Tarka S M
Hershey Foods Corporation, Corporate Technical Center, Hershey, Pennsylvania.
Crit Rev Toxicol. 1982;9(4):275-312. doi: 10.3109/10408448209037495.
The critical review of the literature cited on pharmacology, toxicology, metabolism, and safety assessment clearly demonstrates that cocoa per se has not attracted a great deal of scientific interest because of its long-term usage with no reported adverse effects that would be injurious to man. On the other hand, a great deal of research has been directed towards understanding the pharmacological properties of the methylxanthines--caffeine, theobromine, and theophylline. Much of the emphasis on metabolism, toxicology, teratogenic potential, and safety assessment has been on the evaluation of caffeine. In light of the serious health concerns ascribed to the effects of caffeine and the lack of basic information on theobromine and theophylline, it is imperative that a major research program be undertaken to evaluate these methylxanthines and, of course, cocoa, coffee, and tea. It only will be through elucidating their mechanism of action that we will be in a position to assess their safety. Before committing research efforts to evaluating the long-term effects of these methylxanthines and their respective foodstuffs, which serve as our primary source of exposure, it is critical to initiate more basic research on the metabolism of caffeine, theophylline, and theobromine in several animal species and man. While published reports do appear in this area, it is essential to understand fully the similarities and differences between various animals and man. The influence of dietary factors and drug interactions must also be determined. Before establishing dosage levels for a chronic toxicity study, the pharmacokinetics of the dose must be determined in the species that will be used in long-term studies. This is necessary if there is a dose-dependency in the animal above which saturation may occur and the plasma half-life kinetics change, or shifts occur either in the metabolic pathways of degradation and/or in the route of excretion from the body. The area of teratology must also be thoroughly evaluated. Studies undertaken should include identification and quantitation of the metabolites of caffeine, theophylline, and theobromine in the pregnant animal, the respective pharmacokinetics of each compound, dose-dependency (if this is the case), and their potential teratogenicity. In addition, the influence of other drugs or dietary variables must be included. In addition to teratology, a great deal of research is needed to assess and quantitate fetal and neonatal metabolism of these compounds.(ABSTRACT TRUNCATED AT 400 WORDS)
对药理学、毒理学、代谢及安全性评估方面所引用文献的批判性综述清楚地表明，由于长期食用可可且未报告对人体有害的不良反应，可可本身并未引起大量科学关注。另一方面，大量研究致力于了解甲基黄嘌呤类物质——咖啡因、可可碱和茶碱的药理特性。在代谢、毒理学、致畸潜力及安全性评估方面，大部分重点都放在了对咖啡因的评估上。鉴于人们对咖啡因影响的严重健康担忧以及关于可可碱和茶碱的基础信息匮乏，必须开展一项重大研究项目来评估这些甲基黄嘌呤类物质，当然还有可可、咖啡和茶。只有通过阐明它们的作用机制，我们才能评估其安全性。在投入研究精力评估这些甲基黄嘌呤类物质及其各自作为我们主要接触源的食品的长期影响之前，对咖啡因、茶碱和可可碱在几种动物物种及人体中的代谢开展更多基础研究至关重要。虽然该领域确实有已发表的报告，但充分了解不同动物与人体之间的异同必不可少。饮食因素和药物相互作用的影响也必须确定。在为慢性毒性研究确定剂量水平之前，必须在将用于长期研究的物种中确定该剂量的药代动力学。如果动物存在剂量依赖性，超过该剂量可能会出现饱和现象且血浆半衰期动力学发生变化，或者在降解的代谢途径和/或从体内排泄的途径中发生改变，那么这是必要的。致畸学领域也必须进行全面评估。所开展的研究应包括鉴定和定量怀孕动物体内咖啡因、茶碱和可可碱的代谢物、每种化合物各自的药代动力学、剂量依赖性（如果存在的话）及其潜在致畸性。此外，还必须包括其他药物或饮食变量的影响。除了致畸学，还需要大量研究来评估和定量这些化合物在胎儿和新生儿体内的代谢。（摘要截选至400字）
