Fasting and Brain Health
Nowadays, the variety of food is becoming so abundant that more people are becoming overweight or even obese. The combination of three meals a day and a sedentary lifestyle can cause a series of knock-on effects. Most importantly, overeating dulls the mind and impairs memory. Many studies have found that intermittent fasting makes the brain health more alert.
Eating patterns like eating for restricted periods, alternate day fasting (ADF), and the 5:2 diet not only help with weight control but also positively impact brain health and cognitive function.
How Does Fasting Affect the Brain?
→ Fasting helps produce ketone bodies (the brain’s health favorite fuel)
After 12-36 hours of fasting, the body enters a physiological state of ketosis, which is characterized by low blood glucose levels, depletion of hepatic glycogen reserves, and the liver’s production of fat-derived ketone bodies, which are the brain’s main source of energy.
The liver is the primary site of ketogenesis, but brain astrocytes also produce ketone bodies, which become the brain’s preferred fuel source for up to 70% of its energy needs during the first few days of fasting.
The study found that rodents treated with a ketogenic diet for five days showed improvements in spatial learning and memory. Ketone bodies are not only a source of energy for neurons, but primary blood ketone beta-hydroxybutyrate (BHB) also has an important signaling function.
In hippocampal neurons and cortical neurons, BHB upregulates the expression of brain-derived neurotrophic factor (BDNF) by inhibiting histone deacetylase, an enzyme that inhibits BDNF expression.
→ Fasting improves mitochondrial health
Fasting improves mitochondrial health by upregulating brain-derived neurotrophic factor (BDNF), which promotes the expression of mitochondrial master regulators.BDNF is a key regulator of neuronal function and has antidepressant effects. The most commonly used antidepressant drugs are mediated by BDNF.
It stimulates mitochondrial production, promotes synapse formation and maintenance, stimulates the production and survival of new hippocampal neurons, and enhances neuronal resistance to stress injury and disease.
In addition to BHB and BDNF, fasting promotes the expression of a master mitochondrial regulator, the transcription factor peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α).PGC1α is a central inducer of mitochondrial biogenesis that stimulates mitochondrial formation and increases the number of mitochondria, which in turn enhances neuronal synaptic plasticity and has a positive effect on neuronal bioenergetics.
→ Fasting aids glucose metabolism
Fasting for 3-5 days in humans reduces blood glucose levels by 30-40% and inhibits glycolysis, and fasting every other day for 3 weeks reduces insulin levels on the day of fasting by 50-60%.
In general, fasting for 3-5 days in humans also results in a 60% decrease in the major growth factor insulin-like growth factor (IGF-1), a 5-10 fold increase in one of its major binding proteins, IGF-1 binding protein (IGFBP1), and a 2-3 fold increase in growth hormone (GH) (a rise in growth hormone will ensure muscle mass).
→ Fasting inhibits mTOR and elevates AMPK, favoring autophagy
The balance between cellular synthesis and degradation is governed by two major regulators of metabolism, the target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK).
Under high nutrient conditions, mTOR stimulates protein synthesis and cell growth. In contrast, during fasting, nerve cells in the brain enter a “resource-saving” mode in which AMPK downregulates mTOR to minimize protein synthesis and stimulate autophagy.
Autophagy removes waste products from the cell, leading to cell renewal. In neurodegenerative processes, misfolded proteins (β-amyloid plaques and tau proteins) accumulate in the brain and cause damage, and autophagy helps to remove misfolded proteins and damaged organelles, carry out DNA repair, recycle nutrients, and promote energy production.
→ Fasting protects neurons and neural pathways
Fasting affects fat metabolism by decreasing leptin (associated with a pro-inflammatory state), increasing the hormonal activity of lipocalin (which enhances insulin sensitivity and suppresses inflammation), and growth hormone-releasing peptide (which enhances insulin sensitivity). In addition, growth hormone-releasing peptide stimulates hippocampal synaptic plasticity and neurogenesis, favoring the protection of neurons and neural pathways.
→ Fasting to suppress inflammation improves neuronal survival
Fasting also inhibits inflammation and reduces the expression of pro-inflammatory cytokines, such as interleukin 6 (IL6) and tumor necrosis factor-alpha (TNFα).
Since inflammation is the etiologic agent of many different neurological disorders, fasting’s ability to suppress neurological and systemic inflammation increases neuronal survival.
→ Fasting makes you more attuned to circadian rhythms
Intermittent fasting, where meals are eaten during the 6-10 hours when you are most active during the day, adjusts the peripheral rhythm clock and synchronizes it with the central rhythm clock, resulting in enhanced insulin sensitivity, improved metabolic health, and cognitive function.
Eating at times that don’t match the body’s natural circadian rhythms disrupts the way our organs work, and a study of shift workers found a high susceptibility to chronic diseases such as sleep disorders, cardiovascular disease, peptic ulcers, metabolic syndrome, and breast cancer.
A 2021 study of 883 adults in Italy found that those who limited their food intake to 10 hours a day were less likely to develop cognitive impairment than those on a diet with no time restrictions.
→ Fasting balances the gut microbiome
The gut microbiota is closely linked to brain health, and intermittent fasting can alter the composition of the gut microbiota, which affects the brain through neurological, endocrine, and immune pathways, leading to improved cognitive function.
Research on Fasting and Brain Health
→ Fasting reduces the risk of dementia
A 2022 study interviewed 411 non-demented older adults who underwent multimodal neuroimaging of brain β-amyloid (Aβ) and tau deposition, glucose metabolism, and cerebrovascular damage.
It was found that LMF (less than 3 meals per day) was significantly associated with lower Aβ deposition and reduced risk of Alzheimer’s disease compared to high meal frequency (HMF).
→ Reduces inflammation and boosts immunity
A study that recruited 50 healthy volunteers (21 men and 29 women) to fast for Ramadan found significant reductions in pro-inflammatory cytokines, tumor necrosis factor-alpha, and immune cell counts.
→ Improving Mild Cognitive Impairment in Older Adults
A longitudinal study of the Healthy Longevity Neuroprotective Model for Older Adults followed 99 participants over the age of 60 with mild cognitive impairment for 36 months.
Among the study participants, subjects were categorized into three groups: regular practice of intermittent fasting (r-IF), occasional practice of intermittent fasting (i-IF), and non-intermittent fasting (n-IF)
The results showed that subjects with mild cognitive impairment (MCI) in the r-IF group were free of cognitive impairment and disease (24.3%) compared to the i-IF group (14.2%) and the n-IF group (3.7%). Significant increases in body superoxide dismutase (SOD) activity, reductions in body weight, insulin levels, fasting glucose, malondialdehyde (MDA), C-reactive protein (CRP), and DNA damage, and higher cognitive scores.
→ Reduced oxidative stress, enhanced cognition and learning
Because oxidative stress induces cellular damage and impaired cognitive function and is a known contributor to brain aging, a mouse study examined the protective effects of intermittent fasting on the brain to measure the brain oxidative stress index.
Fifteen, 19, and 15 mice were observed for a total of 11 months, corresponding to the control, intermittent fasting, and high-fat diet groups, respectively.
The study found that the mice in the intermittent fasting group had a thicker CA1 pyramidal cell layer (improving learning and memory) than the control mice, and also increased debris (a dendritic protein) in the cerebral cortex and hippocampus, and there was a trend toward increased expression of the synaptic protein synaptophysin (synapsin) in the cerebral cortex and hippocampus (improving memory and cognition).
Measurements of NeuN, drebrin, and synaptophysin expression in CA1 pyramidal cell layer thickness (Fig. A) and in the cerebral cortex (Fig. B) and hippocampus (Fig. C), as well as BDNF levels in the cerebral cortex and hippocampus (Fig. D)
In addition, two indicators of oxidative stress in the cerebral cortex had protein levels of 4-hydroxy-2-nonenal (HNE) and nitrotyrosine, both of which were reduced in the intermittent fasting group, as well as glutathione disulfide (GSSG) levels, which led to a significant increase in the glutathione/GSSG ratio.
The final results of the experiment indicated that intermittent fasting reduces oxidative stress in the brain, slows down neurodegeneration, and enhances cognitive and learning abilities.