Pilot links intermittent fasting to lower Huntington’s disease severity without weight loss

Findings from a 12-week pilot study reveal that individuals with early-stage Huntington’s disease showed less disease severity after safely completing intermittent fasting, also known as time-restricted eating. Under the protocol, the 20 participants limited their eating window to six to eight hours each day. 

This is the first clinical study to test time-restricted eating in people with Huntington’s disease, according to its authors. Nutrition Insight learns more about the findings from first author, Russell Wells, a medical student at Oregon Health & Science University, US.

“Time-restricted eating has been shown to activate neuroprotective stress-response mechanisms in animal studies,” he says. “Like exercise, fasting challenges cells in a way that forces them to become more efficient at making energy.”

He explains that when cells behave like this, especially brain cells, they are less likely to die. “Fasting also stimulates a cellular cleanup process, known as autophagy, which removes old and damaged proteins.”

“Furthermore, it increases brain-derived neurotrophic factor (BDNF) production — a protein that promotes brain cell growth — and activates antioxidant mechanisms that protect cells from oxidative stress.”

Because weight loss is a major challenge for many people with Huntington’s disease, asking participants to eat within a limited time window initially seemed counterintuitive to the researchers.

However, participants were able to maintain their calorie intake and body weight throughout the trial. “This was arguably the most important finding of the study,” Wells highlights.

“If time-restricted eating was not safe, meaning participants could not maintain their body weight and muscle mass, then it would have no long-term utility as a potential therapeutic strategy. The fact that participants followed the diet so closely without adverse effects is very encouraging.”

Twelve-week fasting protocol

Although researchers have known the genetic cause of Huntington’s disease for decades, no treatments have been approved that slow or stop its progression. This rare, inherited neurological disease gradually damages nerve cells responsible for movement, cognitive, and emotional regulation.

Wells says it can be compared to “having Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis (ALS) at the same time.”

Participants were able to maintain their body weight throughout the trial, which is a typical concern among Huntington’s disease patients.The study hypothesis was based on previous research conducted in animal models showing that intermittent fasting can activate cellular pathways that help protect brain cells. However, researchers were unsure if the approach would be safe for patients with Huntington’s disease, as unintended weight loss is already a concern for this population.

Published in Nature Metabolism, the study enrolled 20 adults with early-stage Huntington’s disease. The participants selected an eating window that fit their daily routine, typically between late morning and early evening, and followed it for 12 weeks.

Throughout the study, researchers encouraged participants to maintain their normal calorie intake and monitored weight and safety.

The approach appeared well-tolerated, according to the study authors. Participants followed the eating schedule on average more than five days per week, reported few side effects, and maintained body weight and lean muscle mass.

Additionally, most participants adapted to the schedule within the first or second week.

Biomarkers reveal progress

The researchers 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.

Participants experienced an average improvement of 0.5 points on a widely used Huntington’s disease severity scale known as the composite Unified Huntington’s Disease Rating Scale (cUHDRS). The score typically declines by about one point annually in people with early-stage disease.

Additionally, blood levels of neurofilament light (NfL), a biomarker released when nerve cells are damaged, fell by an average of 13%. In Huntington’s disease. These levels typically increase over time as the disease progresses.

The research team also examined mitochondrial function in participants’ blood cells. They explain that because mitochondria generate energy for cells, impaired energy production is a hallmark of Huntington’s disease.

The authors found improvements in several measures of mitochondrial activity after the intervention.

“One theory is that fasting acts as a mild stressor that prompts cells to become more efficient,” Wells says. “If cells, including brain cells, become better at producing energy and handling stress, they may be more resilient to the disease process.”

Future clinical research directions

While it is difficult to prove these mechanisms in a human study without samples of brain tissue, Wells says that the improvement in NfL is a strong indicator of the downstream effects, suggesting time-restricted eating does protect brain cells from degeneration. The improvements in mitochondrial function are one explanation for this protection.

Given the study’s small size and lack of a control group, Wells’ team exercised caution when interpreting the findings.

“Our should be interpreted with cautious enthusiasm, cUHDRS more so,” he notes. “Improvement in a clinical score from a study with a single interventional group may represent a placebo effect.”

Larger randomized controlled trials will be required to rule this out, says Wells. “That said, NfL is far less susceptible to any sort of placebo responses.”

“A large body of evidence shows that NfL concentrations in blood and spinal fluid consistently increase over time in people with Huntington’s disease (roughly 10–18% annually). Detecting not only a reduction but a reversal of this trend in just three months is highly notable.”

One of the unique aspects of Huntington’s disease is that some people know years in advance that they carry the genetic mutation, Wells notes.

“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.”