Affiliation of authors: Naturopathic Medicine Department, Bastyr University, Seattle, WA, and the Tahoma Clinic, Kent, WA.
Correspondence to: Matthew Brignall, N.D., Bastyr University, Naturopathic Medicine Department, 8052 16th Ave., N.W., Seattle, WA 98117.
In an editorial in the December 15 issue of the Journal, Dr. James Marshall presents a compelling hypothesis about the apparent disagreement between the epidemiologic and experimental data regarding ß-carotene as a chemopreventative agent (1). He argues that ß-carotene may have been only a marker compound for one or more other protective phytonutrients. Indeed, there are ample data to support such reasoning. However, there is another equally compelling reason for the disparate findings on ß-carotene.
The synthetic form of ß-carotene found in supplements, and hence used in most clinical trials, is the all-trans form. The naturally occurring form of this nutrient contains about 50% trans-isomer and several other forms, the most prevalent being 9-cis-ß-carotene (2,3). While serum concentrations of the highly lipophilic 9-cis isomer are very low, even with supplementation of natural, mixed isomeric carotenoids (2), tissue concentrations of this compound have been measured at 10%20% of total ß-carotene (4). The 9-cis form of ß-carotene has much greater antioxidant activity in humans than the synthetic all-trans form (2). Moreover, in vitro (5) and preliminary human data (3) indicate that the naturally occurring forms of ß-carotene have a better ability to block malignant transformation than the synthetic all-trans isomer. Animal studies (6,7) suggest that the preferred form of carotenes for future studies should be the palm carotenoids, which contain lycopene, lutein, and -carotene, in addition to the mixed isomers of ß-carotene.
In summary, Dr. Marshall's assertion that further investigation of the antimalignant transformation activity of synthetic ß-carotene supplements is not justified seems to be accurate. However, before we dismiss carotenes altogether, we should investigate the effect of palm carotenes in large-scale human trials.
REFERENCES
1
Marshall JR. ß-carotene: a miss for epidemiology. J Natl Cancer Inst 1999;91:20689.
2 Ben-Amotz A, Levy Y. Bioavailability of a natural isomer mixture compared with synthetic all-trans beta-carotene in human serum. Am J Clin Nutr 1996;63:72934.[Abstract]
3 Yeum KJ, Zhu S, Xiao S, Jiang S, Mason J, Russell RM. Beta-carotene intervention trial in premalignant gastric lesions [abstract]. J Am Coll Nutr 1995;14:536.
4 Stahl W, Schwartz W, Sundquist AR, Sies H. cis-trans isomers of lycopene and beta-carotene in human serum and tissues. Arch Biochem Biophys 1992;294:1737.[Medline]
5 Toba T, Shidoji Y, Fujii J, Moriwaki H, Muto Y, Suzuki T, et al. Growth suppression and induction of heat-shock protein-70 by 9-cis-ß-carotene in cervical dysplasia-derived cells. Life Sci 1997;61:83945.[Medline]
6 Okuzumi J, Nishino H, Murakoshi M, Yamane T, Kitao Y, Inagake M, et al. Palm carotene inhibits tumor-promoting activity of bile acids and intestinal carcinogenesis. Oncology 1992;49:4927.[Medline]
7
Narisawa T, Fukaura Y, Hasebe M, Ito M, Aizawa R, Murakoshi M, et al. Inhibitory effects of natural carotenoids, -carotene, ß-carotene, lycopene, and lutein, on colonic aberrant crypt foci formation in rats. Cancer Lett 1996;107:13742.[Medline]
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