Investigating fasting for metabolic health and longevity.

Ageing increases the risk of obesity and related metabolic diseases, emphasizing the need to understand how dietary interventions influence metabolism and metabolic health in older populations. This study aimed to investigate the impact of time‐restricted feeding (TRF) on energy balance, adipose tissue metabolism and overall metabolic health in aged female mice with high‐fat diet (HFD)‐induced obesity. A 10‐week TRF regimen was implemented in aged female mice following 12 weeks of HFD exposure. Mice were either maintained on HFD ad libitum (HFD‐AL) or subjected to TRF with HFD access restricted to a 10 h daily feeding window (HFD‐TRF). Glucose and insulin tolerance tests, meal pattern and indirect calorimetry were measured during the regimen. We showed that TRF partially reversed HFD‐induced weight gain and fat mass accumulation. In white adipose tissue TRF reduced average adipocyte size and increased the heterogeneity in adipocyte size distribution. TRF also led to increased VO2 and VCO2, along with a decreased respiratory efficiency ratio (RER) compared to the HFD‐AL group, particularly during the light phase. Meal pattern analysis showed increased meal frequency during the feeding window in HFD‐TRF mice relative to HFD‐AL. Additionally TRF lowered fasting blood glucose and reduced liver lipid accumulation. At the molecular level TRF induced significant metabolic adaptations in adipose tissue, including upregulation of genes involved in adipogenesis and lipid cycling, as well as depot‐specific alterations in mitochondrial oxidation and circadian rhythm gene expression. In conclusion TRF promotes beneficial metabolic adaptations and may serve as an effective dietary strategy to improve metabolic health in aged females.Key pointsTime‐restricted feeding (TRF) reduced body weight and fat mass, lowered blood glucose and decreased lipid accumulation in the liver.TRF also changed energy fuel utilization, increased metabolic activity of adipose tissue and altered the size and function of fat cells.Altered meal timing can trigger beneficial metabolic changes and suggests that TRF may help protect against obesity‐related diseases during ageing.

The response to lifestyle intervention studies is often heterogeneous, especially in older adults. Subtle responses that may represent a health gain for individuals are not always detected by classical health variables, stressing the need for novel biomarkers that detect intermediate changes in metabolic, inflammatory, and immunity-related health. Here, our aim was to develop and validate a molecular multivariate biomarker maximally sensitive to the individual effect of a lifestyle intervention; the Personalized Lifestyle Intervention Status (PLIS). We used 1 H-NMR fasting blood metabolite measurements from before and after the 13-week combined physical and nutritional Growing Old TOgether (GOTO) lifestyle intervention study in combination with a fivefold cross-validation and a bootstrapping method to train a separate PLIS score for men and women. The PLIS scores consisted of 14 and four metabolites for females and males, respectively. Performance of the PLIS score in tracking health gain was illustrated by association of the sex-specific PLIS scores with several classical metabolic health markers, such as BMI, trunk fat%, fasting HDL cholesterol, and fasting insulin, the primary outcome of the GOTO study. We also showed that the baseline PLIS score indicated which participants respond positively to the intervention. Finally, we explored PLIS in an independent physical activity lifestyle intervention study, showing similar, albeit remarkably weaker, associations of PLIS with classical metabolic health markers. To conclude, we found that the sex-specific PLIS score was able to track the individual short-term metabolic health gain of the GOTO lifestyle intervention study. The methodology used to train the PLIS score potentially provides a useful instrument to track personal responses and predict the participant's health benefit in lifestyle interventions similar to the GOTO study.

Obesity is a chronic disease, representing a significant health problem worldwide. Unhealthy eating habits and sedentarism are key contributors to the development of obesity. Dietary and exercise strategies are the first-line therapies for weight loss or maintenance and have proven effective in controlling weight. However, long-term adherence is challenging, and rapid weight regain often follows intervention cessation. In mice, time-restricted feeding (TRF) and exercise (EXE) independently prevent weight gain and maintain metabolic health, yet weight regain is observed upon cessation. Whether combining TRF and EXE provides longer-lasting benefits remains unclear. Here, we assessed weight and metabolic parameters in Swiss male mice fed with a high-fat diet (HFD) during an 8-wk intervention of TRF (8-h food access in the active phase) or TRF combined with EXE (60-min treadmill running daily) and after cessation and transfer to ad libitum feeding. TRF and EXE interventions successfully mitigate weight gain, improve glycemic homeostasis, and attenuate lipid accumulation in the liver and adipose tissue hypertrophy compared to mice fed HFD ad libitum. However, cessation of both strategies led to rapid weight regain, impaired glycemic control, and increased circulating lipid levels. Although the combination of TRF and EXE led to the lowest body weight and best metabolic health, this group showed no protection against the metabolic impairments observed after TRF cessation alone. In conclusion, TRF and EXE are complementary strategies for managing metabolic health, but cessation of these interventions leads to rapid weight regain and metabolic deterioration, with only partial preservation of select metabolic adaptations. These findings underscore the critical need for sustained adherence to lifestyle interventions in obesity management.NEW & NOTEWORTHY This study demonstrates that combining time-restricted feeding with aerobic training improves weight and metabolic health in Swiss mice fed a high-fat diet. Importantly, we show that most metabolic benefits are lost after intervention cessation. However, insulin sensitivity and aspects of hepatic lipid metabolism are partially maintained after cessation of the intervention. These findings provide new insight into the durability of metabolic improvements induced by lifestyle interventions and highlight the potential of combined dietary and exercise strategies to counteract diet-induced obesity and metabolic dysfunction.

Intermittent Fasting (IF), a dietary modification through time-restricted feeding, has gained significant attention in the past few years owing to its advantages in metabolic health and weight management. Available evidence suggests that IF can improve insulin sensitivity; lower the levels of blood glucose and fat; prevent body fat accumulation; and reduce the risk of obesity-related chronic disease by mitigating oxidative damage and affecting the activity of antioxidant enzymes. However, a number of gaps in knowledge remain regarding IF, especially its long-term safety and the generalisability of IF. This paper discussed the effects of IF on metabolism and body health through the mechanism of high-intensity, nutrient-strong IF. It mentioned that IF led to improved insulin sensitivity, lower blood lipid levels and inhibition of body fat accumulation, and was easier to stick to than daily calorie restriction. Other clinical studies with longer intervals and durations also reported significant effects of IF on weight loss and body health. Long term strict IF is unfavorable for some patients – in particular the elderly and the chronically ill – due to the potential for nutritional and metabolic problems. This study serves as an important reference for the use of IF in health and weight loss management, and offers potential directions for future research. Even though IF showed clear benefits, its safety in the long term and applicability across different populations still need to be validated. Future investigations may look into the long-term effects of IF in different populations, and its potential application in various health conditions.

Intermittent Fasting (IF), a dietary modification through time-restricted feeding, has gained significant attention in the past few years owing to its advantages in metabolic health and weight management. Available evidence suggests that IF can improve insulin sensitivity; lower the levels of blood glucose and fat; prevent body fat accumulation; and reduce the risk of obesity-related chronic disease by mitigating oxidative damage and affecting the activity of antioxidant enzymes. However, a number of gaps in knowledge remain regarding IF, especially its long-term safety and the generalisability of IF. This paper discussed the effects of IF on metabolism and body health through the mechanism of high-intensity, nutrient-strong IF. It mentioned that IF led to improved insulin sensitivity, lower blood lipid levels and inhibition of body fat accumulation, and was easier to stick to than daily calorie restriction. Other clinical studies with longer intervals and durations also reported significant effects of IF on weight loss and body health. Long term strict IF is unfavorable for some patients – in particular the elderly and the chronically ill – due to the potential for nutritional and metabolic problems. This study serves as an important reference for the use of IF in health and weight loss management, and offers potential directions for future research. Even though IF showed clear benefits, its safety in the long term and applicability across different populations still need to be validated. Future investigations may look into the long-term effects of IF in different populations, and its potential application in various health conditions.

Intermittent fasting (IF)/ Time Restricted Feeding (TRF) has emerged as a widely recognised dietary strategy, not only for promoting weight loss but also for its potential benefits to cardiovascular health. IF has been shown to significantly reduce key risk factors for heart disease, including hypertension, high cholesterol, and inflammation. This review examines the potential of intermittent fasting to improve heart health, highlighting its advantages beyond weight management and its promising role in the prevention of heart disease. This narrative review aims to evaluate the impact of intermittent fasting on cardiovascular health focussing on its effects on blood pressure, cholesterol, inflammation, and overall heart function. This review followed IMRAD pattern for non systematic review. The search items like “Time Restricted Feeding”, “Alternate Day Fasting”, “Meal Skipping”, “Intermittent Fasting”, “Caloric Restriction”, “Cardiovascular disease” using Boolean operators AND, OR were used. The databases probed were Google scholar, PubMed, Scopus for relevant research published from 2015 to 2024.The study including both male and female individuals ranging from age group 16-84 years who utilised intermittent fasting as an intervention on cardiovascular health. Initially a total of 1,844 articles were identified through comprehensive database searches. After removing of 1039 duplicates, remaining 805 articles were screened by title and abstract and 788 excluded. Seventeen full text articles were screened for inclusion in this narrative review. Out of 17, 8 full text studies were included in the review. The results of all eight studies revealed that IF/TRF, improves insulin sensitivity, glucose metabolism, liver enzymes, and cardiometabolic health including lipid profiles. Three randomised controlled trials also reported that 4- and 6-hour TRF resulted in mild weight loss over eight weeks. It overall concludes that intermittent fasting is a safe diet therapy and provides a promising effect on cardiovascular and metabolic health.

Background: Over the past several years, intermittent fasting (IF) has been considered a possible dietary treatment for metabolic disorders such as Type 2 Diabetes, Hypertension, Obesity, and High Cholesterol. IF helps improve metabolic health by controlling sugar levels, aiding in fat reduction, and improving insulin responsiveness. However, it remains popular without adequate solid evidence supporting its practicality, effectiveness, or difficulties when implementing IF in a clinical setting. Objective: This study aims to systematically review the literature on the impact of intermittent fasting on various metabolic disorders, focusing on its applications, benefits, challenges, and future potential. The review addresses various intermediate IF fasting cycles and their effects on metabolic health while discussing the benefits alongside the barriers to its use in clinical care. Methods: A systematic literature review was conducted across several scientific databases: PubMed, Scopus, and ScienceDirect, including other sources. The review incorporated articles published from 2019 onwards with the focus being on clinical trials, observational studies, and systematic reviews. Data were selected and combined to reveal distinctive patterns concerning the management of metabolic disorders with fasting, the protocols of fasting employed, and the identified challenges from subjects undergoing IF. A clear systematic review was created by following the PRISMA flowchart. Results: The literature review suggests that intermittent fasting, and particularly the method, has several notable benefits in improving weight, blood sugar levels, and insulin sensitivity among the people with metabolic disorders. However, participants noted difficulty with consistency, irritability, a sharp increase in hunger, and increased stress. The main issues most respondents indicated were insufficient education on IF, social restrictions, and compliance with fasting protocols. Despite all these challenges, many respondents reported being optimistic about the impact of metabolic health in the long run. Conclusion: Research suggests that intermittent fasting can be one of the effective strategies used for metabolic disorder management because it helps achieve weight targets and maintain blood sugar levels. Notwithstanding, other factors such as integration into lifestyle, education, and compliance need to be addressed to promote effective fasting. More studies are needed to investigate the fasting regimen design for easy adoption, barriers to use, and the prolonged effect. IF on metabolic health. The outcome of this review can be beneficial to the public, healthcare stakeholders, and policymakers who intend to use or promote IF as part of their metabolic disorder management plans.

Background: Intermittent fasting (IF) has surged in popularity as a dietary approach for weight management and metabolic health, yet its effects on female reproductive hormones and menstrual cycle regulation remain an area of growing scientific inquiry. This systematic review aims to evaluate the influence of IF on female reproductive hormones and menstrual cycle. Methods: The study followed PRISMA 2020 guidelines, reviewing English-language publications from 2015 to 2025. Editorials, duplicate reviews from the same journal, and papers lacking a DOI were excluded. The literature search was conducted using PubMed, SagePub, SpringerLink, and Google Scholar. Result: A total of 2,172 articles were initially identified through online databases (PubMed, SagePub, SpringerLink, and Google Scholar). After three rounds of screening, eight relevant studies were selected for full-text analysis. Conclusion: IF presents both potential benefits and risks for female reproductive health. While it may aid in weight loss, improve insulin sensitivity, and reduce inflammation, concerns remain about its effects on hormonal circadian rhythms and reproductive function. Individualized approaches that consider metabolic status, hormonal health, and lifestyle factors are essential for optimizing the benefits of IF while minimizing potential adverse effects on female reproductive hormones and menstrual cycles.

The aim of this review is to provide an overview of the present association between Intermittent Fasting (IF), the Gut Microbiota (GM), and the adipocyte with respect to Metabolic Health (MH). A search was carried out through Dialnet, Scielo, Web of Science, Redalyc and PubMed, using keywords such as: "intermittent fasting", "time-restricted feeding", "gut microbiota" and "Metabolic Health". Intermittent fasting (IF) regimens promote weight loss, therefore contributing to improved metabolic health. IF beneficially participates in the modulation of the intestinal microbiome, allowing a continuous interaction with nutrients to be digested and shaping the intestinal immune responses during the development of cardiovascular disease, blood pressure and diabetes mellitus through metabolic activities.

From the Literature

Effects of time-restricted feeding with different feeding windows on metabolic health: A systematic review of human studies

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting reproductive-aged women, characterized by metabolic dysfunction, hyperandrogenism, and ovulatory disturbances. Exercise has emerged as a key non-pharmacological strategy to manage both metabolic and reproductive complications of the syndrome. This review aims to synthesize evidence from the past decade (2014–2024) on the effects of structured exercise interventions, including aerobic, resistance, and high-intensity interval training (HIIT) on metabolic and reproductive health outcomes in women with PCOS. A narrative review was conducted following PRISMA guidelines. Electronic databases (PubMed, Scopus, and Web of Science) were systematically searched for studies published between January 2014 and December 2024. Eligible studies included randomized controlled trials, cohort studies, and systematic reviews examining the independent effects of exercise on insulin sensitivity, body composition, ovulation, menstrual function, and hormonal profiles in women diagnosed with PCOS. Evidence indicates that structured exercise significantly improves insulin resistance, fasting glucose, lipid profiles, and body composition in women with PCOS. Reproductive benefits include increased menstrual regularity, improved ovulation, and reductions in serum testosterone levels. These effects are observed across different exercise modalities and often occur independently of weight loss. Combined training (aerobic + resistance) appears to provide the most comprehensive benefits. Exercise is a clinically effective and low-risk intervention that should be integrated as a central component of PCOS management, regardless of BMI or phenotype. Personalized exercise prescriptions and long-term adherence strategies are essential to maximize therapeutic outcomes. Future research should focus on standardized protocols and long-term reproductive and metabolic follow-up Keyword :Exercise Intervention, Insulin Resistance, Metabolic Health, Polycystic Ovary Syndrome, Reproductive Function.

Purpose of ReviewThis narrative review aimed to provide an overview of the current evidence on the impact of various nutritional strategies on body composition in people living with obesity (PLwO), with particular attention to fat mass (FM), fat-free mass (FFM), and fat distribution.Recent FindingsObesity is increasingly linked to cardiometabolic complications, yet common diagnostic metrics such as body mass index (BMI) do not capture changes in FM or FFM. Recent studies highlight the variable effects of different dietary interventions on body compartments. High-protein and ketogenic diets are associated with greater preservation of FFM and reductions in visceral adipose tissue (VAT), while the Mediterranean diet shows promise for long-term adherence and improvements in metabolic health. Intermittent fasting and time-restricted eating demonstrate efficacy in FM reduction but present mixed results regarding FFM retention and sustainability.SummaryDietary strategies exert diverse effects on body composition in PLwO, underscoring the importance of tailoring interventions to individual metabolic profiles and health goals. Personalized nutrition approaches that prioritize the preservation of lean mass and reduction of VAT, along with sustainable adherence, are critical for optimizing obesity management beyond weight loss alone.Graphical

Time restricted feeding (TRF) as a form of intermittent fasting (IF) has gained popularity because its ability to reduce body mass (BM) without an emphasis on caloric restriction. However, how this dietary protocol may affect health, fitness, and performance in a relatively healthy cohort remains less clear. The purpose of this article was to systematically review the current literature concerning the effect of TRF on anthropometric, metabolic, and fitness parameters in normal-weight adults and overweight and obese individuals. A systematic search of English literature was conducted through databases including PubMed, CINAHL, and Google Scholar. The search was facilitated by using various combinations of key words related to nutritional interventions, i.e., IF and TRF, and outcomes of interest, i.e., BM, body composition, glucose, insulin, lipid, fitness, and performance. The article selection was made based on the inclusion and exclusion criteria concerning the participants’ characteristics, study design, intervention protocols, and targeted dependent variables. Twenty-three full-text longitudinal randomized and nonrandomized controlled studies were selected for this review. Our analysis indicates that TRF can reduce BM and improve nutrient metabolism in both normal- and over-weight individuals. TRF does not appear to alter protein synthesis and fat-free mass nor hamper aerobic fitness and muscular performance among physically active individuals including athletes. In conclusion, TRF as a more easily adaptable form of IF is a promising dietary approach to improving body composition and metabolic health while maintaining fitness and muscular function. However, more research is needed before this dietary protocol can be fully recommended for athletes especially those competing in sports that demand strength and power. Key teaching points and nutritional relevance Time-restricted feeding (TRF) differs from other fasting protocols due to its emphasis on restricting eating window rather than caloric intake and can be more easily adopted by simply skipping a meal. Its deemphasis on caloric restriction appeals to many young and physically active individuals wanting to optimize body composition but needing sufficient energy to support their physical training and daily activity. Much of what is known regarding the impact of TRF on fitness and athletic performance was derived from studies that use the Ramadan fasting protocol, which differs from TRF in terms of protocol duration and feeding schedule. This review concludes that TRF is a promising dietary approach to improving body composition and metabolic health while maintaining fitness and muscular function in both normal- and over-weight individuals. Due to limited evidence concerning TRF and athletic performance, more research is needed before this dietary protocol can be fully recommended for athletes especially those competing in sports that demand strength and power.

BackgroundIntermittent fasting (IF) holds promise for enhancing metabolic health. However, the optimum IF forms and their superiority over continuous energy restriction (CER) remain unclear due to disconnected findings.MethodsWe systematically searched PubMed, Embase, and the Cochrane databases for meta-analyses of randomized controlled trials (RCTs) investigating the association between IF and metabolic health outcomes. Subsequently, we performed an umbrella review and network meta-analysis (NMA) to evaluate the efficacy of different forms of IF (time-restricted eating (TRE), alternate-day fasting (ADF), and 5:2 diet (regular eating for 5 days and energy restriction for 2 days per week)) compared to CER and usual diets on metabolic health outcomes. To assess the certainty of both direct and indirect estimates, we employed the Confidence in Network Meta-Analysis (CINeMA) approach. Additionally, we calculated the surface under the cumulative ranking curve (SUCRA) for each dietary strategy to determine their ranking in terms of metabolic health benefits.ResultsTen of the best and non-redundant meta-analysis studies, involving 153 original studies and 9846 participants, were included. When considering direct evidence only, all IF forms significantly reduced body weight compared to usual diets. In NMA incorporating indirect evidence, all IF regimens also significantly reduced body weight compared to usual diets. In the SUCRA of NMA, IF ranked higher than usual diets or CER in 85.4% and 56.1% of the outcomes, respectively. ADF had the highest overall ranking for improving metabolic health (ranked first: 64.3%, ranked second: 14.3%).ConclusionsOverall, all IF forms demonstrate potentials to improve metabolic health, with ADF appearing to produce better outcomes across investigated outcomes. Further high-quality trials are warranted to confirm the (relative) efficacy of IF on metabolic health.Trial registrationPROSPERO (record no: CRD42022302690).