NMN (β‑Nicotinamide Mononucleotide) is an endogenous molecule found in certain fruits and vegetables. Studies indicate that NAD⁺ levels decline with age, and NMN can penetrate cells to serve as a direct precursor to NAD⁺. Consequently, NMN supplements have emerged as a leading approach to restoring NAD⁺ in the human body.

🧬 Understanding the Evidence Behind NMN Supplementation

NMN is a naturally occurring compound in the human body and certain fruits and vegetables. Over the past decade, its potential role in healthy aging has gained significant interest—particularly due to its ability to boost NAD⁺ levels, a molecule that declines with age and is essential for cellular energy metabolism and DNA repair.

At Leadsynbio, we believe that scientific innovation must be supported by evidence. While our previous article introduced the world’s first human clinical trial on NMN safety, this article delves deeper into multiple peer-reviewed studies—including randomized controlled trials (RCTs) and long-term safety assessments. We analyze NMN safety and efficacy from four perspectives:

🔍 NMN Dose Ranges and Clinical Trial Comparisons

Across studies conducted in Japan, the U.S., China, and India, NMN supplementation has been found to be well tolerated from 250 mg/day up to 900 mg/day, and in some studies, even higher doses (1,250–2,000 mg/day) showed no clinically significant side effects.

💊 NMN Effects Across Age Groups

1. Middle-Aged Adults (40–65 years)

Numerous trials with individuals in this age range report that daily NMN doses of 250–600 mg are both safe and effective at raising NAD⁺. A multicenter randomized study in China demonstrated that 300 mg/day improved insulin sensitivity, NAD⁺ levels, and physical energy—with no lab abnormalities reported over 60 days.^[¹¹]

A 2023 study published in GeroScience tested 300/600/900 mg/day across 80 healthy participants and found:

• Dose-dependent improvements in NAD⁺
• Better 6-minute walking test results
• Peak efficacy at 600 mg/day

2. Older Adults (65–80+ years)

Japanese clinical studies show that even at age 70+, NMN can be beneficial:

• Improved muscle strength (250 mg/day for 12 weeks)^[³]
• Reduced fatigue and better lower-limb function^[⁸]
• Improved sleep quality and reduced drowsiness

In diabetic elderly men (81 years old avg.), NMN was safe over 24 weeks, though physical improvements were limited—pointing to NMN's strong tolerability profile, even in vulnerable populations^.[¹⁴]

⚖️ Long-Term Safety of NMN Supplementation

The longest NMN trial (24 weeks) showed no adverse effects in older adults. Most trials ranged from 8 to 12 weeks, and no significant safety concerns were found in clinical chemistry, liver/kidney markers, or ECGs.

Notably, a 2025 systematic review combining 12 RCTs (513 participants) confirmed:

• Consistent elevation of NAD⁺
• No major shifts in glucose or lipid markers (data still inconclusive)
• Overall safety well-documented across studies^[¹⁶]

✅ Summary and Clinical Implications

• Typical Clinical Dose: 250–300 mg/day
• Effective Dose Range: 250–900 mg/day, with dose-dependent effects
• Most Common Duration: 8–12 weeks
• Demonstrated Safety in Middle-aged and Older Adults: Including participants with certain metabolic risk factors
• High-dose Tolerance (1,250–2,000 mg/day) Observed in Short-term Studies with Healthy Young Adults — long-term safety and effects in other populations remain to be confirmed

At Leadsynbio, we closely monitor the latest clinical insights on NMN and NAD⁺ metabolism, while focusing on our core role as a raw material supplier — delivering compliant, high-quality, and batch-consistent ingredients that lay a reliable foundation for downstream clinical research and commercial applications.

Disclaimer: Information derived from publicly available studies for educational purposes only. Not intended as medical or commercial advice. Proprietary images (if used) require direct rights-holder permission. Unauthorized reproduction prohibited.

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References

[1] Schultz, M. B., & Sinclair, D. A. (2016). Why NAD(+) Declines during Aging: It's Destroyed. Cell metabolism, 23(6), 965–966. https://doi.org/10.1016/j.cmet.2016.05.022

[2] Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature reviews. Molecular cell biology, 22(2), 119–141. https://doi.org/10.1038/s41580-020-00313-x

[3] Okabe, K., Yaku, K., Uchida, Y., Fukamizu, Y., Sato, T., Sakurai, T., Tobe, K., & Nakagawa, T. (2022). Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. Frontiers innutrition, 9, 868640. https://doi.org/10.3389/fnut.2022.868640  

[4]Irie, J. et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocr J 67, 153–160 (2020).

[5]Yoshino, M. et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science 372, 1224–1229 (2021).

[6]Igarashi, M. et al. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. NPJ Aging 8, 5 (2022).

[7]Liao, B. et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: A randomized, double-blind study. J. Int. Soc. Sports Nutr. 18, 54 (2021).

[8]Kim, M. et al. Effect of 12-week intake of nicotinamide mononucleotide on sleep quality, fatigue, and physical performance in older Japanese adults: A randomized, double-blind placebo-controlled study. Nutrients 14, 755 (2022).

[9]Pencina, M. et al. MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults. Gerontology 78,1(2023)

[10]Okabe, K. et al. Oral administration of nicotinamide mononucleotide is safe and efficiently increases blood nicotinamide adenine dinucleotide levels in healthy subjects. Front. Nutr. 9, 868640 (2022).

[11]Hao Huang. A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults. Front. Aging. 3,851698(2022).

[12]Morita, J. et al. Clinical evaluation of changes in biomarkers by oral intake of NMN. Glycative Stress Research 9,2(2022)

[13]Yi, L. et al. The efficacy and safety of β‑nicotinamide mononucleotide (NMN) supplementation in healthy middle‑aged adults: a randomized, multicenter, double‑blind, placebo‑controlled, parallel‑group, dose‑dependent clinical trial. GeroScience 45,29-43(2023)

[14]Akasaka, H. et al. Effects of nicotinamide mononucleotide on older patients withdiabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study. Geriatr Gerontol Int. 23,1(2023)

[15]Fukamizu, Y. et al. Safety evaluation of β‑nicotinamide mononucleotide oral administration in healthy adult men and women. Scientific Reports 12: 114442(2022)

[16]Katayoshi, T. et al. Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long‑term nicotinamide mononucleotide supplementation: a randomized, double‑blind, placebo‑controlled trial. Scientific Reports 13:2786(2023)

[17]Masashi Morifuji et al., Geroscience (2024): 250 mg/day for 12 weeks -> improved walking speed & sleep quality, no adverse effects

[18]Chronic NMN supplementation (250 mg/day) in older men improved NAD⁺ and modestly enhanced muscle performance

[19]Yi L. et al., GeroScience (2022/2023): 300–900 mg/day for 60 days -> increased NAD⁺, walking test, SF‑36; safe

[20]Uthever NMN study (300 mg/day, 60 days) in China: rising NAD⁺/NADH, improved SF‑36, stabilized HOMA‑IR vs placebo

[21]Meta‑analysis (Jiaqi Zhang et al., 2025): NMN elevates NAD⁺; metabolic improvements inconclusive—caution advised