Exercise improves fitness for kids, adults with FA, study finds
12-week trial found no added benefit from energy-boosting supplement
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A combination of exercise and an energy-boosting supplement may improve physical fitness in children and adults with Friedreich’s ataxia (FA), although the added benefit of the supplement over exercise alone remains unclear, according to results from a clinical trial.
Those who participated in a 12-week program combining aerobic and strength training with nicotinamide riboside supplementation saw a significant increase in cardiopulmonary fitness, the body’s ability to supply oxygen to muscles during physical activity, compared with trial participants who did not exercise and received a placebo.
However, researchers found no significant difference between the combination group and participants who followed the same exercise program without supplementation, indicating the study did not show a clear added benefit of the supplement beyond exercise alone.
“The combination of nicotinamide riboside plus exercise for 12 weeks was safe and increased cardiopulmonary fitness in children and adults with Friedreich’s ataxia,” the researchers wrote. “Longer studies are needed to establish whether adding nicotinamide riboside to exercise could be considered as part of a long-term, comprehensive treatment approach.”
The study, “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,” was published in The Lancet Neurology.
Fatigue, safety worries limit participation
FA is caused by mutations that reduce the production of frataxin, a protein needed for cells to generate energy. When frataxin levels are too low, cells in energy-demanding tissues, such as the nervous system, heart, and muscles, gradually deteriorate, leading to FA symptoms including impaired coordination, fatigue, muscle weakness, and difficulty walking. People with FA also have markedly reduced cardiopulmonary fitness.
Although current guidelines recommend exercise to help manage symptoms, clinical evidence in people with FA is limited, and participation is often low due to barriers such as fatigue and safety concerns, the researchers noted.
Studies in other conditions have shown that supplementation with NAD+ precursors — compounds that raise levels of NAD+, a molecule involved in cellular energy production — can improve muscle function. These findings have raised the possibility that increasing NAD+ might complement or enhance the benefits of exercise alone. However, there’s limited research on whether these therapies might improve FA patients’ ability to exercise.
The team of researchers in the U.S. conducted a 12-week clinical trial (NCT04192136) involving 66 people with FA enrolled at a single center in Philadelphia from September 2020 to April 2025.
Half of the participants were children, ages 10 to 17, and half were adults, ages 18 and older. Most (56%) were male. The overall mean age was 20.3. At the start of the study, participants generally had lower-than-average muscle mass and slightly higher body fat compared with reference values for the general population.
Participants were randomly assigned to one of four groups: 17 received a placebo and served as controls, 17 received only the NAD+ precursor nicotinamide riboside, 16 followed a structured exercise program and were given a placebo, and 16 followed the exercise program in addition to supplementation with nicotinamide riboside. All participants completed the study.
The exercise program consisted of three aerobic and two resistance training sessions per week, performed at home under remote supervision. Participants took nicotinamide riboside or placebo orally each day using weight-based dosing: one capsule (300 mg) for patients weighing 24-48 kg (about 53-110 lbs) and three capsules (900 mg) for patients weighing more than 72 kg (about 159 lbs). The study’s main goal was to assess changes in peak oxygen uptake (VO₂), a key measure of cardiopulmonary fitness.
At the end of the 12-week program, participants who received both exercise and nicotinamide riboside showed the greatest improvements in cardiopulmonary fitness. Peak VO₂ increased by 13.2% in the combination group, compared with a 3.9% decline in the control group.
VO₂ rose by 9.5% with exercise alone and 5% with nicotinamide riboside alone, but those changes were not statistically significant compared with controls.
The combination was not significantly more effective than exercise alone, indicating no clear added benefit from the supplement.
Some secondary measures improved. Compared with controls, the combination group reached higher maximum workloads during exercise, and oxygen pulse — a measure of how efficiently the body uses oxygen — improved in both the combination and exercise-only groups. Participants in the combination group also reported spending more time in physical activity and leisure exercise.
The interventions were generally safe and well-tolerated. No serious adverse events were reported, and all side effects were mild or moderate. The most common ones were skin problems (53%), gastrointestinal symptoms (45%), upper respiratory infections (35%), and falls (20%).
Falls, a known barrier to exercise in FA, occurred at similar rates across all groups, and no increase in heart-related or other adverse events was seen in participants assigned to exercise.
In an accompanying commentary, “Targeting exercise, energy, or both in Friedreich’s ataxia,” published in The Lancet Neurology, two researchers in Germany highlighted the study’s implications.
The trial’s findings extend existing clinical evidence on the benefits of exercise in FA by using an objective measure of fitness, such as peak VO₂, and by demonstrating that a home-based intervention is feasible, they wrote. Further studies “are needed to determine durability and clinical significance of fitness gains and to clarify any incremental contribution of nicotinamide riboside beyond structured exercise,” they said.
