Vitamin E supplementation and pneumonia risk in males who initiated smoking at an early age: effect modification by body weight and dietary vitamin C

Abstract

Background: We had found a 14% higher incidence of pneumonia with vitamin E supplementation in a subgroup of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study cohort: participants who had initiated smoking by the age of 20 years. In this study, we explored the modification of vitamin E effect by body weight, because the same dose could lead to a greater effect in participants with low body weight.

Methods: The ATBC Study recruited males aged 50-69 years who smoked at least 5 cigarettes per day at the baseline; it was conducted in southwestern Finland in 1985-1993. The current study was restricted to 21,657 ATBC Study participants who initiated smoking by the age of 20 years; the median follow-up time was 6.0 years. The hospital-diagnosed pneumonia cases were retrieved from the national hospital discharge register (701 cases).

Results: Vitamin E supplementation had no effect on the risk of pneumonia in participants with body weight in a range from 70 to 89 kg (n = 12,495), risk ratio (RR) = 0.99 (95% CI: 0.81 to 1.22). Vitamin E increased the risk of pneumonia in participants with body weight less than 60 kg (n = 1054), RR = 1.61 (1.03 to 2.53), and in participants with body weight over 100 kg (n = 1328), RR = 2.34 (1.07 to 5.08). The harm of vitamin E supplementation was restricted to participants with dietary vitamin C intake above the median.

Conclusion: Vitamin E supplementation may cause harmful effects on health in certain groups of male smokers. The dose of vitamin E used in the ATBC Study, 50 mg/day, is substantially smaller than conventional vitamin E doses that are considered safe. Our findings should increase caution towards taking vitamin E supplements.

Trial registration: ClinicalTrials.gov NCT00342992.

Figures

Figure 1

Vitamin E supplementation and pneumonia risk in subgroups of the ATBC Study participants who started smoking at ≤ 20 years. A) Weight < 60 kg and dietary vitamin C intake > 75 mg/day (n = 468). B) Weight ≥ 100 kg and dietary vitamin C intake > 95 mg/day (n = 613). Nelson-Aalen cumulative hazard functions for vitamin E and no-vitamin E groups are shown. Each step indicates one case of pneumonia. For the difference between the two survival curves, the logrank test gives A) P = 0.0021 and B) P = 0.0020. The survival curves are cut at 7.2 years because the number of participants declines abruptly thereafter. At 6-years of follow-up there were remaining 114 and 126 participants in A), and 146 and 162 participants in B), in the vitamin E and the no-vitamin E groups, respectively.