American College of Physicians: Internal Medicine — Doctors for Adults ®

Tuesday, August 20, 2013

Fish tales and prostate cancer

I suppose it may help diffuse any relevant tensions to get the punch line out of the way: I have a prostate, and in the context of my mostly-plant diet, will continue to eat fish and take a daily omega-3 supplement (krill oil in my case). We will, as well, continue using various omega-3 supplements in varying doses for specific therapeutic purposes in my clinic.

And now, let's turn to the news. Using Google this morning, I found over 8 million Web pages addressing the combination of fish oil and prostate cancer--just shy of 600,000 blogs and over 9,000 news items. Not all of these relate directly to the recent study suggesting a link between fish oil intake and prostate cancer, but many do.

So it's pretty clear I was far from alone in my eagerness to pounce on this story and opine when such headlines as "Fish oils may raise prostate cancer risks, study confirms," embellished with images of fish oil capsules, began populating print media and cyberspace alike. I have benefited from the more insightful reactions of others, mixed up though they may be with a venting of passions.

But I think it's just as well that my wife and I had a couple of vacation days out of town in a place with negligible Internet access while this tale went through the mad, early gyrations of a fish out of water. It would be easier to get the implications of this study wrong than right, and in either direction.

The study does not prove that fish oil intake causes prostate cancer. But nor is the study dismissible rubbish, as the large crowd of fish oil proponents gathered around it with harpoons in hand would like to contend.

The deep into the kelp already and gone after this paper's school of statistical details: differences in the strength of association between prostate cancer and DHA as opposed to EPA, for instance. HuffPost blogger Johnny Bowden does some of this himself, and cites others who have as well. I leave them to it, and you to the risk of drowning in the details accessible with Google or Bing should you choose to ply these waters further.

I went another way altogether, seeking the view from altitude. We are all aware of populations with especially high intake of omega-3 fat; what does epidemiology tell us about their prostate cancer risk?

The big picture is mostly, if not quite entirely, reassuring. A traditional Japanese diet is considerably higher in omega-3 fat than the prevailing Western diet, yet the Japanese have a low rate of prostate cancer. So far, so good. However, studies have shown an association between higher fish intake and higher prostate cancer incidence among Japanese men.

Scandinavian men also consume lots of omega-3 compared to others, and have relatively high rates of prostate cancer. In this population, the association between fish intake and prostate cancer is murky. Salted and smoked fish intake correlates with higher risk, but fish oil intake with lower risk. A study of men in California suggests that some kinds of fish, and even some cooking methods, might increase prostate cancer risk, while other fish and cooking methods might lower it.

And finally, there's the Inuit, who consume omega-3 marine oils at legendary levels. Prostate cancer is rare among them, even when it is sought at autopsy, and omega-3s have been invoked as a potential explanation why.

Where does this leave us? If we are honest about it, whatever our prior inclinations, the answer is: in muddy water, and a bit confused.

The new study inducing all the fuss shows an association between higher levels of omega-3 in the blood at baseline, and the development of prostate cancer during the study follow-up. However, those who went on to develop prostate cancer also had higher PSA levels at baseline, were more educated, and were more likely to have first degree relatives with prostate cancer. If any of these caused these men to increase their intake of omega-3s as a protective measure, the study could be evidence of causality opposite the claimed direction: Perhaps risk for prostate cancer, real or perceived, increased intake of omega-3s, rather than the other way around.

When something as fundamental as the direction of a causal pathway is uncertain, so, too, are any conclusions generated by a study. An observational study such as this should only be used to generate hypotheses, and raise good questions, not answer them definitively.

Does this study raise a legitimate question? While we fans of omega-3s might prefer a rush to dismissal and derision, the reality is yes, it does. As the authors note, this is not the first study to show an association between higher omega-3 levels and prostate cancer. And in population studies around the world, higher intake of fish and higher rates of prostate cancer have run together.

But in populations, high omega-3 levels could mean many things. Perhaps it means intake of contaminants from fish. The omega-3s might be protective, but maybe there is net harm even so if contaminants in fish are carcinogenic. Our native, Stone Age intake of omega-3 fat was thought to be much higher than prevails today, but our Paleolithic forebears were reliably spared exposure to mercury, and PCBs. We, alas, tend to get our fish with just such stowaways along for the ride.

Perhaps Japanese men who eat the most fish eat the least vegetables and are harmed by what they are omitting from their diets, instead of, or in addition to, what they are including.

But even with all of the relevant provisos collated, there is the possibility that omega-3 intake from fish and/or supplements (the new study did not look at sources, so cannot be used to make specific assertions about supplements versus fish) does increase prostate cancer risk. Is this plausible?

Yes, it is. Unexpected, but biologically plausible just the same. Omega-3s are anti-inflammatory, which means that in general they subdue immune system responses. This is likely protective against chronic inflammation, allergy, and autoimmune disease. But while cancer, like other chronic diseases, can be propagated by inflammation, it also involves a rogue cell or cell colony escaping the immune system's constant police work. An attenuation of that immune system vigilance in the form of an anti-inflammatory effect could, conceivably, help give cancer the upper hand. Immune system function is all about balance. Too much inflammation is bad, certainly. Too little, however, might mean increased risk for infection, and potentially, cancer.

That consideration is important. Omega-3 dosing, whether from food or supplement is not a "some is good, more must be better" proposition. There is an optimum we may not yet fully know, although we have cause to think it's more than most of us in modern culture consume. Relevant evidence indicates that our native ratio of omega-3 to omega-6 fat was much higher than prevails in modern diets.

Higher intake of omega-3 has at times been associated with compelling potential benefit. One meta-analysis links higher omega-3 consumption to lower risk of diabetes. Another, just out, and representing almost a million women, shows an inverse association between omega-3 intake and breast cancer risk: more fish oil, less breast cancer. If omega-3 fat truly did raise prostate cancer risk but lower breast cancer risk, I guess we men dining with our wives would need to get used to saying: I certainly WON'T have what she's having!

Is it plausible that higher omega-3 intake increases prostate cancer risk, but decreases breast cancer risk? I suppose the subtleties of carcinogenesis might allow for it, but I find it very far-fetched; if it doesn't stretch the envelope of credibility to the tearing point, it sure comes close. One of these associations is likely to be wrong.

The new study shows an association between higher blood levels of omega-3 and prostate cancer incidence, nothing more. Despite the inclination to burn them in effigy, the authors themselves claimed nothing more than that. Specific assertions about fish oil supplements are products of media distortion, a problem that routinely bedevils the delivery of medical news -- and an issue my next column will show to be a life-and-death concern for us all.

For now, I remain convinced of likely net benefit from the willful inclusion of omega-3s in our diets, from fish and/or plant sources, and from judicious use of supplements. Perhaps excessive intake of omega-3 fat does increase prostate cancer risk, perhaps contaminants in some fish exert that effect, or perhaps the association will prove spurious with more methodologically robust research. We need such research to know for sure.

In the interim, the implications of the new study are prone to distortion in both directions by proponents and opponents alike. Whatever the ideal place for fish oil in our diets, the exaggerations of fish tales make rather dubious food for thought. My advice is to consume them all accordingly.

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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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.

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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 Iowa City, IA, 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.

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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.

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

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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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

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

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