Potential harm of vitamin E supplementation

Department of Public Health
PO Box 41
University of Helsinki
Helsinki FIN-00014
Finland

E-mail: harri.hemila{at}helsinki.fi

Dear Sir:

In their recent Journal review of the safety of vitamins E and C, Hathcock et al (1) stated, "At present, the evidence is not convincing that vitamin E supplementation up to the UL [ie, the tolerable upper intake level, or 1000 mg/d] increases the risk of death due to CVD [cardiovascular disease] or other causes." However, to focus only on the effect on mortality is a very narrow view of safety.

A recent double-blind, placebo-controlled trial in 652 Dutch persons aged 60 y found greater severity of respiratory infections among participants supplemented with 200 mg vitamin E/d than among those not given vitamin E (3). During respiratory episodes, the presence of fever (P = 0.009) and the restriction of activity (P = 0.02) were more common, the number of symptoms was higher (P = 0.03), and the total illness duration was longer (P = 0.02) among the vitamin E-supplemented participants than among those who received no vitamin E. These findings directly point out that some population groups may be harmed by vitamin E supplementation. Thus, when assessing the safety of vitamin E, it is not reasonable to focus only on mortality when there is evidence of aggravation of a disease that is very common.

A further problem in the review by Hathcock et al is their implicit assumption that the population is homogeneous with respect to the potential harmful effects of vitamin E. In the Alpha-Tocopherol Beta-Carotene (ATBC) Study cohort, the effect of vitamin E on the risk of pneumonia was significantly modified by the age of smoking initiation (P = 0.0007) (4). Vitamin E was beneficial to participants who initiated smoking at later ages [relative risk (RR) of pneumonia = 0.65; 95% CI: 0.49, 0.86] but harmful, although not significantly so, to those who initiated smoking at earlier ages (RR = 1.14; 95% CI: 0.98, 1.32). In the ATBC Study, the vitamin E dose was 50 mg/d, which is substantially less than the UL of 1000 mg/d. Thus, the lack of adverse effects in one population group—in this case, those less exposed to cigarette smoking—cannot be directly extrapolated to all people, eg, those who initiated smoking at early ages.

Although there is evidence that, for short-term supplementation, vitamin E in doses of 1 g/d does not cause adverse effects in a large proportion of the general population (1, 2), data from trials by Graat et al (3) and Hemilä et al (4) indicate that much lower doses, eg, 50-200 mg/d of vitamin E, may be harmful to some population groups. The harm associated with such low doses should not be extrapolated directly outside of the particular groups of trial participants, but, at the same time, these 2 trials should not be disregarded in statements that there is no evidence of potential harm from vitamin E supplementation (1).

The current US nutritional recommendations consider that clinical trials of doses above the UL (ie, 1000 mg/d) should not be discouraged (2), which seems to be a justified conclusion, given that participants in controlled trials are carefully selected and followed. However, the lack of benefit in several large controlled trials (5, 6) and the evidence of harm found in some groups (3, 4) provide a sound basis for discouraging large-dose vitamin E self-supplementation in the general population, until subpopulations that might benefit from supplementation are characterized properly.

ACKNOWLEDGMENTS

The author had no conflicts of interest with the study by Hathcock et al.

REFERENCES

1. Hathcock JN, Azzi A, Blumberg J, et al. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr 2005;81:736-45.
2. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academies Press, 2000:186-283.
3. Graat JM, Schouten EG, Kok FJ. Effects of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA 2002;288:715-21.
4. Hemilä H, Virtamo J, Albanes D, Kaprio J. Vitamin E and beta-carotene supplementation and hospital-treated pneumonia incidence in male smokers. Chest 2004;125:557-65.
5. Eidelman RS, Hollar D, Hebert PR, Lamas GA, Hennekens CH. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med 2004;164:1552-6.
6. Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;293:1338-47.