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"Intermittent Fasting"
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Intermittent Fasting and Emotional Regulation: A Psychobiological Framework Integrating Metabolic, Neuroendocrine and Interoceptive Mechanisms
2026
Background/Objectives: Intermittent fasting (IF) has been widely investigated for its metabolic effects, including improvements in insulin sensitivity, lipid metabolism, and inflammatory markers. However, its psychological and experiential dimensions remain comparatively underexplored. The present narrative review examines IF within a psychobiological framework, integrating evidence from metabolic science, neuroendocrinology, and affective neuroscience to explore its potential impact on emotional regulation and interoceptive processes. Methods: A structured narrative literature search was conducted across PubMed, Scopus, and Google Scholar, focusing on studies published between 2010 and 2025. Eligible studies included human and relevant animal research addressing metabolic, hormonal, interoceptive, and psychological responses to IF. Evidence was synthesized thematically to identify convergent mechanisms linking metabolic adaptations to emotional and regulatory outcomes. Results: Available literature suggests that IF is associated with a metabolic shift toward lipid utilization, characterized by increased ketone body production, particularly β-hydroxybutyrate. These adaptations appear to be accompanied by modulation of neuroendocrine pathways and may influence central nervous system functioning through mechanisms potentially related to neuroinflammation, mitochondrial efficiency, and synaptic plasticity. Emerging evidence further suggests that IF may modulate BDNF signaling and gut–brain axis activity, although direct causal pathways in humans remain to be established. At the psychological level, IF is associated with heterogeneous emotional outcomes: structured fasting protocols have been linked to modest improvements in perceived stress and mood in metabolically healthy individuals, whereas irritability, anxiety, or behavioral rigidity may emerge in those with pre-existing psychological vulnerabilities. Individual differences in interoceptive sensitivity, emotion regulation strategies, and moderating biological factors—including sex, circadian timing, and habitual physical activity—appear to influence these responses. Conclusions: Overall, IF may be conceptualized as a context-dependent psychobiological stressor whose effects extend beyond metabolic regulation to include interoceptive and emotional processes. These effects appear bidirectional, potentially promoting psychological resilience in some individuals while increasing the risk of affective destabilization or maladaptive behaviors in others. Current evidence remains limited by a lack of integrative and longitudinal studies combining metabolic and psychological measures. Future research adopting multidisciplinary approaches is needed to clarify the mechanisms underlying individual variability and to better define the potential benefits and risks of IF in both clinical and non-clinical populations.
Journal Article
The Safety of Novel Therapies in Chronic Lymphocytic Leukemia in the Era of Intermittent Fasting: A Pharmacology-Based Review
2024
Intermittent fasting (IF) has recently gained popularity due to its emerging benefits in reducing weight and improving metabolic health. Concurrently, novel agents (NAs) like venetoclax and Bruton tyrosine kinase inhibitors (BTKIs) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Unfortunately, it is unclear whether the associated risks of tumor lysis syndrome (TLS) and gastrointestinal bleeding (GIB) are increased in IF practitioners receiving NAs. This review explored the literature available on the permissibility of IF in CLL patients undergoing treatment with first-line NAs (FLNAs). Literature was scoped to identify IF patterns and the available data on TLS and GIB risks associated with food and fluid intake in CLL patients receiving FLNAs. Although current evidence is insufficient to recommend IF in this population, it may be possible for patients on venetoclax to conservatively practice fluid-liberal IF, provided that adequate hydration and the consistent administration of food are achieved. In contrast, considering the significant risk of TLS and the pharmacokinetics of venetoclax, patients should be discouraged from practicing fluid-restricted IF, especially during the ramp-up phase. Moreover, patients on BTKIs ought to refrain from IF due to the possible risk of GIB until further data are available. Further research is needed to provide conclusive recommendations.
Journal Article
Sex-Specific Responses to Intermittent Fasting: A Narrative Review Across Physiological, Clinical, and Psychosocial Contexts
by
Ortega, Miguel A.
,
Fraile-Martínez, Óscar
,
de Castro-Martínez, Patricia
in
Aging
,
Autophagy
,
Body Composition
2026
Background/Objectives: Intermittent fasting (IF) has gained increasing attention as a nutritional strategy to improve metabolic health, body composition, and disease-related outcomes. However, its effects are often interpreted as broadly uniform, despite growing evidence that biological sex may modulate fasting responses. This narrative review examines sex-specific differences in the physiological, endocrine, clinical, and psychosocial effects of IF in women and men. Methods: We conducted a narrative synthesis of human and preclinical evidence addressing IF protocols, mechanisms, benefits, adverse effects, and sex-related differences. Particular attention was given to substrate metabolism, hormonal regulation, neuroendocrine sensitivity, energy availability, exercise performance, chronic disease management, aging-related outcomes, and psychological or behavioral responses. Results: The available literature suggests that women and men share several beneficial responses to IF, including improvements in body composition and cardiometabolic markers, but may differ in the magnitude, tolerability, and mechanistic basis of these effects. Women appear to show greater sensitivity of reproductive and neuroendocrine function to energetic stress, particularly under conditions of low energy availability, high exercise load, or reproductive vulnerability. In contrast, men may exhibit preserved functional outcomes despite measurable endocrine adaptations, including changes in testosterone dynamics. Across both sexes, responses vary according to fasting protocol, nutritional adequacy, baseline metabolic status, life stage, and clinical context. Conclusions: Current evidence supports a sex-informed and context-specific interpretation of IF rather than universally applicable fasting prescriptions. Direct sex-comparative studies remain scarce, and many conclusions are inferred from parallel male and female studies. Future research should integrate sex as a core biological variable in precision nutrition and fasting-based interventions.
Journal Article
Does Energy Restriction and Loss of Body Fat Account for the Effect of Intermittent Fasting on Cognitive Function?
by
Axen, Kathleen V.
,
Draicchio, Fulvia
in
Adipose Tissue - metabolism
,
Adiposity
,
Alzheimer's disease
2025
Intermittent fasting (IF) and caloric restriction (CR) have garnered attention for their potential to enhance cognitive function, particularly in aging and metabolically compromised populations. This narrative review critically examines whether the cognitive benefits of IF are attributable to its specific fasting patterns or are instead mediated by the production of weight loss, fat loss, and improvements in insulin sensitivity. Evidence from human trials suggests that reductions in body weight, especially visceral adiposity, and improvements in insulin resistance are key factors linked to enhanced cognitive performance. Comparisons between the results of IF and CR trials show comparable cognitive outcomes, supporting the idea that negative energy balance, rather than fasting or altered eating patterns, drive these effects. However, further investigation of specific types of IF patterns, as well as possible cognitive domains to be affected, may identify mechanisms through which IF can yield benefits on neurocognitive health beyond those of loss of body fat and its accompanying inflammatory state.
Journal Article
Intermittent Fasting: A Metabolically Focused Therapeutic Strategy for Obesity
by
Diaz-Garrido, Natalia
,
Bastías-Pérez, Marianela
,
Regaldiz, Alejandro
in
Animals
,
Blood pressure
,
Body composition
2026
The global prevalence of obesity continues to rise and is a significant risk factor for the onset and progression of cardiovascular diseases. Despite the development of new pharmacological therapies, novel strategies are being explored to mitigate the impact of this disease. Intermittent fasting (IF) is a nutritional intervention that has gained popularity and shows potential as an innovative approach to weight management. This study aims to compile scientific evidence on various aspects of fasting, including its physiological effects, the molecular and thermogenic mechanisms involved, and recommendations regarding nutritional strategies during the refeeding period within the eating window. We conducted a narrative review, analyzing evidence available from PubMed/MEDLINE based on studies related to intermittent fasting, thermogenesis, and their associated outcomes. Our results demonstrate the existence of three commonly used IF protocols: alternate day fasting (ADF), periodic fasting (PF), and time-restricted eating (TRE). In addition to its effects on weight loss, IF has demonstrated notable benefits for cardiovascular health, oxidative stress, and metabolic function. Moreover, the interaction between the central nervous system and brown adipose tissue provides an alternative mechanism for the molecular regulation of thermogenesis. Nutritional patterns adopted during intermittent fasting play a crucial role in optimizing outcomes, with particular emphasis on the intake of proteins, fiber, bioactive compounds, and essential fatty acids during the feeding window. In summary, current evidence indicates that intermittent fasting provides a biologically robust framework for studying energy balance and holds promise for developing targeted nutritional interventions.
Journal Article
Adverse events profile associated with intermittent fasting in adults with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials
2024
Background
There is little evidence to comprehensively summarize the adverse events (AEs) profile of intermittent fasting (IF) despite its widespread use in patients with overweight or obesity.
Methods
We searched the main electronic databases and registry websites to identify eligible randomized controlled trials (RCTs) comparing IF versus control groups. A direct meta-analysis using a fixed-effect model was conducted to pool the risk differences regarding common AEs and dropouts. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity.
Results
A total of 15 RCTs involving 1,365 adult individuals were included. Findings did not show a significant difference between IF and Control in risk rate of fatigue [0%, 95% confidence interval (CI), -1% to 2%;
P
= 0.61], headache [0%, 95%CI: -1% to 2%;
P
= 0.86] and dropout [1%, 95%CI: -2% to 4%;
P
= 0.51]. However, a numerically higher risk of dizziness was noted among the IF alone subgroup with non-early time restricted eating [3%, 95%CI: -0% to 6%;
P
= 0.08].
Conclusions
This meta-analysis suggested that IF was not associated with a greater risk of AEs in adult patients affected by overweight or obesity. Additional large-scale RCTs stratified by key confounders and designed to evaluate the long-term effects of various IF regimens are needed to ascertain these AEs profile.
Journal Article
An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study
by
Wilson, Melissa L.
,
Hsu, William C.
,
Huang, Angie W.
in
3-hydroxybutyric acid
,
Adult
,
Analysis
2021
There has been increasing interest in time-restricted eating to attain intermittent fasting’s metabolic benefits. However, a more extended daily fast poses many challenges. This study was designed to evaluate the effects of a 200-calorie fasting-mimicking diet (FMD) energy bar formulated to prolong ketogenesis and mitigate fasting-associated side effects. A randomized, controlled study was conducted comparing the impact of consuming an FMD bar vs. continued water fast, after a 15-h overnight fast. Subjects in the FMD group showed a 3-h postprandial beta-hydroxybutyrate (BHB) level and 4-h postprandial BHB area under the curve (AUC0–4) that were non-inferior to those who continued with the water fast (p = 0.891 and p = 0.377, respectively). The postprandial glucose AUC0–4 in the FMD group was non-inferior to that in the water fast group (p = 0.899). A breakfast group served as a control, which confirmed that the instrument used in home glucose and ketone monitoring functioned as expected. The results indicate that FMD bar consumption does not interfere with the physiological ketogenesis associated with overnight fasting and could be used to facilitate the practice of time-restricted eating or intermittent fasting.
Journal Article
The effect of intermittent fasting on preventing obesity-related early aging from a molecular and cellular perspective
by
Hidayati, Hanik Badriyah
,
Subsomwong, Phawinee
,
Rejeki, Purwo Sri
in
Aging
,
Aging, Premature - prevention & control
,
Animals
2024
Obesity is a global health concern owing to its association with numerous degenerative diseases and the fact that it may lead to early aging. Various markers of aging, including telomere attrition, epigenetic alterations, altered protein homeostasis, mitochondrial dysfunction, cellular senescence, stem cell disorders, and intercellular communication, are influenced by obesity. Consequently, there is a critical need for safe and effective approaches to prevent obesity and mitigate the onset of premature aging. In recent years, intermittent fasting (IF), a dietary strategy that alternates between periods of fasting and feeding, has emerged as a promising dietary strategy that holds potential in counteracting the aging process associated with obesity. This article explores the molecular and cellular mechanisms through which IF affects obesity-related early aging. IF regulates various physiological processes and organ systems, including the liver, brain, muscles, intestines, blood, adipose tissues, endocrine system, and cardiovascular system. Moreover, IF modulates key signaling pathways such as AMP-activated protein kinase (AMPK), sirtuins, phosphatidylinositol 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR), and fork head box O (FOXO). By targeting these pathways, IF has the potential to attenuate aging phenotypes associated with obesity-related early aging. Overall, IF offers promising avenues for promoting healthier lifestyles and mitigating the premature aging process in individuals affected by obesity.
Journal Article
Effects of intermittent fasting on the histology and mRNA expression of major drug-metabolizing cyp450s in the liver of diabetic mice
by
Alsayed, Ahmad R.
,
Jarrar, Qais
,
Madani, Abdalla
in
Animals
,
Cyp450s
,
Cytochrome P-450 Enzyme System - genetics
2023
There is a variation in drug response among patients who practice intermittent fasting. Alteration in the expression of drug-metabolizing enzymes (DMEs) can affect the pharmacokinetics and drug response.
This research aimed to determine the effect of intermittent fasting on the mRNA expression of major drug-metabolizing cyp450s in the liver of diabetic mice.
Thirty-two male Balb/c mice were divided into four groups; control, nonfasting diabetic, non-diabetic fasting, and diabetic fasting mice. Insulin-dependent diabetes was induced in mice by a single high-dose (250 mg/kg) streptozocin. Mice of non-diabetic and diabetic fasting groups were subjected to 10-day intermittent fasting for 17 hours daily. Then, the mRNA expression of mouse phase I DMEs cyp1a1, cyp2c29, cyp2d9, and cyp3a11 was analyzed using real-time polymerase chain reaction. In addition, the liver of mice in all groups was examined for pathohistological alterations.
Diabetes downregulated the mRNA expression of hepatic drug-metabolizing cyp450s in diabetic mice, while intermittent fasting significantly (
< 0.05) increased it. Also, cyp2d9 and cyp3a11 were upregulated in the liver of diabetic fasting mice. These alterations in the gene expression were correlated with the pathohistological alterations, where livers of diabetic mice showed dilatation in the blood sinusoids and inflammatory cells leukocyte infiltrations. Whereas livers of diabetic fasting mice showed almost comparable histological findings to control mice.
Intermittent fasting can protect the liver against diabetes-induced hepatotoxicity and the down-regulation of DME genes in the diabetic liver. These results can explain, at least partly, the inter-individual variation in the drug response during practicing fasting.
Journal Article