Intermittent fasting and the brain – what research reveals about its cognitive benefits

Intermittent fasting (IF) is increasingly recognised as a powerful approach to supporting cognitive function and overall brain health. Research demonstrates that IF can enhance insulin sensitivity, improve mitochondrial efficiency, reduce inflammation and stimulate cellular repair, all of which are essential for maintaining optimal brain performance. These benefits stem from the metabolic adaptations triggered during fasting, which not only help protect neurons but also promote cognitive function in the short term and greater brain resilience over the long term.

In this week’s blog, we explore the biological pathways through which IF supports brain health and share practical nutrition strategies, along with key considerations to be mindful of.

Why metabolic health matters

Cognitive decline is rising globally, driven by many factors including poor metabolic health. Blood sugar fluctuations, impaired insulin signalling and chronic inflammation place significant stress on the brain, disrupting energy supply and communication between neurons. This can manifest as brain fog, fatigue, low mood and poor concentration, long before a formal diagnosis of disease. Supporting metabolic health is therefore essential for protecting short and long-term brain health.

Metabolic dysfunction stems from a complex mix of modern lifestyle and environmental influences that interfere with key regulatory systems. Diets high in refined carbohydrates and inflammatory fats impair glucose control, raise blood sugar and drive insulin resistance, leading to fat accumulation and unstable energy. Chronic stress adds to the burden by raising cortisol, weakening insulin sensitivity, promoting visceral fat and disrupting appetite signals. Sedentary habits and poor sleep further reduce mitochondrial performance and alter hunger hormones, increasing cravings and overeating. Toxin exposure compounds the issue by increasing oxidative stress and affecting detoxification pathways crucial for metabolic balance. 

Intermittent fasting and metabolic switching

IF involves alternating periods of eating and fasting and is often used to support metabolic health. Popular approaches include time restricted eating, the 16:8 method, 5:2 and alternate day fasting. While each varies in duration, all aim to promote metabolic flexibility, the body’s ability to shift between fuel sources. This shift, known as metabolic switching, allows the body to alternate between fed (glucose-burning) and fasted (fat-burning) states. This switching is thought to be at the root of many of IF’s health benefits, from weight loss to improved metabolic health and cellular repair.

After roughly 10 to 12 hours without food, the body begins to deplete its glycogen stores and shifts from burning glucose to burning fat. This metabolic switch triggers the breakdown of fatty acids into ketones, which provide a steady and efficient fuel source. Ketones, such as beta hydroxybutyrate, are not just a backup fuel, they are anti-inflammatory, neuroprotective and energy efficient. In those with poor metabolic flexibility, often due to insulin resistance and high carbohydrate diets, the brain becomes overly dependent on glucose. When glucose dips, this can lead to brain fog, fatigue and mood changes. Efficient switching between fuels helps stabilise energy, sharpen focus and activate protective pathways that support long term brain health. Unlike our ancestors who regularly fasted due to food scarcity, modern eating patterns keep us locked in glucose burning mode, rarely activating fat burning mode. Reintroducing fasting may therefore help restore metabolic balance and unlock the cognitive benefits we have largely lost

Fuelling the brain with ketones

The brain consumes around 20 to 25 percent of the body’s energy, and ketones offer distinct advantages over glucose. For example, they produce more ATP per oxygen molecule, helping to stabilise energy supply. ^[1] They generate fewer reactive oxygen species, which lowers oxidative stress, helping to protect neurons. Ketones also act as signalling molecules that influence gene expression, activating pathways that reduce inflammation and support neuroplasticity. ^[2],^[3] These include AMPK (AMP activated protein kinase), SIRT1 and mTOR suppression, all of which promote mitochondrial health, autophagy and improved brain function. More below.

Autophagy and cellular repair

Autophagy is the body’s natural cellular recycling system, triggered during fasting to clear out damaged proteins and metabolic waste. It signals the body to shift from growth and storage to repair and recycling. In the brain, it helps prevent the buildup of toxic debris linked to conditions such as Alzheimer’s and Parkinson’s, while supporting mitochondrial renewal to keep neurons efficient and resilient. This process is regulated by nutrient-sensing and stress-responsive pathways. A key driver is the AMPK–mTOR axis. Frequent eating, physical inactivity and elevated insulin levels work together to activate the mTOR pathway, a central regulator of anabolic metabolism. When food is abundant and insulin is consistently high, mTOR signals cells to prioritise growth, protein synthesis and fat storage.

Conversely, fasting activates AMPK, a cellular energy sensor, which suppresses mTOR. This shift promotes autophagy, allowing cells to initiate cleanup and regeneration.^[4] Fasting also boosts NAD⁺ levels, activating SIRT1, a longevity-associated enzyme that enhances autophagy and stress resistance. Lower insulin and IGF-1 levels reinforce this shift by downregulating growth signals.^[5] Together, these mechanisms coordinate a cellular renewal process that supports both metabolic and cognitive health.

Mitochondrial biogenesis

During fasting, reduced nutrient availability and lower insulin levels trigger AMPK as mentioned above. Once activated, AMPK stimulates PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a regulator of mitochondrial biogenesis. PGC-1α enhances the expression of genes involved in mitochondrial replication, energy production and antioxidant defence, leading to the creation of new, more efficient mitochondria.^[6] This is especially important for high-energy-demand tissues, like the brain. This renewal process is critical for neurons, which rely heavily on mitochondrial function to maintain synaptic activity, plasticity and long-term cognitive performance.

Inflammation and oxidative stress

Chronic low-grade inflammation and oxidative stress are major contributors to cognitive decline and neurodegeneration. IF helps suppress pro-inflammatory signalling (e.g. NF-κB) and enhances antioxidant defences (e.g. Nrf2), creating a more favourable environment for optimal neuronal health. These effects help preserve synaptic integrity, reduce neuroinflammation and support vascular function.^[7] 

Insulin sensitivity and glucose regulation

IF directly improves insulin sensitivity by reducing insulin levels and allowing cells to regain their responsiveness. During a fast, insulin secretion drops significantly, which helps break the cycle of chronically elevated insulin that often leads to resistance. This low-insulin state prompts the body to switch from burning glucose to using stored fat for energy, a metabolic shift that enhances cellular insulin response over time. The activation of AMPK improves glucose uptake and supports mitochondrial function, further reinforcing insulin sensitivity. ^{[8], [9], [10]}

Dopamine reset

IF may help dopamine signalling by reducing overstimulation and restoring sensitivity to natural rewards. When we fast, the absence of constant food cues, especially highly palatable options, lowers the frequency of dopamine spikes tied to reward-seeking behaviour. This break from continuous stimulation may help dopamine receptors to reset. 

The gut-brain connection

IF supports gut health by allowing the digestive system to rest, repair and rebalance, benefitting the brain directly via the gut–brain axis. Fasting promotes microbial diversity, increasing beneficial bacteria that produce short-chain fatty acids, which help maintain gut barrier integrity and reduce inflammation. This microbial shift also supports neurotransmitter synthesis, particularly serotonin, much of which is produced in the gut. IF lowers exposure to inflammatory triggers and allows time for mucosal healing, helping prevent leaky gut and systemic inflammation, both of which are linked to cognitive decline and mood disturbances. Fasting also activates autophagy in gut epithelial cells, clearing damaged components and supporting tissue regeneration. IF further supports gut health by enhancing the migrating motor complex (MMC), the natural muscle contractions of the small intestine that occur when we are not eating that help prevent bacterial overgrowth and maintain microbial balance. ^{[11], [12]}

BDNF and neuroplasticity

Brain-derived neurotrophic factor (BDNF) is a key protein involved in neurogenesis, synaptic plasticity and learning. BDNF promotes the growth and maintenance of dendrites and synapses and also enhances the production and survival of new neurons from neural stem cells. Fasting increases BDNF expression through multiple mechanisms, including ketone signalling and reduced inflammation.^{[13], [14], [15]}

Nutrition strategies to maximise the benefits of IF

Nutrition plays a pivotal role in amplifying the cognitive and metabolic benefits of IF. Prioritising nutrient-dense foods, especially those rich in magnesium, omega 3 fatty acids, B vitamins and antioxidants support mitochondrial health and protect neuronal integrity. ^[16]

Post-fast meals should balance quality protein, healthy fats and fibre rich carbohydrates to stabilise blood sugar and support insulin sensitivity. Hydration and electrolyte balance are also essential for sustaining energy levels and mental clarity throughout fasting and feeding phases.

Finally minimising processed foods is critical as they can trigger insulin spikes and undermine the metabolic gains of fasting.

Supportive supplements

Targeted supplementation can enhance the neurological benefits of IF by supporting mitochondrial function, reducing inflammation and promoting certain metabolic pathways. Magnesium plays a key role in energy production and neurotransmitter balance, while omega-3 fatty acids (EPA/DHA) promote synaptic plasticity and help reduce neuroinflammation. Chromium and cinnamon are useful for supporting healthy blood glucose balance.^[17] Curcumin helps modulate inflammatory signalling and supports BDNF expression,^[18] and adaptogens such as Rhodiola and Ashwagandha can help mitigate the effects of chronic stress. Nicotinamide riboside is a form of vitamin B3 that helps boost levels of NAD+, a coenzyme essential for mitochondrial function, DNA repair and the activation of sirtuins, particularly SIRT1, mentioned above.^[19]

Phytonutrients  

Several well researched phytochemicals have been shown to support AMPK activation and SIRT1 modulation, central to cellular repair. Resveratrol directly activates SIRT1 and indirectly stimulates AMPK by increasing NAD⁺ availability.^[20] Quercetin modulates SIRT1 while supporting mitochondrial function and antioxidant defences. Curcumin, the active compound in turmeric, influences both AMPK and SIRT1, offering broad anti-inflammatory and cellular protective effects. ^[21]

Electrolytes

During fasting, insulin levels drop, which can lead to increased excretion of sodium and other electrolytes. This shift often contributes to symptoms such as fatigue, headaches and brain fog. Supplementing with an electrolyte complex containing magnesium, potassium and sodium may help maintain electrolyte balance, support nerve and muscle function and prevent dehydration, especially during longer fasts or active periods.

Considerations for intermittant fasting

While IF offers promising cognitive and metabolic benefits, it may not be suitable for everyone and should be practised thoughtfully. IF is most effective when combined with a balanced lifestyle that includes nutrient-dense foods, quality sleep, regular physical activity and effective stress management. Individuals who are pregnant, underweight, have a history of disordered eating, or are taking glucose-lowering or other medications should seek guidance from a healthcare professional before starting any fasting protocol. Additionally, hormonal fluctuations across the menstrual cycle can significantly influence the body’s response to fasting, affecting metabolism, insulin sensitivity, and stress resilience.

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References

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[2] Puchalska, P., & Crawford, P. A. (2017). Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. Cell metabolism, 25(2), 262–284.

[3] Maalouf M, Sullivan PG, Davis L, Kim DY, Rho JM. Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience. 2007 Mar 2;145(1):256-64.

[4] Vasim, I., Majeed, C. N., & DeBoer, M. D. (2022). Intermittent Fasting and Metabolic Health. Nutrients, 14(3), 631.

[5] Mouchiroud, L., Houtkooper, R. H., & Auwerx, J. (2013). NAD⁺ metabolism: a therapeutic target for age-related metabolic disease. Critical reviews in biochemistry and molecular biology, 48(4), 397–408.

[6] Halling JF, Pilegaard H. PGC-1α-mediated regulation of mitochondrial function and physiological implications. Appl Physiol Nutr Metab. 2020 Sep;45(9):927-936.

[7] Mattson M. P. (2012). Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell metabolism, 16(6), 706–722.

[8] Patikorn, C., Roubal, K., Veettil, S. K., Chandran, V., Pham, T., Lee, Y. Y., Giovannucci, E. L., Varady, K. A., & Chaiyakunapruk, N. (2021). Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials. JAMA network open, 4(12), e2139558.

[9] Morales-Suarez-Varela, M., Collado Sánchez, E., Peraita-Costa, I., Llopis-Morales, A., & Soriano, J. M. (2021). Intermittent Fasting and the Possible Benefits in Obesity, Diabetes, and Multiple Sclerosis: A Systematic Review of Randomized Clinical Trials. Nutrients, 13(9),

[10] Wang, X., Li, Q., Liu, Y., Jiang, H., & Chen, W. (2021). Intermittent fasting versus continuous energy-restricted diet for patients with type 2 diabetes mellitus and metabolic syndrome for glycemic control: A systematic review and meta-analysis of randomized controlled trials. Diabetes research and clinical practice, 179, 109003.

[11] Paukkonen, I., Törrönen, E. N., Lok, J., Schwab, U., & El-Nezami, H. (2024). The impact of intermittent fasting on gut microbiota: a systematic review of human studies. Frontiers in nutrition, 11, 1342787.

[12] Terry, N., & Margolis, K. G. (2017). Serotonergic Mechanisms Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance. Handbook of experimental pharmacology, 239, 319–342.

[13] Rothman, S. M., Griffioen, K. J., Wan, R., & Mattson, M. P. (2012). Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health. Annals of the New York Academy of Sciences, 1264(1), 49–63.

[14] Longo, V. D., & Mattson, M. P. (2014). Fasting: molecular mechanisms and clinical applications. Cell metabolism, 19(2), 181–192.

[15] Rothman, S. M., Griffioen, K. J., Wan, R., & Mattson, M. P. (2012). Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health. Annals of the New York Academy of Sciences, 1264(1), 49–63.

[16] Crupi R, Marino A, Cuzzocrea S. n-3 fatty acids: role in neurogenesis and neuroplasticity. Curr Med Chem. 2013;20(24):2953-63.

[17] Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14.

[18] Radbakhsh S, Butler AE, Moallem SA, Sahebkar A. The Effects of Curcumin on Brain-Derived Neurotrophic Factor Expression in Neurodegenerative Disorders. Curr Med Chem. 2024;31(36):5937-5952

[19] Vreones M, Mustapic M, Moaddel R, Pucha KA, Lovett J, Seals DR, Kapogiannis D, Martens CR. Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin. Aging Cell. 2023 Jan;22(1):e13754.

[20] Ciccone L, Piragine E, Brogi S, Camodeca C, Fucci R, Calderone V, Nencetti S, Martelli A, Orlandini E. Resveratrol-like Compounds as SIRT1 Activators. Int J Mol Sci. 2022 Dec 1;23(23):15105.

[21] Sadek MA, Rabie MA, El Sayed NS, Sayed HM, Kandil EA. Neuroprotective effect of curcumin against experimental autoimmune encephalomyelitis-induced cognitive and physical impairments in mice: an insight into the role of the AMPK/SIRT1 pathway. Inflammopharmacology. 2024 Apr;32(2):1499-1518.

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Last updated on 23rd September 2025 by cytoffice