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Key points
- Intermittent fasting (IF) increases neurogenesis and neuroplasticity.
- IF improves quality of life parameters.
- IF can reduce anxiety and depression symptoms.
There has been much discussion about food and mood. Entire organizations, such as the International Society of Nutritional Psychiatry Research and the Center for Nutritional Psychology, exist to investigate and educate on this very topic. And while it is well understood that specific nutritional deficiencies (such as of vitamins B12 and B9, and the trace mineral zinc) and a Western dietary pattern rich in processed foods are strongly associated with mood and cognitive decline,1 it is becoming clear that intermittent fasting has beneficial effects on the gut microbiome and the brain.
The Practice of Human Fasting
Since ancient times,2 humans have engaged in fasting for a variety of reasons and in a variety of ways, including several approaches to intermittent fasting such as: time-restricted eating (TME) and alternate-day/modified alternate-day fasting (ADF). The motivations behind these practices range from religion to weight management, but one of the most interesting outcomes is the positive impact on the brain.
The human brain accounts for approximately 2 percent of the average individuals’ body weight yet it consumes about a quarter of its energy.3 When food is consumed throughout the day, the brain relies on glucose for energy. During extended periods of food deprivation, however, a metabolic shift occurs in which the body and brain begin to utilize energy from fats stores in the form of ketones.4 When this shift from glucose to ketone metabolism occurs, neurons adapt in a number of ways, including, but not limited to:5
- Enhanced production of brain-derived neurotrophic factor (BDNF), key to brain cell growth, survival, learning, and memory, which in turn, reduces neuroinflammation.
- Increased production of transcription factor (peroxisome proliferator-activated receptor gamma coactivator 1 alpha factor), largely responsible for the formation of neuronal synapses and mitochondrial health in the hippocampus, a region of the brain closely associated with learning and memory.
- Inhibition of mTOR, the target for the immunosuppressive and potentially anti-aging antibiotic agent, rapamycin. mTOR downregulation stimulates the clearance of damaged proteins from cells, which protects against the development of neurodegenerative disease.
- Stimulation of fibroblast growth factor 2 (FGF2), which plays a protective role in brain cells as well as strengthening the connections between brain cells for enhanced learning (neuroplasticity).
- Upregulation of gamma-aminobutyric Acid (GABA), the primary excitatory neurotransmitter in the human brain, which is involved in information processing, neuroplasticity, learning, and memory.
- Increased levels of the hormone ghrelin. Produced by the stomach and pancreas, ghrelin increases brain-cell survival and improves attention and executive function.
- Enhanced growth hormone (GH, or somatotropin) production, which is neuroprotective and improves cognitive function, learning, and memory.
Much of the research on fasting has been conducted as preclinical studies, which show microbiota restructuring, increases in beneficial short-chain fatty acids and bile acids, and improved cognition.6,7 But a 2022 human clinical trial8 showed that a fasting:feeding regime of 16:8 hours maintained for three months resulted in significant quality of life improvement including better physical and mental health and reduced fatigue.
While a 2021 meta-analysis published in Nutrients9 showed the fasting groups had lesser anxiety and depression levels, as well as lower body mass index, with no increase in fatigue. Promising as the results are for mental wellness, the effects of fasting on physical benefits of human fasting must also be acknowledged, as the changes in psychological states have been attributed to physiological shifts.10 Another 2022 meta-analysis11 describes fasting-associated lipid-profile and insulin improvements, increased (growth hormone) glucagon, neuroendocrine activation (e.g., increased dopamine), and increased neurogenesis and neuroplasticity (BDNF production) associated with increased serotonin levels.
FInal Thoughts
Although it can be a challenging practice to adopt, intermittent fasting not only helps improve metabolism and reduce body weight,12 it has the potential to improve mood, cognition, and overall mental wellness.
References
1. Lachance L, Ramsey D. Food, mood, and brain health: implications for the modern clinician. Mo Med. 2015 Mar-Apr;112(2):111-5. PMID: 25958655; PMCID: PMC6170050.
2. Patterson RE, Laughlin GA, LaCroix AZ, Hartman SJ, Natarajan L, Senger CM, Martínez ME, Villaseñor A, Sears DD, Marinac CR, Gallo LC. Intermittent Fasting and Human Metabolic Health. J Acad Nutr Diet. 2015 Aug;115(8):1203-12. doi: 10.1016/j.jand.2015.02.018. Epub 2015 Apr 6. PMID: 25857868; PMCID: PMC4516560.
3. Attwell, D.; Laughlin, S.B. An Energy Budget for Signaling in the Grey Matter of the Brain. J. Cereb. Blood Flow Metab. 2001, 21, 1133–1145.
4. Pollay, M.; Stevens, F.A. Starvation-induced changes in transport of ketone bodies across the blood-brain barrier. J. Neurosci. Res. 1980, 5, 163–172
5. Brocchi A, Rebelos E, Dardano A, Mantuano M, Daniele G. Effects of Intermittent Fasting on Brain Metabolism. Nutrients. 2022 Mar 17;14(6):1275. doi: 10.3390/nu14061275. PMID: 35334932; PMCID: PMC8954770.
6. Liu, Z.; Dai, X.; Zhang, H.; Shi, R.; Hui, Y.; Jin, X.; Zhang, W.; Wang, L.; Wang, Q.; Wang, D.; et al. Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment. Nat. Commun. 2020, 11, 855.
7. Hu, Y.; Yang, Y.; Zhang, M.; Deng, M.; Zhang, J.-J. Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion. J Nutr. 2017, 147, 1437–1445.
8. Anic K, Schmidt MW, Furtado L, Weidenbach L, Battista MJ, Schmidt M, Schwab R, Brenner W, Ruckes C, Lotz J, Lackner KJ, Hasenburg A, Hasenburg A. Intermittent Fasting-Short- and Long-Term Quality of Life, Fatigue, and Safety in Healthy Volunteers: A Prospective, Clinical Trial. Nutrients. 2022 Oct 10;14(19):4216. doi: 10.3390/nu14194216. PMID: 36235868; PMCID: PMC9571750.
9. Berthelot E, Etchecopar-Etchart D, Thellier D, Lancon C, Boyer L, Fond G. Fasting Interventions for Stress, Anxiety and Depressive Symptoms: A Systematic Review and Meta-Analysis. Nutrients. 2021 Nov 5;13(11):3947. doi: 10.3390/nu13113947. PMID: 34836202; PMCID: PMC8624477.
10. C. Yang, Q. Ma, H. Zhang et al., “Ten days of complete fasting affected subjective sensations but not cognitive abilities in healthy adults,” European Journal of Nutrition, vol. 60, no. 5, pp. 2747–2758, 2021.
11. Wang Y, Wu R. The Effect of Fasting on Human Metabolism and Psychological Health. Dis Markers. 2022 Jan 5;2022:5653739. doi: 10.1155/2022/5653739.
12. Gu L, Fu R, Hong J, Ni H, Yu K, Lou H. Effects of Intermittent Fasting in Human Compared to a Non-intervention Diet and Caloric Restriction: A Meta-Analysis of Randomized Controlled Trials. Front Nutr. 2022 May 2;9:871682.
