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females, respectively, and represented human intakes of greater than 50 times the theobromine consumption from all chocolate sources at the 90th percentile. The incidence of bilateral diffuse testicular atrophy was increased and spermatogenesis was decreased in male rats fed 5% cocoa. These effects were not unexpected based on previous work, which showed that the testes are a target organ for methylxanthine effects (90).
Several reviews of the reproductive effects of the methylxanthines are available (19, 23, 81, 91). Since the methylxanthines readily cross the placental barrier, exposure begins during gestation. Tests in rats and mice showed birth defects in mice from high doses of caffeine (the human equivalent of 40 cups of coffee at one time); however, there is no scientific evidence linking caffeine with similar abnormalities in humans. Daily caffeine consumption of greater than 300 mg during pregnancy has been associated with reduced birth weights, premature births and spontaneous abortions in some studies; however, study results have been inconsistent and causality has not been established (81, 9294). The FDA has evaluated the scientific evidence on caffeine and concluded that caffeine does not adversely affect reproduction in humans. Nevertheless, pregnant women are advised to consume caffeine in moderation.
Comprehensive studies of cocoa and theobromine revealed no frank teratogenic or embryotoxic effects, although there was delayed calcification of fetal bone at dietary levels of 0.135% theobromine in rats and 0.125% theobromine in rabbits (83, 84). As mentioned previously, the testes have been identified as a target organ in methylxanthine studies in animals. Dietary concentrations of 0.6% theobromine for 4 weeks resulted in testicular atrophy in rats (95). Due to the link between methylxanthine intake and testicular atrophy, Hostetler et al. (86) evaluated the effects of cocoa (which contains both theobromine and caffeine) on reproductive function in rats in a conventional multi-generation exposure study. Continuous exposure to dietary cocoa in rats, providing up to 104 and 126 mg/kg/day of total methylxanthines to males and females, respectively, had no consistent effect on reproductive function over three generations. Based on these results, it is unlikely that consumption of cocoa and cocoa-based products has any potential to adversely affect reproductive capacity in humans.
Fibrocystic breast disease is a catch-all term used to describe fibrocystic changes or benign fibrous lumps in the breast. It is found in more than 50% of women and is believed by some to be a risk factor for breast cancer (37). Women often are advised to abstain from coffee, cola drinks, tea and chocolate to minimize aggravation of this condition. This recommendation is largely based on two
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