Melatonin Supplementation and the Metabolic Syndrome

描述(由申请人提供)：代谢综合征是一系列相互关联的代谢起源的危险因素，似乎会促进动脉粥样硬化性心血管疾病的发展，增加2型糖尿病的风险。尽管存在针对某些代谢综合征成分的强有力的药物治疗，但这些治疗并不完全有效，而且往往伴随着严重的副作用。因此，人们对寻找代谢综合征的替代治疗方法很感兴趣。这项研究计划的长期目标是寻找代谢综合征的补充和替代治疗方法。动物研究和对人类的观察数据表明，补充褪黑激素可能会对一些代谢综合征成分提供保护，包括高血糖、高血压、血脂异常和肥胖。证据还表明，具有代谢综合征成分的个体的褪黑素水平受到抑制，因此特别可能从外源性褪黑素补充中受益。然而，关于补充褪黑素改善代谢综合征成分的能力的实验数据缺乏。因此，我们建议进行一项试验性随机、双盲、安慰剂对照的交叉试验，以获得有关补充褪黑素对患有代谢综合征的成年男性和女性代谢综合征成分的影响的初步数据。我们假设补充褪黑素将安全地缓解这些受试者中的一个或多个代谢综合征成分。36名代谢综合征患者将被招募到这项研究中，通过以下具体目标来解决这一假设： 1)获得褪黑素对代谢综合征患者代谢综合征成分影响的初步数据。 2)探讨睡眠、氧化应激和炎症是否是褪黑素对代谢综合征影响的潜在机制。 3)确定在患有代谢综合征的成人患者中，连续13周每天服用褪黑素补充剂是否有任何不良副作用。 4)确定招募和保留足够数量的代谢综合征患者进行更大规模、更明确研究的可行性。研究结果将为更大规模、更明确的研究提供必要的信息。 与公共健康相关：该项目与公共健康相关，因为它将提供关于褪黑素补充剂改善代谢综合征能力的亟需数据，代谢综合征是心血管疾病和糖尿病的主要风险因素。这项研究还将提供代谢综合征患者长期使用褪黑素的安全性方面亟需的信息。

DESCRIPTION (provided by applicant): The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin that appear to promote the development of atherosclerotic cardiovascular disease and increase risk for type 2 diabetes. Although powerful pharmacological treatments for some metabolic syndrome components exist, these treatments are not entirely effective and are often associated with serious side-effects. Therefore, there is considerable interest in finding alternative treatments for the metabolic syndrome components. The broad, long-term objectives of this research program are to find complementary and alternative treatments for the metabolic syndrome. Animal studies and observational data in humans suggest that supplemental melatonin may provide protection against a number of metabolic syndrome components, including elevated glucose, elevated blood pressure, dyslipidemia, and obesity. Evidence also suggests that individuals with metabolic syndrome components have suppressed melatonin levels, and hence may be particularly likely to benefit from exogenous melatonin supplementation. However, experimental data on the ability of melatonin supplementation to improve metabolic syndrome components are lacking. Accordingly, we propose to conduct a pilot randomized, double-blind, placebo-controlled crossover trial that will obtain preliminary data about the effects of melatonin supplementation on metabolic syndrome components in adult men and women with the metabolic syndrome. We hypothesize that melatonin supplementation will safely alleviate one or more of the metabolic syndrome components in these subjects. Thirty-six metabolic syndrome patients will be recruited into the study to address this hypothesis through the following specific aims: 1) To obtain preliminary data on the effect of melatonin on metabolic syndrome components in persons with metabolic syndrome. 2) To explore whether sleep, oxidative stress, and inflammation are potential mechanisms that mediate the effects of melatonin on metabolic syndrome. 3) To determine whether melatonin supplementation has any adverse side-effects when taken daily for 13 weeks in adults with the metabolic syndrome. 4) To determine the feasibility of recruiting and retaining a sufficient number of metabolic syndrome patients for a larger, more definitive study. Result obtained from the study will provide necessary information for a larger, more definitive study. PUBLIC HEALTH RELEVANCE: This project is relevant to public health because it will provide much needed data on the ability of melatonin supplements to ameliorate the metabolic syndrome, which is a major risk factor for cardiovascular disease and diabetes. This study will also provide much needed information on the safety of long-term melatonin use in metabolic syndrome patients.