NMN was first discovered in 1963 by Chambon et al. alongside discoveries of key enzymes poly-ADP-ribose and poly-ADP-ribose polymerases (PARPs)
). Shortly thereafter its role in the regulation and function of cellular energy metabolism as a precursor in NAD+ biology was well established. However, it wasn’t until more recently that supplemental upregulation of NAD+ using NMN has been examined in human clinical trials.
While it remains of significant interest in the research community there are still many questions that need to be answered before we understand the full therapeutic potential of this impressive molecule. Pharmacokinetic studies suggest that NMN administration will increase the NAD+ in blood and tissue including liver, pancreas, heart, skeletal muscles, kidney, eyes and more, within as little as 15 min. Long-term (1 year) administration at levels up to 300mg/kg was well tolerated in animal models. Human trials have suggested similar results with doses up to 1200mg being well tolerated.
Animal studies have demonstrated pleiotropic effects including anti-diabetic, neurological and cognitive effects. Supplemental improvements were seen in the following4-6, 16-20:
- Moderately increases insulin secretion, insulin sensitivity and reduces insulin resistance
- Helps decrease type 2 diabetes
- Reduces production of inflammatory molecules
- Reduces generation of reactive oxygen species (ROS)
- Helps mitochondrial function and formation of new mitochondria (mitochondrial biogenesis)
- Helps with proper expression of genes and helps with gene repair
- Improves circadian rhythm of the body including “clock gene” which is becoming important for health of the cell
- Suppresses aging-induced weight gain.
- Helps with lipid profile
- Improves skeletal muscle function
- Acts as an anti-aging molecule
- Acts as a caloric restriction mimetic
Study: The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial
What they did?
Published in 2023 this randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial assessed for safety and tolerability of NMN supplementation and its ability to improve a number of metabolic parameters that relate to aging. 80 middle-aged (40-65) healthy adults being randomized for a 60-day clinical trial with once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN. Blood NAD concentration, safety and tolerability of NMN supplementation, physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective general health assessment were all measured at 0, 30 and 60 days.
What they found:
- With no significant adverse events authors concluded it was safe and well tolerated at up to 900 mg oral daily doses
- Results of the six-minute walking test results showed an increase of distances covered during the six min for all three NMN doses
- Biological age was maintained over the 60 days in the NMN supplementation while it increased significantly in placebo during the 60-day trial
- While there was no change in the HOMA-IR
Why it matters:
The results confirmed that orally administered NMN is absorbed by the human digestive tract and into systemic circulation and quickly converted into NAD in human blood. NAD blood levels were increased in a dose dependent manner that was statistically significant up to 600mg/day while 900mg/day did not yield a significant difference. Biological age, and physical endurance were improved over the supplementation period though HOMA-IR was not statistically significant improvement in healthy populations authors suggest that examination in those with insulin dysregulation should be assessed.
Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. 2023 Feb;45(1):29-43. doi: 10.1007/s11357-022-00705-1. Epub 2022 Dec 8. PMID: 36482258; PMCID: PMC9735188.