Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

NMN Supplementation Shows Promise for Aging-related Disorders: Study

Introduction: Nicotinamide mononucleotide (NMN), a compound that increases nicotinamide adenine dinucleotide (NAD+) levels, has shown potential in mitigating aging-related disorders, according to preclinical studies. However, limited human data exists regarding the effects of NMN supplementation on NAD+ levels. In a recent study, researchers investigated the effects of chronic NMN supplementation on blood NAD+ levels and physiological dysfunctions in healthy older individuals. The findings shed light on the potential benefits of NMN in preventing aging-related muscle dysfunctions.

Study Overview:

  • Study Design: A placebo-controlled, randomized, double-blind, parallel-group trial was conducted with aged men who were given 250mg of NMN per day for either 6 or 12 weeks.
  • Safety and Tolerance: NMN supplementation was well tolerated with no significant negative effects reported.
  • Increased NAD+ Levels: Metabolomic analysis of whole blood samples showed that NMN supplementation significantly increased NAD+ and NAD+ metabolite concentrations.
  • Motor Function Improvements: Nominal improvements in gait speed and left grip test performance were observed, suggesting potential benefits for muscle strength. Further validation is required in larger studies.
  • No Effects on Body Composition: NMN supplementation had no significant effects on body composition in older individuals.
  • Potential therapeutic strategy: Chronic oral NMN supplementation may be effective for preventing aging-related muscle dysfunctions in humans, providing a possible therapeutic avenue.

The Importance of NAD+ and NMN:

  • Aging and Diseases: Aging is a risk factor for various diseases, making it important to prevent physiological decline associated with aging.
  • NAD+ and Aging: Decreased NAD+ levels have been closely linked to aging and age-related diseases.
  • Animal studies: Animal studies have demonstrated that administering intermediate NAD+ metabolites like NMN can increase NAD+ concentrations, improve health, and extend lifespan.
  • NAD+ precursors: NAD+ metabolites like NMN and nicotinamide riboside (NR) have been studied in clinical trials.
  • Dietary Sources: While NR is found in milk, NMN is found in foods such as edamame, broccoli, and meat but in low concentrations.
  • Clinical Trials: Purified and concentrated forms of NR and NMN have been used in clinical trials, with NR showing safety and elevation of NAD+ or NAD+-related metabolites in the blood.
  • Recent Studies: Recent studies have reported the safety and positive effects of NMN supplementation, such as increased muscle insulin sensitivity and improved aerobic capacity during exercise.

Study Details:

  • Study Population: The study enrolled 42 healthy older men, with 8 participants excluded due to medical history or abnormal laboratory data and 5 participants excluded for other clinical trials or withdrawal.
  • Randomized Treatment Groups: Participants were randomized into either the placebo group or the 250mg NMN/day group.
  • Safety and Tolerance: NMN supplementation (250mg/day) for 12 weeks was well-tolerated with no serious adverse events reported.
  • Increased NAD+ Levels: NMN effectively increased NAD+ and NAD+-related metabolite levels in whole blood.
  • Motor Function Improvements: NMN supplementation partly improved motor functions, including gait speed and left grip strength.
  • No Effects on Body Composition: NMN had no significant effect on skeletal muscle mass, fat mass, insulin sensitivity, or other metabolic parameters.
  • Other Measures: NMN did not significantly affect audibility, vascular functions, or cognitive function.

Conclusion: Chronic oral supplementation of NMN appears safe and effective for boosting NAD+ metabolism in healthy older men. NMN supplementation may lead to improvements in muscle strength and performance, which are important clinical indicators of aging. The study suggests that NMN may be a potential therapeutic strategy for aging-related disorders, such as sarcopenia. However, further research is required to fully understand the mechanisms and validate the results.

Study Details and Analysis:

  • Ethical Consideration: The study followed the guidelines of the Declaration of Helsinki and was approved by the University of Tokyo Research Ethics Committee.
  • Study Design: The trial was conducted as a placebo-controlled, randomized, double-blind, parallel-group trial.
  • Participant Recruitment: Sixty-five healthy Japanese male participants over the age of 65 were recruited, with specific criteria for inclusion and exclusion.
  • Safety Monitoring: Adverse events were monitored throughout the study, and participants were instructed to report any difficulties or problems.
  • Measurements and Tests: Laboratory measurements included blood tests for various parameters, body composition analysis, physical function tests, and audiology and cognition evaluations.
  • Statistical Analysis: Mixed-model analysis, t-tests, Mann-Whitney U tests, and ANCOVA were employed for statistical analysis.

Supplementary Information and Reporting Summary:

  • Supplementary Information: Additional materials related to the main content, providing extra details or data that support the study, are available in PDF format (195K).
  • Reporting Summary: A larger PDF (1.4M) is provided as a summarized overview of the main document's key findings or results. Both the supplementary information and reporting summary can be referenced for further exploration.

Title of paper: Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

Author(s): Igarashi M, Nakagawa-Nagahama Y, Miura M, Kashiwabara K, Yaku K, Sawada M, Sekine R, Fukamizu Y, Sato T, Sakurai T, Sato J, Ino K, Kubota N, Nakagawa T, Kadowaki T, Yamauchi T.

Year published: 2022

Published in: NPJ Aging

Original article can be found here.

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