Nicotinamide Riboside In Combination with Exercise Improves Cardiopulmonary Fitness in Friedreich's Ataxia

Objectives

To evaluate the effects of aerobic and resistance exercise training, alone and in combination with NR supplementation, on cardiopulmonary (heart-lung) fitness and blood sugar control in children and adults with Friedreich's ataxia.

Journal

The Lancet Neurology

Key Outcomes

• NR supplementation was well-tolerated and increased whole blood NAD+ levels.
• NR combined with exercise produced the greatest improvement in cardiopulmonary fitness, increasing peak VO₂ by about 12.7% compared with baseline. However, this improvement was not significantly better than exercise alone.
• NR + exercise also resulted in a small but significant decrease in HbA1c levels, suggesting a mild improvement in blood sugar control. 
• Additional analyses showed improvements in maximal workload (the highest level of effort achieved during the exercise test) and physical activity levels. 
• NR alone did not meaningfully improve fitness outcomes, but it was associated with reductions in body fat. 
• Exploratory subgroup analyses suggested potential age-related differences in response: children appeared to respond more to NR alone, while adults showed clearer improvements in peak VO₂ with exercise (with or without NR).

Duration

12 weeks

Dose

300, 600, or 900 mg*

*Dosage depended on individual bodyweight.

Study Design

Randomized, placebo-controlled, single-center, phase II trial in 66 children and adults with Friechreich's ataxia. The study used a 2x2 factorial design to test exercise and a supplement, both alone and in combination.