Appetite for Answers: Does Eating on a Schedule Help with Huntington’s Disease?

We know that lifestyle factors – like exercise, sleep, and alcohol consumption – can have an impact on the onset of Huntington’s disease (HD). Another lifestyle factor that people frequently wonder about is diet. A recent review explores the idea that “time-restricted eating”, an approach that limits meals to a specific window each day, could have therapeutic potential for HD. The idea is that timed eating might impact several biological systems affected by HD to improve brain function. But don’t hold the dinner bell, because most findings reviewed in this paper are from animals that model the disease, not from people, and there are some real risks to consider with this approach for people living with HD. Let’s dig into what they found and why you should be cautious. 

Huntington’s Disease: A System-Wide Challenge

HD is a devastating inherited condition caused by a genetic change in the huntingtin gene. This change leads to the production of a faulty protein, known as expanded huntingtin, which can clump together and cause widespread damage in the brain and body.

The symptoms are broad and progressive: uncontrolled movements, trouble with balance, memory, and thinking, and a range of psychiatric symptoms. What makes HD especially hard to treat is how deeply it affects various systems of the body; not just the brain, but also muscles, the heart, and the digestive tract.

Many drugs currently being tested in clinical trials zero in on a single molecular aspect of the disease or are only designed to hit the brain. It’s possible that in order to effectively treat HD long term, we may need a system-wide shift, which is where diet could come into play. 

Some Caveats Up Front

We frequently get asked about the role that diet plays in HD: What’s the best diet to delay onset and dampen symptoms? Has anyone looked into the ketogenic diet? Or the Mediterranean diet? A high fiber diet? We also frequently get asked about intermittent fasting. 

While there have been clinical trials testing some dietary supplements, like creatine and coQ10, those trials were halted for futility. The bottom line is that there are limited robust studies in people around diet as it relates to HD, onset of the disease, or the impact on symptoms. Because of that, most of what we know around these questions is from animals that model HD, and this is the scope of what is reviewed in this paper. 

Thus, everything we discuss in this article must be viewed under that lens and considered within the context that mice aren’t people. What we learn from animals could be informative, but many findings from animal studies have gone on to not be replicated in humans. 

With that said, it’s widely known that how one eats greatly impacts their life. A healthy diet and lifestyle can improve immune function, mood, sleep, brain function, and more. So it’s reasonable to wonder if altering diet could impact HD. A recent review of the academic literature dug into what others have found around time-restricted eating. 

What is Time-Restricted Eating (TRE)?

Time-restricted eating (TRE) is a form of intermittent fasting. Instead of focusing on how much you eat, TRE focuses on when you eat. A typical schedule might allow meals only between 12 PM and 8 PM with nothing but water, tea, or black coffee outside that window.

Unlike long-term calorie restriction (which is notoriously hard to stick to), TRE is sustainable for many people. Interestingly, studies have shown that even without reducing total calories, TRE seems to lead to real physiological changes, like improved metabolism, reduced inflammation, and can promote better brain health.

In the context of HD, some work suggests that TRE might show promise in animal studies. But how can something as simple as when you eat affect something as complex as a neurodegenerative disease?

Despite the interesting science from animals that model HD, TRE isn’t a one-size-fits-all solution, especially for people with HD. A huge concern is weight loss. Many people with HD already struggle with unintentional weight loss and muscle wasting, so fasting is risky.

Autophagy: The Brain’s Cleanup Crew

One of the main ways TRE could help in HD is by kickstarting a cellular cleanup process called autophagy. Think of it as your cells’ garbage disposal system. Autophagy helps break down and recycle damaged cellular parts, including toxic protein clumps like expanded huntingtin.

In people with HD, autophagy doesn’t seem to work as well as it should. Some researchers think that this contributes to the buildup of harmful protein aggregates that damage neurons. But fasting, especially for long enough to deplete the body’s energy stores, could trigger autophagy.

In mice that model HD, TRE seemed to lead to a boost in this cellular recycling. One study suggested that mice fed on an 18:6 fasting schedule (18 hours fasting, 6 hours feeding) seemed to have more autophagy activity and lower expanded huntingtin levels in their brains. 

BDNF: Fuel for Brain Growth

Another key mechanism of TRE could involve a molecule called BDNF, or brain-derived neurotrophic factor. BDNF helps neurons grow, survive, and connect with one another. People with HD have lower levels of BDNF, especially in vulnerable brain areas like the striatum.

However, some research suggests that TRE might trigger the production of ketone bodies that could prompt brain cells to make more BDNF.

In HD mouse models, intermittent fasting seemed to lead to a 3- to 4-fold increase in BDNF and may have produced benefits, like delayed symptom onset, better motor skills, reduced brain atrophy, and fewer protein clumps. In mice, these changes hint at a potential multi-pronged impact from something as basic as adjusting your eating schedule.

Powering Up: Mitochondria and Metabolism

Changes to cellular energy production is another known effect of HD. Mitochondria, the energy factories of cells, appear to undergo fatigue and damage that causes them to not function properly. TRE may help here too.

Fasting activates a certain protein that could help to build new mitochondria and defend against stress that damages them. In HD models, this activation seemed to lead to more energy production and better protection from cellular damage.

There’s even an early case report of a person with HD who tried a combined TRE and ketogenic diet for nearly a year. He reported improved motor function and fewer psychiatric symptoms. However, this is just one case with a self-reported outcome. The placebo effect can be incredibly strong, so this report should be taken with a healthy pinch of salt. 

Resetting the Clock: Circadian Rhythm in HD

Increasing evidence suggests that sleep disturbances and disrupted daily rhythms appear to be common and worsening symptoms in HD. The body’s internal clock, especially in brain areas like the hypothalamus, seems to be impacted by HD, affecting mood, cognition, and overall health.

TRE could help realign these biological clocks. While light resets the brain’s “master clock,” food timing resets “peripheral clocks” in organs like the liver and muscle. In HD mouse models, TRE seemed to improve sleep patterns, activity rhythms, and even heart rate variability, which all suggest better circadian health.

By aligning these clocks, TRE may ease some of the non-motor symptoms that make HD hard to manage.

Diet clearly plays an important role in overall health, but we don’t yet have enough evidence to prescribe specific eating schedules or meal plans to control HD. For now, food should be seen as a supportive tool, not a stand-alone treatment.

Real-World Concerns 

Despite the interesting science from animals that model HD, TRE isn’t a one-size-fits-all solution, especially for people with HD. A huge concern is weight loss. Many people with HD already struggle with unintentional weight loss and muscle wasting, so fasting is risky.

While the average person needs to consume about 2000 calories per day, people with HD may need to consume 5000 to 8000 calories per day. That’s a massive increase! So while someone without HD might be able to consume 2000 healthy calories in a 6 to 8 hour window, consuming 3 to 4 times that amount would be incredibly challenging for anyone. 

Additionally, TRE may be realistic for people in the early stages of HD, or those who carry the gene but haven’t developed symptoms yet, but those with more advanced HD are likely to experience increased episodes of choking. Combining that with trying to consume a large amount of calories in a short amount of time could induce unneeded stress, pressure, and undue risk.

Food as a Tool, Not Yet a Treatment

While it would be nice to believe we can one day delay or control the onset and symptoms of HD simply by adjusting when or what we eat, we’re not there yet. Diet clearly plays an important role in overall health, but we don’t yet have enough evidence to prescribe specific eating schedules or meal plans to control HD. For now, food should be seen as a supportive tool, not a stand-alone treatment.

Regardless of when you eat, whether you carry the gene for HD, are a caregiver, or just care about brain health, what you eat matters too. Food is medicine. A Mediterranean-style diet, rich in protein, fiber, healthy fats, and antioxidants, has been shown to support gut and brain health, and has been shown to support broader benefits outside the context of HD.

To truly understand the effects of diet on HD, blinded clinical trials would be needed. We would need carefully designed human studies to explore whether TRE is truly safe, sustainable, and effective for people with HD, especially in light of the challenges around calorie intake and choking risks. Until then, the science is compelling, but not yet conclusive.

TL;DR – Key Takeaways

• TRE = Time-Restricted Eating, where all meals occur within a set daily window (e.g., 12pm–8pm).
• TRE is not about eating less, but eating on a schedule without reducing calories.
• In HD mouse studies, TRE was suggested to reduce toxic huntingtin protein levels and improve brain health.
• TRE may boost autophagy (cell cleanup), BDNF (brain growth), and cellular energy and defense.
• TRE studies suggested in mice it could help reset circadian rhythms, potentially improving sleep and HD-related behaviors.
• Major concern: weight loss and choking, which are both associated with HD. 
• Human trials are needed to test safety and effectiveness of any diet-related change for HD.
  

Learn More

Full research article, “Dietary fasting and time-restricted eating in Huntington’s disease: therapeutic potential and underlying mechanisms” (open access).