Intermittent fasting (IF), a temporal dietary pattern, has garnered interest in improving anthropometric and metabolic markers. Beyond this, IF appears to recalibrate hormonal circadian rhythms and reshape gut microbiota-two key intermediaries through which IF exerts effects on endocrine, inflammatory, and oncogenic pathways. This review synthesizes research findings of IF on key endocrine systems and outlines its potential implications for oncogenic risk. We primarily examine the effects of IF on hormonal regulation with a particular focus on its relevance to metabolic and oncogenic health outcomes. We explored hormonal alterations induced by various IF protocols and discussed their physiological implications. Controlled observations or interventional studies in both human and animal models were included. Evidence indicates that IF exerts systemic effects on hormonal rhythmicity, including insulin, thyroid hormones, glucocorticoids, and sex hormones, potentially re-establishing homeostatic endocrine function. Moreover, IF influences cancer-related pathways via modulation of endocrine axes and attenuation of inflammatory markers. These mechanisms offer a theoretical basis for IF's potential in attenuating metabolic dysfunction and cancer risk. However, the current research is limited by variations in study designs, short durations, limited cohorts, and population-specific findings, restricting generalizability and applicability. Ultimately, IF represents a multifaceted dietary strategy with the potential to synchronize circadian and hormonal systems, positioning it as a promising intervention in metabolic and endocrine-related conditions. However, whether long-term IF can modulate specific hormonal axes without overt physiological side effects, including sex-specific effects, remains unclear. To establish its clinical relevance and therapeutic safety, validation through well-designed and large-scale human trials is imperative.

sulin, thyroid hormones, and glucocorticoids. Given that intermittent fasting could alter both the level and frequency of hormone secretion, decisions on practicing intermittent fasting should take more considerations on potential detrimental consequences versus beneficial effects pertaining to individual health conditions. Keywords: Intermittent fasting, Circadian rhythm, Insulin, Thyroid hormones, Glucocorticoids INTRODUCTION Technological breakthroughs have caused dramatic changes in human lifestyle. One typical example is that people can work and eat in the evening and even at night, contrary to the traditional diurnal lifestyle of humans [ 1 ]. Cumulative evidence suggests that these lifestyle changes increase the risk of metabolic disorders such as obesity and type 2 diabetes [ 2 ]. Intermittent fasting has gained popularity to manage obesity and diabetes. It refers to various diet regimens that involve periodically conducted fasting [ 3 ]. This protocol is relatively easy to practice for long periods of time compared to continuous calorie reduction (CR), which requires inconvenient calorie counting every day [ 4 ]. One simple approach is alternate-day fasting (ADF), which alternates a day of complete or considerable food restriction with ad libitum food intake for another day. Whole-day fasting (periodic fasting) involves complete or considerable food restriction for 1 to 2 days in a week: for example, the 5:2 diet is to restrict calories by around 75% for 2 days a week. Time-restricted feeding (TRF) allows subjects to eat only for a specific time window during the day. Ramadan fasting, a kind of religious ritual, can be categorized as a type of TRF since meals are consumed only between sunset and dawn during this period. Beneficial effects of intermittent fasting have been extensively reviewed in recent papers [ 5 – 8 ]. For example, intermittent fasting can improve cognitive and learning abilities in rodents [ 9 , 10 ] and activate antioxidant enzymes and a

Systematic review and meta-analysis reveals acutely elevated plasma cortisol following fasting but not less severe calorie restriction ## Abstract Elevated plasma cortisol has been reported following caloric restriction, and may contribute to adverse effects including stress-induced overeating, but results from published studies are inconsistent. To clarify the effects of caloric restriction on plasma cortisol, and to assess cortisol as an indicator of stress during caloric restriction, we conducted a systematic review and meta-analysis of published studies in which cortisol was measured following caloric restriction without other manipulations in humans. We further compared effects of fasting, very low calorie diet (VLCD), and other less intense low calorie diet (LCD), as well as the duration of caloric restriction by meta-regression. Overall, caloric restriction significantly increased serum cortisol level in 13 studies (357 total participants). Fasting showed a very strong effect in increasing serum cortisol, while VLCD and LCD did not show significant increases. The meta-regression analysis showed a negative association between the serum cortisol level and the duration of cal