Vitamin A and Smoking

Article Highlights

Several studies using high dose beta-carotene or beta-carotene and vitamin A failed to show a protective effect against cancer or heart disease.
Some of the same studies showed a higher risk of death from lung cancer or heart disease in smokers who took high dose beta-carotene or beta-carotene and vitamin A than in the placebo group.
Studies suggest beta-carotene from food may be safer than synthetic beta-carotene found in dietary supplements.

Contrary to prior beliefs that high dose beta-carotene and vitamin A supplementation guard against some types of cancer and heart disease, recent evidence suggests potential harmful effects. The Beta-carotene and Retinol Efficacy Trial (CARET) performed by the National Cancer Institute (NCI) showed that 30 mg (100,000 IU) of beta-carotene and 25,000 IU vitamin A failed to decrease the risk of cancer or heart disease.^4,5 The study was stopped 21 months early because it showed that beta-carotene/vitamin A takers who were heavy smokers, ex-smokers or asbestos workers were showing a 28% increased risk of lung cancer in smokers (versus placebo) and a 17% more likely chance of dying, mostly of lung cancer or heart disease. Another study by the NCI in 1994 of more than 29,000 male Finnish smokers taking 20 mg beta-carotene per day had an 18% higher risk of lung cancer and an 8% higher risk of dying from lung cancer or heart disease than placebo.⁶ A 12-year Physicians’ Health Study taking 50 mg (166,667 IU) of beta-carotene every other day in 22,000 mostly non-smoking men showed no benefit or risk.⁷

There are two forms of beta-carotene: in food, all-trans and 9-cis-beta-carotene; in supplements, beta-carotene is entirely the all-trans form of the molecule. The synthetic all-trans beta-carotene has much lower antioxidant activity. Studies have demonstrated that synthetic all-trans beta-carotene may cause genetic damage while natural beta-carotene does not.⁸ This may be the reason that high doses of synthetic beta-carotene may increase cancer and heart disease risk in these groups of individuals.

⁴Omenn GS, et al. Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996;334:1150-1155.

⁵Goodman GE, et al. The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst. 2004;96(23):1743-50.

⁶Heinonen OP, et al. The Alpha-Tocopherol, Beta-Carotene Prevention Study Group. The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330:1029-1035.

⁷Hennekens CH, et al. Lack of effect of long-term supplementation with beta-carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996;334:1145-1149.

⁸Xue KX, et al. Comparative studies on genotoxicityand antigenotoxicity of natural and synthetic beta-carotene stereoisomers. Mutat Res. 1998;418(2- 3):73-78.