Exercise plus a supplement raises fitness in Friedreich's ataxia
Peak oxygen uptake rose by 0.21 liters per minute with combination therapy compared with control, but was not statistically different from exercise alone.
12 weeks, placebo-controlled, registered NCT04192136
Limit: Only 16 participants in the nicotinamide riboside and exercise group
Stake: An author takes fees from Elysium Health, which develops nicotinamide riboside. An author holds patents licensed to Altimmune. Authors also declare ties to 1 more company.
Edited by Boris Djordjevic · AgingResearch.News
In a randomized trial, researchers studied 66 people aged 10 to 40 with Friedreich's ataxia, including 37 males and 29 females, split equally between children and adults. For 12 weeks, participants received daily weight-based doses of 300 to 900 milligrams of nicotinamide riboside, an individualized home exercise program, both, or an inactive control.
Peak oxygen uptake during exercise rose by 0.21 liters per minute in the combination group compared with control. The combination did not differ statistically from exercise alone. Single treatments did not differ statistically from control, with ranges of likely values including no difference. Adverse events were all mild or moderate, mainly digestive issues, falls, respiratory infections, and rashes. Moderate events occurred in seven control participants, six taking the supplement alone, three in the exercise group, and four in the combination group. All participants completed the trial.
Why it matters
Friedreich's ataxia involves progressive neurodegeneration and impaired cardiopulmonary fitness, features shared with physical decline in older age. The trial bears on whether combining cellular metabolic supplements with physical training can help sustain functional capacity when organ systems degenerate.
Caveats
The trial was conducted at a single center over 12 weeks with 66 participants, and combination therapy did not show a statistically significant benefit over exercise alone. The results may not apply to people older than 40, those with heart ejection fractions below 45 percent, or individuals who already meet physical activity guidelines.
From the paper
- Participants
Seventy-four individuals were enrolled, of whom 66 met eligibility criteria and were randomized.
- Who took part
Children and adults (10-40 years of age) with genetically confirmed Friedreich’s ataxia were recruited from clinical practices, website postings, and through a natural history study.
- Duration
Total trial duration for each participant was 12 weeks and included a baseline visit (week 0), a 12-week intervention, and a follow-up visit (week 12).
- Result
The nicotinamide riboside only group experienced a decrease in body fat, whether expressed as visceral fat (−0·08 kg; 95% CI: −0·15, −0·005) or fat mass index Z-score (−0·18; 95% CI: −0·33, −0·02) versus control.
- Harms
There were no serious adverse events.
- Limitation
First, since Friedreich’s ataxia is a rare disorder, our sample was not sufficiently large to permit well-powered subgroup analyses.
- Peak VO2
Differences between active treatment and control were (95% CI, adjusted p-value): nicotinamide riboside only, 0·10 (−0·05, 0·26, p=0.188); exercise only, 0·16 (0·00, 0·31, p=0.103); combination, 0·21 (0·05, 0·36, p=0.0299).
- Maximal workload
With respect to other pre-specified CPET outcomes, maximal workload was increased by combination therapy relative to control, and O₂ pulse was increased similarly by both combination therapy and exercise only (, p.124), both relative to control.
- Physical activity
With respect to non-CPET outcomes, the Physical Activity and Disability Survey-Revised (PADS-R) exercise/leisure activity sub-score increased in response to combination therapy versus control (0·80, 95% CI: 0·13, 1·46).
Quoted word for word from the full text on PubMed Central.
Exercise is part of Bryan Johnson's Blueprint
The paper
Children's Hospital of Philadelphia
The Lancet Neurology, Apr 17, 2026, Open access
