GLP-1 and Fasting: How Unlocking Sugar in the Brain Could Prevent Alzheimer’s

A new study from the Buck Institute has uncovered something remarkable about how our brain works with sugar. For decades, scientists believed that only the brain’s support cells, astrocytes, stored glycogen, the storage form of glucose.

Neurons, the cells responsible for memory, thinking, and learning, were thought to rely solely on fuel delivered moment by moment.

This study has now shown that neurons do store sugar, and how they handle it could make the difference between protecting the brain or accelerating diseases like Alzheimer’s.

The Hidden Role of Sugar in the Brain

Normally, glycogen in neurons can be broken down and funneled into a pathway called the pentose phosphate pathway. This does not provide energy in the way we usually think of glucose metabolism. Instead, it generates NADPH and glutathione, two of the most powerful antioxidants in the body. These compounds protect neurons from oxidative stress, which is one of the major drivers of brain aging and neurodegeneration.

In conditions such as Alzheimer’s and frontotemporal dementia, the tau protein binds to glycogen, trapping it and preventing neurons from using it. That means less glutathione, less protection, and more damage over time.

In the study, when researchers restored the enzyme that breaks down glycogen, called glycogen phosphorylase, neurons were able to unlock their sugar stores, produce antioxidants, reduce tau-related damage, and even extend lifespan in animal models.

Why Fasting and GLP-1 Drugs Are Part of the Solution

Two approaches helped restore glycogen breakdown in neurons.

• Fasting and dietary restriction naturally activated glycogen phosphorylase, helping neurons defend themselves from stress.

• GLP-1 receptor agonists, medications already widely used for diabetes and weight loss, seemed to mimic this effect.

This may help explain why people using GLP-1 drugs such as semaglutide or tirzepatide have shown improvements in brain health markers in some studies. These drugs may not only lower blood sugar and reduce appetite, but also help neurons unlock glycogen to fight oxidative stress.

The Three Main Types of GLP-1 Drugs

GLP-1 drugs are not all the same. There are three main categories.

• GLP-1 receptor agonists (single-acting). Examples include Ozempic, Wegovy (semaglutide), Trulicity (dulaglutide), and Victoza (liraglutide). These mimic the natural GLP-1 hormone, slowing digestion, reducing appetite, and improving insulin sensitivity.

• Dual GLP-1 and GIP agonists. The best-known example is Mounjaro (tirzepatide). These target both GLP-1 and GIP receptors, giving stronger effects on blood sugar and weight loss, and potentially more impact on inflammation.

• Oral GLP-1 drugs. Rybelsus (oral semaglutide) works like injectable GLP-1 medications but is taken by mouth.

The Downsides of GLP-1 Drugs

While these medications can be powerful tools, they are not without risks.

• Nausea, vomiting, and digestive distress are common, especially early on.• Nutrient deficiencies may develop if appetite suppression leads to inadequate food intake.• Muscle loss can occur if weight loss is not supported with protein and resistance training.• Gallbladder problems and rare cases of pancreatitis have been reported.• Long-term effects on the brain and other organs are still being studied.

For this reason, GLP-1 drugs should never be seen as a complete solution. They may help unlock brain defenses, but without addressing root causes such as oxidative stress, poor diet, gut health, insulin resistance, sleep, and toxin exposure, they are only one piece of the puzzle.

Where Peptides Fit Into the Picture

The study highlights how neurons protect themselves when they can unlock stored sugar and produce antioxidants. While fasting and GLP-1 drugs help activate this pathway, there are other tools being studied that support cellular repair and brain protection. One of the most promising areas is peptide therapy.

• Cognitive and neuroprotective peptides such as Cerebrolysin, Dihexa, or Semax and Selank are being studied for their ability to enhance brain repair, synaptic growth, and reduce oxidative stress.

• Metabolic peptides such as Tesamorelin or AOD-9604 can improve insulin sensitivity and body composition, indirectly lowering the metabolic stress that contributes to dementia risk.

• Mitochondrial support peptides such as SS-31 (Elamipretide) work by improving energy production and reducing oxidative damage at the cellular level, similar to what this study showed with glycogen breakdown.

These therapies are still under research, but they align with the same philosophy: reduce oxidative stress, repair cells, and restore the body’s natural defense systems.

How the Gut Connects to Brain Protection

The gut and brain are deeply connected through what is called the gut–brain axis. When the gut is inflamed or leaky, toxins and inflammatory molecules can move into circulation and trigger oxidative stress in the brain. This fuels the very same pathways of damage seen in Alzheimer’s and other neurodegenerative diseases.

Supporting gut integrity is not just about digestion. It is also about protecting neurons. By lowering systemic inflammation, improving nutrient absorption, and calming the immune system, we create the conditions for the brain to heal and defend itself.

Peptides for Gut and Inflammation Support

Some peptides being studied show promise in supporting gut repair and reducing inflammation.

• BPC-157, often called the gut healing peptide, supports repair of the intestinal lining, reduces inflammation, and may help protect against leaky gut. By calming gut-driven oxidative stress, it indirectly benefits the brain.

• Thymosin Beta-4 (TB-500) has strong anti-inflammatory and tissue-healing properties that extend beyond the gut. It could help lower systemic inflammation, which is a driver of brain aging.

• KPV is a peptide fragment with potent anti-inflammatory effects in the gut. It is being explored for conditions such as colitis but may also help calm immune activation more broadly.

These peptides do not directly act on neurons the way fasting or GLP-1 drugs do, but they reduce the systemic inflammation and oxidative stress that make neurons more vulnerable in the first place.

Optimized Hormones and Brain Protection

Hormones are powerful messengers that influence how the brain ages and repairs itself. When balanced, they support resilience and repair. When imbalanced, oxidative stress rises and neurons become more vulnerable.

• Estrogen protects neurons, supports synaptic growth, and enhances antioxidant pathways. In women, low estrogen after menopause increases dementia risk. Progesterone has calming, anti-inflammatory effects on the brain.

• Testosterone supports memory, mood, and energy. Low levels in both men and women are linked with cognitive decline and reduced resilience.

• Thyroid hormones drive cellular energy. Low thyroid function slows detoxification and reduces brain energy.

• Cortisol and DHEA regulate the stress response. Chronic stress raises cortisol, which accelerates brain aging, while low DHEA reduces repair capacity.

When hormones are optimized, neurons respond more effectively to oxidative stress and repair damage. This also makes strategies such as fasting, GLP-1 therapies, and peptides more effective, since the body is no longer fighting against an underlying imbalance.

Getting to the Root Cause

The most powerful part of this study is the reminder that the body has built-in healing systems. Neurons already know how to protect themselves, but they need the right conditions.

• Fasting and metabolic flexibility allow neurons to switch fuel sources, activate glycogen breakdown, and boost antioxidant defenses.

• Nutrient-dense diets supply the raw materials needed for glutathione production and cellular repair.

• Gut and liver health support detoxification and reduce the toxic burden that fuels oxidative stress.

• Balanced hormones and steady blood sugar prevent the chronic inflammation that drives brain aging.

Whether or not someone uses GLP-1 medications or peptides, the real goal is to create an environment where the brain can thrive naturally. This means reducing stress, repairing cells, and preventing disease from taking hold.

This discovery is groundbreaking because it connects lifestyle, fasting, and even modern drugs to a single pathway inside the brain: the way neurons use sugar. It reminds us that health is never about one pill or protocol. It is about understanding how the body is designed to heal and supporting those systems in a comprehensive way.

GLP-1 medications, peptides, and optimized hormones may become important tools for some people, especially in the context of diabetes, obesity, and possibly dementia prevention. But they are not replacements for the root-cause work: restoring metabolic health, building resilience, and creating lasting cellular repair.

The hopeful message is this: whether through fasting, diet, lifestyle, hormone optimization, or carefully chosen therapies, we have more influence over our brain health than ever before.