by Stephen Daniells
16 August 2011
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
published in the European Journal of
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.
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.
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
“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.
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
After 11 years of data collection, the researchers had documented
1,101 deaths, of which 513 were from cancer and 264 from
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
supplementation and cancer, cardiovascular, and all-cause
mortality in a German prospective cohort
Authors: K. Li, R. Kaaks, J. Linseisen, S. Rohrmann