Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study

Karol Mateusz Pencina, Rodrigo Valderrabano, Benjamin Wipper, Ariela R. Orkaby, Kieran F. Reid, Thomas Storer, Alexander P. Lin, Sai Merugumala, Lauren Wilson, Nancy Latham, Catherine Ghattas-Puylara, Noelle E. Ozimek, Ming Cheng, Avantika Bhargava, Yusnie Memish-Beleva, Brian Lawney, Siva Lavu, Pamela M. Swain, Rajendra S. Apte, David A. SinclairDavid Livingston, Shalender Bhasin

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1968-1980
Number of pages13
JournalThe Journal of clinical endocrinology and metabolism
Volume108
Issue number8
DOIs
StatePublished - Jul 14 2023

Keywords

  • blood pressure
  • geroscience
  • lipids
  • metabolic effects
  • muscle bioenergetics
  • physical function
  • β-nicotinamide mononucleotide

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