In a pilot study, patients engaging in intermittent fasting demonstrated improvements in Huntington’s disease, a neurodegenerative condition currently considered untreatable. However, the study’s size and limitations call for more research [1].
Fast to survive
Huntington’s disease is an inherited, progressive neurodegenerative disorder caused by an expansion of a repeated DNA sequence in the HTT gene, which encodes the huntingtin protein. Like many neurodegenerative diseases, it is also age-related, with average age of onset between 30 and 50 (juvenile onset happens in about 5% to 10% of cases). The disease affects movement, cognition, and behavior. Although the mutation is the underlying cause, environmental factors may influence when symptoms emerge and how the disease progresses [2].
Currently, no disease-modifying treatments for Huntington’s exist. However, studies in mouse models have shown benefits from intermittent fasting (also known as time-restricted eating, TRE). This led the authors of the new study from Oregon Health & Science University, published in Nature Metabolism, to set up a small pilot trial of TRF in Huntington’s patients.
Twenty people with early-stage Huntington’s completed the study. Their average age was 45, and half were women. The researchers excluded people with unstable weight, high malnutrition risk, significant medical conditions, or cognitive impairment severe enough to prevent participation. Importantly, 60% started with an overweight or obese BMI.
Huntington’s score improves
After a one-week period recording their usual habits, participants adopted a self-selected eating window of 6 to 8 hours for 12 weeks. All participants chose relatively late schedules, with eating beginning between 10 a.m. and 1 p.m. and ending between 6 p.m. and 8 p.m.
Importantly, people with Huntington’s can experience unintended weight loss, which a shorter eating window might exacerbate. However, most patients were able to both adhere to the protocol and largely maintain their weight (a non-significant average loss of 1.12 kilograms was recorded), alleviating the researchers’ concerns.
Having established feasibility and tolerability, the researchers compared neurological assessments at baseline and on follow-up. The composite Unified Huntington’s Disease Rating Scale, a metric combining motor symptoms, functional capacity, and cognitive performance, improved by an average of 0.50 points. This study did not include a control group, but the authors note that this score typically declines by approximately one point per year in early-stage disease. While there was a clear improvement in two of the cognitive tests, the motor score improved modestly, and its significance did not survive multiple-testing correction in the primary analysis.
“This is the first time this approach has been formally studied in people with Huntington’s disease,” said Russell Wells, a fourth-year OHSU medical student and lead author of the study. “We found that participants were able to follow the eating schedule, maintain their weight and show encouraging improvements in clinical and biological measures that are important in Huntington’s disease. These results suggest time-restricted eating deserves further study in a larger clinical trial.”
Energy metabolism affected
Looking beyond clinical tests, the researchers measured plasma neurofilament light (NfL), a structural nerve-fiber protein that can enter the blood when nerves are injured. NfL decreased over the intervention period: the mean individual percentage reduction was 12.6%, while the median reduction was 6.4%. Although a decrease in NfL does not prove slowing of neurodegeneration, earlier longitudinal research specifically reports rising NfL levels as Huntington’s progresses.
“We saw a reversal of the trend we would normally expect,” Wells said. “Neurofilament light typically rises as neurodegeneration continues, but after three months we observed a significant decrease. For a pilot study, that was a remarkable finding.”
The clinical and NfL findings raised a mechanistic question: did the intervention alter cellular energy metabolism, which is disrupted in Huntington’s? The researchers isolated peripheral blood mononuclear cells, a group of circulating immune cells that includes lymphocytes and monocytes, and measured oxygen consumption.
After the intervention, the cells showed higher respiration. The team also found that this increased respiration was linked to increased production of the cellular energy currency ATP. Nonmitochondrial oxygen consumption increased as well.
“One theory is that fasting acts as a mild stressor that prompts cells to become more efficient,” Wells said. “If cells, including brain cells, become better at producing energy and handling stress, they may be more resilient to the disease process.”
The study had several important caveats, apart from lacking a control group and blinding. For instance, the participants also received nutritional guidance and physical-activity recommendations. The average amount of self-reported physical activity rose by 37 minutes a week, while calorie consumption dropped slightly. At least some of the improvement could have originated from these factors rather than from TRE itself.
“One of the unique aspects of Huntington’s disease is that some people know years in advance that they carry the genetic mutation,” Wells said. “That creates a window of opportunity to explore interventions that might delay onset or slow progression. Lifestyle approaches such as time-restricted eating could someday become an important part of that strategy.”
Literature
[1] Wells, R.G., Neilson, L.E., McHill, A.W. et al. (2026). Effects of time-restricted eating in early-stage Huntington’s disease: a pilot study. Nat Metab.
[2] Novati, A., Nguyen, H. P., & Schulze-Hentrich, J. M. (2022). Environmental stimulation in Huntington disease patients and animal models. Neurobiology of Disease, 171, 105725.
[3] Wang, H. B., et al. (2018). Time-restricted feeding improves circadian dysfunction as well as motor symptoms in the Q175 mouse model of Huntington’s disease. eNeuro, 5(1), ENEURO.0431-17.2017.
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