Nutrition
Antioxidant vitamins increase mortality?
By David Liu, Ph. D.
Apr 19, 2008 - 11:57:10 AM

SATURDAY April 19, 2008 (foodconsumer.org) -- A recent meta-analysis conducted by Goran Bjelakovic and colleagues from University of Nis in Nis, Serbia suggests that beta carotene, vitamin A and vitamin E may increase the risk of death.  The study was published Feb 28 in the Journal of American Medical Association.

The analysis was based on data from selected 68 randomized trials involving 232,606 participants.  Forty-seven low-bias trials of 180,938 participants showed antioxidant supplements increased mortality by 5 percent. Specifically beta carotene was associated with a 7 percent increase in the death risk, vitamin A 16 percent and vitamin E 4 percent.

The researchers suggested that the common notion that antioxidants provide benefits by counteracting with free radicals, which are believed to be the cause of many chronic diseases, may not be valid.

One of reasons antioxidants do more harm than good, the researchers explained, is because by eliminating free radicals, they interfere with some essential defensive mechanisms like apoptosis, phagocytosis and detoxification.

The researchers also suggested that the apparently increased risk of death in those who used antioxidant vitamins may be due to the way the vitamins are made.  They said antioxidant supplements are synthetic and not subjected to the same rigorous toxicity studies as other pharmaceutical agents.   Therefore, the results of the study may not be applicable to vitamins found in fruits and vegetables, the researchers suggested.

The study caused quite a bit of stir in the academia and some discomfort in some health advocates.  Naturalnews.com said the study deliberately left out hundreds of trials that involved no deaths and picked only a few dozens of trials involving deaths suggesting that the study was biased.

Critical comments came not just from health advocates like naturalnews.com.  In the issue of the publication, five groups of researchers sent a letter to express concerns about the methodology and results of the study, both of which may have been severely biased.  As a result, readers can be seriously misled by the results.  Of course, the researchers defended the integrity of their study in response to those letters.

The following is what the researchers found:

Beta carotene used singly significantly increased mortality. This effect was not significant when combined with other supplements. After exclusion of high-bias risk and selenium trials, beta carotene singly or combined significantly increased mortality.

Vitamin A given singly or in combination with the other supplements did not significantly affect mortality. After exclusion of high-bias risk and selenium trials, vitamin A singly or combined significantly increased mortality.

Vitamin E given singly or in combination with the other supplements did not significantly affect mortality. Vitamin E given singly in high (≥1000 IU) or low dose (<1000 IU) did not significantly affect mortality (RR, 1.07; 95% CI, 0.91-1.25; I2 = 0% and RR, 1.00; 95% CI, 0.94-1.07; I2 = 13.0%, respectively). After exclusion of high-bias risk and selenium trials, vitamin E given singly or combined significantly increased mortality.

One concern, according to a scientist affiliated with foodconsumer.org, is the doses of the antioxidant supplements used in the trials.  According to the researchers, the dose of beta carotene used in all the primary and secondary prevention trials ranged from 1.2 to 50.0 mg, vitamin A from 1333 to 200,000 IU, and vitamin E 10 to 5000 IU.  The differences were just too huge for the outcomes to be compared without errors introduced. The researchers did find the influence of the dosage was significant.

The foodconsumer.org scientist commented that the benefits of vitamin A, E and beta carotene will continue to be controversial. The key point consumers should keep in mind now and forever is that when it comes to the toxicity of any substance, the dose makes the difference.