Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, TX;
Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, TX.
Am J Clin Nutr. 2017 Aug;106(2):675-683. doi: 10.3945/ajcn.117.152520. Epub 2017 Jun 21.
l-Methionine (Met) is an essential amino acid for humans and is important for protein synthesis and the formation of polyamines and is involved in the synthesis of many metabolites, including homocysteine. Free-Met supplements have been claimed to have multiple positive effects; however, it remains unclear what the exact tolerance level is. With aging, Met metabolism changes, and increased plasma homocysteine is more apparent. High plasma concentrations of homocysteine are assumed to be associated with a high risk of developing atherosclerosis. We estimated the no-observed-adverse-effect level (NOAEL) and the lowest-observed-adverse-effect level (LOAEL) of supplemented, oral, free Met in healthy older adults by examining the increase in plasma homocysteine as the primary determinant. We provided capsules with free Met to 15 healthy older adult subjects for 4 wk at climbing dosages of, on average, 9.2, 22.5, 46.3 and 91 mg · kg body weight · d with washout periods of 2 wk between each intake. Before, at 2 and 4 wk during, and 2 wk after each dosage, we studied a complete panel of biochemical blood variables to detect possible intolerance to increased Met intake. Plasma homocysteine and body composition were measured, and tolerance, quality of life, and cognitive function were assessed via questionnaires. Plasma homocysteine was elevated with the highest dose of supplemented Met. The estimated NOAEL of supplemented Met was set at 46.3 mg · kg body weight · d, and the estimated LOAEL of supplemented Met was set at 91 mg · kg body weight · d (on the basis of the actual intakes) in subjects independent of sex. No signs of intolerance were observed via questionnaires or other blood variables at the LOAEL. There were no meaningful changes in body composition. On the basis of plasma homocysteine, the NOAEL of supplemented Met intake is 46.3 and the LOAEL is 91 mg · kg body weight · d in healthy older adults. Both the NOAEL and LOAEL are not associated with meaningful effects on health and wellbeing. This trial was registered at clinicaltrials.gov as NCT02566434.
l-蛋氨酸（Met）是人体必需的氨基酸，对蛋白质合成和多胺的形成很重要，参与许多代谢物的合成，包括同型半胱氨酸。游离 Met 补充剂据称具有多种积极作用，但确切的耐受水平尚不清楚。随着年龄的增长，Met 代谢发生变化，血浆同型半胱氨酸水平升高更为明显。高血浆同型半胱氨酸浓度被认为与动脉粥样硬化风险增加有关。我们通过检查血浆同型半胱氨酸的增加作为主要决定因素，估计健康老年人口服补充游离 Met 的无观察不良效应水平（NOAEL）和最低观察不良效应水平（LOAEL）。我们为 15 名健康老年人提供了含有游离 Met 的胶囊，连续 4 周，剂量逐渐增加，平均每天 9.2、22.5、46.3 和 91mg·kg 体重·d，每次摄入之间有 2 周的洗脱期。在每个剂量前、2 周和 4 周期间以及每个剂量后 2 周，我们研究了一整套生化血液变量，以检测对增加 Met 摄入的可能不耐受。测量血浆同型半胱氨酸和身体成分，并通过问卷评估耐受性、生活质量和认知功能。随着补充 Met 的最高剂量，血浆同型半胱氨酸升高。补充 Met 的估计 NOAEL 设定为 46.3mg·kg 体重·d，补充 Met 的估计 LOAEL 设定为 91mg·kg 体重·d（基于实际摄入量），在独立于性别的受试者中。在 LOAEL 下，通过问卷或其他血液变量未观察到不耐受迹象。身体成分没有明显变化。基于血浆同型半胱氨酸，健康老年人补充 Met 摄入的 NOAEL 为 46.3mg·kg 体重·d，LOAEL 为 91mg·kg 体重·d。NOAEL 和 LOAEL 均与健康和福祉的有意义影响无关。该试验在 clinicaltrials.gov 上注册为 NCT02566434。
