Building a Better Health Care System: Why the Next Blockbuster Drug Probably Won’t Be a Drug at All

A recent meta-analysis published in the American Journal of Clinical Nutrition suggests that coenzyme Q10 is of benefit in congestive heart failure. For those who like the idea that food and nutrients can be excellent medicine, this paper is interesting at the very least. But there is a case to be made that it is far more than that. There is a case to be made that it is, in a word, miraculous.

For resurrection, after all, is a miracle. And according to a paper published in the Annals of Internal Medicine in April of 2000, coenzyme Q10 for heart failure was a dead concept. The authors reported 13 years ago that “coenzyme Q10 has been studied in randomized, blinded, and controlled studies and … these studies have found no detectable benefit” and that “coenzyme Q10 should not be recommended for treatment of heart failure.”

The final nail had been driven into the CoQ10-for-heart-failure hypothesis 13 years ago — and yet now, it’s back. If that’s not a miracle — then what is going on?

First, a bit of relevant orientation. The condition in question here, congestive heart failure, occurs in particular in the aftermath of one or more heart attacks (myocardial infarctions) which cause portions of the heart muscle to die for want of oxygen. Those areas stop pumping, of course, and the whole heart does its job less well.

The pumping efficiency of the heart is routinely measured using ultrasound as the “left ventricular ejection fraction” (LVEF), which, as the name suggests, is the proportion of blood the left ventricle is able to pump out of itself when it contracts. Roughly 55 to 70 percent is considered normal. High values can occur when the heart is stiff and muscle-bound, and tend to mean the heart empties well, but fills poorly. Congestive heart failure is associated with low values.

And that, in principle is where coenzyme Q10 (also known as ubiquinone, because it is all but “ubiquitous” in plants, albeit at very low concentrations) comes in. A coenzyme supports the work of one or more enzymes, and CoQ10 supports enzymes in the mitochondria, the energy generators of our cells, that transfer electrons. Perhaps you recall ATP, the body’s principal form of stored energy, from high school biology. Well, CoQ10 helps us make it.

Since ATP represents stored energy muscle cells can use to contract, and inadequate contraction is the problem in congestive heart failure, it is plausible that coenzyme Q10 might help.

So why didn’t it in the April, 2000 study in the Annals? Well, of course it’s possible that it really doesn’t work. Not every good and plausible idea is right — that’s why we need good science and unbiased methods. We fall all too readily in love with our own hypotheses, and only robust, objective methods can save us from that tendency.

But there’s another good explanation. The study in question enrolled a total of 55 adults — of whom nine failed to finish. The study lasted a total of six months. So, in 46 adults already on what was optimal medication for congestive heart failure at the time, CoQ10 for six months did not produce a discernible improvement in the LVEF.

The problem with that was revealed almost exactly a year later. In May of 2001, results of the CAPRICORN trial were published in the Lancet. CAPRICORN demonstrated that the proprietary drug carvedilol, patented and marketed as Coreg by GlaxoSmithKline, was effective in reducing mortality from congestive heart failure. It did so by enrolling nearly 2,000 patients and following them for a span of years.

Had carvedilol been studied in 46 patients for six months, it’s quite clear that nothing of consequence would have been seen. Presumably, on that basis, the final nail might have been driven into the carvedilol-for-heart-failure hypothesis. But a huge trial, costing many millions of dollars, and funded by the company that stood to profit from its results — precluded that unhappy outcome.

What would the result have been if coenzyme Q10 had been studied in 2,000 people followed for years? Nobody knows. Since no one company can patent CoQ10, no entity is motivated to fund such a trial. Certainly the new meta-analysis, which pools data from multiple smaller studies, suggests the results of a larger trial of CoQ10 might be very different. I have been aware of this possibility all along, have recommended CoQ10 to some of my patients with heart failure, and been impressed with the apparent effects on more than one occasion.

My clinical practice since 2000 is an Integrative Medicine Center I direct. I have taken some heat over the years for my support of integrative medicine from self-appointed arbiters of science. But, in fact, I have no special interest in CAM or integrative medicine. I just have a special interest in helping my patients get better — and conventional medicine hasn’t always gotten the job done.

Neither, of course, does CAM — so the open-minded skeptic looks at both with the same cautious eye.

It is well established that much, even most, of what constitutes conventional medicine is just tradition and not truly evidence-based by today’s standards. My own work in evidence mapping, a technique colleagues and I invented that was subsequently adopted by the World Health Organization, reveals that the evidence base underlying practices in CAM is quite diverse. The simple summary of it all is that there is both baby and bathwater in CAM and conventional medicine alike, and it requires open-mindedness and unbiased methods to distinguish between them.

It also requires money, which brings us full circle.

Reports of nails in CAM’s coffin tend to be premature — because the many unpatentable modalities in the realm of CAM do not inspire huge and costly trials. We need such trials to know for sure what does and doesn’t work. In the absence of them, we have absence of evidence, not evidence of absence — and need to avoid a rush to judgment. I believe at this point that CoQ10 is beneficial in heart failure — but don’t know for sure.

The story of CoQ10’s resurrection for heart failure across a span of more than a decade is in fact, not a tale of miracles. It’s all about money.

David Katz, MD, MPH, FACPM, FACP, is the founding (1998) director of Yale University’s Prevention Research Center. This piece first appeared at The Huffington Post.

4 replies »

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  2. Fascinating to quibble over CoQ10, when there is zero evidence that the EHRs, CPOEs, and CDSs improve outcomes or reduce costs, and these devices cost $ billons and cause deaths. Did anyone ever die from CoQ 10?
    Just wondering.

  3. I understand where you are coming from, but how do you know that the effect CoQ10 in your patients wasn’t due to placebo effect?

    There are more than enough supplements out there that do nothing, and in the worst cases, they keep people from using medications that would really help them.