Beta carotene supplementation and age-related maculopathy in a randomized trial of US physicians. Six-year supplementation with alpha-tocopherol and beta-carotene and age-related maculopathy. Randomized trials of primary prevention of cardiovascular disease in women. An investigator's view.
To test whether beta carotene supplementation affects the incidence of age-related maculopathy (ARM) in a large-scale randomized trial.
                Randomized, double-masked, placebo-controlled trial among 22 071 apparently healthy US male physicians aged 40 to 84 years. Participants were randomly assigned to receive beta carotene (50 mg every other day) or placebo. Main Outcome Measure Incident ARM responsible for a reduction in best-corrected visual acuity to 20/30 or worse.
                After 12 years of treatment and follow-up, there were 162 cases of ARM in the beta carotene group vs 170 cases in the placebo group (relative risk [RR], 0.96; 95% confidence interval [CI], 0.78-1.20). The results were similar for the secondary end points of ARM with or without vision loss (275 vs 274 cases; RR, 1.01; 95% CI, 0.86-1.20) and advanced ARM (63 vs 66 cases; RR, 0.97; 95% CI, 0.69-1.37).
                These randomized data relative to 12 years of treatment among a large population of apparently healthy men indicate that beta carotene supplementation has no beneficial or harmful effect on the incidence of ARM. Long-term supplemental use of beta carotene neither decreases nor increases the risk of ARM. Animal research and observational studies in man suggest a protective effect of antioxidant vitamins in the development of age-related maculopathy (ARM).
                The ATBC study, a population-based, controlled clinical trial of alpha-tocopherol and beta carotene to prevent lung cancer, took place in Finland between 1984 and 1993. Over 29,000 smoking males aged 50 to 69 years were randomly assigned to alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both of these, or placebo. We performed an end-of-trial ophthalmological examination on a random sample of 941 participants aged 65 years or more from two of the fourteen study areas, to discover if the five to eight-year intervention with alpha-tocopherol and/or beta-carotene had been associated with a difference in ARM prevalence. Age-related maculopathy was assessed using colour photographs of the macula.
                Altogether, 269 cases of ARM were found; there were more cases in the AT group (32%; 75/237), BC group (29%; 68/234), and combined antioxidant group (28%; 73/257) than in the placebo group (25%; 53/213). However, neither substance was significantly associated with the risk of ARM in a logistic regression analysis controlling for possible risk factors.
                No beneficial effect of long-term supplementation with alpha-tocopherol or beta-carotene on the occurrence of ARM was detected among smoking males. In recent years, increasing attention has focused on the need for more research to be conducted in women on health issues directly relevant to women. No one would disagree that the need for such studies is both crucial and timely. However, while the need for more research in women is urgent, the planning and conduct of such studies must always be driven by good science. Specifically, investigations in women may have unique and important scientific and logistic problems which must be recognized and addressed. However, if the trials are well designed and conducted, they will provide a sound and reliable body of data upon which to base rational clinical decision making and public health recommendations for women from women. These general issues are discussed in the context of a particular trial, the Women's Health Study, a randomized trial of the risks and benefits of low-dose aspirin, beta-carotene and vitamin E in the primary prevention of cardiovascular disease and cancer among healthy women.
There is accumulating evidence that taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. There is no evidence with respect to other antioxidant supplements, such as vitamin C, lutein and zeaxanthin, or any of the commonly marketed multivitamin combinations. Although generally regarded as safe, vitamin supplements may have harmful effects and clear evidence of benefit is needed before they can be recommended. People with AMD should see the related Cochrane review 'Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration' written by the same review team.