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Thursday, July 11, 2013

CoQ&A

A study just reported at the Heart Failure 2013 Congress in Lisbon, Portugal indicates that co-enzyme Q10 (CoQ10) is effective in congestive heart failure, improving both function and survival. This is of considerable importance to the use of CoQ10, of potentially great significance for the treatment of heart failure, and of far more profound relevance to the entire endeavor of biomedical advance.

Congestive heart failure is an increasingly prevalent condition around the world as the chronic disease epidemiology of modern living takes over the globe, and populations live longer. The most common variety of CHF, as it is known, involves weakening of the muscle in the heart's left ventricle following bouts of ischemia and/or infarction (heart attack). Areas of heart muscle stop pumping because they are starved for oxygen, and the heart becomes a less efficient pump overall.

The consequences of this are just what they would be when any pump stops working right: whatever it is pumping backs up and pools. In the case of the left ventricle, that substance is blood, and it backs up first into the lungs. This causes shortness of breath, limits exercise tolerance, and can make it hard to lie down flat. But it can also lead to something called acute pulmonary edema, when the volume of fluid in the lungs creates severe breathlessness. Essentially, this is drowning, but the fluid is coming from within, rather than without.

Heart failure is, as noted, increasingly prevalent. When severe, it can limit function to the point of making walking nearly impossible. It waxes and wanes with diet, activity, stress, and more in an often unpredictable pattern that results in frequent need for hospitalization, and very high costs. And over a span of decades, very few medications have been identified that work well to treat CHF, and far fewer that lower the associated mortality risk.

Which brings us back to CoQ10. The new study showed it did both, and that's just about astounding. Co-enzyme Q10, also known as ubiquinol, is a compound found widely in plants, but in very low concentrations. Our bodies need it, using it to facilitate the vital, energy-generating process of electron transport in our mitochondria, the power-plants residing in our cells.

We can make CoQ10, but not with great efficiency, and get much of what we need from food. Levels in our bodies rise and fall with dietary intake, and with other exposures. For example, statin drugs used routinely to treat high cholesterol deplete CoQ10 levels. In my personal clinical experience, and the common clinical experience, supplementation of CoQ10 often ameliorates the muscle soreness that is rate-limiting for use of statins.

Proponents of CoQ10, and there have long been many particularly in the natural medicine world, have asserted its value in treating high cholesterol, high blood pressure, periodontal disease, heart failure, low energy, and more. One always worries when a medical remedy starts sounding like a Ginsu knife: "It slices, it dices, it feeds your fish, it bathes your children...!" But actually, the mechanism of action of CoQ10 is so very near the bedrock of our metabolism, it makes sense that it would affect every organ system, and have implications for almost every condition. As an example, every condition is worsened by a deficiency of oxygen, and improved when we have enough. The notion of a legitimately, universally relevant "remedy" is not entirely unprecedented.

The current study, which thus far has only been presented at a conference, albeit a prestigious one, and not yet published in full in the peer-reviewed literature, appears to be a game-changer. The trial was conducted in nine countries, enrolled hundreds of patients, and followed them for two years. It had all the right bells and whistles, too: It was randomized, double-blinded, and placebo-controlled.

The punch line was refreshingly straightforward: The CoQ10 group had half the mortality rate, and half as many adverse cardiac events, as the placebo group. Both findings were of clear statistical significance. That they were of stunning clinical significance is all but self-evident, but it embellishes the case to note that a drug to lower mortality in congestive heart failure has not been identified in over a decade.

What makes this study truly astonishing, and causes it to reverberate through modern medicine far beyond the topics of either CoQ10 or heart failure, is that the very possibility of such an effect was overtly dismissed that same decade ago. In 2000, a paper in the Annals of Internal Medicine purported to show that co-enzyme Q10 did not work for heart failure. An accompanying editorial went further, declaring the co-enzyme Q10 hypothesis dead.

But this was a study of just several dozen patients, followed for a few months. In a tale I've told before, this was in contrast to a study of the patented drug, Carvedilol, published around the same time and demonstrating its value in heart failure. The study of Carvedilol enrolled thousands, and lasted years.

And so that 2000 study of CoQ10 did not generate meaningful evidence of absent effects; rather, it left us with a rather meaningless absence of evidence. I have long argued, including at an Institute of Medicine summit, that just such scenarios require us to think of medical evidence more fluidly than just "yes" or "no." Absence of evidence is not evidence of absence, and thinking it is mistakes the subtleties of incremental advance and shades of gray for the black-and-white of a light switch. Science doesn't work that way.

But there is a very vocal group, self-proclaimed as guardians of science, who argue that it does. For my defense of such notions as the possibility that CoQ10 might work for heart failure after all, I have been feathered, if not tarred, in cyberspace. All water off a duck's back in light of the new study.

I hasten to add I did not believe that CoQ10 worked for heart failure in the absence of good evidence. I just believed we had an absence of good evidence. I believed we had a good Q, and no clear A.

One would like to think that the Q&A that drives biomedical advance is about what matters most. But the long and tortuous timeline associated with the attachment of the right A to CoQ suggests it has a lot to do with patents, and profits, and what pays the most. CoQ10 is all but ubiquitous in plants, and you can't patent parsley. We talk a lot about evidence-based medicine, but the playing field for generating evidence is far from level. Patent-holders perennially have the home-field advantage.

That CoQ10 almost certainly works for heart failure is important to the clinical use of CoQ10, and important to patients and doctors dealing with heart failure. But it is perhaps even more important to all of medicine that CoQ10 is being shown to work more than a decade after the very possibility of it doing so was ruled out. Biomedical advance is forestalled, and the human condition compromised, when absence of evidence is not only tolerated, but mistaken for evidence of absence.

We can avoid the repetition of that mistake by keeping our minds open. Not so open our brains fall out, of course, but carefully open just the same. For we now have an exceptional medical story to prove a rule: A closed mind is a menace to every other organ.

David L. Katz, MD, FACP, MPH, FACPM, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care. He is a board certified specialist in both Internal Medicine, and Preventive Medicine/Public Health, and Associate Professor (adjunct) in Public Health Practice at the Yale University School of Medicine. He is the Director and founder (1998) of Yale University's Prevention Research Center; Director and founder of the Integrative Medicine Center at Griffin Hospital (2000) in Derby, Conn.; founder and president of the non-profit Turn the Tide Foundation; and formerly the Director of Medical Studies in Public Health at the Yale School of Medicine for eight years. This post originally appeared on his blog at The Huffington Post.

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Blog log

Members of the American College of Physicians contribute posts from their own sites to ACP Internistand ACP Hospitalist. Contributors include:

Albert Fuchs, MD
Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000.

And Thus, It Begins
Amanda Xi, ACP Medical Student Member, is a first-year medical student at the OUWB School of Medicine, charter class of 2015, in Rochester, Mich., from which she which chronicles her journey through medical training from day 1 of medical school.

Auscultation
Ira S. Nash, MD, FACP, is the senior vice president and executive director of the North Shore-LIJ Medical Group, and a professor of Cardiology and Population Health at Hofstra North Shore-LIJ School of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Diseases and was in the private practice of cardiology before joining the full-time faculty of Massachusetts General Hospital.

Zackary Berger
Zackary Berger, MD, ACP Member, is a primary care doctor and general internist in the Division of General Internal Medicine at Johns Hopkins. His research interests include doctor-patient communication, bioethics, and systematic reviews.

Controversies in Hospital Infection Prevention
Run by three ACP Fellows, this blog ponders vexing issues in infection prevention and control, inside and outside the hospital. Daniel J Diekema, MD, FACP, practices infectious diseases, clinical microbiology, and hospital epidemiology in Iowa City, Iowa, splitting time between seeing patients with infectious diseases, diagnosing infections in the microbiology laboratory, and trying to prevent infections in the hospital. Michael B. Edmond, MD, FACP, is a hospital epidemiologist in Richmond, Va., with a focus on understanding why infections occur in the hospital and ways to prevent these infections, and sees patients in the inpatient and outpatient settings. Eli N. Perencevich, MD, ACP Member, is an infectious disease physician and epidemiologist in Iowa City, Iowa, who studies methods to halt the spread of resistant bacteria in our hospitals (including novel ways to get everyone to wash their hands).

db's Medical Rants
Robert M. Centor, MD, FACP, contributes short essays contemplating medicine and the health care system.

Suneel Dhand, MD, ACP Member
Suneel Dhand, MD, ACP Member, is a practicing physician in Massachusetts. He has published numerous articles in clinical medicine, covering a wide range of specialty areas including; pulmonology, cardiology, endocrinology, hematology, and infectious disease. He has also authored chapters in the prestigious "5-Minute Clinical Consult" medical textbook. His other clinical interests include quality improvement, hospital safety, hospital utilization, and the use of technology in health care.

DrDialogue
Juliet K. Mavromatis, MD, FACP, provides a conversation about health topics for patients and health professionals.

Dr. Mintz' Blog
Matthew Mintz, MD, FACP, has practiced internal medicine for more than a decade and is an Associate Professor of Medicine at an academic medical center on the East Coast. His time is split between teaching medical students and residents, and caring for patients.

Everything Health
Toni Brayer, MD, FACP, blogs about the rapid changes in science, medicine, health and healing in the 21st century.

FutureDocs
Vineet Arora, MD, FACP, is Associate Program Director for the Internal Medicine Residency and Assistant Dean of Scholarship & Discovery at the Pritzker School of Medicine for the University of Chicago. Her education and research focus is on resident duty hours, patient handoffs, medical professionalism, and quality of hospital care. She is also an academic hospitalist.

Glass Hospital
John H. Schumann, MD, FACP, provides transparency on the workings of medical practice and the complexities of hospital care, illuminates the emotional and cognitive aspects of caregiving and decision-making from the perspective of an active primary care physician, and offers behind-the-scenes portraits of hospital sanctums and the people who inhabit them.

Gut Check
Ryan Madanick, MD, ACP Member, is a gastroenterologist at the University of North Carolina School of Medicine, and the Program Director for the GI & Hepatology Fellowship Program. He specializes in diseases of the esophagus, with a strong interest in the diagnosis and treatment of patients who have difficult-to-manage esophageal problems such as refractory GERD, heartburn, and chest pain.

I'm dok
Mike Aref, MD, PhD, FACP, is an academic hospitalist with an interest in basic and clinical science and education, with interests in noninvasive monitoring and diagnostic testing using novel bedside imaging modalities, diagnostic reasoning, medical informatics, new medical education modalities, pre-code/code management, palliative care, patient-physician communication, quality improvement, and quantitative biomedical imaging.

Informatics Professor
William Hersh, MD, FACP, Professor and Chair, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, posts his thoughts on various topics related to biomedical and health informatics.

David Katz, MD
David L. Katz, MD, MPH, FACP, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care.

Just Oncology
Richard Just, MD, ACP Member, has 36 years in clinical practice of hematology and medical oncology. His blog is a joint publication with Gregg Masters, MPH.

KevinMD
Kevin Pho, MD, ACP Member, offers one of the Web's definitive sites for influential health commentary.

MD Whistleblower
Michael Kirsch, MD, FACP, addresses the joys and challenges of medical practice, including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When he's not writing, he's performing colonoscopies.

Medical Lessons
Elaine Schattner, MD, FACP, shares her ideas on education, ethics in medicine, health care news and culture. Her views on medicine are informed by her past experiences in caring for patients, as a researcher in cancer immunology, and as a patient who's had breast cancer.

Mired in MedEd
Alexander M. Djuricich, MD, FACP, is the Associate Dean for Continuing Medical Education (CME), and a Program Director in Medicine-Pediatrics at the Indiana University School of Medicine in Indianapolis, where he blogs about medical education.

More Musings
Rob Lamberts, MD, ACP Member, a med-peds and general practice internist, returns with "volume 2" of his personal musings about medicine, life, armadillos and Sasquatch at More Musings (of a Distractible Kind).

Prescriptions
David M. Sack, MD, FACP, practices general gastroenterology at a small community hospital in Connecticut. His blog is a series of musings on medicine, medical care, the health care system and medical ethics, in no particular order.

Reflections of a Grady Doctor
Kimberly Manning, MD, FACP, reflects on the personal side of being a doctor in a community hospital in Atlanta.

The Blog of Paul Sufka
Paul Sufka, MD, ACP Member, is a board certified rheumatologist in St. Paul, Minn. He was a chief resident in internal medicine with the University of Minnesota and then completed his fellowship training in rheumatology in June 2011 at the University of Minnesota Department of Rheumatology. His interests include the use of technology in medicine.

Technology in (Medical) Education
Neil Mehta, MBBS, MS, FACP, is interested in use of technology in education, social media and networking, practice management and evidence-based medicine tools, personal information and knowledge management.

Peter A. Lipson, MD
Peter A. Lipson, MD, ACP Member, is a practicing internist and teaching physician in Southeast Michigan. The blog, which has been around in various forms since 2007, offers musings on the intersection of science, medicine, and culture.

Why is American Health Care So Expensive?
Janice Boughton, MD, FACP, practiced internal medicine for 20 years before adopting a career in hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling.

World's Best Site
Daniel Ginsberg, MD, FACP, is an internal medicine physician who has avidly applied computers to medicine since 1986, when he first wrote medically oriented computer programs. He is in practice in Tacoma, Washington.

Other blogs of note:

American Journal of Medicine
Also known as the Green Journal, the American Journal of Medicine publishes original clinical articles of interest to physicians in internal medicine and its subspecialities, both in academia and community-based practice.

Clinical Correlations
A collaborative medical blog started by Neil Shapiro, MD, ACP Member, associate program director at New York University Medical Center's internal medicine residency program. Faculty, residents and students contribute case studies, mystery quizzes, news, commentary and more.

Interact MD
Michael Benjamin, MD, ACP member, doesn't accept industry money so he can create an independent, clinician-reviewed space on the Internet for physicians to report and comment on the medical news of the day.

PLoS Blog
The Public Library of Science's open access materials include a blog.

White Coat Rants
One of the most popular anonymous blogs written by an emergency room physician.

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