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reported (75). The effects of caffeine on strength are variable, and may be related to sensitivity differences based on muscle type. Other studies suggested that caffeine enhances endurance in submaximal, long-term exercises including cross-country skiing, cycling and running (7580). Subjects consuming caffeine before exercise generally increased their total work output and time to exhaustion (76, 77, 80). Numerous other studies failed to demonstrate any significant effects. These inconsistent results suggest that caffeine's effects may be mediated by other variables including training, dietary patterns, type of exercise and prior use of caffeine.

Other Health-Related Effects

Public concern with the safety and health-related effects of the methylxanthines has grown over the last 2030 years. Much of the public concern originated in the early 1970s as a result of the Food and Drug Administration's (FDA's) directive to re-examine the safety of food additives that were generally recognized as safe (GRAS), including caffeine. In 1978, the Select Committee on GRAS Substances issued its report in which the world's scientific literature on the health aspects of caffeine was reviewed (81). Although the attention focused on the safety of dietary caffeine, questions were also raised concerning the safety of theobromine due to its structural similarity to caffeine.

To address these questions, the major worldwide producers of chocolate initiated a comprehensive toxicological testing program on theobromine and cocoa. The program included a comprehensive review of the literature (19) as well as studies to determine the acute toxicity (19), genotoxicity (82), teratogenicity (83, 84), carcinogenicity (85) and reproductive effects (86).

Toxicity/Carcinogenicity

Median lethal dose (LD50) values of 200 mg/kg for caffeine and 950 mg/kg for theobromine have been determined in the rat (19, 81). The structural differences in these two compounds and the resulting absorption kinetics may account for the variation in LD50 values (19). In humans, the fatal oral dose of caffeine is estimated to be 10 g (28). However, deaths from caffeine overdoses are rare, since gastric irritation and vomiting typically occur before toxic amounts are absorbed (87, 88). Reports of toxicity are associated with consumption of caffeine-containing medications (87, 89); there are no reports of acute toxicity from caffeine ingested in foods and beverages (45).

There are even fewer reports on the toxicological effects of theobromine and cocoa. In rats fed up to 5% cocoa in the diet for 104 weeks, no evidence of chronic toxicity or carcinogenicity was observed (85). This cocoa level provided a methylxanthine intake of 60 and 75 mg/kg body weight/day for males and

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