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Monday, August 26, 2013

Even more studies you should ignore

Back when I was a medical student (in the Cretaceous Period) we were taught that someone once did a study comparing folic acid levels in the blood of cancer patients compared to the blood of healthy patients. The cancer patients had, on average, significantly lower folic acid levels. And the ones with the largest, fastest growing tumors tended to have the lowest folic acid levels. "Aha," they thought. "Something about folic acid deficiency predisposes them to cancer. We should give folic acid to cancer patients." Bad idea. A randomized trial showed that cancer patients given folic acid died sooner than those given placebo.

What happened? Low folic acid levels are a consequence, not a cause, of cancer. Folic acid is needed to synthesize DNA, and DNA synthesis is necessary for one cell to divide into two cells. So folic acid gets used up by rapidly dividing cells, like cancer cells. Giving cancer patient folic acid just gives their tumor a helping hand. (This roundabout insight led to medications that block folic acid metabolism which are used as chemotherapy to this day.)

The main lesson here is that correlation tells us almost nothing about causation. That means if A and B occur together, we say that they are correlated, but we have to be very careful not to assume that one causes the other. A might cause B, or B might cause A, or they may both be caused by some other factor that we're not paying attention to. This is the cognitive error that the farmer makes when he notices that the daily number of deaths of his livestock correlates with sales of ice cream in the town's ice cream parlor. He figures that some waste from the ice cream is contaminating his feed or water. He lobbies the legislature to ban ice cream sales around his farm. He doesn't realize that the rise in ice cream sales and his livestock deaths are both caused by very hot days.

This week a study was published that encourages just such a mistake. It should be universally ignored, but a handful of patients have already emailed me about it, and it's receiving a fair amount of confused media attention.

Before we look at the study, we need to learn a little about omega-3 polyunsaturated fatty acids. Omega-3 fatty acids are the predominant molecules in fish oil. They have been proven to lower triglycerides. They have gained popularity in the last few years, though the most recent trials (reviewed last year by The Medical Letter) have failed to show that they prevent stroke or heart attacks. There is certainly no convincing reason for the general population to be taking fish oil.

This week's study, published in the Journal of the National Cancer Institute, compared blood levels of omega-3 fatty acids in patients with prostate cancer to those levels in healthy adults. Prostate cancer patients had higher levels of omega-3 fatty acids. Note that the study had nothing to do with fish oil supplements or diet. None of the study subjects were asked about supplements or how frequently they ate fish. The only comparison was blood levels of omega-3 fatty acids of people with prostate cancer to healthy people.

This should remind you of the ancient folic acid study.

The study authors conclude that this should make us worry about the risks of increasing omega-3 fatty acids in our diet, and some of the media coverage warns that fish oil supplements may increase the risk of prostate cancer, but the study proves no such thing. Other possibilities are that prostate cancer patients produce elevated levels of omega-3 fatty acids, or that some unknown metabolic defect both increases prostate cancer risk and elevates omega-3 fatty acid blood levels.

The only way to know for sure is to randomize lots of people to fish oil capsules or to placebo, follow them, and count the resultant prostate cancer. That study hasn't been done, but that study would deserve our attention.

So am I saying that fish oil is safe and everyone should resume taking it? No. It has no proven benefits (except possibly for elevated triglycerides). That the connection to prostate cancer is unproven isn't a reason to take it.

Who knows? Maybe after a randomized trial is done and the biological connection is meticulously worked out this might lead to a new prostate cancer test or treatment. Then medical students not yet born will learn about it as an example of the importance of not confusing correlation with causation.

Learn more:
Hold The Salmon: Omega-3 Fatty Acids Linked to Higher Risk of Cancer (Time)
Too Much Fish Oil Might Boost Prostate Cancer Risk, Study Says (US News)
Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial (Journal of the National Cancer Institute article, abstract available without subscription)
Fish Oil Supplements (The Medical Letter, by subscription only)

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. Holding privileges at Cedars-Sinai Medical Center, he is also an assistant clinical professor at UCLA's Department of Medicine. This post originally appeared at his blog.

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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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