Could Fasting Help Promote Brain Health?

Could Fasting Help Promote Brain Health?

Key takeaways:

  • Fasting shifts the body from glucose to ketones, which provide an efficient and supportive fuel source for the brain.

  • Several mechanisms that occur during prolonged fasting (like autophagy) may also have promising brain benefits as well.  

  • Both intermittent and prolonged fasting methods offer unique benefits that may help boost cognitive health.


When people think about fueling the brain, they most likely think of fueling with food—not going without it. Yet growing research shows that giving your body a strategic break from calories through fasting can actually support your brain’s long-term health. 

Why? Fasting activates powerful metabolic and cellular processes that may sharpen mental clarity, protect against age-related decline, and even lower the risk of cognitive disease. In this post, we’ll explore the science behind these processes, examine how different fasting methods may support brain vitality, and highlight their potential to reduce the risk of cognitive decline while also promoting overall longevity.


What happens to the brain in a fasting state? 

When you fast, your brain doesn’t shut down—it adapts. In fact, fasting triggers a metabolic shift that changes how your brain is fueled. Under normal circumstances, your body runs primarily on glucose (stored in the form of glycogen). But during fasting, those glycogen reserves are gradually depleted. After roughly 24 hours without food, the body initiates a major shift known as ketogenesis. At this stage, the liver converts fatty acids from the body’s stored fat into ketone bodies, which take over as the body’s—and the brain’s—primary fuel source.

These ketone bodies, including beta-hydroxybutyrate and acetoacetate, serve two important roles. In prolonged starvation, they can be life-saving by preserving energy for critical functions. In shorter-term fasts, they mobilize fat stores to keep the body running smoothly. While most people recognize this fat-burning effect as a reason to fast, fewer realize that ketosis can profoundly impact the brain as well—in fact, ketones are often described as a kind of “super fuel” for the brain. They can supply up to 70% of the brain’s energy needs, often more efficiently than glucose, and provide added neuroprotective benefits. Considering the brain consumes nearly 20% of the body’s total energy, this switch is no small feat. It may help explain why many people report heightened focus, sharper thinking, and improved mental clarity post-fast (and even sometimes during!).


Fasting methods and their impact on brain health

Different fasting methods trigger overlapping, but distinct, biological processes that can benefit the brain. Here’s how intermittent fasting and prolonged fasting may impact brain health, according to research on the subject.

Intermittent Fasting (IF)


Intermittent fasting (IF) is an eating pattern that involves alternating between periods of eating and fasting. Popular approaches include time-restricted eating (TRE) such as 12:12/circadian eating (fasting 12 hours and eating in a 12-hour window, often aligned with circadian rhythm) or 16:8 (fasting 16 hours with an 8-hour eating window), as well as the 5:2 method, where five days of normal eating are paired with two non-consecutive days of significant calorie reduction. Key brain-related effects of IF have been shown to include:

  • Ketone production: Even in shorter fasts, glycogen depletion prompts ketone generation. These ketones fuel the brain more efficiently than glucose and can supply up to 70% of its energy needs. Many people report sharper focus and improved mood during IF as a result.

  • Improved insulin sensitivity: IF improves insulin signaling and may protect against “type 3 diabetes,” the term used for insulin resistance in the brain linked to Alzheimer’s disease. Ongoing calorie restriction protocols in older adults have also been associated with lower risk of cognitive decline.

  • BDNF upregulation & synaptic plasticity: Animal studies show that IF enhances expression of the brain-derived neurotrophic factor (BDNF) protein. The BDNF protein supports neurogenesis, neuronal survival, and synaptic plasticity, which strengthen the connections between brain cells responsible for learning and memory.

  • Neurogenesis: In mouse studies, intermittent calorie restriction has boosted neurogenesis in key regions of the brain such as the hippocampus (learning and memory), hypothalamus, and brainstem. This process of forming new nerve cells in the brain may translate into better protection against age-related decline.

  • Reduced inflammation & oxidative stress: IF can lower markers of inflammation and boost antioxidant defenses. By reducing reactive oxygen species (ROS) and dampening overproduction of cytokines, IF may help prevent the cellular damage and blood-brain barrier disruption that contribute to neurodegeneration.

Prolonged Fasting 

Prolonged fasting refers to abstaining from food for 72 hours or more. This type of fast, which can include extended water fasts and the 5-Day Fasting Mimicking Diet (FMD), triggers deeper physiological responses than shorter fasts. Evidence from animal models and mechanistic studies suggests prolonged fasting may support brain health in several ways, including:

  • Deeper ketosis: With glycogen depleted, ketones become the primary fuel for the brain, supporting cognitive resilience and potentially stronger neuroprotective effects than shorter fasts. While this deeper ketosis may not occur for all people during prolonged fasting, some level of cellular cleanup, or autophagy, occurs regardless.

  • Autophagy activation: Fasting triggers cellular recycling and removal of damaged proteins. In animal models, this process has been linked to the clearance of amyloid plaques, which are associated with neurodegenerative diseases like Alzheimer’s; in fact, preclinical trials in mice show FMD can reduce Alzheimer’s-related plaques and improve memory.

  • Neurogenesis: Animal studies indicate prolonged fasting can stimulate the generation of new neurons in regions involved in learning and memory.

  • Mitochondrial health: Longer fasts help clear damaged mitochondria and stimulate the production of new, healthier ones, which is critical for maintaining brain function.

  • Reduced inflammation and oxidative stress: Sustained fasting appears to lower inflammation and oxidative stress, which may help protect neurons.

Pre-clinical & real-world insights: Fasting-Mimicking Diet (FMD) 

Even though prolonged fasting may provide many benefits, extended water fasts are often difficult to sustain and come with risks. The FMD offers an easier and more sustainable approach, providing nourishment while keeping the body in a fasted state. Although human research on the FMD’s effects on brain health is still limited, further research is needed to fully understand its potential effects. However, early and real-world observations include: 

  • Psychological benefits: In one study, patients combining psychotherapy with FMD reported greater gains in self-esteem and overall psychological quality of life compared to those receiving psychotherapy alone.

  • Cognitive effects: Many participants describe feeling more alert, focused, and mentally clear following the five-day program.

While those observations highlight areas explored in humans, the following preclinical studies in mice have also shown promising insights into the mechanisms through which FMD may influence the brain:

While promising, these pre-clinical findings remain limited to animal models, and further research is needed to determine how they might translate to humans.


Easy ways to maximize fasting for brain health 

If you’re thinking about exploring fasting as a means of improving longevity and overall wellness– including support for brain health–here are a few tips to help maximize your fasting experience for best results:


  • Be patient with yourself, and listen to your body as it responds to the process.  

  • Prioritize hydration, drinking plenty of water and herbal teas if your fasting method allows. 

  • For intermittent fasting, focus on nutrient-dense foods and Longevity Diet principles during eating windows

  • Incorporate other brain-healthy habits like gentle exercise, quality sleep, and stress management. 

  • Consider a structured approach like Prolon’s 5-Day FMD, which offers a pre-formulated, safe, and clinically-proven path to prolonged fasting benefits.

Although much remains to be discovered about fasting’s role in preventing and treating cognitive decline, current evidence is promising. If you’re considering incorporating fasting into your routine, be sure to consult your healthcare provider first.




Sources: 


MDPI. “The Potential of Fasting-Mimicking Diet as a Preventive and Curative Strategy for Alzheimer’s Disease.” Website. 

National Library Of Medicine. National Center For Biotechnology Information. “Alzheimer's Disease Is Type 3 Diabetes–Evidence Reviewed.” Website. 

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National Library Of Medicine. National Center For Biotechnology Information. “Clearing the Brain’s Cobwebs: The Role of Autophagy in Neuroprotection.” Website. 

National Library Of Medicine. National Center For Biotechnology Information. “Clinical review: Ketones and brain injury.” Website. 

National Library Of Medicine. National Center For Biotechnology Information. “Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even Without Weight Loss in Men with Prediabetes.” Website. 

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National Library Of Medicine. National Center For Biotechnology Information. “The Impact of Intermittent Fasting on Brain-Derived Neurotrophic Factor, Neurotrophin 3, and Rat Behavior in a Rat Model of Type 2 Diabetes Mellitus.” Website.

National Library Of Medicine. National Center For Biotechnology Information. “The Role of BDNF as a Biomarker in Cognitive and Sensory Neurodegeneration.” Website.

Science Direct. “Intermittent fasting and cognitive performance – Targeting BDNF as potential strategy to optimise brain health.” Website.

Science Direct. “The neuroprotective effects of intermittent fasting on brain aging and neurodegenerative diseases via regulating mitochondrial function.” Website. 

Wiley. Journal of Clinical Psychology. “Efficacy of a fasting-mimicking diet in functional therapy for depression: A randomised controlled pilot trial.” Website.

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