NAD+ PRECURSORS (NMN AND NR) AFTER 50: WHAT THE HUMAN TRIALS ACTUALLY SHOW

NMN and NR are sold as the fix for age-related NAD+ decline. The human trials are honest about a split result: they reliably do the one thing they're supposed to do at the blood level, and they mostly don't do the thing people are buying them for.

What They Reliably Do

Every randomized trial that measured it found the same thing: nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) raise blood NAD+. In an 80-person, dose-finding trial in healthy middle-aged adults, all three NMN doses (300, 600, and 900 mg/day) significantly raised blood NAD+ over 60 days compared to placebo, with the largest rise at 600–900 mg (Yi et al. 2023, GeroScience). A separate trial in healthy older men found the same at a lower 250 mg/day dose over 6–12 weeks (Igarashi et al. 2022, NPJ Aging). In older adults with mild cognitive impairment, 1 g/day of NR produced a 2.6-fold increase in blood NAD+ (p<0.001) over 10 weeks (Orr et al. 2023, GeroScience). At the studied doses — up to 1,200 mg/day of NMN, up to 1 g/day of NR — none of these trials reported a safety signal.

The part that's still unsettled is whether raising the blood number does anything for muscle, strength, or performance.

Where It Falls Apart: Muscle and Strength

The most direct answer comes from a 2025 systematic review and meta-analysis in the Journal of Cachexia, Sarcopenia and Muscle, pooling randomized controlled trials in adults averaging 60.9 to 83 years old (Prokopidis et al. 2025). Across the pooled trials, NMN showed no significant effect on skeletal muscle index, handgrip strength (left or right), gait speed, or the 5-time chair stand test. A narrative synthesis in the same paper found no improvement in knee extension strength, short physical performance battery scores, or thigh muscle mass either. NR fared no better in its own subgroups — it was associated with a longer 6-minute walk distance specifically in people with peripheral artery disease, but with worse physical-performance scores in people with mild cognitive impairment. The authors' own conclusion: current evidence does not support NMN or NR supplementation for preserving muscle mass and function in adults over 60.

A separate 2025 meta-analysis in Current Pharmaceutical Biotechnology pooling a different, smaller set of 9 studies (412 participants) reached a different verdict — it reported a significant NMN effect on gait speed (standardized mean difference 0.34, 95% CI 0.03–0.66, p=0.033) and on liver ALT. Both papers exist, they pooled overlapping but not identical trials, and they disagree. That's reported here rather than resolved, because picking whichever one sounds more favorable isn't a real answer.

Two mechanistic trials add texture rather than resolution. In 32 elderly adults (55–80) given NR plus pterostilbene before an experimentally induced muscle injury, the combination was safe but did not improve muscle stem cell recruitment or any measure of muscle regeneration afterward (Jensen et al. 2022, JCI Insight). In the healthy-older-men NMN trial above, the authors reported "nominally significant" improvements in gait speed and left-hand grip strength — their own wording flags this as needing validation in a larger trial, not as a settled finding — with no change in body composition. And in the NR/MCI trial, walking speed actually improved in the placebo group (a practice effect from repeating the test) while the NR group showed no change.

The One Place a Positive Signal Shows Up

Aerobic capacity is where the two most favorable trials point. In 48 recreationally trained runners, a 6-week trial of NMN at 300, 600, or 1,200 mg/day alongside regular training found that oxygen uptake, percentage of VO2max, and power output at both ventilatory thresholds increased more in the medium- and high-dose groups than in the placebo group. But VO2max itself, peak power, and O2-pulse did not differ between groups (Liao et al. 2021, Journal of the International Society of Sports Nutrition) — sub-maximal efficiency markers moved; the actual aerobic ceiling didn't. In the same 80-person dose-finding trial cited above for NAD+ levels, 6-minute walk distance was significantly longer at every NMN dose compared to placebo at both 30 and 60 days, with the best result at 600–900 mg (Yi et al. 2023). That trial's lead author is an employee of Abinopharm, a company that manufactures NAD+ precursor ingredients — disclosed in the paper's own conflict-of-interest statement, and worth knowing when reading its results.

The Evidence Gap

I ran an actual PubMed search for a randomized trial of NAD+ precursors in trained masters athletes — it returned zero results. To confirm the search itself wasn't the problem, I ran the same kind of search for creatine in masters athletes as a control, which returned six real papers on the first pass. So the null result is real: I could not find a trial testing NMN or NR in anyone already training seriously past 50. Every trial above sits in "healthy middle-aged adults," "healthy older men," "recreational runners," or a clinical population (mild cognitive impairment, peripheral artery disease, an induced muscle injury) — not in a population that looks like WPP's audience.

The Regulatory Wrinkle

In November 2022, the FDA determined that NMN was excluded from the legal definition of a dietary supplement, because a company had already filed an investigational new drug application for it — a determination that made retail NMN sales legally ambiguous even though the market kept selling it. According to multiple industry trade-press reports, the FDA sent letters dated September 29, 2025 reversing that position: NMN is no longer considered excluded from the dietary supplement definition and may proceed through the New Dietary Ingredient pathway. This is a regulatory status update reported by industry press, not a scientific finding — it says nothing about whether NMN works, only that its legal footing changed. NR was never subject to the 2022 exclusion in the first place.

The Protocol

What the trials actually support, at this point:

• NMN and NR reliably raise blood NAD+ at every dose tested — that part is about as consistent as this literature gets.
• The best available meta-analysis in older adults found no effect on muscle mass, grip strength, gait speed, or chair-stand performance. A smaller, differently-pooled meta-analysis disagrees on gait speed specifically. Neither settles the question.
• The clearest positive signal sits in sub-maximal aerobic markers and walking distance, in two trials that are either not in an over-50 population (the runners) or industry-affiliated (the dose-finding trial) — not a reason to dismiss them, but a reason not to oversell them.
• No trial has tested this in trained masters athletes specifically. That's the honest gap, not a reason to assume it would or wouldn't work there.
• Doses studied ranged from 250 mg to 1,200 mg/day of NMN and up to 1 g/day of NR, for weeks to a few months, with no reported safety signal at those doses and durations. No dose is recommended here — those are simply the numbers the trials used.