NMN and NR for Muscle Preservation: What the Clinical Evidence Actually Shows

What the trials actually measured

Most human NMN and NR research measured NAD+ in blood or blood cells, not in muscle. Blood NAD+ rose in randomized trials: NMN 250 mg/day for 12 weeks in 30 healthy adults [6]; NMN 300, 600 or 900 mg/day for 60 days in 80 middle-aged adults, highest at 600 and 900 mg [2]; NR 500 mg twice daily for 6 weeks in a crossover trial of adults aged 55-79 [12]; and NR 1,500 mg twice daily for 4 weeks in 20 people with Parkinson's disease, where blood NAD+ rose up to 5-fold [9].

Whether a blood rise reaches muscle, and whether it changes strength or mass, is the question the muscle trials addressed.

The muscle biopsy trial: NR and aged muscle

In 12 men aged 70-80, NR 1 g/day for 21 days in a randomized, placebo-controlled crossover trial did not significantly increase muscle NAD+ itself. A marker of NAD+ synthesis (NAAD) and nicotinamide clearance products did rise, so the NR reached muscle and was metabolized. Mitochondrial bioenergetics, grip strength and insulin sensitivity were unchanged [4].

Yoshino 2021: NMN and insulin sensitivity

A 10-week randomized, placebo-controlled, double-blind study published in Science in 2021 evaluated NMN 250 mg/day in postmenopausal women with prediabetes who were overweight or obese; 25 women completed it [5].

Insulin-stimulated glucose disposal, measured with a hyperinsulinemic-euglycemic clamp, increased after NMN and did not change after placebo, and skeletal muscle insulin signaling increased. Genes related to muscle remodeling, including platelet-derived growth factor receptor beta, were up-regulated [5].

The reported outcomes were insulin sensitivity and muscle signaling rather than muscle size or strength. The study was small, and a published comment and the authors' response disputed the analysis [5].

The 2025 meta-analysis: no effect on muscle outcomes

A 2025 systematic review and meta-analysis in the Journal of Cachexia, Sarcopenia and Muscle pooled randomized trials of NMN and NR against placebo in older adults with mean ages from 60.9 to 83 years. For NMN, none of the muscle outcomes differed significantly from placebo: skeletal muscle index, handgrip strength, gait speed, and the five-times chair stand test [3].

A separate 2025 meta-analysis of 12 randomized trials with 513 participants found NMN significantly raised blood NAD+, but most clinical outcomes, including fasting glucose, triglycerides and cholesterol, were not significantly different from control. The authors wrote that benefits of NMN may be exaggerated, and rated risk of bias as some concerns in seven trials and high in five [13].

NR in obese men: no metabolic improvement

Forty sedentary obese men aged 40-70 with a BMI above 30 took NR 1,000 mg twice daily, or placebo, for 12 weeks. Insulin sensitivity by clamp, endogenous glucose production, glucose disposal, energy expenditure, lipolysis and body composition did not improve, and there were no serious adverse events [8].

The smaller signals

Some trials reported improvements that were nominal or not specific to the supplement:

• In healthy older men, NMN 250 mg/day for 6 or 12 weeks raised blood NAD+ and metabolites. Gait speed and left grip showed nominal improvements that the authors said needed confirmation in larger studies, and there was no effect on body composition [1].
• In 80 healthy middle-aged adults, NMN raised blood NAD, and six-minute walk distance was greater than placebo in all NMN groups. The trial did not establish that NMN preserves muscle mass [2].
• In 108 older Japanese adults, NMN 250 mg once daily for 12 weeks was compared in morning and afternoon dosing against placebo. The afternoon NMN group had the largest effect on the five-times sit-to-stand test (d=0.72) and on drowsiness (d=0.64), but all groups, including placebo, improved on the sit-to-stand test [14].

Doses used in human trials

The trials used these doses; they are not official recommendations.

• NMN 250 mg/day for 6 to 12 weeks [6][1][14]
• NMN 300, 600 or 900 mg/day for 60 days [2]
• NMN 1,250 mg once daily for up to 4 weeks [7]
• NR 1 g/day for 21 days in older men [4]
• NR 1,000 mg twice daily (2,000 mg/day) for 12 weeks [8]
• NR 1,500 mg twice daily (3,000 mg/day) for 4 weeks [9]

Safety and tolerability

Short trials have been reassuring. NMN 1,250 mg once daily for up to 4 weeks in 31 healthy adults produced no severe adverse events and no changes beyond normal physiological variation in blood, urine or body composition tests [7]. NMN 250 mg/day for 12 weeks in 30 adults produced no laboratory abnormalities and no obvious adverse effects [6], and NMN 300 to 900 mg/day for 60 days in 80 adults raised no safety issues on adverse-event, laboratory or clinical monitoring [2].

With NR, a randomized crossover trial in healthy middle-aged and older adults found NR was well tolerated and increased NAD+ metabolism [12]. NR 2,000 mg/day for 12 weeks in 40 obese men produced no serious adverse events and normal safety blood tests [8], and NR 3,000 mg/day for 4 weeks in people with Parkinson's disease produced no moderate or severe adverse events [9].

Human safety data beyond about 12 weeks are lacking, and small sample sizes limit interpretation of physiological outcomes. Pregnant or breastfeeding women, children, and people with cancer or kidney or liver disease were not studied in these trials, so safety in those groups is unknown [11].

Regulatory status of NMN and NR

Both are sold in the US as oral dietary supplements, and neither is an FDA-approved drug. No NAD+-precursor product is approved by FDA to treat aging or any disease [10].

Trade press reported that in 2022 FDA told two NMN ingredient makers that NMN could not be marketed as a supplement. FDA's response letter to a citizen petition, dated 2025-09-29, reversed that position. Law-firm and trade reports of the letter say FDA now concludes NMN is not excluded from the supplement definition because it found evidence NMN was marketed as a supplement in the US before it was authorized for drug investigation [10][15]. NMN is still a new dietary ingredient, so a maker must file an NDI notification, or rely on a prior notification covering its supplier's ingredient, before selling it [10].

For NR, FDA responded to a company GRAS notice (GRN 000635) on 2016-08-03 with a no-questions letter and stated that it had not made its own GRAS determination [16].