A potential interaction between beta-carotene intake and smoking on the risk of tobacco-related cancers was investigated in 59,910 women participating in the French Etude Epidemiologique de Femmes de la Mutuelle Generale de l'Education Nationale. After a median follow-up period of 7.4 years, 700 women had developed cancers known to be associated with smoking (e.g., lung, head and neck, urinary tract, digestive tract, cervix, thyroid, and ovary). Among women who had never smoked, there was a significant inverse association between beta-carotene intake from both diet and supplements and the risk of all smoking-related cancers (p for trend = 0.03). Supplement users had a 56% lower risk of developing such cancers, compared with women in the lowest tertile of beta-carotene intake.

In contrast, among women who had ever smoked (including current and former smokers), increasing beta-carotene intake was associated with an increase in the incidence of smoking-related cancers (p for trend = 0.09). Smokers who took beta-carotene supplements had more than twice the risk of such cancers as did women in the lowest tertile of beta-carotene intake (hazard ratio = 2.14; 95% confidence interval, 1.16-3.97). Tests for interaction between beta-carotene intake and smoking were statistically significant (p for trend < 0.02).

Comment: Previous randomized controlled trials have shown that supplementation with synthetic beta-carotene (which differs somewhat from naturally occurring beta-carotene) increased the incidence of lung cancer in smokers. The results of the present study are consistent with those clinical trials, but also suggest that beta-carotene supplements reduce the risk of certain cancers in nonsmokers. It is possible that chemicals in cigarette smoke react with beta-carotene, causing the formation of compounds that have deleterious effects on human health. Such a toxic interaction has previously been demonstrated between beta-carotene and alcohol: supplementation with beta-carotene increased the severity of ethanol-induced liver disease in rats.

In most cases, the best way to consume beta-carotene is by eating fruits and vegetables, which contain a wide array of different carotenoids. Supplementation with beta-carotene by itself might deplete other carotenoids that have health benefits. There are a few instances in which beta-carotene supplementation is indicated, such as for the treatment of erythropoietic protoporphyria and oral leukoplakia. Beta-carotene supplements may also help prevent sunburn and slow the progression of HIV disease.

Touvier M, et al. Dual association of beta-carotene with risk of tobacco-related cancers in a cohort of French women. J Natl Cancer Inst. 2005;97:1338-1344.