TY - JOUR
T1 - Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults
T2 - A Physiologic Study
AU - Pencina, Karol Mateusz
AU - Valderrabano, Rodrigo
AU - Wipper, Benjamin
AU - Orkaby, Ariela R.
AU - Reid, Kieran F.
AU - Storer, Thomas
AU - Lin, Alexander P.
AU - Merugumala, Sai
AU - Wilson, Lauren
AU - Latham, Nancy
AU - Ghattas-Puylara, Catherine
AU - Ozimek, Noelle E.
AU - Cheng, Ming
AU - Bhargava, Avantika
AU - Memish-Beleva, Yusnie
AU - Lawney, Brian
AU - Lavu, Siva
AU - Swain, Pamela M.
AU - Apte, Rajendra S.
AU - Sinclair, David A.
AU - Livingston, David
AU - Bhasin, Shalender
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Context: Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Context: Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - blood pressure
KW - geroscience
KW - lipids
KW - metabolic effects
KW - muscle bioenergetics
KW - physical function
KW - β-nicotinamide mononucleotide
UR - http://www.scopus.com/inward/record.url?scp=85164393138&partnerID=8YFLogxK
U2 - 10.1210/clinem/dgad027
DO - 10.1210/clinem/dgad027
M3 - Article
C2 - 36740954
AN - SCOPUS:85164393138
SN - 0021-972X
VL - 108
SP - 1968
EP - 1980
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 8
ER -