, Rastogi SS. Effect of antioxidant‐rich foods on plasma ascorbic acid, cardiac enzyme, and lipid peroxide levels in patients hospitalized with acute myocardial infarction. Journal of the American Dietetic Association 1995;95(7):775‐80.
Singh RB, Niaz MA, Ghosh S. Effect on central obesity and associated disturbances of low‐energy, fruit‐ and vegetable‐enriched prudent diet in north Indians. Postgraduate Medical Journal 1994;70(830):895‐900.
Singh RB, Rastogi SS, Verma R, Bolaki L, Singh R. An Indian experiment with nutritional modulation in acute myocardial infarction. American Journal of Cardiology 1992;69(9):879‐85.
Singh RB, Rastogi SS, Verma R, Laxmi B, Singh R, Ghosh S, et al. Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of one year follow up. BMJ 1992;304(6833):1015‐9.

Sirtori 1992 {published data only}

Sirtori CR, Gatti E, Tremoli E, Galli C, Gianfranceschi G, Franceschini G, et al. Olive oil, corn oil, and n‐3 fatty acids differently affect lipids, lipoproteins, platelets, and superoxide formation in type II hypercholesterolemia. American Journal of Clinical Nutrition 1992;56(1):113‐22.

SLIM 2008 {published data only}

Roumen C, Corpeleijn E, Feskens EJ, Mensink M, Saris WH, Blaak EE, et al. Impact of 3‐year lifestyle intervention on postprandial glucose metabolism: the SLIM study. Diabetic Medicine 2008;25(5):597‐605.

Sopotsinskaia 1992 {published data only}

Sopotsinskaia EB, Balitskii KP, Tarutinov VI, Zhukova VM, Semenchuk DD, Kozlovskaia SG, et al. Experience with the use of a low‐calorie diet in breast cancer patients to prevent metastasis [Opyt primeneniia nizkokaloriinoi diety u bol'nykh rakom molochnoi zhelezy s tsel'iu profilaktiki metastazi]. Voprosy Onkologii 1992;38(5):592‐9.

Stanford NAP 1997 {published data only}

Howard PB, Winkleby MA, Albright CL, Bruce B, Fortmann SP. The Stanford Nutrition Action Program: a dietary fat intervention for low‐literacy adults. American Journal of Public Health 1997;87(12):1971‐6.

Stanford Weight 1994 {published and unpublished data}

Williams PT, Krauss RM, Stefanick ML, Vranizan KM, Wood PD. Effects of low‐fat diet, calorie restriction, and running on lipoprotein subfraction concentrations in moderately overweight men. Metabolism 1994;43(5):655‐63.

Starmans 1995 {published data only}

Starmans KM, Lustermans FT, Kragten HA, Struijker BH, Rilla H. Lowering cholesterol in patients with mild hypercholesterolaemia does not improve functional properties of large arteries [Abstract]. Netherlands Journal Of Medicine 1995;46:A70.

Steinbach 1996 {published data only}

Steinbach M. A Romanian contribution to the epidemiology and prevention of cardiovascular diseases. Romanian Journal of Internal Medicine 1996;34(1‐2):137‐48.

Steptoe 2001 {published data only}

Steptoe A, Kerry S, Rink E, Hilton S. The impact of behavioral counselling on stage of change in fat intake, physical activity, and cigarette smoking in adults at increased risk of coronary heart disease. American Journal of Public Health 2001;91(2):265‐9.

Stevens 2002 {published and unpublished data}

Stevens VJ, Glasgow RE, Toobert DJ, Karanja N, Smith KS. One‐year results from a brief, computer‐assisted intervention to decrease consumption of fat and increase consumption of fruits and vegetables. Preventive Medicine 2003;36(5):594‐600.
Stevens VJ, Glasgow RE, Toobert DJ, Karanja N, Smith KS. Randomized trial of a brief dietary intervention to decrease consumption of fat and increase consumption of fruits and vegetables. American Journal of Health Promotion 2002;16(3):129‐34.

Stevenson 1988 {published data only}

Stevenson DW, Darga LL, Spafford TR, Ahmad N, Lucas CP. Variable effects of weight loss on serum lipids and lipoproteins in obese patients. International Journal of Obesity 1988;12(6):495‐502.

Strychar 2009 {published and unpublished data}

Strychar I, Cohn JS, Renier G, Rivard M, Aris‐Jilwan N, Beauregard H, et al. Effects of a diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on postmeal triglyceride concentrations and other cardiovascular risk factors in type 1 diabetes. Diabetes Care 2009;32(9):1597‐9.

Sweeney 2004 {published data only}

Sweeney M. Effects of very low‐fat diets on anginal symptoms. Medical Hypotheses 2004;63(3):553.

Søndergaard 2003 {published and unpublished data}

Søndergaard E, Møller JE, Egstrup K. Effect of dietary intervention and lipid‐lowering treatment on brachial vasoreactivity in patients with ischemic heart disease and hypercholesterolemia. American Heart Journal 2003;145(5):E19.

TAIM 1992 {published data only}

Davis BR, Blaufox MD, Hawkins CM, Langford HG, Oberman A, Swencionis C, et al. Trial of antihypertensive interventions and management. Design, methods, and selected baseline results. Controlled Clinical Trials 1989;10(1):11‐30.
Davis BR, Blaufox MD, Oberman A, Wassertheil SS, Zimbaldi N, Cutler JA, et al. Reduction in long‐term antihypertensive medication requirements. Effects of weight reduction by dietary intervention in overweight persons with mild hypertension. Archives of Internal Medicine 1993;153(15):1773‐82.
Davis BR, Oberman A, Blaufox MD, Wassertheil SS, Hawkins CM, Cutler JA, et al. Effect of antihypertensive therapy on weight loss. The Trial of Antihypertensive Interventions and Management Research Group. Hypertension 1992;19(4):393‐9.
Langford HG, Davis BR, Blaufox D, Oberman A, Wassertheil‐Smoller S, et al. Effect of drug and diet treatment of mild hypertension on diastolic blood pressure. The TAIM Research. Hypertension 1991;17(2):210‐7.
Oberman A, Wassertheil‐Smoller S, Langford HG, Blaufox MD, Davis BR, Blaszkowski T, et al. Pharmacologic and nutritional treatment of mild hypertension: changes in cardiovascular risk status. Annals of Internal Medicine 1990;112(2):89‐95.
Wassertheil‐Smoller S, Davis BR, Breuer B, Chee JC, Oberman A, Blaufox MD. Differences in precision of dietary estimates among different population subgroups. Annals of Epidemiology 1993;3(6):619‐28.
Wassertheil‐Smoller S, Oberman A, Blaufox MD, Davis B, Langford H. The Trial of Antihypertensive Interventions and Management (TAIM) Study. Final results with regard to blood pressure, cardiovascular risk, and quality of life. American Journal of Hypertension 1992;5(1):37‐44.
Wylie‐Rosett J, Wassertheil‐Smoller S, Blaufox MD, Davis BR, Langford HG, Oberman A, et al. Trial of antihypertensive intervention and management: greater efficacy with weight reduction than with a sodium‐potassium intervention. Journal of the American Dietetic Association 1993;93(4):408‐15.

Tapsell 2004 {published data only (unpublished sought but not used)}

Tapsell LC, Hokman A, Sebastiao A, Denmeade S, Martin G, Calvert GD, et al. The impact of usual dietary patterns, selection of significant foods and cuisine choices on changing dietary fat under 'free living' conditions. Asia Pacific Journal of Clinical Nutrition 2004;13(1):86‐91.

THIS DIET 2008 {published data only}

Tuttle KR, Shuler LA, Packard DP, Milton JE, Daratha KB, Bibus DM, et al. Comparison of low‐fat versus Mediterranean‐style dietary intervention after first myocardial infarction (from The Heart Institute of Spokane Diet Intervention and Evaluation Trial). American Journal of Cardiology 2008;101(11):1523‐30.

TOHP I 1992 {published data only}

Kumanyika SK, Hebert PR, Cutler JA, Lasser VI, Sugars CP, Steffen Batey L, et al. Feasibility and efficacy of sodium reduction in the Trials of Hypertension Prevention, phase I. Hypertension 1993;22(4):502‐12.
Satterfield S, Cutler JA, Langford HG, Applegate WB, Borhani NO, Brittain E, et al. Trials of hypertension prevention. Annals of Epidemiology 1991;1(5):455‐71.
Stevens VJ, Corrigan SA, Obarzanek E, Bernauer E, Cook NR, Hebert P, et al. Weight loss intervention in phase I of the trials of hypertension prevention. The TOHP Collaborative Research Group. Archives of Internal Medicine 1993;153(7):849‐58.
The Trials of Hypertension Prevention Collaborative Research Group. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I. JAMA 1992;267(9):1213‐20.
Whelton PK, Hebert PR, Cutler J, Applegate WB, Eberlein KA, Klag MJ, et al. Baseline characteristics of participants in phase I of the Trials of Hypertension Prevention. Annals of Epidemiology 1992;2(3):295‐310.
Whelton PK, Kumanyika SK, Cook NR, Cutler JA, Borhani NO, Hennekens CH, et al. Efficacy of nonpharmacologic interventions in adults with high‐normal blood pressure: results from phase 1 of the Trials of Hypertension Prevention. American Journal of Clinical Nutrition 1997;65(2 Suppl):652S‐60S.

TONE 1997 {published data only}

Whelton PK, Appel LJ, Espeland MA, Applegate WB, Ettinger‐WH J, Kostis JB, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA 1998;279(11):839‐46.
Whelton PK, Babnson J, Appel LJ, Charleston J, Cosgrove N, Espeland MA, et al. Recruitment in the Trial of Nonpharmacologic Intervention in the Elderly (TONE). Journal of the American Geriatrics Society 1997;45(2):185‐93.

Toobert 2003 {published data only}

Toobert DJ, Glasgow RE, Strycker LA, Barrera M, Radcliffe JL, Wander RC, et al. Biologic and quality‐of‐life outcomes from the Mediterranean Lifestyle Program: a randomized clinical trial. Diabetes Care 2003;26(8):2288‐93.

Towle 1994 {published data only}

Towle LA, Bergman EA, Joseph E. Low‐fat bison‐hybrid ground meat has no effects on serum lipid levels in a study of 12 men. Journal of the American Dietetic Association 1994;94(5):546‐8.

TRANSFACT 2006 {published data only}

Chardigny JM. Do trans fatty acids from industrially produced sources and from natural sources have the same effect on cardiovascular disease risk factors in healthy subjects? Results of the Trans Fatty Acids Collaboration (TRANSFACT) study. American Journal of Clinical Nutrition 2008;108(3):558‐66.
Chardigny JM, Malpuech‐Brugere C, Dionisi F, Bauman DE, German B, Mensink RP, et al. Rationale and design of the TRANSFACT project phase I: a study to assess the effect of the two different dietary sources of trans fatty acids on cardiovascular risk factors in humans. Contemporary Clinical Trials 2006;27(4):364‐73.

Treatwell 1992 {published and unpublished data}

Sorensen G, Morris DM, Hunt MK, Hebert JR, Harris DR, Stoddard A, et al. Work‐site nutrition intervention and employees' dietary habits: the Treatwell program. American Journal of Public Health 1992;82(6):877‐80.

Tromsø Heart 1989 {published data only}

Knutsen SF, Knutsen R. The Tromsø Heart Study: family approach to intervention on CHD. Feasibility of risk factor reduction in high‐risk persons‐‐project description. Scandinavian Journal of Social Medicine 1989;17(1):109‐19.

Troyer 2010 {published and unpublished data}

Racine EF, Lyerly J, Troyer JL, Warren‐Findlow J, McAuley WJ. The influence of home‐delivered dietary approaches to stop hypertension meals on body mass index, energy intake, and percent of energy needs consumed among older adults with hypertension and/or hyperlipidemia. Journal of the Academy of Nutrition & Dietetics 2012;112(11):1755‐62.
Troyer JL, Racine EF, Ngugi GW, McAuley WJ. The effect of home‐delivered Dietary Approach to Stop Hypertension (DASH) meals on the diets of older adults with cardiovascular disease. American Journal of Clinical Nutrition 2010;91(5):1204‐12.

UK PDS 1996 {published data only}

Turner R, Cull C, Holman R. United Kingdom Prospective Diabetes Study 17: a 9‐year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non‐insulin‐dependent diabetes mellitus. Annals of Internal Medicine 1996;124(1 Pt 2):136‐45.
Turner RC, Holman RR. Lessons from UK prospective diabetes study. Diabetes Research and Clinical Practice 1995;28(Suppl):S151‐7.

Urbach 1952 {published data only}

Urbach R, Hildreth EA, Wackerman MT. The therapeutic uses of low fat, low cholesterol diets: I. Treatment of essential familial xanthomatosis. Journal of Clinical Nutrition 1952;1(1):52‐6.

Uusitupa 1993 {published data only}

Uusitupa M, Laitinen J, Siitonen O, Vanninen E, Pyorala K. The maintenance of improved metabolic control after intensified diet therapy in recent type 2 diabetes. Diabetes Research and Clinical Practice 1993;19(3):227‐38.

Vavrikova 1958 {published data only}

Vavrikova J. Essential fatty acids, lipid metabolism, and atherosclerosis [letter]. Lancet 1958;1:1337.

Verheiden 2003 {published data only (unpublished sought but not used)}

Verheiden MW, Van der Veen JE, Van Zadelhoff WM, Bakx C, Koelen MA, Van den Hoogen HJ, et al. Nutrition guidance in Dutch family practice: behavioural determinants of reduction in fat consumption. American Journal of Clinical Nutrition 2003;77(Suppl):1058S‐64S.

Wass 1981 {published data only}

Wass VJ, Jarrett RJ, Meilton V, Start MK, Mattock M, Ogg CS, et al. Effect of a long‐term fat‐modified diet on serum lipoprotein levels of cholesterol and triglyceride in patie. Clinical Science 1981;60(1):81‐6.

Wassertheil 1985 {published data only}

Wassertheil SS, Blaufox MD, Langford HG, Oberman A, Cutter G, Pressel S. Prediction of response to sodium intervention for blood pressure control. Journal of Hypertension.Supplement 1986;4(5):S343‐6.
Wassertheil SS, Langford HG, Blaufox MD, Oberman A, Hawkins M, Levine B, et al. Effective dietary intervention in hypertensives: sodium restriction and weight reduction. Journal of the American Dietetic Association 1985;85(4):423‐30.

WATCH 1999 {published and unpublished data}

Ockene IS, Hebert JR, Ockene JK, Saperia GM, Stanek E, Nicolosi R, et al. Effect of a physician‐delivered nutrition counselling training and an office‐support program on saturated fat intake, weight, and serum lipid measurements in a hyperlipidemic population: Worcester Area Trial for Counseling in Hyperlipidemia. Archives of Internal Medicine 1999;159(7):725‐31.

Watts 1988 {published data only}

Watts GF, Ahmed W, Quiney J, Houlston R, Jackson P, Iles C, et al. Effective lipid lowering diets including lean meat. BMJ (Clinical Research Ed.) 1988;296(6617):235‐7.

Weintraub 1992 {published data only}

Weintraub M, Sundaresan PR, Schuster B. Long‐term weight control study. VII (weeks 0 to 210). Serum lipid changes. Clinical Pharmacology and Therapeutics 1992;51(5):634‐41.

Westman 2006 {published data only}

Westman EC, Yancy WS, Olsen MK, Dudley T, Guyton JR. Effect of a low‐carbohydrate, ketogenic diet program compared to a low‐fat diet on fasting lipoprotein subclasses. International Journal of Cardiology 2006;110(2):212‐6.

Weststrate 1998 {published data only}

Weststrate JA, Meijer GW. Plant sterol enriched margarines and reduction of plasma total‐and LDL‐cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects. European Journal of Clinical Nutrition 1998;52(5):334‐43.

WHEL 2007 {published data only}

Bardwell WA, Profant J, Casden DR, Dimsdale JE, Ancoli‐Israel S, Natarajan L, et al. The relative importance of specific risk factors for insomnia in women treated for early‐stage breast cancer. Psycho‐Oncology 2008;17(1):9‐18.
Caan BJ, Flatt SW, Rock CL, Ritenbaugh C, Newman V, Pierce JP, et al. Low‐energy reporting in women at risk for breast cancer recurrence. Women's Healthy Eating and Living Group. Cancer Epidemiology, Biomarkers & Prevention 2000;9(10):1091‐7.
Gold EB, Flatt SW, Pierce JP, Bardwell WA, Hajek RA, Newman VA, et al. Dietary factors and vasomotor symptoms in breast cancer survivors: the WHEL Study. Menopause 2006;13(3):423‐33.
Gold EB, Pierce JP, Natarajan L, Stefanick ML, Laughlin GA, Caan BJ, et al. Dietary pattern influences breast cancer prognosis in women without hot flashes: the women's healthy eating and living trial. Journal of Clinical Oncology 2009;27(3):352‐9.
Hernandez‐Valero MA, Thomson CA, Hernandez M, Tran T, Detry MA, Theriault RL, et al. Comparison of baseline dietary intake of Hispanic and matched non‐Hispanic white breast cancer survivors enrolled in the Women's Healthy Eating and Living study. Journal of the American Dietetic Association 2008;108(8):1323‐9.
Hong S, Bardwell WA, Natarajan L, Flatt SW, Rock CL, Newman VA, et al. Correlates of physical activity level in breast cancer survivors participating in the Women's Healthy Eating and Living (WHEL) Study. Breast Cancer Research & Treatment 2007;101(2):225‐32.
Hyder JA, Thomson CA, Natarajan L, Madlensky L, Pu M, Emond J, et al. Adopting a plant‐based diet minimally increased food costs in WHEL Study. American Journal of Health Behavior 2009;33(5):530‐9.
Madlensky L, Natarajan L, Flatt SW, Faerber S, Newman VA, Pierce JP, et al. Timing of dietary change in response to a telephone counseling intervention: evidence from the WHEL study. Health Psychology 2008;27(5):539‐47.
Mortimer JE, Flatt SW, Parker BA, Gold EB, Wasserman L, Natarajan L, et al. Tamoxifen, hot flashes and recurrence in breast cancer. Breast Cancer Research & Treatment 2008;108(3):421‐6.
Newman VA, Thomson CA, Rock CL, Flatt SW, Kealey S, Bardwell WA, et al. Achieving substantial changes in eating behavior among women previously treated for breast cancer: an overview of the intervention. Journal of the American Dietetic Association 2005;105(3):382‐91.
Paxton RJ, Jones LA, Chang S, Hernandez M, Hajek RA, Flatt SW, et al. Was race a factor in the outcomes of the Women's Health Eating and Living Study?. Cancer 2011;117(16):3805‐13.
Pierce JP. A randomized trial of the effect of a plant‐based dietary pattern on additional breast cancer events and survival: The Women's Healthy Eating and Living (WHEL) Study. Controlled Clinical Trials 2002;23(6):728‐56.
Pierce JP. Diet and breast cancer prognosis: making sense of the Women's Healthy Eating and Living and Women's Intervention Nutrition Study trials. Current Opinion in Obstetrics & Gynecology 2009;21(1):86‐91.
Pierce JP, Faerber S, Wright FA, Rock CL, Newman V, Flatt SW, et al. A randomized trial of the effect of a plant‐based dietary pattern on additional breast cancer events and survival: the Women's Healthy Eating and Living (WHEL) Study. Controlled Clinical Trials 2002;23(6):728‐56.
Pierce JP, Natarajan L, Caan BJ, Flatt SW, Kealey S, Gold EB, et al. Dietary change and reduced breast cancer events among women without hot flashes after treatment of early‐stage breast cancer: subgroup analysis of the Women's Healthy Eating and Living Study. American Journal of Clinical Nutrition 2009;89(5):1565S‐71S.
Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial. JAMA 2007;298(3):289‐98.
Pierce JP, Natarajan L, Sun S, Al‐Delaimy W, Flatt SW, Kealey S, et al. Increases in plasma carotenoid concentrations in response to a major dietary change in the women's healthy eating and living study. Cancer Epidemiology, Biomarkers & Prevention 2006;15(10):1886‐92.
Pierce JP, Newman VA, Flatt SW, Faerber S, Rock CL, Natarajan L, et al. Telephone counseling intervention increases intakes of micronutrient‐ and phytochemical‐rich vegetables, fruit and fiber in breast cancer survivors. Journal of Nutrition 2004;134(2):452‐8.
Rock CL, Flatt SW, Laughlin GA, Gold EB, Thomson CA, Natarajan L, et al. Reproductive steroid hormones and recurrence‐free survival in women with a history of breast cancer. Cancer Epidemiology, Biomarkers & Prevention 2008;17(3):614‐20.
Rock CL, Flatt SW, Newman V, Caan BJ, Haan MN, Stefanick ML, et al. Factors associated with weight gain in women after diagnosis of breast cancer. Women's Healthy Eating and Living Study Group. Journal of the American Dietetic Association 1999;99(10):1212‐21.
Rock CL, Flatt SW, Thomson CA, Stefanick ML, Newman VA, Jones L, et al. Plasma triacylglycerol and HDL cholesterol concentrations confirm self‐reported changes in carbohydrate and fat intakes in women in a diet intervention trial. Journal of Nutrition 2004;134(2):342‐7.
Rock CL, Natarajan L, Pu M, Thomson CA, Flatt SW, Caan BJ, et al. Longitudinal biological exposure to carotenoids is associated with breast cancer‐free survival in the Women's Healthy Eating and Living Study. Cancer Epidemiology, Biomarkers & Prevention 2009;18(2):486‐94.
Saquib N, Flatt SW, Natarajan L, Thomson CA, Bardwell WA, Caan B, et al. Weight gain and recovery of pre‐cancer weight after breast cancer treatments: evidence from the women's healthy eating and living (WHEL) study. Breast Cancer Research & Treatment 2007;105(2):177‐86.
Saxe GA, Madlensky L, Kealey S, Wu DP, Freeman KL, Pierce JP, et al. Disclosure to physicians of CAM use by breast cancer patients: findings from the Women's Healthy Eating and Living Study. Integrative Cancer Therapies 2008;7(3):122‐9.

WHO primary prev 1979 {published data only}

WHO Primary prevention trial. Primary prevention of ischaemic heart disease: WHO coordinated cooperative trial. A summary report. Bulletin Of The World Health Organization 1979;57(5):801‐5.

WHT 1990 {published and unpublished data}

Bowen D. The role of participation in the women's health trial: feasibility study in minority populations. Preventive Medicine 2000;31(5):474‐80.
Bowen D, Clifford CK, Coates R, Evans M, Feng Z, Fouad M, et al. The Women's Health Trial feasibility study in minority populations: design and baseline descriptions. Annals of Epidemiology 1996;6(6):507‐19.
Bowen DJ, Kestin M, McTiernan A, Carrell D, Green P. Effects of dietary fat intervention on mental health in women. Cancer Epidemiology, Biomarkers and Prevention 1995;4(5):555‐9.
Gorbach SL, Morrill LA, Woods MN, Dwyer JT, Selles WD, Henderson M, et al. Changes in food patterns during a low‐fat dietary intervention in women. Journal of the American Dietetic Association 1990;90(6):802‐9.
Henderson MM, Kushi LH, Thompson DJ, Gorbach SL, Clifford CK, Insull W, et al. Feasibility of a randomized trial of a low‐fat diet for the prevention of breast cancer: dietary compliance in the Women's Health Trial Vanguard Study. Preventive Medicine 1990;19(2):115‐33.
Insull W, Henderson MM, Prentice RL, Thompson DJ, Clifford C, Goldman S, et al. Results of a randomized feasibility study of a low‐fat diet. Archives of Internal Medicine 1990;150(2):421‐7.
Kristal AR, White E, Shattuck AL, Curry S, Anderson GL, Fowler A, et al. Long‐term maintenance of a low‐fat diet: durability of fat‐related dietary habits in the Women's Health Trial. Journal of the American Dietetic Association 1992;92(5):553‐9.
Prentice RL, Kakar F, Hursting S, Sheppard L, Klein R, Kushi LH. Aspects of the rationale for the Women's Health Trial. Journal of the National Cancer Institute 1988;80(11):802‐14.
Self S, Prentice R, Iverson D, Henderson M, Thompson D, Byar D, et al. Statistical design of the Women's Health Trial. Controlled Clininical Trials 1988;9(2):119‐36.
Sheppard L, Kristal AR, Kushi LH. Weight loss in women participating in a randomised trial of low‐fat diets. American Journal of Clinical Nutrition 1991;54(5):821‐8.
Urban N, Baker M. The Women's Health Trial as an investment. Medical Decision Making 1989;9(1):59‐64.
White E, Shattuck AL, Kristal AR, Urban N, Prentice RL, Henderson MM, et al. Maintenance of a low‐fat diet: follow‐up of the Women's Health Trial. Cancer Epidemiology, Biomarkers and Prevention 1992;1(4):315‐23.

WHT Feasibility 2003 {published and unpublished data}

Bowen D, Clifford CK, Coates R, Evans M, Feng Z, Fouad M, et al. The Women's Health Trial Feasibility Study in Minority Populations: design and baseline descriptions. Annals of Epidemiology 1996;6(6):507‐19.
Hall WD, Feng Z, George VA, Lewis CE, Oberman A, Huber M, et al. Low‐fat diet: effect on anthropometrics, blood pressure, glucose, and insulin in older women. Ethnicity and Disease 2003;13(3):337‐43.

Wilke 1974 {published data only}

Wilke H, Frahm H. Influence of low‐caloric‐diet and d‐triiodothyronine on serum lipids and body weight (author's trans) [Verhalten der Serumlipide und des Körpergewichts unter Reduktionsdiät und medikamentöser Behandlung mit D‐Trijodthyronin]. Medizinische Klinik 1974;69(48):1986‐9.

Williams 1990 {published data only}

Williams PT, Krauss RM, Vranizan KM, Wood PS. Changes in lipoprotein subfractions during diet‐induced and exercise‐induced weight loss in moderately overweight men. Circulation 1990;81(4):1293‐304.

Williams 1992 {published data only}

Williams PT, Krauss RM, Vranizan KM, Albers JJ, Wood PD. Effects of weight‐loss by exercise and by diet on apolipoproteins A‐I and A‐II and the particle‐size distribution of high‐density lipoproteins in men. Metabolism: Clinical and Experimental 1992;41(4):441‐9.

Williams 1994 {published data only}

Williams PT, Stefanick ML, Vranizan KM, Wood PD. The effects of weight loss by exercise or by dieting on plasma high‐density lipoprotein (HDL) levels in men with low, intermediate, and normal‐to‐high HDL at baseline. Metabolism 1994;43(7):917‐24.

Wilmot 1952 {published data only}

Wilmot VA, Swank RL. The influence of low fat diet on blood lipid levels in health and in multiple sclerosis. American Journal of the Medical Sciences 1952;223(1):25‐34.

Wing 1998 {published data only}

Wing RR, Venditti E, Jakicic JM, Polley BA, Lang W. Lifestyle intervention in overweight individuals with a family history of diabetes. Diabetes Care 1998;21(3):350‐9.

WINS UK 2011 {published and unpublished data}

Parry BM, Milne JM, Yadegarfar G, Rainsbury RM. Dramatic dietary fat reduction is feasible for breast cancer patients: Results of the randomised study, WINS (UK) ‐ stage 1. European Journal of Surgical Oncology 2011;37(10):848‐55.

WOMAN 2007 {published data only}

Kuller LH, Kriska AM, Kinzel LS, Simkin‐Silverman LR, Sutton‐Tyrrell K, Johnson BD, et al. The clinical trial of Women On the Move through Activity and Nutrition (WOMAN) study. Contemporary Clinical Trials 2007;28(4):370‐81.

Wood 1988 {published data only}

Wood PD, Stefanick ML, Dreon DM, Frey HB, Garay SC, Williams PT, et al. Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise. New England Journal of Medicine 1988;319(18):1173‐9.

Woollard 2003 {published data only}

Woollard J, Burke V, Beilin LJ, Verheijden M, Bulsara MK. Effects of a general practice‐based intervention on diet, body mass index and blood lipids in patients at cardiovascular risk. Journal of Cardiovascular Risk 2003;10(1):31‐40.

Working Well 1996 {published data only}

Sorensen G, Thompson B, Glanz K, Feng Z, Kinne S, DiClemente C, et al. Work site‐based cancer prevention: primary results from the Working Well Trial. American Journal of Public Health 1996;86(7):939‐47.

Zock 1995 {published and unpublished data}

Zock PL. Dietary Fatty Acids and Risk Factors for Coronary Heart Disease: Controlled Studies in Healthy Volunteers [PhD thesis]. Wageningen, Netherlands: Landbouwuniversiteit te Wageningen, 1995.
Zock PL, Mensink RP, Harryvan J, De Vries JH, Katan MB. Fatty acids in serum cholesteryl esters as quantitative biomarkers of dietary intake in humans. American Journal of Epidemiology 1997;145(12):1114‐22.

4S 1994

Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344(8934):1383‐9.

ACC/AHA 2013

Stone NJ, Robinson J, Lichtenstein AH, BaireyMerz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S1‐S45. [DOI: 10.1161/01.cir.0000437738.63853.7a]

Alonso 2006

Alonso Á, Ruiz‐Gutierrez V, Martínez‐González MÁ. Monounsaturated fatty acids, olive oil and blood pressure: epidemiological, clinical and experimental evidence. Public Health Nutrition 2006;9(2):251‐7.

Astrup 2000

Astrup A, Ryan L, Grunwald GK, Storgaard M, Saris W, Melanson E, et al. The role of dietary fat in body fatness: evidence from a preliminary meta‐analysis of ad libitum low‐fat dietary intervention studies. British Journal of Nutrition 2000;83(Suppl 1):S25‐32.

Astrup 2011

Astrup A, Dyerberg J, Elwood P, Hermansen K, Hu FB, Jakobsen MU, et al. The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010?. American Journal of Clinical Nutrition 2011;93(4):684–8.

Berkley 1995

Berkley CS, Hoaglin DC, Mosteller F, Colditz GA. A random‐effects regression model for meta‐analysis. Statistics in Medicine 1995;14(4):395‐411.

Blann 1995

Blann AD, Jackson P, Bath PM, Watts GF. von Willebrand factor, a possible indicator of endothelial cell damage, decreases during long‐term compliance with a lipid‐lowering diet. Journal of Internal Medicine 1995;237(6):557‐61.

Briel 2009

Briel M, Ferreira‐Gonzalez I, You JJ, Karanicolas PJ, Akl EA, Wu P, et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta‐regression analysis. BMJ 2009;338:b92. [DOI: 10.1136/bmj.b92]

Brunner 1997

Brunner E, White I, Thorogood M, Bristow A, Curle D, Marmot M. Can dietary interventions change diet and cardiovascular risk factors? A meta‐analysis of randomized controlled trials. American Journal of Public Health 1997;87(9):1415‐22.

Bucher 1996

Bucher HC, Cook RJ, Guyatt GH, Lang JD, Cook DJ, Hatala R, et al. Effects of dietary calcium supplementation on blood pressure: a meta‐analysis of randomised controlled trials. JAMA 1996;275(13):1016‐22.

Chalmers 1990

Chalmers I, Adams M, Dickersin K, Hetherington J, Tarnow‐Mordi W, Meinert C, et al. A cohort study of summary reports of controlled trials. JAMA 1990;263(10):1401‐5.

Clarke 1997

Clarke R, Frost C, Collins R, Appleby P, Peto R. Dietary lipids and blood cholesterol: quantitative meta‐analysis of metabolic ward studies. BMJ 1997;314(7074):112‐7.

Davey Smith 1993

Davey Smith G, Song F, Sheldon TA. Cholesterol lowering and mortality: the importance of considering initial level of risk. BMJ 1993;306(6889):1367‐73.

Dayton 1965

Dayton S, Hashimoto S, Rosenblum D, Pearce M. Vitamin E status of humans during prolonged feeding of unsaturated fats. Journal of Laboratory and Clinical Medicine 1965;65(5):739‐47.

De Caterina 2010

De Caterina R, Scarano M, Marfisi RM, Lucisano G, Palma F, Tatasciore A, et al. Cholesterol‐lowering interventions and stroke. Journal of the American College of Cardiology 2010;55(3):198‐211.

Denke 1995

Denke MA. Cholesterol‐lowering diets. A review of the evidence. Archives of Internal Medicine 1995;155(1):17‐26.

Ebrahim 1997

Ebrahim S, Davey Smith G. Systematic review of randomised controlled trials of multiple risk factor interventions for preventing coronary heart disease. BMJ 1997;314(7095):1666.

Eckel 2013

Eckel RH, Jakicic JM, Ard JD, De Jesus JM, Houston Miller N, Hubbard VS, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013;129((25 suppl 2)):S76‐99. [DOI: 10.1161/01.cir.0000437740.48606.d1]

Egger 1997

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple graphical test. BMJ 1997;315(7109):629‐34.

ESC/EAS 2011

The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). ESC/EAS Guidelines for the management of dyslipidaemias. European Heart Journal 2011;32(14):1769‐1818. [DOI: 10.1093/eurheartj/ehr158]

Fraker 2007

Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J, et al. 2007 Chronic angina: focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina. Circulation 2007;116(23):2762‐72.

Gofman 1949

Gofman JW, Lindgren FT, Elliott HA. Ultracentrifugal studies of lipoproteins of human serum. Journal of Biological Chemistry 1949;179(2):973‐9.

Harcombe 2015

Harcombe Z, Baker JS, Cooper SM, Davies B, Sculthorpe N, DiNicolantonio JJ, et al. Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977and 1983: a systematic review and meta‐analysis. Open Heart 2015;2(1):e000196. [DOI: 10.1136/openhrt‐2014‐000196]

Hauck 1991

Hauck WW, Gilliss CL, Donner A, Gortner S. Randomisation by cluster. Nursing Research 1991;40(6):356‐8.

Hegsted 1965

Hegsted DM, McGandy RB, Myers ML, Stare FJ. Quantitative effects of dietary fat on serum cholesterol in man. American Journal of Clinical Nutrition 1965;17(5):281‐95.

Hegsted 2000

Hegsted DM. From chick nutrition to nutrition policy. Annual Review of Nutrition 2000;20:1‐19.

Hession 2009

Hession M, Rolland C, Kulkarni U, Wise A, Broom J. Systematic review of randomized controlled trials of low‐carbohydrate vs. low‐fat/low‐calorie diets in the management of obesity and its comorbidities. Obesity Reviews 2009;10(1):36‐50.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60.

Higgins 2011

Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Howard 2010

Howard BV, Curb JD, Eaton CB, Kooperberg C, Ockene J, Kostis JB, et al. Low‐fat dietary pattern and lipoprotein risk factors: the Women's Health Initiative dietary modification trial. American Journal of Clinical Nutrition 2010;91(4):860‐74.

JBS3 2014

JBS3 Board. Joint British Societies' consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart 2014;100 Suppl 2:ii1‐ii67. [DOI: 10.1136/heartjnl‐2014‐305693]

Kagan 1974

Kagan A, Harris BR, Winkelstein W, Johnson KG, Kato H, Syme SL, et al. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: demographic, physical, dietary and biochemical characteristics. Journal of Chronic Disease 1974;27(7‐8):345‐64.

Kasim 1993

Kasim SE, Martino S, Kim P‐N, Khilnani S, Boomer A, Depper J, et al. Dietary and anthropometric determinants of plasma lipoproteins during a long‐term low‐fat diet in healthy women. American Journal of Clinical Nutrition 1993;57(2):146‐53.

Katan 2010

Katan MB, Brouwer IA, Clarke R, Geleijnse JM, Mensink RP. Saturated fat and heart disease. American Journal of Clinical Nutrition 2010;92(2):459‐60; author reply 460‐1.

Keys 1950

Keys A, Mickelsen O, Miller Ev, Carleton B. The relation in man between cholesterol levels in the diet and in the blood. Science 1950;112(2899):79‐81.

Keys 1986

Keys A, Menotti A, Karvonen MJ, Aravanis C, Blackburn H, Buzina Rm, et al. The diet and 15‐year death rate in the seven countries study. American Journal of Epidemiology 1986;124(6):903‐15.

Kodama 2009

Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Sato M, et al. Influence of fat and carbohydrate proportions on the metabolic profile in patients with type 2 diabetes: a meta‐analysis. Diabetes Care 2009;32(5):959‐65.

Kristal 2005

Kristal AR, Peters U, Potter JD. Is it time to abandon the food frequency questionnaire?. Cancer Epidemiology, Biomarkers and Prevention 2005;14(12):2826‐8.

Law 1991

Law MR, Frost CD, Wald NJ. By how much does dietary salt restriction lower blood pressure?. BMJ 1991;302(6780):811‐24.

Law 1994

Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease?. BMJ 1994;308(6925):367‐73.

Lefebvre 2011

Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from cochrane‐handbook.org2011.

Lenz 2007

Lenz M, Steckelberg A, Richter B, Mühlhauser I. Meta‐analysis does not allow appraisal of complex interventions in diabetes and hypertension self‐management:a methodological review. Diabetologia 2007;50(7):1375–83.

Lichtenstein 2006

Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, Franch HA, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 2006;114(1):82‐96.

Lopez‐Espinoza 1984

Lopez‐Espinoza I, Howard WJ, Mann JI, Carter RD, Hockaday TD. Fatty acid composition of platelet phospholipids in non‐insulin‐dependent diabetics randomized for dietary advice. British Journal of Nutrition 1984;52(1):41‐7.

Malhotra 2014

Malhotra A, Shafiq N, Arora A, Singh M, Kumar R, Malhotra S. Dietary interventions (plant sterols, stanols, omega‐3 fatty acids, soy protein and dietary fibers) for familial hypercholesterolaemia. Cochrane Database of Systematic Reviews 2014, Issue 6. [DOI: 10.1002/14651858.CD001918.pub3]

Marchioli 1994

Marchioli R, Prieto JC, Tognoni G. Surrogate end‐points: the case of trials on coronary atherosclerotic plaque regression. Clinical Trials and Meta‐Analyses 1994;29(2‐3):139‐76.

Mensink 1992

Mensink RP, Katan MB. Effect of dietary fatty acids on serum lipids and lipoproteins: a meta‐analysis of 27 trials. Arteriosclerosis and Thrombosis 1992;12(8):911‐9.

Mensink 2003

Mensink RP, Zock PL, Kester ADM, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta‐analysis of 60 controlled trials. American Journal of Clinical Nutrition 2003;77(5):1146‐55.

Michels 2009

Michels KB, Willett WC. The women's health initiative randomized controlled dietary modification trial: a post‐mortem. Breast Cancer Research and Treatment 2009;114(1):1‐6.

Mozaffarian 2010

Mozaffarian D, Micha R, Wallace S. Effects of coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta‐analysis of randomized controlled trials. PLOS Medicine 2010;7(3):e1000252.

Ness 1997

Ness AR, Powles JW. Fruit and vegetables, and cardiovascular disease: a review. International Journal of Epidemiology 1997;26(1):1‐13.

NICE 2014

National Institute of Health and Care Excellence. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. www.nice.org.uk/guidance/cg181/resources/guidance‐lipid‐modification‐cardiovascular‐risk‐assessment‐and‐the‐modification‐of‐blood‐lipids‐for‐the‐primary‐and‐secondary‐prevention‐of‐cardiovascular‐disease‐pdf 2014 (accessed 25th May 2015).

O'Gara 2014

O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, De Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST‐elevationmyocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013;127(4):e362‐e425. [DOI: 10.1161/CIR.0b013e3182742cf6]

Oliver 1953

Oliver MF, Boyd GS. The plasma lipids in coronary artery disease. British Heart Journal 1953;15(4):387‐90.

Oliver 2000

Oliver MF. Pioneer research in Britain into atherosclerosis and coronary heart disease ‐ an historical review. Atherosclerosis 2000;150(1):1‐12.

Patterson 2003

Patterson RE, Kristal A, Rodabough R, Caan B, Lillington L, Mossavar‐Rahmani Y, et al. Changes in food sources of dietary fat in response to an intensive low‐fat dietary intervention: early results from the Women's Health Initiative. Journal of the American Dietetic Association 2003;103(4):454‐60.

Prentice 2007

Prentice RL. Observational studies, clinical trials, and the women's health initiative. Lifetime Data Analysis 2007;13(4):449‐62.

Rees 2013

Rees K, Dyakova M, Wilson N, Ward K, Thorogood M, Brunner E. Dietary advice for reducing cardiovascular risk. Cochrane Database of Systematic Reviews 2013, Issue 12. [DOI: 10.1002/14651858.CD002128.pub5]

Rimm 1996

Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine or spirits?. BMJ 1996;312(7033):731‐6.

Robertson 1977

Robertson TL, Kato H, Rhoads GG, Kagan A, Marmot M, Syme SL, et al. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Incidence of myocardial infarction and death from coronary heart disease. American Journal of Cardiology 1977;39(2):239‐43.

Robinson 2009

Robinson JG, Wang S, Smith BJ, Jacobson TA. Meta‐analysis of the relationship between non‐high‐density lipoprotein cholesterol reduction and coronary heart disease risk. Journal of the American College of Cardiology 2009;53(4):316‐22.

Rubins 1995

Rubins HB. Cholesterol in patients with coronary heart disease: how low should we go?. Journal of General Internal Medicine 1995;10(8):464‐71.

Ryle 1949

Ryle JA, Russell WT. The natural history of coronary disease. A clinical and epidemiological study. British Heart Journal 1949;11(4):370.

Scarborough 2010

Scarborough P, Rayner M, Van Dis I, Norum K. Meta‐analysis of effect of saturated fat intake on cardiovascular disease: overadjustment obscures true associations. American Journal of Clinical Nutrition 2010;92(2):458‐9; author reply 459.

Schatzkin 2003

Schatzkin A, Kipnis V, Carroll RJ, Midthune D, Subar AF, Bingham S, et al. A comparison of a food frequency questionnaire with a 24‐hour recall for use in an epidemiological cohort study: results from the biomarker‐based Observing Protein and Energy Nutrition (OPEN) Study. International Journal of Epidemiology 2003;32(6):1054‐62.

Schwab 2014

Schwab U, Lauritzen L, Tholstrup T, Haldorssoni T, Riserus U, Uusitupa M, Becker W. Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type‐2 diabetes, cardiovascular disease, and cancer: a systematic review. Food & Nutrition Research2014; Vol. 58:25145. [DOI: 10.3402/fnr.v58.25145]

Shah 2007

Shah M, Adams‐Huet B, Garg A. Effect of high‐carbohydrate or high‐cis‐monounsaturated fat diets on blood pressure: a meta‐analysis of intervention trials. American Journal of Clinical Nutrition 2007;85(5):1251‐6.

Sharp 1998

Sharp S. Meta‐analysis regression. Stata Technical Bulletin 1998;42:16‐22.

Sheppherd 2009

Shepperd S, Lewin S, Straus S, Clarke M, Eccles MP, Fitzpatrick R, et al. Can we systematically review studies that evaluate complex interventions?. PLoS Medicine / Public Library of Science 2009;6(8):e1000086.

SIGN 1996

Scottish Intercollegiate Guidelines Network. Obesity in Scotland, integrating prevention with weight management. SIGN publication no. 81996.

Siri‐Tarino 2010

Siri‐Tarino PW, Sun Q, Hu FB, Krauss RM. Meta‐analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. American Journal of Clinical Nutrition 2010;91(3):535‐46.

Skeaff 2009

Skeaff CM, Miller J. Dietary fat and coronary heart disease: summary of evidence from prospective cohort and randomised controlled trials. Annals of Nutrition and Metabolism 2009;55(1‐3):173‐201.

Stamler 2010

Stamler J. Diet‐heart: a problematic revisit. American Journal of Clinical Nutrition 2010;91(3):497‐9.

Stein 2006

Stein K. After the media feeding frenzy: whither the Women's Health Initiative Dietary Modification Trial?. Journal of the American Dietetic Association 2006;106(6):794‐800.

Sterne 2001

Sterne JA, Bradburn MJ, Egger M. Meta‐analysis in STATA. In: Egger M, Davey Smith G, Altman DG editor(s). Systematic Reviews in Health Care: Meta‐analysis in Context. London: BMJ Books, 2001.

Sterne 2009

Sterne JA. Meta‐Analysis in Stata: an Updated Collection from the Stata Journal. Texas, USA: STATA Press, 2009.

Stovold 2014

Stovold E, Beecher D, Foxlee R, Noel‐Storr A. Study flow diagrams in Cochrane systematic review updates: an adapted PRISMA flow diagram. Systematic Reviews 2014;3:54. [DOI: 10.1186/2046‐4053‐3‐54]

Thorogood 1996

Thorogood M. Nutrition. In: Lawrence M, Neil A, Mant D, Fowler G editor(s). Prevention of Cardiovascular Disease: an Evidence‐Based Approach. Kings Lynn: Oxford University Press, 1996:54‐66.

Walsh 1995

Walsh JME, Grady D. Treatment of hyperlipidaemia in women. JAMA 1995;274(14):1152‐8.

Weggemans 2001

Weggemans RM, Zock PL, Katan MB. Dietary cholesterol from eggs increases the ratio of total cholesterol to high‐density lipoprotein cholesterol in humans: a meta‐analysis. American Journal of Clinical Nutrition 2001;73(5):885‐91.

Yngve 2006

Yngve A, Hambraeus L, Lissner L, Serra Majem L, Vaz de Almeida MD, Berg C, et al. Invited Commentary. The Women's Health Initiative. What is on trial: nutrition and chronic disease? Or misinterpreted science, media havoc and the sound of silence from peers. Public Health Nutrition 2006;9(2):269‐72.

Yu‐Poth 1999

Yu‐Poth S, Zhao G, Etherton T, Naglak M, Jonnalagadda S, Kris‐Etherton PM. Effects of the National Cholesterol Education Program's Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta‐analysis. American Journal of Clinical Nutrition 1999;69(4):632‐46.

References to other published versions of this review

Jump to:

Hooper 2000

Hooper L, Summerbell CD, Higgins JPT, Thompson RL, Clements G, Capps N, et al. Reduced or modified dietary fat for preventing of cardiovascular disease. Cochrane Database of Systematic Reviews 2000, Issue 2. [DOI: 10.1002/14651858.CD002137]

Hooper 2001

Hooper L, Summerbell CD, Higgins JPT, Thompson RL, Capps N, Davey Smith G, et al. Dietary fat intake and prevention of cardiovascular disease: systematic review. BMJ 2001;322(7289):757‐63.

Hooper 2011

Hooper L, Summerbell CD, Thompson R, Sills D, Roberts FG, Moore HJ, et al. Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database of Systematic Reviews 2011, Issue 7. [DOI: 10.1002/14651858.CD002137.pub2]

Hooper 2012

Hooper L, Summerbell CD, Thompson R, Sills D, Roberts FG, Moore HJ, et al. Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database of Systematic Reviews 2012, Issue 5. [DOI: 10.1002/14651858.CD002137.pub3]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Jump to:

Black 1994

Methods

RCT

Participants

People with non‐melanoma skin cancer (USA)
CVD risk: low
Control: randomised 67, analysed 58
Intervention: randomised 66, analysed 57
Mean years in trial: 1.9
% male: control 67%, intervention 54%
Age: mean control 52.3 (SD 13.2), intervention 50.6 (SD 9.7)

Ethnicity: white 100% (excluded from study if of Asian, Black, Hispanic or American Indian ancestry)

Statins use allowed: Unclear

% taking statins: Not reported

Interventions

Reduced fat vs usual diet

Control aims: no dietary advice
Intervention aims: total fat 20%E, protein 15%E, CHO 65%E

Control methods: no dietary change, 4‐month intervals clinic examination by dermatologist

Intervention methods: 8 x weekly classes plus monthly follow‐up sessions, with behavioural techniques being taught following individual approach (not clear if in a group or individual). 4‐month intervals clinic examination by dermatologist

Intervention delivered face‐to‐face by a dietitian

Total fat intake, %E ("during study" months 4 ‐ 24): cont 37.8 (SD 4.1), int 20.7 (SD 5.5) (mean difference ‐17.10, 95% CI ‐18.88 to ‐15.32) significant reduction

Saturated fat intake, %E ("during study", months 4 ‐ 24): cont 12.8 (SD 2.0), int 6.6 (SD 1.8), (mean difference ‐6.20, 95% CI ‐6.90 to ‐5.50) significant reduction

PUFA intake, %E ("during study", months 4 ‐ 24): cont 7.8 (SD 1.4), int 4.5 (SD 1.3), (mean difference ‐3.30, 95% CI ‐3.79 to ‐2.81) significant reduction

PUFA n‐3 intake: not reported

PUFA n‐6 intake: Linoleic acid, Control 16.9 (SD 5.6) g, Int 8.5 (SD 3.3) g

MUFA intake, %E ("during study", months 4 ‐ 24): cont 14.4 (SD 1.7), int 7.6 (SD 2.2), (mean difference ‐6.80, 95% CI ‐7.52 to ‐6.08) significant reduction

CHO intake, %E ("during study", months 4 ‐ 24): cont 44.6 (SD 6.9), int 60.3 (SD 6.3), (mean difference 15.70, 95% CI 13.29 to 18.11) significant increase

Protein intake, %E ("during study", months 4 ‐ 24): cont 15.7 (SD 2.4), int 17.7 (SD 2.2), (mean difference 2.00, 95% CI 1.16 to 2.84) significant increase

Trans fat intake: not reported

Replacement for saturated fat: CHO and protein (by dietary aims and achievements)

Style: diet advice

Setting: community

Outcomes

Stated trial outcomes: incidence of actinic keratosis and non‐melanoma skin cancer
Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: cardiovascular deaths

Secondary outcomes: cancer deaths (none)

Tertiary outcomes: none (weight data provided, but no variance info)

Notes

Study duration 24 months.

Study aim was to achieve low‐fat diet, but the study achieved a statistically significant reduction in saturated fat intake in the low‐fat group compared to control.

SFA reduction achieved.

Total serum cholesterol: not reported

At 2 years control ‐1.5 kg n = 50?, intervention ‐1 kg n = 51?

Trial dates: Study dates not reported (but still recruiting at first publication in 1994)

Funding: National Cancer Institute

Declarations of Interest of primary researchers: none stated, all authors work for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"list of randomly generated numbers"

Allocation concealment (selection bias)

Unclear risk

Randomisation method not clearly described

Blinding (performance bias and detection bias)
All outcomes

High risk

Physician blinding: adequate
Participant blinding: inadequate

Incomplete outcome data (attrition bias)
All outcomes

Low risk

For mortality. Unclear for other outcomes

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists asked for data

Free of systematic difference in care?

High risk

Minor, all have 4‐monthly clinic visits, the intervention group had 8 behavioural technique classes that the control group did not have

Stated aim to reduce SFA

High risk

Aim to reduce SFA not stated

Achieved SFA reduction

Low risk

Statistically significant SFA reduction achieved

Achieved TC reduction

Unclear risk

Not reported

Other bias

Low risk

None noted
DART 1989

Methods

Factorial RCT

Participants

Men recovering from an MI (UK)
CVD risk: high
Control: randomised 1015, analysed unclear
Intervention: randomised 1018, analysed unclear
Mean years in trial: control 1.9, randomised 1.9
% male: 100%
Age: mean control 56.8, intervention 56.4 < 70)

Ethnicity: not stated

Statins use allowed? Unclear, but there do not appear to have been any medication‐based exclusion criteria and included participants were taking anti‐hypertensives, anti‐anginals, anti‐coagulants, anti‐platelet, digoxin and "other cardiac drugs".

% taking statins: Not reported, but only 5.4% were taking "other cardiac drugs" which may have included statins

Interventions

Reduced and modified fat vs usual diet

Control aims: no dietary advice on fat, weight reducing advice if BMI > 30
Intervention aims: reduce fat intake to 30%E, increase P/S to 1.0, weight‐reducing advice if BMI > 30

Note: This was a factorial trial, and so some in each group were randomised to increased fatty fish and/or increased cereal fibre.

Control methods: dietitians provided 'sensible eating' advice without specific information on fats

Intervention methods: dietitians provided the participants and their wives with initial individual advice and a diet information sheet; participants were revisited for further advice, recipes, encouragement at 1, 3, 6, 9, 12, 15, 18 and 21 months

Intervention delivered individually face‐to‐face by a dietitian

Total fat intake, %E (through study): cont 35 (SD 6), int 31 (SD 7) (mean difference ‐4.00, 95% CI ‐4.57 to ‐3.43) significant reduction

Saturated fat intake, %E (through study): cont 15 (SD3), int 11 (SD3), (mean difference ‐4.00, 95% CI ‐4.26 to ‐3.74) significant reduction

PUFA intake (through study)⁑: cont 7 (SD unclear), int 9 (SD unclear), (mean difference 2.00, 95% CI 1.57 to 2.43 assuming SDs of 5) significant increase

PUFA n‐3 intake: EPA, Control 0.6 (SD 0.7) g/wk, Int 2.4 (SD 1.4) g/wk

PUFA n‐6 intake: not reported

MUFA intake (through study)⁑: cont 13 (SD unclear), int 11 (SD unclear) (mean difference ‐2.00, 95% CI ‐2.43 to ‐1.57 assuming SDs of 5) significant reduction

CHO intake (through study): cont 44 (SD 6),int 46 (SD 7) (mean difference 2.00, 95% CI 1.43 to 2.57) significant increase

Protein intake (through study): cont 17 (SD 4), int 18 (SD 4) (mean difference 1.00, 95% CI 0.65 to 1.35) significant increase

Trans fat intake: not reported

Replacement for saturated fat: PUFA and CHO (by dietary aims), PUFA, CHO and protein (by dietary achievements)

Style: diet advice

Setting: community

Outcomes

Stated trial outcomes: mortality, reinfarction
Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: cardiovascular deaths (including stroke deaths) plus non‐fatal MI

Secondary outcomes: cancer deaths, total MI, non‐fatal MI, CHD mortality, CHD events (total MI)

Tertiary outcomes: total and HDL cholesterol

Notes

Study duration 24 months

Study aim was to achieve low fat diet with raised P/S ratio and saturated fat intake in the intervention group was significantly lower than in the control group.

SFA reduction aimed and achieved.

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.26 (95% CI ‐0.36 to ‐0.16), statistically significant reduction

⁑Estimated by subtraction (assuming total fat = SFA + PUFA + MUFA) or using the ratio (assuming P/S = PUFA/SFA)

Trial dates: Study dates not reported (published in 1989)

Funding: Welsh Scheme for the Development of Health and Social Research, Welsh Heart Research Foundation, Flora Project, Health Promotion Research Trust. (Seven Seas Health Care and Duncan Flockhart provided the MaxEPA capsules and Norgene provided 'Fybranta' tablets ‐ but these were not used in the comparison discussed in this systematic review)

Declarations of Interest of primary researchers: none stated, all authors work for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

randomised using sealed envelopes

Allocation concealment (selection bias)

Unclear risk

Unclear if envelopes were opaque

Blinding (performance bias and detection bias)
All outcomes

High risk

Physician blinding: yes
Participant blinding: unclear

Incomplete outcome data (attrition bias)
All outcomes

Low risk

GPs contacted for information on mortality and morbidity when participants did not attend

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as we asked all trialists for data

Free of systematic difference in care?

High risk

Different levels of advice appear to have been provided. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

Low risk

Statistically significant TC fall

Other bias

Low risk

None noted
Houtsmuller 1979

Methods

RCT

Participants

Adults with newly‐diagnosed diabetes (The Netherlands)
CVD risk: moderate

Control: 51 randomised, unclear how many analysed (all analysed re deaths)
Intervention: 51 randomised, unclear how many analysed (all re deaths)

Mean years in trial: unclear (max duration 6 years)
% male: 56% overall
Age: mean unclear

Baseline total fat intake: int cont

Baseline saturated fat intake: int cont

Ethnicity: not stated

Statins use allowed? Unclear

% taking statins: Not reported (probably none as too early, pre‐1980)

Interventions

Modified fat vs usual diet

Control aims: SFA 35%E, CHO 50%E, protein 15%E
Intervention aims: total fat 40%E, 1/3 linoleic acid, CHO 45%E, protein 15%E

Control methods: unclear, surveyed by dietitian

Intervention methods: unclear, surveyed by dietitian

Intervention appears to be delivered by dietitian but no clear details on format or frequency.

Total fat intake: not reported

Saturated fat intake: not reported (mean difference unclear)

PUFA intake: not reported

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake: not reported

CHO intake: not reported

Protein intake: not reported

Trans fat intake: not reported

Replacement for saturated fat: mainly PUFA (based on dietary aims)

Style: diet advice?

Setting: community

Outcomes

Stated trial outcomes: progression of diabetic retinopathy
Data available on total mortality? no
Cardiovascular mortality? no
Events available for combined cardiovascular events: total MI and angina

Secondary outcomes: total cholesterol, TGs (data read off graph), CHD mortality (fatal MI), CHD events (MI, angina)

Notes

Study duration 6 years. Study aim was for control group to take 35%E as saturated fat, and the intervention group 40%E from fat, of which 33% was from linoleic acid (so saturated fat < 27%E), but saturated fat intake during trial not reported

SFA reduction aimed (unclear whether achieved).

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.47(95% CI ‐0.76 to ‐0.18), statistically significant reduction

Trial dates: Study recruitment 1973 to (unclear)

Funding: Dutch Heart Foundation

Declarations of Interest of primary researchers: none stated, all authors work for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Participants matched in pairs then randomised

Allocation concealment (selection bias)

Unclear risk

Randomisation method not clearly described

Blinding (performance bias and detection bias)
All outcomes

High risk

Neither participants nor physicians appear blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Unclear, deaths, cancer and CV events are drop‐outs, trialists asked for data ‐ unclear if any data missing

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as we asked all trialists for data

Free of systematic difference in care?

Unclear risk

Level and type of intervention unclear. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Unclear risk

SFA intake not reported

Achieved TC reduction

Low risk

Statistically significant TC fall

Other bias

Low risk

None noted
Ley 2004

Methods

RCT

Participants

People with impaired glucose intolerance or high normal blood glucose (New Zealand)
CVD risk: moderate
Control: unclear how many randomised (176 between both groups), unclear how many analysed (112 between both groups at 5 years)
Intervention: as above
Mean years in trial: 4.1 over whole trial
% male: control 80%, intervention 68%
Age: mean control 52.0 (SE 0.8), intervention 52.5 (SE 0.8)

Ethnicity: European 67% int, 77% control, Maori 11% int, 7% control, Pacific islander 20% int, 13% control, Other 3% int, 4% control (outcomes not provided by ethnicity)

Statins use allowed? Unclear

% taking statins: Not reported

Interventions

Reduced fat vs usual diet

Control aims: usual diet
Intervention aims: reduced fat diet (no specific goal stated)

Control methods: usual intake plus general advice on healthy eating consistent with the New Zealand guidelines and standard dietary information for people with nutrition‐related problems upon entering the trial

Intervention methods: monthly small group meetings to follow a 1‐year structured programme aimed at reducing fat in the diet, includes education, personal goal setting, self monitoring

Total fat intake, %E (at 1 year): int 26.1 (SD 7.7), cont 33.6 (SD 7.8) (mean difference ‐7.50, 95% CI ‐10.37 to ‐4.63) significant reduction

Intervention delivered in small face‐to‐face groups but unclear by whom

Saturated fat intake, %E (at 1 year): cont 13.4 (SD 4.7), int 10.0 (SD 4.2) (mean difference ‐3.40, 95% CI ‐5.05 to ‐1.75) significant reduction

PUFA intake, %E (at 1 year): cont 4.8 (SD 1.6), int 4.0 (SD 1.4) (mean difference ‐0.80, 95% CI ‐1.36 to ‐0.24) significant reduction

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake, %E (at 1 year): cont 11.8 (SD 3.1), int 8.9 (SD 2.8) (mean difference ‐2.90, 95% CI ‐3.99 to ‐1.81) significant reduction

CHO intake, %E (at 1 year): cont 45.8 (SD 10.9), int 54.2 (SD 10.5) (mean difference 8.40, 95% CI 4.44 to 12.36) significant increase

Protein intake, %E (at 1 year): cont 16.6 (SD 3.9), int 18.4 (SD 3.5), (mean difference 1.80, 95% CI 0.43 to 3.17) significant increase

Trans fat intake: not reported

Replacement for saturated fat: carbohydrate and protein (based on dietary achievements)

Style: diet advice

Setting: community

Outcomes

Stated trial outcomes: lipids, glucose, blood pressure
Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: MI, angina, stroke, heart failure

Secondary outcomes: total MI, stroke, cancer diagnoses, cancer deaths, CHD events (MI or angina)

Tertiary outcomes: weight, total, LDL and HDL cholesterol, TGs, BP

Notes

Study duration over 4 years

Study aim was to reduce total fat (not saturated fat), but saturated fat intake in the intervention group was significantly lower than in the control group.

SFA reduction achieved.

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.05 (95% CI ‐0.46 to 0.36), NO statistically significant reduction and smaller than 0.20

Trial dates: Recruitment 1988 to 1990

Funding: National Heart Foundation of New Zealand, Aukland Medical Research Foundation, Lotteries Medical Board and the Health Research Council of New Zealand.

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Unmarked opaque envelopes were opened by the person recruiting, unable to alter allocation later

Allocation concealment (selection bias)

Low risk

Unmarked opaque envelopes were opened by the person recruiting, unable to alter allocation later

Blinding (performance bias and detection bias)
All outcomes

High risk

Participants were not blinded, outcome assessors were

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Unclear, deaths, cancer and CV events are drop‐outs, trialists were asked for data ‐ unclear if any data missing

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as we asked all trialists for data

Free of systematic difference in care?

High risk

See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

High risk

Aim to reduce SFA not stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

High risk

TC fall small (0.05 mmol/L only) and not statistically significant

Other bias

Low risk

None noted
Moy 2001

Methods

RCT

Participants

Middle‐aged siblings of people with early CHD, with at least 1 CVD risk factor (USA)
CVD risk: moderate
Control: randomised 132, analysed 118
Intervention: randomised 135, analysed 117
Mean years in trial: 1.9
% male: control 49%, intervention 55%
Age: control mean 45.7 (SD 7), intervention 46.2 (SD 7)

Ethnicity: African‐American 18% int, 25% control (remainder of group ethnicity not described, and outcomes not presented by ethnicity)

Statins use allowed? Unclear (raised LDL cholesterol was a condition of entry, so use of statins probably minimal)

% taking statins: Not reported

Interventions

Reduced fat intake vs usual diet

Control aim: usual care

Intervention aim: total fat 40 g/d or less

Control methods: usual physician care with risk factor management at 0, 1 and 2 years

Intervention methods: Individualised counselling by trained nurse, appointments 6 ‐ 8 weekly for 2 years

Intervention delivered individually, face‐to‐face by a trained nurse.

Total fat intake, %E (at 2 years): int 34.1 (SD unclear), cont 38.0 (SD unclear) (mean difference ‐3.90, 95% CI ‐6.46 to ‐1.34 assuming SDs of 10) significant reduction

Saturated fat intake, %E (at 2 years): int 11.5 (SD unclear), cont 14.4 (SD unclear) (mean difference ‐2.90, 95% CI ‐4.18 to ‐1.62 assuming SDs of 5) significant reduction

PUFA intake: not reported

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake: not reported

CHO intake: not reported

Protein intake: not reported

Trans fat intake: not reported

Replacement for saturated fat: unclear

Style: diet advice

Setting: community

Outcomes

Stated trial outcomes: dietary intake
Data available on total mortality? yes, no deaths
Cardiovascular mortality? yes, no deaths
Events available for combined cardiovascular events: total MI, stroke, unstable angina, PVD and PTCA

Secondary outcomes: cancer diagnoses (no events), cancer deaths (none), stroke, total and non‐fatal MI, CHD mortality (none), CHD events (MI or angina)

Tertiary outcomes: BMI, HDL and LDL cholesterol, TG

Notes

Study duration 2 years

Study aim was to reduce total fat based on ATPII dietary guidelines, and preliminary work established that this intervention reduced saturated fat and dietary cholesterol, and saturated fat intake was significantly lower than in the control group

SFA reduction aimed and achieved

Total serum cholesterol not reported, but LDL was, difference between intervention and control, mmol/L: ‐0.29 (95% CI ‐0.54 to ‐0.04), statistically significant reduction

Trial dates: Study recruitment 1991 to 1994

Funding: National Institute of Nursing Research, General Clinical Research Center of the National Institutes of Health

Declarations of Interest of primary researchers: none stated, all authors work for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomly assigned via computerised schema after all eligible siblings from a family had been screened

Allocation concealment (selection bias)

Unclear risk

Randomisation method not clearly described

Blinding (performance bias and detection bias)
All outcomes

High risk

Participants and trialists clear about their allocation

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Unclear, deaths, cancer and CV events are drop‐outs, trialists were asked for data ‐ unclear if any data missing

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists asked for data

Free of systematic difference in care?

High risk

Differences in frequency of follow up, but unclear what differences in care occurred between the physician and nurse‐led care. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

Low risk

Statistically significant LDL fall (though TC not reported)

Other bias

Low risk

None noted
MRC 1968

Methods

RCT

Participants

Free‐living men who have survived a first MI (UK)
CVD risk: high
Control: randomised 194, analysed 181 at 2 years
Intervention: randomised 199, analysed 172 at 2 years
Mean years in trial: control 3.7, intervention 3.8
% male: 100
Age: unclear (all < 60)

Ethnicity: not stated

Statins use allowed? Unclear (anti‐coagulants allowed, but few other medications appear to have been used)

% taking statins: Not reported (probably none as too early, pre‐1980)

Interventions

Modified fat vs usual diet

Control aims: usual diet
Intervention aims: reduce dietary fat to 35 g fat per day, add 84 g soya oil per day

Control methods: usual diet plus reducing diet (reduced CHO) for weight management for overweight men

Intervention methods: instructed to follow a dietary regimen removing saturated fat from the diet plus daily dose of 85 g soya oil; half of it had to be taken unheated. Reduced CHO diet for weight management in overweight men

Intervention appears to be delivered and supervised by trial dietitian but unclear how often.

Total fat intake, %E (at 3.5 years): int 46 (SD unclear), cont 43 (SD unclear) (mean difference 3.00, 95% CI 0.91 to 5.09 assuming SDs of 10) significant increase

Saturated fat intake: not reported (mean difference unclear)

PUFA intake: not reported

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake: not reported

CHO intake: not reported

Protein intake: not reported

Trans fat intake: not reported

Replacement for saturated fat: mainly PUFA (based on dietary goals)

Style: diet advice & supplement (soy oil)

Setting: community

Outcomes

Stated trial outcomes: MI or sudden death
Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: cardiovascular deaths and fatal or non‐fatal MI

Secondary outcomes: total and non‐fatal MI, stroke, cancer deaths, CHD mortality, CHD events (CHD mortality or non‐fatal MI)

Tertiary outcomes: none (data for weight, total cholesterol and BP, but no variance info)

Notes

Study duration over 6 years

Study aim for intervention "saturated fats were replaced by polyunsaturated fats", but saturated fat intakes during trial were not reported.

SFA reduction aimed

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.64 (95% CI unclear), reduction > 0.20

For all, data at 4 years, control n = 89, intervention n = 88

Weight change: control ‐3 kg, intervention 0 kg

Total cholesterol change: control ‐0.47 mmol/L, intervention ‐1.11 mmol/L

Systolic BP change: control 0 mmHg, intervention +2 mmHg

Diastolic BP change: control +3 mmHg, intervention ‐1 mmHg

Trial dates: Study recruitment 1960 to 1965, analysed 1967

Funding: Medical Research Council

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"using random numbers, by blocks within hospitals"

Allocation concealment (selection bias)

Unclear risk

Randomisation method not clearly described

Blinding (performance bias and detection bias)
All outcomes

High risk

Physician blinding: adequate
Participant blinding: inadequate

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Data collection was thorough, but some participants dropped out and contact was lost, so some events may have been missed

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

High risk

Unlikely as control group continued diet as usual, intervention group were likely to have had additional contact. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Unclear risk

SFA intake not reported

Achieved TC reduction

Low risk

Although statistical significance was not reported or calculable, TC in the intervention group was 0.64 mmol/L lower than in the control group, a large fall (and almost certainly statistically significant)

Other bias

Low risk

None noted
Oslo Diet‐Heart 1966

Methods

RCT

Participants

Men with previous MI (Norway)
CVD risk: high
Control: randomised 206, analysed 148 (at 5 years)
Intervention: randomised 206, analysed 152 (at 5 years)
Mean years in trial: control 4.3, intervention 4.3
% male: 100
age: mean control 56.3, intervention 56.2 (all 30 ‐ 67)

Ethnicity: ethnicity not mentioned

Statins use allowed? Unclear (medications not mentioned as exclusion criteria, most appeared to be on anti‐coagulant medications, statins not mentioned)

% taking statins: Not reported (probably none as too early, pre‐1980)

Interventions

Modified fat diet vs control

Control aims: no dietary advice but direct questions answered, supplement = 1 vitamin tablet daily
Intervention aims: reduce meat and dairy fats, increase fish, vegetables, supplement ‐ 1 vitamin tablet daily, 0.5 L soy bean oil per week (free to 25% of participants), sardines in cod liver oil (free at certain times to encourage compliance)

Control methods: usual diet

Intervention methods: continuous instruction and supervision by dietitian, including home visits, letters and phone calls

Total fat intake: unclear (note ‐ intake of total fat, carbohydrate, protein and sugar was assessed in 17 "especially conscientious and positive" as well as intelligent dieters, but this is not reported here as unlikely to be representative, and lacking control group data)

Saturated fat intake: unclear (mean difference unclear)

PUFA intake: unclear

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake: unclear

CHO intake: unclear

Protein intake: unclear

Trans fat intake: unclear

Replacement for saturated fat: PUFA (based on dietary goals)

Style: diet advice and supplement (food)

Setting: community

Outcomes

Stated trial outcomes: coronary heart disease morbidity and mortality
Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: total MI, sudden death, stroke, angina

Secondary outcomes: non‐fatal and total MI, stroke, CHD mortality (fatal MI and sudden death), CHD events (MI, angina and sudden death)

Tertiary outcomes: weight, total cholesterol, systolic and diastolic BP (but no variance information is provided)

Notes

Study duration over 4 years

Study aim was to reduce serum cholesterol by a diet "low in saturated fats and in cholesterol, and rich in highly unsaturated fats", saturated fat intakes during study were not reported

SFA reduction aimed (reduction unclear as not measured except in a highly compliant subgroup)

Total serum cholesterol, difference between intervention and control, mmol/L: ‐1.07 (95% CI unclear), reduction > 0.20

Weight change from baseline was ‐0.5 kg in the control group (n ˜ 155), ‐2.5 kg in the intervention group (n ˜ 160) to 51 months

Total cholesterol change from baseline was ‐0.46 mmol/L in the control group and ‐1.53 mmol/L in the intervention group at 51 months

Systolic BP at baseline was 153.8 mmHg in control and 159.0 in intervention, and mean sBP through trial was 154.3 mmHg in control and 158.2 mmHg in the intervention group

Diastolic BP at baseline was 93.5 mmHg in control and 97.1 mmHg in intervention, through trial mean dBP was 95.5 mmHg in control and 98.6 mmHg in intervention participants

Trial dates: Recruitment 1956 to 1958

Funding: Det Norske Råd for Hjerte‐ og karsyk‐dommer, A/S Freia Chokoladefabriks Arbeidsfond for Ernærings‐forskning, JL Tiedemanns Tobaksfabrik Joh H Andresens medisinske fond, plus A/S Farmacöytisk Industri provided a multivitamin free of charge, DE‐NO‐FA and Lillleborg Fabriker provided soy bean oil at reduced prices, the Research Laboratory of the Norwegian Canning Industry, Stavanger Preserving Co and Kommendal Packing Comp provided Norwegian sardines in cod liver oil free to those in the intervention group.

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"table of random numbers used", by Prof Knut Westlund

Allocation concealment (selection bias)

Low risk

Randomisation appears to have occurred before medical examination within the study

Blinding (performance bias and detection bias)
All outcomes

High risk

Participants were aware of their allocation as was the main trialist. Outcomes were categorised by a diagnostic board, but their blinded status was unclear

Incomplete outcome data (attrition bias)
All outcomes

Low risk

The participants who could not be directly followed up for the 5 years were followed until death or study end through personal interviews, or contact with their physicians or relatives

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

High risk

Dietetic input level very different, although medical care appeared similar. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Unclear risk

SFA intake not reported

Achieved TC reduction

Low risk

Although statistical significance was not reported or calculable, TC in the intervention group was 1.07 mmol/L lower than in the control group, a large fall (and almost certainly statistically significant)

Other bias

Low risk

None noted
Oxford Retinopathy 1978

Methods

RCT

Participants

Newly‐diagnosed non‐insulin‐dependent diabetics (UK)
CVD risk: moderate
Control: randomised unclear (249 split between the 2 groups, 125?), analysed for mortality unclear (all but 2 overall at 16 years)
Intervention: randomised unclear (249 split between the 2 groups, 125?), analysed as above
Mean years in trial: overall 9.3?
% male: overall 49
Age: mean overall 47.1 (all < 65)

Ethnicity: not stated

Statins use allowed? Unclear

% taking statins: Not reported (probably none as too early, pre‐1980)

Interventions

Reduced and modified dietary fat vs average diet

Control aims: total fat 40%E, PUFA 12%E, protein 20%E, CHO 40%E (reducing simple sugars), 1500 kcal/day
Intervention aims: total fat 26%E, PUFA 16%E, protein 20%E, CHO 54%E (reducing simple sugars), 1500 kcal/day

Control methods: dietary advice from diabetes dietitian

Intervention methods: dietary advice from diabetes dietitian

Total fat intake, %E (at 7 ‐ 9 years)§: int 32 (SD unclear), cont 41 (SD unclear) (mean difference ‐9.00, 95% CI ‐11.48 to ‐6.52 assuming SDs of 10) significant reduction

Saturated fat intake, %E (at 7 ‐ 9 years)§: int 10.7 (SD unclear), cont 20.4 (SD unclear) (mean difference ‐9.70, 95% CI ‐10.94 to ‐8.46 assuming SD of 5) significant reduction

PUFA intake, %E (at 7 ‐ 9 years)§: int 11.8 (SD unclear), cont 2.1 (SD unclear) (mean difference 9.70, 95% CI 8.46 to 10.94 assuming SDs of 5) significant increase

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake, %E (at 7 ‐ 9 years)§: int 9.5 (SD unclear), cont 18.6 (SD unclear) (mean difference ‐9.10, 95% CI ‐10.34 to 7.86 assuming SDs of 5) significant reduction

Carbohydrate intake: not reported

Protein intake: not reported

Trans fat intake: not reported

Replacement for saturated fat: PUFA and CHO (based on dietary goals and achievements)

Style: diet advice

Setting: community (outpatients clinic)

Outcomes

Stated trial outcomes: retinopathy
Data available on total mortality? yes, but unable to ascertain from which intervention groups (34 deaths at 10 years)
Cardiovascular mortality? no
Events available for combined cardiovascular events: none

Secondary outcomes: none

Tertiary outcomes: BMI, total cholesterol

Notes

Study duration over 9 years

Study aim was to reduce total fat and increase PUFAs (so reducing saturates), and saturated fat intake in the intervention group was significantly lower than in the control group

SFA reduction achieved.

Total serum cholesterol, difference between intervention and control, mmol/L: 0.07 (95% CI ‐0.34 to 0.48), NO statistically significant reduction and smaller than 0.20

§validity of these data is questionable as it represents only 3 intervention and 3 control participants. Source: Lopez‐Espinoza 1984

Trial dates: Recruitment 1973 to 1976

Funding: Oxford Diabetes Trust, British Diabetic Association, International Sugar Research Foundation Inc

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"random number sequence, provided and allotted by a separate agency" (Prof Richard Peto)

Allocation concealment (selection bias)

Low risk

"random number sequence, provided and allotted by a separate agency" (Prof Richard Peto)

Blinding (performance bias and detection bias)
All outcomes

High risk

Participants not blinded, physicians unclear

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Unclear, deaths, cancer and CV events are drop‐outs ‐ unclear if any data missing

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

Low risk

Dietetic advice for both groups. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

High risk

Aim to reduce SFA not stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

High risk

No statistically significant TC fall, and difference only 0.07 mmol/L

Other bias

Low risk

None noted
Rose corn oil 1965

Methods

RCT

Participants

Men (?) with angina or following MI (UK)
CVD risk: high
Control: randomised 26, analysed 18

Intervention ‐ corn: randomised 26, analysed 13
Mean years in trial: control 1.7, corn 1.5
% male: unclear (100%?)
Age: mean control 58.8, corn 52.6 (all <70)

Ethnicity: not stated

Statins use allowed? Unclear (anti‐coagulants not allowed, but all participants received conventional treatments at the discretion of their physicians)

% taking statins: Not reported (probably none as too early, pre‐1980)

Interventions

Modified fat vs usual diet

Control aims: usual diet

Intervention aims ‐ corn: restrict dietary fat, plus 80 g/day corn oil provided

Control methods: usual physician care plus follow‐up clinic monthly, then every 2 months, no dietary fat advice or oil provided

Intervention methods: usual physician care plus follow‐up clinic monthly, then every 2 months, dietary fat advice plus oil provided

Unclear how the advice was delivered or by whom

Total fat intake, %E (at 18 months): corn 50.5 (SD unclear), cont 32.6 (SD unclear) (mean difference 17.90, 95% CI 10.77 to 25.03 assuming SDs of 10) significant increase

Saturated fat intake: unclear (mean difference unclear)

PUFA intake: unclear

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake: unclear

CHO intake, %E (at 18 months): corn 36.5 (SD unclear), cont 51.5 (|SD unclear) (mean difference ‐15.00, 95% CI ‐29.27 to ‐0.73 assuming SDs of 20) significant reduction

Protein intake, %E (at 18 months): corn 11.0 (SD unclear), cont 13.2 (SD unclear) (mean difference ‐2.20, 95% CI ‐5.77 to 1.37 assuming SDs of 5) no significant difference

Trans fat intake: unclear

Replacement for saturated fat: mainly PUFA (based on aims and achievements)

Style: diet advice and supplement (oil)

Setting: community

Outcomes

Stated trial outcomes: cardiac events
Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: cardiovascular deaths, non‐fatal MI, angina, stroke

Secondary outcomes: stroke (none), non‐fatal and total MI, CHD mortality (fatal MI and sudden death), CHD events (all MI and sudden death)

Tertiary outcomes: total cholesterol

Notes

Study duration 2 years

Study aim was to reduce total fat (by restricting fatty meat, sausages, pastry, ice cream, cheese, cake, milk, eggs and butter) and prescribe vegetable oil (so reducing saturates), but saturated fat intakes during intervention were not reported

SFA reduction aimed (but unclear whether achieved as SFA intake not reported)

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.58 (95% CI ‐1.42 to 0.26), NO statistically significant reduction but > 0.20

Trial dates: unclear, published in 1965

Funding: probably unfunded (they thank the Paddington General Hospital for clinic facilities, and St Mary's and Paddington General Hospital physicians for referral of patients, but no funding acknowledged)

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"sealed envelopes"

Allocation concealment (selection bias)

Unclear risk

Unclear if envelopes were opaque

Blinding (performance bias and detection bias)
All outcomes

High risk

Physician blinding: inadequate
Participant blinding: inadequate

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Some lost to follow‐up by 2 years, so some events may have been missed

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

Low risk

All received conventional treatments at the discretion of the physicians, all attended a special follow‐up clinic. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Unclear risk

SFA intake not reported

Achieved TC reduction

High risk

Although the TC in the intervention group was 0.58 mmol/L lower than in the control group, this was not statistically significant in this small study

Other bias

Low risk

None noted
Rose olive 1965

Methods

RCT

Participants

Men (?) with angina or following MI (UK)
CVD risk: high
Control: randomised 26, analysed 18
Intervention ‐ olive: randomised 28, analysed 12

Mean years in trial: control 1.7, olive 1.5
% male: unclear (100%?)
Age: mean control 58.8, olive 55.0 (all < 70)

Ethnicity: Not stated

Statins use allowed? Unclear (anti‐coagulants not allowed, but all participants received conventional treatments at the discretion of their physicians)

% taking statins: Not reported (probably none as too early, pre‐1980)

Interventions

Modified fat vs usual diet

Control aims: usual diet
Intervention aims ‐olive: restrict dietary fat, plus 80 g/day olive oil provided

Control methods: usual physician care plus follow‐up clinic monthly, then every 2 months, no dietary fat advice or oil provided

Intervention methods: usual physician care plus follow‐up clinic monthly, then every 2 months, dietary fat advice plus oil provided

Unclear how the advice was delivered or by whom

Total fat intake, %E (at 18 months): olive 46.2 (SD unclear), cont 32.6 (SD unclear) (mean difference 13.60, 95% CI 6.30 to 20.90 assuming SDs of 10) significant increase

Saturated fat intake: unclear (mean difference unclear)

PUFA intake: unclear

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake: unclear

CHO intake, %E (at 18 months): olive 42.2 (SD unclear), cont 51.5 (SD unclear) (mean difference ‐9.30, 95% CI ‐23.91 to 5.31 assuming SDs of 20) no significant difference

Protein intake, %E (at 18 months): olive 9.6 (SD unclear), cont 13.2 (SD unclear) (mean difference ‐3.60, 95% CI ‐7.25 to 0.05 assuming SDs of 5) no significant difference

Trans fat intake: unclear

Replacement for saturated fat: mainly MUFA (based on dietary aims)

Style: diet advice and supplement (oil)

Setting: community

Outcomes

Stated trial outcomes: cardiac events
Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: cardiovascular deaths, non‐fatal MI, angina, stroke

Secondary outcomes: stroke (none), non‐fatal and total MI, CHD mortality (fatal MI and sudden death), CHD events (all MI and sudden death)

Tertiary outcomes: total cholesterol

Notes

Study duration 2 years

Study aim was to reduce total fat (by restricting fatty meat, sausages, pastry, ice cream, cheese, cake, milk, eggs and butter) and prescribe vegetable oil (so reducing saturates), but saturated fat intakes during intervention were not reported

SFA reduction aimed (but unclear whether achieved as SFA intake not reported)

Total serum cholesterol, difference between intervention and control, mmol/L: 0.30 (95% CI ‐0.93 to 1.53), NO statistically significant reduction, mean total cholesterol rose

Trial dates: unclear, published in 1965

Funding: probably unfunded (they thank the Paddington General Hospital for clinic facilities, and St Mary's and Paddington General Hospital physicians for referral of patients, but no funding acknowledged)

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions

Simon 1997

Methods

RCT

Participants

Women with a high risk of breast cancer (USA)
CVD risk: low
Control: randomised 96, analysed 75
Intervention: randomised 98, analysed 72
Mean years in trial: control 1.8, intervention 1.7
% male: 0
Age: mean control 46, intervention 46

Ethnicity: White 89%, African‐American 9%, Hispanic 2%

Statins use allowed? No (those on lipid‐lowering medications were excluded)

% taking statins: 0%

Interventions

Reduced fat vs usual diet

Control aims: usual diet
Intervention aims: total fat 15%E

Control methods: continued usual diet

Intervention methods: Bi‐weekly individual dietetic appointments over 3 months followed by monthly individual or group appointments, including education, goal setting, evaluation, feedback and self monitoring

Intervention delivered face‐to‐face by a dietitian

Total fat intake, %E (at 12 months)§: int 17.6 (SD 5.8), cont 33.8 (SD 7.4) (mean difference ‐16.20, 95% CI ‐18.34 to ‐14.06) significant reduction

Saturated fat intake, %E (at 12 months)§: int 6.0 (SD 3.0), cont 12.1 (SD 5.2) (mean difference ‐6.10, 95% CI ‐7.47 to ‐4.73) significant reduction

PUFA intake, %E (at 12 months)§: int 3.8 (SD 1.7), cont 7.3 (SD 4.1) (mean difference ‐3.50, 95% CI ‐4.51 to ‐2.49) significant reduction

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake, %E (at 12 months)§: int 6.1 (SD 3.0), cont 12.8 (SD 6.3) (mean difference ‐6.70, 95% CI ‐8.29 to ‐5.11) significant reduction

CHO intake: not reported

Protein intake: not reported

Trans fat intake: not reported

Replacement for saturated fat: unclear, either carbohydrate or protein (based on aims and achievements)

Style: diet advice

Setting: community

Outcomes

Stated trial outcomes: intervention feasibility
Data available on total mortality? yes (2 deaths, but not clear in which arms)
Cardiovascular mortality? no
Events available for combined cardiovascular events: none

Secondary outcomes: cancer diagnosis (8 diagnoses, but not clear in which arms)

Tertiary outcomes: weight, total, LDL and HDL cholesterol, TGs

Notes

Study duration 2 years

Study aim was to reduce total fat to 15%E (saturated fat not mentioned), but saturated fat intake in the intervention group was significantly lower than in the control group

SFA reduction achieved

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.34 (95% CI ‐0.64 to ‐0.04), statistically significant reduction

§Kasim 1993

Trial dates: Recruitment 1987 to 1989

Funding: Marilyn J Smith Fund, Harper‐Grace Hospitals, the Wesley Foundation, National Cancer Institute, Karmanos Cancer Institute Core Grant, the United Foundation of Detroit

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions except PN Kim who was affiliated with Wesley Health Strategies (now Health Strategies, which offers a "full‐service health and fitness centre with an educated fitness staff and spacious workout areas", see healthstrategiesfitness.com/)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Stratified by age and randomised (block size 2)

Allocation concealment (selection bias)

Unclear risk

Randomisation method not clearly described

Blinding (performance bias and detection bias)
All outcomes

High risk

Participants knew their allocation, unclear whether physicians did

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Unclear, deaths, cancer and CV events are drop‐outs ‐ unclear if any data missing

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

High risk

Very different contact time with dietitian, but medical appointments same in both groups. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

High risk

Aim to reduce SFA not stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

Low risk

Statistically significant TC fall

Other bias

Low risk

None noted
STARS 1992

Methods

RCT

Participants

Men with angina referred for angiography (UK)
CVD risk: high
Control: unclear randomised (30?), analysed 24
Intervention: unclear how many randomised (30?), analysed 26
Mean years in trial: control 2.9, intervention 3.0
% male: 100
age: mean control 53.9, intervention 48.9 (all < 66)

Ethnicity: not stated

Statins use allowed? No (1 arm of the trial, not described here, prescribed cholestyramine)

% taking statins: 0%

Interventions

Reduced and modified fat diet vs usual diet

Control aims: no diet intervention but advised to lose weight if BMI > 25
Intervention aims: total fat 27%E, SFA 8 ‐ 10%E, omega‐3 and omega‐6 PUFA 8%E, increase in plant‐derived soluble fibre, dietary cholesterol 100 mg/1000 kcal, advised to lose weight if BMI > 25

Control methods: usual care but no formal dietetic counselling. They were counselled against smoking if appropriate and advised about daily exercise level

Intervention methods: Usual care plus dietetic individual assessment of diet and advice. Further dietetic counselling and food stuffs were given to participants who did not achieve or maintain certain levels of serum cholesterol reduction

Initial intervention was delivered individually face‐to‐face by a dietitian and follow‐up by a clinician

Total fat intake, %E (through study): int 27 (SD 7), cont 37 (SD 5) (mean difference ‐10.00, 95% CI ‐13.35 to ‐6.65) significant reduction

Saturated fat intake, %E (through study): int 9 (SD 3), cont 16 (SD 4) (mean difference ‐7.00, 95% CI ‐8.97 to ‐5.03) significant reduction

PUFA intake, %E (through study)§: int 7 (SD 2), cont 5 (SD 2) (mean difference 2.00, 95% CI 0.89 to 3.11) significant increase

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake, %E (through study)§: int 10 (SD 4), cont 17 (SD 5) (mean difference ‐7.00, 95% CI ‐9.52 to ‐4.48) significant reduction

CHO intake, %E (through study)§: int 49 (SD 7), cont 41 (SD 7) (mean difference 8.00, 95% CI 4.12 to 11.88) significant increase

Protein intake, %E (through study)§: int 19 (SD 4), cont 18 (SD 2) (mean difference 1.00, 95% CI ‐0.73 to 2.73) no significant effect

Trans fat intake: not reported

Replacement for saturated fat: CHO and PUFA (based on aims and achievements)

Style: diet advice

Setting: community

Outcomes

Stated trial outcomes: angiography
Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: cardiovascular deaths, non‐fatal MI, angina, stroke, CABG, angioplasty, stroke, total MI, , CHD events, plus cancer deaths (none)

Secondary outcomes: total, HDL, LDL cholesterol, TGs, total/HDL and LDL/HDL ratios, 2‐hour post‐load glucose (weight and BP "remained similar" but were not reported, Lp(a) reported but as geometric means)

Notes

Study duration 3 years

Study aim was to reduce saturated fats (to 8 ‐ 10%E), and saturated fat intake in the intervention group was significantly reduced

SFA reduction aimed and achieved

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.76 (95% CI ‐1.19 to ‐0.33), statistically significant reduction

§Blann 1995

Trial dates: Study dates not reported (published in 1992)

Funding: Unilever plc, the Chemical Pathology Fund of St Thomas' Hospital, and Bristol‐Meyers Ltd

Declarations of Interest of primary researchers: none stated, all authors work for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"blinded random cards issued centrally by statistician advisor"

Allocation concealment (selection bias)

Low risk

"blinded random cards issued centrally by statistician advisor"

Blinding (performance bias and detection bias)
All outcomes

High risk

Physician blinding: unclear
Participant blinding: inadequate

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Unclear, deaths, cancer and CV events are drop‐outs ‐ unclear if any data missing

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

High risk

Usual care in both groups, dietetic counselling only in the intervention group. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

Low risk

Statistically significant TC fall

Other bias

Low risk

None noted
Sydney Diet‐Heart 1978

Methods

RCT

Participants

Men with previous MI (Australia)
CVD risk: high
Control: randomised 237, analysed 221 at 2 years
Intervention: randomised 221, analysed 205 at 2 years
Mean years in trial: control 4.3, intervention 4.3
% male: 100
Age: mean control 49.1 (SD 6.5), intervention 48.7 (SD 6.8)

Ethnicity: not stated

Statins use allowed? Unclear (use of medication did not appear to be an exclusion criteria)

% taking statins: Not reported (probably none as too early, pre‐1980)

Interventions

Modified fat diet vs usual diet

Control aims: reduction in energy if overweight, no other specific dietary advice, allowed to use PUFA margarine instead of butter
Intervention aims: SFA 10%E, PUFA 15%E, reduction in energy if overweight, dietary chol < 300 mg/day

Control methods: no specific dietary instruction (except re weight)

Intervention methods: advised and tutored individually, diet assessed 3 times in 1st year and twice annually thereafter

Intervention was delivered face‐to‐face individually but unclear by whom

Total fat intake, %E ("during follow up"): int 38.3 (SD 5.9), cont 38.1 (SD 5.4) (mean difference 0.20, 95% CI ‐0.88 to 1.28) no significant difference

Saturated fat intake, %E ("during follow up"): int 9.8 (SD 2.6), cont 13.5 (SD 3.2) (mean difference ‐3.70, 95% CI ‐4.25 to ‐3.15) significant reduction

PUFA intake, %E ("during follow up"): int 15.1 (SD 4.3), cont 8.9 (SD 3.5) (mean difference 6.20, 95% CI 5.45 to 6.95) significant increase

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake, %E ("during follow up"): int 11.5 (SD 2.1), cont 13.8 (SD 2.5) (mean difference ‐2.30, 95% CI ‐2.74 to ‐1.86) significant reduction

CHO intake, %E ("during follow up"): int 40.9 (SD 7.3), cont 40.3 (SD 7.3) (mean difference 0.60, 95% CI ‐0.79 to 1.99) no significant difference

Protein intake, %E ("during follow up"): int 15.2 (SD 2.8), cont 15.7 (SD 3.4) (mean difference ‐0.50, 95% CI ‐1.09 to 0.09) no significant difference

Trans fat intake: not reported

Primary replacement for saturated fat: mainly PUFA (based on dietary aims and achievements)

Style: diet advice

Setting: community

Outcomes

Stated trial outcomes: cardiovascular mortality and morbidity
Data available on total mortality? yes
Cardiovascular mortality? yes (exact events included not stated)
Events available for combined cardiovascular events: none

Secondary outcomes: CHD deaths (exact events included not stated)

Tertiary outcomes: total cholesterol, TG, BMI, sBP, dBP

Notes

Study duration 7 years

Study aim was saturated fat 10%E, and saturated fat intake in the intervention group was less than 80% of that in the control (73%)

SFA reduction aimed and achieved

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.30 (95% CI ‐0.51 to ‐0.09), statistically significant reduction

Trial dates: Recruitment 1966 to [unclear] and followed for 2 to 7 years

Funding: Life Insurance Medical Research Fund of Australia and New Zealand

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"random numbers"

Allocation concealment (selection bias)

Unclear risk

Randomisation method not clearly described

Blinding (performance bias and detection bias)
All outcomes

High risk

Physician blinding: adequate
participant blinding: inadequate

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Survival analysis used

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

High risk

Advice and follow‐up in intervention group, not in control. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

Low risk

Statistically significant TC fall

Other bias

Low risk

None noted
Veterans Admin 1969

Methods

RCT

Participants

Men living at the Veterans Administration Center (USA)
CVD risk: low
Control: randomised 422, analysed 422
Intervention: randomised 424, analysed 424
Mean years in trial: control 3.7, intervention 3.7
% male: 100
Age: mean control 65.6, intervention 65.4 (all 54 ‐ 88)

Ethnicity: White 90%, African‐American 7%, Asian 1%, Mexican 1%, other 1%

Statins use allowed? Unclear (only 4 participants were taking nicotinic acid, 17 diuretics, 56 digitalis, none on heparin)

% taking statins: Not reported (probably none as too early, pre‐1980)

Interventions

Modified fat vs usual diet

Control aims: provided, total fat 40%E
Intervention aims: total fat 40%E, ⅔ of SFA replaced by unsaturated fats, dietary chol reduced

Control methods: whole diet provided

Intervention methods: whole diet provided

Total fat intake, %E (during trial): int 38.9 (SD unclear), cont 40 (SD unclear) (mean difference ‐1.10, 95% CI ‐2.45 to 0.25 assuming SDs of 10) no significant difference

Saturated fat intake, %E (during trial): int 8.3 (SD unclear), cont 18.5 (SD unclear) (mean difference ‐10.20, 95% CI ‐10.87 to ‐9.53 assuming SDs of 5) significant reduction

PUFA intake, %E (during trial)§: int 16.0 (SD ?), cont 4.9 (SD 0.10) (mean difference 11.10, 95% CI 10.62 to 11.58 assuming missing SD was 5) significant increase

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake, %E (during trial)⁑: not reported, approx int 14.0, cont 17.2 (mean difference ‐3.20, 95% CI ‐3.87 to ‐2.53) significant reduction

CHO intake, %E (during trial)⁑: not reported, approx int 45.9, cont 44.8 (mean difference 1.10, 95% CI ‐1.60 to 3.80 assuming SDs of 20) no significant difference

Protein intake, %E (during trial)§: int 15.2 (SD ?), cont 15.2 (SD ?) (mean difference 0.00, 95% CI ‐0.67 to 0.67 assuming SDs of 5) no significant difference

Trans fat intake: not reported

Replacement for saturated fat: mainly PUFA (based on dietary aims and achievements)

Style: diet provided

Setting: residential institution

Outcomes

Stated trial outcomes: mortality, heart disease
Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: sudden death, definite MI, definite stroke, angina, PV events

Secondary outcomes: cancer deaths, cancer diagnoses, stroke, non‐fatal MI, total MI, CHD deaths (fatal MI and sudden death due to CHD), CHD events (any MI or sudden death due to CHD)

Tertiary outcomes: none (some data on total cholesterol, but no variance info)

Notes

Study duration over 8 years

Study aim was to replace 66% of saturated fat by unsaturated fats, and saturated fat intake in the intervention group was significantly lower than in control

SFA reduction aimed and achieved

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.37 (95% CI ‐0.77 to 0.03), NO statistically significant reduction but reduction > 0.20

§Dayton 1965

⁑Estimated by subtraction (assuming total fat = SFA + PUFA + MUFA or energy intake = energy from fat + CHO + protein)

Trial dates: Recruitment 1959 to 1967

Funding: Veterans Administration, Aruthur Dodd Fuller Foundation, National Heart Institute, Los Angeles County Heart Association, plus gifts of foods from Mazola corn oil and Mazola margarine, the National Soybean Processors Association, Pitman‐Moore Company (Emdee margarine) and Hi‐Saff Imitation Ice‐cream from Frozen Desserts Company. Edgmar Farms donated milk refrigeration equipment.

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"table of random numbers used"

Allocation concealment (selection bias)

Unclear risk

Randomisation method not clearly described

Blinding (performance bias and detection bias)
All outcomes

Low risk

physician blinding: adequate
participant blinding: adequate

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All followed up via Veterans Admin system

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

Low risk

All ate centre food as usual. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

High risk

No statistically significant TC fall, though fall was > 0.20 mmol/L

Other bias

Low risk

None noted
WHI with CVD 2006

Methods

RCT

Participants

Post‐menopausal women aged 50 ‐ 79 with CVD at baseline (USA)
CVD risk: high
Control: randomised 1369, analysed 1369
Intervention: randomised 908, analysed 908
Mean years in trial: control 8.1, intervention 8.1
% male: 0
Age: mean (women both with and without CVD at baseline) int 62.3 (SD 6.9), control 62.3 (SD 6.9)

Ethnicity (women both with and without CVD at baseline): white 82%, black 11%, Asian or pacific islander 2%, unknown 1%, American Indian or Alaskan native < 1%. No statistically significant effects of the intervention on CHD events was seen for any ethnic subgroup

Statins use allowed? Yes

% taking statins: 12% of women recruited were on lipid‐lowering medication (these were a mixture of participants with and without CVD at baseline)

Interventions

Reduced fat vs usual diet

Control: diet‐related education materials
Intervention: low‐fat diet (20%E from fat), reducing saturated fat to 7%E, with increased fruit and vegetables

Control methods: given copy of 'Dietary Guidelines for Americans'

Intervention methods: 18 group sessions with trained and certified nutritionists in the 1st year, quarterly maintenance sessions thereafter, focusing on diet and behaviour modification

Intervention delivered face‐to‐face in a group by nutritionists

Intake data all relate to the full WHI cohort (not divided by whether participants have CVD at baseline or not):

Total fat intake, %E (at 6 years): int 28.8 (SD 8.4), cont 37.0 (SD 7.3) (mean difference ‐8.20, 95% CI ‐8.34 to ‐8.06) significant reduction

Saturated fat intake, %E (at 6 years): int 9.5 (SD3.2), cont 12.4 (SD3.1) (mean difference ‐2.90, 95% CI ‐2.96 to ‐2.84 for full WHI population) significant reduction

PUFA intake, %E (at 6 years)§: int 6.3 (SD?), cont 7.6 (SD?) (mean difference ‐1.30, 95% CI ‐1.72 to ‐0.88 assuming missing SDs were 5) significant reduction

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake, %E (at 6 years)§: int 11.1 (SD?), cont 14.3 (SD?) (mean difference ‐3.20, 95% CI ‐3.62 to ‐2.78 assuming unclear SDs were 5) significant reduction

CHO intake, %E (at 6 years)§: int 53.9 (SD?), cont 46.3 (SD?) (mean difference 7.60, 95% CI 5.91 to 9.29 assuming SDs of 20) significant increase

Protein intake, %E (at 6 years)§: int 17.7 (SD?), cont 17.0 (SD?) (mean difference 0.70, 95% CI 0.28 to 1.12 assuming SDs of 5) significant increase

Trans fat intake, %E (at 6 years)§: int 1.8 (SD?), cont 2.4 (SD?) (mean difference unclear, no SDs assumed)

Replacement for saturated fat: mainly CHO, some protein (based on dietary achievement)

Style: dietary advice

Setting: community

Outcomes

Stated trial outcomes: breast cancer, mortality, other cancers, cardiovascular events, diabetes

Data available on total mortality? yes
Cardiovascular mortality? yes
Events available for combined cardiovascular events: CHD, stroke, heart failure, angina, peripheral vascular disease, revascularisation, pulmonary embolism, DVT

Secondary outcomes: cancer deaths*, cancer diagnoses*, stroke, non‐fatal MI

Tertiary outcomes: weight, BMI, total, LDL and HDL cholesterol, TGs, systolic and diastolic BP

* these are only available for the whole cohort, not split between low and high CVD risk groups

Notes

Study duration over 8 years

Study aim was to reduce total fat to 20%E, reduce saturated fat to 7%E and increase fruit and vegetable intake (Patterson 2003), and saturated fat intake in the intervention group was significantly lower than in control

SFA reduction aimed and achieved.

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.09 (95% CI ‐0.15 to ‐0.02), statistically significant reduction

§Amongst the 881 intervention and 1373 control participants with blood samples at baseline, with or without CVD at baseline (Howard 2010).

Trial dates: Recruitment was between 1993 and 1998

Funding: National Heart, Lung and Blood Institute of the National Institutes of Health

Declarations of Interest of primary researchers: Declarations vary from paper to paper, but this is a typical one from Beresford 2006 "Dr Black has received research grants from Pfizer and AstraZeneca, was on the speakers bureaus for Pfizer, Novartis, Sanofi‐Aventis, Bristol‐Meyers Squibb, Searle, Pharmacia, and Boehringer and served as a consultant of on an advisory board for Myogen, Merck Sharp and Dohme, Novartis, Mylan‐Bertek, Pfizer, Bristol‐Meyers Squibb, and Sanofi‐Aventis. Dr Howard has served on the advisory boards of Merck, Schering Plough, and the Egg Nutrition Council, has received research support from Merck and Pfizer, and has consulted for General Millls. Dr Assaf is an employee of Pfizer. No other disclosures were reported."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer algorithm

Allocation concealment (selection bias)

Low risk

Computer algorithm

Blinding (performance bias and detection bias)
All outcomes

High risk

Participants aware of allocation

Incomplete outcome data (attrition bias)
All outcomes

Low risk

ITT analysis

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

High risk

Intervention participants received 18 group sessions with behavioural modification plus quarterly maintenance sessions thereafter, control groups received a leaflet. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

Low risk

Aim to reduce SFA stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

Low risk

Statistically significant TC fall

Other bias

Low risk

None noted
WHI without CVD 2006

Methods

RCT

Participants

Post‐menopausal women aged 50 ‐ 79 without CVD at baseline (USA)
CVD risk: low
Control: randomised 29,294, analysed 29,294
Intervention: randomised 19,541, analysed 19,541
Mean years in trial: control 8.1, intervention 8.1
% male: 0
Age: mean (both with and without CVD at baseline) int 62.3 (SD 6.9), control 62.3 (SD 6.9)

Ethnicity (women both with and without CVD at baseline): white 82%, black 11%, Asian or pacific islander 2%, unknown 1%, American Indian or Alaskan native < 1%. No statistically significant effects of the intervention on CHD events was seen for any ethnic subgroup

Statins use allowed? Yes

% taking statins: 12% of women recruited were on lipid‐lowering medication (these were a mixture of participants with and without CVD at baseline)

Interventions

Reduced fat vs usual diet

Control: diet‐related education materials
Intervention: low‐fat diet (20% E from fat), reduce saturated fat to 7%E with increased fruit and vegetables

Control methods: given copy of 'Dietary Guidelines for Americans'

Intervention methods: 18 group sessions with trained and certified nutritionists in the 1st year, quarterly maintenance sessions thereafter, focusing on diet and behaviour modification

Intervention delivered face‐to‐face in a group by nutritionists

Intake data all relate to the full WHI cohort (not divided by whether participants have CVD at baseline or not):

Total fat intake, %E (at 6 years): int 28.8 (SD 8.4), cont 37.0 (SD 7.3) (mean difference ‐8.20, 95% CI ‐8.34 to ‐8.06) significant reduction

Saturated fat intake, %E (at 6 years): int 9.5 (SD3.2), cont 12.4 (SD3.1) (mean difference ‐2.90, 95% CI ‐2.96 to ‐2.84 for full WHI population) significant reduction

PUFA intake, %E (at 6 years)§: int 6.3 (SD?), cont 7.6 (SD?) (mean difference ‐1.30, 95% CI ‐1.72 to ‐0.88 assuming missing SDs were 5) significant reduction

PUFA n‐3 intake: not reported

PUFA n‐6 intake: not reported

MUFA intake, %E (at 6 years)§: int 11.1 (SD?), cont 14.3 (SD?) (mean difference ‐3.20, 95% CI ‐3.62 to ‐2.78 assuming unclear SDs were 5) significant reduction

CHO intake, %E (at 6 years)§: int 53.9 (SD?), cont 46.3 (SD?) (mean difference 7.60, 95% CI 5.91 to 9.29 assuming SDs of 20) significant increase

Protein intake, %E (at 6 years)§: int 17.7 (SD?), cont 17.0 (SD?) (mean difference 0.70, 95% CI 0.28 to 1.12 assuming SDs of 5) significant increase

Trans fat intake, %E (at 6 years)§: int 1.8 (SD?), cont 2.4 (SD?) (mean difference unclear, no SDs assumed)

Replacement for saturated fat: mainly carbohydrate, some protein (based on dietary achievement)

Style: dietary advice

Setting: community

Outcomes

Stated trial outcomes: breast cancer, mortality, other cancers, cardiovascular events, diabetes

Data available on total mortality? yes*
Cardiovascular mortality? yes
Events available for combined cardiovascular events: CHD, stroke, heart failure, angina, peripheral vascular disease, revascularisation, pulmonary embolism, DVT

Secondary outcomes: cancer deaths*, cancer diagnoses*, stroke, non‐fatal MI, diabetes diagnosis*

Tertiary outcomes: weight, BMI, total, LDL and HDL cholesterol, TGs, systolic and diastolic BP (Lp(a) and HOMA reported as geometric means)

* these are only available for the whole cohort, not split between low and high CVD risk groups

Notes

Study duration over 8 years

Study aim was to reduce total fat to 20%E, reduce saturated fat to 7%E and increase fruit and vegetable intake (Patterson 2003), and saturated fat intake in the intervention group was significantly lower than in control

SFA reduction aimed and achieved

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.09 (95% CI ‐0.15 to ‐0.02), statistically significant reduction

§Amongst the 881 intervention and 1373 control participants with blood samples at baseline, with or without CVD at baseline (Howard 2010).

Trial dates: Recruitment was between 1993 and 1998

Funding: National Heart, Lung and Blood Institute of the National Institutes of Health

Declarations of Interest of primary researchers: Declarations vary from paper to paper, but this is a typical one from Beresford 2006 "Dr Black has received research grants from Pfizer and AstraZeneca, was on the speakers bureaus for Pfizer, Novartis, Sanofi‐Aventis, Bristol‐Meyers Squibb, Searle, Pharmacia, and Boehringer and served as a consultant of on an advisory board for Myogen, Merck Sharp and Dohme, Novartis, Mylan‐Bertek, Pfizer, Bristol‐Meyers Squibb, and Sanofi‐Aventis. Dr Howard has served on the advisory boards of Merck, Schering Plough, and the Egg Nutrition Council, has received research support from Merck and Pfizer, and has consulted for General Millls. Dr Assaf is an employee of Pfizer. No other disclosures were reported."

WINS 2006

Methods

RCT

Participants

Women with localised resected breast cancer (USA)
CVD risk: low

Control: 1462 randomised, 1462 analysed

Intervention: 975 randomised, 975 analysed

Mean years in trial: overall 5.0
% men: 0
Age: control mean 58.5 (95% CI 43.6 to 73.4), intervention mean 58.6 (95% CI 44.4 to 72.8) (all post‐menopausal)

Ethnicity: 85% white, 5% black, 4% Hispanic, 5% Asian or pacific islander, <1% American Indian or unknown (no outcome data based on ethnicity)

Statins use allowed? Not stated (statins not mentioned in inclusion or exclusion criteria within trial protocol)

% taking statins: Not reported

Interventions

Reduced fat intake vs usual diet

Control aims: minimal nutritional counselling focused on nutritional adequacy
Intervention aims: total fat 15 ‐ 20%E

Control methods: 1 baseline dietetic session plus 3‐monthly sessions

Intervention methods: 8 bi‐weekly individual dietetic sessions plus 3‐monthly contact and optional monthly group sessions, incorporating individual fat gram goals, social cognitive theory, self monitoring, goal setting, modelling, social support and relapse prevention and management

Intervention was delivered face‐to‐face individually by trained dietitian

Total fat intake, %E (at 1 year): int 20.3 (SD 8.1), cont 29.2 (SD 7.4) (mean difference ‐8.90, 95% CI ‐9.53 to ‐8.27) Total fat %E (at 5 years): int 23.2 (SD 8.4) n = 380, cont 31.2 (SD 8.9) n = 648 (mean difference ‐8.00, 95% CI ‐9.09 to ‐6.91) significant reduction

Saturated fat intake*, %E (at 1 year): int 6.4 (SD 0.14 [4.4]), cont 9.8 (SD 0.15 [5.7]) (mean difference ‐3.40, 95% CI ‐3.80 to ‐3.00 assuming reported SDs were actually SEs) significant reduction

PUFA intake*, %E (at 1 year): int 4.5 (SD 0.09 (2.8)), cont 6.4 (SD 0.10 (3.8)) (mean difference ‐1.90, 95% CI ‐2.16 to ‐1.64) significant reduction

PUFA n‐3 intake: not reported by study arm

PUFA n‐6 intake: not reported by study arm

MUFA intake*, %E (at 1 year): int 7.6 (SD 0.14 (4.4)), cont 11.5 (SD 0.16 (6.1)) (mean difference ‐3.90, 95% CI ‐4.32 to ‐3.48) significant reduction

CHO intake, %E (at 6 months): int 60.8 (SD 19.6), cont 50.5 (SD 14.8) (mean difference 10.30, 95% CI 8.85 to 11.75) significant increase

Protein intake, %E (at 6 months): int 19.1 (SD 5.2), cont 17.6 (SD 4.1) (mean difference 1.50, 95% CI 1.11 to 1.89) significant increase

Trans fat intake: not reported

Replacement for saturated fat: CHO and protein (based on dietary achievement)

Style: dietary advice

Setting: community

Outcomes

Stated trial outcomes: dietary fat intake, total cholesterol, weight and waist

Data available on total mortality? yes
Cardiovascular mortality? no
Events available for combined cardiovascular events: none

Secondary outcomes: cancer diagnoses

Tertiary outcomes: weight, BMI, total cholesterol

Notes

Study duration 5 years

Study aim was to reduce total fat to 15 ‐ 20%E, but saturated fat intake in the intervention group was significantly lower than in control

SFA reduction achieved

Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.14 (95% CI ‐0.34 to 0.05), NO statistically significant reduction and reduction < 0.20

*SDs appear incorrect, probably SEs?

Trial dates: Recruitment 1994 to 2001

Funding: National Cancer Institute, Breast Cancer Research Foundation, American Institute for Cancer Research

Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions except that Njeri Karanja worked for Kaiser Permanente Center for Health Research, Bette Caan for Kaiser Permanente Medical Group, and Barbara L Winters for Campbell's Soup Company.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random stratified permuted block design, carried out at the statistical co‐ordinating centre of WINS

Allocation concealment (selection bias)

Low risk

Random stratified permuted block design, carried out at the statistical co‐ordinating centre of WINS

Blinding (performance bias and detection bias)
All outcomes

High risk

Participants not blinded, not relevant for assessment of mortality by researchers

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All assessed.

Selective reporting (reporting bias)

Low risk

Not relevant for primary and secondary outcomes as all trialists were asked for data

Free of systematic difference in care?

High risk

Differences in attention ‐ more time for those in intervention group. See Control and Intervention Methods in Interventions section of the Table of Characteristics of Included Studies

Stated aim to reduce SFA

High risk

Aim to reduce SFA not stated

Achieved SFA reduction

Low risk

SFA reduction achieved

Achieved TC reduction

High risk

No statistically significant TC fall

Other bias

Low risk

None noted

%E = percent of total energy intake
ATPII ‐ Adult treatment panel II
CABG = coronary artery bypass graft
CHD = coronary heart disease
CHO = carbohydrates
chol = cholesterol
CI = confidence interval
CVD = cardiovascular disease
dBP = diastolic blood pressure
DVT = deep vein thrombosis
HOMA = homeostatic model assessment
Lp(a) = lipoprotein
MI = myocardial infarction
MUFA = monounsaturated fats
P/S = polyunsaturated/saturated fat ratio
PCTA = percutaneous transluminal coronary angioplasty
PUFA = polyunsaturated fats
PVD = peripheral vascular disease
RCT = randomised controlled trial
sBP = systolic blood pressure
SD = standard deviation
SE = standard error
SFA = saturated fats
TC = total cholesterol
TG = triglyceride

Characteristics of excluded studies [ordered by study ID]

Jump to:

Study

Reason for exclusion

Agewall 2001

Multifactorial intervention

Ammerman 2003

No appropriate control group (and not low fat vs modified fat)

Anderson 1990

Follow‐up less than 24 months

Aquilani 2000

No appropriate control group (and not low fat vs modified fat)

Arntzenius 1985

No appropriate control group (and not low fat vs modified fat)

Aro 1990

Intervention and randomised follow‐up less than 6 months

ASSIST 2001

Intervention is not dietary fat modification or low fat diet

Australian Polyp Prev 95

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Azadbakht 2007

Follow‐up less than 24 months

Bakx 1997

Multifactorial intervention

Ball 1965

Study aim was to assess effects of a low‐fat diet and methods state that the "nature of the fat consumed was not altered". Saturated fat content of diet was not reported.

Barnard 2009

Weight reduction encouraged in the conventional diet, but not in the vegan diet arm

Barndt 1977

No appropriate control group (and not low fat vs modified fat)

Baron 1990

Multifactorial intervention

Barr 1990

Intervention and randomised follow‐up less than 6 months

Barsotti 1991

Complex paper in Italian, unclear whether cardiovascular events occurred, contact with authors not established

Baumann 1982

Intervention and randomised follow‐up less than 6 months

BDIT Pilot Studies 1996

Study aim was to reduce total fat intake to 15%E with no specific intervention on saturated fat. Saturated fat in intervention group was more than 80% of that in the control group.

Beckmann 1995

Intervention is not dietary fat modification or low‐fat diet

beFIT 1997

Follow‐up less than 24 months

Beresford 1992

Intervention and randomised follow‐up less than 6 months

Bergstrom 1967

Intervention and randomised follow‐up less than 6 months

Bierenbaum 1963

No appropriate control group (and not low fat vs modified fat)

Bloemberg 1991

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Bloomgarden 1987

Multifactorial intervention

Bonk 1975

Trial, unclear if randomised, contact could not be established with trialists

Bonnema 1995

No appropriate control group (and not low fat vs modified fat)

Bosaeus 1992

Intervention and randomised follow‐up less than 6 months

Boyd 1988

Follow‐up less than 24 months

Brehm 2009

Unclear whether any relevant events occurred, not able to contact trialists

Brensike 1982

No appropriate control group (and not low fat vs modified fat)

BRIDGES 2001

Follow‐up less than 24 months

Broekmans 2003

Intervention is not dietary fat modification or low fat diet

Brown 1984

No appropriate control group (and not low fat vs modified fat)

Bruce 1994

No appropriate control group (and not low fat vs modified fat)

Bruno 1983

Multifactorial intervention

Butcher 1990

Intervention and randomised follow‐up less than 6 months

Byers 1995

No appropriate control group (and not low fat vs modified fat)

Caggiula 1996

No appropriate control group (and not low fat vs modified fat)

Canadian DBCP 1997

Unable to establish contact with authors to provide data on numbers of deaths and CV events

CARMEN 2000

Follow‐up less than 24 months

CARMEN sub‐study 2002

Follow‐up less than 24 months

Cerin 1993

Intervention and randomised follow‐up less than 6 months

Chan 1993

Intervention and randomised follow‐up less than 6 months

Chapman 1950

Intervention and randomised follow‐up less than 6 months

Charbonnier 1975

Intervention and randomised follow‐up less than 6 months

Cheng 2004

Intervention and randomised follow‐up less than 6 months

Chiostri 1988

Intervention and randomised follow‐up less than 6 months

Choudhury 1984

Intervention and randomised follow‐up less than 6 months

Clark 1997

Multifactorial intervention

Clifton 1992

Intervention and randomised follow‐up less than 6 months

Cobb 1991

Intervention and randomised follow‐up less than 6 months

Cohen 1991

Intervention is not dietary fat modification or low fat diet

Cole 1988

Intervention and randomised follow‐up less than 6 months

Colquhoun 1990

Intervention and randomised follow‐up less than 6 months

Consolazio 1946

Intervention and randomised follow‐up less than 6 months

Cox 1996

Multifactorial intervention

Croft 1986

Intervention is not dietary fat modification or low fat diet

Curzio 1989

Follow‐up less than 24 months

Da Qing IGT 1997

Intervention is not dietary fat modification or low‐fat diet

Dalgard 2001

No appropriate control group (and not low fat vs modified fat)

DAS 2000

No appropriate control group (and not low fat vs modified fat)

DASH 1997

Intervention and randomised follow‐up less than 6 months

Davey Smith 2005

Multifactorial intervention

De Boer 1983

Intervention and randomised follow‐up less than 6 months

De Bont 1981

Neither mortality nor cardiovascular morbidity data available as study data have been lost

DeBusk 1994

Multifactorial intervention

DEER 1998

Duration 1 year only

Delahanty 2001

No appropriate control group (and not low fat vs modified fat)

Delius 1969

Intervention is not dietary fat modification or low fat diet

Demark 1990

Intervention and randomised follow‐up less than 6 months

Dengel 1995

No appropriate control group (and not low fat vs modified fat)

Denke 1994

Intervention and randomised follow‐up less than 6 months

Diabetes CCT 1995

Intervention is not dietary fat modification or low fat diet

Diet & Hormone Study 2003

Duration 1 year only

DIET 1998

Multifactorial intervention

Ding 1992

Intervention and randomised follow‐up less than 6 months

DIRECT 2009

Unable to establish contact with authors to establish whether relevant events occurred

DO IT 2006

Intervention aim was for a "mediterranean diet" with total fat 27 ‐ 30%E, protein 15 ‐ 18%E, CHO 50 ‐ 55%E, no specific aim to reduce saturated fat (though polyunsaturated margarine given to intervention group), and intervention group saturated fat was more than 80% of that in the control.

Dobs 1991

No appropriate control group (and not low fat vs modified fat)

Due 2008

Follow‐up less than 24 months

Duffield 1982

Multifactorial intervention

Dullaart 1992

Study authors confirmed that no deaths or cardiovascular events occurred during the study.

Eating Patterns 1997

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Ehnholm 1982

Intervention and randomised follow‐up less than 6 months

Ehnholm 1984

Intervention and randomised follow‐up less than 6 months

Eisenberg 1990

Intervention and randomised follow‐up less than 6 months

Elder 2000

No appropriate control group (and not low fat vs modified fat)

Ellegard 1991

Intervention and randomised follow‐up less than 6 months

Esposito 2003

No appropriate control group (and not low fat vs modified fat)

Esposito 2004

Unable to establish contact with authors to assess whether any relevant events occurred

EUROACTION 2008

Multifactorial intervention

FARIS 1997

Multifactorial intervention

Fasting HGS 1997

No appropriate control group (and not low fat vs modified fat)

Ferrara 2000

No appropriate control group (and not low fat vs modified fat)

Fielding 1995

Intervention and randomised follow‐up less than 6 months

Finnish Diabet Prev 2000

Multifactorial intervention

Finnish Mental Hosp 1972

Not randomised (cluster‐randomised, but < 6 clusters)

Fisher 1981

Intervention and randomised follow‐up less than 6 months

FIT Heart 2011

Authors confirmed that differences between intervention and control groups included smoking and physical activity, as well as dietary changes

Fleming 2002

No appropriate control group (and not low fat vs modified fat)

Fortmann 1988

Intervention is not dietary fat modification or low fat diet

Foster 2003

Weight reduction in 1 arm but not the other

Frenkiel 1986

Follow‐up less than 24 months

FRESH START 2007

Participants were newly diagnosed with cancer

Gambera 1995

Intervention and randomised follow‐up less than 6 months

Gaullier 2007

No appropriate control group (and not low fat vs modified fat)

Ginsberg 1988

Intervention and randomised follow‐up less than 6 months

Gjone 1972

Intervention and randomised follow‐up less than 6 months

Glatzel 1966

No appropriate control group (and not low fat vs modified fat)

Goodpaster 1999

No appropriate control group (and not low fat vs modified fat)

Grundy 1986

Intervention and randomised follow‐up less than 6 months

Hardcastle 2008

Multifactorial intervention

Harris 1990

Intervention and randomised follow‐up less than 6 months

Hartman 1993

No appropriate control group (and not low fat vs modified fat)

Hartwell 1986

No appropriate control group (and not low fat vs modified fat)

Hashim 1960

Intervention and randomised follow‐up less than 6 months

Haufe 2011

Aim was to reduce total fat or reduce carbohydrate, but no saturated fat aims were stated, and effects of the diets on saturated fat intakes were unclear.

Haynes 1984

Intervention is not dietary fat modification or low fat diet

Heber 1991

Intervention and randomised follow‐up less than 6 months

Heine 1989

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Hellenius 1995

The study aimed for weight loss in 1 arm and not in the comparison arm

Heller 1993

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Hildreth 1951

No appropriate control group (and not low fat vs modified fat)

Holm 1990

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Horlick 1957

Intervention and randomised follow‐up less than 6 months

Horlick 1960

Intervention and randomised follow‐up less than 6 months

Howard 1977

Intervention and randomised follow‐up less than 6 months

Hunninghake 1990

Intervention and randomised follow‐up less than 6 months

Hutchison 1983

No appropriate control group (and not low fat vs modified fat)

Hyman 1998

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Iacono 1981

Not randomised, Intervention and randomised follow‐up less than 6 months

IMPACT 1995

Multifactorial intervention

Iso 1991

No appropriate control group (and not low fat vs modified fat)

Ives 1993

Multifactorial intervention

Jalkanen 1991

Multifactorial intervention

Jerusalem Nut 1992

Intervention and randomised follow‐up less than 6 months

Jula 1990

Multifactorial intervention

Junker 2001

Intervention and randomised follow‐up less than 6 months

Karmally 1990

Intervention and randomised follow‐up less than 6 months

Karvetti 1992

Multifactorial intervention

Kastarinen 2002

Multifactorial intervention

Kather 1985

Intervention and randomised follow‐up less than 6 months

Katzel 1995

Intervention is not dietary fat modification or low fat diet

Kawamura 1993

Intervention and randomised follow‐up less than 6 months

Keidar 1988

Intervention and randomised follow‐up less than 6 months

Kempner 1948

No appropriate control group (and not low fat vs modified fat)

Keys 1957a

Intervention and randomised follow‐up less than 6 months

Keys 1957b

Intervention and randomised follow‐up less than 6 months

Keys 1957c

Intervention and randomised follow‐up less than 6 months

Khan 2003

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

King 2000

Intervention and randomised follow‐up less than 6 months

Kingsbury 1961

Intervention and randomised follow‐up less than 6 months

Koopman 1990

Intervention and randomised follow‐up less than 6 months

Koranyi 1963

Unclear whether randomised, unable to contact authors to discuss

Korhonen 2003

Multifactorial intervention

Kriketos 2001

Intervention and randomised follow‐up less than 6 months

Kris 1994

Intervention and randomised follow‐up less than 6 months

Kristal 1997

Multifactorial intervention

Kromhout 1987

No appropriate control group (and not low fat vs modified fat)

Kummel 2008

Intervention is not dietary fat modification or low‐fat diet

Laitinen 1993

Multifactorial intervention

Laitinen 1994

Multifactorial intervention

Lean 1997

Follow‐up less than 24 months

Leduc 1994

Multifactorial intervention

Lewis 1958

Intervention and randomised follow‐up less than 6 months

Lewis 1981

Intervention and randomised follow‐up less than 6 months

Lewis 1985

Multifactorial intervention

Lichtenstein 2002

Intervention and randomised follow‐up less than 6 months

Lim 2010

Unable to establish contact with authors to gain access to data on health outcomes (none reported in paper)

Linko 1957

Intervention and randomised follow‐up less than 6 months

Lipid Res Clinic 1984

No appropriate control group (and not low fat vs modified fat)

Little 1990

Intervention and randomised follow‐up less than 6 months

Little 2004

Intervention is not dietary fat modification or low‐fat diet

Lottenberg 1996

Intervention and randomised follow‐up less than 6 months

Luszczynska 2007

No appropriate control group (and not low fat vs modified fat)

Lyon Diet Heart 1994

Intervention is not dietary fat modification or low‐fat diet

Lysikova 2003

Intervention and randomised follow‐up less than 6 months

Macdonald 1972

Intervention and randomised follow‐up less than 6 months

Mansel 1990

Intervention is not dietary fat modification or low‐fat diet

MARGARIN 2002

No appropriate control group (and not low fat vs modified fat)

Marniemi 1990

Both intervention groups aimed to lose weight, while the control group did not.

Mattson 1985

Intervention and randomised follow‐up less than 6 months

McAuley 2005

Follow‐up less than 24 months

McCarron 1997

Intervention and randomised follow‐up less than 6 months

McCarron 2001

Intervention is not dietary fat modification or low‐fat diet

McKeown‐Eyssen 1994

Intervention aim was to reduce total fat and increase dietary fibre (saturated fat not mentioned), and no saturated fat intakes during trial reported

McManus 2001

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

McNamara 1981

Intervention and randomised follow‐up less than 6 months

Medi‐RIVAGE 2004

Weight reduction for some low‐fat diet participants (those with BMI > 25) but not in Mediterranean group

MeDiet 2002

Follow‐up less than 24 months

Mensink 1987

Intervention and randomised follow‐up less than 6 months

Mensink 1989

Intervention and randomised follow‐up less than 6 months

Mensink 1990a

Intervention and randomised follow‐up less than 6 months

Mensink 1990b

Intervention and randomised follow‐up less than 6 months

Metroville Health 2003

Unable to establish contact with authors to assess whether any relevant events occurred

Michalsen 2006

Diet plus stress management vs no intervention

Miettinen 1994

Intervention and randomised follow‐up less than 6 months

Millar 1973

No appropriate control group (and not low fat vs modified fat)

Miller 1998

Intervention and randomised follow‐up less than 6 months

Miller 2001

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Milne 1994

No appropriate control group (and not low fat vs modified fat) ‐ the high CHO diet is neither 'usual' or 'low fat' to compare with the modified fat diet

Minnesota Coronary 1989

Although the study proceeded for over 4 years participants (patients) came and went and mean follow‐up was only 1 year

Minnesota HHP 1990

No appropriate control group (and not low fat vs modified fat)

Mojonnier 1980

Unable to establish contact with authors to assess whether any relevant events occurred

Mokuno 1988

Intervention and randomised follow‐up less than 6 months

Mortensen 1983

Intervention and randomised follow‐up less than 6 months

MRFIT substudy 1986

Intervention and randomised follow‐up less than 6 months

MSDELTA 1995

Intervention and randomised follow‐up less than 6 months

MSFAT 1997

Follow‐up less than 24 months

Mujeres Felices 2003

Diet and breast self examination vs no intervention

Mutanen 1997

Intervention and randomised follow‐up less than 6 months

Muzio 2007

Intervention and randomised follow‐up less than 6 months

Naglak 2000

Unable to establish contact with authors to assess whether any relevant events occurred

NAS 1987

Intervention and randomised follow‐up less than 6 months

National Diet Heart 1968

Follow‐up less than 24 months

NCEP weight 1991

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Neil 1995

No appropriate control group (and not low fat vs modified fat)

Neverov 1997

Multifactorial intervention

Next Step 1995

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Nordoy 1971

Intervention and randomised follow‐up less than 6 months

Norway Veg Oil 1968

No appropriate control group (and not low fat vs modified fat)

Nutrition Breast Health

Follow‐up less than 24 months

O'Brien 1976

Intervention and randomised follow‐up less than 6 months

ODES 2006

The study aimed for weight loss in 1 arm and not in the other arm

Oldroyd 2001

Multifactorial intervention

Ole Study 2002

Follow‐up less than 24 months

OLIVE 1997

Unable to establish contact with authors to assess whether any relevant events occurred

ORIGIN 2008

Intervention is not dietary fat modification or low‐fat diet

Oslo Study 2004

Multifactorial intervention

Pascale 1995

Multifactorial intervention

PEP 2001

Multifactorial intervention

PHYLLIS 1993

No appropriate control group (and not low fat vs modified fat)

Pilkington 1960

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Polyp Prevention 1996

Intervention aim was to reduce total fat and increase dietary fibre, fruit and vegetables (saturated fat not mentioned), and no saturated fat intakes during trial reported.

POUNDS LOST 2009

All study arms (low or high total fat) prescribed low saturated fat intake (8%E), no usual fat comparator

PREDIMED 2008

Total fat goals in the low‐fat arm were unclear and authors confirmed that aims were non‐specific (if aims < 30%E this study would be included)

PREMIER 2003

Follow‐up less than 24 months

Pritchard 2002

The study aimed for weight loss in 1 arm and not in the comparison arm

Puget Sound EP 2000

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Rabast 1979

Intervention and randomised follow‐up less than 6 months

Rabkin 1981

Intervention and randomised follow‐up less than 6 months

Radack 1990

Intervention and randomised follow‐up less than 6 months

Rasmussen 1995

Intervention and randomised follow‐up less than 6 months

Reaven 2001

Intervention and randomised follow‐up less than 6 months

Reid 2002

No appropriate control group (and not low fat vs modified fat)

Renaud 1986

Not randomised

Rivellese 1994

Follow‐up less than 24 months

Rivellese 2003

Intervention and randomised follow‐up less than 6 months

Roderick 1997

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Roman CHD prev 1986

Multifactorial intervention

Rose 1987

No appropriate control group (and not low fat vs modified fat)

Sarkkinen 1995

Follow‐up less than 24 months

Schaefer 1995a

Intervention and randomised follow‐up less than 6 months

Schaefer 1995b

Intervention and randomised follow‐up less than 6 months

Schectman 1996

Multifactorial intervention

Schlierf 1995

Multifactorial intervention

Seppanen‐Laakso 1992

Intervention and randomised follow‐up less than 6 months

Seppelt 1996

Follow‐up less than 24 months

Singh 1991

Multifactorial intervention

Singh 1992

No appropriate control group (and not low fat vs modified fat)

Sirtori 1992

Intervention and randomised follow‐up less than 6 months

SLIM 2008

Multifactorial intervention

Sopotsinskaia 1992

The study aimed for weight loss in 1 arm and not in the comparison arm

Stanford NAP 1997

Intervention and randomised follow‐up less than 6 months

Stanford Weight 1994

The study aimed for weight loss in 1 arm and not in the comparison arm

Starmans 1995

Intervention and randomised follow‐up less than 6 months

Steinbach 1996

Multifactorial intervention

Steptoe 2001

No appropriate control group (and not low fat vs modified fat)

Stevens 2002

Diet plus breast self examination vs no intervention

Stevenson 1988

No appropriate control group (and not low fat vs modified fat)

Strychar 2009

Follow‐up less than 24 months

Sweeney 2004

Intervention is not dietary fat modification or low fat diet

Søndergaard 2003

Follow‐up less than 24 months

TAIM 1992

Intervention is not dietary fat modification or low fat diet

Tapsell 2004

Unable to establish contact with authors to assess whether any relevant events occurred

THIS DIET 2008

All study arms prescribed low saturated fat intake, no usual fat comparator

TOHP I 1992

Multifactorial intervention

TONE 1997

Intervention is not dietary fat modification or low‐fat diet

Toobert 2003

Multifactorial intervention

Towle 1994

Intervention and randomised follow‐up less than 6 months

TRANSFACT 2006

Intervention and randomised follow‐up less than 6 months

Treatwell 1992

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Tromsø Heart 1989

Multifactorial intervention

Troyer 2010

Longest duration only 12 months

UK PDS 1996

No appropriate control group (and not low fat vs modified fat)

Urbach 1952

No appropriate control group (and not low fat vs modified fat)

Uusitupa 1993

Multifactorial intervention

Vavrikova 1958

Intervention and randomised follow‐up less than 6 months

Verheiden 2003

Unable to establish contact with authors to assess whether any relevant events occurred

Wass 1981

Intervention and randomised follow‐up less than 6 months

Wassertheil 1985

Intervention is not dietary fat modification or low fat diet

WATCH 1999

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Watts 1988

Intervention and randomised follow‐up less than 6 months

Weintraub 1992

No appropriate control group (and not low fat vs modified fat)

Westman 2006

Intervention is not dietary fat modification or low fat diet

Weststrate 1998

Intervention and randomised follow‐up less than 6 months

WHEL 2007

Study aimed to reduce total fat, but saturated fat goals were not mentioned, and saturated fat intake in the intervention group was more than 80% of that in the control (81%)

WHO primary prev 1979

Multifactorial intervention

WHT 1990

Neither mortality nor cardiovascular morbidity data available as such data were not collected in the study

WHT Feasibility 2003

Neither mortality nor cardiovascular morbidity data available (only decided after contact with at least 1 author)

Wilke 1974

Intervention and randomised follow‐up less than 6 months

Williams 1990

Intervention is not dietary fat modification or low‐fat diet

Williams 1992

Intervention is not dietary fat modification or low‐fat diet

Williams 1994

Intervention is not dietary fat modification or low‐fat diet

Wilmot 1952

No appropriate control group (and not low fat vs modified fat)

Wing 1998

No appropriate control group (and not low fat vs modified fat)

WINS UK 2011

Stated aim was to reduce total fat by 50%, no saturated fat aims

WOMAN 2007

Lifestyle intervention includes exercise and weight as well as diet

Wood 1988

Intervention is not dietary fat modification or low‐fat diet

Woollard 2003

Multifactorial intervention including smoking, weight, exercise and alcohol components

Working Well 1996

Multifactorial intervention

Zock 1995

Intervention and randomised follow‐up less than 6 months

Data and analyses

Open in table viewer
Comparison 1. SFA reduction vs usual diet ‐ Primary outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

12

55858

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.90, 1.05]
Analysis 1.1
Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 1 All‐cause mortality.

Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 1 All‐cause mortality.

2 Cardiovascular mortality Show forest plot

12

53421

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.80, 1.12]
Analysis 1.2
Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 2 Cardiovascular mortality.

Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 2 Cardiovascular mortality.

3 Combined cardiovascular events Show forest plot

13

53300

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.72, 0.96]
Analysis 1.3
Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 3 Combined cardiovascular events.

Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 3 Combined cardiovascular events.

Open in table viewer
Comparison 2. SFA reduction vs usual diet ‐ secondary health events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Myocardial infarctions Show forest plot

11

53167

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.80, 1.01]
Analysis 2.1
Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 1 Myocardial infarctions.

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 1 Myocardial infarctions.

2 Non‐fatal MI Show forest plot

9

52834

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.80, 1.13]
Analysis 2.2
Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 2 Non‐fatal MI.

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 2 Non‐fatal MI.

3 Stroke Show forest plot

8

50952

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.89, 1.12]
Analysis 2.3
Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 3 Stroke.

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 3 Stroke.

4 CHD mortality Show forest plot

10

53159

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.84, 1.15]
Analysis 2.4
Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 4 CHD mortality.

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 4 CHD mortality.

5 CHD events Show forest plot

12

53199

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.74, 1.03]
Analysis 2.5
Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 5 CHD events.

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 5 CHD events.

6 Diabetes diagnoses Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 2.6
Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 6 Diabetes diagnoses.

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 6 Diabetes diagnoses.

Open in table viewer
Comparison 3. SFA reduction vs usual diet ‐ other secondary outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Total cholesterol, mmol/L Show forest plot

14

7115

Mean Difference (IV, Random, 95% CI)

‐0.24 [‐0.36, ‐0.13]
Analysis 3.1
Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 1 Total cholesterol, mmol/L.

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 1 Total cholesterol, mmol/L.

2 LDL cholesterol, mmol/L Show forest plot

5

3291

Mean Difference (IV, Random, 95% CI)

‐0.19 [‐0.33, ‐0.05]
Analysis 3.2
Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 2 LDL cholesterol, mmol/L.

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 2 LDL cholesterol, mmol/L.

3 HDL cholesterol, mmol/L Show forest plot

6

5147

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.02, 0.01]
Analysis 3.3
Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 3 HDL cholesterol, mmol/L.

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 3 HDL cholesterol, mmol/L.

4 Triglycerides, mmol/L Show forest plot

7

3845

Mean Difference (IV, Random, 95% CI)

‐0.08 [‐0.21, 0.04]
Analysis 3.4
Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 4 Triglycerides, mmol/L.

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 4 Triglycerides, mmol/L.

5 total cholesterol /HDL ratio Show forest plot

3

2985

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.33, 0.13]
Analysis 3.5
Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 5 total cholesterol /HDL ratio.

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 5 total cholesterol /HDL ratio.

6 LDL /HDL ratio Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only
Analysis 3.6
Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 6 LDL /HDL ratio.

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 6 LDL /HDL ratio.

7 Lp(a), mmol/L Show forest plot

2

2882

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.00, 0.00]
Analysis 3.7
Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 7 Lp(a), mmol/L.

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 7 Lp(a), mmol/L.

8 Insulin sensitivity Show forest plot

4

Mean Difference (IV, Random, 95% CI)

Subtotals only
Analysis 3.8
Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 8 Insulin sensitivity.

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 8 Insulin sensitivity.

8.1 HbA1c (glycosylated haemoglobin), %

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 GTT (glucose tolerance test), glucose at 2 hours, mmol/L

3

249

Mean Difference (IV, Random, 95% CI)

‐1.69 [‐2.55, ‐0.82]

8.3 HOMA

1

2832

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.04, 0.04]

Flow diagram for review
Figures and Tables -
Figure 1

Flow diagram for review

Navigate to figure in ReviewOpen in new tab

Methodological quality summary: review authors' judgements about each methodological quality item for each included study. Please note that while Rose 1965 (Rose corn oil 1965; Rose olive 1965) and WHI 2006 (WHI with CVD 2006; WHI without CVD 2006) each appear twice in this summary, they are each a single trial. Rose 1965 was a 3‐arm trial and we have used the two intervention arms separately in the review, while WHI 2006 provided some data separately for people with or without CVD at baseline.
Figures and Tables -
Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study. Please note that while Rose 1965 (Rose corn oil 1965; Rose olive 1965) and WHI 2006 (WHI with CVD 2006; WHI without CVD 2006) each appear twice in this summary, they are each a single trial. Rose 1965 was a 3‐arm trial and we have used the two intervention arms separately in the review, while WHI 2006 provided some data separately for people with or without CVD at baseline.

Navigate to figure in ReviewOpen in new tab

Forest plot of comparison: 1 SFA reduction vs usual diet ‐ health events, outcome: 1.1 All‐cause mortality.
Figures and Tables -
Figure 3

Forest plot of comparison: 1 SFA reduction vs usual diet ‐ health events, outcome: 1.1 All‐cause mortality.

Navigate to figure in ReviewOpen in new tab

Funnel plot of comparison: fat modification or reduction vs usual diet ‐ total mortality.
Figures and Tables -
Figure 4

Funnel plot of comparison: fat modification or reduction vs usual diet ‐ total mortality.

Navigate to figure in ReviewOpen in new tab

Forest plot of comparison: 1 SFA reduction vs usual diet ‐ Primary outcomes, outcome: 1.2 Cardiovascular mortality.
Figures and Tables -
Figure 5

Forest plot of comparison: 1 SFA reduction vs usual diet ‐ Primary outcomes, outcome: 1.2 Cardiovascular mortality.

Navigate to figure in ReviewOpen in new tab

Forest plot of comparison: 1 SFA reduction vs usual diet ‐ Primary outcomes, outcome: 1.3 Combined cardiovascular events.
Figures and Tables -
Figure 6

Forest plot of comparison: 1 SFA reduction vs usual diet ‐ Primary outcomes, outcome: 1.3 Combined cardiovascular events.

Navigate to figure in ReviewOpen in new tab

Funnel plot of comparison: fat modification or reduction vs usual diet ‐ combined cardiovascular events.
Figures and Tables -
Figure 7

Funnel plot of comparison: fat modification or reduction vs usual diet ‐ combined cardiovascular events.

Navigate to figure in ReviewOpen in new tab

Exploring saturated fat cut‐offs.
Figures and Tables -
Figure 8

Exploring saturated fat cut‐offs.

Navigate to figure in ReviewOpen in new tab

Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 1 All‐cause mortality.
Figures and Tables -
Analysis 1.1

Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 1 All‐cause mortality.

Navigate to figure in ReviewOpen in new tab

Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 2 Cardiovascular mortality.
Figures and Tables -
Analysis 1.2

Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 2 Cardiovascular mortality.

Navigate to figure in ReviewOpen in new tab

Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 3 Combined cardiovascular events.
Figures and Tables -
Analysis 1.3

Comparison 1 SFA reduction vs usual diet ‐ Primary outcomes, Outcome 3 Combined cardiovascular events.

Navigate to figure in ReviewOpen in new tab

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 1 Myocardial infarctions.
Figures and Tables -
Analysis 2.1

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 1 Myocardial infarctions.

Navigate to figure in ReviewOpen in new tab

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 2 Non‐fatal MI.
Figures and Tables -
Analysis 2.2

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 2 Non‐fatal MI.

Navigate to figure in ReviewOpen in new tab

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 3 Stroke.
Figures and Tables -
Analysis 2.3

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 3 Stroke.

Navigate to figure in ReviewOpen in new tab

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 4 CHD mortality.
Figures and Tables -
Analysis 2.4

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 4 CHD mortality.

Navigate to figure in ReviewOpen in new tab

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 5 CHD events.
Figures and Tables -
Analysis 2.5

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 5 CHD events.

Navigate to figure in ReviewOpen in new tab

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 6 Diabetes diagnoses.
Figures and Tables -
Analysis 2.6

Comparison 2 SFA reduction vs usual diet ‐ secondary health events, Outcome 6 Diabetes diagnoses.

Navigate to figure in ReviewOpen in new tab

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 1 Total cholesterol, mmol/L.
Figures and Tables -
Analysis 3.1

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 1 Total cholesterol, mmol/L.

Navigate to figure in ReviewOpen in new tab

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 2 LDL cholesterol, mmol/L.
Figures and Tables -
Analysis 3.2

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 2 LDL cholesterol, mmol/L.

Navigate to figure in ReviewOpen in new tab

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 3 HDL cholesterol, mmol/L.
Figures and Tables -
Analysis 3.3

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 3 HDL cholesterol, mmol/L.

Navigate to figure in ReviewOpen in new tab

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 4 Triglycerides, mmol/L.
Figures and Tables -
Analysis 3.4

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 4 Triglycerides, mmol/L.

Navigate to figure in ReviewOpen in new tab

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 5 total cholesterol /HDL ratio.
Figures and Tables -
Analysis 3.5

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 5 total cholesterol /HDL ratio.

Navigate to figure in ReviewOpen in new tab

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 6 LDL /HDL ratio.
Figures and Tables -
Analysis 3.6

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 6 LDL /HDL ratio.

Navigate to figure in ReviewOpen in new tab

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 7 Lp(a), mmol/L.
Figures and Tables -
Analysis 3.7

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 7 Lp(a), mmol/L.

Navigate to figure in ReviewOpen in new tab

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 8 Insulin sensitivity.
Figures and Tables -
Analysis 3.8

Comparison 3 SFA reduction vs usual diet ‐ other secondary outcomes, Outcome 8 Insulin sensitivity.

Navigate to figure in ReviewOpen in new tab
Summary of findings for the main comparison. Summary of findings: What is the effect of reducing saturated fat compared to usual saturated fat on CVD risk in adults? (Note: for the full set of GRADE tables see additional tables 24 to 28)

Low saturated fat compared with usual saturated fat for CVD risk

Patient or population: people at any baseline risk of CVD

Intervention: reduction of saturated fat intake

Comparison: usual saturated fat intake

Outcomes

Relative effect
(95% CI)

Absolute effects

(per 10,000)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

All‐cause mortality

follow‐up mean duration 56 months1

RR 0.97 (0.90 to 1.05)

17 fewer

(from 57 fewer to 29 more)

55,858
(12)

⊕⊕⊕⊝
moderate2,3,4,5,6

Critical importance

Cardiovascular mortality

follow‐up mean duration 53 months1

RR 0.95 (0.80 to 1.12)

10 fewer
(from 39 fewer to 23 more)

53,421
(12)

⊕⊕⊕⊝
moderate2,3,4,5,6

Critical importance

Combined cardiovascular events

follow‐up mean duration 52 months1

RR 0.83 (0.72 to 0.96)

138 fewer

(from 33 fewer to 228 fewer)

53,300
(13)

⊕⊕⊕⊝
moderate2,4,6,7,8

Critical importance

Myocardial infarctions

follow‐up mean duration 55 months

RR 0.90 (0.80 to 1.01)

32 fewer

(from 63 fewer to 3 more)

53,167
(11)

⊕⊕⊕⊝
moderate2,3,4,5,6

Critical importance

Non‐fatal MI

follow‐up mean duration 55 months1

RR 0.95 (0.80 to 1.13)

13 fewer

(from 51 fewer to 33 more)

52,834
(9)

⊕⊕⊕⊝
moderate2,3,4,5,9

Critical importance

Stroke

follow‐up mean duration 59 months1

RR 1.00 (0.89 to 1.12)

0 fewer

(from 25 fewer to 25 more)

50,952
(8)

⊕⊕⊕⊝
moderate2,3,4,5,9

Critical importance

CHD mortality

follow‐up mean duration 65 months1

RR 0.98 (0.84 to 1.15)

3 fewer

(from 25 fewer to 23 more)

53,159
(10)

⊕⊕⊕⊝
moderate2,3,4,5,6

Critical importance

CHD events

follow‐up mean duration 59 months1

RR 0.87 (0.74 to 1.03)

80 fewer

(from 160 fewer to 19 more)

53,199
(12)

⊕⊕⊝⊝
low2,4,5,6,10

Critical importance

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio; CHD: coronary heart disease.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Minimum study duration was 24 months

2These large RCTs of relatively long duration were well randomised but fewer than half had good allocation concealment (the rest were unclear). Blinding was only well‐conducted in 1 RCT, however blinding is very difficult in trials of dietary fat intake. Incomplete outcome data were variable, and most included studies had systematic differences in care (i.e. intervention group had more time or attention than the control group). We noted no other biases. We downgraded each study once for a combination of these issues around validity and issues around precision. The level of compliance with interventions involving long‐term behaviour change, such as those used in these studies, can vary widely. This is likely to attenuate the pooled effect and bias it towards the null.

3No important heterogeneity; I² ≤ 30%

4These RCTs directly assessed the effect of lower vs usual saturated fat intake on health outcomes of interest. Participants included men and women with and without CVD at baseline (also some participants with CVD risk factors like diabetes, or at risk of cancers).

5The 95% CI crosses 1.0 and does not exclude important benefit or harm.

6The funnel plot did not suggest any small‐study (publication) bias.

7Potentially important heterogeneity was identified; I² = 65%. However, the heterogeneity was partly explained by the degree of saturated fat reduction, and the degree of cholesterol lowering achieved (in subgrouping and in meta‐regression). For this reason we did not downgrade the study for inconsistency.

8The 95% CI does not cross 1.0 or a threshold of important harm.

9Too few studies to reliably assess small‐study bias (< 10 RCTs)

10Important heterogeneity; I² = 66%.

Figures and Tables -
Summary of findings for the main comparison. Summary of findings: What is the effect of reducing saturated fat compared to usual saturated fat on CVD risk in adults? (Note: for the full set of GRADE tables see additional tables 24 to 28)
Navigate to table in Review
Table 1. Comparison of study interventions for included RCTs

Reference

Population

CVD risk category

Is intervention delivered to Individual or group?

intervention given by?

Face‐to‐face or other?

Number of visits

Is intervention advice only or other intervention?

Black 1994

People with non‐melanoma skin cancer

Low

Unclear

Dietitian

Face‐to‐face

8 x weekly classes then monthly follow‐up sessions

Advice (behaviour techniques learning)

DART 1989

Men recovering from a MI

High

Individual

Dietitian

Face‐to‐face

9

Advice (diet advice, recipes and encouragement)

Houtsmuller 1979

Adults with newly‐diagnosed diabetes

Moderate

Unclear

Dietitian

Unclear

Unclear

Advice?

Ley 2004

People with impaired glucose intolerance or high normal blood glucose

Moderate

Small group

Unclear

Face‐to‐face

Monthly meetings

Advice (education, personal goal setting, self‐monitoring)

Moy 2001

Middle‐aged siblings of people with early CHD, with at least 1 CVD risk factor

Moderate

Individual

Trained nurse

Face‐to‐face

6 ‐ 8 weekly for 2 years

Advice (individualised counselling sessions)

MRC 1968

Free‐living men who have survived a 1st MI

High

Individual

Dietitian

Face‐to‐face

Unclear

Advice and supplement (soy oil)

Oslo Diet‐Heart 1966

Men with previous MI

High

Individual

Dietitian

Face‐to‐face and other

Unclear

Advice and supplement (food)

Oxford Retinopathy 1978

Newly‐diagnosed non‐insulin‐dependent diabetics

Moderate

Individual

Diabetes dietitian

Face‐to‐face

After 1 month then at 3‐month intervals

Advice

Rose corn oil 1965

Men (?) with angina or following MI

High

Unclear

Unclear

Unclear

Follow‐up clinic monthly, then every 2 months

Advice and supplement (oil)

Rose olive 1965

Men (?) with angina or following MI

High

Unclear

Unclear

Unclear

Follow‐up clinic monthly, then every 2 months

Advice and supplement (oil)

Simon 1997

Women with a high risk of breast cancer

Low

Individual followed by individual or group

Dietitian

Face‐to‐face

Bi‐weekly over 3 months followed by monthly

Advice (individualised eating plan and counselling sessions)

STARS 1992

Men with angina referred for angiography

High

individual

Dietitian

Face‐to‐face

Clinic visits at 3‐months intervals

Advice

Sydney Diet‐Heart 1978

Men with angina referred for angiography

High

Individual

Unclear

Face‐to‐face

3 times in 1st year and twice annually thereafter

Advice

Veterans Admin 1969

Men living at the Veterans Administration Center

Low

Individual

Unclear (whole diet provided)

N/A

N/A

Diet provided

WHI with CVD 2006

Post‐menopausal women aged 50 ‐ 79 with CVD at baseline

High

Group

Nutritionists

Face‐to‐face

18 sessions/ 1st yr and quarterly maintenance sessions after

Advice

WHI without CVD 2006

Post‐menopausal women aged 50 ‐ 79 without CVD at baseline

Low

Group

Nutritionists

Face‐to‐face

18 sessions/ 1st yr and quarterly maintenance sessions after

Advice

WINS 2006

Women with localised resected breast cancer

Low

Individual followed by group

Dietitian

Face‐to‐face

8 bi‐weekly sessions, then 3‐monthly contact and optional monthly sessions

Advice

N/A: not applicable
Figures and Tables -
Table 1. Comparison of study interventions for included RCTs
Navigate to table in Review
Table 2. Number of participants and number of outcomes for dichotomous variables (by intervention arm)

Participants

All‐cause mortality

CV mortality

CVD events

MI

Non‐fatal MI

Stroke

CHD mortality

CHD events

Diabetes Diagnoses

Black 1994

133

133

133

133

0

0

0

0

0

0

DART 1989

2033

2033

2033

2033

2033

2033

0

2033

2033

0

Houtsmuller 1979

102

0

0

102

102

0

0

102

102

0

Ley 2004

176

176

176

176

176

0

176

0

176

0

Moy 2001

267

0

0

235

235

235

235

0

267

0

MRC 1968

393

393

393

393

393

393

393

393

393

0

Oslo Diet‐Heart 1966

412

412

412

412

412

412

412

412

412

0

Oxford Retinopathy 1978

249 (data not provided by arm)

0

0

0

0

0

0

0

0

0

Rose corn oil 1965

41

41

41

41

41

41

0

41

41

0

Rose olive 1965

39

39

39

39

39

39

0

39

39

0

Simon 1997

194 (data not provided by arm)

0

0

0

0

0

0

0

0

0

STARS 1992

60

55

55

55

55

0

55

0

55

0

Sydney Diet‐Heart 1978

458

458

458

0

0

0

0

458

0

0

Veterans Admin 1969

846

846

846

846

846

846

846

846

846

0

WHI with CVD 2006

2277

0

2277

2277

0

2277

2277

2277

2277

0

WHI without CVD 2006

48835

48835

46558

46558

48835

46558

46558

46558

46558

48835

WINS 2006

2437

2437

0

0

0

0

0

0

0

0

Total Participants

58509

55858

53421

53300

53167

52834

50952

53159

53204

48835

Percent of participants for this outcome

100%

95%

91%

91%

91%

90%

87%

91%

91%

83%

These numbers are the numbers of participants in each study who were available for assessment of outcomes within meta‐analysis (not necessarily the number of participants randomised within the trial).

Figures and Tables -
Table 2. Number of participants and number of outcomes for dichotomous variables (by intervention arm)
Navigate to table in Review
Table 3. Number of participants and number of participants with data for continuous outcomes (by intervention arm)

Participants

Total cholesterol

LDL cholesterol

HDL cholesterol

Triglycerides

TG/HDL ratio

Total cholesterol/HDL ratio

LDL/HDL ratio

LP (a)

Insulin sensitivity

Black 1994

133

0

0

0

0

0

0

0

0

0

DART 1989

2033

1855

0

1855

0

0

0

0

0

0

Houtsmuller 1979

102

96

0

0

96

0

0

0

0

96

Ley 2004

176

103

103

103

103

0

103

0

0

103

Moy 2001

267

0

235

235

235

0

0

0

0

0

MRC 1968

393

177

0

0

0

0

0

0

0

0

Oslo Diet‐Heart 1966

412

329

0

0

0

0

0

0

0

0

Oxford Retinopathy 1978

249

58

0

0

0

0

0

0

0

0

Rose corn oil 1965

41

22

0

0

0

0

0

0

0

0

Rose olive 1965

39

24

0

0

0

0

0

0

0

0

Simon 1997

194

72

71

72

71

0

0

0

0

0

STARS 1992

55

50

50

50

50

0

50

50

50

50

Sydney Diet‐Heart 1978

458

458

0

0

458

0

0

0

0

0

Veterans Admin 1969

846

843

0

0

0

0

0

0

0

0

WHI with CVD 2006

2277

0

0

0

0

0

0

0

0

0

WHI without CVD 2006

48835

2832

2832

2832

2832

0

2832

0

2832

2832

WINS 2006

2437

196

0

0

0

0

0

0

0

0

Total Participants

58952

7115

3291

5147

3845

0

2985

50

2882

3081

Percent of participants for this outcome

100%

12%

6%

9%

7%

0%

5%

0.1%

5%

5%

These numbers are the numbers of participants in each study who were available for assessment of outcomes within meta‐analysis (not necessarily the number of participants randomised within the trial).

Figures and Tables -
Table 3. Number of participants and number of participants with data for continuous outcomes (by intervention arm)
Navigate to table in Review
Table 4. All‐cause mortality, sensitivity analyses

Analysis

RR (95% CI) of all‐cause mortality

I²

No. of events

No. of participants

Main analysis

0.97 (0.90 to 1.05)

3%

3276

> 55,000

Sensitivity analyses

Stated aim to reduce SFA

0.97 (0.89 to 1.06)

11%

3231

> 53,000

SFA significantly reduced

0.99 (0.92 to 1.06)

0%

3095

> 54,000

TC significantly reduced

0.96 (0.83 to 1.11)

33%

2871

> 52,000

Minus WHI

0.96 (0.84 to 1.11)

12%

872

> 7000

Mantel‐Haenszel fixed‐effect

0.98 (0.91 to 1.04)

3%

3276

> 55,000

Peto fixed‐effect

0.97 (0.90 to 1.05)

16%

3276

> 55,000

SFA: saturated fatty acids
TC: total cholesterol

Figures and Tables -
Table 4. All‐cause mortality, sensitivity analyses
Navigate to table in Review
Table 5. All‐cause mortality, subgroup data

Analysis, P value for subgroup differences

RR (95% CI) of all‐cause mortality

I²

No. of events

No. of participants

Subgroup by replacement

P = 0.79

PUFA replacement

0.96 (0.82 to 1.13)

26%

824

> 4000

MUFA replacement

3.00 (0.33 to 26.99)

N/A

4

52

CHO replacement

0.98 (0.91 to 1.05)

0%

2677

> 53,000

Protein replacement

0.98 (0.91 to 1.06)

0%

2673

> 53,000

Subgroup by duration, P = 0.60

Up to 24 months

0.99 (0.78 to 1.26)

0%

236

> 2000

> 24 to 48 months

0.96 (0.83 to 1.12)

0%

414

> 1000

> 48 months

1.00 (0.79 to 1.27)

55%

2618

> 52,000

Unclear duration

0.33 (0.07 to 1.61)

N/A

8

> 100

Subgroup by baseline SFA, P = 0.48

Up to 12%E SFA

1.18 (0.60 to 2.32)

N/A

34

> 2400

> 12 to 15%E SFA

1.01 (0.86 to 1.19)

26%

2706

> 51,000

> 15 to 18%E SFA

0.35 (0.04 to 3.12)

N/A

4

55

> 18%E SFA

0.98 (0.83 to 1.15)

N/A

351

846

Subgroup by SFA change, P = 0.31

Up to 4%E SFA difference

1.02 (0.88 to 1.19)

26%

2737

> 53,000

> 4 to 8%E SFA difference

0.41 (0.08 to 2.07)

0%

7

> 100

> 8%E SFA difference

0.98 (0.83 to 1.15)

N/A

351

> 800

Subgroup by sex, P = 0.40

Men

0.96 (0.83 to 1.11)

13%

830

> 4000

Women

0.98 (0.91 to 1.06)

0%

2438

> 51,000

Mixed, men and women

0.33 (0.07 to 1.61)

N/A

8

176

Subgroup by CVD risk, P = 0.40

Low CVD risk

0.98 (0.91 to 1.05)

0%

2792

> 52,000

Moderate CVD risk

0.33 (0.07 to 1.61)

N/A

8

176

Existing CVD

0.97 (0.90 to 1.05)

33%

476

> 3000

Subgroup by serum TC reduction,

P = 0.85

TC reduced by ≥ 0.2 mmol/L

0.96 (0.81 to 1.14)

32%

823

> 4000

TC reduced by < 0.2 mmol/L

0.98 (0.91 to 1.06)

0%

2450

> 51,000

Unclear TC change

0.51 (0.05 to 5.46)

N/A

3

> 100

Subgroup by decade of publication, P = 0.28

1960s

0.92 (0.80 to 1.07)

2%

532

> 1700

1970s

1.49 (0.95 to 2.34)

N/A

67

458

1980s

0.98 (0.76 to 1.25)

N/A

224

2033

1990s

0.41 (0.08 to 2.07)

0%

7

188

2000s

0.98 (0.83 to 1.15)

5%

2446

> 51,000

CHO: carbohydrate
CVD: cardiovascular disease
MUFA: mon‐unsaturated fatty acid
N/A: not applicable
PUFA: polyunsaturated fatty caid
SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 5. All‐cause mortality, subgroup data
Navigate to table in Review
Table 6. CVD mortality, sensitivity analyses

Analysis

RR (95% CI) of CVD mortality

I²

No. of events

No. of participants

Main analysis

0.95 (0.80 to 1.12)

30%

1096

>53000

Sensitivity analyses

Stated aim to reduce SFA

0.96 (0.81 to 1.13)

32%

1089

> 53,000

SFA significantly reduced

0.96 (0.79 to 1.18)

42%

945

> 52,000

TC significantly reduced

1.00 (0.86 to 1.16)

19%

942

> 52,000

Minus WHI

0.92 (0.72 to 1.18)

40%

563

> 4000

Mantel‐Haenszel fixed‐effect

0.95 (0.85 to 1.07)

30%

1096

> 53,000

Peto fixed‐effect

0.95 (0.84 to 1.08)

41%

1096

> 53,000

SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 6. CVD mortality, sensitivity analyses
Navigate to table in Review
Table 7. CVD mortality, subgroup data

Analysis, P value for subgroup differences

RR (95% CI) of CVD mortality

I²

No. of events

No. of participants

Subgroup by replacement

P = 0.79

PUFA replacement

0.95 (0.73 to 1.25)

55%

553

> 4000

MUFA replacement

3.00 (0.33 to 26.99)

N/A

4

52

CHO replacement

0.99 (0.86 to 1.14)

0%

745

> 51,000

Protein replacement

0.99 (0.86 to 1.14)

0%

741

> 51,000

Subgroup by duration, P = 0.33

Up to 24 months

1.26 (0.54 to 2.94)

26%

213

> 2000

> 24 to 48 months

0.79 (0.57 to 1.08)

14%

194

> 1000

> 48 months

1.01 (0.79 to 1.30)

54%

685

> 49,000

Unclear duration

0.25 (0.03 to 2.19)

N/A

5

> 100

Subgroup by baseline SFA, P = 0.13

Up to 12%E SFA

N/A

> 12 to 15%E SFA

1.04 (0.88 to 1.24)

19%

803

> 51,000

> 15 to 18%E SFA

0.35 (0.04 to 3.12)

N/A

4

55

> 18%E SFA

0.70 (0.51 to 0.96)

N/A

138

846

Subgroup by SFA change, P = 0.08

Up to 4%E SFA difference

1.05 (0.89 to 1.24)

21%

801

>51000

> 4 to 8%E SFA difference

0.29 (0.05 to 1.70)

0%

6

> 100

> 8%E SFA difference

0.70 (0.51 to 0.96)

N/A

152

> 900

Subgroup by sex, P = 0.45

Men

0.96 (0.73 to 1.25)

48%

559

> 4000

Women

1.00 (0.84 to 1.19)

0%

533

> 48,000

Mixed, men and women

0.25 (0.03 to 2.19)

NA

5

176

Subgroup by CVD risk, p=0.26

Low CVD risk

0.84 (0.60 to 1.16)

54%

568

> 47,000

Moderate CVD risk

0.25 (0.03 to 2.19)

NA

5

176

Existing CVD

1.04 (0.83 to 1.31)

33%

524

> 5000

Subgroup by serum TC reduction,

P = 0.57

TC reduced by ≥ 0.2 mmol/L

0.95 (0.73 to 1.25)

55%

553

> 4000

TC reduced by < 0.2 mmol/L

1.00 (0.84 to 1.18)

0%

542

> 49,000

Unclear TC change

0.20 (0.01 to 4.15)

N/A

2

> 100

Subgroup by decade of publication, P = 0.04

1960s

0.78 (0.63 to 0.97)

2%

289

> 1700

1970s

1.59 (0.99 to 2.55)

N/A

62

458

1980s

1.01 (0.77 to 1.31)

N/A

201

> 2000

1990s

0.29 (0.05 to 1.70)

0%

6

188

2000s

0.99 (0.83 to 1.18)

0%

538

> 49,000

CHO: carbohydrate
CVD: cardiovascular disease
MUFA: mon‐unsaturated fatty acid
N/A: not applicable
PUFA: polyunsaturated fatty caid
SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 7. CVD mortality, subgroup data
Navigate to table in Review
Table 8. CVD events, sensitivity analyses

Analysis

RR (95% CI) of CVD events

I²

No. of events

No. of participants

Main analysis

0.83 (0.72 to 0.96)

65%

4377

> 53,000

Sensitivity analyses

Stated aim to reduce SFA

0.84 (0.72 to 0.97)

69%

4354

> 52,000

SFA significantly reduced

0.91 (0.79 to 1.04)

53%

4012

> 52,000

TC significantly reduced

0.81 (0.68 to 0.98)

77%

4092

> 52,000

Minus WHI

0.75 (0.61 to 0.91)

51%

932

> 4000

Mantel‐Haenszel fixed‐effect

0.93 (0.88 to 0.98)

65%

4377

> 53,000

Peto fixed‐effect

0.92 (0.86 to 0.98)

72%

4377

> 53,000

SFA: saturated fatty ac5d
TC: total cholesterol

Figures and Tables -
Table 8. CVD events, sensitivity analyses
Navigate to table in Review
Table 9. CVD events, subgroup data

Analysis, P value for subgroup differences

RR (95% CI) of CVD events

I²

No. of events

No. of participants

Subgroup by replacement

P = 0.14

PUFA replacement

0.73 (0.58 to 0.92)

69%

884

> 3000

MUFA replacement

1.00 (0.53 to 1.89)

NA

22

52

CHO replacement

0.93 (0.79 to 1.08)

57%

3785

> 51,000

Protein replacement

0.98 (0.90 to 1.06)

15%

3757

> 51,000

Subgroup by duration, P = 0.15

Up to 24 months

0.96 (0.78 to 1.16)

0%

330

> 2000

> 24 to 48 months

0.73 (0.56 to 0.95)

50%

383

> 1000

> 48 months

0.93 (0.79 to 1.11)

75%

3599

> 49,000

Unclear duration

0.43 (0.17 to 1.08)

NA

65

> 200

Subgroup by baseline SFA, P = 0.13

Up to 12%E SFA

NA

> 12 to 15%E SFA

0.98 (0.91 to 1.05)

6%

3765

> 51,000

> 15 to 18%E SFA

0.41 (0.22 to 0.78)

NA

28

55

> 18%E SFA

0.79 (0.63 to 1.00)

NA

219

846

Subgroup by SFA change, P = 0.005

Up to 4%E SFA difference

0.98 (0.91 to 1.05)

6%

3763

> 51,000

> 4 to 8%E SFA difference

0.40 (0.22 to 0.74)

0%

30

> 100

> 8%E SFA difference

0.79 (0.63 to 1.00)

NA

219

> 800

Subgroup by sex, P = 0.05

Men

0.80 (0.69 to 0.93)

24%

859

> 3000

Women

1.00 (0.88 to 1.14)

60%

3445

> 48,000

Mixed, men and women

0.59 (0.23 to 1.49)

71%

73

> 500

Subgroup by CVD risk, P = 0.67

Low CVD risk

0.89 (0.75 to 1.06)

40%

3130

> 47,000

Moderate CVD risk

0.59 (0.23 to 1.49)

71%

73

> 500

Existing CVD

0.86 (0.71 to 1.05)

63%

1174

> 5000

Subgroup by serum TC reduction,

P = 0.03

TC reduced by ≥ 0.2 mmol/L

0.74 (0.59 to 0.92)

63%

887

> 4000

TC reduced by < 0.2 mmol/L

0.99 (0.90 to 1.08)

15%

3488

> 49,00

Unclear TC change

0.20 (0.01 to 4.15)

NA

2

> 100

Subgroup by decade of publication, P , 0.0001

1960s

0.79 (0.69 to 0.91)

0%

546

> 1700

1970s

0.27 (0.14 to 0.52)

NA

38

102

1980s

0.92 (0.74 to 1.15)

NA

283

> 2000

1990s

0.40 (0.22 to 0.74)

0%

30

188

2000s

0.99 (0.89 to 1.11)

25%

3480

> 49,000

CHO: carbohydrate
CVD: cardiovascular disease
MUFA: mon‐unsaturated fatty acid
N/A: not applicable
PUFA: polyunsaturated fatty caid
SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 9. CVD events, subgroup data
Navigate to table in Review
Table 10. Metaregression of effects of SFA reduction on cardiovascular events

Regression factor

No. of studies

Constant

Coefficient (95% CI)

P value

Proportion of between study variation explained

Change in SFA as %E

8

0.01

0.05 (‐0.03 to 0.13)

0.16

89%

Change in SFA as % of control

8

0.26

0.01 (‐0.01 to 0.03)

0.14

89%

Baseline SFA as %E

8

0.68

‐0.06 (‐0.15 to 0.04)

0.19

81%

Change in TC, mmol/L

12

0.03

0.69 (0.05 to 1.33)

0.04

99%

Change in PUFA as %E

5

‐0.01

‐0.02 (‐0.08 to 0.03)

0.25

100%

Change in MUFA as %E

5

‐0.26

‐0.03 (‐0.14 to 0.09)

0.50

‐87%

Change in CHO as %E

7

‐0.11

‐0.00 (‐0.05 to 0.05)

0.92

‐273%

Change in total fat intake as %E

9

‐0.17

‐0.01 (‐0.03 to 0.01)

0.28

100%

Gender*

13

‐0.17

‐0.14 (‐0.63 to 0.35)

0.55

‐13%

Study duration

13

‐0.47

0.00 (‐0.01 to 0.02)

0.76

‐24.8

CVD risk at baseline**

13

‐0.44

0.03 (‐0.48 to 0.55)

0.89

‐39%

*0 = women, 1 = mixed, 2 = men
** 1 = Low CVD risk, 2 = Moderate CVD risk, 3 = existing CVD
CHO: carbohydrate
CVD: cardiovascular disease
MUFA: mon‐unsaturated fatty acid
PUFA: polyunsaturated fatty caid
SFA: saturated fatty acid

Figures and Tables -
Table 10. Metaregression of effects of SFA reduction on cardiovascular events
Navigate to table in Review
Table 11. Myocardial infarction (fatal and non‐fatal), sensitivity analyses

Analysis

RR (95% CI) of any MI

I²

No. of events

No. of participants

Main analysis

0.90 (0.80 to 1.01)

10%

1714

> 53,000

Sensitivity analyses

Stated aim to reduce SFA

0.89 (0.78 to 1.02)

17%

1707

> 53,000

SFA significantly reduced

0.94 (0.85 to 1.04)

0%

1520

> 52,000

TC significantly reduced

0.89 (0.76 to 1.05)

26%

1561

> 52,000

Minus WHI

0.85 (0.73 to 0.98)

1%

608

> 4000

Mantel‐Haenszel fixed‐effect

0.92 (0.84 to 1.01)

10%

1714

> 53,000

Peto fixed‐effect

0.92 (0.83 to 1.01)

31%

1714

> 53,000

SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 11. Myocardial infarction (fatal and non‐fatal), sensitivity analyses
Navigate to table in Review
Table 12. Myocardial infarction (fatal and non‐fatal), subgroup data

Analysis, P value for subgroup differences

RR (95% CI) of any MI

I²

No. of events

No. of participants

Subgroup by replacement

P = 0.48

PUFA replacement

0.83 (0.67 to 1.02)

29%

591

> 3000

MUFA replacement

1.40 (0.51 to 3.85)

N/A

12

52

CHO replacement

0.96 (0.86 to 1.06)

0%

1392

> 51,000

Protein replacement

0.96 (0.86 to 1.07)

0%

1389

> 51,000

Subgroup by duration, P = 0.78

Up to 24 months

0.95 (0.77 to 1.17)

0%

300

> 2000

> 24 to 48 months

0.83 (0.64 to 1.06)

0%

207

> 1000

> 48 months

0.81 (0.54 to 1.24)

78%

1194

> 49,000

Unclear duration

0.41 (0.02 to 7.73)

71%

13

> 200

Subgroup by baseline SFA, P = 0.50

Up to 12%E SFA

N/A

> 12 to 15%E SFA

0.96 (0.87 to 1.07)

0%

1392

> 51,000

> 15 to 18%E SFA

0.52 (0.05 to 5.39)

N/A

3

55

> 18%E SFA

0.76 (0.55 to 1.05)

N/A

125

846

Subgroup by SFA change, P = 0.50

Up to 4%E SFA difference

0.96 (0.87 to 1.07)

0%

1392

> 51,000

> 4 to 8%E SFA difference

0.52 (0.05 to 5.39)

N/A

3

55

> 8%E SFA difference

0.76 (0.55 to 1.05)

N/A

125

> 800

Subgroup by sex, P = 0.35

Men

0.85 (0.73 to 0.98)

0%

592

> 3000

Women

0.97 (0.86 to 1.09)

N/A

1106

> 48,000

Mixed, men and women

0.75 (0.13 to 4.47)

51%

16

> 500

Subgroup by CVD risk, P = 0.96

Low CVD risk

0.90 (0.72 to 1.13)

49%

1231

> 49,000

Moderate CVD risk

0.75 (0.13 to 4.47)

51%

16

> 500

Existing CVD

0.87 (0.74 to 1.03)

0%

467

> 2000

Subgroup by serum TC reduction,

P = 0.12

TC reduced by ≥ 0.2 mmol/L

0.83 (0.70 to 0.98)

9%

592

> 4000

TC reduced by < 0.2 mmol/L

0.98 (0.87 to 1.10)

0%

1122

> 49,000

Unclear TC change

Subgroup by decade of publication, P = 0.23

1960s

0.80 (0.64, 1.00)

10%

313

1731

1970s

0.08(0.0, 1.33)

N/A

6

102

1980s

0.91 (0.73, 1.14)

N/A

276

2033

1990s

0.52 (0.05, 5.39)

N/A

3

55

2000s

0.98 (0.87, 1.10)

0%

1116

> 49,000

CHO: carbohydrate
CVD: cardiovascular disease
MUFA: mon‐unsaturated fatty acid
N/A: not applicable
PUFA: polyunsaturated fatty caid
SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 12. Myocardial infarction (fatal and non‐fatal), subgroup data
Navigate to table in Review
Table 13. Non‐fatal myocardial infarction, sensitivity analyses

Analysis

RR (95% CI) of non‐fatal MI

I²

No. of events

No. of participants

Main analysis

0.95 (0.80 to 1.13)

27%

1348

> 52,000

Sensitivity analyses

Stated aim to reduce SFA

0.95 (0.80 to 1.13)

27%

1348

> 52,000

SFA significantly reduced

0.91 (0.72 to 1.25)

60%

1225

> 51,000

TC significantly reduced

0.97 (0.79 to 1.19)

45%

1296

> 51,000

Minus WHI

0.81 (0.64 to 1.04)

0%

242

> 3000

Mantel‐Haenszel fixed‐effect

0.94 (0.85 to 1.05)

27%

1348

> 52,000

Peto fixed‐effect

0.94 (0.84 to 1.05)

27%

1348

> 52,000

SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 13. Non‐fatal myocardial infarction, sensitivity analyses
Navigate to table in Review
Table 14. Non‐fatal myocardial infarction, subgroup analyses

Analysis, P value for subgroup differences

RR (95% CI) of non‐fatal MI

I²

No. of events

No. of participants

Subgroup by replacement

P = 0.62

PUFA replacement

0.80 (0.63 to 1.03)

0%

233

> 3000

MUFA replacement

1.20 (0.42 to 3.45)

N/A

11

52

CHO replacement

0.99 (0.73 to 1.35)

75%

1188

> 50,000

Protein replacement

0.99 (0.73 to 1.35)

75%

1188

> 50,000

Subgroup by duration, P = 0.64

Up to 24 months

0.83 (0.57 to 1.22)

0%

103

> 2000

> 24 to 48 months

0.82 (0.53 to 1.27)

10%

84

> 1000

> 48 months

1.01 (0.74 to 1.38)

73%

1161

> 49,000

Unclear duration

Subgroup by baseline SFA, P = 0.43

Up to 12%E SFA

N/A

> 12 to 15%E SFA

1.00 (0.75 to 1.35)

64%

1191

> 51,000

> 15 to 18%E SFA

> 18%E SFA

0.62 (0.31 to 1.21)

N/A

34

846

Subgroup by SFA change, P = 0.43

Up to 4%E SFA difference

1.00 (0.75 to 1.35)

64%

1191

> 51,000

> 4 to 8%E SFA difference

> 8%E SFA difference

0.62 (0.31 to 1.21)

N/A

34

> 800

Subgroup by sex, P = 0.35

Men

0.81 (0.63 to 1.03)

0%

239

> 3000

Women

1.10 (0.73 to 1.64)

85%

1106

> 48,000

Mixed, men and women

2.02 (0.19 to 21.94)

N/A

3

> 200

Subgroup by CVD risk, P = 0.61

Low CVD risk

0.87 (0.68 to 1.12)

19%

968

> 47,000

Moderate CVD risk

2.02 (0.19 to 21.94)

N/A

3

> 200

Existing CVD

1.00 (0.76 to 1.31)

N/A

377

> 5000

Subgroup by serum TC reduction,

P = 0.14

TC reduced by ≥ 0.2 mmol/L

0.80 (0.62 to 1.03)

0%

234

> 3000

TC reduced by < 0.2 mmol/L

1.11 (0.77 to 1.60)

71%

1114

> 48,000

Unclear TC change

Subgroup by decade of publication, P = 0.34

1960s

0.84 (0.62, 1.13)

0%

157

1743

1970s

1980s

0.74 (0.48, 1.14)

NA

82

2033

1990s

2000s

1.11 (0.76, 1.61)

71%

1109

> 49,000

CHO: carbohydrate
CVD: cardiovascular disease
MUFA: mon‐unsaturated fatty acid
N/A: not applicable
PUFA: polyunsaturated fatty caid
SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 14. Non‐fatal myocardial infarction, subgroup analyses
Navigate to table in Review
Table 15. Stroke (any type and outcome), sensitivity analyses

Analysis

RR (95% CI) of stroke

I²

No. of events

No. of participants

Main analysis

1.00 (0.89 to 1.12)

0%

1125

> 50,000

Sensitivity analyses

Stated aim to reduce SFA

1.00 (0.90 to 1.12)

0%

1119

> 50,000

SFA significantly reduced

0.99 (0.88 to 1.12)

2%

1120

> 50,000

TC significantly reduced

1.02 (0.91 to 1.14)

0%

1084

> 49,000

Minus WHI

0.63 (0.35 to 1.14)

0%

49

> 2000

Mantel‐Haenszel fixed‐effect

0.99 (0.89 to 1.11)

0%

1125

> 50,000

Peto fixed‐effect

0.99 (0.88 to 1.13)

18%

1125

> 50,000

SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 15. Stroke (any type and outcome), sensitivity analyses
Navigate to table in Review
Table 16. Stroke (any time and outcome), subgroup analyses

Analysis, P value for subgroup differences

RR (95% CI) of stroke

I²

No. of events

No. of participants

Subgroup by replacement

P = 0.69

PUFA replacement

0.68 (0.37 to 1.27)

0%

41

> 1700

MUFA replacement

CHO replacement

1.01 (0.90 to 1.13)

0%

1083

> 49,000

Protein replacement

1.01 (0.89 to 1.15)

11%

1082

> 49000

Subgroup by duration, P = 0.17

Up to 24 months

1.01 (0.06 to 15.93)

N/A

2

> 200

> 24 to 48 months

0.57 (0.30 to 1.11)

0%

36

> 900

> 48 months

1.02 (0.91 to 1.14)

0%

1079

> 49,000

Unclear duration

0.20 (0.02 to 1.68)

N/A

6

196

Subgroup by baseline SFA, P = 0.36

Up to 12%E SFA

N/A

> 12 to 15%E SFA

1.01 (0.90 to 1.13)

0%

1084

> 49,000

> 15 to 18%E SFA

0.35 (0.01 to 8.12)

N/A

1

55

> 18%E SFA

0.59 (0.30 to 1.15)

N/A

35

846

Subgroup by SFA change, P = 0.36

Up to 4%E SFA difference

1.01 (0.90 to 1.13)

0%

1084

> 49,000

> 4 to 8%E SFA difference

0.35 (0.01 to 8.12)

N/A

1

55

> 8%E SFA difference

0.59 (0.30 to 1.15)

N/A

35

> 800

Subgroup by sex, P = 0.35

Men

0.63 (0.33 to 1.18)

0%

39

> 1300

Women

1.02 (0.91 to 1.14)

0%

1076

> 48,000

Mixed, men and women

0.37 (0.07 to 1.97)

0%

8

> 400

Subgroup by CVD risk, P = 0.42

Low CVD risk

0.86 (0.52 to 1.42)

59%

597

> 47,000

Moderate CVD risk

0.37 (0.07 to 1.97)

0%

8

> 400

Existing CVD

1.01 (0.86 to 1.18)

0%

518

> 2000

Subgroup by serum TC reduction,

P = 0.24

TC reduced by ≥ 0.2 mmol/L

0.70 (0.38 to 1.28)

0%

43

> 1900

TC reduced by < 0.2 mmol/L

1.01 (0.89 to 1.15)

11%

1082

> 49,000

Unclear TC change

Subgroup by decade of publication, P=0.79

1960s

0.92 (0.31, 2.69)

23%

40

1651

1970s

1980s

1990s

0.35 (0.01, 8.12)

N/A

1

55

2000s

1.01 (0.90, 1.13)

0%

1084

> 49,000

CHO: carbohydrate
CVD: cardiovascular disease
MUFA: mon‐unsaturated fatty acid
N/A: not applicable
PUFA: polyunsaturated fatty caid
SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 16. Stroke (any time and outcome), subgroup analyses
Navigate to table in Review
Table 17. CHD mortality, sensitivity analyses

Analysis

RR (95% CI) of CHD mortality

I²

No. of events

No. of participants

Main analysis

0.98 (0.84 to 1.15)

21%

886

> 53,000

Sensitivity analyses

Stated aim to reduce SFA

0.98 (0.84 to 1.15)

21%

886

> 53,000

SFA significantly reduced

1.02 (0.87 to 1.20)

17%

735

> 52,000

TC significantly reduced

1.00 (0.83 to 1.20)

33%

786

> 52,000

Minus WHI

0.97 (0.76 to 1.24)

37%

494

> 4000

Mantel‐Haenszel fixed‐effect

0.98 (0.86 to 1.12)

21%

886

> 53,000

Peto fixed‐effect

0.98 (0.85 to 1.13)

39%

886

> 53,000

SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 17. CHD mortality, sensitivity analyses
Navigate to table in Review
Table 18. CHD mortality, subgroup data

Analysis, P value for subgroup differences

RR (95% CI) of CHD mortality

I²

No. of events

No. of participants

Subgroup by replacement

P = 0.80

PUFA replacement

0.98 (0.74 to 1.28)

49%

491

> 4000

MUFA replacement

3.00 (0.33 to 26.99)

N/A

4

52

CHO replacement

1.01 (0.86 to 1.18)

0%

586

> 50,000

Protein replacement

1.01 (0.86 to 1.18)

0%

586

> 50,000

Subgroup by duration, P = 0.33

Up to 24 months

1.02 (0.78 to 1.33)

0%

203

> 2000

> 24 to 48 months

0.87 (0.64 to 1.19)

N/A

141

> 1000

> 48 months

1.03 (0.79 to 1.34)

52%

537

> 49,000

Unclear duration

0.09 (0.01 to 1.60)

N/A

5

> 100

Subgroup by baseline SFA, P = 0.35

Up to 12%E SFA

N/A

> 12 to 15%E SFA

1.06 (0.90 to 1.25)

11%

644

> 51,000

> 15 to 18%E SFA

> 18%E SFA

0.82 (0.55 to 1.21)

N/A

91

> 800

Subgroup by SFA change, P = 0.35

Up to 4%E SFA difference

1.06 (0.90 to 1.25)

11%

644

> 51,000

> 4 to 8%E SFA difference

> 8%E SFA difference

0.82 (0.55 to 1.21)

N/A

91

> 800

Subgroup by sex, P = 0.26

Men

0.98 (0.79 to 1.23)

30%

489

> 4000

Women

1.01 (0.83 to 1.24)

0%

392

> 48,000

Mixed, men and women

0.09 (0.01 to 1.60)

N/A

5

> 100

Subgroup by CVD risk, P = 0.23

Low CVD risk

0.95 (0.78 to 1.16)

0%

400

> 47,000

Moderate CVD risk

0.09 (0.01 to 1.60)

N/A

5

> 100

Existing CVD

1.03 (0.83 to 1.27)

22%

481

> 5000

Subgroup by serum TC reduction,

P = 0.73

TC reduced by ≥ 0.2 mmol/L

0.96 (0.75 to 1.24)

42%

491

> 4000

TC reduced by < 0.2 mmol/L

1.02 (0.83 to 1.25)

0%

395

> 48,000

Unclear TC change

Subgroup by decade of publication, P = 0.62

1960s

0.84 (0.66, 1.06)

23%

40

1651

1970s

0.54 (0.03, 9.26)

75%

63

560

1980s

1.00 (0.76, 1.30)

N/A

194

2033

1990s

2000s

1.01 (0.83, 1.24)

0%

392

> 48,000

CHO: carbohydrate
CVD: cardiovascular disease
MUFA: mon‐unsaturated fatty acid
N/A: not applicable
PUFA: polyunsaturated fatty caid
SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 18. CHD mortality, subgroup data
Navigate to table in Review
Table 19. CHD events, sensitivity analyses

Analysis

RR (95% CI) of CHD events

I²

No. of events

No. of participants

Main analysis

0.87 (0.74 to 1.03)

66%

3307

> 53,000

Sensitivity analyses

Stated aim to reduce SFA

0.87 (0.74 to 1.03)

66%

3307

> 53,000

SFA significantly reduced

1.95 (0.82 to 1.10)

49%

2988

> 52,000

TC significantly reduced

0.85 (0.70 to 1.03)

75%

3034

> 52,000

Minus WHI

0.80 (0.61 to 1.03)

59%

758

> 4000

Mantel‐Haenszel fixed‐effect

0.93 (0.87 to 0.99)

66%

3307

> 53,000

Peto fixed‐effect

0.92 (0.86 to 0.99)

72%

3307

> 53,000

SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 19. CHD events, sensitivity analyses
Navigate to table in Review
Table 20. CHD events, subgroup analyses

Analysis, P value for subgroup differences

RR (95% CI) of CHD events

I²

No. of events

No. of participants

Subgroup by replacement

P = 0.28

PUFA replacement

0.76 (0.57 to 1.00)

71%

737

> 3000

MUFA replacement

1.50 (0.62 to 3.61)

N/A

15

52

CHO replacement

0.98 (0.83 to 1.14)

55%

2846

> 51,000

Protein replacement

0.99 (0.88 to 1.12)

41%

2833

> 51,000

Subgroup by duration, P = 0.72

Up to 24 months

1.01 (0.76 to 1.35)

5%

307

> 2000

> 24 to 48 months

0.79 (0.55 to 1.14)

50%

251

> 1000

> 48 months

0.93 (0.76 to 1.14)

79%

2703

> 49,000

Unclear duration

0.60 (0.10 to 3.58)

81%

46

> 200

Subgroup by baseline SFA, P = 0.09

Up to 12%E SFA

N/A

> 12 to 15%E SFA

0.99 (0.88 to 1.12)

34%

2837

> 51,000

> 15 to 18%E SFA

0.30 (0.09 to 0.98)

N/A

13

60

> 18%E SFA

0.77 (0.56 to 1.04)

N/A

138

> 800

Subgroup by SFA change, P = 0.09

Up to 4%E SFA difference

0.99 (0.88 to 1.12)

34%

2837

> 51,000

>4 to 8%E SFA difference

0.30 (0.09 to 0.98)

N/A

13

60

>8%E SFA difference

0.77 (0.56 to 1.04)

N/A

138

> 800

Subgroup by sex, P = 0.39

Men

0.84 (0.70 to 1.02)

35%

708

> 3000

Women

1.02 (0.84 to 1.23)

77%

2549

> 48,000

Mixed, men and women

0.88 (0.18 to 4.36)

76%

50

> 500

Subgroup by CVD risk, P = 0.95

Low CVD risk

0.90 (0.76 to 1.05)

33%

2236

> 47,000

Moderate CVD risk

0.88 (0.18 to 4.36)

76%

50

> 500

Existing CVD

0.94 (0.75 to 1.17)

61%

1021

> 5000

Subgroup by serum TC reduction,

P = 0.06

TC reduced by ≥ 0.2 mmol/L

0.75 (0.58 to 0.99)

65%

738

> 4000

TC reduced by < 0.2 mmol/L

1.03 (0.87 to 1.21)

44%

2569

> 49,000

Unclear TC change

Subgroup by decade of publication, P < 0.001

1960s

0.84 (0.68, 1.05)

30%

419

1731

1970s

0.27 (0.14, 0.52)

N/A

38

102

1980s

0.91 (0.73, 1.14)

N/A

276

2033

1990s

0.33 (0.10, 1.09)

N/A

13

57

2000s

1.03 (0.86, 1.23)

48%

2561

> 49,000

CHO: carbohydrate
CVD: cardiovascular disease
MUFA: mon‐unsaturated fatty acid
N/A: not applicable
PUFA: polyunsaturated fatty caid
SFA: saturated fatty acid
TC: total cholesterol

Figures and Tables -
Table 20. CHD events, subgroup analyses
Navigate to table in Review
Table 21. Process outcome data (secondary outcomes)

Outcome

Effect (95% CI)

I²

No. of studies (participants)

Differential effect by replacement?

Summary

TC, mmol/L

‐0.24 (‐0.36 to ‐0.13)

60%

13 (7115)

No, P = 0.20

TC reduced

LDL, mmol/L

‐0.19 (‐0.33 to ‐0.05)

37%

5 (3291)

No, P = 0.16

LDL reduced

HDL, mmol/L

‐0.01 (‐0.02 to 0.01)

0%

7 (5183)

No, P = 0.99

No effect

TG, mmol/L

‐0.08 (‐0.21 to 0.04)

51%

7 (3845)

No, P = 0.12

No effect

TG/HDL ratio

N/A

N/A

N/A

N/A

No data

TC/HDL ratio

‐0.10 (‐0.33 to 0.13)

24%

3 (2985)

No, P = 0.45

No effect

LDL/HDL ratio

‐0.36 (‐0.92 to 0.20)

N/A

1 (50)

N/A

Unclear

Lipoprotein (a), mmol/L

0.00 (‐0.00 to 0.00)

0%

2 (2882)

No, P = 1.00

No effect

Diabetes diagnosis

RR 0.96 (0.90 to 1.02)

N/A

1 (> 48,000; 3342 diagnoses)

No, P = 1.00

No effect

HbA1c, %

N/A

N/A

N/A

N/A

No data

Glucose 2 hrs post GTT, mmol/L

‐1.69 (‐2.55 to ‐0.82)

45%

3 (249)

N/A

Reduced

HOMA

0.00 (‐0.04 to 0.04)

NA

1 (2832)

N/A

No effect

GTT: glucose tolerance test
HOMA: homeostatic model assessment
TC: total cholesterol
TG: triglyceride

Figures and Tables -
Table 21. Process outcome data (secondary outcomes)
Navigate to table in Review
Table 22. Potential harms (secondary outcomes)

Outcome

Effect (95% CI)

I²

No. of studies (participants)

Differential effect by replacement?

Summary

Cancer diagnoses

RR 0.94 (0.83 to 1.07)

33%

4 (> 52,000; 5476 diagnoses)

No, P = 0.33

No effect

Cancer deaths

RR 1.00 (0.61 to 1.64)

49%

5 (> 52,000; 2472 deaths)

No, P = 0.94

No effect

Body weight, kg

MD ‐1.97 (‐3.67 to ‐0.27)

72%

6 (4541)

No, P = 1.00

Weight loss

BMI, kg/m²

MD ‐0.50 (‐0.82 to ‐0.19)

55%

6 (5553)

No, P = 0.41

BMI reduced

Systolic BP, mmHg

MD ‐0.19 (‐1.36 to 0.97)

0%

5 (3812)

No, P = 0.97

No effect

Diastolic BP, mmHg

MD ‐0.36 (‐1.03 to 0.32)

0%

5 (3812)

No, P = 1.00

No effect

BMI: body mass index
MD: mean difference
RR: risk ratio

Figures and Tables -
Table 22. Potential harms (secondary outcomes)
Navigate to table in Review
Table 23. SFA cut‐off data

Cut‐ off

RR of all‐cause mortality

RR of CVD mortality

RR of CVD events

RR of MI

RR of non‐fatal MI

RR of stroke

RR of CHD mortality

RR of CHD events

7%E

1.11 (0.58 to 2.12)

0.20 (0.01 to 4.15)

0.20 (0.01 to 4.15)

N/A

N/A

N/A

N/A

N/A

8%E

1.11 (0.58 to 2.12)

0.20 (0.01 to 4.15)

0.20 (0.01 to 4.15)

N/A

N/A

N/A

N/A

N/A

9%E

0.99 (0.84 to 1.15)

0.69 (0.51 to 0.94)

0.79 (0.62 to 0.99)

0.76 (0.55 to 1.05)

0.62 (0.31 to 1.21)

0.59 (0.30 to 1.15)

0.82 (0.55 to 1.21)

0.77 (0.56 to 1.04)

10%E

0.99 (0.90 to 1.09)

0.97 (0.74 to 1.26)

0.89 (0.74 to 1.07)

0.93 (0.80 to 1.08)

0.99 (0.69 to 1.41)

1.00 (0.89 to 1.12)

1.05 (0.83 to 1.32)

0.93 (0.75 to 1.14)

11%E

1.00 (0.88 to 1.12)

0.95 (0.73 to 1.24)

0.88 (0.74 to 1.05)

0.94 (0.84 to 1.06)

0.99 (0.69 to 1.41)

0.98 (0.83 to 1.14)

1.02 (0.87 to 1.20)

0.94 (0.77 to 1.15)

12%E

0.99 (0.91 to 1.07)

0.96 (0.79 to 1.18)

0.91 (0.79 to 1.04)

0.94 (0.85 to 1.04)

0.95 (0.72 to 1.25)

0.99 (0.88 to 1.12)

1.02 (0.87 to 1.20)

0.95 (0.82 to 1.10)

13%E

1.02 (0.83 to 1.25)

0.93 (0.63 to 1.38)

0.78 (0.61 to 1.00)

0.87 (0.73 to 1.04)

0.72 (0.50 to 1.03)

0.54 (0.29 to 1.00)

1.06 (0.76 to 1.48)

0.84 (0.63 to 1.12)

CHD coronary heart disease
CVD cardiovascular disease
MI myocardial infarction
N/A not applicable (no relevant studies)
RR: risk ratio
SFA saturated fat, as percentage of energy

Figures and Tables -
Table 23. SFA cut‐off data
Navigate to table in Review
Table 24. GRADE profile: What is the effect of replacing some saturated fat with other fats, protein or CHO in adults?

Quality assessment

No of participants

(study event rate%)

Effect

Quality

Importance

No of studies

Design 1

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Reduced

saturated fat intake

Usual saturated fat intake

Relative effect
(95% CI)

Absolute effects

(per 10,000)

All‐cause mortality (follow‐up mean 56 months1)

12

RCTs

no serious risk of

bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

1377/22819

(6%)

1899/33039

(5.7%)

RR 0.97

(0.9 to 1.05)

17 fewer

(from 57 fewer to 29 more)

♁♁♁O
MODERATE

CRITICAL

Cardiovascular mortality (follow‐up mean 53 months1)

12

RCTs

no serious risk of

bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

483/21844
(2.2%)

613/31577
(1.9%)

RR 0.95
(0.8 to 1.12)

10 fewer
(from 39 fewer to 23 more)

♁♁♁O

MODERATE

CRITICAL

Cardiovascular events (follow‐up mean 52 months1)

13

RCTs

no serious risk of

bias2

serious inconsistency7

no serious indirectness4

no serious imprecision8

none6

1774/21791
(8.1%)

2603/31509
(8.3%)

RR 0.83
(0.72 to 0.96)

138 fewer

(from 33 fewer to 228 fewer)

♁♁♁O

MODERATE

CRITICAL

Fatal and non‐fatal myocardial infarction (follow‐up mean 55 months1)

11

RCTs

no serious risk of

bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

717/21725
(3.3%)

997/31442
(3.2%)

RR 0.90
(0.8 to 1.01)

32 fewer

(from 63 fewer to 3 more)

♁♁♁O

MODERATE

CRITICAL

Non‐fatal myocardial infarction (follow‐up mean 55 months1)

9

RCTs

no serious risk of

bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none9

547/21559
(2.5%)

801/31275
(2.6%)

RR 0.95
(0.8 to 1.13)

13 fewer

(from 51 fewer to 33 more)

♁♁♁O
MODERATE

CRITICAL

Stroke (follow‐up 59 mean months1)

8

RCTs

no serious risk of

bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none9

453/20602
(2.2%)

672/30350
(2.2%)

RR 1.00
(0.89 to 1.12)

0 fewer

(from 25 fewer to 25 more)

♁♁♁O
MODERATE

CRITICAL

CHD mortality (follow‐up mean 65 months1)

10

RCTs

no serious risk of

bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none 6

401/21714
(1.8%)

485/31445
(1.5%)

RR 0.98
(0.84 to 1.15)

30 fewer

(from 25 fewer to 23 more)

♁♁♁O
MODERATE

CRITICAL

CHD events (follow‐up mean 59 months1)

12

RCTs

no serious risk of

bias2

serious inconsistency10

no serious indirectness4

serious imprecision5

none 6

1346/21743
(6.2%)

1961/31456
(6.2%)

RR 0.87
(0.74 to 1.03)

80 fewer

(from 160 fewer to 19 more)

♁♁OO
LOW

CRITICAL

1Minimum study duration was 24 months.

2These large RCTs of relatively long duration were well randomised and almost half had good allocation concealment (the rest were unclear). Blinding was only well‐conducted in 1 RCT, however blinding is very difficult in trials of dietary fat intake. Incomplete outcome data were variable, and most included studies had systematic differences in care (i.e. intervention group had more time or attention than the control group). These risks to validity were combined with risks from imprecision, and outcomes were downgraded once for a combination of both issues. We noted no other biases. We noted that the level of compliance with interventions involving long‐term behaviour change, such as those used in these studies, can vary widely. This is likely to attenuate the pooled effect and bias it towards the null.

3No important heterogeneity; I² ≤ 30%

4These RCTs directly assessed the effect of lower vs usual saturated fat intake on health outcomes of interest. Participants included men and women with and without CVD at baseline (also some participants with CVD risk factors like diabetes, or at risk of cancers).

5 The 95% CI crosses 1.0 and does not exclude important benefit or harm

6The funnel plot did not suggest any small study (publication) bias

7Potentially important heterogeneity was identified; I² = 65%. However, the heterogeneity was partly explained by the degree of saturated fat reduction, and the degree of cholesterol lowering achieved (in subgrouping and in meta‐regression).

8The 95% CI does not cross 1.0 or a threshold of important harm.

9Too few studies to reliably assess publication bias (< 10 RCTs).

10Important heterogeneity; I² = 66%

Figures and Tables -
Table 24. GRADE profile: What is the effect of replacing some saturated fat with other fats, protein or CHO in adults?
Navigate to table in Review
Table 25. GRADE profile: What is the effect of replacing some saturated fat with PUFA* on risk of CVD in adults?

Quality assessment

No of participants

(study event rate %)

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Reduced

saturated fat intake

Usual saturated fat intake

Relative effect
(95% CI)

Absolute effects

(per 10,000)

All‐cause mortality (follow‐up mean 56 months1)

7

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

406/2123
(19.1%)

418/2115
(19.8%)

RR 0.96 (0.82 to 1.13)

79 fewer

(from 360 fewer to 256 more)

♁♁♁O
MODERATE

CRITICAL

Cardiovascular mortality (follow‐up mean 55 months1)

7

RCTs

no serious risk of bias2

serious inconsistency7

no serious indirectness4

serious imprecision5

none6

266/2123
(12.5%)

287/2128
(13.5%)

RR 0.95 (0.73 to 1.25)

67 fewer

(from 364 fewer to 337 more)

♁♁OO
LOW

CRITICAL

Cardiovascular events (follow‐up mean 53 months1)

7

RCTs

no serious risk of bias2

serious inconsistency8

no serious indirectness4

no serious imprecision9

none6

390/1953
(20%)

494/1942
(25.4%)

RR 0.73 (0.58 to 0.92)

687 fewer

(from 204 fewer to 1068 fewer)

♁♁♁O
MODERATE

CRITICAL

Fatal and non‐fatal myocardial infarction (follow‐up mean 53 months1)

7

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

269/1953
(13.8%)

322/1942
(16.6%)

RR 0.83 (0.67 to 1.02)

282 fewer

(from 547 fewer to 33 more)

♁♁♁O
MODERATE

CRITICAL

Non‐fatal myocardial infarction (follow‐up mean 53 months1)

5

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

104/1875
(5.5%)

129/1863
(6.9%)

RR 0.8 (0.63 to 1.03)

138 fewer

(from 256 fewer to 21 more)

♁♁♁O
MODERATE

CRITICAL

Stroke (follow‐up mean 63 months1)

4

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

very serious10

none6

17/856
(2%)

24/850
(2.8%)

RR 0.68 (0.37 to 1.27)

90 fewer

(from 178 fewer to 76 more)

♁OOO
VERY LOW

CRITICAL

CHD mortality (follow‐up mean 36 months1)

7

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

240/2147
(11.2%)

251/2151
(11.7%)

RR 0.98 (0.74 to 1.28)

23 fewer

(from 303 fewer to 327 more)

♁♁♁O
MODERATE

CRITICAL

CHD events (follow‐up mean 53 months1)

7

RCTs

no serious risk of bias2

serious inconsistency11

no serious indirectness4

serious imprecision5

none6

329/1956
(16.8%)

408/1944
(21%)

RR 0.76 (0.57 to 1.0)

504 fewer

(from 902 fewer to 0 more)

♁♁OO
LOW

CRITICAL

* Polyunsaturated fatty acids replacing saturated fatty acids in individual studies were predominantly of plant origin.

1 Minimum study duration was 24 months.

2 These large RCTs of relatively long duration were well randomised but fewer than half had good allocation concealment (the rest were unclear). Blinding was only well‐conducted in 1 RCT, however blinding is very difficult in trials of dietary fat intake. In about half the included studies, it was unclear if outcome data were incomplete and most studies had systematic differences in care (i.e. intervention group had more time or attention than the control group). We noted no other biases. Not downgraded for bias, however we note that the level of compliance with interventions involving long‐term behaviour change, such as those used in many of these studies, can vary widely. This is likely to attenuate the pooled effect and bias it towards the null.

3 No important heterogeneity; I² < 50%
4 These RCTs directly assessed the effect of reducing saturated fat, and replacing it with other dietary sources of energy, compared to usual diet, on health outcomes of interest. Participants included men and women with and without CVD at baseline.
5 The 95% CI crosses 1.0 and does not exclude important benefit or harm.

6 Too few studies to reliably assess publication bias (< 10 RCTs).

7 Important heterogeneity; I² = 55%

8 Important heterogeneity; I² = 69%.Subgrouping suggested greater effects on cardiovascular events with greater reduction in SFA intake, higher baseline SFA intake and greater serum total cholesterol reduction (meta‐regression not carried out).

9 95% CI does not cross threshold of important benefit or harm.

Figures and Tables -
Table 25. GRADE profile: What is the effect of replacing some saturated fat with PUFA* on risk of CVD in adults?
Navigate to table in Review
Table 26. GRADE profile: What is the effect of replacing some saturated fat with MUFA on risk of CVD in adults?

Quality assessment

No of participants

(study event rate%)

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Reduced

saturated fat intake

Usual saturated fat intake

Relative effect
(95% CI)

Absolute effects

(per 10,000)

All‐cause mortality (follow‐up mean 24 months)

1

RCTs

serious risk of bias1

no serious inconsistency2

no serious indirectness3

very serious imprecision4

none5

3/26
(11.5%)

1/26
(3.8%)

RR 3.0

(0.33 to 26.99)

769 more

(from 258 fewer to 9996 more)

♁OOO
VERY LOW

CRITICAL

Cardiovascular mortality (follow‐up mean 24 months)

1

RCTs

serious risk of bias1

no serious inconsistency2

no serious indirectness3

very serious imprecision4

none5

3/26
(11.5%)

1/26
(3.8%)

RR 3.0

(0.33 to 26.99)

769 more

(from 258 fewer to 9996 more)

♁OOO
VERY LOW

CRITICAL

Cardiovascular events (follow‐up mean 24 months)

1

RCTs

serious risk of bias1

no serious inconsistency2

no serious indirectness3

very serious imprecision4

none5

11/26
(42.3%)

11/26
(42.3%)

RR 1.0

(0.53 to 1.89)

0 fewer

(from 1988 fewer to 3765 more)

♁OOO
VERY LOW

CRITICAL

Fatal and non‐fatal myocardial infarction (follow‐up mean 24 months)

1

RCTs

serious risk of bias1

no serious inconsistency2

no serious indirectness3

very serious imprecision4

none5

7/26
(26.9%)

5/26
(19.2%)

RR 1.4 (0.51 to 3.85)

769 more

(from 942 fewer to 5481 more)

♁OOO
VERY LOW

IMPORTANT

Non‐fatal myocardial infarction (follow‐up mean 24 months)

1

RCTs

serious risk of bias1

no serious inconsistency2

no serious indirectness3

very serious

imprecision4

none5

6/26
(23.1%)

5/26
(19.2%)

RR 1.2 (0.42 to 3.45)

385 more

(from 1115 fewer to 4711 more)

♁OOO
VERY LOW

IMPORTANT

Stroke

0

No studies identified reporting this outcome

CHD mortality (follow‐up mean 24 months)

1

RCTs

serious risk of bias1

no serious inconsistency2

no serious indirectness3

very serious imprecision4

none5

3/26
(11.5%)

1/26
(3.8%)

RR 3

(0.33 to 26.99)

769 more

(from 258 fewer to 9996 more)

♁OOO
VERY LOW

IMPORTANT

CHD events (follow‐up mean 24 months)

1

RCTs

serious risk of bias1

no serious inconsistency2

no serious indirectness3

very serious imprecision4

none5

9/26
(34.6%)

6/26
(23.1%)

RR 1.5 (0.62 to 3.61)

1154 more

(from 877 fewer to 6023 more)

♁OOO
VERY LOW

IMPORTANT

1This single, very small RCT of relatively long duration was well randomised, but had an unclear risk of bias in terms of allocation concealment and incomplete outcome data, and lacked participant blinding; however blinding is very difficult in trials of dietary fat intake. We downgraded it for serious risk of bias.
2Only one trial

3This RCT directly assessed the effect of reducing saturated fat, and replacing it with other dietary sources of energy, compared to usual diet, on health outcomes of interest. Participants included men with CVD at baseline.

4The 52 participants in the relevant arms of this trial experienced relatively few events. As a result, there were wide to very wide confidence intervals. In addition, the 95% CI crosses 1.0 and does not exclude important benefit or harm.

5Too few studies to reliably assess publication bias (< 10 RCTs).

Figures and Tables -
Table 26. GRADE profile: What is the effect of replacing some saturated fat with MUFA on risk of CVD in adults?
Navigate to table in Review
Table 27. GRADE profile: What is the effect of replacing some saturated fat with CHO on risk of CVD in adults?

Quality assessment

No of participants

(study event rate %)

Effect

Quality

Importance

No of studies

Design1

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Reduced

saturated fat intake

Usual saturated fat intake

Relative effect
(95% CI)

Absolute effects

(per 10,000)

All‐cause mortality (follow‐up mean 48 months2)

6

RCTs

no serious risk of bias3

no serious inconsistency4

no serious indirectness5

serious imprecision6

none7

1080/21715
(5%)

1597/31954
(5%)

RR 0.98 (0.91 to 1.05)

10 fewer

(from 45 fewer to 25 more)

♁♁♁O
MODERATE

CRITICAL

Cardiovascular mortality (follow‐up mean 46 months2)

6

RCTs

no serious risk of bias3

no serious inconsistency4

no serious indirectness5

serious imprecision6

none7

316/20740
(1.5%)

429/30492
(1.4%)

RR 0.99 (0.86 to 1.14)

1 fewer

(from 20 fewer to 20 more)

♁♁♁O
MODERATE

CRITICAL

Cardiovascular events (follow‐up mean 46 months2)

6

RCTs

no serious risk of bias3

serious inconsistency9

no serious indirectness5

serious imprecision6

none7

1512/20740
(7.3%)

2273/30492
(7.5%)

RR 0.93 (0.79 to 1.08)

52 fewer

(from 157 fewer to 60 more)

♁♁OO
LOW

CRITICAL

Fatal and non‐fatal myocardial infarction (follow‐up mean 51 months2)

4

RCTs

no serious risk of bias3

no serious inconsistency4

no serious indirectness5

serious imprecision6

none7

572/20674
(2.8%)

820/30425
(2.7%)

RR 0.96 (0.86 to 1.06)

11 fewer

(from 38 fewer to 16 more)

♁♁♁O
MODERATE

IMPORTANT

Non‐fatal myocardial infarction (follow‐up mean 60 months2)

3

RCTs

no serious risk of bias3

serious inconsistency9

no serious indirectness5

serious imprecision6

none7

470/20559
(2.3%)

718/30309
(2.4%)

RR 0.99 (0.73 to 1.35)

2 fewer

(from 64 fewer to 83 more)

♁♁OO
LOW

IMPORTANT

Stroke (follow‐up mean 60 months2)

4

RCTs

no serious risk of bias3

no serious inconsistency4

no serious indirectness5

serious imprecision6

none7

435/19656
(2.2%)

648/29410
(2.2%)

RR 1.01 (0.9 to 1.13)

2 more

(from 22 fewer to 29 more)

♁♁♁O
MODERATE

IMPORTANT

CHD mortality (follow‐up mean 60 months2)

3

RCTs

no serious risk of bias3

no serious inconsistency4

no serious indirectness5

serious imprecision6

none7

255/20559
(1.2%)

331/30309
(1.1%)

RR 1.01 (0.86 to 1.18)

1 more

(from 15 fewer to 20 more)

♁♁♁O
MODERATE

IMPORTANT

CHD events (follow‐up mean 51 months2)

5

RCTs

no serious risk of bias3

serious inconsistency8

no serious indirectness5

serious imprecision6

none7

1140/20677
(5.5%)

1706/30427
(5.6%)

RR 0.98 (0.83 to 1.14)

11 fewer

(from 95 fewer to 79 more)

♁♁OO
LOW

IMPORTANT

1There was insufficient information across all studies to make any determination about the type of carbohydrate used as replacement.

2Minimum study duration was 24 months.
3These large RCTs of relatively long duration were well randomised, most had good allocation concealment (the rest were unclear) and most were not at risk for bias in terms of incomplete outcome data. In no studies was blinding well‐conducted; however blinding is very difficult in trials of dietary fat intake. All studies had systematic differences in care (i.e. intervention group had more time or attention than the control group). No other biases noted. Not downgraded for bias, however we note that the level of compliance with interventions involving long‐term behaviour change, such as those used in these studies, can vary widely. This is likely to attenuate the pooled effect and bias it towards the null.

4No important heterogeneity; I² = 0%.
5These RCTs directly assessed the effect of reducing saturated fat, and replacing it with other dietary sources of energy, compared to usual diet, on health outcomes of interest. Participants included men and women with and without CVD at baseline.

6The 95% CI crosses 1.0 and does not exclude important benefit or harm.

7Too few studies to reliably assess publication bias (< 10 RCTs).

8Important heterogeneity; I² = 55%.

Figures and Tables -
Table 27. GRADE profile: What is the effect of replacing some saturated fat with CHO on risk of CVD in adults?
Navigate to table in Review
Table 28. GRADE profile: What is the effect of replacing some saturated fat with protein on the risk of CVD in adults?

Quality assessment

No of participants

(study event rate%)

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Reduced

saturated fat intake

Usual saturated fat intake

Relative effect
(95% CI)

Absolute effects

(per 10,000)

All‐cause mortality (follow‐up mean 50 months1)

5

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

1079/21688
(5%)

1594/31926
(5%)

RR 0.98 (0.91 to 1.06)

10 fewer

(from 45 fewer to 30 more)

♁♁♁O
MODERATE

CRITICAL

Cardiovascular mortality (follow‐up mean 48 months1)

5

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

315/20713
(1.5%)

426/30464
(1.4%)

RR 0.99 (0.86 to 1.14)

1 fewer

(from 20 fewer to 20 more)

♁♁♁O
MODERATE

CRITICAL

Cardiovascular events (follow‐up mean 48 months1)

5

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

1504/20713
(7.3%)

2253/30464
(7.4%)

RR 0.98 (0.9 to 1.06)

15 fewer

(from 74 fewer to 44 more)

♁♁♁O
MODERATE

CRITICAL

Fatal and non‐fatal myocardial infarction (follow‐up mean 56 months1)

3

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

571/20647
(2.8%)

818/30397
(2.7%)

RR 0.96 (0.86 to 1.07)

11 fewer

(from 38 fewer to 19 more)

♁♁♁O
MODERATE

IMPORTANT

Non‐fatal myocardial infarction (follow‐up mean 60 months1)

3

RCTs

no serious risk of bias2

serious inconsistency7

no serious indirectness4

serious imprecision5

none6

470/20559
(2.3%)

718/30309
(2.4%)

RR 0.99 (0.73 to 1.35)

2 fewer

(from 64 fewer to 83 more)

♁♁OO
LOW

IMPORTANT

Stroke (follow‐up mean 72 months1)

3

RCTs

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

435/19629
(2.2%)

647/29382
(2.2%)

RR 1.01 (0.89 to 1.15)

2 more

(from 24 fewer to 33 more)

♁♁♁O
MODERATE

IMPORTANT

CHD mortality (follow‐up mean 60 months1)

3

randomised trials

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

255/20559
(1.2%)

331/30309
(1.1%)

RR 1.01 (0.86 to 1.18)

1 more

(from 15 fewer to 20 more)

♁♁♁O
MODERATE

IMPORTANT

CHD events (follow‐up mean 56 months1)

4

randomised trials

no serious risk of bias2

no serious inconsistency3

no serious indirectness4

serious imprecision5

none6

1137/20647
(5.5%)

1696/30397
(5.6%)

RR 0.99 (0.88 to 1.12)

6 fewer

(from 67 fewer to 67 more)

♁♁♁O
MODERATE

IMPORTANT

1Minimum study duration was 24 months.
2These large RCTs of relatively long duration were well randomised, most had good allocation concealment (the rest were unclear) and most were not at risk for bias in terms of incomplete outcome data. In no studies was blinding well‐conducted, however blinding is very difficult in trials of dietary fat intake. All studies had systematic differences in care (i.e. intervention group had more time or attention than the control group). We noted no other biases. Not downgraded for bias; however we note that the level of compliance with interventions involving long‐term behaviour change, such as those used in these studies, can vary widely. This is likely to attenuate the pooled effect and bias it towards the null.
3No important heterogeneity; I2 <50%.
4These RCTs directly assessed the effect of reducing saturated fat, and replacing it with other dietary sources of energy, compared to usual diet, on health outcomes of interest. Participants included men and women with and without CVD at baseline.

5The 95% CI crosses 1.0 and does not exclude important benefit or harm.

6Too few studies to reliably assess publication bias (< 10 RCTs).

7Important heterogeneity; I² = 75%.

Figures and Tables -
Table 28. GRADE profile: What is the effect of replacing some saturated fat with protein on the risk of CVD in adults?
Navigate to table in Review
Comparison 1. SFA reduction vs usual diet ‐ Primary outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

12

55858

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.90, 1.05]

2 Cardiovascular mortality Show forest plot

12

53421

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.80, 1.12]

3 Combined cardiovascular events Show forest plot

13

53300

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.72, 0.96]
Figures and Tables -
Comparison 1. SFA reduction vs usual diet ‐ Primary outcomes
Navigate to table in Review
Comparison 2. SFA reduction vs usual diet ‐ secondary health events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Myocardial infarctions Show forest plot

11

53167

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.80, 1.01]

2 Non‐fatal MI Show forest plot

9

52834

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.80, 1.13]

3 Stroke Show forest plot

8

50952

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.89, 1.12]

4 CHD mortality Show forest plot

10

53159

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.84, 1.15]

5 CHD events Show forest plot

12

53199

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.74, 1.03]

6 Diabetes diagnoses Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Figures and Tables -
Comparison 2. SFA reduction vs usual diet ‐ secondary health events
Navigate to table in Review
Comparison 3. SFA reduction vs usual diet ‐ other secondary outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Total cholesterol, mmol/L Show forest plot

14

7115

Mean Difference (IV, Random, 95% CI)

‐0.24 [‐0.36, ‐0.13]

2 LDL cholesterol, mmol/L Show forest plot

5

3291

Mean Difference (IV, Random, 95% CI)

‐0.19 [‐0.33, ‐0.05]

3 HDL cholesterol, mmol/L Show forest plot

6

5147

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.02, 0.01]

4 Triglycerides, mmol/L Show forest plot

7

3845

Mean Difference (IV, Random, 95% CI)

‐0.08 [‐0.21, 0.04]

5 total cholesterol /HDL ratio Show forest plot

3

2985

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.33, 0.13]

6 LDL /HDL ratio Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Subtotals only

7 Lp(a), mmol/L Show forest plot

2

2882

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.00, 0.00]

8 Insulin sensitivity Show forest plot

4

Mean Difference (IV, Random, 95% CI)

Subtotals only

8.1 HbA1c (glycosylated haemoglobin), %

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 GTT (glucose tolerance test), glucose at 2 hours, mmol/L

3

249

Mean Difference (IV, Random, 95% CI)

‐1.69 [‐2.55, ‐0.82]

8.3 HOMA

1

2832

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.04, 0.04]
Figures and Tables -
Comparison 3. SFA reduction vs usual diet ‐ other secondary outcomes
Navigate to table in Review