Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
J Clin Endocrinol Metab. 2023 Jul 14;108(8):1968-1980. doi: 10.1210/clinem/dgad027.
Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases.
We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions.
Thirty overweight or obese adults, ≥ 45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics.
Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference -1.9 [-3.3, -0.5] kg, P = .008); diastolic blood pressure (difference -7.01 [-13.44, -0.59] mmHg, P = .034); total cholesterol (difference -26.89 [-44.34, -9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (-18.73 [-31.85, -5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group.
MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults.
烟酰胺腺嘌呤二核苷酸 (NAD) 水平随年龄的增长而下降，并且 NAD 的年龄相关性下降被认为是与年龄相关疾病的原因。
我们评估了通过给予其前体 β-烟酰胺单核苷酸 (MIB-626，Metro International Biotech，伍斯特，MA) 来增加 NAD 的安全性和生理效应，该药物用于有发生与年龄相关疾病风险的成年人。
30 名超重或肥胖成年人，年龄≥45 岁，按 2:1 的比例随机分为 2 组，分别每天服用 2 次 MIB-626 片剂，每次 2 片，每片含有 500mg 微晶 β-烟酰胺单核苷酸或安慰剂，共 28 天。研究结果包括安全性；NAD 及其代谢产物；体重；肝、肌肉和腹内脂肪；胰岛素敏感性；血压；血脂；身体机能和肌肉生物能量学。
两组之间的不良事件相似。MIB-626 治疗可显著增加循环中 NAD 及其代谢产物的浓度。体重（差值-1.9[-3.3，-0.5]kg，P=0.008）；舒张压（差值-7.01[-13.44，-0.59]mmHg，P=0.034）；总胆固醇（差值-26.89[-44.34，-9.44]mg/dL，P=0.004），低密度脂蛋白（LDL）胆固醇（差值-18.73[-31.85，-5.60]mg/dL，P=0.007），而非高密度脂蛋白胆固醇在 MIB-626 组比安慰剂组显著降低。MIB-626 组的肌肉力量、肌肉疲劳性、有氧能力和爬楼梯能力的变化与安慰剂组相比没有显著差异。两组胰岛素敏感性和肝内及腹内脂肪均无变化。
在超重或肥胖、中年和老年成年人中给予 MIB-626 可安全地增加循环 NAD 水平，并显著降低总 LDL 和非-HDL 胆固醇、体重和舒张压。这些数据为更大规模的试验提供了依据，以评估增加 NAD 在改善老年人心脏代谢结局方面的疗效。
