Affiliations of authors: M. Gerber, M. Saintot, Groupe d'Epidémiologie Métabolique, Centre de Recherche en Cancérologie, INSERM-CRLC, Montpellier, France; P. Grolier, P. Borel, Equipe "Vitamines," Unité Maladies Métaboliques et micronutriments, INRA Centre de Theix, Saint-Genès Champanelle, France.
Correspondence to: Mariette Gerber, M.D., Ph.D., D.Sc., Groupe d'Epidémiologie Métabolique, Centre de Recherche en Cancérologie, INSERM-CRLC, 34298 Montpellier Cedex 5, France.
In his editorial, Marshall (1) discusses most of the arguments that explain the lack of protective effect of ß-carotene supplementation and does not agree with the interpretation of the results from nutritional epidemiology as the best explanation.
All nutritional epidemiologists agree that dietary assessment methods are rather imprecise if not erroneous, rendering the nutrient exposure estimation exceedingly complex.
This argument is weaker when prospective epidemiologic studies rely on plasma ß-carotene concentrations. Although intraindividual variations in plasma levels exist (2), the large numbers of measurements in prospective studies (3,4) are likely to alleviate this problem. But the other argument put forth by Marshall (1), which is that ß-carotene is confounded by other nutrients present in the same food as ß-carotene, is valid in these studies, and plasma levels of ß-carotene may also be the marker of fruit and vegetable intake.
We propose that nutritional epidemiologists also take into consideration factors other than food intake that might influence the plasma ß-carotene levels. We have some human and experimental evidence that plasma ß-carotene levels are influenced by other types of exposure (e.g., exposure to oxidative stress and xenobiotics).
We undertook a study to assess the effect of atmospheric photo-oxidants nitrogen dioxide (NO2) and ozone (O3) on the plasma levels of antioxidants in subjects exposed to these pollutants. NO2 and O3 exposures were measured independently for 5 days with passive monitors (Palmes [Gradbo, U.K.] and Passam [Passam Ag, Switzerland] tubes were used for NO2 and O3, respectively), and intake of foods rich in carotenoids was assessed. We showed a substantially lower level of ß-carotene in the plasma of subjects with the higher exposure, mainly that of O3 (5,6) (Table 1). This lower level can result from the oxidative stress induced by photo-oxidant inhalation. Experimental studies offer additional insight into these findings. In rats injected with xenobiotics (e.g., tetrachlorobiphenyl, benzo[a]pyrene, or ethanol), an increase in cytochrome P450 levels and related activities was observed after 3, 5, 7, and 9 days. The ß-carotene dioxygenase activity was increased by 300% (7). The increase in ß-carotene dioxygenase activity can enhance the conversion of ß-carotene to retinol and to other subsequent metabolic derivatives. As a result, the level of ß-carotene might steadily decrease in situations of long-term exposure. Therefore, there are two possible mechanisms to explain decreased plasma level of ß-carotene induced by exposure to xenobiotics: the depletion of ß-carotene in conditions of oxidative stress, and alternatively, the increase in ß-carotene dioxygenase activity, which enhances the conversion of ß-carotene to retinal. The latter explanation that might be possible in the subjects exposed to atmospheric pollutants (including benzo[a]pyrene) is supported by the observed decrease in plasma carotenoids (ß-carotene,
-carotene, and cryptoxanthine), which are precursors of retinal, whereas the effect on other antioxidants (e.g., other carotenoids, vitamin E, glutathione, and glutathione peroxidase) is inconsistent and results in no alteration of the total antioxidant capacity of the plasma (results not shown).
|
REFERENCES
1
Marshall JR. ß-carotene: a miss for epidemiology. J Natl Cancer Inst 1999;91:20689.
2
Rautalahti M, Albanes D, Haukka J, Roos E, Gref CG, Virtamo J. Seasonal variation of serum concentrations of ß-carotene and -tocopherol. Am J Clin Nutr 1993;57:5516.[Abstract]
3
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;330:102935.
4
Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334:11505.
5 Bernard N, Saintot M, Astre C, Gerber M. Personal exposure to nitrogen dioxide pollution and effect on plasma antioxidants. Arch Environ Health 1998;53:1228.[Medline]
6 Saintot M, Bernard N, Astre C, Gerber M. Ozone exposure and blood antioxidants: a study in a periurban area in southern France. Arch Environ Health 1999;54:349.[Medline]
7 Grolier P, Duszka C, Bachmann H, Borel P, Desbarat A, Pattison P, et al. Gordon conference on carotenoids [abstract]. Ventura; 1998.
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |