The effect ofβ-carotene on the mortality of male smokers is modified bysmoking and by vitamins C and E: evidence against a uniform effectof nutrient

Abstract

A previous analysis of the Alpha-Tocopherol Beta-Carotene (ATBC) Study on male smokers found thatβ-carotene supplementation increased the risk ofpneumonia 4-fold in those who started smoking at the age of≥21 years and smoked≥21 cigarettes/d (a subgroup of 7 % of the study population). Thepresent study hypothesised thatβ-carotene increases mortality in the same subgroup. The ATBC Study (1985–1993) recruited 29 133 Finnish male smokers(≥5 cigarettes/d) aged 50–69 years. Cox regression models were constructed to estimate the effect ofβ-carotene supplementation in subgroups.β-Caroteneincreased mortality (risk ratio 1·56; 95 % CI 1·06, 2·3) in those who started to smoke at≥21 years and smoked≥21 cigarettes/d. Within this subgroup,there was strong evidence of further heterogeneity. The effect ofβ-carotene supplementation was further modified by dietary vitamin C intake, fruit andvegetable intake (P=0·0004), and by vitamin E supplementation (P=0·011). Thus, harm fromβ-carotene was not uniform within the study population.Interactions betweenβ-carotene and vitamins C and E were seen only within a subgroup of 7 % of the ATBC participants, and therefore should not beextrapolated to the general population. Heterogeneity of theβ-carotene effect on mortality challenges the validity of previous meta-analyses that havepooled many diverse antioxidants for one single estimate of effect using the assumption that a single estimate equally applies to all antioxidants andall people. Trial registration: ClinicalTrials.gov NCT00342992.