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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 Sinclair, David Livingston, Shalender Bhasin
The Journal of Clinical Endocrinology & Metabolism 2023 108(8):1968-1980

Bibliography

PubMed
PMID 36740954
PubMed Central
PMC11491622
Funding
Supported by Metro International Biotech and academic aging-research infrastructure including the Boston Claude D. Pepper Older Americans Independence Center.
Competing interests
The study used MIB-626 from Metro International Biotech, and several authors had employment, financial, advisory, patent, or research relationships relevant to Metro International Biotech or NAD/NMN commercialization.

Study snapshot

DesignSingle-center, randomized, double-blind, placebo-controlled, parallel-group physiologic study with concealed block randomization, stratified by sex, and 2:1 allocation.
ModelOverweight or obese adults aged 45 years or older.
Sample30 randomized in a 2:1 ratio: 21 to MIB-626 and 9 to placebo. Two randomized participants did not complete the study; all 30 randomized participants were included in the intent-to-treat analyses.
InterventionMIB-626 microcrystalline β-NMN 1000 mg twice daily (2000 mg/day) versus placebo.
Duration28 days.
EndpointsCirculating NAD+ and NAD metabolome; Body weight; Blood pressure; Lipids; Insulin sensitivity; Liver and intra-abdominal fat; Muscle performance and bioenergetics; Safety

What the study showed, in plain terms

Thirty overweight or obese middle-aged and older adults received 2,000 mg/day MIB-626 or placebo for 28 days. The formulation substantially increased circulating NAD+ and related metabolites.

Compared with placebo, the MIB-626 group had larger short-term reductions in body weight, diastolic blood pressure and several cholesterol measures. Insulin sensitivity, liver and abdominal fat, muscle strength, fatigability and aerobic measures did not show comparable between-group improvements. The study was small and industry-linked, so the cardiometabolic findings need independent replication.

Key findings

  • MIB-626 substantially increased circulating NAD+ and NAD-related metabolites.
  • Body weight fell more in the MIB-626 group than placebo over 28 days.
  • Diastolic blood pressure and total, LDL and non-HDL cholesterol decreased more with MIB-626.
  • Insulin sensitivity, liver/intra-abdominal fat and several muscle-performance outcomes did not significantly differ between groups.
  • Adverse-event rates were similar between groups.

What this study can and cannot tell us

The trial enrolled only 30 people and lasted four weeks. Multiple physiologic outcomes were assessed, increasing the importance of replication. The tested product was a pharmaceutical-grade microcrystalline NMN formulation, so findings should not automatically be generalized to retail NMN supplements. Industry relationships were substantial.

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