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

Thursday, November 1, 2012

Multiple concerns about multivitamins

My regular readers already know my deep skepticism about the benefit of vitamin supplements in well-nourished healthy people. My post last year summarized the available studies about many vitamins and ran under the headline "A Reminder to Dump Your Multivitamin." Thus far, large randomized studies about vitamins have tended to study a single vitamin at a time usually in fairly high doses. That makes a lot of sense. If you want to figure out if vitamin E prevents heart attacks, design a trial in which lots of people get either vitamin E or placebo. (It doesn't prevent heart attacks.)

Recently the Journal of the American Medical Association published the results of the first large randomized trial to study the effects of a multivitamin. The trial began in 1997 and enrolled 14,641 male U.S. physicians aged 50 years or older. It randomized the men to a daily multivitamin or a placebo.

The multivitamin used was the same formulation as the formulation of Centrum Silver at the time, which has 30 different vitamins and minerals. The men were followed for an average of 11 years. New diagnoses of cancer (except non-melanoma skin cancer) and deaths were counted for both groups.

It's important to note that this was part of a larger study to test the effects of a multivitamin on cancer, cardiovascular disease, eye disease and cognitive decline. The current results publish only the cancer findings. The effects on cardiovascular disease, eye disease, and cognitive decline will be published separately.

Especially to a skeptic like me, the results were interesting. The multivitamin group had slightly fewer new cancer diagnoses than the placebo group. The media is reporting the decrease as an 8% lower risk, which is true, but I don't think gives us a clear mental image of the magnitude of the benefit.

Imagine two groups each of 769 older men. If one group took the multivitamin for a year and the other group took the placebo for a year, the vitamin group would have 13 new cases of cancer and the placebo group would have 14. So for every 769 men taking a multivitamin for a year one new diagnosis of cancer is prevented.

Total mortality and mortality due to cancer were the same in both groups. The study was too small to detect differences in occurrence rates of specific types of cancers (i.e. lung cancer, colon cancer, etc.).

Two objections demand to be raised. First, why would you test 30 different vitamins and minerals together? It's conceivable that some of the ingredients have synergistic effects and work differently in combination than they do individually, but it seems that the scientific method suggests the opposite approach. First figure out the effects of each ingredient, then test some combination. The current results leave us completely mystified about which of the ingredients (or combination of ingredients) is responsible for the effect.

The authors state that the trial studied the effects of multivitamins because so many people take them, but I am left wondering whether the trial was designed to raise our understanding or increase Centrum Silver sales. (Pfizer, which sells Centrum Silver, supplied the placebo and the multivitamin for the trial, though it did not design or conduct the study. The study was funded by the NIH.)

The other objection is that the difference between the cancer incidences in the two groups barely rose to the level of statistical significance. Bear with me while I delve into the statistics briefly. Statisticians use a measure called a P value to decide whether a measured difference between two groups might have been due to chance alone and not due to the intervention being studied.

The P value answers this question: If the intervention being studied is actually irrelevant (in this instance, if the multivitamin and the placebo have equivalent health effects) how likely is it that the two groups would show such different numbers (in cancer incidence, in this case) by chance alone? By convention, any P value less than 0.05 is considered statistically significant.

That is an arbitrary choice agreed on by statisticians, but there is no math or science behind that number. We just need some cut-off point, so we decided that 0.05 is statistically significant and 0.06 is not. That still means that for all the randomized trials we do, if the null hypothesis is true (meaning, if the medicine is just like the placebo) 1 time in 20 we'll get a result that shows that the two are different in a statistically significant way, meaning we'll get a false result by chance. The P value in this trial for the difference in cancer incidence for the two groups was 0.04. Yes, that's statistically significant, but just barely.

So what can we conclude?

First of all, this teaches us nothing about multivitamins in women or in men under 50.

Second, the design of the trial is very solid. It was randomized and blinded. So we should take the result at face value, that for men over 50 taking a multivitamin daily makes a small decrease in the risk of cancer (but not in dying of cancer). This effect is much smaller than quitting smoking. So it makes a lot of sense to quit smoking before you try to figure out whether or not to take a multivitamin.

My suggestion for now is to wait for the rest of the results from the trial. For example, if the cardiovascular results are even slightly negative, suggesting that the multivitamin increases stroke or heart attack risk by a small amount, that may overwhelm the cancer benefit.

For the time being I'm still not recommending a multivitamin for healthy adults, or taking one myself.

Learn more:

Multivitamin Cuts Cancer Risk, Large Study Finds (Wall Street Journal) Daily multivitamin appears to slightly lower cancer risk in older men (Los Angeles Times Booster Shots) Multivitamin Use Linked to Lowered Cancer Risk (New York Times) Multivitamins in the Prevention of Cancer in Men, The Physicians' Health Study II Randomized Controlled Trial (Journal of the American Medical Association) A Reminder to Dump Your Multivitamin (my post from last year reviewing the current studies about vitamin supplements, with links to my prior posts about vitamins)

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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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.

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.

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.

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.

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).

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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