A double-blinded, randomised clinical trial revealed that NMN supplementation is associated with an increase in blood NAD concentrations, which could lead to better functional outcomes and quality of life among middle-aged and older adults.
Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which is needed in major biological processes such as cellular redox regulation and metabolism, and DNA repair. Blood NAD concentration declines with chronological age in animals and humans.
“This post-hoc analysis of a randomised, double-blinded, controlled clinical trial of NMN supplementation indicates that blood NAD concentration changes are dose-dependent but exhibit high interindividual variability,” wrote the researchers in this preprint, which is published in medRxiv but has not yet been peer-reviewed.
“The improvements associated with higher NAD concentration change were larger in measurements taken after 60 days of supplementation.”
Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. Additionally, while inter-individual variability in the increase of blood NAD after NMN supplementation has been observed in previous studies, there are no studies reporting the relationship between change in blood NAD concentration following NMN supplementation and ageing-related clinical outcomes.
Therefore, researchers did a post-hoc analysis of a clinical trial that was conducted in India. They wanted to determine a target NAD concentration improvement needed to optimise the health effects of NMN supplementation.
The study design of this clinical trial was first reported in 2021. The trial was conducted in Lotus Healthcare and Aesthetics Clinic and Sunad Ayurved in Pune, India. Generally healthy 40- to 65-year-old individuals were included in this 60-day study.
Participants were randomised into four groups receiving placebo or daily NMN supplements of 300 mg, 600 mg, and 900 mg respectively. Age, sex, BMI, blood biological age and HOMA-IR were recorded at baseline and day 60. In addition, blood NAD concentration, 6-minute walk test, and 36-item short-form survey (SF36) scores were measured at baseline, 30 days, and 60 days.
The researchers found that NMN supplementation could improve blood NAD concentration but observed that individual responses to the effects of NMN varied greatly.
“A significant dose-dependent increase in NAD concentration change was observed following NMN supplementation, with a large coefficient of variation (29.2–113.3%) within group. The increase in NAD concentration change was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score,” wrote the researchers.
The results showed that 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.
However, due to the varied response rates to the effects of NMN, the researchers recommended monitoring changes in blood NAD concentration, and that a personalised dosage for NMN supplementation should be administered as needed.
“The median effect dose of NAD concentration change 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 NAD concentration change after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalised dosage regimens and optimising NMN utilisation,” concluded the researchers.
However, they said that further studies on personalised NAD precursor supplements and optimal blood NAD concentration are needed.
“It is important to note that no established guideline for an optimal therapeutic window of blood NAD concentration exists, thus closer monitoring of blood NAD for a longer follow-up duration is needed in future studies. All results have to be treated with caution due to the relatively small sample size.
“Factors that could influence baseline NAD concentrations should be taken into account in future larger trials,” said the researchers.
Source: MedRxiv
DOI: https://www.medrxiv.org/content/10.1101/2024.02.19.24303025v1
“Towards personalized nicotinamide mononucleotide (NMN) supplementation: nicotinamide adenine dinucleotide (NAD) concentration”
Authors: Ajla Hodzic Kuerec, Weilan Wang et al.
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