NAD(+) Intermediates: The Biology and Therapeutic Potential of NMN and NR

NAD(+) Intermediates: The Biology and Therapeutic Potential of NMN and NR


Research on NAD+ biology has gained significant momentum, shedding light on age-associated decline and diseases. Two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied and offer exciting prospects for preventive and therapeutic interventions.

Unraveling NAD+ Metabolism:

  • Historical Background:

    NAD+ was discovered in 1906 and its role in redox reactions and NAD+ biosynthesis was gradually uncovered.

  • Key Discoveries:

    The discovery of NMN and NMNAT in the 1960s and 2000s, respectively, led to further research in NAD+ biology.

  • Dietary Sources:

    NR and NMN are present in daily foods and human milk.

  • Age-Related NAD+ Decline:

    NAD+ levels decline with age and contribute to age-associated pathophysiologies.

Therapeutic Potential of NR and NMN:

  • Pharmacokinetics and Metabolic Fate:

    The pharmacokinetics and metabolic fates of NMN and NR are still being investigated.

  • Tissue-Specific Behavior:

    NMN and NR exhibit distinct behavior, and their fates depend on tissue distribution and expression levels of NAD+ biosynthetic enzymes, nucleotidases, and transporters.

  • Proposed Concept:

    A comprehensive concept connecting NAD+ metabolism to aging and longevity in mammals has been proposed.

  • Translation to Human Health:

    The stage is set to test whether the promising preclinical results can be translated to improve human health.

Therapeutic Efficacy of NMN:

  • Administration and Effects:

    NMN administration improves age-associated pathophysiologies in various tissues and shows efficacy in diseases such as diabetes, neurodegenerative disorders, and kidney injury.

  • Safety and Tolerance:

    Long-term oral administration of NMN has shown to be safe and well-tolerated in mice.

Therapeutic Efficacy of NR:

  • Supplementation Impact:

    NR boosts NAD+ levels beyond conventional B vitamin metabolism.

  • Metabolic Benefits:

    NR supplementation has shown efficacy in improving metabolic health, muscle disorders, liver health, and nervous system function.

  • Therapeutic Potential:

    NR holds promise as a therapeutic strategy for overall health improvement and treatment of various conditions.

Comparing NMN and NR:

  • Benchmarks Yet to be Conducted:

    Head-to-head comparisons between NMN and NR effects across pathophysiological conditions have not been conducted.

  • Unknown Mechanisms:

    The downstream mechanisms mediating the beneficial effects of NAD+ supplementation are still unclear.

Pharmacokinetics of NMN and NR:

  • NMN Uptake and Distribution:

    NMN rapidly appears in plasma and target tissues after administration, with unclear cellular uptake mechanisms.

  • NR Metabolism:

    NR is likely converted into nicotinamide before tissue uptake.

  • Distinct Behavior:

    NMN and NR exhibit different in vivo behavior and kinetics, requiring further investigation.

The NAD World Concept and Beyond:

  • Systemic Regulatory Mechanism:

    The "NAD World" concept proposes a systemic regulatory mechanism for aging and longevity control, with NMN and NR as key components.

  • Revisiting Subcellular Compartments:

    The compartmentalization of NAD+ biosynthesis is being questioned, with potential distinct machinery in different subcellular compartments.

  • Towards Breakthroughs:

    Exciting developments in NAD+ biology offer new opportunities for breakthroughs and effective interventions in humans.


The research on NAD+ biology and its intermediates NR and NMN provides promising avenues for combating age-associated decline and diseases. With ongoing investigations and clinical trials, potential therapeutic applications of NMN and NR are being explored, bringing hope for improved human health in the future.

Note: The manuscript is still undergoing editing and proofreading before final publication. The authors have stated that they have no competing financial interests.

Title of paper: NAD(+) Intermediates: The Biology and Therapeutic Potential of NMN and NR

Author(s): Yoshino J, Baur JA, Imai SI.

Year published: 2018

Published in: Cell Metab

Original article can be found here.

Back to blog

Looking For A 99% Pure NMN Supplement?

Reversal NMN is tested and verified by a third party lab. Trusted by many. Delivered worldwide via DHL Express.

Frequently Asked Questions (FAQ'S)