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NMN and NR: Research Progress and Application Value of NAD+ Precursors in Anti-Aging

Views: 1000     Author: Lin LIU     Publish Time: 2025-09-25      Origin: Site

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NMN and NR: Research Progress and Application Value of NAD+ Precursors in Anti-Aging

In the research on anti-aging mechanisms, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), as key precursor substances of nicotinamide adenine dinucleotide (NAD+), have become research hotspots in the field of life sciences in recent years due to their ability to exert physiological functions by regulating intracellular NAD+ levels. Based on published clinical and basic research findings, this article systematically elaborates on the mechanisms of action, food sources, and safety of NMN and NR, providing scientific references for research and applications in relevant fields.


1. Core Mechanism: The Key Role of NAD+ in Cellular Physiological Functions

As a widely existing redox coenzyme in human cells, NAD+ participates in thousands of biological catalytic reactions and serves as a core molecule for energy metabolism and cellular homeostasis maintenance. Its physiological functions are mainly reflected in three aspects:
  • Energy Metabolism Regulation: In the processes of glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation, NAD+ acts as an electron carrier to mediate the energy conversion of carbohydrates, fats, and proteins in food, generating adenosine triphosphate (ATP) that can be directly utilized by cells, thus providing an energy basis for cellular activities;

  • Mitochondrial Function Maintenance: NAD+ can activate the sirtuin protein family, promote mitophagy and functional repair, maintain the structural integrity of mitochondria, and thereby ensure the efficiency of cellular energy supply;

  • DNA Damage Repair: By activating repair-related enzymes such as poly (ADP-ribose) polymerase (PARP), NAD+ participates in the recognition and repair of intracellular DNA damage, reduces DNA mutations caused by environmental stress (e.g., radiation, oxidative stress), and maintains the normal proliferation and differentiation of cells.


Studies have shown that with aging and the impact of unhealthy lifestyles (e.g., high-sugar diet, chronic stress), intracellular NAD+ levels in the human body show a progressive decline, and the activity of NAD+-consuming enzymes (e.g., CD38, PARP) increases, further accelerating NAD+ depletion. This imbalance of NAD+ homeostasis is closely associated with age-related physiological dysfunction and the occurrence of diseases, including neurodegenerative diseases (e.g., Alzheimer's disease), metabolic diseases (e.g., diabetes), cardiovascular diseases, eye diseases, and even mental disorders.


It should be specially noted that due to its molecular structural characteristics, NAD+ cannot be directly absorbed through oral administration or across cell membranes, so it cannot be used as a direct supplement. Therefore, supplementing NAD+ precursor substances has become the core strategy to increase intracellular NAD+ levels, and NMN and NR are the two most well-studied natural precursors.


2. Physiological Functions and Research Evidence of NMN and NR

Both NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are naturally occurring NAD+ precursor compounds that can be converted into NAD+ through different metabolic pathways, thereby exerting the following physiological effects. Relevant conclusions have been confirmed by multiple basic and clinical studies:
  • Increasing NAD+ Levels and Ameliorating Age-Related Physiological Decline: In model organisms such as yeast, nematodes, and mice, supplementation with NMN or NR can significantly increase NAD+ levels in tissues and organs, extend biological lifespan, improve physiological indicators such as motor ability and cognitive function in elderly individuals, and alleviate physiological decline;

  • Metabolic Disease Intervention: Preclinical studies have shown that NMN can promote insulin secretion from pancreatic β-cells, improving insulin resistance, diabetes, and diabetic neuropathy; NR can reduce liver steatosis induced by a high-fat diet in mice and prevent fatty liver;

  • Neuroprotective Effect: In vitro cell experiments and animal model studies have confirmed that NMN and NR can activate sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3) proteins by increasing NAD+ levels, reduce neuronal apoptosis caused by oxidative stress, decrease β-amyloid deposition and tau hyperphosphorylation in the brain of Alzheimer's disease model mice, and reduce various pathological features of Alzheimer's disease;

  • Cardiovascular Protection: In a mouse model of myocardial ischemia-reperfusion injury, NMN pretreatment can reduce cardiomyocyte necrosis and improve cardiac function; NR can lower blood pressure in hypertensive rats, improve vascular endothelial function, and protect the heart and blood vessels;

  • Multi-Organ Protection and Telomere Maintenance: Clinical studies in humans have shown that oral administration of NMN or NR can increase NAD+ levels in tissues such as the pancreas, liver, adipose tissue, heart, skeletal muscle, kidneys, testes, eyes, and blood vessels, improve muscle strength and vascular elasticity in elderly individuals, and extend telomeres.


3. Natural Food Sources of NMN and NR

NMN and NR naturally exist in daily foods but in low contents, which are insufficient to meet the human body's supplementary needs through dietary intake. The specific sources are as follows:
  • Food Sources of NMN: Mainly present in plant-based foods, with edamame having the highest content (0.47–1.88 mg/100g), followed by vegetables such as avocado (0.36–1.60 mg/100g), broccoli, cauliflower, cucumber, cabbage, and tomato; Seafood (e.g., shrimp, crab) and raw meat contain lower levels (0.06–0.42 mg/100g);

  • Food Sources of NR: Mainly derived from animal-based foods, including dairy products such as whole milk, cheese, and yogurt, fish such as salmon and tuna, and poultry and livestock meats such as chicken and beef; NR content in plant-based foods is extremely low.



4. Safety Research of NMN and NR


Up to now, multiple human clinical trials have confirmed the safety of NMN and NR within the recommended dosage, with no serious adverse reactions observed. The specific research results are as follows:
  • Dosage Safety: Existing studies show that the maximum safe oral dosage of NMN is 1250 mg/day, and that of NR is 2000 mg/day;

  • Short-Term Supplementation Safety: A randomized controlled trial involving healthy adults showed that oral administration of 250 mg NMN daily for 12 weeks significantly increased whole-blood NAD+ levels in subjects, with no abnormalities in clinical indicators such as blood routine, liver and kidney function, and electrolytes, and no adverse reactions such as gastrointestinal discomfort or allergies;

  • Medium- and Long-Term Supplementation Safety: A 60-day intervention trial conducted in healthy people aged 40–65 years showed that oral administration of 300 mg NMN daily had good tolerance and no harmful effects, and the serum NAD+/NADH (reduced NAD+) ratio of subjects increased by 38% compared with the placebo group;

  • Metabolic Safety: A pharmacokinetic study of single oral administration of NMN in healthy men showed that NMN can be rapidly absorbed and metabolized into NAD+, with no accumulation of unmetabolized prototype drugs, and the metabolites in urine are non-toxic. Oral NMN is considered feasible and may be a strategy to alleviate age-related diseases.


5. Summary and Outlook

As key precursor substances of NAD+, NMN and NR exhibit clear physiological activities in anti-aging, metabolic regulation, neuroprotection, and cardiovascular maintenance by increasing intracellular NAD+ levels. Existing clinical studies have confirmed their safety within the recommended dosage. In the future, with the development of more large-sample, long-term follow-up human clinical trials, the application value of NMN and NR in the intervention of age-related diseases will be further clarified, providing new scientific means to improve the health quality of the elderly population.

It should be noted that the supplementation of NMN and NR should be conducted within the scientific dosage range and combined with healthy lifestyles such as a balanced diet and regular work and rest to give full play to their physiological effects.




Important Reminder:All content in this article is for general reference only and is provided solely to offer information support for practitioners in the nutrition and health industry. Descriptions related to efficacy are supported by corresponding data, but they do not represent claims or guidance for consumers. Content related to health, medical care, and technological applications is for reference only. For medical matters, please consult professional medical institutions and follow medical advice. This article does not provide any medical recommendations.


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