Beta-carotene: Safety Assessment

The United Kingdom’s Expert Group on Vitamins and Minerals (EVM) last assessed vitamins and minerals for safety in 2003 and, where sufficient data were available, set a so-called Safe Upper Level (SUL) or Guidance Level for each micronutrient. This SUL or Guidance Level reflects the safe maximum amount of a micronutrient that will not cause any side effects when taken daily from all sources for a lifetime.

This value applies to nonsmokers and considers only the intake of isolated beta-carotene from dietary supplements in addition to conventional dietary intake. The safe daily intake limit does not apply to heavy smokers or to persons exposed to asbestos. For healthy nonsmokers, no evidence exists that high beta-carotene intake, either in isolated form or via conventional foods, causes adverse effects.Amounts up to 300 mg of beta-carotene daily for several years as a high-dose drug for the treatment of erythropoietic protoporphorphorphyria (EPP) have remained without adverse effects in otherwise healthy nonsmokers. Also, increased beta-carotene intake cannot lead to vitamin A overdose with corresponding symptoms of overdose because beta-carotene is absorbed in a controlled manner and is converted to vitamin A only when needed. Intake of large amounts of beta-carotene (30 mg per day or more), both in the form of supplements and conventional foods, can lead to carotenoderma (yellowing of the skin). However, the yellowing of the skin is not associated with any health problems and goes away after beta-carotene intake is reduced. For smokers, the precautionary principle is:

For isolated beta-carotene from supplements and fortified foods, 2 studies in smokers and asbestos workers show an increased risk of bronchial carcinoma (lung cancer):

• In the so-called ATBC study (The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial) with 29,133 participants, daily intake of 20 mg beta-carotene, taken for 5 to 8 years, resulted in an 18% higher bronchial carcinoma (lung cancer) rate.
• The CARET study (The Beta-Carotene Cancer and Retinol Efficiency Trial) of 18,314 participants showed a 28% higher rate of bronchial carcinoma with 30 mg of beta-carotene per day, taken for 21 months, than in the placebo group (control group).

Participants in both studies were heavy smokers, weaned smokers, or former asbestos workers. However, this is contrasted with 2 other large studies, which found no adverse effects with comparable amounts of beta-carotene:

• In the Physicians Health study of 22,071 participants (11% of participants were smokers, 39% were weaned smokers), taking 50 mg of beta-carotene every other day, taken over a 13-year period, resulted in no adverse effects with respect to bronchial carcinoma rates or tumor rates (cancer rates) in general.
• Similarly, in the Heart Protection Study with 20,536 participants and an intake of 20 mg beta-carotene daily, over a period of 5 years, no negative effects were demonstrated.

One clue to the difference in results may be the effect of beta-carotene supplementation on blood beta-carotene concentrations. As the study situation shows, beta-carotene supplementation seems to be harmless in smokers only if it does not increase blood plasma beta-carotene levels above 3 µmol/l. This possibly critical blood plasma level of more than 3 µmol beta-carotene per liter was reached or exceeded in both the ATBC study and the CARET study, whereas the levels in the Physicians’ Health Study and also in the Heart Protection Study were lower.

Conclusion

No direct dose-response relationship for isolated beta-carotene can be derived from the studies to date. Therefore, it remains unclear at what level isolated beta-carotene has adverse effects in smokers. For reasons of caution, heavy smokers are therefore advised against high beta-carotene intake in the form of dietary supplements over a longer period of time.Quantities of isolated beta-carotene in the lower estimate range of 2 mg pronounced by the DGE are absolutely safe even for heavy smokers and do not lead to elevated blood plasma levels above 3 µmol/l. High beta-carotene intake via conventional foods did not lead to any undesirable side effects even in smokers. The consumption of beta-carotene-rich fruits and vegetables is therefore also possible for these individuals without any restrictions. With a normal mixed diet, that is, an intake of beta-carotene equal to the range of estimated values of 2 to 4 mg pronounced by the DGE, the beta-carotene concentration in blood plasma reaches values of 0.4 to 0.75 µmol/l (200 to 400 µg/l).