Compendium of NMN Multidimensional Efficacy Trials from the Past Five Years

As a key precursor of NAD?, NMN became the "celebrity molecule" of anti-aging research after it was shown in 2013 to reverse aging phenotypes in mice.

Can the striking animal data be reproduced in humans?

Human trials conducted over the past five years have begun to answer that question. Drawing on nine authoritative publications, this article dissects the real-world efficacy of NMN in terms of physical performance, metabolic regulation, skin care and more, using hard clinical data.

NMN Basic Mechanism

Before diving into the benefits, it helps to understand how NMN works. After ingestion, NMN enters cells via two main routes:

1. Direct transport through the SLC12A8 transporter in the small intestine.

2. Conversion to nicotinamide riboside (NR) followed by uptake via equilibrative nucleoside transporters.

Both routes ultimately raise intracellular NAD? levels.

NAD? declines by 3-5 % per year with age; after age 40 the drop accelerates, leading to mitochondrial dysfunction and impaired DNA repair.

By replenishing NAD?, NMN activates sirtuins such as SIRT1 and SIRT3, thereby modulating aging-related physiology.

Five core benefits of NMN

1. Physical Performance:

An "Endurance Booster" for Middle-Aged and Older Adults

Multiple randomized, placebo-controlled trials show that NMN improves physical performance in a dose- and time-dependent manner.

In a multicenter study of 80 healthy adults aged 40-65, subjects received 300 mg, 600 mg, 900 mg NMN or placebo daily.

After 60 days:

- All NMN groups significantly outperformed placebo in the six-minute walk test; the 600 mg and 900 mg groups showed the largest gains.

- Biological age (based on blood biomarkers) rose in the placebo group but remained stable in all NMN groups.

Efficacy changes over 60 days in the placebo group and the three NMN treatment groups.

In adults ≥ 65 y, a"time-window"effect emerged: 250 mg NMN taken between 18:00 and bedtime improved five-times-sit-to-stand performance (effect size 0.72) and reduced daytime sleepiness more than morning dosing, likely because aging disrupts the circadian rhythm of NAD? metabolism.

2. Metabolic Regulation:

Precision Improvement of Insulin Sensitivity

NMN's metabolic benefits are most evident in pre-diabetic individuals.

A 2021 Science study enrolled 25 overweight/obese post-menopausal women with pre-diabetes. After 10 weeks of 250 mg NMN daily, insulin-stimulated glucose disposal rose by 25 ± 7 % versus no change with placebo.

Effect of the NMN group (n = 13) and the placebo group (n = 12) on insulin-stimulated glucose disposal rate.

Mechanistic work showed tissue specificity: NMN enhanced phosphorylation of AKT (Ser473/Thr308) and mTOR (Ser2448) in skeletal muscle, restoring insulin signaling, but had no significant effect on liver or adipose tissue.

In healthy adults, 250 mg NMN increased post-prandial insulin from 6.95 to 39.2 mIU mL?1, indicating modulation of insulin secretion even in normoglycemic subjects.

3. Skin Care:

Barrier Reinforcement at the Genetic Level

Dryness and loss of elasticity are visible signs of skin aging. An 8-week, double-blind trial in 50 subjects with dry, lax skin found that 125 mg NMN daily significantly increased water content and visco-elasticity (R2 parameter) of the left cheek versus placebo.

Cellular assays showed NMN up-regulates gene expression of collagen, aquaporin-3 and elastin, strengthening moisture retention and firmness. The effective dose for skin is far lower than that required for metabolic effects, indicating higher cutaneous sensitivity.

4. Cardiovascular Protection:

A Potential"Vascular Guardian"

Dedicated cardiovascular outcome trials are ongoing, but pre-clinical and indirect human data are encouraging.

NMN activates SIRT1/SIRT3 pathways, improves mitochondrial function, curbs oxidative stress and dampens inflammation.

NMN improves cardiovascular disease through multiple signaling pathways.

Animal studies show reduced infarct size after ischemia/reperfusion and slowed atherosclerosis.

In humans, long-term NMN blunts post-prandial hyperinsulinemia—a known cardiovascular risk factor—suggesting a potential preventive role.

5. Safety:

Excellent Tolerability with Chronic Use

Safety is paramount. Trials over the past five years consistently report good tolerability at routine doses.

In the study cited above, 900 mg NMN daily for 60 days produced no serious adverse events; hematology, hepatic and renal indices remained normal.

Trials in older adults and pre-diabetic women yielded identical conclusions even after 12 weeks.

A systematic review found only 8.2 % of subjects reported minor complaints (mouth ulcers, acid reflux) with no clear causal link to NMN.

Limitations and Caveats

• - High inter-individual variability: plasma NMN increment differs markedly among subjects, so some may derive little benefit.
• - Long-term effects unknown: most follow-ups are 3-6 months; data beyond one year are scarce.
• - Misconceptions: NMN is not a"miracle drug" and cannot replace pharmacotherapy. NAD? may be a biomarker of cellular stress rather than the singular driver of aging; no single molecule can address the multifactorial nature of aging.

Five years of human trials have moved NMN from mouse hope to clinical reality. By raising NAD? levels, NMN can improve physical function, modulate metabolism and benefit skin in middle-aged and older adults, all with a favorable safety profile at standard doses.

It should be viewed as an adjunct to a healthy lifestyle, not a universal anti-aging key.

With β-nicotinamide mononucleotide now filed as a new cosmetic ingredient in China and the National Health Commission reopening the food-additive application process in 2025, the range of NMN-containing products is set to expand. Larger, longer trials will further clarify its true value in the anti-aging arena.

References:

• [1] Yi L, Maier A B, Tao R, 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[J]. Geroscience, 2023, 45(1): 29-43.
• [2] Yu B, Jing X, Jia L, et al. The versatile multi-functional substance NMN: its unique characteristics, metabolic properties, pharmacodynamic effects, clinical trials, and diverse applications[J]. Frontiers in pharmacology, 2024, 15: 1436597.
• [3] Wen J, Syed B, Kim S, et al. Improved Physical Performance Parameters in Patients Taking Nicotinamide Mononucleotide (NMN): A Systematic Review of Randomized Control Trials[J]. Cureus, 2024, 16(8).
• [4] Deng H, Ding D, Ma Y, et al. Nicotinamide mononucleotide: research process in cardiovascular diseases[J]. International Journal of Molecular Sciences, 2024, 25(17): 9526.
• [5] Kim M, Seol J, Sato T, 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[J]. Nutrients, 2022, 14(4): 755.
• [6] Yoshino M, Yoshino J, Kayser B D, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women[J]. Science, 2021, 372(6547): 1224-1229.
• [7] Yamane T, Imai M, Bamba T, et al. Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects[J]. Clinical Nutrition ESPEN, 2023, 56: 83-86.
• [8] Rahman S U, Qadeer A, Wu Z. Role and potential mechanisms of nicotinamide mononucleotide in aging[J]. Aging and disease, 2024, 15(2): 565.
• [9] Shimamoto, Y.; Ono, T.; Sawabe, A. Examination of the Effects of a Food Containing Nicotinamide Mononucleotide on Skin Function and Safety. Jpn. Pharmacol. Ther. 2023, 51, 75-87.

*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.

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