PIN - POINTING

Supplement use doesn't help and may harm, study finds
By Rob Stein
The Washington Post



Supplements that millions of Americans take to stave off disease and slow the aging process do not boost longevity and appear to actually increase the risk of dying, according to the most comprehensive study of whether popular "antioxidants" help users live longer.
The analysis, which pooled data from 68 studies involving more than 232,000 people, found no evidence that taking beta-carotene, Vitamin A or Vitamin E extends life span. In fact, the analysis indicated that the supplements increase the likelihood of dying by about 5 percent. Vitamin C and selenium appeared to have no impact — either way — on longevity.
The study does not address the question of multivitamins.
Based on the findings, published in today's issue of the Journal of the American Medical Association (JAMA), the researchers warned that consumers should be cautious about taking supplements containing the nutrients. At least 150 million Americans regularly take dietary supplements that often include antioxidants.
"The message is: We shouldn't be putting anything in our mouths until we know whether it works," said Christian Gluud of the Copenhagen University Hospital in Denmark, who led the study. "It appears as if these substances may be harmful."
Representatives of the vitamin industry, as well as some other researchers, disputed the findings, criticizing the study for, among other things, including people who were already sick. People tend to take vitamins to stay healthy, they said.
"There's a large body of data that shows that antioxidant supplementation is beneficial," said Andrew Shao of the Council for Responsible Nutrition, an industry group. "The message to the average consumer is: Don't pay attention to this. This doesn't apply to you. You can go ahead and continue taking your antioxidant supplements in addition to the other things you do in your life to stay healthy."
But Gluud and his colleagues defended the findings, saying that the study used careful methods developed by the Cochrane Collaboration, an independent nonprofit effort to methodically assess medical claims.
The analysis included many large studies involving healthy people, and the increased risk was clear after accounting for factors that could confuse the findings, Gluud said.
Other researchers, while noting that supplements are useful for people who have nutritional deficiencies, said the findings should prompt people to reconsider whether to continue taking megadoses in an effort to live longer.

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"This study shows that these products do not prolong life and may actually shorten it," said Paul Coates, who directs the Office of Dietary Supplements at the National Institutes of Health (NIH). "If you are taking antioxidant supplements, it would be a good idea to review the results of this study, reflect on why you are taking them and what you hope to gain."
The findings do not necessarily apply to antioxidants found naturally in fruits, vegetables and other foods, Gluud and other researchers stressed.
But the findings are consistent with evidence suggesting that some nutrients may be harmful at high doses or could interfere with the body's natural defenses, the researchers said.
"By taking these supplements, you might be impeding your immune system's ability to fight off disease or risk factors for chronic disease," said Edgar Miller III of Johns Hopkins University, who in 2004 reported similar findings about Vitamin E. "People are taking these supplements with the presumption that they will live longer or better. This shows they are not living longer and in fact may be at higher risk of dying."
Other researchers were cautious about concluding that the substances were dangerous but said the study added to the now large body of evidence indicating that the hoped-for health benefits have not materialized.
"They probably won't kill you, but they're not going to do any good for you if what you want is to live longer," said Donald Berry, a professor of biostatistics at the University of Texas M.D. Anderson Cancer Center in Houston.
Antioxidant supplements became a multibillion-dollar business after studies indicated that the substances may promote health by mopping up damaging "free radicals," which are natural byproducts of cellular processes.
But a series of studies testing the benefits of taking antioxidants and other nutritional supplements has been disappointing. Another study released Monday found that consuming garlic does not lower cholesterol. And several studies have even been alarming, indicating, for example, that beta-carotene increased rather than decreased the risk of lung cancer among smokers, and that Vitamin E appeared to boost the overall risk of death.
Gluud and his colleagues combed the scientific literature for every study about antioxidants published since 1990 and found 68 involving 232,606 people.
Among those, the researchers identified 47 trials involving 180,938 subjects that they classified as "low-bias" because they did the best job of eliminating factors that might produce faulty results.
Subjects in those 47 studies were randomly assigned to get real vitamins or placebos.
When they analyzed that data, the researchers found that those taking any antioxidant were 5 percent more likely to die than those who were not.
With Vitamin E, the risk rose 4 percent; with beta-carotene, 7 percent; and with Vitamin A, 16 percent. The actual causes of death in most studies were unknown, however.
Even though the possible increased risk was relatively small, the "public health consequences may be substantial" because of the large number of people taking the substances, the researchers said.
Vitamin C and selenium did not appear to have any effect on the risk of dying. But Gluud said that "the verdict is still out on those two."
Efforts are still under way to assess the value of taking individual antioxidants for specific purposes, including a large federal study that is testing whether Vitamin E and selenium reduce prostate-cancer risk.
Material from The Associated Press and the South Florida Sun-Sentinel is included in this report.
Copyright © The Seattle Times Company
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Mega Multivitamin Use Risks Prostate Cancer

By Crystal Phend, Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
May 15, 2007


Add Your Knowledge™ Additional Prostate Cancer Coverage


BETHESDA, Md., May 15 -- Men who take multi-vitamin supplements more than once a day are twice as likely to die of prostate cancer as men who never take supplements, researchers confirmed. Action Points

Explain to interested men that more than daily use of multivitamin supplements does not appear to reduce their risk of prostate cancer and may even increase it.


Caution patients that the study did not suggest that regular multivitamin use, whether occasionally or once daily, significantly increased risk of prostate cancer.
They were also at elevated risk of advanced prostate cancer compared with never users, reported Karla A. Lawson, Ph.D., of the National Cancer Institute here, and colleagues.


The researchers reported the outcomes of the National Institutes of Health -- AARP Diet and Health Study in the May 16 issue of the Journal of the National Cancer Institute.


The large, prospective investigation adds credence to the possibility of harm from antioxidant supplements as found in prior systematic reviews and meta-analyses, according to an accompanying editorial.


The findings "underscore the possibility that antioxidant supplements could have unintended consequences for our health," wrote Goran Bjelakovic, M.D., of the University of Nis, Serbia, and Christian Gluud, M.D., of the Copenhagen University Hospital.


The few previous prospective studies had suggested that multivitamin use may protect men from developing prostate cancer but speed its progression once begun, Dr. Lawson and colleagues wrote.


Because more than a third of American adults take vitamins, the researchers noted, "any association between intake of multivitamin supplements and the risk or severity of prostate cancer would have important consequences for public health," the researchers wrote.


The prospective study included 295,344 men aged 50 to 71 and free of cancer at enrollment in 1995 and 1996.


Their multivitamin use was assessed at baseline using a self-administered, food-frequency questionnaire. Five percent used multivitamins more than seven times a week; 36% took a multivitamin daily.


Among the participants, 41% reported using a one-a-day type supplement, 12% reported using a theragran type (vitamins plus iron) supplement, and 6% reported use of a stress-tab type supplement (primarily B vitamins). Half of the supplements used were multivitamins.


Outcomes were followed using subsequent questionnaires, Social Security Administration death records, and state cancer registries.


Over five years of follow-up, 10,241 developed incident prostate cancer. These cases included 8,765 localized and 1,476 advanced cancers. A separate mortality analysis found 179 cases of fatal prostate cancer over six years of follow-up.


Among the findings in a multivariate adjusted analysis, the researchers reported (more than daily use versus never users):


No association between multivitamin use and risk of prostate cancer overall (relative risk 1.06, 95% confidence interval 0.97 to 1.17).
No association between multivitamin use and risk of localized prostate cancer (RR 1.02, 95% CI 0.92 to 1.14).
Increased risk of advanced prostate cancer (RR 1.32, 95% CI 1.04 to 1.67).
Elevated risk of fatal prostate cancers (RR 1.98, 95% CI 1.07 to 3.66).
Higher incidence rates for advanced prostate cancer (143.8 versus 113.4 per 100,000 person-years).
Higher incidence rates for fatal prostate cancer (18.9 versus 11.4 per 100,000 person-years).


The associations were strongest in men with a family history of prostate cancer or those who took selenium, β-carotene, or zinc.


"Thus, excessive intake of certain individual micronutrients that are used in combination with multivitamins may be the underlying factor that is related to risk and not the multivitamins themselves," the researchers wrote.


Among men with prostate cancer in the family, heavy multivitamin use (more than seven times per week) more than doubled advanced prostate cancer risk (RR 2.48, 95% CI 1.45 to 4.23) and fatal prostate cancer risk (RR 16.41, 95% CI 2.62 to 102.68).


Heavy use of selenium yielded a 37% increased risk of localized prostate cancer (P=0.008 for interaction) Although based on a small sample, those who took more than seven multivitamins a week and were also taking a selenium supplement were at 5.8-fold higher risk of fatal prostate cancer than those not taking a selenium supplement (P=0.037 for interaction).


The association between heavy multivitamin use and advanced prostate cancer was somewhat modified by β-carotene use (P=0.036 for trend).


Men who used a zinc supplement in addition to heavy multivitamin use were at significantly elevated risk of fatal prostate cancer (RR 4.36, 95% CI 1.83 to 10.39 versus daily or less than daily multivitamin use).


This "could be due to nonessential, potentially harmful trace elements contained in zinc supplements, such as cadmium, a known carcinogen," the researchers said.


They noted that their study was limited by lack of information on duration of multivitamin use.


Also, they said, heavy multivitamin users were more likely to have prostate cancer screening using prostate specific antigen.


While this could have biased diagnosis of localized prostate cancer, "increased multivitamin use due to early symptoms of prostate cancer cannot account for the increased risk of fatal prostate cancer among heavy multivitamin users because the association persisted and even strengthened when we disregarded those diagnosed in the initial years of follow-up," the researchers noted.


Regardless, they concluded, "the possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation."


The reason why dietary intake of vitamins has been shown beneficial with mixed or negative results for supplements, editorialists Drs. Bjelakovic and Gluud suggested, may be because of differences between natural and synthetic vitamins.


"Antioxidant supplements in pills are synthetic, factory processed, and may not be safe compared with their naturally occurring counterparts," they wrote.


Or, they added, it could be that the populations they have been tested in already get their full daily requirement of vitamins and trace elements from diet. They pointed out that the American diet provides 120% of the recommended dietary allowances for beta-carotene, vitamin A, and vitamin C, and that dietary vitamin E deficiency has never been reported in the United States.


They also suggested a possible mechanism for the negative findings: "Reactive oxygen species in moderate concentrations are essential mediators of reactions by which the body gets rid of unwanted cells. Thus, if administration of antioxidant supplements decreases free radicals, it may interfere with essential defensive mechanisms for ridding the organism of damaged cells, including those that are precancerous and cancerous."


The editorialists also suggested a need for further study, possibly including testing of supplements similar to pharmaceutical products.


The research was supported by the National Cancer Institute. Neither the researchers nor the editorialists reported information on financial conflicts of interest.



Additional Prostate Cancer Coverage


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Additional source: Journal of the National Cancer Institute
Source reference:
Lawson KA, et al "Multivitamin Use and Risk of Prostate Cancer in the National Institutes of Health -- AARP Diet and Health Study" J Natl Cancer Inst 2007;99: 754-764.

Additional source: Journal of the National Cancer Institute
Source reference:
Bjelakovic G, Gluud C "Surviving Antioxidant Supplements" J Natl Cancer Inst 2007;99:742-743.