Yoshino · Science (New York, N.Y.) 2021 · randomized placebo-controlled double-blind trial · n=?

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.

Cited 429 times in the scientific literature.

Level 2 - randomized trial

Randomized, placebo-controlled, double-blind trial in humans

PubMed 33888596 · doi:10.1126/science.abe9985 · record verified 2026-08-27

What was done

A 10-week, randomized, placebo-controlled, double-blind clinical trial evaluated the effect of nicotinamide mononucleotide (NMN) supplementation on metabolic function. Participants were postmenopausal women who were overweight or obese and had prediabetes. The researchers assessed insulin-stimulated glucose disposal using a hyperinsulinemic-euglycemic clamp, evaluated skeletal muscle insulin signaling through the phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR), and analyzed muscle gene expression.

What was found

The abstract reports directional changes without numeric values or effect sizes. Insulin-stimulated glucose disposal and skeletal muscle insulin signaling (AKT and mTOR phosphorylation) increased following NMN supplementation, with no changes observed in the placebo group. NMN supplementation also upregulated the expression of platelet-derived growth factor receptor beta and other genes involved in muscle remodeling.

Why it matters

This study provides randomized human evidence that oral NMN supplementation can enhance skeletal muscle insulin sensitivity and activate metabolic signaling pathways in prediabetes, translating prior rodent findings on NAD+ biosynthesis to a clinical population.

Limits

The abstract omits sample size, participant counts per group, specific NMN dosages, quantitative effect sizes, and p-values. Findings are restricted to overweight or obese postmenopausal women with prediabetes and cannot be generalized to men, other age groups, or healthy populations. The 10-week duration does not provide data on long-term safety, durability, or clinical outcomes such as progression to type 2 diabetes.

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