A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects
A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects
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DOI：
10.1093/ajcn/nqy132
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发表时间：
2018-08-01
影响因子：
7.1
通讯作者：
Jessen, Niels
中科院分区：
文献类型：
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作者：
Dollerup, Ole L.;Christensen, Britt;Jessen, Niels
背景：动物研究表明，烟酰胺核苷(NR)对肥胖和2型糖尿病模型的胰岛素敏感性和肝脏脂肪变性有积极作用。NR是一种NAD(+)前体，是维生素B-3家族的成员，现在可以作为非处方补充剂使用。尽管来自临床前试验的数据看起来是一致的，但潜在的效果和安全性还需要在人类临床试验中进行评估。目的：本研究的目的是测试饮食中补充NR在12wk周期内的安全性，以及在肥胖、胰岛素抵抗男性中改善胰岛素敏感性和其他代谢参数的可能性。设计：在一项由研究者发起的随机、安慰剂对照、双盲、平行分组设计的临床试验中，40名健康、久坐的男性的体重指数(BMI)和GT；30 kg/m(2)，年龄40-70岁，随机分为两组，每组12 wk，每日2次，每次1000 mg。我们通过高胰岛素正血糖钳夹技术和间接量热法以及氚葡萄糖和棕榈酸酯标记的底物来确定补充NR对胰岛素敏感性的影响。采用全身双能X线骨密度仪(DXA)和核磁共振扫描仪(MRI)测定大鼠的体成分和脂肪质量分布，用磁共振光谱仪测定肝内脂肪含量。结果：补充NR不能改善大鼠的胰岛素敏感性、内源性葡萄糖的生成、葡萄糖的代谢和氧化。类似地，补充NR对静息能量消耗、脂肪分解、脂质氧化或身体成分没有影响。结论：补充剂量为2000 mg/d的12wk的NR是安全的，但不能改善肥胖、胰岛素抵抗男性的胰岛素敏感性和全身糖代谢。
Background: Animal studies suggest a positive role for nicotinamide riboside (NR) on insulin sensitivity and hepatic steatosis in models of obesity and type 2 diabetes. NR, an NAD(+) precursor, is a member of the vitamin B-3 family now available as an over-the-counter supplement. Although data from preclinical trials appear consistent, potential effects and safety need to be evaluated in human clinical trials.Objective: The aim of this study was to test the safety of dietary NR supplementation over a 12-wk period and potential to improve insulin sensitivity and other metabolic parameters in obese, insulin-resistant men.Design: In an investigator-initiated randomized, placebo-controlled, double-blinded, and parallel-group designed clinical trial, forty healthy, sedentary men with a body mass index (BMI) > 30 kg/m(2), age-range 40-70 y were randomly assigned to 12 wk of NR (1000 mg twice daily) or placebo. We determined the effects of NR supplementation on insulin sensitivity by a hyperinsulinemic euglycemic clamp and substrate metabolism by indirect calorimetry and labeled substrates of tritiated glucose and palmitate. Body composition and fat mass distribution were determined by whole-body dual-energy X-ray absorptiometry (DXA) and MRI scans, and measurements of intrahepatic lipid content were obtained by MR spectroscopy.Results: Insulin sensitivity, endogenous glucose production, and glucose disposal and oxidation were not improved byNR supplementation. Similarly, NR supplementation had no effect on resting energy expenditure, lipolysis, oxidation of lipids, or body composition. No serious adverse events due to NR supplementation were observed and safety blood tests were normal.Conclusion: 12 wk of NR supplementation in doses of 2000 mg/d appears safe, but does not improve insulin sensitivity andwhole-body glucose metabolism in obese, insulin-resistant men.