In a 12-week pilot investigation, researchers observed that people diagnosed with early-stage Huntington’s disease experienced reduced disease severity after safely undertaking intermittent fasting, also referred to as time-restricted eating. This inaugural clinical trial of time-restricted eating for Huntington’s disease enrolled 20 volunteers who confined their daily meals to a six-to-eight-hour period each day during the study overall.
Russell Wells, the lead author and a medical student at Oregon Health & Science University, notes that animal studies have demonstrated time-restricted eating can trigger protective stress responses in cells, particularly brain cells, reducing their likelihood of dying.
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.
Study Findings
Initially, researchers were concerned about asking Huntington’s disease patients to eat within a limited window due to their weight loss challenges, but participants managed to maintain their calorie intake and body weight during the trial.
Wells highlights that this was arguably the most important finding of the study. 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.
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The study involved 20 early-stage Huntington’s disease patients who chose a daily eating window fitting their routine and adhered to it for 12 weeks, with researchers monitoring calorie intake, weight, and safety.
Participants adhered to the eating schedule for over five days weekly on average, reported minimal side effects, and preserved both body weight and lean muscle mass, indicating good tolerance.
Clinical and Biological Measures
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).
Additionally, blood levels of neurofilament light (NfL), a biomarker released when nerve cells are damaged, fell by an average of 13%. The research team also examined mitochondrial function in participants’ blood cells and 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, says Wells. If cells, including brain cells, become better at producing energy and handling stress, they may be more resilient to the disease process. The improvements in mitochondrial function are one explanation for this protection.
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Despite the study’s small scale and absence of a control group, the reduction in neurofilament light levels strongly suggests time-restricted eating may protect brain cells, though larger trials are needed for confirmation.
Larger randomized controlled trials will be required to rule out any potential placebo effects, says Wells. Detecting not only a reduction but a reversal of the trend in NfL concentrations in just three months is highly notable, especially considering that NfL concentrations in blood and spinal fluid consistently increase over time in people with Huntington’s disease.
The research team is now planning to conduct larger studies to confirm the findings and determine the long-term effects of time-restricted eating on Huntington’s disease. The study’s results were published in Nature Metabolism, and provide new hope for the development of effective treatments for this devastating disease.
Mitochondria generate energy for cells, and impaired energy production is a hallmark of Huntington’s disease. By improving mitochondrial function, time-restricted eating may help to protect brain cells from degeneration.
The fact that NfL levels fell by an average of 13% in just three months is a strong indication that time-restricted eating may be having a positive effect on the disease process.
