Brief Critical Review - ENCOGNITIVE.COM Q10 Supplementation and Heart Failure.pdfvegetables, and fruits. A typical Western diet provides 3 to 5 mg of CoQ10 daily, of which approximately

June 2007(I): 286–293Brief Critical Review

Coenzyme Q10 Supplementation and Heart FailureUma Singh, PhD, Sridevi Devaraj, PhD, and Ishwarlal Jialal MD, PhD

Cardiovascular disease (CVD) is the leading cause ofmorbidity and mortality in the Western world. Oxida-tive stress appears to play a pivotal role in athero-sclerosis. Coenzyme Q10 (CoQ10), one of the mostimportant antioxidants, is synthesized de novo byevery cell in the body. Its biosynthesis decreases withage and its deficit in tissues is associated with degen-erative changes of aging, thus implicating a possibletherapeutic role of CoQ10 in human diseases. There isevidence to support the therapeutic value of CoQ10 asan adjunct to standard medical therapy in congestiveheart failure. However, much further research is re-quired, especially in the use of state-of-the-art tech-niques to assess functional outcomes in patients withcongestive heart failure.

Key words: cardiovascular disease, coenzyme Q10,heart failure© 2007 International Life Sciences Institute

doi: 10.1301/nr.2007.jun.286–293

INTRODUCTION

Cardiovascular disease (CVD) remains the principalcause of death in both developed and developing coun-tries, accounting for roughly 20% of all worldwidedeaths per year. Oxidative stress plays an important rolein atherosclerosis, and thus there has been considerableinterest in using various dietary antioxidants in heartdisease treatment and prevention. Coenzyme Q10(CoQ10) is regarded as one of the most important anti-oxidants. CoQ10 biosynthesis decreases with age and its

deficit in tissues is associated with degenerative changesappearing in the course of aging.1,2

Coenzyme Q10, also known as ubiquinone,ubiquinol, and ubidecarenone, is a lipid-soluble ben-zoquinone with 10 repeated isoprenyl units in the sidechain (Figure 1). CoQ10 is a naturally occurring,ubiquitous, fat-soluble quinone in eukaryotic cells andis available in the United States as an over-the-counternutritional supplement. It has been used for 35 yearsas adjunctive therapy for various cardiovascular dis-orders. CoQ10, which refers to both the oxidized andreduced forms of the redox pair (as ubiquinone andubiquinol), is an obligatory component of the mito-chondrial electron transport chain for ATP synthesis.3

Tissues generally synthesize CoQ10 from farnesyldiphosphate and tyrosine. Iron, magnesium, and vita-min B6 are cofactors for CoQ10 biosynthesis. CoQ10can be obtained from dietary sources of meat, fish,vegetables, and fruits. A typical Western diet provides3 to 5 mg of CoQ10 daily, of which approximatelytwo-thirds is derived from meat and poultry. However,total absorption of CoQ10 is thought to be less than10%. Tissues with high energy requirements, such asthe heart, kidney, liver, and skeletal muscle, containhigh amounts of CoQ10.3

COENZYME Q10 AS A PRIMARYANTIOXIDANT

One function of CoQ10 is as an antioxidant. Itsreduced form, ubiquinol, protects membrane phospho-lipids and mitochondrial membrane proteins, as wellas DNA, from free-radical-induced oxidative damage.Not only can ubiquinol act to remove oxygen radicals,but it can also reduce tocopheryl radicals and semide-hydroascorbate back to tocopherol and ascorbate, re-spectively. The ubiquinone formed in this process isreduced back to ubiquinol in the electron transportchain by metabolic supply of NADH or NADPH.4,5

These antioxidant functions for CoQ10 take on muchlarger significance with the evidence that CoQ10 ispresent in all cellular membranes, not just mitochon-dria.2 Ubiquinol has also been reported to protect LDLfrom oxidation.6

Drs. Singh, Devaraj, and Jialal are with the Labo-ratory for Atherosclerosis and Metabolic Research,University of California-Davis Medical Center, Sacra-mento, California.

Please address all correspondence to: Dr. I. Jialal,Director of the Laboratory for Atherosclerosis and Met-abolic Research, 4635 2nd Avenue, Room #3000, Re-search Building 1, University of California-Davis, Sacra-mento, CA 95817; Phone: 916-734-6590; Fax: 916-734-6593; E-mail: [email protected].

286 Nutrition Reviews�, Vol. 65, No. 6

Circulating Plasma Values, Dosage, andFormulation of Coenzyme Q10

In the circulation, CoQ10 is mainly carried by li-poproteins, mostly in LDL particles,3,7 where it is pre-dominantly in its reduced form. HDL also contains smallamounts of CoQ10. The circulating concentrations ofCoQ10 may be useful to assess its status and also tomonitor response to CoQ10 supplementation. The meanplasma CoQ10 concentration (total) in healthy subjects isreported to be approximately 1.1 �M.8 However, thecirculating CoQ10 status does not necessarily reflecttissue status, which may explain the discrepancy inclinical improvement observed in patients with appar-ently normal plasma values. The dosage of CoQ10 em-ployed in treating CVD patients generally ranges from100 to 200 mg/d. Furthermore, being a lipophilic sub-stance, the efficacy of absorption of orally administeredCoQ10 is poor. CoQ10 supplementation leads to anincrease in plasma CoQ10 concentration, the extent ofwhich depends on the dosage, duration, and the type offormulation. A solubilized formulation of CoQ10 hasbeen shown to have increased bioavailability.3

Coenzyme Q10 and Its Deficiency in Tissues inDisease

Myocardial tissues of CVD patients are reported tobe deficient in CoQ10. Littarru et al.9 first reported itsdeficiency in heart disease. These authors reported that75% of cardiac surgery patients had decreased CoQ10 inblood and in myocardium with increased disease sever-ity. Furthermore, Folkers et al.10 reported low myocar-dial CoQ10 in patients with aortic and mitral wall dis-ease, diabetic cardiopathy, and congenital valvulardefects. Later, the same group of investigators11 reportedthat, compared with people with less-severe heart failure(class I and II), people with more-severe heart failure(class III and IV) had lower plasma and myocardialCoQ10, suggesting an increased risk of a CoQ10 defi-ciency as heart disease worsens.

Healthy subjects generally have 95% of theirplasma CoQ10 in a reduced form. Importantly, coro-nary artery disease (CAD) patients have been reportedto have a lower plasma ratio of reduced to oxidizedCoQ10 compared with controls,12 suggesting thatCAD patients were exposed to higher levels of oxida-tive stress. It is important to mention that the deter-mination of this CoQ10 ratio may be compromised bythe susceptibility of reduced CoQ10 to oxidation,which could result in erroneous conclusions, possiblyaccounting for the negative findings in other studiesdescribed later in this review.

Kontush et al.13 reported significantly decreasedlevels of plasma CoQ10 in 38 hyperlipidemic and 30healthy subjects, with a negative correlation notedbetween plasma triglyceride and CoQ10. Hanaki etal.14 measured the ratios of total cholesterol (TC) toHDL-cholesterol (TC/HDL-C) and LDL-cholesterol toCoQ10 (LDL-C/CoQ10) in 245 control subjects and72 patients (38 men and 34 women) who had ischemicheart disease or evidence of ischemic changes onelectrocardiography. A greater difference in LDL-C/CoQ10 (43%) than TC/HDL-C (17%) was reportedbetween the patients and the normal subjects. Thus,the LDL-C/CoQ10 ratio was suggested to be a sensi-tive indicator of atherosclerosis risk.

Oxidative stress also plays an important role invascular disease in diabetes. Hasegawa et al.15 re-ported decreased ubiquinol levels in diabetics (n � 11type 2 diabetes mellitus with diabetic duration of6.5 � 1.5 y) compared with control subjects (n � 4).Recently, Lim et al.16 measured plasma CoQ10 con-centrations (ubiquinol as well as ubiquinone) in 60subjects with normal glucose tolerance (fasting plasmaglucose � 5.5 mmol/L), 63 subjects with impairedfasting glucose (fasting plasma glucose 5.6 – 6.9mmol/L), and 69 subjects with type 2 diabetes mellitus(fasting plasma glucose � 6.9 mmol/L). These authorsreport a stepwise reduction in the plasma ubiquinolfraction from normal glucose tolerance (NGT) com-pared with impaired fasting glucose (IFG) and diabe-tes mellitus (DM) (DM vs. IFG vs. NGT; P � 0.001).In contrast, the plasma ubiquinone/ubiquinol ratio sig-nificantly increased from normal glucose tolerance toimpaired fasting glucose to diabetes mellitus (DM vs.IFG vs. NGT; P � 0.01).

COENZYME Q10 AND ITS ROLE INCARDIOVASCULAR DISEASE

CoQ10 has some inconsistent beneficial effects inmany disease states. Most of the consistent evidence fora positive outcome with regard to CoQ10 therapy is incongestive heart failure (CHF) patients.

Figure 1. Structure of coenzyme Q10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone).

287Nutrition Reviews�, Vol. 65, No. 6

Coenzyme Q10 and Its Role in Cardiomyopathyand Heart Failure in Adults

A significant correlation has been reported betweenmyocardial tissue ATP content and systolic and diastolicleft ventricular indices in heart disease. Patients withdilated and restrictive cardiomyopathy demonstrate lowblood and myocardial concentrations of CoQ10, whichmay explain the underlying energy deficiency in theheart muscle, related impaired heart function, and thepossible benefit of supplemental CoQ10 in improving theefficiency of energy production in human heart tissue.9-11

There is clear-cut evidence to show that CoQ10 acts atthe mitochondrial level to improve the efficiency ofenergy production in human heart tissue.17 This is dem-onstrated by CoQ10 localization and relative abundancein the mitochondria and the fundamental role of CoQ10in mitochondrial bioenergetics.

The inotropic action of CoQ10, which increases thecontractile force of the heart to improve cardiac output,has also been suggested as another interesting role ofCoQ10 in aiding heart function in heart failure.18 It issuggested that supplemental CoQ10 may also improveutilization of oxygen at the cellular level, and possiblybenefit patients with coronary insufficiency.

Pioneering studies on the role of CoQ10 in improv-ing heart function in adult patients with heart failurewere first carried out in Japan in the 1960s.19 Since then,evidence has been accumulating regarding the use ofCoQ10 as an adjunct to conventional therapy in adultswith cardiomyopathy, CHF, and other forms of heartdisease.20-22 There have been over 40 controlled trials ofthe clinical effect of CoQ10 on CVD, a majority ofwhich show benefit in subjective (quality of life, de-crease in hospitalizations) and objective (increased leftventricular ejection fraction, stroke index) parameters.22

In 1997, Soja and Morensten23 published a meta-analysis of controlled clinical trials of CoQ10 supple-mentation and heart disease published during the years1986–1995. For inclusion in this meta-analysis, a studyhad to be a double-blinded, placebo-controlled study ofCoQ10 treatment in cases of CHF with a prerequisite forthe reporting of complete data set. Fourteen potentiallyeligible published studies were found at that time, butonly eight of these clinical trials23 met the inclusioncriteria for a reliable meta-analysis. The remaining sixstudies were excluded because of a lack of suitable data.The relevant effect parameters investigated in the studiesincluded in the meta-analysis were stroke volume, car-diac output, ejection fraction, cardiac index, end diastolicvolume index, systolic time intervals (PEP/LVET), andtotal work capacity (Wmax). Seven out the eight studiesdocumented statistical significant improvement for all ofthe effect parameters, except the PEP/LVET and Wmax,

in the CoQ10-supplemented group. For example, theaverage patient in the CoQ10 group had a better scorewith regard to stroke volume and cardiac output than76% and 73%, respectively, of the patients in the placebogroup. Based on the clinical trial evidence evaluated inthe meta-analysis, it was concluded that CoQ10 had awell-documented basis as an adjunctive treatment ofCHF.

However, the validity of this meta-analysis has beenrecently questioned by Sander et al.24 on the basis thatSoja and Morensten23 believed that “it was possible toavoid having to reduce and weight the calculated effectsizes.” Thus, Sander et al.24 cautioned that not weighingeffect sizes undermines the validity of the previousmeta-analysis. Furthermore, Sander et al.24 reported thatof the eight studies comprising the previous meta-anal-ysis, only one study was neutral. Thus, these authors24

recently published a new meta-analysis (Figure 2) ofdouble-blinded, prospective, placebo-controlled, paral-lel, and crossover trials of CoQ10 to evaluate the impactof CoQ10 therapy on ejection fraction and cardiac out-put. The analysis was based on an updated systematicliterature search conducted between 1966 and 2005.Sander et al.24 found that since the publication of theprevious meta-analysis, four additional randomized, con-trolled trials evaluating the effects of CoQ10 on ejectionfraction had been published. Thus, a total of 18 random-ized, placebo-controlled CoQ10 trials evaluating CoQ10treatment in heart failure patients were now available.24

In reviewing these studies, the authors excluded onestudy because none of the specified end points wereevaluated25; another study was excluded because it wassingle-blinded26; two studies were excluded because co-enzyme Q10 was only one component of a proprietarycompound27,28; and three studies were excluded due to alack of data.29-31 Of the remaining 11 clinical trials, 10studies evaluated ejection fraction (N � 277) and twostudies evaluated cardiac output (N � 42). CoQ10 sup-plemental doses ranged from 60 to 200 mg/d, and treat-ment periods ranged from 1 to 6 months. Sander et al.24

concluded from their analysis that there was a significant3.7% (95%CI 1.59–5.77) net improvement in ejectionfraction in the patients receiving CoQ10 treatment. Amore profound effect (6.74% [95% CI 2.63–10.86]) onejection fraction was found among CoQ10-treated pa-tients not receiving angiotensin-converting enzyme in-hibitors. In the CoQ10 group, mean cardiac output in-creased 0.28 L/min (95% CI 0.03–0.53). These authors24

further reported that initially they had made an assump-tion that patients with a more severe form of heart failure(NYHA class IV) would benefit the most from CoQ10treatment based on a report by Folkers et al.11 suggestinggreater deficiency of CoQ10 as the disease worsens.However, their disease-severity subgroup analysis did


not support this assumption. Thus, Sander et al.24 sug-gested that compared with progressed heart failure, inwhich many myocytes may be severely damaged, lessdiseased hearts may possess more salvageable myocytesthat could respond to CoQ10’s potent antioxidant prop-erties. Overall, it was concluded from the new meta-analysis that CoQ10 treatment enhances systolic functionin chronic heart failure, but its effectiveness may bereduced with concomitant use of current standard thera-pies.24

Additional Considerations of the PotentialBenefits of Coenzyme Q10 Treatment

The largest controlled CoQ10 trial25 on adult car-diomyopathy and CHF was reported in 1993 and in-volved a total of 641 patients. However, this study25 wasnot included in the reported meta-analyses. The trial wasa double-blind, placebo-controlled study with NYHAclass III and IV patients using a dose of 2 mg CoQ10/

kg/d (n � 319) or placebo (n � 322) for 1 year. Thefindings of this study showed significant improvementsin arrhythmias and a reduction in the number of hospitaladmissions (38% to 61%). Similarly, the episodes ofpulmonary edema or cardiac asthma were reduced com-pared with the control group (20 versus 51 and 97 versus198, respectively). No differences in death rates weredocumented. In a follow-up study, the same group ofinvestigators32 evaluated cardiac hemodynamics duringexercise in CHF patients in a small randomized double-blind, placebo-controlled, crossover trial (n � 6 treatedwith 150 mg CoQ10/d for 4 weeks). The study showedsignificant improvements in ejection fraction. The sametrends were recorded for the stroke volume and cardiacoutput. Importantly, this sub-study was part of the meta-analyses reported earlier.23,24

Furthermore, another study33 not included in thesecond meta-analysis reported a significant improvementin volume load ejection fraction, arteriovenous oxygendifference, and quality of life assessment, following the

Figure 2. Effect of coenzyme Q10 on ejection fraction and cardiac output.


administration of 100 mg of CoQ10/d or placebo for 3months in 69 patients with severe chronic cardiomyo-pathy and CHF. It needs to be emphasized that theseclinical trials used CoQ10 as an adjunct to conventionaltherapy in adult patients. Also, in another controlledtrial34 with 22 heart failure patients (NYHA class II andIII) treated with 200 mg of CoQ10/d for 3 months, amarked improvement in left ventricular ejection fractionwas demonstrated. In addition, Rosenfeldt et al.17 re-ported improved mitochondrial efficiency and increasesin mitochondrial tolerance to in vitro hypoxia-reoxygen-ation stress following preoperative CoQ10 therapy (300mg/d) or placebo for 2 weeks in 35 patients undergoingcardiac surgery. The study also revealed increased myo-cardial and cardiac mitochondrial CoQ10 levels in thesepatients.

A trial35 with CoQ10 in patients undergoing cardiacvalve replacement has also reported significant improve-ment in postoperative hemodynamics from intravenousand intracoronary CoQ10 treated “round the operativeperiod” (n � 12 each, CoQ10/control group). In thatstudy, plasma malonaldehyde concentration and serumcardiac creatine kinase in the CoQ10 group were signif-icantly lower than in the control group, while erythrocytesuperoxide dismutase activity in the CoQ10 group wassignificantly higher. The authors35 suggested that CoQ10treatment plays a beneficial protective role during car-diac valve replacement through its antioxidant proper-ties.

Berman et al.29 carried out a prospective double-blind study in 27 patients with end-stage heart failureawaiting heart transplantation. The patients were ran-domly allocated to receive either 60 mg/d of Ultrasome-CoQ10 (a special preparation to increase intestinal ab-sorption) or placebo for 3 months. The study groupshowed significant improvement in the 6-minute walktest, NYHA functional classification, nocturia, and fa-tigue and a decrease in dyspnea. However, no significantchanges were noted in echocardiography parameters (di-mensions and contractility of cardiac chambers) or thelevels of atrial natriuretic factor and tumor necrosisfactor in blood. Thus, it was concluded that the admin-istration of CoQ10 to heart transplant patients led to asignificant improvement in functional status, clinicalsymptoms, and quality of life, with no objective changesin echocardiogram measurements or atrial natriureticfactor or tumor necrosis factor blood levels. The au-thors29 suggested that CoQ10 may serve as an optionaladdition to the pharmacologic armamentarium of pa-tients with end-stage heart failure. However, the apparentdiscrepancy between significant clinical improvementand unchanged cardiac status requires further investiga-tion.

In contrast to numerous studies reporting positive

results with CoQ10, no improvements were observed inthree controlled clinical trials36-38; all three studies werepart of the second meta-analysis.24 Permanetter et al.36

demonstrated no possible therapeutic effects of ubiqui-none (3 � 33.3 mg or appoximately 99.9 mg of CoQ10/d), administered orally in a placebo-controlled, double-blind cross-over study (N � 25) in patients sufferingfrom idiopathic dilated cardiomyopathy. Watson et al.37

also reported null effects of oral CoQ10 therapy (3 �33.3 mg or appoximately 99.9 mg/d) in 27 patients withleft ventricular dysfunction. An oral treatment for 3months increased plasma levels of CoQ10 to more thantwice basal values, but had no positive effects on restingleft ventricular systolic function. More recently, Khattaet al.38 showed null effects of CoQ10 therapy in 46patients with CHF receiving standard medical therapy. Adose of 200 mg/d of CoQ10 or placebo for 6 months didnot affect ejection fraction, peak oxygen consumption, orexercise duration in these patients. The possible reasonsfor this might be small sample size, severity, and dura-tion of the disease. Also, optimum clinical benefit ofcoenzyme Q10 requires plasma levels of CoQ10 to beabove the normal range so as to enhance its tissue uptakeand thus maximize mitochondrial bioenergetics of theheart muscle.

Coenzyme Q10 and Myocardial Infarction

The heart muscle may become oxygen-deprived(ischemic) as the result of myocardial infarction or dur-ing cardiac surgery. Increased generation of reactiveoxygen species when the heart muscle’s oxygen supplyis restored (reperfusion) is thought to be an importantcontributor to myocardial damage occurring during isch-emia-reperfusion. Furthermore, acute myocardial infarc-tion is also reported to be associated with CoQ10 defi-ciency. In this context, a randomized, double-blindcontrolled trial was carried out in acute myocardialinfarction patients allocated to either CoQ10 (120 mg/d;n � 73) or B vitamins (n � 71) for 1 year.39 The extentof cardiac disease, elevation in cardiac enzymes, leftventricular enlargement, previous coronary artery dis-ease, and elapsed time from symptom onset to infarctionat entry in study showed no significant differences be-tween the two groups. This study found that the totalcardiac events (24.6% vs. 45.0%), including nonfatalinfarction (13.7% vs. 25.3%) and cardiac deaths, weresignificantly lower in the intervention group comparedwith the control group. Plasma levels of vitamin E (32.4vs. 22.1 �M) and HDL cholesterol (1.26 vs. 1.12 mM)increased, whereas thiobarbituric acid reactive sub-stances, malondialdehyde (1.9 vs. 3.1 pmol/L), and dieneconjugates were reduced in the CoQ10 group compared


with the control group. Fatigue was more common in thecontrol group than the CoQ group (40.8% vs. 6.8%).

Coenzyme Q10 and Pediatric Cardiomyopathy

Pediatric cardiomyopathy (PCM) represents a groupof rare and heterogeneous disorders that often results indeath. While there is a large body of literature on adultcardiomyopathy, the clinical evidence for a potential roleof CoQ10 in PCM is based primarily upon data fromadult heart failure patients.

Elshershari et al.40 have demonstrated the potentialusefulness of CoQ10 in treating PCM. This appears to bethe first such study on the use of CoQ10 in PCM. In thistrial, children 2 months to 11 years old with idiopathicdilated cardiomyopathy were first stabilized and thentreated with oral CoQ10 at a dose of 10 mg/kg/d as anadjunct to conventional therapy. Overall, there was ahighly significant improvement in their cardiac function.The objective measures were significant improvement infractional shortening (17.3%–30%) and an increase inejection fraction (41%–60.3%). Although the samplesize in this study was small (n � 6), the authors empha-sized the importance of the promising findings, whichneed to be followed up. Thus, based upon the biochem-ical rationale and a large body of evidence on the clinicalbenefit in adults with various types of cardiomyopathyand heart failure, and also in children and adults withmitochondrial cytopathies, the outlook for CoQ10 ther-apy in PCM is promising. Additional studies on thepotential usefulness of CoQ10 supplementation as anadjunct to conventional therapy in PCM, particularly inchildren with dilated cardiomyopathy, are therefore war-ranted.

Coenzyme Q10-Drug Interactions

HMG-CoA Reductase Inhibitors (Statins)

Hypercholesterolemia is a well-known risk factorfor coronary heart disease (CHD), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in-hibitors or statins have been the most effective means oflowering total cholesterol levels and thereby the risks ofCHD. The enzyme HMG-CoA reductase converts HMG-CoA to mevalonate, which constitutes a committed stepin the biosynthesis of cholesterol. Mevalonate is also aprecursor of CoQ10 and, consequently, statin thera-py41-44 has been shown to reduce CoQ10 levels, whichraises the speculation that a reduction in CoQ10 levelsmay promote the myopathy that has been associated withstatin therapy as a result of mitochondrial damage. Thisnegative outcome has been suggested to be prevented byCoQ10 supplementation.41,45 However, studies supple-

menting CoQ10 to prevent the adverse effects of statintherapy are not definitive and are not recommended atthis time. Furthermore, an earlier study46 reported low-ered plasma CoQ10 levels and elevated lactate/pyruvateratios in patients treated with statin, consistent withmitochondrial dysfunction in these patients.

On the contrary, Bleske et al.47 reported no differ-ence in CoQ10 levels in 12 healthy volunteers followinga 4-week treatment with 20 mg of pravastatin or 10 mgof atorvastatin in a randomized crossover trial. Theinclusion of healthy volunteers and the short study periodmay account for the lack of effects seen in this study.Furthermore, a prospective case-control study has beenreported very recently48 and concluded that althoughpravastatin lowers plasma CoQ10 concentrations, it doesnot appear to predict the risk of recurrent CVD events. Itis pertinent to note the suggestion that blood CoQ10concentration should be reported only after normalizingto total lipid or cholesterol levels because CoQ10 circu-lates with lipoproteins and levels of CoQ10 are highlydependent upon levels of circulating lipids.49,50 Giventhe lipid-lowering effects of statins, it is therefore unclearwhether these drugs actually decrease CoQ10 levelsindependent of a reduction in circulating lipids. Also,very few studies have examined CoQ10 content in targetorgans; thus, it is not clear whether statin therapy affectsCoQ10 concentrations in the body’s tissues.51 At present,more research is needed to determine whether CoQ10supplementation might be beneficial for those takingHMG-CoA reductase inhibitors.

Warfarin

CoQ10 is structurally related to vitamin K and ispostulated to have pro-coagulant effects. Concomitantuse of warfarin (Coumadin) and CoQ10 has been re-ported52 to decrease the anticoagulant effect of warfarinin at least four cases. Thus, caution is advised for theconcomitant use of CoQ10 and warfarin. Blood testsshould be performed to monitor and assess clotting time(prothrombin time) frequently, especially in the first 2weeks.

Additionally, because of CoQ10’s potential hypo-glycemic and hypotensive effects, although not discussedin the present review, monitoring is also advised,53

especially when using CoQ10 adjunctively with pre-scription medications.

CONCLUSIONS

As reported by the Task Force on Clinical ExpertConsensus Documents Writing Committee to Developan Expert Consensus Document on Complementary andIntegrative Medicine,54 it is clear that, unlike established


therapies such as angiotensin-converting enzyme inhib-itors, beta blockers, and aldosterone antagonists, themortality benefit for CoQ10 is not yet established. Thereported consensus further mentioned that one uniqueformulation of CoQ10 has received FDA orphan drugstatus for treating mitochondrial disorders. The value ofCoQ10 in CVD and with statin use has not been clearlyestablished. Its potential utility appears to be in CHF.However, much further research is required, especiallyusing state-of-the-art techniques such as echocardiogra-phy and ventriculography refractory to standard therapyto assess functional outcomes in patients with CHF.Also, future studies looking at long-term outcomes arerequired to confirm the efficacy of CoQ10 in heart failurepatients as adjunctive or alternative therapy to currenttherapeutic regimens.

ACKNOWLEDGEMENT

This paper was supported in part by NIH Grant K-24AT 00596 (to IJ).

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