by Stephen Daniells

16 August 2011

from NutraIngredients-USA Website


Users of antioxidant vitamin supplements may be at reduced risk of cancer mortality, as well as premature death in general, suggests data from the European Prospective Investigation into Cancer and Nutrition (EPIC.)


Antioxidant vitamin supplement use at the start of the study was associated with a 48 percent reduction in the risk of cancer mortality over 11 years of study, according to findings published in the European Journal of Nutrition.

In addition, the risk of all-cause mortality was reduced by 42 percent in people who were supplement users at the start of the study, report scientists from the German Cancer Research Centre and the University of Zurich.



‘Sick-user effect’?

General multivitamin/mineral supplementation, however, was not associated with any impact on mortality risks.

And on the flip side, the EPIC researchers note that people who started taking supplements after the start of the study were at a higher risk of cancer mortality and so-called all-cause mortality, said the researchers.

“The significantly increased risks of cancer and all-cause mortality among baseline non-users who started taking supplements during follow-up may suggest a ‘sick-user effect’, which researchers should be cautious of in future observational studies,” they wrote.



Methodological challenges

Commenting independently on the research, Professor Jeff Blumberg, director of the Antioxidants Research Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, said he agreed that based on a,

“small number of users of antioxidant vitamin supplements and lack of detailed information on dose, contents, and durations of use,” there appears to be a statistically modest reduction in cancer and all-cause mortality.

“Some other studies are consistent with this finding and others are not. Why? Because the methodological challenge of conducting observational studies on the effect of dietary supplements is great and fraught with serious confounding variables (including the difficulty of accurately assessing the product[s] and their use),” he observed.




An attempt to bring together the science was made in 2007, with the publication of a meta-analysis by Goran Bjelakovic et al. and from the Copenhagen Trial Unit at the Copenhagen University Hospital in Denmark in the Journal of the American Medical Association (Vol. 297, pp. 842-857).

The meta-analysis concluded that vitamins A and E, and beta-carotene may increase mortality risk by up to 16 per cent.

On the other hand, vitamin C did not have an effect on mortality and the antioxidant mineral selenium was associated with a nine per cent decrease in all-cause mortality.

Following publication of the Bjelakovic paper, numerous scientists and dietary supplement trade associations questioned the methodology, particularly the exclusion of over 400 clinical trials from the data set because no deaths were reported.



Revisiting old data

Recently, a team of internationally renowned antioxidant scientists, including Prof Blumberg, re-analyzed the data used by Bjelakovic et al., and arrived at a different set of conclusions.

This re-analysis, published in Nutrients, found that 36 percent of the trials showed a positive outcome or that the antioxidant supplements were beneficial, 60 percent had a null outcome, while only four percent found negative outcome.



New data

The EPIC scientists based their findings on analysis of intakes of 23,943 people, all free of cancer and heart disease at the start of the study.

After 11 years of data collection, the researchers had documented 1,101 deaths, of which 513 were from cancer and 264 from cardiovascular conditions.

Data analysis showed that users of antioxidant vitamin supplements at the start of the study had a significantly reduced risk of both cancer mortality and all-cause mortality, while people who started taking supplements after the study had started had significantly increased risks.

“Based on limited numbers of users and cases, this study suggests that supplementation of antioxidant vitamins might possibly reduce cancer and all-cause mortality,” they concluded.




Prof Blumberg added that an issue he has always found interesting is the definition of ‘regular use’ of a dietary supplement.

“In this study, which is not unlike others, using a supplement as little as 25 percent of the typical indication counts as regular use. In other words, for 5 doses or one week of use per month when the label states ‘take daily’,” he said.

“If this was a study of a drug and adherence was this poor, a null outcome would be dismissed as meaningless due to non-compliance.”
Vitamin/mineral supplementation and cancer, cardiovascular, and all-cause mortality in a German prospective cohort (EPIC-Heidelberg)”
Authors: K. Li, R. Kaaks, J. Linseisen, S. Rohrmann