Fasting the brain for mental health.

Unfavorable socioeconomic and geopolitical conditions such as poverty, violence and inequality increase vulnerability to mental disorders. Also, exposure to a poor nutrition such as high-energy dense (HED) diets has been linked to alterations in brain function, leading to anxiety, addiction, and depression. HED diets rich in saturated fatty acids or obesity can activate the innate immune system in the brain, especially microglia, increasing proinflammatory cytokines such as interleukin 1 beta (IL1-β) and interleukin 6 (IL-6), in part, by the stimulation of toll-like receptor 4 (TLR4) and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Intermittent fasting (IF), an eating protocol characterized by alternating periods of fasting with periods of eating, has gained recognition as a weight-management strategy to reduce obesity. Accordingly, during IF inflammation and brain function can be modulated by production of ketone bodies and modulation of the intestinal microbiota, which also promote the induction of brain-derived neurotrophic factor (BDNF), which is involved in neurogenesis and neuronal plasticity. Although IF has contributed to reduce body weight and improve metabolic profiles, its influence on mental health remains an evolving field of research. Here, we provide experimental evidence supporting the role of IF reducing neuroinflammation as a valuable approach to improve mental health.