Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Medical Research Laboratory, Department of Clinical Medicine.
Am J Clin Nutr. 2018 Aug 1;108(2):343-353. doi: 10.1093/ajcn/nqy132.
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.
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.
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/m2, 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.
Insulin sensitivity, endogenous glucose production, and glucose disposal and oxidation were not improved by NR 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.
12 wk of NR supplementation in doses of 2000 mg/d appears safe, but does not improve insulin sensitivity and whole-body glucose metabolism in obese, insulin-resistant men. This trial was registered at clinicaltrials.gov as NCT02303483.
动物研究表明，烟酰胺核糖（NR）在肥胖和 2 型糖尿病模型中对胰岛素敏感性和肝脂肪变性具有积极作用。NR 是 NAD+的前体，属于维生素 B-3 家族，现在作为非处方药供应。尽管来自临床前试验的数据似乎一致，但仍需要在人体临床试验中评估其潜在作用和安全性。
本研究旨在测试在 12 周内补充 NR 的安全性，并评估其对肥胖、胰岛素抵抗男性胰岛素敏感性和其他代谢参数的潜在改善作用。
在一项由研究者发起的随机、安慰剂对照、双盲、平行组设计的临床试验中，40 名健康、久坐的男性，BMI>30kg/m2，年龄在 40-70 岁之间，随机分为 12 周的 NR（每天两次 1000mg）或安慰剂组。我们通过高胰岛素-正常血糖钳夹来确定 NR 补充对胰岛素敏感性的影响，并通过间接热量测定和氚标记葡萄糖和棕榈酸的示踪底物来测定底物代谢。全身双能 X 射线吸收法（DXA）和磁共振成像（MRI）扫描用于测定身体成分和脂肪质量分布，磁共振波谱（MRS）用于测定肝内脂质含量。
NR 补充并未改善胰岛素敏感性、内源性葡萄糖生成、葡萄糖摄取和氧化。同样，NR 补充对静息能量消耗、脂肪分解、脂质氧化或身体成分也没有影响。没有因 NR 补充而导致的严重不良事件，安全性血液检查正常。
每天 2000mg 的 NR 补充剂量为 12 周似乎是安全的，但不能改善肥胖、胰岛素抵抗男性的胰岛素敏感性和全身葡萄糖代谢。本试验在 clinicaltrials.gov 上注册为 NCT02303483。
