It is well-established that chronic stress—prolonged exposure to psychological and/or physical strain—serves as a risk factor for depression, anxiety, and various other mental disorders. Earlier research indicates that chronic stress compromises the integrity of myelin, the fatty insulating layer surrounding nerve fibers that facilitates efficient electrical signal transmission between brain cells.
Identifying lifestyle modifications that can reverse or mitigate the harmful effects of chronic stress on the brain may prove valuable, as it could help prevent or delay the onset of multiple psychiatric conditions. Recently, some scientists have been exploring the potential brain benefits of intermittent fasting—a dietary pattern characterized by alternating periods of eating and fasting.
Prior studies demonstrate that intermittent fasting can enhance metabolism and help reduce inflammation, the body’s natural response to illness or injury. However, its effects on human mental health and well-being have yet to be clearly established.
Researchers from the Center for Forensic Psychiatric Expertise at Chiba University and the First Affiliated Hospital of Zhengzhou University recently investigated how intermittent fasting influences mood, energy levels, behavior, and brain function in mice exposed to prolonged stress. Their findings, published in the journal Translational Psychiatry, suggest that this dietary intervention may reverse stress-induced myelin damage and lessen depression-like behaviors by boosting the diversity of gut bacteria.
“Although intermittent fasting improves metabolic and inflammatory processes, its impact on stress-induced depression and demyelination remains unclear,” wrote Xin Ding, Rumi Murayama, and their colleagues in their paper. “We explored whether intermittent fasting alleviates depression-like behavior and myelin deficits in mice subjected to chronic restraint stress, and whether these effects are linked to modulation of the gut microbiota.”
In their study, the scientists subjected adult male mice to prolonged psychological stress. They then divided the mice into two groups: one group had unrestricted access to food, while the other was fed only during specific time windows, following an intermittent fasting regimen.
“Adult male C57BL/6J mice underwent 14-day chronic stress while either on an ad libitum diet or an intermittent fasting schedule,” wrote Ding, Murayama, and their team. “Chronic stress induced pronounced depression-like phenotypes—characterized by increased immobility in the forced swim test and reduced sucrose preference—without affecting locomotor activity, whereas intermittent fasting significantly attenuated these behavioral abnormalities.”
Overall, the researchers found that mice that could eat freely throughout the day suffered more from chronic stress than those adhering to intermittent fasting. Specifically, the fasting group appeared to derive greater pleasure from food, exhibited higher energy levels, and displayed fewer depressive behaviors.
The team also assessed myelin condition in the animals’ brains using two methods: Black-Gold II staining and immunofluorescence for myelin basic protein (MBP). They observed that mice on the CRS (i.e., free-feeding) diet showed myelin damage in several brain regions linked to emotional regulation, decision-making, and memory—including the corpus callosum, medial prefrontal cortex, and hippocampus. Notably, the intermittent fasting regimen seemed to reverse these effects.
Ding, Murayama, and their colleagues also conducted additional analyses to better understand the mechanisms by which intermittent fasting counteracted the detrimental effects of chronic stress on myelin. Their results indicate that intermittent fasting altered the gut microbiome, increasing the abundance of beneficial bacteria in the digestive tract that appeared to repair or protect myelin in the brain.
“16S rRNA sequencing revealed that intermittent fasting shifts gut microbiota diversity and microbial community composition under stress conditions,” the authors wrote. “Species-level analysis identified a positive correlation of Prevotellamassilia timonensis and Muricoprocola aceti with myelin integrity and improved behavioral outcomes, while Anaeroplasma abactoclasticum showed a negative correlation. Functional pathway prediction further indicated that intermittent fasting partially normalizes stress-induced changes in microbial metabolic functions.”
Although the results of this study are preliminary and have not yet been confirmed in humans, they suggest that intermittent fasting holds promise for reducing or reversing the negative effects of chronic stress on the brain. Other research groups may soon build on these findings and attempt to replicate them in other rodents, primates, or even humans.
“Taken together, these results demonstrate that intermittent fasting mitigates depression-like behavior and preserves myelin integrity in mice exposed to chronic stress, potentially through gut microbiota-mediated mechanisms,” wrote Ding, Murayama, and their colleagues. “Thus, it may represent a promising non-pharmacological strategy for alleviating stress-related neurobiological dysfunction.”
If the findings are corroborated in human studies, they could ultimately guide the development of new intermittent-fasting-based dietary interventions aimed at reducing the risk of depression or other mental disorders in people experiencing chronic stress.
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