Beta-Carotene: The Controversy Continues

Alternative Medicine Review, Dec, 2000 by Lyn Patrick

Carotenoids as Pro-oxidants

Carotenoids, as a class, are particularly vulnerable to free radical attack due to their long chains of conjugated double bonds,[65] A pro-oxidant effect has been seen in in vitro and animal studies, both in high concentrations and in the presence of tocopherol deficiencies.[66] The gas phase of cigarette smoke contains high levels of oxidants (nitric oxide) that have been shown to interact with lipid membranes to induce lipid peroxidation and protein oxidation to form protein-bound carbonyl groups.[67] The protein-carbonyl groups result in the inactivation of crucial enzymes such as creatine kinase and lecithin-cholesterol acyltransferase.[67]

Carotenoids interact with cigarette smoke-containing oxidants. Depletion of carotenoids and tocopherol, particularly trans-[Beta]-carotene, alpha-tocopherol, and lycopene, has been demonstrated in cigarette smoke-exposed human plasma.[68] As [Beta]-carotene acts as a scavenger of nitrogen oxides in cigarette smoke, [Beta]-apo-carotenals and other carotene oxidation products are created that, if not effectively neutralized by other antioxidants (specifically tocopherol and ascorbate), may initiate cell damage that could lead to neoplasm.[65] Multiple studies have substantiated that tocopherols (both alpha and gamma) protect carotenoids from auto-oxidation.[69,70] Ascorbate also acts to protect both tocopherol and [Beta]-carotene from oxidative damage and has been shown to preserve [Beta]-carotene in oxidized human LDL.[71,72]

The theory that [Beta]-carotene becomes an oxidant in the plasma and possibly tissues of smokers appears to be probable given the low antioxidant levels of smokers' blood.[68] Whether or not these carotenoid radicals can initiate cancer is, however, disputed. Baker[73] and colleagues examined a model of liposomes exposed to cigarette smoke. They found that [Beta]-carotene neither enhanced lipid peroxidation in membranes nor contributed to the depletion of other antioxidants. They concluded, "The data strongly suggest that, although [Beta]-carotene is readily oxidized by smoke, pro-oxidant effects are unlikely to account for the apparent enhancement of lung cancer in smokers taking this supplement."

One actual benefit of [Beta]-carotene's pro-oxidant effect may be its action in tumor cells. Carotenoids as a class appear to act as oxidizing agents selectively in tumor cells by increasing the production of heat shock proteins which ultimately enhance tumor cytotoxicity.[74]

Conclusion

The issues of absorption and metabolism of carotenoids are full of unanswered questions. The significant inter-individual and intra-individual variations in absorption of [Beta]-carotene indicate the possible effect of medications, individual variations in gut pH, subclinical fat malabsorption, and intestinal dysbiosis that exist outside of overt fat malabsorption and gastrointestinal disease.

Competitive inhibition of different carotenoids appears to occur in single-dosing studies but only bears out in long-term human studies that involve smoking populations. It is not clear whether there is an interaction between synthetic [Beta]-carotene and cigarette smoke that may have caused lower lutein levels in the Finnish Smokers Study.