Form of intermittent fasting may help slow Huntington’s, pilot study shows
Time-restricted eating limits daily calorie intake to 6-to-8-hour window
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Time-restricted eating (TRE), a form of intermittent fasting that limits daily calorie intake to a six-to-eight-hour window, may help slow the progression of Huntington’s disease, according to results from a three-month pilot study.
Study participants were able to maintain their body weight while showing reductions in disease severity measures and a nerve damage biomarker, along with better cellular energy production.
“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,” Russell Wells, a fourth-year medical student at Oregon Health & Science University (OHSU) and first author of the study, said in a university news story. “These results suggest time-restricted eating deserves further study in a larger clinical trial.”
The findings were described in the study “Effects of time-restricted eating in early-stage Huntington’s disease: a pilot study,” which was published in Nature Metabolism.
Weight loss a major challenge for many people with Huntington’s
Huntington’s is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric problems. It is caused by mutations in the HTT gene. While genetics influences disease onset, emerging evidence links lifestyle factors to disease progression.
TRE is a form of intermittent fasting that limits daily calorie intake to a certain time window. It has shown protective effects in animal models of Huntington’s, but scientists have never tested TRE in people with the condition. One reason is that restricting dietary intake could worsen the weight loss that typically occurs in Huntington’s patients.
“When Russell first brought me the idea, I was skeptical,” said Amie Hiller, MD, a professor of neurology in the OHSU School of Medicine and the study’s senior author. “Weight loss is a major challenge for many people with Huntington’s disease, so asking them to eat within a limited time window seemed counterintuitive.”
Still, the team at OHSU conducted a pilot study (NCT06490367) to assess the feasibility, safety, and effects of TRE in 10 women and 10 men with early-stage Huntington’s.
I was worried about the fasting, but it became pretty easy
After initial testing and a one-week lead-in period in which participants recorded their habits, they chose a daily eating interval of six to eight hours that would be followed for 12 weeks (about three months). They also received written guidance on nutrient-dense foods and physical activity.
During the TRE phase, participants were asked to complete a daily survey to track meal and sleep times and log meals in an app twice per week.
Regarding adherence, participants kept to an eating interval of eight hours or less on a mean of 75.6 days, or 5.3 days per week. Their mean eating interval fell from 10.3 hours during the lead-in to 7.6 hours during TRE.
“I was worried that I would struggle with the fasting part, but it became pretty easy and sort of matches my own hunger window,” said study participant Anna White, who had previously followed a ketogenic diet (high-fat, low-carb diet) to slow Huntington’s progression. “I am never hungry for breakfast anyway, so I could start my eating at 11 a.m. and finish by 5 to 7 p.m. easily.”
Overall disease severity lessened
Body weight and fat-free mass (body weight minus body fat) remained stable. A statistical analysis of weekly self-reported weights detected a small downward trend, for a total estimated loss of 0.7 kg (less than 1% of initial weight).
While mean daily calorie intake decreased significantly, by 168 kcal, and self-reported physical activity increased significantly, by a mean of 37 minutes per week, diet quality did not change significantly, as estimated with the Dietary Inflammatory Index and the Mediterranean diet scales.
No serious or moderate adverse events were reported, but one participant reported fatigue while fasting that interrupted daily activities.
Overall disease severity lessened, as indicated by significantly lower scores on the composite Unified Huntington’s Disease Rating Scale. Scores on the Symbol Digit Modalities Test, a measure of cognitive processing speed, and the Verbal Fluency Test, a measure of verbal memory and cognitive flexibility, also improved significantly.
A total of 11 participants reported a global reduction in symptoms, eight reported no change, and one reported minor worsening.
If future studies confirm these findings, this could become an approach available to people regardless of where they live or their financial resources.
Notably, blood levels of neurofilament light chain protein (NfL), a marker of nerve damage, significantly decreased by a mean of 12.6%, contrasting with the reported increase of 10% to 18% annually across Huntington’s stages.
“We saw a reversal of the trend we would normally expect,” Wells said. “[NfL] typically rises as neurodegeneration continues, but after three months we observed a significant decrease. For a pilot study, that was a remarkable finding.”
The researchers also found significant increases in four measures of cellular respiration, a process that reflects cell energy production, in patient blood cells after TRE.
“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.”
Hiller added: “If future studies confirm these findings, this could become an approach available to people regardless of where they live or their financial resources.”
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