Intermittent Fasting Research Articles (Page 1)

Time-restricted feeding induces white adipose browning and improves metabolic health independent of weight loss: an integrative multi-omics study.

Background: Eating during the appropriate time of day can mitigate changes in autonomic cardiovascular risk factors. The goal of this study is to determine the mechanism(s) that connect the timing of feeding to changes in the autonomic regulation of heart rate (HR) in mice. Hypothesis: The timing of feeding behavior modifies autonomic input to the heart to mask circadian rhythms in the HR. Methodology: Wild-type (WT) and inducible cardiomyocyte-specific knockout of the RRAD gene (cRADKO) mice were implanted with telemetry devices to continuously record HR using electrocardiography, core body temperature (Tb), and activity. The cRADKO mice were used to test the role of autonomic regulation, because the cardiac response to β-adrenergic stimulation relies on Rad disinhibition of voltage-gated calcium channels. WT mice were housed in 12-hour light: 12-hour dark cycles (LD) with ad libitum food (ALF) access at room temperature were exposed to thermoneutrality. Mice were subjected to light cycle time-restricted feeding (TRF) for 6 days, followed by constant darkness (DD) for 3 days, and returned to ALF for 3 days under DD. The change in HR associated with autonomic nervous system regulation (ΔHR) was quantified across the 24-hour cycle by subtracting the experimentally measured HR and the intrinsic HR (HR measured after autonomic inhibition and adjusted for Tb). Results: Housing mice (n=6/sex) in thermoneutrality decreased HR in mice. Mice with ALF access housed in LD had 24-hour rhythms in HR, Tb, and activity that all peaked in phase alignment during the dark cycle. One day after starting light cycle TRF, the onset of the 24-hour rhythm in HR and ΔHR (but not activity) shifted by 8-10 hours to align with food access during the light cycle (p<0.0001; ALF vs TRF). Switching TRF mice from LD to DD did not alter the onset of the day-night rhythms in HR, ΔHR, or activity. Returning the TRF mice housed in DD to ALF access re-aligned the onset of the HR and ΔHR rhythms with activity rhythms. Repeating control and cRADKO mice (n=5-6/group) showed similar results with light cycle TRF as WT mice. The day-night HR rhythm in cRADKO was 25% larger compared to control (p<0.05), suggesting the realignment of HR is largely mediated by the vagal input. Conclusions: The data show that the timing of feeding behavior in mice drives the phase of the day-night rhythm in autonomic regulation of HR, and TRF can mask the circadian rhythm in the autonomic regulation of HR.

Intermittent fasting (IF) has gained growing interest for its potential metabolic benefits. However, the unique physiological aspects of Ramadan fasting (RF), a culturally and religiously significant form of dry IF, remain underexplored, particularly regarding liver disease. RF imposes distinct metabolic and circadian challenges through prolonged daily fasting and altered meal timing, placing considerable demands on hepatic adaptability. Given the liver's essential role in energy balance, metabolism, and inflammation, as well as the high prevalence of liver disease in many Muslim-majority regions, it is crucial to better understand how RF impacts liver health. This review synthesizes current evidence on how RF can impact liver function, including its effects on insulin sensitivity, autophagy, gut microbiota, gene expression, and inflammation-related pathways. We further reviewed the clinical implications of RF across the broad spectrum of liver conditions, from metabolic dysfunction-associated steatotic liver disease (MASLD) to advanced cirrhosis, hepatocellular carcinoma (HCC), and post-transplant states. By addressing this knowledge gap, this review offers an evidence-based foundation for culturally sensitive and risk-stratified fasting recommendations in individuals with liver disease.

Circadian rhythms, governed by central and peripheral clocks, orchestrate nearly all aspects of human physiology, including metabolism, endocrine function, neuroimmune activity, and behavior. Emerging evidence reveals that these oscillations are closely intertwined with the gut microbiota, which itself displays diurnal fluctuations in composition and metabolite production. This bidirectional regulation establishes a dynamic circadian–microbiota axis that synchronizes nutrient processing, hormonal secretion, immune surveillance, and neural signaling. Disruption of this temporal alignment, through genetic, environmental, or lifestyle factors, precipitates systemic dysregulation, fostering metabolic syndrome, endocrine imbalance, immune dysfunction, neuropsychiatric vulnerability, cardiovascular alterations, and carcinogenesis. Mechanistic studies highlight that microbial-derived metabolites such as short-chain fatty acids, bile acids, and indoles act as circadian cues, while host clock genes modulate microbial ecology and intestinal barrier integrity. These insights underscore the translational potential of circadian precision medicine, in which time-restricted feeding, probiotics, prebiotics, and chronotherapy restore synchrony between microbial and host clocks. This review synthesizes current knowledge on circadian modulation of microbiota-mediated crosstalk across metabolic, neural, immune, and endocrine pathways, emphasizing its implications for health, disease, and novel therapeutic strategies.

Resistance to androgen deprivation therapy remains a major clinical challenge in prostate cancer, necessitating alternative therapeutic strategies. The androgen receptor (AR) plays a central role in driving resistance through mechanisms including enhanced AR signaling, DNA repair, and autophagy. In this issue of Cancer Research, Cordova and colleagues identify a metabolic vulnerability in AR protein synthesis, showing that alternate-day fasting (ADF) impairs AR translation by inducing ribosome collisions on AR mRNA. This stress response activates kinases such as p38 MAPK and selectively reduces AR protein levels, independent of transcription or protein stability. Notably, ADF enhances the efficacy of enzalutamide across multiple prostate cancer models. Unlike conventional AR-targeting approaches, ADF reveals a posttranscriptional dependency of AR expression under nutrient stress while sparing most other proteins. These findings highlight a novel translational vulnerability in prostate cancer and support combining dietary interventions with AR-targeted therapies to overcome resistance and improve patient outcomes. See related article by Cordova et al., p. 4182.

Intermittent fasting (IF) has attained considerable popularity, often advocated as an effective treatment for weight control and metabolic well-being. Recent studies, however, underscore potential negative effects linked to intermittent fasting in teenagers. Research conducted by experts from the Technical University of Munich, LMU Hospital Munich, and Helmholtz Munich indicates that fasting in adolescence hinders the growth of pancreatic beta cells, adversely affecting insulin synthesis and increasing the risk of metabolic disorders. Intermittent fasting modifies essential physiological functions, such as insulin control, neurodevelopment, and hormonal stability. Inhibition of the mTOR pathway impedes beta-cell proliferation, while glucose deficiency impacts cognitive function and psychological balance. Furthermore, intermittent fasting may exacerbate disordered eating patterns in adolescents, increasing the risk of metabolic diseases. In light of these issues, healthcare practitioners and legislators must prioritize a balanced diet and advise against uncontrolled fasting habits among teenagers. Additional study is necessary to ascertain the long-term effects of intermittent fasting on human metabolic and neurological health.

Disrupted rhythms and dysfunction: A chronobiological perspective on polycystic ovary syndrome.

Wei-dong granules ameliorate functional dyspepsia via multi-targeted gut-brain axis modulation.

The Proteomic Analysis of Intermittent Fasting Alone or with GLP-1RA in NAFLD Rats

The doubly labeled water (DLW) intake-balance method estimates energy intake (EI) during weight loss using the time-weighted average of total daily energy expenditure (TDEE) and changes in body energy stores. Because TDEE declines rapidly during the early phase of weight loss, an early additional measurement is recommended. This study aimed to develop regression models that estimate time-weighted TDEE using fewer interim measurements and determine if EI accuracy is maintained during a 12-month weight loss intervention. Data from a behavioral weight loss intervention (Dietary Caloric Restriction versus intermittent Fasting Trial, "DRIFT") were used. TDEE, body weight, and body composition were measured at months 0, 1, 6, and 12. Regression models using only two or three time points were used to estimate time-weighted TDEE at months 6 and 12, respectively. Models were validated using bootstrap sampling, and time-weighted TDEE and percent caloric restriction (% CR) were compared to a reference approach. Models demonstrated strong predictive performance (R 2 = 0.911-0.982). Limits of agreement with the reference model were 121.1-274.5 kcal/day for TDEE and 4.5%-10.3% for % CR, without significant bias. Using a regression modeling approach, we demonstrate the DLW intake-balance method maintains accuracy during weight loss without early-phase TDEE measurements. ClinicalTrials.gov identifier: NCT03411356.

Objective: Intermittent fasting (IF) is a dietary pattern alternating between periods of eating and fasting, known for its metabolic, hormonal, and anti-inflammatory benefits. This review aims to explore the molecular, physiological, and clinical links between IF and skin health. Methods: A comprehensive review of recent preclinical and clinical literature was conducted, focusing on the effects of IF on skin biology, including modulation of oxidative stress, induction of autophagy, hormonal regulation, and interactions between the gut and skin. Results: Evidence suggests that IF may enhance skin regeneration, delay ageing, and improve inflammatory skin disorders such as acne, psoriasis, and eczema. Mechanistically, IF downregulates IGF-1 and mTOR signalling, enhances antioxidant defences, promotes autophagy, and modulates the immune response. Preliminary clinical findings also indicate potential benefits in photoaging, wound healing, and tissue repair. However, most data are preclinical, with limited human trials. Conclusion: IF represents a promising nonpharmaceutical strategy for improving skin health and managing dermatological conditions. Future research should focus on developing standardised protocols, molecular profiling, and assessing long-term safety in diverse populations.

The effects of intermittent fasting on sleep quality and cardiometabolic health outcomes in adults with overweight/obesity status: a systematic review and meta-analysis of randomized controlled trials.

Obesity, a worldwide epidemic, is often accompanied by renal dysfunction or accelerating kidney disease. Intermittent fasting (IF) has become a popular weight loss approach, but the data for obesity-related kidney disease are very limited. Moreover, there is currently no combined omics study on its related metabolism, mechanisms, and pathways. The purpose of this study was to examine the preventive effect of IF on renal injury induced by a high-fat diet (HFD) and to explore the related pathways based on an omics analysis. We used an HFD to induce obesity-related renal injury. During IF intervention, the mice were allowed free access to regular chow every other day and were not provided food on the other day. Our result found that IF could effectively prevent obesity-related renal injury in glomerular morphological changes and urine components. Metabolomic and transcriptomic analyses revealed that IF affected the thermogenesis pathway, cholesterol metabolism pathway, and glycerolipid and glycerophospholipid metabolism pathways, and prevented and alleviated obesity-related renal injury through inflammation pathways and the insulin resistance pathway. This research would provide valuable data for the prevention and treatment of kidney diseases related to obesity.

To summarize the available knowledge on the effect of eating frequency and intermittent fasting to prevent and manage obesity. Eating schedule variability is associated with excess weight. Increasing eating frequency in those who eat three times a day or less does not lead to weight reduction. Intermittent fasting diets may enhance lipolysis, insulin sensitivity, adipose remodeling, and restore gut microbial diversity. Intermittent fasting diets appeared more effective than unrestricted diets and non-inferior to continuous energy restriction in producing weight loss. Intermittent fasting diets appeared more effective than unrestricted diets and non-inferior to continuous energy restriction in producing weight loss. Intermittent fasting may provide some additional benefits for lipid profiles, glucose control, and liver steatosis, but not for blood pressure. Possible benefits on gingival inflammation and detrimental effects on hair growth should warrant further investigation. Reduced eating frequency and intermittent fasting diets are effective lifestyle interventions for weight loss. The preference for intermittent fasting over continuous energy restriction should depend on the patient to maximize adherence.

This study explores the psychosocial and lifestyle factors influencing perceived biological aging among middle-aged Chinese women. A total of 39 participants aged 40 and above completed a 46-item questionnaire assessing health status, stress, emotional support, diet, physical activity, and aging perception. Participants were categorized into low, moderate, or high aging groups based on self-reported indicators. Women in the low-aging group reported greater emotional and partner support, lower family-related stress, healthier diets, and more frequent self-care and physical activity. In contrast, high-aging participants experienced greater stress, digestive discomfort, sedentary habits, and exposure to secondhand smoke and alcohol. Interestingly, intermittent fasting was most common in the moderate-aging group. These findings underscore the significant role of psychosocial resilience and modifiable lifestyle behaviors in shaping aging perceptions. The study advocates for holistic, culturally sensitive interventions to support healthy aging in women, particularly those navigating caregiving, career, and health demands during midlife.

Background: Vitamin D supplementation may influence oxidative stress, but evidence in populations following specific dietary patterns is limited. Methods: In this non-randomized, two-group exploratory study, 50 Orthodox nuns received vitamin D supplementation (2000 IU/day orally) for 16 weeks, whereas 50 age-matched women following time-restricted eating (TRE) served as controls receiving no supplementation. Anthropometric parameters, serum 25-hydroxyvitamin D [25(OH)D], and oxidative stress markers—total antioxidant capacity (TAC), glutathione (GSH), and thiobarbituric acid reactive substances—were measured at baseline and post-intervention. Results: At baseline, both groups were comparable in anthropometric and oxidative stress markers, except for serum 25-hydroxyvitamin D [25(OH)D], which was lower in the intervention group. Following supplementation, serum 25(OH)D increased from 15.77 ± 5.21 to 31.24 ± 7.87 ng/mL (p = 0.031) in Orthodox nuns. No significant changes were observed for TAC (0.93 ± 0.11 to 0.97 ± 0.09, p = 0.081) and GSH (6.01 ± 1.55 to 5.81 ± 1.41, p = 0.069), whereas TBARS decreased significantly (7.32 ± 1.31 to 6.94 ± 1.21, p = 0.041). No significant changes were observed in controls under TRE. Changes (Δ) in all variables represented the post–pre difference over the 16-week period. Pearson correlations showed no significant associations between Δ25(OH)D and ΔTAC (r = −0.244, p = 0.346), ΔGSH (r = 0.110, p = 0.675), or ΔTBARS (r = −0.116, p = 0.657). In multivariable regression adjusted for age, weight, body fat percentage, and baseline 25(OH)D, Δ25(OH)D was not an independent predictor of oxidative stress marker changes; however, weight (β = 0.08, p = 0.011) and body fat percentage (β = −0.13, p = 0.014) were associated with reductions in TBARS. Conclusions: In conclusion, sixteen weeks of vitamin D supplementation in women adhering to Orthodox fasting produced no consistent improvements in oxidative stress markers. While a small reduction in TBARS was observed, this effect was modest and appeared indirect, being more closely associated with decreases in body weight and fat mass than with vitamin D status itself. Taken together, our findings indicate an overall neutral impact of vitamin D on redox balance, suggesting that any antioxidant benefit is likely secondary to metabolic or adiposity-related changes.

Intermittent fasting (IF) has emerged as a promising strategy for managing obesity and related metabolic disorders. Although metabolic adaptations in adipose tissue during IF are well documented, the specific reprogramming of white adipose tissue (WAT) under prolonged cycles of fasting and refeeding remains incompletely understood. Using mass spectrometry-based approaches, including liquid chromatography (LC) and capillary electrophoresis (CE), we identified a marked increase in inositol monophosphates (InsP1s) in obese adipose tissue following extended IF. Specifically, myo-inositol-1-phosphate and myo-inositol-3-phosphate, which are typically present at low levels in gonadal WAT (gWAT) of diet-induced obese mice, were significantly elevated after 15 cycles of IF. Additionally, extended IF upregulated the expression levels of inositol tetrakisphosphate 1-kinase (ITPK1) and inositol monophosphatase 1 (IMPA1), two key enzymes involved in InsP1 metabolism. These increases coincide with reductions in body weight and fat mass, as well as improved insulin sensitivity. This reprogramming was further supported by enhanced tricarboxylic acid (TCA) cycle activity. Collectively, these findings suggest the inositol monophosphate pathway as a novel mechanism underlying fasting-induced metabolic adaptation in adipose tissue and highlight the potential of these metabolites as biomarkers for obesity and related metabolic conditions.

A randomised controlled trial of short-term Intermittent Energy Restriction [IER] versus Continuous Energy Restriction [CER] on body fat stores and measures of insulin resistance in women with obesity at increased risk of breast cancer

This study investigated the impact of intermittent fasting (IF) on older rats by administering plasma from 12-month-old male Sprague Dawley rats subjected to 35 days of IF, with 18-hour fasting intervals followed by 6-hour feeding periods. Over this period, 0.5 ml of plasma was transferred bi-daily to 24-month-old male rats, totaling 15 infusions. Infrared spectroscopy-based qualitative and quantitative analyses revealed significant changes in lipid, protein, and nucleic acid profiles, varying by tissue type and fasting regimen. Histological examination showed structural enhancements in the ileum and colon, along with reduced inflammatory markers TNF-α and COX-2, particularly with IF plasma. Additionally, plasma transfer markedly improved gut microbiota composition, increasing alpha diversity and adjusting the Firmicutes to Bacteroidetes ratio. High-Performance Liquid Chromatography results indicated elevated levels of key cecal short-chain fatty acids, suggesting enhanced gut health. These findings highlight the potential of plasma from intermittently fasting rats in modulating biomolecular profiles, intestinal tissue structure, gut microbiota, and SCFA production, offering integrated insights into intestinal health improvements.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21183-3.

The "Warburg effect", a metabolic adaptation observed in dividing cells, involves a shift from mitochondrial oxidative phosphorylation to cytoplasmic glucose metabolism. This metabolic process is characterized by increased cellular uptake of glucose and glutamine, elevated intracellular pH and sodium levels, enhanced protection against oxidative stress, altered autophagy, and increased lactate production. Initially identified by Otto Warburg in cancer cells, the Warburg effect is now recognized as a common feature of all dividing cells, prioritizing biomass production for cell proliferation over energy generation for specialized cellular functions. Indeed, the Warburg effect is emerging as an important feature not only in cancer but also in a range of metabolic, endocrine, and neurological chronic disorders, including type 2 diabetes, heart and kidney failure, therapy-refractory epilepsy, Alzheimer's and Parkinson's diseases, chronic fatigue syndrome, and post-viral syndromes. The prevailing notion that "dysfunctional mitochondria" are the primary cause of the "energy deficit" observed in these conditions may be misleading. Instead, this "energy deficit" can result from cells reprogramming their metabolism to support cell division. Additionally, in these disorders, senescent cells are abundant, exhibiting a Warburg-like metabolism with cell cycle arrest and enhanced anabolic activity. This review explores the multifaceted role of the Warburg effect in type 2 diabetes and other metabolic and endocrine chronic disorders and examines the therapeutic potential of different interventions such as intermittent fasting, ketogenic diets, ketone supplements, and sodium/glucose co-transporter 2 inhibitors. Through a comprehensive analysis of existing literature, we aim to shed light on the mechanisms underlying these interventions and their potential impact on disease progression and patient outcomes.