Coenzyme Q10 for heart failure: The hype and the science

Could a product sold as a dietary supplement really be delivering the benefits that advocates have claimed for decades? That’s what you might be wondering about coenzyme Q10, following recent stories like:

What’s caused all the excitement about CoQ10 is the Q-SYMBIO trial, more properly called “The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure”, presented at the European Society of Cardiology conference last month. I’d normally wait for the full article to come out, and will review it if possible at that time, but the results are too interesting to ignore so I’ll dive into the study and the reaction – which is equally as interesting for advocates of science-based medicine.

Coenzyme Q10 (CoQ10) has a long and mixed history filled with both promise and disappointment. Also known as vitamin Q10, ubiquinone, or ubidecarenone, CoQ10 isn’t actually vitamin, as the body produces its own supply. CoQ10 is found in most cells of the body, with high concentrations in the heart, liver, kidney, and pancreas. Its function seems to include antioxidant effects as well as acting as a cofactor in multiple metabolic pathways. Supplementation can push blood levels much higher than anything the body can produce on its own. While trials with supplements have been small and somewhat equivocal, CoQ10 seems to effectively treat rare cases of coenzyme Q-10 deficiency, as well as conditions resulting in mitochondrial deficiencies. At least one formulation of CoQ10 has been FDA-approved as an orphan drug for the treatment of these rare disorders. The majority of the CoQ10 research (and it’s considerable) has focused on cardiovascular disease such as congestive heart failure and angina, but there is also some limited study of its use in diabetes, hypertension, chronic fatigue, and a long list of other conditions. Finally there’s the question of whether it’s useful for preventing “statin”-drug-induced muscle pain, where the bottom line seems to be “maybe”. In general, most of the studies have been poorly designed and had small sample sizes, giving lots of results which are promising but little that is unambiguously positive. This hasn’t stopped advocates, particularly supplement vendors, from recommending it as a panacea for just about anything, and even adding it to products like cosmetics. Given what appears to be a reasonably good safety profile, CoQ10 is a supplement advocate’s dream: a “natural” product that seems safe and may actually work.

But is CoQ10 actually a supplement at all? The line between supplements and therapeutic drugs isn’t an easy one to define. Vitamins can be treated like drugs (e.g., niacin) and some drugs are rebranded as supplements if they can’t pass the evidence standards to be approved drug products. Natural substances can be marketed as both supplements and drugs (e.g., magnesium) or as drugs alone (e.g., epinephrine). There is not always a clear line, and the variations between countries can be striking. It generally seems to be based more on evaluations of safety than that of efficacy. This may in part explain the varying use of CoQ10 around the world. It’s probably most widely used in Japan, which coincidentally is also the world’s biggest supplier. There it’s apparently used as a routine treatment for congestive heart failure, where it was approved for this purpose almost 40 years ago. It’s also used Europe and Russia, though the U.S. and Japanese markets make up 85% of the world’s consumption. Supplement or drug, what matters is whether it works when it’s evaluated using objective standards. So describing a supplement like CoQ10 as an “alternative” or “complementary” treatment for heart failure is using misleading terminology. As has been said before, there is no such thing as alternative medicine: There is medicine, which are treatments shown to work, and treatments which are unproven to work, or proven not to work.  Medicine does not fail to work in a conventional sense and yet work in some “alternative” sense.

The study

It has not been established that CoQ10 helps in heart failure, but smaller studies have shown improvements in exercise tolerance and other measures, though not consistently. Observed benefits may be due to the prevention of oxidative damage (antioxidant) or to some other mechanism that has not yet been determined. The evidence to date suggests that at best, CoQ10 may offer some benefit to patients already taking other drugs for heart failure but still experiencing significant disease effects. The current study was quite simple by design, with what appears to be a meaningful and unambiguous endpoint: major adverse cardiac event (MACE) including hospitalization due to worsening CHF, cardiovascular death, and cardiac transplantation. The Q-SYMBIO trial included 17 centres across 8 countries, and randomized 420 people with moderate-to-severe heart failure into two groups: One which took 100mg of CoQ10 three times daily, the other a placebo. All continued their regular medications. Patients had an average ejection fraction of 31% (that’s not good) and they were, on average, 62 years of age. After two years:

  • 14% on CoQ10 experienced a major adverse cardiac event, versus 25% in the placebo group (p=0.003).
  • 9% of patients on CoQ10 died, versus 17% in the placebo group (p=0.01).

These are remarkable results for any treatment, and are particularly impressive if patients were already optimized on medical treatments (which isn’t clear). And if they are validated, then CoQ10 offers a dramatic benefit to patients with heart failure.  But is the effect real? Notwithstanding the fact that we don’t actually have the full paper to critique, criticisms and concerns have been raised:

  • The trial took over 10 years to complete, which is long for a trial with a two year endpoint, suggesting difficulty recruiting patients. The trial was first described over a decade ago.
  • We don’t know the medications the participants were taking, and if they would still be considered appropriate and optimal, based on today’s evidence.
  • The mortality rate of about 9% per year seemed low for a population this ill.
  • Reporting and documentation of harms is not well described.
  • The benefit seems implausibly good, and similar benefits haven’t been observed in other endpoints, consistently, in other trials of CoQ10.
  • What we know about how CoQ10 might work is inconsistent with what’s been seen with statin trials in patients with heart failure. Statins lower CoQ10 levels, but don’t worsen CHF.
  • As cardiology studies go, this is a small trial. It’s not clear if it was powered to detect mortality differences. The small numbers of deaths leads to imprecise estimates of risk reductions.
Coenzyme Q10 manufactured by Pharma Nord

Coenzyme Q10 manufactured by Pharma Nord

Interestingly (supplement proponents and conspiracy theorists, please note) this trial has Big Pharma’s fingers all over it. Sponsors included the International Coenzyme Q10 Association (the advocacy organization), Kaneka Corporation of Osaka (the manufacturer) and Pharma Nord (the marketer) which sells products containing coenzyme Q10. So much for the old trope that that pharma’s trying to suppress dietary supplements, or that pharma won’t study it because it’s not patentable. With the global market for the chemical estimated at $835 billion (in 2009), it’s not surprising that there’s a lot of interest in expanding the use of this compound. The sponsorship doesn’t invalidate the study, but it does make me more cautious about drawing any conclusion until the full publication is available and has been subjected to peer review.

Investigator spin

The study still hasn’t been subjected to peer review, but the lead investigator is already calling for widespread use:

Professor Mortensen said: “CoQ10 is the first new medication to improve survival in chronic heart failure and it should be added to standard therapy.”

and he went on, describing a mechanism of action:

“Other heart failure medications block rather than enhance cellular processes and may have side effects. Supplementation with CoQ10, which is a natural and safe substance, corrects a deficiency in the body and blocks the vicious metabolic cycle in chronic heart failure called the energy starved heart.”

Natural. Safe. Mortensen has clearly drunk deeply from the CoQ10 Kool-Aid. And I can understand (in part) his enthusiasm, given the results he’s reporting. But has he really found a holy grail for CHF patients? It’s rare that a single trial results in a major change in medical practice. If you’re a regular reader of this blog you’ll know that many of us are fans of the research of John Ioannidis, particularly his work showing that new and often exciting scientific results rarely hold up to scrutiny, and more importantly, replication. More simply, most published research findings are false. In particular, follow-up studies can invalidate highly-cited initial studies. So a strong, unexpected effect in a single trial should be a red flag for skepticism. Replication is absolutely essential, and cardiologists are unlikely to endorse CoQ10 as a validated treatment until that occurs. This isn’t a bias against supplements, it’s good science at work. In the case of cardiology and antioxidants, there is very good reason for caution. When hype outpaces the evidence, unanticipated harms can result. Millions took antioxidant vitamins for years thinking that they were heart healthy, when evidence eventually showed they are at best, useless, and at worst, harmful.

Risks and harms

Coenzyme appears to be a safe product with few harms documented. Trials consistently report no significant adverse effects. The most common manageable side effect is stomach upset, which can be reduced by dividing the dose throughout the day (as was done in this study). The other downside to the product is the cost, which can be considerable, although CoQ10 prices seem to vary dramatically between brands and there’s a lack of information to help sort out the products which provide the best value-for-money.


Whether CoQ10 becomes an routine treatment for heart failure remains to be seen. The Q-SYMBIO results are surprisingly good, and for that reason, there is good reason to be skeptical. The history of medicine is replete with stories of breakthrough studies that subsequently fail to be replicated. Yet despite knowing this, we continue to make the same mistake again and again. When something appears to be too good to be true, it almost always is. Until the Q-SYMBIO study is published and replicated, I’ll remain skeptical of CoQ10′s role in heart failure.

Posted in: Clinical Trials, Herbs & Supplements

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25 thoughts on “Coenzyme Q10 for heart failure: The hype and the science

  1. rork says:

    Good, except for knee-jerk “It’s not clear if it was powered to detect mortality differences.” Save complaining about power for cases where no differences are found, but you wanted a difference. Was it powered enough? They found a pretty big difference, eh, did ya get that part? Do we want even bigger data – that’s always true.
    Multi-center study is usually a good sign (be nice to know the centers though), and so is simple endpoint. Press-release science, and the not-modest (and fuzzy) tone of Mortensen is less appreciated. Please give me long term followup and a hazard model though.

  2. The Q-SYMBIO results are surprising good, and for that reason, there are good reason to be skeptical.

    When results are bad, its a good reason to be skeptical
    When results are mediocre, its a good reason to be skeptical
    When results are good, its a good reason to be skeptical

    SBM in a nutshell.

    1. Janet Camp says:

      You seem to be “getting it” at last. Until results are replicated and samples are large enough to have statistical meaning, rational people will be skeptical.

      1. Chris says:

        Skepticism does not seem, at least to me, to be the right approach to take when treating patients. In the face of clinical evidence, a few reasonable mechanisms of action(ROS scavenging and replacing CoQ10 lost due to statin usage), as well as a lack of harm due to treatment, it seems quite reasonable to take an optimistic position and encourage usage.

        1. Mie says:

          But can the lack of harm during the treatment cannot be assessed reliably on the basis of this one trial alone? If you go & prescribe CoQ10 to patients taking statins just like you would prescribe any medication, you’re talking about trust issues and financial issues as well.

          Not to mention the ethical side. Treatments should be tested rigorously and not be based on “oh well, it may work and it probably cannot harm anyone …” way of thinking.

          1. Chris says:

            Treatments should absolutely not be tested rigorously in a clinical setting. They should be tested, ideally, exactly long enough to ascertain that the benefits outweigh the risks. At the point at which there no longer exists a state of equipoise between the treatment options there is an ethical imperative to provide the more effective treatment.

            As to the question of harm, CoQ10 is well characterized outside of this study. There is no reason to suspect that it has a significant side effect profile, at least when placed against compelling results like these. That isn’t to say the results are completely valid. There are questions remaining about adverse patient selection, etc. that are unanswered which calls into question the results On the whole, however, results like this that follow from a reasonable mechanism of action should be taken seriously and implemented in the absence of a compelling harm.

    2. Calli Arcale says:

      I would tend to agree, since critical thinking is never misplaced. “Skeptical” does not mean “disbelieve”, incidentally, though the colloquial usage has rather sloppily come to imply that. It means to question. And as the good Doctor* once said, “A scientist’s job is to ask questions.” So yes, you are quite right. ;-)

      * Tom Baker, naturally.

    3. That should be the mantra for EVERYTHING that involves science, medicine, pharmaceuticals and healthcare in general. In fact, you could argue, this should be the mantra for life.

    4. NorrisL says:

      Well FBA, I have often disagreed with your comments, but today I find myself agreeing with you…..always remain sceptical

  3. WilliamLawrenceUtridge says:

    And what’s the problem with that? It interferes with sales? SBM’s commentary isn’t really needed when there is a broad and strong consensus within the medical community, though even then it will be ventured. Where SBM does the most good is in challenging the hype and rhetoric of the lay press (who do a terrible job reporting on science in order to attract readers) and SCAM promoters (who do an even worse job in order to maintain and increase their incomes). Your alternative, which seems to be to place the results into the usual “anything done by Big Pharma is bad” category, isn’t particularly helpful. If Big Pharma disappeared, nobody would make drugs or vaccines, and our mortality rates would soar to their pre-medical heights. Certainly the quacks, homeopaths and acupuncturists would do better business, it just wouldn’t help anyone else.

    Ideas need challenge, particularly when they are based on bad research or oversold. Skepticism in a nutshell.

  4. marilynmann says:

    I agree that the study needs to be replicated in a much larger trial before it can become part of standard therapy for heart failure. The size of the benefit seems unreasonably large and one wonders why, coenzyme q10 has such a large effect on mortality in HF, why statins have not caused harm in HF. It is possibly, however, that statins cause both harm and benefit in HF and that the results of little or no net benefit are due to the benefit and harm canceling each other out. The problem with that argument is that statins have never been shown to decrease mortality by 50% in any population.

    Still, I know of no reason, as of now, why a much larger RCT of coenzyme q10 should not be organized in order to see if there is a benefit of coenzyme q10 in HF. Most likely, if there is one, it is much smaller than was shown in this trial. This implies that it would take a much larger trial to find such a benefit.

  5. angorarabbit says:

    I think I’ve survived the login identity change…

    I think the most important point here is the mantra: “Unpublished data do not exist.” It is shameful how professional societies will talk up and sell unpublished findings that have not yet gone through peer-review. I can think of instances where this is important, for example, if a clinical trial is sufficiently strong that a change of practice or evaluation of on-going trials is essential because patient lives are at risk. But this didn’t meet that bar.

    Note that the 9% vs 17% values was all-cause mortality. It was a lesser p-value for cardiac-related mortality. Hmm.

    Finally, I am disappointed that cardiac function of survivors wasn’t quantified at the trial’s end, since %EF <31% appeared to be an entry criterion. This is a nice way to dodge a bullet – did q10 or did it not improve cardiac function? If not, then we have to question the mechanism of action. Is it really addressing a q10 insufficiency or is there something else going on? And if it is an antioxidant (which I fail to get excited over) then why didn't we see these benefits with the zillion other antioxidants that have been exhaustively tested over the years? I smell a problem mechanistically.

  6. wolf 10 says:

    I was diagnosed with Chronic Fatigue Syndrome after many, many tests (my insurance company must hate me) but no doctor raised the possibility of a mitochondrial disorder or the possibility of a CoQ10 deficiency.

    Would such a possibility have been ruled out by lab work or testing typically performed or lack of certain symptom? Perhaps I’ll just start taking the stuff and see what happens.

    In terms of safety and expense it beats other things currently on offer such as Rituxan and Ampligen, if not proven effectiveness.

    1. Coenzyme Q10 deficiency can be tested at the Metametrix Clinical Laboratory. A naturopath can order the testing kit for you. There is a review of naturopathic nutritional regimens for Chronic Fatigue published in Alternative Medicine Review journal, it will give you further info

      1. Janet Camp says:

        Oh, look! A quack test, a quack treatment and a quack “journal” all rolled into one!

      2. BillyJoe says:

        Are advertisements now allowed at SBM?

        1. I have a lab that will provide you with a tool kit that will test for the lack of unicornium-pulvis, a special protein produced in your energy glands (google the latin). The results can only be interpreted by an adequately trained professional (who is incidentally trained on this test by me).
          Replacement of this protein will cure cancer, hypertension, diabetes, any chronic pain, any neuropathic pain. And there are no side effects with treatment. [moderator: don't block, note the sarcasm]

      3. NorrisL says:

        After my last post, now I have to disagree with you

    2. WilliamLawrenceUtridge says:

      If you have a mitochondrial disorder, you don’t have chronic fatigue syndrome, you have a diagnosis missed after much testing. I’m not sure which is better.

      You’re probably better off ignoring FastBuckArtist’s article, which is from 2000. In most sciences, 13 years is a very long time. Also note that it’s recommendation seems to be, unsurprisingly, supplements. They’re low-risk (and profitable for naturopaths and Big Pharma, who manufactures them), but there’s no guarantee CFS is something so simple as vitamin deficiency. In fact, if it was something so simple, it’d be trivially easy to cure.

      Again, CFS is a wastebasket diagnosis made up of doubtless multitudes of entities, the sole uniting factor of which is fatigue. Some people will have undiagnosed physiological issues, some will be tired due to purely psychological issues, some will be neurological. The idea that there is “one” CFS is extremely questionable, it’s still a diagnosis of exclusion.

      Be very cautious in getting testing from naturopaths – their tests are often unverified, and will give wildly unreliable results. In some cases the test will give the same list of supplements to whoever supplies a sample, irrespective their actual issue (and sometimes species). Unlike recognized, FDA-approved tests, there’s no validation. If there was, if the tests were proven to recognize a meaningful problem, they would be used by real doctors, who would only give you nutritional supplements in the case of a genuine deficiency.

      Good luck, CFS is a shitty diagnosis.

      1. wolf 10 says:

        Thanks, I only go to real doctors, mostly at Stanford. With a few exceptions, I think they do a pretty good job.

  7. WilliamLawrenceUtridge says:

    Excellent, good luck with your continuing search for answers. And please be quite wary of SCAM promoters, they substitute confidence for evidence, to the detriment of your wallet (and often quality of life). Doctors do make mistakes, but fatigue is a particularly problematic symptom since it is incredibly nonspecific. I’ve a lot of sympathy for CFS patients and their doctors.

    1. wolf 10 says:

      Truly, fatigue seems to be a symptom of a very high percentage of all diseases known to man.

      Fortunately my symptoms are less severe than those of some others I’ve read about. Although often housebound right now, I have a good day or two several times a month. I even have had months-long periods of almost complete remission. A year ago I was up and down a thirty-foot ladder and the year before that I was replacing a portion of my house’s foundation. Now I’m seven months into a period where I’m flat on my back most of the time. Its quite weird.

      Again, thanks for your advice and encouragement.

  8. Mie says:

    “Treatments should absolutely not be tested rigorously in a clinical setting. They should be tested, ideally, exactly long enough to ascertain that the benefits outweigh the risks.”

    But isn’t this just a case of semantics? To me, “rigorously” means precisely that what you stated.

    “As to the question of harm, CoQ10 is well characterized outside of this study. There is no reason to suspect that it has a significant side effect profile, at least when placed against compelling results like these. That isn’t to say the results are completely valid. There are questions remaining about adverse patient selection, etc. that are unanswered which calls into question the results On the whole, however, results like this that follow from a reasonable mechanism of action should be taken seriously and implemented in the absence of a compelling harm.”

    Nothing you stated really changes what I stated above. There’s simply not enough evidence to recommend the use of CoQ10. Just because there’s no compelling evidence of harm doesn’t mean that it should be used – we’d have to see solid evidence of the benefits to make such a recommendation. Compare e.g. many dietary supplements.

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