Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40 to 65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NADΔ) was observed following NMN supplementation, with a large coefficient of variation (29.2-113.3%) within group. The increase in NADΔ was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NADΔ for the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9-20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5-16.5 nmol/L), respectively. Because of the high interindividual variability of the NADΔ after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization.

Large interindividual variability in blood NAD response to NMN supplement was observed.

The median effective dose of blood NAD concentration improvement to achieve clinically significant improvement in functional outcome and quality of life was around 15 nmol/L.

A close monitoring of NAD concentration change and personalized regimen of NMN supplements is needed.

L.Y. is an employee of Abinopharm, Inc., R.T. and Z.L. are employees of Aba Chemicals, Co.. The other authors declare no conflict of interest.

NCT04823260 in ClinicalTrials.gov, and CTRI/2021/03/032421 in Clinical Trial Registry - India.

The clinical trial is fully funded by Aba Chemicals Co. (Shanghai, China) and Abinopharm, Inc. (Connecticut, USA).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The ethical approval was obtained from the Royal Ethics Committee, Pune, India. The ethics committee is duly registered with Drugs Controller General of India (DCGI) via number - ECIV45/Indt/MII/2013/RR-19. The trial was monitored by ProRelix Services LLP, a clinical research organization (CRO), Pune, India.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data available on request from the authors.