Alpha memo: nicotinamide riboside exercise performance

One-sentence alpha: Nicotinamide riboside supplementation may improve exercise performance only when recipients are NAD(P)H-deficient, with the same molecule impairing performance in young/replete animals. Receipt 1: "The NAD+ precursor nicotinamide riboside decreases exercise performance in rats" (2016) — Chronic 21-day NR administration at 300 mg/kg/day in young Wistar rats showed a tendency toward worse swimming performance versus saline controls. Receipt 2: "Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study" (2020) — Acute NR supplementation in older men (who exhibited lower erythrocyte NAD(P)H and higher urine F₂-isoprostanes at baseline) increased NAD(P)H levels, decreased oxidative stress, and improved VO₂-related performance, while no comparable benefit appeared in young subjects. Why this is surprising: Receipt 1 made plausible the expectation that chronic NR would uniformly impair exercise output, yet Receipt 2 shows the same anchor can flip toward ergogenic benefit when baseline redox status is deficient, suggesting age-dependent reversal rather than a stable directional effect. Caveats/falsifiers:

• Population limits: rat data are in young male Wistar rats at one dose (300 mg/kg/day, 21 days); human data are acute dosing in 12 young vs. 12 old men — chronic, sex-specific, and dose-response effects remain uncharacterized.
• A decisive falsifier would be a chronic NR trial in older humans with documented NAD(P)H deficiency that fails to show any exercise or redox improvement, or equivalently, a young/replete cohort that is harmed acutely.