Levels of nicotinamide adenine dinucleotide (NAD) are relevant to mitochondrial function and decline with age for reasons that are only partially explored. Proximate causes are well outlined, the faltering of salvage and synthesis pathways due to lower levels of necessary molecules, but the connections to deeper causes of aging remain to be mapped. When it comes to NAD+ upregulation via vitamin B3 derivatives, boosting the operation of those pathways, there is more human data for nicotinamide riboside (NR) than for nicotinamide mononucleotide (NMN), so it is interesting to see the trial data here. It remains a question as to whether approaches that upregulate NAD are worth pursuing, given that they don't appear be any better than regular exercise programs at raising NAD levels, and the clinical trial data that assessed actual benefits to patients is very mixed.
It has been widely reported that mammalian intracellular NAD levels decrease significantly during aging and the decline has profound impact on aging related health issues. β-Nicotinamide mononucleotide (NMN) supplementation as a precursor to boost intracellular NAD has proven highly effective and safe in many animal studies. However, only limited number of human clinical trials have been done on NMN.
This randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent human clinical trial was done at two clinical centers in Pune, India. 84 healthy middle-aged and older adults (40 - 65 years old) of both males and females were screened. 80 were recruited, randomized, and stratified in 1:1:1:1 ratio for a 60-day clinical study with once daily oral dosing of placebo, 300mg, 600mg, and 900mg NMN which were dispensed and monitored by principal investigators at the clinical centers.
Blood intracellular NAD levels were found statistically significantly increased among all NMN treated groups. The mean percentage increases of blood cellular NAD levels over baselines at day 30 were 21.20%, 151.70%, 390.70%, and 312.82% for placebo, 300mg, 600mg, and 900mg respectively while at day 60, the increases were 45.10%, 175.80%, 470.30%, and 364.31% for placebo, 300mg, 600mg, and 900mg respectively. The similar results were observed with the distances in six-minute walking test for physical endurance assessment. The mean percentage increases of the distance walked in six minutes over baselines were -4.56%, 13.88%, 38.10%, and 31.48% at day 30 and 1.60%, 23.64%, 50.18%, and 48.4% at day 60 for placebo, 300mg, 600mg, and 900mg respectively.