Antioxidant Supplements Up Death Risk

Study Shows No Benefit, Slightly Higher Death Risk for Antioxidant Supplements

Medically Reviewed by Louise Chang, MD on February 27, 2007
From the WebMD Archives

Feb. 27, 2007 – Use of the popular antioxidant supplements beta-carotene,vitamin E, or vitamin A slightly increases a person's risk of death, anoverview of human studies shows.

The study also shows no benefit -- and no harm -- for vitamin C supplements.Selenium supplements tended to very slightly reduce risk of death.

Oxidative stress -- caused by highly reactive "free radical"compounds circulating in the blood -- is a factor in most diseases.

Antioxidants sweep up these free radicals. It seems to be a no-brainer thattaking antioxidant supplements would protect your health. But it may not bethat simple.

A new, detailed analysis of human studies of beta-carotene, vitamin A, andvitamin E shows that people who take these antioxidant supplements don't liveany longer than those who don't take them. In fact, those who take thesupplements have an increased risk of death.

The finding, reported in TheJournal of the American MedicalAssociation, comes from Goran Bjelakovic, MD, DrMedSci, of the Universityof Nis in Serbia; Christian Gluud, MD, DrMedSci, of Copenhagen UniversityHospital in Denmark; and colleagues.

"Our findings have already changed the way I counsel my patients aboutantioxidant supplements," Bjelakovic tells WebMD in an email interview."According to our findings, beta-carotene, vitamin A, and vitamin E cannotbe recommended. I am telling them that they should stop using thesesupplements."

"There is no reason to take anything that hasn't been proven beneficial.And these antioxidant supplements do not seem beneficial at all," Gluudtells WebMD.

Not everyone agrees. Nutritionist Andrew Shao, PhD, is vice president forscientific and regulatory affairs at the Council for Responsible Nutrition, asupplement-industry trade group.

"Consumers can feel confident in relying on their antioxidantsupplements as they always have," Shao tells WebMD. "They can continueto take them knowing they will provide the same benefits -- and this articledoes not change that."

Antioxidant Supplements and Death Risk

Bjelakovic, Gluud, and colleagues analyzed data from 68 randomized clinicaltrials of antioxidant supplements that included 232,606 people. When theylooked at all the trials together, they found that the supplements offered nobenefit but did no harm.

However, some of the trials were more exactly controlled than others. Therewere 21 trials that had a "high bias risk." These trials had one ormore problems with randomizing study participants to the supplement or placebogroups, with blinding both the participants and the investigators to whetherparticipants received supplements or placebos, and/or with following up on allparticipants until the end of the study.

So the researchers looked only at the 47 "low-bias-risk" studies --which included nearly 181,000 participants and which did not include peopletaking selenium. They found that:

  • Taking vitamin A supplements increased the risk of death by 16%.
  • Taking beta-carotene supplements increased the risk of death by 7%.
  • Taking vitamin E supplements increased the risk of death by 4%.
  • Taking vitamin C supplements did not have any effect on risk of death.

Shao says it just isn't fair to study antioxidants in this way.

"What these authors have done is combine studies that are incrediblydissimilar in all sorts of ways," he says. "These studies looked atdifferent nutrients at different doses at different durations with differentlengths of follow-up -- and in different populations, ranging from folks whowere incredibly healthy to people with cancer and other diseases."

Moreover, Shao says, the researchers looked only at studies in which peopledied. That left out 405 clinical trials, which he says skews the results infavor of death risk. And he points out that the researchers original 68 studiesdid not show any harm from supplements.

"These questions cause one to step back and wonder if the findings arerelevant to the healthy population that uses these supplements to maintainhealth and avoid chronic disease," Shao says. "That is a point theydon't make: that antioxidants are not used to treat cancer or heart disease.They are used for disease prevention."

Edgar R. Miller III, MD, PhD, associate professor of medicine at JohnsHopkins University, in 2004 analyzed clinical trials of vitamin E. He foundthat high doses of vitamin E did more harm than good. Miller has high praisefor the Bjelakovic/Gluud study.

"This is a great study. It is the highest form of scientificevidence," Miller tells WebMD. "I don't think that [Shao's] criticismis legitimate. I argue this is the best technique to analyze all thisinformation."

Gluud and Bjelakovic strongly disagree that they "cherry picked"only studies that fit some preconceived conclusion. They point out that all oftheir methods are "transparent" and open to public view.

"Anyone is welcome to criticize our research," Gluud says. "Butmy question is, what is your evidence? I think the parties that want to sell oruse these antioxidant supplements in the dosages used in these trials, theywant [to see only] positive evidence that it works beneficially."

Advice to Consumers

Kathleen Zelman, MPH, RD, LD, is director of nutrition for WebMD. Shereviewed the Bjelakovic/Gluud study for this article.

"This is a very comprehensive, to-be-respected analysis. This isn't justanother study coming out," Zelman says. "The bottom line is thatantioxidant supplements are not a magic bullet for disease prevention. We hopedmaybe they were, but they are not."

If you are interested in protecting your health, Zelman says, pills aren'tthe answer.

"There is no single food or nutrient that is going to be the answer. Thesecret really is lifestyle," she says. "And the most important thingsabout lifestyle are being at a healthy weight, being physically active, andeating a healthy diet."

Shao says he's not persuaded to stop taking antioxidant supplements.

"I take antioxidant supplements every day," he says. "I knowmore about these nutrients than most people do, including the authors of thisstudy, who are not nutritionists. This does not change a thing for me. You cantake that to the bank."

Zelman has this advice: If you plan to continue taking antioxidantsupplements, don't exceed the recommended daily doses.

"For nutritional insurance, my suggestion would be a once-dailymultivitamin," she says. "But for those people who take multiplesupplements, and are going to continue to do so, heed the warning and be sureto respect the safe upper dosage limits."

"If you are in doubt, take the time and go to your doctor and talk withher or him," Gluud advises.

Show Sources

SOURCES: Bjelakovic, G. TheJournal of the American Medical Association, Feb. 28, 2007; vol 297: pp 842-857. Goran Bjelakovic, MD, DrMedSci, University of Nis, Serbia (email interview).Christian Gluud, MD, DrMedSci, Copenhagen University Hospital, Denmark.Andrew Shao, PhD, vice president for scientific and regulatory affairs, Council for Responsible Nutrition, Washington, D.C. Edgar R. Miller III, MD, PhD, associate professor of medicine, Johns Hopkins University, Baltimore. Kathleen Zelman, MPH, RD, LD, director of nutrition, WebMD, Atlanta.

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