© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 12, 1016,
June 21, 2000
© 2000 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: ß-Carotene: a Miss for Epidemiology
Correspondence to: James R. Marshall, Ph.D., Arizona Cancer Center, 1515 North Campbell Ave. 2964, P.O. Box 245024, Tucson, AZ 85724-5024.
The comments of Brignall and Lamson and of Gerber et al. are most helpful. Chemoprevention recommendations must be based on multiple data sources, ranging from in vitro to in vivo animal experiments to observational studies and experiments among humans.
The cis isomer of ß-carotene found in many fruits and vegetables may indeed have superior antioxidant activity, and synthetic supplements may be mostly of trans configuration. However, the cis isomer disappears rapidly after ingestion; it has been suggested that the disappearance of this cis isomer may have to do with its being consumed in antioxidative activity (1). Other experiments among humans and other mammalian systems (2,3) suggest that most of the cis isomer is converted in the intestinal lumen to trans configuration and never reaches the bloodstream. On the other hand, cis isomer is found in tissue (3).
We are short on human-based experimental evidence, but the associations observed in observational studies could be due to isomers found in foodstuffs and not in the synthetic compound. The associations could be artifacts of a staggering array of other nutrients. Incorporating input from cellular and animal experimentation and from human observation and experimentation, as we attempt to appropriately link chemopreventive recommendations to human nutrition, will remain a serious challenge in the years ahead.
Gerber et al. propose that variance in the level of plasma ß-carotene could be determined, not just by intake, but by oxidative stress or by exposure to xenobiotics, such as trichlorobiphenyl or ethanol. In these cases, an association of plasma ß-carotene with cancer risk could be confounded by the exposure that decreases the ß-carotene. Adequate control for the exposure would eliminate the association. Imperfect measurement of that exposure, though, would render control for it inadequate; ß-carotene could appear to decrease the risk, even with adjustment for the exposure.
Disentangling these effects will require judicious and creative use of human experimental data. Epidemiology, with the measurement properties of all evaluated factors carefully monitored, may also have a role.
REFERENCES
1
Ben-Amotz A, Levy Y. Bioavailability of a natural isomer mixture compared with synthetic all-trans ß-carotene in human serum. Am J Clin Nutr 1996;63:729–34.
2 You CS, Parker RS, Goodman KJ, Swanson JE, Corso TN. Evidence of cis-trans isomerization of 9-cis-ß-carotene during absorption in humans. Am J Clin Nutr 1996;64:177–83.[Abstract]
3
Erdman JW Jr, Thatcher AJ, Hofmann NE, Lederman JD, Block SS, Lee CM, et al. All-trans ß-carotene is absorbed preferentially to 9-cis ß-carotene, but the latter accumulates in the tissues of domestic ferrets (Mustela putorius puro). J Nutr 1998;128:2009–13.
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