Smoliga James M, Colombo E Sage, Campen Matthew J
Institute for Human Health and Sports Science Research, Department of Physical Therapy, High Point University, High Point, NC 27262, USA.
Aging (Albany NY). 2013 Jul;5(7):495-506. doi: 10.18632/aging.100579.
In recent years, the wealth of basic science research supporting resveratrol's potential to treat, delay, and even prevent age-related chronic diseases has led to a number of human clinical trials. While such translational research has yielded promising results in clinical populations, recently published conflicting results from studies evaluating resveratrol's potential for primary prevention of chronic disease in healthy / asymptomatic individuals have generated considerable controversy and do not initially appear consistent with findings from animal models. We argue that trials targeting healthy humans are often fundamentally flawed owing to inappropriate use of paradigms only applicable to populations with overt clinical disease and the consequent misleading (typically negative) results can severely retard advancement of drug development. To appropriately perform translational research centered on resveratrol as a primary prevention agent in non-clinical populations, it is critical to utilize study designs which can provide adequate information on clinically relevant outcome measures, avoid paradigms and assumptions from interventions which are specific to clinical populations, and maintain realistic expectations compared to interventions which provide the theoretical maximal response (e.g., caloric restriction and aerobic exercise training).
近年来，大量基础科学研究表明白藜芦醇具有治疗、延缓甚至预防与年龄相关的慢性疾病的潜力，这引发了多项人体临床试验。虽然这类转化研究在临床人群中取得了有前景的结果，但最近发表的关于评估白藜芦醇在健康/无症状个体中对慢性病一级预防潜力的研究结果相互矛盾，引发了相当大的争议，且乍一看与动物模型的研究结果不一致。我们认为，针对健康人的试验往往存在根本性缺陷，因为不恰当地使用了仅适用于有明显临床疾病人群的范式，由此产生的误导性（通常为阴性）结果可能会严重阻碍药物研发的进展。要以白藜芦醇作为非临床人群一级预防药物进行适当的转化研究，关键是要采用能够提供有关临床相关结局指标充分信息的研究设计，避免采用针对临床人群干预措施的范式和假设，并与能提供理论最大反应的干预措施（如热量限制和有氧运动训练）相比保持现实的期望。
