Possible heterogeneity in the effects of vitamins C and E
by Harri Hemilä
This text is
based on pp 68-69 of Hemilä
(2006)
These documents have up to date links to documents that are available
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the net.
Harri Hemilä
Department of Public Health
University of Helsinki,
Helsinki, Finland
harri.hemila@helsinki.fi
A common feature of the discussions of the physiological effects of
vitamins C and E has been the implicit assumption that their effects
are similar in all people. If such an assumption was valid, it would
allow extrapolation of any study findings widely, given that the trial
is well conducted and so large that the results are accurate. The
validity of this assumption, that the effects of these vitamins are
similar over the population, is thus of fundamental importance.
For example, Pauling (1971a; pp 35-6) assumed that the findings of the
Ritzel trial (1961) could be directly extrapolated to the general
population without considering that the positive effects of vitamin C
found in the trial may be valid, but not appropriate for extrapolation
because of the special conditions of a trial with schoolchildren in a
skiing camp. Similar careless extrapolation from the findings of a
single small trial (N = 617) was recently carried out by Hamer and
Meydani (2004), who calculated that "Given that 34 million elderly
people live in nursing homes, this would translate into more
than 5 million fewer elderly nursing home residents contracting upper
respiratory tract infections in a year,"
with their estimate of the effect being based on a marginally
significant finding of RR = 0.84 (95% CI: 0.69-1.00; Meydani et al.
2004), whereas a much larger trial (N = 21,796) found that vitamin E
supplementation had no overall effect on common cold incidence (Paper
III; Hemilä & Kaprio 2004). Another recent example of this
implicit assumption of similar effects is seen in the meta-analysis of
the potentially deleterious effect of vitamin E supplementation by
Miller et al. (2005 [see Hemilä 2005f]), which was based on the
assumption that there is a universal threshold level, so that higher
intakes of vitamin E would progressively increase the risk of harm in
all people equally. Thus, the implicit assumption of similar effects in
all people is common to
many considerations of the effects of vitamins C and E.
An important finding in the current thesis was that the effects of
daily vitamin C and E supplementation on the incidence of the common
cold and pneumonia seem to be modified by various factors, so that the
effects of these two vitamins vary between different population groups.
Consequently, the assumption of similar effects in all people seems not
to be valid.
If the effects of daily vitamin C and E supplementation vary
substantially between different subpopulations, the heterogeneity of
the effect evidently means a need for careful consideration of goals
when planning new trials on these vitamins. Assuming heterogeneity,
further trials should try to identify and characterize the population
groups or living conditions in which these vitamins might be
beneficial, rather than re-examining the effects on ordinary Western
people for whom the studies already available have not found any
meaningful overall benefits from daily supplementation.
References
Hemilä H (2005f) High-dosage vitamin E supplementation and
all-cause mortality [letter]. Ann Intern
Med 143:156-7 * comments on: Miller et al. (2005)
Hemilä H, Kaprio J (2004) Vitamin E and respiratory tract
infections in elderly persons [letter]. JAMA 292:2834
* comments on: Meydani et al. (2004)
Meydani SN, Leka LS, Fine BC, et al. (2004) Vitamin E and respiratory
tract infections in elderly nursing home residents: a randomized
controlled trial. JAMA
292:828-36
Ritzel G (1961) Kritische Beurteilung des Vitamins C als Prophylacticum
und Therapeuticum der Erkältungskrankheiten [in German;
Critical
analysis of the role of vitamin C in the treatment of the common cold].
Helv
Med Acta 28:63-8 TRANSLATION
