Consuming excessive amounts of beta-carotene may block vitamin A actions

New US in vitro experiments suggest that high concentrations of certain naturally occurring molecules derived from beta-carotene may be associated with health hazards under specific conditions. An adequate intake of beta-carotene remains recommended.

These scientists manufactured a series of beta-carotene-derived molecules in vitro that match those that exist in nature (1). They then exposed these molecules to conditions mimicking their metabolism and action in the body. Of the 11 molecules produced, five appeared to inhibit action of vitamin A, which provides its health benefits by activating hundreds of genes critical to human vision, bone and skin health, metabolism, and immune function. After analyzing blood samples obtained from six healthy human volunteers, the scientists found that some of these vitamin A-antagonizing molecules were present in every sample studied, thus suggesting that they are a common product of beta-carotene metabolism.

The researchers commented that, in theory, diets very high in beta-carotene may increase blood levels of such anti-vitamin A molecules. It remained unclear which environmental and biological conditions would be most likely to cause the production of these molecules. When beta-carotene is metabolized, it is broken in half by an enzyme, which in turn produces two vitamin A molecules. Molecules that antagonize vitamin A seem to be produced when beta-carotene is broken in a different place by processes that are not yet fully understood. Studies have suggested that oxidative stress, which can result from smoking and exposure to air pollution, can lead to higher production of these anti-vitamin A molecules. The findings might explain the outcome of two clinical trials that had left scientists puzzled for years: people at high risk of lung cancer – heavy smokers and asbestos workers – were given massive doses (10 to 15-fold the recommended doses) of beta-carotene over a long period of time, which was associated with an increased lung cancer risk (2,3). Other large trials did not show this effect (4,5).

The scientists emphasized that they do not recommend against adequate beta-carotene intake, as the carotenoids’ antioxidant properties could be associated with protecting cells and regulating cell growth and death, all of which play a role in multiple disease processes. In moderate doses, beta-carotene could be an important and safe source of vitamin A.

1. Eroglu A. et al. Naturally-occurring eccentric cleavage products of provitamin A beta-carotene function as antagonists of retinoic acid receptors. Journal of Biological Chemistry. Published online May 2012.
   
   
2. The Alpha-Tocopherol, Beta Carotene Cancer 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(15):1029–1035.
   
   
3. Omenn G. S. et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996; 88(21):1550–1559.
   
   
4. Hennekens C. H. 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(18):1145–1149.
   
   
5. Lee I.-M. et al. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Womens´ Health Study. J Natl Cancer Inst. 1999; 91: 2102–2109.