Study characteristics

Methods

Setting: UK (Cambridge and Newcastle)

Design: randomisation by minimisation with even distribution of participants in each group by age sex and BMI, parallel group.

Dates: trial dates not reported

Intervention duration: 16 weeks

Follow‐up: no postintervention follow‐up

Focus: to compare the effects of different levels of whole grain diets (2 intervention groups) to replace refined grains in the diets of overweight and obese people who were not whole grain consumers on markers of cardiovascular risk.

Participants

N: 316 randomised (to 3 groups) (85/105 completers in the lower‐dose intervention group, 81/105 in the higher‐dose intervention group, and 100/106 in the control group).

Inclusion criteria: overweight or obese adults, aged 18 to 65 years, BMI > 25 kg/m², consuming < 30 g whole grains/day.

Exclusion criteria: BMI < 25 kg/m²; habitual consumption of > 30 g/day whole grain; CVD, diabetes, or hyperlipidaemia; smoking > 20 cigarettes/day; history of substance abuse; recent weight change; desire to diet; or absence during a period of the intervention.

Age (years): intervention (lower dose): 45.9 SD 10.1; intervention (higher dose): 45.7 SD 9.9; control: 45.6 SD 10.0

Sex (% men): intervention (lower dose): 50.0%; intervention (higher dose): 51.2%%; control: 49.0%

Ethnicity: British (ethnic composition not reported)

Baseline cardiovascular risk status: all reported as medians.

BMI (kg/m²): intervention (lower dose): 30.0 SD 3.7; intervention (higher dose): 30.3 SD 4.5; control: 30.0 SD 4.0

Total cholesterol (mmol/L): intervention (lower dose): 5.1 SD 0.8; intervention (higher dose): 5.3 SD 1.0; control: 5.2 SD 1.0

HDL cholesterol (mmol/L): intervention (lower dose): 1.3 SD 0.3; intervention (higher dose): 1.3 SD 0.2; control: 1.3 SD 0.3

LDL cholesterol (mmol/L): intervention (lower dose): 3.2 SD 0.7; intervention (higher dose): 3.3 SD 0.8; control: 3.2 SD 0.9

Systolic blood pressure (mmHg): intervention (lower dose): 125.5 SD 16.1; intervention (higher dose): 129.5 SD 15.5; control: 127.3 SD 14.8

Diastolic blood pressure (mmHg): intervention (lower dose): 79.0 SD 9.8; intervention (higher dose): 79.0 SD 9.3; control: 79.8 SD 10.2

Medications used: not reported

Interventions

Whole grain group 1: (lower whole grain; 60 g WG/d as 3 servings for 16 weeks) (n = 105 randomised, 85 completed)

Whole grain group 2: (higher whole grain; 60 g WG/d as 3 servings for 8 weeks, then 120 g WG/d as 5 servings for 8 weeks) (n = 105 randomised, 81 completed)

Control: (usual diet) (n = 106 randomised, 100 completed)

Description of dietary intervention: the 2 intervention groups were provided with a range of whole grain foods (whole wheat bread, Shredded Wheat Fruitful, Cheerios, porridge oats, brown basmati rice, whole wheat pasta, Weetabix, porridge, oat bars, and whole grain crisps) and asked to substitute ‘like for like’ for refined grain foods to a prescribed amount. The approach was chosen to reflect choices of whole grains in a free‐living population.

Incentives: not reported

Co‐interventions in both groups: none

Assessment of dietary adherence: FFQ (7‐day recall) at weeks 8 and 16

Was the diet energy reduced? no

Comparability of diet composition: There was an (P < 0.05) increase in carbohydrate intake in both whole grain groups at week 8 and week 16, and between control and whole grain group 1 and whole grain group 2. There was also an increase in total energy intake in whole grain group 1 at week 8 and wholegrain group 2 at week 16. There was an increase in protein in whole grain group 1 at week 8 and whole grain group 2 at week 16. Percentage energy from fat decreased in whole grain group 2 at weeks 8 and 16. Dietary fibre increased in both whole grain groups at both week 8 and week 16. (See Table 1.)

Change in diet over time: Whole grain intake (estimated from FFQ data): at baseline WG intake was < 20 g/day for each group; for the control group, WG intake averaged 19 (SD 19.9) g/d; for whole grain group 1, WG intake was 74 (SD 28.5) g/d averaged for weeks 8 and 16 (no significant difference between week 8 and 16); for whole grain group 2, WG intake was 83 (SD 3) g/d at week 8 and 115 (SD 39.6) g/d at week 16. (See Table 1.)

There were differences between baseline and intervention groups in frequency of consumption of breads and breakfast cereals at week 16 (P < 0.05):

• bread: control: 1.46/day (SD 1.46); whole grain group 1: 1.99 (SD 5); whole grain group 2: 3.06 (SD 1.93);

• breakfast cereals: control: 0.57 (SD 0.50); whole grain group 1: 1.00 (SD 0.52); whole grain group 2: 1.00 (SD 0.65).

A difference between whole grain group 2 and control was seen for fruit intake after 16 weeks (p<0.005).

There were no differences in other food groups (meat, fish, potatoes, rice and pasta, dairy and egg products, milk, spreads, sweets and snacks, vegetables.

Outcomes

Total cholesterol, HDL cholesterol, LDL cholesterol, triacylglycerides (TAG; mmol/L), weight (kg), body fat (%), systolic BP (mm Hg), diastolic BP (mmHg), NEFA (mmol/L), markers of insulin sensitivity, endothelial function, inflammatory and coagulatory status. States no conflicts of interest for any authors.

Funding/conflicts of interest

Fully funded by UK Food Standards Agency (project N02036). Study foods were provided by commercial suppliers (Cereal Partners Worldwide, Weetabix, Allied Bakeries, PepsiCo).

Notes

The authors noted that "the participants appeared to include the whole grain foods as a dietary addition as opposed to the dietary substitution that was explicitly requested". This conclusion is supported by the diet composition data. Adverse effects: 3 participants in both whole grain groups reported intolerance to study foods, none in control group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Participants were randomly allocated (using an MS‐DOS based computer program at each study centre)"; minimisation was used to ensure even distribution within each group by age, sex, and BMI

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Researcher collecting anthropometric data was not blind to allocation (secondary outcome). Lipid analysis not specifically reported to have been blind.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Attrition greater in both whole grain intervention groups than in control group (85/105 completers in the lower‐dose intervention group, 81/105 in the higher‐dose intervention group, and 100/106 in the control group). Characteristics of those lost to follow‐up not completed. Some reasons provided but not for all dropouts.

Intention to treat analysis

Unclear risk

Not reported. Only outcomes for completers reported, so probably not done.

Selective reporting (reporting bias)

Unclear risk

Reports all relevant outcomes, but not enough information to judge.

Groups comparable at baseline

Low risk

Comparable for lipids (total, HDL, LDL, TAG), blood pressure, and anthropometry

Other bias

Low risk

Sample size of 254 participants was calculated to detect a 10% decrease in LDL cholesterol with a 0.05 significance level and 80% power. Allowing for an estimated dropout of 15%, a target of 100 participants per treatment group was proposed. This was achieved.

Study characteristics

Methods

Setting: Finland (Kuopio) and Italy (Naples)

Design: parallel groups (with stratification for sex, age, and BMI).

Dates: March 2008 to May 2014

Intervention duration: 12 weeks

Follow‐up: no postintervention follow‐up

Focus: to compare the effects of diets containing whole grain rye or wheat cereals compared to refined grains on markers of metabolic syndrome in people with metabolic syndrome.

Participants

N: 146 randomised (62/71 completers in the whole grain intervention group and 61/75 in the control group).

Inclusion criteria: male and female, aged 40 to 65 years, with metabolic syndrome (diagnosed on National Cholesterol Education Program criteria).

Exclusion criteria: diabetes and/or renal failure (serum creatinine > 1.5 mg/dL), liver abnormalities (ALT/AST ratio 2 times above normal values), anaemia (haemoglobin < 12 g/dL), any other chronic disease, or if they used any drug able to influence glucose and lipid metabolism and inflammation (corticosteroid hormones other than inhaled corticosteroids, hypolipidaemic and/or anti‐inflammatory drugs); however, in the Kuopio study centre the use of cholesterol lowering medications (statins) was allowed.

Age (years): 40 to 65 years, otherwise not reported.

Sex (% men): whole grain intervention: 46.9%; control: 47.5%

Ethnicity: Italian and Finnish (ethnic composition not reported)

Baseline cardiovascular risk status:

BMI (kg/m²): whole grain intervention: 31.6 (4.6); control: 31.3 (4.4)

Total cholesterol (mmol/L): whole grain intervention: 5.15 (1.09); control: 5.28 (0.93)

HDL cholesterol (mmol/L): whole grain intervention: 6 (0.36); control: 4 (0.31)

LDL cholesterol (mmol/L): whole grain intervention: 3.26 (0.98); control: 3.41 (0.80)

Systolic blood pressure (mmHg): whole grain intervention: 133 (15); control: 135 (14)

Diastolic blood pressure (mmHg): whole grain intervention: 84 (9); control: 86 (8)

Medications used: in the Kuopio study centre, some individuals were using cholesterol‐lowering medication (10 in the whole grain intervention group and 10 in the control group), however sensitivity analyses were conducted after excluding these people.

Interventions

Whole grain diet group: (wheat and rye whole grain)

Control: (refined cereal foods), differed between centres

Description of dietary intervention: whole grain wheat and rye products (and smaller amounts of oat and barley), most with a low postprandial glucose and/or insulin response. The only difference between the whole grain and the control diet was the inclusion of a fixed amount of whole grain or refined cereal products as the main carbohydrate source. Aimed to include 90% sourdough bread and 10% endosperm rye bread. Naples ‐ whole grain products including whole wheat bread (plus some endosperm rye bread), whole wheat pasta, barley kernels, whole grain oat biscuits and breakfast cereals (all bran sticks and flakes). Kuopio ‐ whole grain and control diets aimed to include 20% to 25% of the total daily energy intake as study breads. The type of bread consumed by the Kuopio participants was 50% commercial whole grain rye bread, 40% endosperm rye bread, and 10% sourdough whole wheat bread, and participants were advised to replace their habitual potato consumption with 210 g dry weight of whole wheat pasta per week, and were given whole oat biscuits for snacks. Test products in both diets provided free of charge on a weekly basis. Also given written instructions and recipes.

Incentives: not reported

Co‐interventions in both groups: none

Assessment of dietary adherence: 4‐day and 7‐day food records and plasma alkylresorcinols

Was the diet energy reduced? no

Comparability of diet composition: energy intake increased in intervention and control groups P < 0.02 from baseline, but no significant difference between groups at 12 wks. Significant increased protein, PUFA, total fibre, and cereal fibre between WG group and control at 12 wks (P < 0.05). (See Table 1.)

Change in diet over time: not reported

Outcomes

Peripheral insulin sensitivity assessed by FSIGT, lipids and inflammatory markers, body weight, blood pressure, waist circumference, short‐chain fatty acids

Funding/conflicts of interest

European Commission (6th Framework Programme, project HEALTHGRAIN FOOD‐CT‐2005‐514008), Raisio plc Research Foundation (Raisio is a commercial organisation that makes cereal products), the Nordic Centre of Excellence (projects HELGA and SYSDIET). Barilla G&R F.lli.SpA, Parma, Italy and Raisio Nutrition Ltd, Finland provided some of the cereal products for the study participants.

Notes

Stable body weight, body fat composition, and waist circumference maintained during the intervention.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation was carried out by means of a computerised random allocation list.

Allocation concealment (selection bias)

Low risk

Allocation was carried out by personnel not involved in the study.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Anthropometric data collection does not appear to have been blind (secondary outcome). Lipid analysis appears to have been blind.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Differential rates of attrition between groups, and characteristics of those lost to follow‐up not reported (62/71 completers in the whole grain intervention group and 61/75 in the control group).

Intention to treat analysis

Unclear risk

Not reported. Only outcomes for completers reported, so probably not done.

Selective reporting (reporting bias)

Unclear risk

Reports all relevant outcomes, but not enough information to judge.

Groups comparable at baseline

Low risk

Comparable for lipids (total, HDL, LDL, TAG), blood pressure, anthropometry, and age

Other bias

Unclear risk

Power calculations used insulin sensitivity as outcome variable (not a primary outcome of this review). Power relevant to lipids, blood pressure, or BMI not reported. The 2 centres had different nutritional constituent parts and respective controls. 10 participants in each group had lipid‐lowering medications.

Study characteristics

Methods

Setting: USA

Design: randomised parallel study

Dates: March 2009 to May 2011

Intervention duration: 12 weeks (6 weeks weight maintenance diet, followed by 6 weeks weight loss diet)

Follow‐up: no postintervention follow‐up

Focus: to compare the effects of whole grain diets compared to refined grains in people with or at risk of metabolic syndrome (overweight and obese individuals with increased waist circumference and 1 or more other MetS criteria).

Participants

N: 60 randomised (25/28 completers in the whole grain intervention group and 25/32 in the control group).

Inclusion criteria: male and female, aged 35 to 55 years (overweight and obese individuals with BMI 25 to 42 kg/m²; with increased waist circumference >/= 102 cm in men and >/= 88 cm in women; and 1 or more other MetS criteria: fasting plasma glucose >/= 100 mg/dL, fasting serum triglycerides >/= 150 mg/dL, BP >/= 130/85 mmHg and/or fasting serum HDL cholesterol < 50 mg/dL in women or < 40 mg/dL in men).

Exclusion criteria: use of medications affecting glucose or lipid metabolism, frequent (> 4 times/wk) use of anti‐inflammatory medications, pregnancy or lactation, smoking, high alcohol intake (> 14 drinks/wk), and diagnosed CVD, diabetes, or inflammatory disease.

Age (years): 35 to 55 years: whole grain: 46.4 (SD 5.9); control: 45.8 (SD 6.0)

Sex (% men): whole grain: 48%; control: 52%

Ethnicity: US (ethnic composition not reported)

Baseline cardiovascular risk status:

BMI (kg/m²): whole grain intervention: 32.9 (3.5); control: 33.5 (4.0)

Total cholesterol (mmol/L): not reported

HDL cholesterol (mmol/L): whole grain intervention: 6 (0.28); control: 1.06 (0.39)

LDL cholesterol (mmol/L): not reported

Systolic blood pressure (mmHg): whole grain intervention: 123 (12); control: 125 (12)

Diastolic blood pressure (mmHg): whole grain intervention: 83 (10); control: 85(6)

Medications used: whole grain group: 48%; control: 40%. Blood pressure medications were allowed.

Interventions

Whole grain diet group (whole grain products, variety of grain types)

Control (refined grain products)

Description of dietary intervention: the whole grain diet group consumed all WG products from a variety of grain types; those receiving the control diet consumed the refined grain counterpart. The top 3 grains consumed were wheat, oats, and rice with the whole grain diet and wheat, rice, and corn with the refined grain diet. Wheat products constituted 77% of the whole grain diets and 63% of the control diets. Diets were tailored to individual energy requirements; the whole grain diets contained between 163 and 301 g/whole grain per day, and the refined grain diets no whole grains. Both diets comprised an isocaloric weight maintenance diet for 6 weeks followed by an energy‐reduced diet for the next 6 weeks (reduced by ~500 kilocalories/d). All meals and snacks were prepared at metabolic kitchens on the university campus. Participants had to go to the kitchen to pick up or eat their meals.

Incentives: not reported

Co‐interventions in both groups: none

Assessment of dietary adherence: compliance forms (all food provided)

Was the diet energy reduced? yes

Comparability of diet composition: both diets were designed to have the same macronutrient composition and to meet National Cholesterol Education Program guidelines for saturated fat (< 7% E), mono‐ and polyunsaturated fats (~10% and ~7% E), total cholesterol (< 200 mg/d), and total fibre (> 20 g/d). Participants consumed all study foods and did not consume any additional non‐study foods on 86% of reported days. Physical activity levels were stable. (See Table 1.)

Change in diet over time: not reported

Outcomes

Primary: weight, BMI, waist circumference, triglycerides, HDL cholesterol, glucose, systolic BP, diastolic BP. Secondary: total adiponectin, HMW adiponectin, leptin, TC:HDL ratio, LDL cholesterol, CRP, IL‐6, TNF‐alpha, insulin, HOMA‐IR, RMR, % adipose tissue.

Funding/conflicts of interest

Bell Institute of Health and Nutrition (General Mills, Inc.) and National Institutes of Health grant M01RR10732. The first author was supported by a Nestle fellowship, alkylresorcinol analysis was funded by Cereal Partners Worldwide (a joint venture between General Mills, Inc. and Nestle SA).

Notes

To enhance compliance, participants were given the option of taking a 1‐ to 2‐week break after the first 6‐week diet period.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"randomly assigned ... using a computer‐generated random number assignment"

Allocation concealment (selection bias)

Unclear risk

"An unblinded study coordinator stratified participants by age, sex and BMI"

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

"Outcome assessors (i.e. nurses and technicians) were blinded"

Incomplete outcome data (attrition bias)
All outcomes

High risk

Reasons for attrition reported: 7 lost to follow‐up in control group (none due to diet issues), 3 lost to follow‐up in whole grain group (2 due to diet issues), similar rates of loss to follow‐up, but differential rates in those withdrawing because of the diet.

Intention to treat analysis

Unclear risk

"Per protocol analysis included only the data from participants who completed both phases of the study"

Selective reporting (reporting bias)

Unclear risk

Reports all relevant outcomes but not enough information to judge.

Groups comparable at baseline

Low risk

Yes, except for triglycerides, which were higher in the control group. Unclear risk for triglycerides

Other bias

Unclear risk

Power calculations used body composition (% of abdominal AT) as outcome variable (not a primary outcome of this review), which required a sample size of 50. This was met, but power relevant to measuring changes in lipids or blood pressure not reported.

Study characteristics

Methods

Setting: USA

Design: parallel RCT with stratified randomisation by sex (male or female) and BMI status (BMI < 40 or >/= 40 kg/m²).

Dates: trial opened to accrual September 2005, enrolment completed August 2006.

Intervention duration: 12 weeks

Follow‐up: no postintervention follow‐up

Focus: to determine whether including whole grain foods in a hypocaloric (reduced by 500 kilocalories/d) diet enhances weight loss and improves CVD risk factors in obese adults with metabolic syndrome.

Participants

N: 50 randomised (24/25 completers in the whole grain intervention group and 23/25 in the control group).

Inclusion criteria: men and women were eligible if they had a BMI (in kg/m²) >/= 30 and met 3 of 5 National Cholesterol Education Program Adult Treatment Panel III criteria for metabolic syndrome:

1. triacylglycerol concentrations >/= 150 mg/dL,

2. HDL cholesterol concentrations < 40 mg/dL in men or < 50 mg/dL in women,

3. fasting glucose concentrations >/= 100 mg/dL,

4. systolic blood pressure >/= 30 mmHg or diastolic blood pressure >/= 85 mmHg (or both),

5. waist circumference >/= 102 cm in men or 88 cm in women.

Exclusion criteria: diagnosed with type 1 or 2 diabetes, CVD, cancer, or any other serious medical condition or if they were using any medications known to affect glucose, insulin, cholesterol, or reproductive hormones; people who smoked, drank > 2 alcoholic beverages/d, or consumed a diet high in whole grains (> 3 servings/d); or who were pregnant or lactating.

Age (years): 24 to 63 years. Whole grain group mean age: 45.4 (SD 8); refined grain group mean age 46.6 (SD 9.7).

Sex (% men): whole grain group: 48%; refined grain group: 52%

Ethnicity: US (48/50 white; 1/50 African‐American; 1/50 Hispanic)

Baseline cardiovascular risk status:

BMI (kg/m²): whole grain intervention: 35.54 (4.1); control: 36.1 (4.9)

Total cholesterol mmol/L: whole grain intervention: 4.91 (1.22); control: 4.86 (0.64)

LDL cholesterol, mmol/L: whole grain intervention: 3.08 (1.02); control: 2.96 (0.51)

HDL cholesterol, mmol/L: whole grain intervention: 1.07 (0.23); control: 1.06 (0.2)

Systolic blood pressure (mmHg): whole grain intervention: 123 (9.4); control: 130.3 (13.3), P = 0.03

Diastolic blood pressure (mmHg) : whole grain intervention: 83.2 (8.3); control: 82.0 (7.5)

Medications used: not reported, other than that participants on medications known to affect glucose, insulin, cholesterol, or reproductive hormones were excluded.

Interventions

Whole grain diet group: based on a range of whole grains

Control: refined cereal foods

Description of dietary intervention:
The whole grain group were given a target number of daily whole grain servings (4, 5, 6, or 7 servings/d) based on their energy needs. The whole grain group were given a list and description of whole grain foods to help them identify foods to include in their diet, and they were encouraged to select foods for which a whole grain was listed as the first ingredient. They were advised to consume 3 daily servings of whole grain foods for the first 2 wks of the study, and then to increase to their target number of daily whole grain servings for the remaining 10 wks. Participants in the refined grain group were also given a list of whole grain foods and were asked not to consume any of these foods during the study period. A registered dietitian met individually with each participant at baseline to discuss the dietary intervention and provided educational materials.

Additionally, both groups were asked to eat 5 servings of fruits and vegetables, 3 servings of low‐fat dairy products, and 2 servings of lean meat, fish, or poultry, per day, based on 2005 dietary guidelines for Americans. The target macronutrient composition was 55% of energy as carbohydrate, 30% of energy as fat (with an emphasis on unsaturated fats), and 15% of energy as protein.

Incentives: not reported

Co‐interventions in both groups: participants in both groups were encouraged to engage in moderate physical activity for 30 min per session 3 times/wk.

Assessment of dietary adherence: 3‐day diet record (and a diet satisfaction questionnaire)

Was the diet energy reduced? yes (target energy deficit ~500 kilocalories/d)

Comparability of diet composition: yes. Energy intake decreased (P < 0.001) from baseline in both diet groups (as both were weight loss diets). The percentage of energy from carbohydrate and protein increased (P < 0.01), and from fat decreased (P < 0.001) in both diet groups compared with baseline. Participants in the whole grain group increased their intake of total, insoluble, and soluble fibre by 50%, 52%, and 47%, respectively, and those in the refined grain group increased their intakes by 7%, 5%, and 14%, respectively. (See Table 1.)

Change in diet over time: as above

Outcomes

Systolic and diastolic BP; lipids (LDL cholesterol, HDL cholesterol, triacylglycerol); anthropometric measures, including weight and BMI; apolipoprotein A1/B; glycaemic measures; satisfaction with diet.

Funding/conflicts of interest

General Mills Bell Institute of Health and Human Nutrition, grant no. K24 HD01476 and M01 RR10732 from the National Institutes of Health, and construction grant no. C06 RR016499 (to the General Clinical Research Center of The Pennsylvania State University).

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Participants were assigned to either a whole grain or refined‐grain hypocaloric diet with the use of a stratified randomization scheme"

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Attrition and reasons for loss to follow‐up fully reported.

Intention to treat analysis

Unclear risk

Analysis only reported for completers.

Selective reporting (reporting bias)

Unclear risk

All outcomes fully reported, but not enough information to judge.

Groups comparable at baseline

Unclear risk

Yes, except for systolic BP and the percentage of the LDL‐III subclass, which were higher (P=0.03) at baseline in the refined grain group than in the whole grain group; however, there were no other differences at baseline between the groups.

Other bias

Unclear risk

Power calculations used weight as outcome variable (not a primary outcome of this review), which required a sample size of 50. This was met, but power relevant to measuring changes in lipids or blood pressure not reported.

Study characteristics

Methods

Setting: Denmark (Copenhagen)

Design: parallel‐group RCT

Dates: not reported

Intervention duration: 12 weeks (after a 2‐week run‐in period)

Follow‐up: no postintervention follow‐up

Focus: to compare energy‐restricted diets based on whole grain wheat compared to refined grain wheat in overweight or obese postmenopausal women.

Participants

N: 79 were randomised after the run‐in period, and a total of 72 women completed the study (38/42 in the whole grain wheat group and 34/37 in the refined grain wheat group).

Inclusion criteria: BMI 27 to 37 kg/m², age 45 to 70 years, and 1‐year postmenopausal (self reported).

Exclusion criteria: smoking, chronic illnesses (diabetes or CVD), untreated hypertension
(> 160/100 mmHg), elevated fasting total cholesterol (> 6.5 mmol/L) or glucose (> 7.0 mmol/L), use of dietary supplements, food dislikes or intolerances relevant to the study, and use of medications (except antihypertensives).

Age (years): 45 to 70 years, otherwise not reported.

Sex (% men): 0% (all female)

Ethnicity: Danish (ethnic composition not reported)

Baseline cardiovascular risk status:

The study reports there was no difference in any of the baseline characteristics.

BMI (kg/m²): whole grain intervention: 30.0 (SEM 0.4); control: 30.4 (SEM 0.6)

Total cholesterol (mmol/L): whole grain intervention: 5.57 (SEM 0.16); control: 5.61 (SEM 0.14)

HDL cholesterol (mmol/L): whole grain intervention: 1.24 (0.04 SEM); control: 1.28 (0.04 SEM)

LDL cholesterol (mmol/L): whole grain intervention: 3.75 (0.16 SEM); control: 3.75 (0.13 SEM)

Systolic blood pressure (mmHg): whole grain intervention: 133 (2 SEM); control: 138 (4 SEM)

Diastolic blood pressure (mmHg): whole grain intervention: 85.5 (1.4 SEM); control: 87.3 (1.6 SEM)

Medications used: 10 women in each group used antihypertensive medications.

Interventions

Whole grain diet group: whole grain wheat

Control: refined wheat foods

Description of dietary intervention: whole grain wheat foods as part of an energy‐restricted diet to provide 105 g of whole grains daily. The whole grain or refined grain foods were intended to replace ~2 MJ of the participants' habitual diet, and both groups were asked to consume 62 g of bread, 60 g pasta (uncooked), and 28 g of biscuits daily. There was no restriction on consumption of other cereal products. Both groups were asked to consume an energy‐restricted diet with a deficit of at least 1250 kJ/d but not less than 5000 kJ/d, with minimum protein intake of 60 g/d. The participants met with a dietitian at least 5 times during the study. Food provided biweekly.

Incentives: not reported

Co‐interventions in both groups: none

Assessment of dietary adherence: food diary (self reported) (note only 57 of 72 women who completed the study kept food diaries eligible for data analysis).

Was the diet energy reduced? yes (~1250 kJ/d deficit)

Comparability of diet composition: total self reported energy intake similar at weeks 1 to 6: whole grain 5830 kJ/d (SEM 190) and refined grain 5900 kJ/d (SEM 280), but higher in refined grain group for weeks 7 to 12: whole grain 6060 kJ/d (SEM 150) and refined grain 6330 (SEM 180) kJ/d. Carbohydrate also appears to be higher in the refined grain group, but SEM and P values not reported. (See Table 1.)

Change in diet over time: reported at 4, 8, 12 weeks. (See Table 1.)

Outcomes

Systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, insulin, HOMA‐IR, glycated haemoglobin, hsCRP, IL‐6, body weight, BMI, waist circumference, FFM.

Funding/conflicts of interest

European Commission in the Communities 6th Framework Programme, Project HEALTHGRAIN (FOOD‐CT‐2005‐514008), the University of Copenhagen, Faculty of Life Sciences and LMC FOOD Research School. Authors M Petronio and G Riboldi are employed by Barilla, and AB Ross is employed by Nestle.

Notes

There was a concomitant increase in energy intake and carbohydrate intake in the refined grain group.

Authors report that non‐compliance in the refined grain group did not reflect a lack of intake of refined grain foods, but instead was due to high intake of whole grain products other than the foods provided.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"participants were randomly allocated", but method not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up and reasons for dropout similar in both groups. Whole grain 4/42 lost, refined grain 3/37 lost. However, only 57 of 72 food diaries eligible for analysis, reasons not reported.

Intention to treat analysis

Unclear risk

Intention‐to‐treat analysis performed for anthropometric outcomes, no differences in ITT analysis compared to completers. Intention‐to‐treat analysis not done for lipids and blood pressure outcomes.

Selective reporting (reporting bias)

Unclear risk

Only 57 of 72 food diaries eligible for analysis, reasons not reported.

Groups comparable at baseline

Low risk

States no difference.

Other bias

Unclear risk

Power calculations used weight as outcome variable (not a primary outcome of this review), which required a sample size of 72 (36 in each group). This was met, but power relevant to measuring changes in lipids or blood pressure not reported.

Study characteristics

Methods

Setting: Finland

Design: parallel‐group RCT

Dates: recruitment and screening October 2007 to November 2008, intervention periods were carried out during January 2008 to June 2009.

Intervention duration: 12 weeks

Follow‐up: no postintervention follow‐up

Focus: to investigate the effects of whole grain, fish, and bilberries on serum metabolic profile and lipid transfer protein activities in people with metabolic syndrome.

Participants

N: 131 were randomised (34/42 completers in the whole grain intervention and 35/45 completers in the control group).

Inclusion criteria: 40 to 70 years of age, impaired glucose metabolism (FPG 5.6 to 6.9 mmol/L) or in OGTT 2 hour (plasma glucose 7.8 to 11.0 mmol/L) and 2 of the following: BMI 26 to 39 kg/m², waist circumference > 102 cm in men and > 88 cm in women, serum TG > 1.7 mmol/L, HDL < 1.0 mmol/L in men and < 1.3 mmol/L in women, or blood pressure >= 130 or >= 85 mmHg.

Exclusion criteria: BMI > 40 kg/m²; fasting serum triglyceride concentration > 3.5 mmol/L; fasting serum cholesterol > 8 mmol/L; type 1 or 2 diabetes; abnormal liver, kidney, or thyroid function; large alcohol intake (women > 16, men > 24 doses (4 cL liquor or equivalent) during week); inflammatory bowel disease; disease that prevents participation; neuroleptic cortisone medication.

Age (years): 40 to 70 years; mean age in whole grain enriched diet group 58 (SD 8) and in control group 59 (SD 7).

Sex (% men): whole grain intervention: 50%, control: 51%

Ethnicity: Caucasian (understood to be white)

Baseline cardiovascular risk status:

The study reports there was no difference in any of the baseline characteristics.

BMI (kg/m²): whole grain intervention: 31.4 (SD 3.4); control: 31.0 (SD 3.6)

Total cholesterol (mmol/L): whole grain intervention: 5.1 (SD 1.0); control: 5.4 (SD 1.0)

HDL cholesterol (mmol/L): whole grain intervention: 1.2 (SD 0.4); control: 1.3 (SD 0.3)

LDL cholesterol (mmol/L): whole grain intervention: 3.2 (SD 0.8); control: 3.4 (SD 0.8)

Systolic blood pressure (mmHg): whole grain intervention: 135 (SD 16); control: 139 (SD 12)

Diastolic blood pressure (mmHg): whole grain intervention: 86 (SD 8); control: 88 (SD 7)

Medications used:

Statins: 10/34 (29%) intervention; 9/35 (26%) control

Hormonal replacement therapy: 4/34 (11%) intervention; 3/34 (9%) control

Beta‐blocker or diuretics: 12/34 (35%) intervention; 9/35 (25.7%) control

Interventions

Whole grain diet group: whole grain wheat and rye bread

Control: refined wheat foods

Description of dietary intervention: the whole grain group replaced their habitual grain products with whole grain breads and a bread with low postprandial insulin response. Products covered 20% to 25% of total energy intake and were delivered to the participants. The fibre contents of the breads were 6.9% (endosperm rye bread), 6.4% (whole grain wheat bread), and 10% to 14% (commercial whole grain rye breads). 1 portion of habitually used grain product, e.g. a slice of low‐fibre wheat bread, was allowed daily to increase compliance. Pasta with a fiber content of 6% was also delivered and was instructed to be consumed at the dose equal to 3.5 dL of uncooked pasta per week. Participants were given whole grain oat biscuits of which they were allowed to consume 1 portion per day on a voluntary basis. Biscuits contained 8 to 8.5 g/100 g of dietary fibre and 16 to 18 g/100 g of fat, of which 4.3 to 7.7 g was saturated.

The control group replaced their habitually used breads with refined wheat breads (dietary fiber 3 to 4.3 g/100 g) and other cereal products, e.g. pasta, with low‐fibre products (< 6 g/100 g dietary fibre). Participants were allowed to eat a maximum of 1 to 2 portions of rye products per day.

Incentives: not reported

Co‐interventions in both groups: none

Assessment of dietary adherence: 4‐day food record at baseline, three 4‐day food records at weeks 3, 7, and 11.

Was the diet energy reduced? no

Comparability of diet composition: yes. In the whole grain group, the intake of total fat decreased, but there was no change in the quality of dietary fat. Fibre intake increased in the whole grain group, whereas it decreased in the control group. (See Table 1.)

Change in diet over time: reported at baseline, 12 weeks. (See Table 1.)

Outcomes

Gene expression, glucose metabolism, plasma lipidomic profiles

Funding/conflicts of interest

Funding was provided by Academy of Finland (The Research Program on Nutrition, Foods and Health (ELVIRA), Decision number 117844 for MU and 117996 for MO), European Commission in the Communities 6th Framework Programme, Project HEALTHGRAIN (FOOD‐CT‐2005‐514008, for HM and KP), Sigrid Juselius Foundation, The Finnish Diabetes Research Foundation, Nordic Centre of Excellence on Systems Biology in Controlled Dietary Interventions and Cohort Studies (SYSDIET, 070014), TEKES 70103/06, The EVO‐fund of Kuopio University Hospital (5254), Fazer bakeries Oy, Vaasan & Vaasan Oy, KE Leipa¨ Oy, Leipomo Ruista¨hka¨, Leipomo Koskelonseutu, Raisio Oyj, Pakkasmarja Oy, Joswola Oy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Notes

This was a 3‐arm RCT (HealthyDiet, not relevant to this review: whole grain and low postprandial insulin response grain products, fatty fish 3 times a week, and bilberries 3 portions per day; whole grain: whole grain and low postprandial insulin response grain products; control: refined wheat breads and cereal products).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"The randomisation was conducted based on a randomisation table"

Allocation concealment (selection bias)

Unclear risk

"Participants were randomly assigned by the study nurse to one of the following groups: HealthyDiet, wholegrain or control"

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not stated. In the CONSORT checklist they mention N/A.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Reasons for attrition were reported and numbers provided: 24.4% in the control and 19% in the intervention.

Intention to treat analysis

Unclear risk

Analysis only reported for completers.

Selective reporting (reporting bias)

Low risk

All outcomes intended to measure in the protocol were reported.

Groups comparable at baseline

Low risk

Yes. "There were no significant differences in the characteristics between the groups at baseline"

Other bias

Unclear risk

Power calculations used glucose metabolism as outcome variable (not a primary outcome of this review), which required a sample size of 111 (37 in each group). This was nearly met, but power relevant to measuring changes in lipids or blood pressure not reported.

Study characteristics

Methods

Setting: USA (Bloomington, IN and St Petersburg, FL)

Design: randomised parallel‐arm controlled trial

Dates: trial dates not reported

Intervention duration: 12 weeks

Follow‐up: no postintervention follow‐up

Focus: to compare the effect on LDL cholesterol and other cardiovascular disease markers of whole grain oat ready‐to‐eat cereal compared to energy‐matched low‐fibre foods as part of a dietary program for weight loss in overweight and obese adults.

Participants

N: 204 randomised, 80/101 completed in whole grain oat ready‐to‐eat cereal group; 73/103 completed in the control group.

Inclusion criteria: free‐living overweight and obese adults, BMI 25 to 40 kg/m² with baseline LDL cholesterol 3.4 to 5.2 mmol/L, aged 20 to 65 years.

Exclusion criteria: participants who reported a weight change of 4.5 kg during the previous 2 months; use of weight loss medications within 2 months before screening or supplements, programs, or meal replacement products within 2 weeks before screening; use of drugs (within 4 weeks before screening), supplements, or foods (within 2 weeks before screening) known to alter lipid levels; use of fibre‐containing supplements within 2 weeks before screening; daily consumption of oat or barley products (e.g. ready‐to‐eat oat‐based cereals, oatmeal, or oat bran) or frequent consumption of foods rich in viscous fibre within 2 weeks of screening; clinically significant abnormal laboratory test results (e.g. triglycerides >/= 4.5 mmol/L, glucose >/= 7.0 mmol/L, creatinine >/= 114.4 μmol/L, and alanine aminotransferase and aspartate aminotransferase levels 1.5 times the upper limit of normal), uncontrolled hypertension (systolic/diastolic blood pressures >/= 160/100 mmHg); a history of cardiac, renal, hepatic, endocrine, pulmonary, biliary, pancreatic, gastrointestinal, or neurologic disorders, or cancer in the past 2 years; known sensitivity to any of the ingredients in the study foods; a history of weight‐reducing surgery; a history of eating disorders or alcohol abuse; or use of thyroid hormones (except stable dose replacement therapy) or systemic corticosteroids.

Age (years): whole grain oat group: 50.1 (SEM); control: 47.5 (SEM 1.3)

Sex (% men): whole grain oat group: 24.7%; control: 17.9%

Ethnicity: US:

• whole grain oat group: non‐Hispanic white 69/77; African‐American 6/77; Hispanic 1/77; other 1/77

• control group: non‐Hispanic white 55/67; African‐American 5/67; Hispanic 4/67; other 3/67

Baseline cardiovascular risk status:

BMI (kg/m²): whole grain intervention: 32.2 (SEM 0.6); control: 32.0 (SEM 0.5)

Total cholesterol (mmol/L): whole grain intervention: 6.00 (SEM 0.08); control: 5.92 (SEM 0.08)

HDL cholesterol (mmol/L): whole grain intervention: 1.24 (0.03); control: 1.24 (0.04)

LDL cholesterol (mmol/L): whole grain intervention: 4.02 (0.05); control: 4.00 (0.06)

Triglyceride (mmol/L): whole grain intervention: 1.65 (SEM 0.0.9); control: 1.48 (SEM 0.0.8)

Systolic blood pressure (mmHg): whole grain intervention: 127.2 (SEM 1.2); control: 122.6 (SEM 1.3) (P = 0.01)

Diastolic blood pressure (mmHg): whole grain intervention: 79.4 (0.9); control: 78.3 (1.00)

Medications used: not reported

Interventions

Whole grain diet group: whole grain oat ready‐to‐eat cereal

Control: low‐fibre cereal foods

Description of dietary intervention: 2 portions per day of whole grain ready‐to‐eat oat cereal or energy‐matched low‐fibre foods (control) such as corn cereals, white toast, plain bagels, English muffins, pretzels, soda crackers, or rice cakes, as part of a reduced‐energy (~500 kilocalories/day deficit) dietary program that encouraged limiting consumption of foods high in energy and fat, portion control, and regular physical activity. All participants were asked to avoid foods rich in viscous soluble fibre such as barley, oatmeal and oat bran products except for the study products provided to the whole grain oat cereal group. The whole grain oat ready‐to‐eat cereal (Cheerios, General Mills, Minneapolis, MN) was packaged in ~40 g portions by the manufacturer. A registered dietitian met biweekly with participants to monitor and reinforce dietary changes.

Incentives: not reported

Co‐interventions in both groups: regular physical activity (30 to 60 min/day) was encouraged in both groups as part of the intervention. Physical activity was assessed using a 7‐day recall questionnaire. At baseline, the mean activity scores above resting were 118.4 (SEM 7.6) metabolic equivalent hours in the whole grain oat group and 118.3 (SEM 10.0) in the control group. Physical activity scores increased by 9.1% (SEM 4%) in the whole grain group and 15% (SEM 5.2%) (P = 0.710) in the control group.

Assessment of dietary adherence: 3‐day self reported diaries recording compliance with provided foods, participant interview, and review of unused foods. The whole grain oat group consumed 96.8% (SEM 0.6) of the expected servings of study foods, and the control group consumed 95.7% (SEM 0.7) (P = 0.202).

Was the diet energy reduced? yes (~500 kilocalories/day deficit)

Comparability of diet composition: (See Table 1.) As designed, both groups reduced energy intakes; there was no difference between groups at week 12, although the control group showed a larger reduction in energy intake at week 4. The percentage of total daily energy intake from carbohydrate was greater at week 12 in the whole grain oat group than in the control group (P = 0.017). Total and soluble fibre increased as expected.

Change in diet over time: as above for energy. (See Table 1.)

Outcomes

Total cholesterol, LDL cholesterol, HDL cholesterol, non‐HDL cholesterol, triglycerides, BMI, waist circumference, midarm circumference, triceps skinfold thickness

Funding/conflicts of interest

General Mills Bell Institute of Health and Nutrition, Minneapolis, MN. 3 of the authors are employees of General Mills, 3 authors are employees of Provident Clinical Research and received research grant support from General Mills to conduct the study. 1 author is an employee of Meridien Research and received research grant support from General Mills.

Notes

Adverse effects: the frequencies of adverse events (of any type, whether related to the study products or not) were reported to be similar between groups (59.8% for the whole grain group and 52.4% for the control group, P = 0.321). The most common adverse events in both groups were respiratory tract infection, sinusitis, and pharyngitis. Most adverse events were mild and not related to the study product. Adverse events the authors considered related to the study products were nausea (2 people in the whole grain oat group), flatulence (2 people in the whole grain oat group), gastroenteritis (1 person in the control group), gastroesophageal reflux (1 person in the control group), and vomiting (1 person in the control group). Adverse events that led to drop out from the study were an infectious cyst (1 control) and spinal stenosis (1 control), but the study authors did not consider these to be related to the study product.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"participants were randomly assigned"; method of randomisation not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported for anthropometry or lab measurements

Incomplete outcome data (attrition bias)
All outcomes

High risk

More participants completed study in whole grain oat group than in control group. 20 withdrew consent in control group, 11 in whole grain oat group; both groups lost n = 7 to follow‐up; 2 in control group reported adverse events; 1 in WG group reported product too filling. There was differential dropout between groups.

Intention to treat analysis

Unclear risk

Modified intention‐to‐treat analyses done. Of 101 participants randomised to whole grain oat group, 86 were included in MITT analysis (15 were excluded as they did not have at least 1 postrandomisation lipid value or the blood draw was invalid). Of 103 randomised to control group, 87 were included in MITT analysis (16 were excluded as they did not have at least 1 postrandomisation lipid value or the blood draw was invalid). Sensitivity analyses conducted using MITT and completers data. Results also presented as per‐protocol subset of MITT.

Selective reporting (reporting bias)

Unclear risk

Blood pressure data not fully reported; no outcome data given.

Groups comparable at baseline

Unclear risk

Yes, for all reported measures, except for systolic blood pressure, which was higher in the whole grain oat group compared to control (127.2 SEM 1.2 vs 122.6 SEM 1.3). However, outcome data not reported for systolic blood pressure. Reported only for the per‐protocol subset.

Other bias

Low risk

Power calculations: a sample size of 128 (64 per arm) was expected to provide 80% power to detect a difference of 5% between groups in the per cent change from baseline in LDL cholesterol, assuming a 10% pooled standard deviation for the LDL cholesterol response. This sample size was achieved in both the analysis on completers and the MITT analysis.

Study characteristics

Methods

Setting: UK (Aberdeen, Scotland)

Design: parallel‐group RCT, stratified by sex, age, and BMI

Dates: September 2005 to December 2008

Intervention duration: 12 weeks (following 4‐week run‐in)

Follow‐up: no postintervention follow‐up

Focus: to assess the effects of consumption of 3 daily portions of whole grains (2 intervention groups: wheat only or a mixture of wheat and oats) compared to refined grains on markers of cardiovascular disease risk in people at relatively high risk.

Participants

N: 226 randomised (73/77 completers in the whole grain wheat intervention group; 70/73 in the whole grain wheat and oats group; and 63/76 in the control group).

Inclusion criteria: male and female, aged 40 to 65 years with a BMI between 18.5 and 35. Sedentary or moderately active (< 2 aerobic sessions/wk) people or those with signs of metabolic syndrome or moderate hypercholesterolaemia.

Exclusion criteria: people with CVD, diabetes, fasting blood glucose > 7.0 mmol/L, asthma, systolic BP > 160 mmHg and diastolic BP > 99 mmHg, thyroid conditions, eating disorders, high intake of whole grain foods, or taking regular medication or supplements known to affect any of the outcomes.

Age (years): 40 to 65 years recruited: whole grain wheat group mean age 51.6 (SEM 0.8); whole grain wheat + oats: 52.1 (SEM 0.9); refined grain (control group): 51.8 (SEM 0.8).

Sex (% men): whole grain wheat group: 52%; whole grain wheat + oats: 51%; refined grain (control group): 48%.

Ethnicity: Scottish (ethnic composition not reported)

Baseline cardiovascular risk status:

BMI (kg/m²): whole grain wheat group: 28.0 (SEM 0.5); whole grain wheat + oats: 27.0 (SEM 0.4); control: 28.0 (SEM 0.5); P = 0.221

Total cholesterol (mmol/L): whole grain wheat group: 5.46 (SEM 0.14); whole grain wheat + oats: 5.57 (SEM 0.12); control: 5.94 (SEM 0.14); P = 0.087

HDL cholesterol (mmol/L): whole grain wheat group: 1.55 (SEM 0.04); whole grain wheat + oats: 1.62 (SEM 0.05); control: 1.62 (SEM 0.06); P = 0.506

LDL cholesterol (mmol/L): whole grain wheat group: 3.45 (SEM 0.11); whole grain wheat + oats: 3.45 (SEM 0.11); control: 3.66 (SEM 0.12); P = 0.365

Triglycerides (TAG): whole grain wheat group: 1.27 (SEM 0.08); whole grain wheat + oats: 2 (SEM 0.06); control: 1.49 (SEM 0.11); P = 0.012

Systolic blood pressure (mmHg): whole grain wheat group: 125.9 (SEM 1.4); whole grain wheat + oats: 131.7 (SEM 1.4); control: 131.2 (SEM 1.4); P = 0.019

Diastolic blood pressure (mmHg): whole grain wheat group: 75.7 (SEM 0.8); whole grain wheat + oats: 78.4 (SEM 0.8); control: 79.1 (SEM 0.8); P = 0.26

Medications used: monitored but not reported

Interventions

Whole grain diet group: 2 intervention groups: whole grain wheat and whole grain wheat and oats

Control: refined grain foods

Description of dietary intervention: after a 4‐week run‐in period on the refined grain diet, the intervention groups had 3 servings/d of refined cereal foods replaced by either 3 servings of whole wheat foods (70 to 80 g wholemeal bread and 30 to 40 g whole grain cereals) or with 1 serving of whole wheat foods and 2 servings of oats. The study foods, both refined and whole grain, were products widely available from UK food retailers. Apart from the whole grain foods supplied, participants selected their own foods to eat and advice on which foods to replace with whole grain servings was standardised to each participant's regular diet.

Incentives: not reported

Co‐interventions in both groups: none

Assessment of dietary adherence: 7‐day food diaries, 3 times during the intervention.

Was the diet energy reduced? no

Comparability of diet composition: no differences in macronutrients, except for fibre (as expected). (See Table 1.)

Change in diet over time: reported at baseline and week 12. (See Table 1.)

Outcomes

Total cholesterol, triglycerides (TAG), HDL cholesterol, LDL cholesterol, Apo A‐I, Apo B, BMI waist circumference, systolic BP, diastolic BP, pulse pressure, heart rate, stiffness index, insulin, glucose, HOMA‐IR, revised QUICKI, h CRP, IL‐6

Funding/conflicts of interest

UK Food Standards Agency (grant NO2035), Scottish government (Rural and Environment Research and Analysis Directorate). Oat cakes were supplied by Paterson Arran Ltd.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Web‐based randomisation system, random permuted blocks stratified by age, gender, and BMI

Allocation concealment (selection bias)

Low risk

Off‐site allocation

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcome assessors blind.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up higher in control group: 63/76 completers, 11 voluntarily withdrew, 2 excluded; whole grain wheat group 73/77 completers, 4 voluntarily withdrew; whole grain wheat + oats group 70/73 completers, 2 voluntarily withdrew, 1 excluded. Reasons for higher withdrawal in control group not clear.

Intention to treat analysis

Unclear risk

Not reported

Selective reporting (reporting bias)

Unclear risk

Blood pressure outcomes provided by author as not reported in publications except graphically. Unclear if all variables reported at baseline are outcomes.

Groups comparable at baseline

Unclear risk

Yes, except for both systolic and diastolic blood pressure, which were lower in the whole grain wheat group than in the whole grain wheat + oats group and the control group

Other bias

Low risk

Sample size was based on total cholesterol and LDL cholesterol. Power calculations indicated 60 participants per group would give sufficient power to detect effects of 5% to 7%. This was met.

Study characteristics

Methods

See above

Participants

See above

Interventions

See above

Outcomes

See above

Funding/conflicts of interest

See above

Notes

See above

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

See above

Allocation concealment (selection bias)

Low risk

See above

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

See above

Incomplete outcome data (attrition bias)
All outcomes

High risk

See above

Intention to treat analysis

Unclear risk

See above

Selective reporting (reporting bias)

Unclear risk

See above

Groups comparable at baseline

Unclear risk

See above

Other bias

Low risk

See above

Study characteristics

Methods

Setting: China

Design: parallel‐group RCT (stratified by sex and 5‐year age category)

Dates: 2009 onwards (initial screening conducted in 2009)

Intervention duration: 16 weeks

Follow‐up: no postintervention follow‐up

Focus: to compare the effects of replacing white rice with brown rice in the diets of middle‐aged Chinese men and women with diabetes or a high risk for diabetes.

Participants

Faculty and staff of a large university in Shanghai who had metabolic syndrome.

N: 202 randomised (to 2 groups); 193 completed overall. 98/101 completers in brown rice group; 95/101 completers in white rice group.

Inclusion criteria: people with MetS defined as presenting with at least 3 of the following components:

1. central obesity: waist circumference >/= 90 cm in men or >/= 80 cm in women,

2. elevated triglycerides: triglycerides >/= 1.7 mmol/L,

3. reduced HDL cholesterol: HDL cholesterol < 1.03 mmol/L in men or < 1.30 mmol/L in women,

4. elevated blood pressure >/= 130/85 mmHg or previously diagnosed hypertension, or using antihypertensive medications,

5. elevated fasting glucose >/= 5.6 mmol/L, previously diagnosed diabetes, or using hypoglycaemic agents.

Exclusion criteria: history of severe kidney disease, cardiovascular disease, stroke, cancer, or psychological disorders as well as pregnant or lactating women were excluded.

Age (years): white rice group: 49.8 SD 7.1; brown rice group: 49.6 SD 6.7

Sex (% men): white rice group: 53.5%; brown rice group: 53.5%

Ethnicity: Chinese

Baseline cardiovascular risk status: mean (SD) or (95% confidence interval (CI))

BMI (kg/m²): white rice: 25.4 SD 2.5; brown rice: 25.9 SD 3.4; P = 0.22

Total cholesterol (mmol/L): white rice: 5.55 SD 1.33; brown rice: 5.44 SD 1.27; P = 0.55

HDL cholesterol (mmol/L): white rice: 1.31 SD 0.38; brown rice: 1.22 SD 0.34; P = 0.08

LDL cholesterol (mmol/L): white rice: 3.93 SD 8; brown rice: 3.81 SD 1; P = 0.46

Triglycerides (mmol/L): white rice: 1.78 (95% CI 1.21 to 2.39); brown rice: 1.81 (95% CI 1.30 to 2.53); P = 0.48

Systolic blood pressure (mmHg): white rice: 129 SD 15; brown rice: 129 SD 16; P = 0.82

Diastolic blood pressure (mmHg): white rice: 85 SD 10; brown rice: 86 SD 10; P = 0.42

Medications used:

antihypertensive agents (% using): white rice: 44.6; brown rice: 29.7; P = 0.03

hypoglycaemic agents (% using): white rice: 5.0; brown rice: 4.0; P = 0.73

lipid‐lowering agents (% using): white rice: 3.0; brown rice: 3.0; P = 1.00

Interventions

White rice: the 2 types of rice in the study were from the same batch; the white rice was produced by further milling the brown rice. Both types of rice were cooked in the same steam box under the same conditions.

Brown rice: from the same batch as the white rice as described above.

Description of dietary intervention: the cooked rice was packaged into 225 g servings (equivalent to 100 g cooked rice) and provided to participants at designated university campus cafeterias during the lunch hour from Monday to Fridays. Participants took cooked rice home for dinner and meals on Saturdays. They were encouraged to eat ad libitum and were permitted to consume other staple foods only on Sundays. They were instructed to maintain their usual dietary pattern regarding other food selections.

Incentives: not reported

Co‐interventions in both groups: none

Assessment of dietary adherence: compliance was monitored by researchers weighing leftovers in the cafeteria and was calculated as the frequency of consumption of the prescribed type of rice divided by the frequency of consumption of total staple carbohydrates throughout the intervention. Participants recorded the amount of rice they consumed at home using electronic scales provided by the researchers. Dietary intake measured using a 3‐day diet record was obtained at baseline and every 4 weeks during follow‐up.

Was the diet energy reduced? no

Comparability of diet composition: adherence to diets was high: mean adherence 90.0 +/‐ 17.1% in the white rice group and 88.7 +/‐ 23.3% in the brown rice group; P for difference = 0.20. There was no difference in energy intake between groups over the intervention period, but lower intake of carbohydrates (P = 0.03) and dairy products in the brown rice group (P = 0.02). There was no difference in protein, fat, dietary cholesterol, vegetables, fruits, red meat, poultry, or seafood. Dietary fibre was higher in the brown rice group, as would be expected (P < 0.0001). (See Table 1.)

Change in diet over time: reported at weeks 4, 8, 12, and 16. (See Table 1.)

Outcomes

BMI, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, glucose, insulin, HOMA‐IR

Funding/conflicts of interest

Supported by Chief Scientist Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, National Basic Research Program of China, National Natural Science Foundation of China.

Notes

No between‐group differences were found for any markers except serum LDL concentration, which decreased more in the white rice group that in the brown rice group (P = 0.02). However, this effect was only observed among participants with diabetes (n = 47). Among participants with diabetes, a greater reduction in diastolic blood pressure was observed in the brown rice group than in the white rice group (P = 0.02).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"randomly assigned (stratified by sex and 5y age category)", but method of randomisation not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

All researchers not directly in contact with study participants (dietitians, laboratory technicians, and statisticians) were unaware of group allocations. Not possible for participants to be unaware of their group assignment due to differences in appearance and texture of the brown and white rice.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

98/101 completers in brown rice group; 95/101 completers in white rice group. The 6 withdrawals in the white rice group were due to busy schedule (n = 4); loss of interest (n = 1); or stroke unrelated to intervention. The 3 withdrawals in the brown rice group were due to a busy schedule or heart disease unrelated to the intervention.

Intention to treat analysis

Low risk

Intention‐to‐treat analysis done for all relevant outcomes.

Selective reporting (reporting bias)

Unclear risk

All outcomes of relevance to this review that were reported at baseline were reported at follow‐up.

Groups comparable at baseline

Unclear risk

Higher proportion of participants with diabetes (P = 0.03) and participants on antihypertensive medication (P = 0.03) in the white rice group at baseline

Other bias

Unclear risk

Sample size calculation based on fasting glucose outcome, which is not a relevant outcome for this review.