Nicotinamide Mononucleotide (NMN) supplementation has been widely explored as a potential strategy for increasing NAD+ levels, a coenzyme essential for cellular energy production, DNA repair, and longevity-related pathways. However, while NMN has demonstrated promising results in preclinical models, despite what extensive marketing by from supplement companies might tell us: human clinical trials have produced mixed findings.
Two recent studies provide insight into the complexities of NMN supplementation, revealing both its metabolic potential and the challenges that hinder its widespread application.
As ever, please talk to your doctor or medical practitioner most familiar with your medical history before implementing any changes in diet, exercise, or lifestyle, especially if you are under treatment. Links to all studies at the bottom of the page.
NMN’s Effect on NAD+ and Metabolic Health
One of the most consistent findings across NMN research is its ability to increase blood NAD+ levels. A meta-analysis of 12 randomised controlled trials, Zhang J et al. (2024), confirmed that NMN supplementation reliably elevates NAD+ concentrations in humans. However, the translation of this biochemical effect into meaningful metabolic benefits remains unclear.
In terms of glucose metabolism, NMN supplementation did not lead to significant changes in fasting glucose, insulin sensitivity, or HbA1c levels. This suggests that while NMN may replenish NAD+, it does not necessarily improve glucose regulation in healthy individuals or those with mild metabolic dysfunction. Interestingly, one study found that NMN improved muscle insulin sensitivity in prediabetic women, yet systemic glucose regulation remained unchanged. This indicates that NMN’s effects may be tissue-specific, influencing some metabolic processes without altering overall blood glucose levels.
The lipid profile findings were similarly inconclusive. While NMN supplementation had no significant impact on total cholesterol, LDL-C, or HDL-C, a modest reduction in triglyceride levels was observed in overweight and obese individuals. This suggests that NMN’s benefits may be more pronounced in populations with pre-existing metabolic dysfunction rather than in healthy individuals. However, the clinical significance of this triglyceride reduction remains uncertain, particularly when compared to established lipid-lowering interventions.
Why Some Individuals Respond to NMN and Others Do Not
One of the most striking findings across both studies is the considerable variability in individual responses to NMN supplementation. Clinical trials consistently show that while some individuals experience a substantial increase in NAD+ levels, others exhibit minimal or no response. These individuals, known as "non-responders", contrast sharply with "responders" who not only show significant increases in NAD+ but may also experience metabolic benefits.
Response Type | % of Participants | Change in NAD+ Levels |
High Responders | 30% | ↑ 50–100% |
Moderate Responders | 30% | ↑ 20–50% |
Non-Responders | 40% | ↔ 0–10% |
Several factors may explain this variability. Genetics appears to play a major role, as differences in NAD+ synthesising and NAD+ consuming enzymes can determine how efficiently an individual processes NMN. Additionally, gut microbiota composition has been shown to influence NMN metabolism, with certain bacteria converting NMN into alternative metabolites that do not directly contribute to NAD+ synthesis.
A critical unanswered question is whether non-responders can be converted into responders through alternative dosing strategies, co-supplementation with other nutrients, or gut microbiota modulation.
A major limitation of NMN supplementation is its bioavailability - how much NMN actually reaches tissues in its active form. The studies reveal that a significant portion of orally ingested NMN is broken down in the gut and liver, reducing its availability for direct NAD+ synthesis.
Context Matters: Who Benefits Most from NMN?
One key takeaway from these studies is that NMN’s effects may depend on the health status and age of the individual.
Healthy individuals with adequate NAD+ levels may experience little to no benefit from NMN supplementation.
Older adults or those with metabolic conditions (e.g., obesity, hypertension, prediabetes) may see greater improvements in energy metabolism and cardiovascular health.
Athletes and physically active individuals might experience enhanced recovery and mitochondrial function, but more data is needed to confirm this.
In this context, NMN might be most effective as a targeted intervention (based on testing one's NAD+ levels) rather than a general supplement for the broader population.
Safety Considerations, Unanswered Questions and Fake Products
The safety profile of NMN appears favourable, with most clinical trials reporting only mild gastrointestinal side effects such as bloating and nausea. However, long-term effects remain unknown. Some concerns have been raised about potential cancer risks, as NAD+ is essential for cell survival, including the survival of cancerous cells. While no human studies have confirmed this risk, further investigation is warranted before NMN can be widely recommended for long-term use.
Sandalova et al. (2024) found that NMN (and Urolithin A) supplements often contain amounts differing from their labels. Of 15 NMN products, 2 had higher-than-labeled amounts, while most contained less.
A previous report showed 14 of 22 brands had under 1% of the claimed NMN, with 3 containing none.
Final Thoughts
NMN supplementation clearly raises NAD+ levels, but whether this translates into significant metabolic benefits depends on individual factors such as genetics, gut microbiota and baseline health status. While some individuals experience noticeable improvements in triglyceride levels and muscle insulin sensitivity, others show little or no response. Bioavailability also remains a challenge.
Despite common claims that muscle aging is linked to declining NAD+ levels, clinical evidence is limited and a direct causal relationship remains unproven. While exercise consistently enhances muscle health and NAD+ metabolism, its benefits surpass those of NAD+ precursor supplementation, highlighting physical activity as the more effective intervention against muscle aging.
For now, NMN may be most beneficial for individuals with NAD+ deficiencies or metabolic impairments, while its effects in healthy adults remain uncertain.
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Studies and Resources
Zhang J, Poon ET, Wong SH. Efficacy of oral nicotinamide mononucleotide supplementation on glucose and lipid metabolism for adults: a systematic review with meta-analysis on randomized controlled trials. Crit Rev Food Sci Nutr. 2024 Aug 8:1-19. doi: 10.1080/10408398.2024.2387324. Epub ahead of print. PMID: 39116016.
Benjamin C, Crews R. Nicotinamide Mononucleotide Supplementation: Understanding Metabolic Variability and Clinical Implications. Metabolites. 2024 Jun 18;14(6):341. doi: 10.3390/metabo14060341. PMID: 38921475; PMCID: PMC11205942.
Sandalova E, Li H, Guan L, Raj SD, Lim TG, Tian E, Kennedy BK, Maier AB. Testing the amount of nicotinamide mononucleotide and urolithin A as compared to the label claim. Geroscience. 2024 Oct;46(5):5075-5083. doi: 10.1007/s11357-024-01257-2. Epub 2024 Jun 27. PMID: 38935229; PMCID: PMC11335992.
Chubanava S, Treebak JT. Regular exercise effectively protects against the aging-associated decline in skeletal muscle NAD content. Exp Gerontol. 2023 Mar;173:112109. doi: 10.1016/j.exger.2023.112109. Epub 2023 Jan 25. PMID: 36708750.
Wang P, Chen M, Hou Y, Luan J, Liu R, Chen L, Hu M, Yu Q. Fingerstick blood assay maps real-world NAD+ disparity across gender and age. Aging Cell. 2023 Oct;22(10):e13965. doi: 10.1111/acel.13965. Epub 2023 Aug 28. PMID: 37641521; PMCID: PMC10577551.
Nadeeshani H, Li J, Ying T, Zhang B, Lu J. Nicotinamide mononucleotide (NMN) as an anti-aging health product - Promises and safety concerns. J Adv Res. 2021 Aug 11;37:267-278. doi: 10.1016/j.jare.2021.08.003. PMID: 35499054; PMCID: PMC9039735.
Navas, L.E., Carnero, A. NAD+ metabolism, stemness, the immune response, and cancer. Sig Transduct Target Ther 6, 2 (2021). https://doi.org/10.1038/s41392-020-00354-w
de Guia RM, Agerholm M, Nielsen TS, Consitt LA, Søgaard D, Helge JW, Larsen S, Brandauer J, Houmard JA, Treebak JT. Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle. Physiol Rep. 2019 Jul;7(12):e14139. doi: 10.14814/phy2.14139. PMID: 31207144; PMCID: PMC6577427.
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