Tier 2 — strong

Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial

Lin KY, Bucha A, McSweeney K, Wade KL, Karaj A, Tamaroff J, O'Malley S, Chung NM, Cilenti NA, Wanner J, Adzika GK, Mesaros C, Blair IA, Rojsajjakul T, Serai S, Farmer J, Bryant K, Lu Y, Harhay MO, Weber DR, Paridon SM, Seifert EL, Putt ME, Zamani P, Baur JA, Lynch DR, McCormack SE
The Lancet. Neurology 2026 25; 5; 469-481

Bibliography

PubMed
PMID 42009009
PubMed Central
PMC13162205
DOI
10.1016/s1474-4422(26)00082-7
Funding
US National Institutes of Health and Friedreich’s Ataxia Research Alliance support.
Competing interests
Disclosures include research, advisory and trial-related relationships; some authors were employed by the Friedreich’s Ataxia Research Alliance.

Study snapshot

DesignSingle-center randomized 2-by-2 factorial phase II trial
ModelHuman participants
Sample66 people with Friedreich’s ataxia; 33 children and 33 adults
InterventionWeight-based NR 300, 600 or 900 mg per dose, with or without individualized exercise, versus placebo arms
Duration12 weeks
EndpointsPeak oxygen uptake; adverse events

What the study showed, in plain terms

NR plus exercise improved peak oxygen uptake relative to the no-exercise placebo group, but did not outperform exercise alone. NR alone did not meet the efficacy threshold.

Key findings

NR plus exercise improved peak oxygen uptake relative to the no-exercise placebo group, but did not outperform exercise alone. NR alone did not meet the efficacy threshold.

What this study can and cannot tell us

Small factorial trial in a specific genetic disorder; the combination result cannot be attributed to NR alone or generalized to usual aging.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology