NMN, Muscle Insulin Sensitivity in Prediabetic Women (PubMed)

What did the 2021 NMN trial in prediabetic women find?

Yoshino and colleagues randomized postmenopausal women with prediabetes who were overweight or obese to NMN 250 mg/day or placebo for 10 weeks, double-blind [1]. Mean age was about 61-62 and mean BMI about 33-34; 25 women completed the trial, 13 on NMN and 12 on placebo [1].

The trial measured insulin-stimulated glucose disposal with a hyperinsulinemic-euglycemic clamp, which holds insulin at a fixed elevated level and measures how much glucose tissue takes up. Disposal rose 25 ± 7% after NMN and did not change after placebo [1]. In skeletal muscle, phosphorylation of AKT and mTOR rose with NMN and not with placebo, and expression of PDGFRβ and other genes related to muscle remodeling increased [1].

How much weight can one 25-woman trial carry?

The population was narrow: postmenopausal women, overweight or obese, with prediabetes [1]. Men, younger adults and people with established type 2 diabetes were not included in this trial, so it says nothing about them.

The analysis was also contested. A published Comment disputed the analysis of the trial, and the authors published a Response [1].

Did weight or HbA1c change?

No. Over the 10 weeks there was no group-by-time difference in body weight or HbA1c; the HbA1c interaction p value was 0.396 [1]. The clamp measurement moved while HbA1c did not differ between groups.

Does nicotinamide riboside do the same thing?

NR is the other oral NAD+ precursor in human trials, and its insulin-sensitivity results are negative.

Dollerup and colleagues randomized 40 sedentary men with obesity (BMI over 30, aged 40-70) to NR 1,000 mg twice daily — 2,000 mg/day — or placebo for 12 weeks [4]. Insulin sensitivity by hyperinsulinemic-euglycemic clamp, endogenous glucose production, and glucose disposal and oxidation were not improved, and energy expenditure, lipolysis and body composition were not improved either; there were no serious adverse events and safety blood tests were normal [4].

A second NR trial looked at muscle NAD+ itself. Twelve men aged 70-80 took NR 1 g/day for 21 days in a placebo-controlled crossover [5]. Muscle NAD+ did not rise (210 vs 197 pmol/mg, p=0.22), although a marker of NAD+ synthesis, NAAD, doubled, and mitochondrial respiration, grip strength, insulin sensitivity and muscle blood flow were unchanged [5].

What do the pooled analyses show?

A 2025 systematic review and meta-analysis pooled 12 studies with 513 participants. NMN significantly raised blood NAD, but most clinical outcomes, including fasting glucose, triglycerides and cholesterol, were not significantly different from control; the authors judged risk of bias to be of some concern in 7 studies and high in 5, and suggested that the benefits of NMN may be exaggerated [6].

A separate 2025 meta-analysis of NMN and NR in older adults (mean ages 60.9 to 83) found no significant effect of NMN on skeletal muscle index, handgrip strength, gait speed or the 5-times chair stand test [7].

What dose was studied, and what is known about safety?

NMN trials have used different doses and durations: 250 mg/day for 6 or 12 weeks in older men [8]; 300, 600 or 900 mg/day for 60 days in 80 middle-aged adults [9]; and 1,250 mg/day for up to 4 weeks in 31 adults aged 20-65 [10]. There is no official recommended dose for NMN.

Safety findings, trial by trial:

• In the prediabetes trial, no adverse events were reported [1].
• NMN 250 mg/day for 12 weeks in 30 healthy adults caused no abnormalities in physiological and laboratory tests and no obvious adverse effects [11].
• NMN 300, 600 or 900 mg/day for 60 days in 80 adults raised no safety issues on adverse-event, laboratory and clinical monitoring [9].
• NMN 1,250 mg once daily for up to 4 weeks in 31 healthy adults aged 20-65 caused no severe adverse events and no changes beyond normal physiological variation in hematology, biochemistry, urine or body composition [10].

The limits are duration and size. Trials have run weeks, not years, and enrolled between 12 and 140 people; human safety data beyond about 12 weeks are lacking [3]. Pregnant or breastfeeding women, children, and people with cancer or kidney or liver disease were not studied in the cited trials, so safety in these groups is unknown [3]. A cancer risk from long-term NAD+ boosting has been raised as a theoretical concern; no human data were identified [3].

No human drug-interaction studies of NMN or NR have been identified, so nothing can be said about whether NMN is safe with, or interacts with, any particular prescription drug [3].

Is NMN an approved drug?

No. NMN and NR are sold in the US as oral dietary supplements, neither is an FDA-approved drug, and no NAD+-precursor product is approved by FDA to treat aging or any disease [2].

FDA's position has moved. Its response letter of 2025-09-29 to a citizen petition concluded that NMN is not excluded from the dietary supplement definition, so NMN may be lawfully marketed as a supplement, subject to new-dietary-ingredient notification rules [2]. That reversed the position FDA reportedly took in 2022. Injectable or IV NAD+ is a compounded product, not an FDA-approved drug [12].