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Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension

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References

References to studies included in this review

Digiesi 1990 {published data only}

Digiesi V, Cantini F, Brodbeck B. Effect of coenzyme Q10 on essential arterial hypertension. Current Therapeutic Research May 1990;47:841‐5.

Yamagami 1986 {published data only}

Yamagami T, Takagt M, Akagami H, Kubo H, Toyama S, Okamoto T, et al. Effect of coenzyme Q10 on essential hypertension, a double blind controlled study. Biomedical and Clinical Aspects of Coenzyme Q 1986;5:337‐43.

Young 2012 {published data only}

Young JM, Florkowski CM, Molyneux SL, McEwan RG, Frampton CM, Nicholls MG, et al. A randomized, double‐blind, placebo‐controlled crossover study of Coenzyme Q10 therapy in hypertensive patients with the metabolic syndrome. American Journal of Hypertension Feb 2012;25(2):261‐270.

References to studies excluded from this review

Burke 2001 {published data only}

Burke BE, Neuenschwander R, Olson RD. Randomized, double‐blind, placebo‐controlled trial of Coenzyme Q10 in isolated systolic hypertension. Southern Medical Journal 2001;94(11):1112‐7.

Digiesi 1994 {published data only}

Digiesi V, Cantini F, Oradei A, Bisi G, Guarino GC, Brocchi A, et al. Coenzyme Q10 in essential hypertension. Molecular Aspects of Medicine 1994;15 Suppl:s257‐63.

Drzewoski 1981 {published data only}

Drzewoski J, Folkers K, Richardson PC, Shizukuishi S, Baker LE. Usefulness of coenzyme Q10 in the treatment of hypertension. Polski Tygodnik Lekarski 1981;36(27):997‐1001.

Eghtesadi 2012 {published data only (unpublished sought but not used)}

Eghtesadi S, Jazayeri S, Rezai N, Heidari I, Shidfar F, Haghighi H. Study of the effect of CoQ10 on paraoxonase activity, total antioxidant capacity, malondialdehyde, HSCRP, LIPID profile and glycemic control in type 2 diabetic patients. 19th European Congress on Obesity, ECO2012 2012;5:129.

Folkers 1981 {published data only}

Folkers K, Drzewoski J, Richardson PC, Ellis J, Shizukuishi S, Baker L. Bioenergetics in clinical medicine. XVI. Reduction of hypertension in patients by therapy with coenzyme Q10. Res Comm Chem Pathol Pharmacol 1981;31(1):129‐40.

Hata 1977 {published data only}

Hata S, Kunida H, Oyama Y. Antihypertensive effects of coenzyme Q10 in essential hypertension ‐ in relation to the renin‐aldosterone system. Horumon to Rinsho ‐ Clinical Endocrinology 1977;25(9):1019‐23.

Hodgson 2002 {published data only}

Hodgson JM, Watts GF, Playford DA, Burke V, Croft KD. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. European Journal of Clinical Nutrition 2002;56:1137‐42.

Langsjoen 1994 {published data only}

Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. Molecular Aspects of Medicine 1994;15 Suppl:S265‐72.

Shah 2007 {published data only}

Shah SA, Sander S, Cios D, Lipeika J, Kluger J, White CM. Electrocardiographic and hemodynamic effects of coenzyme Q10 in healthy individuals: a double‐blind, randomized controlled trial. Annals of Pharmacotherapy 2007;41(3):420‐5.

Shcherbakova 2010 {published data only (unpublished sought but not used)}

Shcherbakova AG, Sigitova ON. Assessment of quality of life after inclusion of coenzyme Q10 in the scheme of treatment of women with arterial hypertension and elevated risk of cardiovascular complications. Kardiologiia 2010;50(12):19‐21.

Singh 1999 {published data only}

Singh RB, Niaz MA, Rastogi SS, Shukla PK, Thakur AS. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. Journal of Human Hypertension 1999;13:203‐8.

Burt 1995

Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, et al. Prevalence of hypertension in the US adult population. Hypertension. 1995;25(3):303‐4.

CHEP 2015

Daskalopoulou SS, Rabi DM, Zarnke K, for the Canadian Hypertension Education Program. The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Canadian Journal of Cardiology2015; Vol. 31, issue 5:549‐68.

Heran 2008a

Heran BS, Wong MMY, Heran IK, Wright JM. Blood pressure lowering efficacy of angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD003823.pub2]

Heran 2008b

Heran BS, Wong MMY, Heran IK, Wright JM. Blood pressure lowering efficacy of angiotensin receptor blockers for primary hypertension. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD003822.pub2]

Heran 2012

Heran BS, Galm BP, Wright JM. Blood pressure lowering efficacy of alpha blockers for primary hypertension. Cochrane Database of Systematic Reviews 2012, Issue 8. [DOI: 10.1002/14651858.CD004643.pub3]

Langsjoen 1985

Langsjoen PH, Vadhanavikit S, Folkers K. Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q10. Proceedings of the National Academy of Sciences of the United States of America June 1985;82:4240‐4.

Mann 2005

Mann J. The Indo‐Mediterranean diet revisited. Lancet 2005;366:353‐4.

McCarty 1999

McCarty MF. Coenzyme Q versus hypertension: does CoQ decrease endothelial superoxide generation?. Medical Hypotheses 1999;53(4):300–4.

Musini 2008

Musini VM, Fortin PM, Bassett K, Wright JM. Blood pressure lowering efficacy of renin inhibitors for primary hypertension. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD007066.pub2]

Musini 2009a

Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for hypertension in the elderly. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD000028.pub2]

Musini 2009b

Musini VM, Wright JM. Factors affecting blood pressure variability: lessons learned from two systematic reviews of randomized controlled trials. PLoS One 2009;4(5):e5673. [PUBMED: 19479061]

Musini 2014

Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure‐lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database of Systematic Reviews 2014, Issue 5. [DOI: 10.1002/14651858.CD003824.pub2]

Niklowitz 2007

Niklowitz P, Sonnenschein A, Janetzky B, Andler W, Menke T. Enrichment of coenzyme Q10 in plasma and blood cells: defence against oxidative damage. International Journal of Biological Sciences 2007;3(4):257‐62.

O'Brien 2005

O’Brien E, Asmar R, Beilin L, Imai Y, Mancia G, Mengden T, et al. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. Journal of Hypertension 2005;23:697–701.

Pickering 2005

Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, et al. Recommendations for blood pressure measurement in humans and experimental animals : Part 1: Blood pressure measurement in humans: A statement for professionals from the subcommittee of professional and public education of the American Heart Association Council on High Blood Pressure Research. Hypertension 2005;45:142‐61.

Quinzii 2007

Quinzii CM, DiMauro S, Hirano M. Human Coenzyme Q10 Deficiency. Neurochemical Research 2007;32:723–7.

Rosendfeldt 2003

Rosenfeldt F, Hilton D, Pepe S, Krum H. Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure. BioFactors (Oxford, England) 2003;18:91‐100.

Rosenfeldt 2007

Rosenfeldt FL, Haas SJ, Krum H, Hadj A, Ng K, Leong J‐Y, et al. Coenzyme Q10 in the treatment of hypertension: a meta‐analysis of the clinical trials. Journal of Human Hypertension 2007;21:297–306.

White 2005

White C. Suspected research fraud: difficulties of getting at the truth. BMJ 2005;331(7511):281‐8.

References to other published versions of this review

Ho 2009

Ho MJ, Bellusci A, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD007435.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Jump to:

Digiesi 1990

Methods

Randomized, placebo‐controlled, cross‐over trial.

2 week washout period, 10 week treatment period, 2 week treatment suspension, 10 week cross‐over treatment.

Participants

18 patients (4 women, 14 men) with essential hypertension, WHO stages 1 and 2, average age 55.9 years (range 42 to 66 years). Patients older than 70 years, renal failure or body weight > 90 kg excluded.

Interventions

Intervention: Monotherapy with 100 mg oral coenzyme Q10 daily for 10 weeks

Control: Placebo

Outcomes

Resting supine SBP and DBP at 10 weeks

Notes

Sources of funding not stated.

Small study size.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote "...patients were randomly assigned... then each patient in group A crossed over to placebo treatment and each patient in group B crossed over to CoQ treatment..."

Does not describe the sequence generation process.

Allocation concealment (selection bias)

High risk

Insufficient information provided. Does not describe how allocation concealment was ensured.

Blinding (performance bias and detection bias)
Blood Pressure

High risk

No information provided as to whether blinding was achieved.

Incomplete outcome data (attrition bias)
Blood Pressure

Low risk

No missing outcome data.

Selective reporting (reporting bias)

High risk

BP reported was stated as end of treatment. BPs at other times were not reported.

Other bias

High risk

No indication as to how patients were selected, "eighteen subjects were selected from among those presenting with essential arterial hypertension," so they could have been selected based on previous response to CoQ10.

BP standard deviations are lower and not as variable as would be expected.

Yamagami 1986

Methods

Randomized, placebo‐controlled, double blind trial.
Washout period of 4 weeks or more with stable baseline BP. Measurement every 2 weeks for 12 weeks.

Participants

52 patients with essential hypertension (BP > 150/90 mm Hg) were selected at random from the outpatient clinic of The Center for Adult Diseases in Osaka, Japan.

20 patients (8 men and 12 women, mean age 60 years) with low CoQ10 and low SDH‐Q reductase activity were accepted. Conventional hypertension therapies were continued without change.

Interventions

Intervention: Monotherapy with 33.3 mg CoQ10 3x daily (100 mg/day)

Control: Placebo

Outcomes

SBP and DBP at 2 week intervals (no description of position of patient or method of BP measurement).

Notes

Sources of funding not stated.

Limited to patients with low CoQ10 levels, who could be particularly responsive to BP lowering effect of intervention.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "A total of 20 patients was randomized..."

Does not describe the sequence generation process.

Allocation concealment (selection bias)

Unclear risk

"The capsules were numbered and the code was kept... until all trial had been over." Not clear whether numbers were random or in sequence.

Blinding (performance bias and detection bias)
Blood Pressure

Unclear risk

Quote [direct quotation, note typographical errors]: "The capsules were numbered and the code was kept... until all trial had been over... After all data were fixed in each case, key code was opened and the change of blood pressure was compared between coQ group and placebo group."

Comment: insufficient information about how key codes were assigned.

Incomplete outcome data (attrition bias)
Blood Pressure

Low risk

No missing outcome data.

Selective reporting (reporting bias)

Low risk

BP data at all time points was provided.

Other bias

Low risk

SD data is as would be expected.

Young 2012

Methods

Randomized, placebo‐controlled, double blind cross‐over trial.

Participants

30 patients (15 men, 15 women) with metabolic syndrome and inadequate BP control (SBP ≥ 140 or ≥ 130 for patients with type 2 diabetes) on an unchanged, anti‐hypertensive regimen. Patients with significant comorbidities (cardiovascular, renal, hepatic, metabolic, etc.) were excluded.

Interventions

Cross‐over with CoQ10 (100 mg BID) and placebo added to current, unchanged, conventional hypertensive regimen. Patients taking antioxidant vitamin supplementation, including CoQ10, before the trial were excluded (no washout period). A washout period of 4 weeks was present between treatment periods.

Outcomes

Mean 24‐hour ambulatory SBP and DBP, MAP, pulse pressure, HR, mean daytime and nighttime BP and HR, clinic BP (sitting, mean of 3 measurements after 5 minutes of rest) and HR, plasma CoQ10 levels.

Notes

Compliance, safety data and adverse events also documented.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Randomization was performed in permutation blocks of six from a computer‐generated randomization list by a statistician with no clinical involvement in the study."

Allocation concealment (selection bias)

Low risk

"The study treatments were dispensed by an independent pharmacist in identical numbered bottles with the lowest available number allocated to each sequential participant."

Blinding (performance bias and detection bias)
Blood Pressure

Low risk

"Participants and investigators administering the treatment and assessing outcomes were blinded to treatment assignment and to plasma coenzyme Q10 levels." "Both Q‐Gel and placebo were supplied by Tishcon (Salisbury, MD), and were identical in appearance and taste."

Incomplete outcome data (attrition bias)
Blood Pressure

Low risk

The authors performed a modified intention‐to‐treat analysis: "Of 60 potential participants screened, 31 entered and 30 completed the study and were included in the analysis." The reason for withdrawal from the study of the 1 study participant was obtained by electronic communication from the study authors ‐ the patient had an increase in BP medication during the study.

Selective reporting (reporting bias)

Low risk

All primary and secondary outcomes were reported.

Other bias

Low risk

Research was supported by a grant from the National Heart Foundation of New Zealand (Grant Number 1155). Coenzyme Q10 (Q‐Gel) and placebo capsules were supplied by Tishcon, Salisbury, MD. Authors declared no conflicts of interest.

Characteristics of excluded studies [ordered by study ID]

Jump to:

Study

Reason for exclusion

Burke 2001

Washout period was only 10 days.

Digiesi 1994

No placebo control.

Drzewoski 1981

No placebo control.

Eghtesadi 2012

Only an abstract available

Folkers 1981

No placebo control.

Hata 1977

Trial is not randomized, no parallel placebo group. Washout period is only 1 to 2 weeks.

Hodgson 2002

Included mostly patients with normal blood pressure, baseline BP ranged from 127/75 to 136/80 mm Hg and therefore, did not meet hypertension criteria.

Langsjoen 1994

No placebo control.

Shah 2007

Treatment period was less than 3 weeks (longest post‐dose period was 8 hours).

Shcherbakova 2010

Not a placebo controlled trial

Singh 1999

Not likely a double blinded trial as different treatment groups met separately. Changes in antihypertensive medications were allowed and occurred during the trial.

Data and analyses

Open in table viewer
Comparison 1. Coenzyme Q10 vs Placebo: Clinic data

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mean difference in SBP Show forest plot

2

50

Mean Difference (Fixed, 95% CI)

‐3.68 [‐8.86, 1.49]

Analysis 1.1

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 1 Mean difference in SBP.

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 1 Mean difference in SBP.

2 Mean difference in DBP Show forest plot

2

50

Mean Difference (Fixed, 95% CI)

‐2.03 [‐4.86, 0.81]

Analysis 1.2

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 2 Mean difference in DBP.

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 2 Mean difference in DBP.

3 Mean difference in HR Show forest plot

1

Mean Difference (Fixed, 95% CI)

Subtotals only

Analysis 1.3

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 3 Mean difference in HR.

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 3 Mean difference in HR.

Open in table viewer
Comparison 2. Coenzyme Q10 vs Placebo: 24 hr BP measurements

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mean Difference in SBP Show forest plot

1

Mean Difference (Fixed, 95% CI)

Subtotals only

Analysis 2.1

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 1 Mean Difference in SBP.

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 1 Mean Difference in SBP.

2 Mean Difference in DBP Show forest plot

1

Mean Difference (Fixed, 95% CI)

Subtotals only

Analysis 2.2

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 2 Mean Difference in DBP.

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 2 Mean Difference in DBP.

3 Mean Difference in HR Show forest plot

1

Mean Difference (Fixed, 95% CI)

Subtotals only

Analysis 2.3

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 3 Mean Difference in HR.

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 3 Mean Difference in HR.

PRISMA Study flow diagram
Figures and Tables -
Figure 1

PRISMA Study flow diagram

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Forest plot of comparison: 1 Coenzyme Q10 vs Placebo: Clinic data, outcome: 1.1 Mean difference in SBP.
Figures and Tables -
Figure 3

Forest plot of comparison: 1 Coenzyme Q10 vs Placebo: Clinic data, outcome: 1.1 Mean difference in SBP.

Forest plot of comparison: 1 Coenzyme Q10 vs Placebo: Clinic data, outcome: 1.2 Mean difference in DBP.
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Coenzyme Q10 vs Placebo: Clinic data, outcome: 1.2 Mean difference in DBP.

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 1 Mean difference in SBP.
Figures and Tables -
Analysis 1.1

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 1 Mean difference in SBP.

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 2 Mean difference in DBP.
Figures and Tables -
Analysis 1.2

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 2 Mean difference in DBP.

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 3 Mean difference in HR.
Figures and Tables -
Analysis 1.3

Comparison 1 Coenzyme Q10 vs Placebo: Clinic data, Outcome 3 Mean difference in HR.

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 1 Mean Difference in SBP.
Figures and Tables -
Analysis 2.1

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 1 Mean Difference in SBP.

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 2 Mean Difference in DBP.
Figures and Tables -
Analysis 2.2

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 2 Mean Difference in DBP.

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 3 Mean Difference in HR.
Figures and Tables -
Analysis 2.3

Comparison 2 Coenzyme Q10 vs Placebo: 24 hr BP measurements, Outcome 3 Mean Difference in HR.

Coenzyme Q10 compared with placebo for primary hypertension

Patient population: patients with primary hypertension

Settings: primary care in Japan and New Zealand

Intervention: coenzyme Q10 100 to 200 mg daily

Comparison: placebo

Outcomes

Mean difference in BP mmHg

[95% CI]

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

End of treatment SBP

(over 12 weeks)

‐3.7 mm Hg

(‐8.9 to 1.5)

50

(2)

⊕⊕⊕⊝
moderate1

End of treatment DBP

(over 12 weeks)

‐2.0 mm Hg

(‐4.8 to 0.8)

50

(2)

⊕⊕⊕⊝
moderate1

Withdrawals due to adverse effects

30

(1)

Effect estimate not available; only one study reported this outcome but had no events in either study arm.

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.

1. Downgraded due to large confidence intervals from a small sample size and small number of included studies.

Figures and Tables -
Comparison 1. Coenzyme Q10 vs Placebo: Clinic data

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mean difference in SBP Show forest plot

2

50

Mean Difference (Fixed, 95% CI)

‐3.68 [‐8.86, 1.49]

2 Mean difference in DBP Show forest plot

2

50

Mean Difference (Fixed, 95% CI)

‐2.03 [‐4.86, 0.81]

3 Mean difference in HR Show forest plot

1

Mean Difference (Fixed, 95% CI)

Subtotals only

Figures and Tables -
Comparison 1. Coenzyme Q10 vs Placebo: Clinic data
Comparison 2. Coenzyme Q10 vs Placebo: 24 hr BP measurements

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mean Difference in SBP Show forest plot

1

Mean Difference (Fixed, 95% CI)

Subtotals only

2 Mean Difference in DBP Show forest plot

1

Mean Difference (Fixed, 95% CI)

Subtotals only

3 Mean Difference in HR Show forest plot

1

Mean Difference (Fixed, 95% CI)

Subtotals only

Figures and Tables -
Comparison 2. Coenzyme Q10 vs Placebo: 24 hr BP measurements