Research on the Effects of Coenzyme Q10 on the Cardiovascular System in Health and Disease

Prof. Franklin L. Rosenfeldt
Baker Heart Research Institute
Alfred Hospital
Monash University

Basic Cardiovascular Function

In a variety of laboratory and animal experiments, coenzyme Q10 has been shown to be effective in reducing the adverse effects of ischaemia/reperfusion injury.  It can enhance energy production in mitochondria and cells and improve clinical outcomes.  (Rosenfeldt et al 2002, Rosenfeldt et al 2003 & Rosenfeldt et al 2004)

 

Coenzyme Q10 in Hypertension
There have been twelve clinical trials of coenzyme Q10 in the treatment of hypertension.  Four were prospective randomised trials and eight were before and after studies.   Overall the twelve trials showed a fall in blood pressure of 17 mm Hg  systolic and 10 mm Hg diastolic.   Coenzyme Q10 has shown to be particularly effective with hypertension in diabetics where it not only lowers blood pressure but also improves diabetic control.    The mechanism of action of coenzyme Q10 in hypertension is almost certainly as an antioxidant, where it scavenges oxygen free radicals, protects the endothelium from oxygen free radical attack and thus improves vascular dilatation by nitric oxide. (Burke et al 2001, Digiesi et al 1992, Digiesi et al 1994, Folkers et al 1981, Hodgson et al 2002, Langsjoen et al 1994, Rosenfeldt, et al 2003, Singh et al 1999, Yamagami et al 1975 ).

 

Coenzyme C10 In Heart Failure
A review of all the published trials of Coenzyme Q10 in heart failure was first published in 1997.  This showed a beneficial effect of Coenzyme Q10.  We updated the findings for this analysis by analysing nine randomised trials of Coenzyme Q10 in heart failure published up to 2003 (Rosenfeldt et al 2003).   Only prospective randomised double-blind and placebo control trials were included in that analysis.  The three parameters with adequate numbers of patients for meaningful analysis were Coenzyme Q10 levels (five trials) ejection fraction at rest (seven trials) and mortality (five trials).    Other parameters were measured in only two trials each.  For CoQ10 levels (279 patients), the weighted mean difference was 1.4 mcg/ul representing an increase of 161%.  For ejection fraction at rest (384 patients) the weighted mean difference showed a trend in favour of CoQ10 of 1.9% (95% confidence limits - 0.13 to 3.9%).    An updated meta-analysis has been published recently (Sander et al 2006).  This meta-analysis included 11 randomised trials of Coenzyme Q10 in heart failure including cross-over and parallel trial designs.  The main end-point of resting ejection fraction showed an absolute 3.7% net improvement (p < 0.0006).  Stroke index also increased by 5.8 ml (p = 0.02).  Sub-group analyses showed that the ejection fraction improvement was more pronounced when studies of NYHA Class 4 were excluded, when only idiopathic cardiomyopathy was evaluated and among patients not receiving angiotensin converting enzyme (ACE) inhibitors.   When the results were re-analysed using a less conservative statistical test (fixed affects modelling) than was used for the initial analysis (random effects modelling), increases in cardiac output, cardiac index and stroke volume all became significant.   

In light of the encouraging findings of the above mentioned meta-analyses it is not unreasonable to recommend to patients with symptomatic heart failure despite conventional therapy or those who are experiencing side effects from conventional therapy (especially ACE inhibitors) to take 150 – 300 mg of CoQ10 daily and to monitor Coenzyme Q10 blood levels and a clinical response (Pepe, Rosenfeldt, et al 2006).

 

Coenzyme Q10 in Cardiac Surgery
Coenzyme Q10 has been used in the cardiothoracic surgical setting in order to offset reperfusion-related increases in free radical formation and oxidative stress.  From 1982 to 2004 at least eight controlled trials of CoQ10 in cardiac surgery have been published (Tanaka et al., 1982, Shiguma et al. 1983, Sunamori et al. 1991, Judy et al., 1993, Chello et al., 1994, Chen et al, 1994, Taggart et al, 1996, Zhou et al., 1999, Rosenfeldt et al, 2005).  All but one of these have shown a beneficial effects of some kind.  The one trial showing an absence of effect (Taggart et al., 1996) used oral CoQ10 for only 12 hours before surgery, an inadequate time frame for sufficient dosing to increase myocardial levels.   A prospective randomised placebo controlled trial from our unit of 300 mg per day of oral CoQ10 for two weeks preoperatively in 121 coronary bypass or valve replacement procedures showed increased mitochondrial CoQ10 content, increased efficiency of mitochondrial energy production and improved contractile function in myocardial trabeculae (Rosenfeldt, et al., 2005). 

 

Cardiac Arrhythmias
There is some anecdotal experimental and clinical evidence of a beneficial effect of coenzyme Q10 in cardiac arrhythmias.   This would make sense in light of the effect of coenzyme Q10 in improving cellular membrane function and energy production thus reducing the myocardial ischaemia that can generate arrhythmias.

 

Side Effects and Drug Interactions
Coenzyme Q10 is essentially devoid of side effects.  There are occasional reports of gastrointestinal upset but no other major side effects.

 

Does Coenzyme Q10 Interfere with Warfarin?
The literature contains a case report describing a reduction in the efficacy of warfarin caused by Coenzyme Q10.  However, a subsequent prospective randomised trial of Coenzyme Q10, showed no effect of coenzyme Q10 on coagulation status in patients receiving Warfarin therapy.   In summary anticoagulation should be closely monitored during the initiation or withdrawal of Coenzyme Q10 therapy (Engelsen et al 2002).

 

Dosage
Doses between 150-300 mg per day are used for heart failure or hypertension.  Ideally, dosage is adjusted according to serum coenzyme Q10 levels in the blood.  Therapeutic effects are most likely when serum levels are increased to twice normal.

 

Conclusions
There is accumulating laboratory and clinical evidence of the efficacy of coenzyme Q10 in a variety of cardiovascular disorders.  Not all of these have been conclusively proven, but in the absence of side effects, it is reasonable to administer coenzyme Q10 to selected patients with various types of cardiovascular disease and gauge the response.

References

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