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Should you take any supplement?
MULTIVITAMINS - [written by Dr. Bruce Ames] Ten years ago I proposed that the risk of cancer was increased by chronic, suboptimal consumption of micronutrients (approximately 40 essentail minerals, vitamins, amino acids, and fatty acids) and that this should be easily remediable. …In 2006, I proposed the "triage theory", which provides a unifying rationale for expanding my original proposal t include a causal link between micronutrient deficiencies and chronic disease. [I want to provide justification for] implementation of inexpensive public health programs that can significantly reduce chronic disease incidence and increase life span. Triage theory posits that when supply of a micronutrient is inadequate, nature selects for a rebalancing of metabolism….that ensures survival of the organism at the expense of less critical metabolism… High consumption of calorie-rich, micronutrient-poor unbalanced diets exacerbates the problem…There is little societal concern because no overt patho9logies have been associated with marginal to modertate levels of deficiency. The triage theory predicts that the pathology is insidious…[Three measurable consequences are likely to be] increased DNA damage (future cancer), immune dysfunction (future severe infection…) and mitochondrial decay (future cognitive dysfunction and accelerated brain aging). (Link: Multivitamins: Source: Bruce Ames "Foreward: Prevention of Cancer, and the Other Degenerative Diseases of Aging, Through Nutrition"; added 6/2009)
MULTIVITAMINS: The Archives of Internal Medicine recently stated multivitamin use had no benefit. "I believe nothing could be further from the truth." The study was an observational study, not a randomized controlled trial. Note that 90% of the US does not meet the recommended dietary intake for vitamin E, 40% for vitamin A, 30% for vitamin C, and 50% for magnesium. And most are deficient in vitamin D. The study author wrote :Multivitamins may still be useful as a form of [health] insurance for people with poor eating habits." And multivitamin formulations vary considerably. (Link: Multivitamins: Source: Linus Pauling Institute Research Newsletter Spring/Summer 2009; added 6/2009)
February, 2009 - the debate continues! Many people have contacted me about the recent media attention to a New York Times article [BELOW] suggesting that multivitamins are not worthwhile. The Linus Pauling Institute is an extremely distinguished nutrition research institute, and they have written a rebuttal to that article [BELOW THE TIMES ARTICLE], which the Institute was kind enough to send me. It provides a clear explanation why one should not trust media reports.
HERE IS THE NEW YORK TIMES ARTICLE
Vitamin Pills: A False Hope?
By TARA PARKER-POPE Published: February 16, 2009 Ever since the Nobel Prize -winning biochemist Linus Pauling first promoted “megadoses” of essential nutrients 40 years ago, Americans have been devoted to their vitamins . Today about half of all adults use some form of dietary supplement , at a cost of $23 billion a year. But are vitamins worth it? In the past few years, several high-quality studies have failed to show that extra vitamins, at least in pill form, help prevent chronic disease or prolong life. The latest news came last week after researchers in the Women’s Health Initiative study tracked eight years of multivitamin use among more than 161,000 older women . Despite earlier findings suggesting that multivitamins might lower the risk for heart disease and certain cancers, the study, published in The Archives of Internal Medicine, found no such benefit. Last year, a study that tracked almost 15,000 male physicians for a decade reported no differences in cancer or heart disease rates among those using vitamins E and C compared with those taking a placebo. And in October, a study of 35,000 men dashed hopes that high doses of vitamin E and selenium could lower the risk of prostate cancer . Of course, consumers are regularly subjected to conflicting reports and claims about the benefits of vitamins, and they seem undeterred by the news — to the dismay of some experts. “I’m puzzled why the public in general ignores the results of well-done trials,” said Dr. Eric Klein, national study coordinator for the prostate cancer trial and chairman of the Cleveland Clinic’s Glickman Urological and Kidney Institute. “The public’s belief in the benefits of vitamins and nutrients is not supported by the available scientific data.” Everyone needs vitamins, which are essential nutrients that the body can’t produce on its own. Inadequate vitamin C leads to scurvy, for instance, and a lack of vitamin D can cause rickets . But a balanced diet typically provides an adequate level of these nutrients, and today many popular foods are fortified with extra vitamins and minerals. As a result, diseases caused by nutrient deficiency are rare in the United States. In any event, most major vitamin studies in recent years have focused not on deficiencies but on whether high doses of vitamins can prevent or treat a host of chronic illnesses. While people who eat lots of nutrient-rich fruits and vegetables have long been known to have lower rates of heart disease and cancer, it hasn’t been clear whether ingesting high doses of those same nutrients in pill form results in a similar benefit. In January, an editorial in The Journal of the National Cancer Institute noted that most trials had shown no cancer benefits from vitamins — with a few exceptions, like a finding that calcium appeared to lower the recurrence of precancerous colon polyps by 15 percent. But some vitamin studies have also shown unexpected harm, like higher lung cancer rates in two studies of beta carotene use. Another study suggested a higher risk of precancerous polyps among users of folic acid compared with those in a placebo group. In 2007, The Journal of the American Medical Association reviewed mortality rates in randomized trials of antioxidant supplements . In 47 trials of 181,000 participants, the rate was 5 percent higher among the antioxidant users. The main culprits were vitamin A, beta carotene and vitamin E; vitamin C and selenium seemed to have no meaningful effect. “We call them essential nutrients because they are,” said Marian L. Neuhouser, an associate member in cancer prevention at the Fred Hutchinson Cancer Research Center in Seattle. “But there has been a leap into thinking that vitamins and minerals can prevent anything from fatigue to cancer to Alzheimer’s . That’s where the science didn’t pan out.” Everyone is struggling to make sense of the conflicting data, said Andrew Shao, vice president for scientific and regulatory affairs at the Council for Responsible Nutrition, a vitamin industry trade group. Consumers and researchers need to “redefine our expectations for these nutrients,” he said. “They aren’t magic bullets.” Part of the problem, he said, may stem from an inherent flaw in the way vitamins are studied. With drugs, the gold standard for research is a randomized clinical trial in which some patients take a drug and others a placebo. But vitamins are essential nutrients that people ingest in their daily diets; there is no way to withhold them altogether from research subjects. Vitamins given in high doses may also have effects that science is only beginning to understand. In a test tube, cancer cells gobble up vitamin C, and studies have shown far higher levels of vitamin C in tumor cells than are found in normal tissue. The selling point of antioxidant vitamins is that they mop up free radicals, the damaging molecular fragments linked to aging and disease. But some free radicals are essential to proper immune function, and wiping them out may inadvertently cause harm. In a study at the University of North Carolina , mice with brain cancer were given both normal and vitamin-depleted diets . The ones who were deprived of antioxidants had smaller tumors , and 20 percent of the tumor cells were undergoing a type of cell death called apoptosis, which is fueled by free radicals. In the fully nourished mice, only 3 percent of tumor cells were dying. “Most antioxidants are also pro-oxidants,” said Dr. Peter H. Gann, professor and director of research in the department of pathology at the University of Illinois at Chicago. “In the right context and the right dose, they may be able to cause problems rather than prevent them.” Scientists suspect that the benefits of a healthful diet come from eating the whole fruit or vegetable, not just the individual vitamins found in it. “There may not be a single component of broccoli or green leafy vegetables that is responsible for the health benefits,” Dr. Gann said. “Why are we taking a reductionist approach and plucking out one or two chemicals given in isolation?” Even so, some individual vitamin research is continuing. Scientists are beginning to study whether high doses of whole-food extracts can replicate the benefits of a vegetable-rich diet. And Harvard researchers are planning to study whether higher doses of vitamin D in 20,000 men and women can lower risk for cancer and other chronic diseases. “Vitamin D looks really promising,” said Dr. JoAnn E. Manson, the chief of preventive medicine at Brigham and Women’s Hospital and an investigator on several Harvard vitamin studies. “But we need to learn the lessons from the past. We should wait for large-scale clinical trials before jumping on the vitamin bandwagon and taking high doses.”
Are Multivitamins Useless? A response by the Linus Pauling Institute to an article published in the February 2009 issue of the Archives of Internal Medicine [which the New York Times article above is responding to above].
A study published recently in the medical journal Archives of Internal Medicine (Arch Intern Med. 2009;169(3):294-304), which followed 161,808 women from the Women's Health Initiative over eight years, claimed to provide "convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease, or total mortality in postmenopausal women." This message was immediately sent around the world by the news media, leading people everywhere to believe that taking a daily multivitamin does no good and is a waste of money. Is it, really? Actually, nothing could be further from the truth.
The study was an observational study, not a randomized controlled trial. Both types of studies are called "epidemiological" or population-based studies, but there is a fundamental difference between the two of them. As its name implies, an observational study "observes" what people do, what they eat, what dietary supplements they take, how they live, and what kind of diseases they develop. Randomized controlled trials take a group of subjects and randomly assign half of them to get a specific treatment, for example, a certain pharmaceutical drug or vitamin, and the other half gets a dummy pill, or placebo. After several years, researchers assess whether those who got the actual treatment develop less disease than those who got the placebo.
Every epidemiologist will tell you that observational studies cannot establish cause-and-effect relationships; they only can observe associations. For example, a study may find that intake of a certain vitamin was associated with a lower incidence of a specific disease. Whether that vitamin was the cause for the decreased disease risk cannot be answered by an observational study. In order to answer that question, a randomized controlled trial is necessary. In other words, every epidemiologist knows that observational studies are only good enough to generate a new hypothesis, like "multivitamins might not lower risk of heart disease", but this hypothesis needs to be tested in randomized controlled trials to either prove it, establishing a cause-and-effect relationship, or refute it. Unless and until such trials have been conducted, one cannot draw any conclusions regarding causality, let alone make recommendations for the public.
Observational studies are only hypothesis-generating because they are notoriously difficult to evaluate and interpret. For example, the data are based on information collected from the participants, which is often selective and inaccurate (called "recall bias"). Behavior can change appreciably over eight years of observation. Multivitamin formulations vary considerably, and participants may have changed brands during the study. Most importantly, people who volunteer to be part of these studies are generally healthier than the average person - they are more health conscious, have a healthier diet, exercise more, etc., which can significantly affect the outcome of the study (called "healthy enrollee effect").
In the study, 41.5% of the participating women took multivitamins, and these multivitamin users were healthier than the non-users. Multivitamin users were more likely than non-users to be Caucasian, live in the Western U.S., drink moderate amounts of alcohol, smoke less, have a lower body mass index and a higher level of education, and report being physically more active and eat more fruits and vegetables and less fat. Each of these factors can strongly influence the multivitamin users' risk of disease, which makes it very difficult, if not impossible, to tease out the role of multivitamins alone. Epidemiologists use statistical models, in this case the "proportional hazards model," that they claim allows "adjusting" their data for all of these factors, but they often do not acknowledge that these statistical models are based on many assumptions and are imperfect, and are applied to incomplete and inaccurate data.
Here is the dizzying list of factors for which adjustments were made to the data in the study, quoting directly from the paper: "age; race/ethnicity; years since menopause (<5, 5-10, 10-15, and >15 years); body mass index; education; alcohol use; smoking; general health; history of bilateral oophorectomy [or ovariectomy, the surgical removal of one or both ovaries]; geographic region; physical activity; duration of prior postmenopausal estrogen therapy use (0, <5, 5-10, 10-15, and >15 years); duration of prior postmenopausal estrogen plus progesterone use (0, <5, 5-10, 10-15, and >15 years); fruit and vegetable intake; percentage of energy from fat; single supplements of vitamin C, E, or calcium and any other single supplement use and stratified according to age (5-year groups), and hormone therapy trial randomization assignment or study enrollment."
Because all of these adjustments were made using imperfect data and an imperfect statistical model, they are very unlikely to reveal the true effect of multivitamins. Furthermore, despite the statisticians' best efforts to take all of these "confounding" factors into consideration, there are numerous additional factors left that haven't been discovered yet or were not measured in the study. This phenomenon is called "residual confounding" and is a major reason why observational studies can only generate hypotheses. In contrast, in randomized controlled trials subjects are randomly assigned to treatment or placebo, so all confounding factors, even the unknown ones, should be distributed equally between the two groups. That's why well-designed, randomized controlled trials are superior to observational studies and, in contrast to observational studies, can establish cause-and-effect relationships.
Given these considerations, it appears inappropriate for the authors of the study to conclude that it provides "convincing evidence" for multivitamins having little or no effect on cancer or cardiovascular disease risk. The evidence is far from convincing; it is suggestive at best. In addition, while endpoints like cancer, heart disease, and death are important, it is possible, for example, that a daily multivitamin helps protect against other diseases, improves immune or brain function, or promotes general health. Also, eight years of multivitamin supplementation in women over 50 years of age, as assessed in the study, may be too little too late to have a significant effect. Obviously, the data do not apply to men, because they have a different risk profile for cardiovascular diseases and hormone-dependent cancers, among many other reasons.
The reality is that most people in the U.S. have a poor diet and don't come close to consuming the recommended nine servings of fruit and vegetables every day. As a consequence, high percentages of the U.S. population do not meet the recommended dietary allowances — set by the U.S. Institute of Medicine — for many vitamins and essential minerals, including vitamins A, C, E, and K, folic acid, zinc, magnesium, and calcium. For example, data from the National Health and Nutrition Examination Survey indicate that over 90% of the population doesn't meet the recommended dietary intake for vitamin E, over 40% for vitamin A, 30% for vitamin C, and 50% for magnesium. And evidence is accumulating that most people in the U.S. are vitamin D deficient.
Given the reality that people will not improve their diet and often cannot afford to buy more fruits and vegetables, the next best thing and most cost-effective solution is to take a multivitamin. Despite the cynics' assertion that "popping vitamins is a waste of money," taking a daily multivitamin costs less than 10 cents a day. Even Dr. JoAnn Manson, a principal investigator of the Women's Health Initiative and co-author of the study, acknowledges that "the research doesn't mean multivitamins are useless. Multivitamins may still be useful as a form of [health] insurance for people with poor eating habits." And let's not fool ourselves, that's the large majority of the people in this country!
Linus Pauling Institute | Oregon State University
571 Weniger Hall | Corvallis, Oregon 97331-6512
phone: 541-737-5075 | fax: 541-737-5077
March, 2008 - EARLIER debate !
Multivitamin and cancer risk-Harvard Medical School Health Publications Press Release - http://www.health.harvard.edu/ March 3, 2008
It’s time to reassess the value, safety of multivitamin use, says the Harvard Men's Health Watch
Although physician-scientists and supplement manufacturers are often at odds, they don’t spend much time sparring over multivitamins. In fact, half the physicians on the Harvard Men’s Health Watch advisory board report taking a multivitamin themselves. In recent years, Harvard Men’s Health Watch has also endorsed these popular supplements, reasoning that even if they don’t help, they won’t hurt. However, the March 2008 issue of the newsletter states that a reappraisal of that advice is in order.
Harvard Men’s Health Watch notes that some recent studies have linked multivitamin use to prostate cancer. More convincingly, studies have linked high intakes of folic acid to colon polyps, the precursors of colorectal cancer. Researchers speculate that high intakes of folic acid, which was first added to grain products in the 1990s, may have contributed to an increase in colorectal cancers in the mid-1990s.
What does all of this have to do with multivitamins? Now that folic acid is added to so many grain products, it’s easy to see how a healthy diet, combined with a multivitamin, could boost a person’s daily intake to 1,000 mcg or more, potentially increasing the risk of colorectal and possibly prostate and breast cancers.
In light of this research, Harvard Men’s Health Watch suggests that the average man give up the multivitamin, at least until scientists solve the puzzle of folic acid and cancer. However, if you stop taking a multivitamin, consider taking a vitamin D supplement, the newsletter says. The typical diet for most men and women doesn’t supply enough of this crucial vitamin, and while sun exposure boosts vitamin D production, it has health risks of its own.
October, 2006 - the debate continues!
An article in October of 2006 in the American Journal of Clinical Nutrition, " The dubious use of vitamin-mineral supplements in relation to cardiovascular disease", compells me to write a rebuttal. You can read the abstract of the article here. In summary, the study concludes "there is no evidence of a protective efffect of anotioxidant or B vitamin supplements on the progression of atherosclerosis." The author's conclusion differs sharply from a vast body of evidence to the contrary. As one who has long advocated the use of certain supplements, I would like to explain why I have a completely different opinion.
First, the meta-analysis the author considers accepted evidence from only 16 of 2,311 studies they considered. The authors felt that the standards for the remaining 2,295 studies were inadequate. However, I published in 2006 my own criteria for an effective trial of the value of water-soluble supplements, "Design for a study to determine optimal dosage of ascorbic acid and alpha-tocopherol in humans", Moser, L. R. and A. B. Ordman, AGE 28: 77-84(2006). I do not believe any of the 16 studies the author considered met my standards. Therefore, it is reasonable that the criteria for this meta-analysis may have led the authors to a false conclusion.
Second, one must recognize that each expert has a personal background of which we are unaware. The late Dr. Victor Herbert believed that no vitamin supplement of any kind, particulary vitamin C, was of any value. A host of distinguished scientists and physicians ardently disagreed with him, and pointed out the serious flaws in some of his research, yet he had a distinguished career and many publications in peer-reviewed journals. Therefore, it is reasonable that particular articles may disagree with the predominant view and be incorrect.
Third, the study makes no mention of mechanisms underlying the effects attributed to particular vitamin combinations. There are well-established mechanisms by which folate can prevent DNA mutations, and direct measurement of serious DNA defects in people deficient in folate. There are clear mechanisms by which vitamins C and E prevent the buildup of plaque in the arteries, and direct measurement of healthier arterial compliance in people in response to vitamin C. It is therefore reasonable that certain supplements will reduce risk of disease.
Fourth, there is no consideration of risk-benefit analysis of the various nutritional supplements. The authors cite an erroneous report that vitamin E may be hazardous, even though that report has been refuted by a host of top experts. There is a substantial likely reduction in risk for a host of diseases if one takes vitamins like C, D, and E, and no evidence for increased risk except for excessive levels of particular supplements like vitamin A, beta-carotene, iron, and selenium. It is therefore worthwhile to gamble on substantial benefit while risking only minor expense.
For the above four reasons, I hope you will consider discussing with your health professional the dosages considered for your age and gender described at Nutrition Investigator.
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