Intermittent fasting has strong mechanistic plausibility and a growing clinical evidence base. Here's what the controlled trials actually show — and where the limitations are.
Intermittent fasting moved from internet subculture to mainstream clinical research over roughly a decade, generating a genuine body of RCT evidence. The research is now large enough to draw some reliable conclusions — and to see where the initial enthusiasm outran the data.
Time-restricted eating (TRE) produces modest metabolic benefits in people with metabolic dysfunction. The strongest evidence is in individuals with obesity, insulin resistance, or metabolic syndrome. Multiple RCTs show improvements in insulin sensitivity, blood glucose, blood pressure, and lipid profiles. In metabolically healthy people, the effects are smaller and less consistent.
Most weight loss from IF comes from caloric restriction, not the timing per se. When calories are controlled in RCTs, time-restricted eating shows modest additional benefits beyond caloric restriction alone. The primary mechanism for weight loss is that a compressed eating window reduces total caloric intake. This isn't a knock on IF — reducing eating opportunity is a legitimate strategy — but the mechanistic framing is often overstated.
Autophagy upregulation is real but timing is uncertain in humans. Animal studies showing autophagy induction during fasting are well-replicated. The human studies are fewer and suggest the relevant fasting duration in humans is likely longer (24+ hours) than the 16-hour eating windows of typical TRE protocols. Claims about daily 16:8 protocols producing significant autophagy in humans are ahead of the evidence.
Cognitive effects during fasting are mixed. Some studies show improved alertness and focus during the fasted state, mediated by ketone production and reduced insulin. Others show impaired performance on attention tasks, particularly in the early weeks before adaptation. Individual variation is large.
Adherence diverges from compliance in long-term studies. Most IF RCTs run 8–12 weeks. Longer studies show substantial dropout, and the metabolic benefits in completers may overstate what typical adherence produces.
Athletic performance considerations. Training fasted shows neutral to slightly negative effects on performance in most sports. Strength training specifically shows reduced performance in fasted conditions for most people, though some adapt.
TRE is a useful tool for some people — particularly those who find it easier to skip a meal than to restrict within meals, and those with metabolic dysfunction. The evidence doesn't support it as universally superior to other dietary approaches. Individual response is highly variable, making it a strong candidate for personal experimentation.
Evidence is mixed
Most weight-loss benefits are explained by reduced caloric intake, not timing per se. Effects in metabolically healthy individuals are smaller than popular accounts suggest.
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Is isocaloric intermittent fasting superior to calorie restriction? A systematic review and meta-analysis of RCTs.
This meta-analysis found that while isocaloric intermittent fasting (IF) can be an effective weight management strategy, it is generally not superior to isocaloric calorie restriction (CR) for improving overall health markers, suggesting IF is a comparable alternative rather than a definitively better approach when calories are matched.
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Evidence base
50 papers
Hamsho M, Shkorfu W, Ranneh Y +1 more · Nutr Metab Cardiovasc Dis · 2025 · 7 citations
This meta-analysis found that while isocaloric intermittent fasting (IF) can be an effective weight management strategy, it is generally not superior to isocaloric calorie restriction (CR) for improving overall health markers, suggesting IF is a comparable alternative rather than a definitively better approach when calories are matched.
Read the breakdown →Wang B, Wang C, Li H · Nutr J · 2025 · 10 citations
This meta-analysis found that intermittent fasting significantly reduces body weight, BMI, total cholesterol, "bad" LDL cholesterol, and diastolic blood pressure in overweight and obese adults, with benefits for triglycerides emerging after 12 weeks, and Alternate Day Fasting showing superior results for weight loss and LDL compared to Time-Restricted Eating.
Read the breakdown →Yan S , Wang C , Zhao H +6 more · Food Funct · 2020 · 11 citations
This meta-analysis of 25 studies found that various fasting interventions significantly reduced body weight, BMI, fat mass, waist circumference, LDL cholesterol, triglycerides, and blood pressure in people with overweight or obesity, providing a strong basis for self-experimentation with structured fasting for these outcomes.
Read the breakdown →Trevor J. Orchard, Marinella Temprosa, Ronald Goldberg +4 more · Annals of Internal Medicine · 2005 · 938 citations
This study found that an intensive lifestyle intervention (targeting 7% weight loss and 150 minutes of exercise per week) reduced the risk of developing metabolic syndrome by 41%, and metformin (850 mg twice daily) reduced it by 17% over 3.2 years in people at
Read the breakdown →Laura R. Saslow, Sarah Kim, Jennifer Daubenmier +7 more · PLoS ONE · 2014 · 229 citations
A 3-month pilot study found that a very low carbohydrate, high-fat diet led to a 0.6% greater reduction in HbA1c and a higher rate of diabetes medication reduction compared to a moderate carbohydrate, low-fat, calorie-restricted diet in overweight or obese individuals with type 2 diabetes or prediabetes.
Read the breakdown →James A. Betts, Judith D. Richardson, Enhad A. Chowdhury +3 more · American Journal of Clinical Nutrition · 2014 · 204 citations
This study found that eating breakfast daily led to higher physical activity levels and greater overall calorie intake in lean adults, without changing resting metabolism or body weight, but did result in more stable blood sugar levels later in the day compared to extended fasting.
Read the breakdown →Replacing sitting time with standing or stepping: associations with cardio-metabolic risk biomarkers
Geneviève N. Healy, Elisabeth Winkler, Neville Owen +2 more · European Heart Journal · 2015 · 323 citations
Replacing 2 hours of sitting per day with standing was associated with modest improvements in blood sugar and blood fats (11% lower triglycerides, 2% lower fasting glucose), while replacing sitting with stepping (walking) was associated with larger improvements including 11% lower BMI, 7.5 cm smaller waist circumference, and 11% lower 2-hour blood glucose — suggesting that even standing breaks are beneficial, but movement is better.
Read the breakdown →Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain
Rachel R. Markwald, Edward L. Melanson, Mark R. Smith +4 more · Proceedings of the National Academy of Sciences · 2013 · 799 citations
Insufficient sleep is associated with obesity, yet little is known about how repeated nights of insufficient sleep influence energy expenditure and balance. We studied 16 adults in a 14- to 15-d-long inpatient study and quantified effects of 5 d of insufficient sleep, equivalent to a work week, on energy expenditure and energy intake compared with adequate sleep. We found that insufficient sleep increased total daily energy expenditure by ∼5%; however, energy intake--especially at night after dinner--was in excess of energy needed to maintain energy balance. Insufficient sleep led to 0.82 ± 0.47 kg (±SD) weight gain despite changes in hunger and satiety hormones ghrelin and leptin, and peptide YY, which signaled excess energy stores. Insufficient sleep delayed circadian melatonin phase and also led to an earlier circadian phase of wake time. Sex differences showed women, not men, maintained weight during adequate sleep, whereas insufficient sleep reduced dietary restraint and led to weight gain in women. Our findings suggest that increased food intake during insufficient sleep is a physiological adaptation to provide energy needed to sustain additional wakefulness; yet when food is easily accessible, intake surpasses that needed. We also found that transitioning from an insufficient to adequate/recovery sleep schedule decreased energy intake, especially of fats and carbohydrates, and led to -0.03 ± 0.50 kg weight loss. These findings provide evidence that sleep plays a key role in energy metabolism. Importantly, they demonstrate physiological and behavioral mechanisms by which insufficient sleep may contribute to overweight and obesity.
Slaven Stekovic, Sebastian J. Hofer, Norbert J. Tripolt +28 more · Cell Metabolism · 2019 · 397 citations
Michelle Harvie, Claire Wright, Mary Pegington +13 more · British Journal Of Nutrition · 2013 · 453 citations
Intermittent energy restriction may result in greater improvements in insulin sensitivity and weight control than daily energy restriction (DER). We tested two intermittent energy and carbohydrate restriction (IECR) regimens, including one which allowed ad libitum protein and fat (IECR+PF). Overweight women (n 115) aged 20 and 69 years with a family history of breast cancer were randomised to an overall 25 % energy restriction, either as an IECR (2500-2717 kJ/d, < 40 g carbohydrate/d for 2 d/week) or a 25 % DER (approximately 6000 kJ/d for 7 d/week) or an IECR+PF for a 3-month weight-loss period and 1 month of weight maintenance (IECR or IECR+PF for 1 d/week). Insulin resistance reduced with the IECR diets (mean - 0·34 (95% CI - 0·66, - 0·02) units) and the IECR+PF diet (mean - 0·38 (95% CI - 0·75, - 0·01) units). Reductions with the IECR diets were significantly greater compared with the DER diet (mean 0·2 (95% CI - 0·19, 0·66) μU/unit, P= 0·02). Both IECR groups had greater reductions in body fat compared with the DER group (IECR: mean - 3·7 (95% CI - 2·5, - 4·9) kg, P= 0·007; IECR+PF: mean - 3·7 (95% CI - 2·8, - 4·7) kg, P= 0·019; DER: mean - 2·0 (95% CI - 1·0, 3·0) kg). During the weight maintenance phase, 1 d of IECR or IECR+PF per week maintained the reductions in insulin resistance and weight. In the short term, IECR is superior to DER with respect to improved insulin sensitivity and body fat reduction. Longer-term studies into the safety and effectiveness of IECR diets are warranted.
Mattea Müller, Manuel A. González Hernández, Gijs H. Goossens +6 more · Scientific Reports · 2019 · 322 citations
, normal or impaired glucose metabolism), associations between SCFA (faecal and fasting circulating) and circulating metabolites, substrate oxidation and IS were investigated. In a subgroup (n = 93), IS was determined using a hyperinsulinemic-euglycemic clamp. Data were analyzed using multiple linear regression analysis adjusted for sex, age and BMI. Fasting circulating acetate, propionate and butyrate concentrations were positively associated with fasting GLP-1 concentrations. Additionally, circulating SCFA were negatively related to whole-body lipolysis (glycerol), triacylglycerols and free fatty acids levels (standardized (std) β adjusted (adj) -0.190, P = 0.023; std β adj -0.202, P = 0.010; std β adj -0.306, P = 0.001, respectively). Circulating acetate and propionate were, respectively, negatively and positively correlated with IS (M-value: std β adj -0.294, P < 0.001; std β adj 0.161, P = 0.033, respectively). We show that circulating rather than faecal SCFA were associated with GLP-1 concentrations, whole-body lipolysis and peripheral IS in humans. Therefore, circulating SCFA are more directly linked to metabolic health, which indicates the need to measure circulating SCFA in human prebiotic/probiotic intervention studies as a biomarker/mediator of effects on host metabolism.
Sarah J. Hallberg, Amy L. McKenzie, Paul T. Williams +8 more · Diabetes Therapy · 2018 · 408 citations
Carbohydrate restriction markedly improves glycemic control in patients with type 2 diabetes (T2D) but necessitates prompt medication changes. Therefore, we assessed the effectiveness and safety of a novel care model providing continuous remote care with medication management based on biometric feedback combined with the metabolic approach of nutritional ketosis for T2D management. We conducted an open-label, non-randomized, controlled, before-and-after 1-year study of this continuous care intervention (CCI) and usual care (UC). Primary outcomes were glycosylated hemoglobin (HbA1c), weight, and medication use. Secondary outcomes included fasting serum glucose and insulin, HOMA-IR, blood lipids and lipoproteins, liver and kidney function markers, and high-sensitivity C-reactive protein (hsCRP). 349 adults with T2D enrolled: CCI: n = 262 [mean (SD); 54 (8) years, 116.5 (25.9) kg, 40.4 (8.8) kg m2, 92% obese, 88% prescribed T2D medication]; UC: n = 87 (52 (10) years, 105.6 (22.15) kg, 36.72 (7.26) kg m2, 82% obese, 87% prescribed T2D medication]. 218 participants (83%) remained enrolled in the CCI at 1 year. Intention-to-treat analysis of the CCI (mean ± SE) revealed HbA1c declined from 59.6 ± 1.0 to 45.2 ± 0.8 mmol mol−1 (7.6 ± 0.09% to 6.3 ± 0.07%, P < 1.0 × 10−16), weight declined 13.8 ± 0.71 kg (P < 1.0 × 10−16), and T2D medication prescription other than metformin declined from 56.9 ± 3.1% to 29.7 ± 3.0% (P < 1.0 × 10−16). Insulin therapy was reduced or eliminated in 94% of users; sulfonylureas were entirely eliminated in the CCI. No adverse events were attributed to the CCI. Additional CCI 1-year effects were HOMA-IR − 55% (P = 3.2 × 10−5), hsCRP − 39% (P < 1.0 × 10−16), triglycerides − 24% (P < 1.0 × 10−16), HDL-cholesterol + 18% (P < 1.0 × 10−16), and LDL-cholesterol + 10% (P = 5.1 × 10−5); serum creatinine and liver enzymes (ALT, AST, and ALP) declined (P ≤ 0.0001), and apolipoprotein B was unchanged (P = 0.37). UC participants had no significant changes in biomarkers or T2D medication prescription at 1 year. These results demonstrate that a novel metabolic and continuous remote care model can support adults with T2D to safely improve HbA1c, weight, and other biomarkers while reducing diabetes medication use. NCT02519309. Virta Health Corp. Treatments for type 2 diabetes (T2D) have improved, yet T2D and being overweight are still significant public health concerns. Blood sugar in patients with T2D can improve quickly when patients eat significantly fewer dietary carbohydrates. However, this demands careful medicine management by doctors, and patients need support and frequent contact with health providers to sustain this way of living. The purpose of this study was to evaluate if a new care model with very low dietary carbohydrate intake and continuous supervision by a health coach and doctor could safely lower HbA1c, weight and need for medicines after 1 year in adults with T2D. 262 adults with T2D volunteered to participate in this continuous care intervention (CCI) along with 87 adults with T2D receiving usual care (UC) from their doctors and diabetes education program. After 1 year, patients in the CCI, on average, lowered HbA1c from 7.6 to 6.3%, lost 12% of their body weight, and reduced diabetes medicine use. 94% of patients who were prescribed insulin reduced or stopped their insulin use, and sulfonylureas were eliminated in all patients. Participants in the UC group had no changes to HbA1c, weight or diabetes medicine use over the year. These changes in CCI participants happened safely while dyslipidemia and markers of inflammation and liver function improved. This suggests the novel care model studied here using dietary carbohydrate restriction and continuous remote care can safely support adults with T2D to lower HbA1c, weight, and medicine use.
Intermittent Fasting and Human Metabolic Health
Ruth E. Patterson, Gail A. Laughlin, Andrea Z. LaCroix +8 more · Journal of the Academy of Nutrition and Dietetics · 2015 · 390 citations
Cardiometabolic Risk in Patients With First-Episode Schizophrenia Spectrum Disorders
Christoph U. Correll, Delbert G. Robinson, Nina R. Schooler +13 more · JAMA Psychiatry · 2014 · 390 citations
IMPORTANCE: The fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear. OBJECTIVE: To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity. DESIGN, SETTING, AND PARTICIPANTS: Baseline results of the Recovery After an Initial Schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment. EXPOSURE: Prebaseline antipsychotic treatment was based on the community clinician's and/or patient's decision. MAIN OUTCOMES AND MEASURES: Body composition and fasting lipid, glucose, and insulin parameters. RESULTS: In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A1c based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P<.01) but not elevated metabolic parameters (except triglycerides to HDL-C ratio [P=.04]). Conversely, antipsychotic treatment duration correlated significantly with higher non-HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P≤.01). In multivariable analyses, olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P≤.02). CONCLUSIONS AND RELEVANCE: In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.
Leigh Breen, Keith Stokes, Tyler A. Churchward‐Venne +5 more · The Journal of Clinical Endocrinology & Metabolism · 2013 · 385 citations
BACKGROUND: Alterations in muscle protein metabolism underlie age-related muscle atrophy. During periods of muscle disuse, muscle protein synthesis is blunted, and muscle atrophy occurs in young and old. The impact of a short reduction in physical activity on muscle protein metabolism in older adults is unknown. PURPOSE: The aim of this study was to investigate the impact of 14 days of reduced daily steps on fasted and fed-state rates of myofibrillar protein synthesis (MPS) to provide insight into the mechanisms for changes in muscle mass and markers of metabolic health. METHODS: Before and after 14 days of reduced daily step-count, 10 healthy older adults (age, 72 ± 1 y) underwent measures of insulin sensitivity, muscle strength, physical function, and body composition. Using a primed constant infusion of L-[ring-(13)C6]phenylalanine with serial muscle biopsies, basal, postabsorptive, and postprandial rates of MPS were determined before and after the 14-day intervention. RESULTS: Daily step-count was reduced by approximately 76% to 1413 ± 110 steps per day. Leg fat-free mass was reduced by approximately 3.9% (P < .001). Postabsorptive insulin resistance was increased by approximately 12%, and postprandial insulin sensitivity was reduced by approximately 43% after step reduction (P < .005). Concentrations of TNF-α and C-reactive protein were increased by approximately 12 and 25%, respectively, after step reduction (P < .05). Postprandial rates of MPS were reduced by approximately 26% after the intervention (P = .028), with no difference in postabsorptive rates. CONCLUSION: The present study demonstrates that 14 days of reduced steps in older adults induces small but measurable reductions in muscle mass that appear to be underpinned by reductions in postprandial MPS and are accompanied by impairments in insulin sensitivity and systemic inflammatory markers and postprandial MPS.
Dietary Energy Density Is Associated With Obesity and the Metabolic Syndrome in U.S. Adults
Jason A. Mendoza, Adam Drewnowski, Dimitri Christakis · Diabetes Care · 2007 · 272 citations
OBJECTIVE: Rising obesity rates have been linked to the consumption of energy-dense diets. We examined whether dietary energy density was associated with obesity and related disorders including insulin resistance and the metabolic syndrome. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study using nationally representative data of U.S. adults > or =20 years of age from the 1999-2002 National Health and Nutrition Examination Survey (n = 9,688). Dietary energy density was calculated based on foods only. We used a series of multivariate linear regression models to determine the independent association between dietary energy density, obesity measures (BMI [in kilograms per meters squared] and waist circumference [in centimeters]), glycemia, or insulinemia. We used multivariate Poisson regression models to determine the independent association between dietary energy density and the metabolic syndrome as defined by the National Cholesterol and Education Program (Adult Treatment Panel III). RESULTS: Dietary energy density was independently and significantly associated with higher BMI in women (beta = 0.44 [95% CI 0.14-0.73]) and trended toward a significant association in men (beta = 0.37 [-0.007 to 0.74], P = 0.054). Dietary energy density was associated with higher waist circumference in women (beta = 1.11 [0.42-1.80]) and men (beta = 1.33 [0.46-2.19]). Dietary energy density was also independently associated with elevated fasting insulin (beta = 0.65 [0.18-1.12]) and the metabolic syndrome (prevalence ratio = 1.10 [95% CI 1.03-1.17]). CONCLUSIONS: Dietary energy density is an independent predictor of obesity, elevated fasting insulin levels, and the metabolic syndrome in U.S. adults. Intervention studies to reduce dietary energy density are warranted.
Andrea M. Spaeth, David F. Dinges, Namni Goel · SLEEP · 2013 · 444 citations
STUDY OBJECTIVES: Examine sleep restriction's effects on weight gain, daily caloric intake, and meal timing. DESIGN: Repeated-measures experiments assessing body weight at admittance and discharge in all subjects (N = 225) and caloric intake and meal timing across days following 2 baseline nights, 5 sleep restriction nights and 2 recovery nights or across days following control condition nights in a subset of subjects (n = 37). SETTING: Controlled laboratory environment. PARTICIPANTS: Two hundred twenty-five healthy adults aged 22-50 y (n = 198 sleep-restricted subjects; n = 31 with caloric intake data; n = 27 control subjects; n = 6 with caloric intake data). INTERVENTIONS: Approximately 8-to-1 randomization to an experimental condition (including five consecutive nights of 4 h time in bed [TIB]/night, 04:00-08:00) or to a control condition (all nights 10 h TIB/night, 22:00-08:00). MEASUREMENTS AND RESULTS: Sleep-restricted subjects gained more weight (0.97 ± 1.4 kg) than control subjects (0.11 ± 1.9 kg; d = 0.51, P = 0.007). Among sleep-restricted subjects, African Americans gained more weight than Caucasians (d = 0.37, P = 0.003) and males gained more weight than females (d = 0.38, P = 0.004). Sleep-restricted subjects consumed extra calories (130.0 ± 43.0% of daily caloric requirement) during days with a delayed bedtime (04:00) compared with control subjects who did not consume extra calories (100.6 ± 11.4%; d = 0.94, P = 0.003) during corresponding days. In sleep-restricted subjects, increased daily caloric intake was due to more meals and the consumption of 552.9 ± 265.8 additional calories between 22:00-03:59. The percentage of calories derived from fat was greater during late-night hours (22:00-03:59, 33.0 ± 0.08%) compared to daytime (08:00-14:59, 28.2 ± 0.05%) and evening hours (15:00-21:59, 29.4 ± 0.06%; Ps < 0.05). CONCLUSIONS: In the largest, most diverse healthy sample studied to date under controlled laboratory conditions, sleep restriction promoted weight gain. Chronically sleep-restricted adults with late bedtimes may be more susceptible to weight gain due to greater daily caloric intake and the consumption of calories during late-night hours. CITATION: 2013;36(7):981-990.
Eating and shift work – effects on habits, metabolism and performance
Arne Löwden, Cláudia Roberta de Castro Moreno, Ulf Holmbäck +2 more · Scandinavian Journal of Work Environment & Health · 2010 · 485 citations
Compared to individuals who work during the day, shift workers are at higher risk of a range of metabolic disorders and diseases (eg, obesity, cardiovascular disease, peptic ulcers, gastrointestinal problems, failure to control blood sugar levels, and metabolic syndrome). At least some of these complaints may be linked to the quality of the diet and irregular timing of eating, however other factors that affect metabolism are likely to play a part, including psychosocial stress, disrupted circadian rhythms, sleep debt, physical inactivity, and insufficient time for rest and revitalization. In this overview, we examine studies on food and nutrition among shift workers [ie, dietary assessment (designs, methods, variables) and the factors that might influence eating habits and metabolic parameters]. The discussion focuses on the quality of existing dietary assessment data, nutritional status parameters (particularly in obesity), the effect of circadian disruptions, and the possible implications for performance at work. We conclude with some dietary guidelines as a basis for managing the nutrition of shift workers.
Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential
Yu-Ling Xiao, Yue Gong, Ying-Jia Qi +2 more · Signal Transduction and Targeted Therapy · 2024 · 176 citations
This comprehensive review of over 300 studies found that specific dietary interventions—particularly calorie restriction, fasting-mimicking diets, and ketogenic diets—can modulate immune function, slow disease progression, and enhance treatment efficacy in cancer, neurodegenerative diseases, autoimmune conditions, and metabolic disorders, but the mechanisms are still poorly understood and most evidence comes from animal models or short-term human trials.
Read the breakdown →Lauren Duckworth, Paul Gately, Duncan Radley +3 more · Obesity · 2009 · 31 citations
This study found that an energy-restricted high-protein diet (25% protein) was no more effective than a standard-protein diet (15% protein) for weight loss, body composition, or managing hunger and mood in overweight and obese children participating in an 8-week weight-loss program, with overall hunger increasing regardless of diet.
Read the breakdown →R L Bijlani, Rama P. Vempati, Raj Kumar Yadav +5 more · The Journal of Alternative and Complementary Medicine · 2005 · 301 citations
OBJECTIVES: The objective of the study was to study the short-term impact of a brief lifestyle intervention based on yoga on some of the biochemical indicators of risk for cardiovascular disease and diabetes mellitus. DESIGN: The variables of interest were measured at the beginning (day 1) and end (day 10) of the intervention using a pre-post design. SETTING: The study is the result of operational research carried out in our Integral Health Clinic (IHC). The IHC is an outpatient facility which conducts 8-day lifestyle modification programs based on yoga for prevention and management of chronic disease. A new course begins every alternate week of the year. SUBJECTS: The study is based on data collected on 98 subjects (67 male, 31 female), ages 20-74 years, who attended one of our programs. The subjects were a heterogeneous group of patients with hypertension, coronary artery disease, diabetes mellitus, and a variety of other illnesses. INTERVENTION: The intervention consisted of asanas (postures), pranayama (breathing exercises), relaxation techniques, group support, individualized advice, lectures and films on the philosophy of yoga and the place of yoga in daily life, meditation, stress management, nutrition, and knowledge about the illness. OUTCOME MEASURES: The outcome measures were fasting plasma glucose and serum lipoprotein profile. These variables were determined in fasting blood samples, taken on the first and last day of the course. RESULTS: Fasting plasma glucose, serum total cholesterol, low-density lipoprotein (LDL) cholesterol, very- LDL cholesterol, the ratio of total cholesterol to high density lipoprotein (HDL) cholesterol, and total triglycerides were significantly lower, and HDL cholesterol significantly higher, on the last day of the course compared to the first day of the course. The changes were more marked in subjects with hyperglycemia or hypercholesterolemia. CONCLUSIONS: The observations suggest that a short lifestyle modification and stress management education program leads to favorable metabolic effects within a period of 9 days.
Michal Rein, Orly Ben-Yacov, Anastasia Godneva +12 more · BMC Medicine · 2022 · 132 citations
BACKGROUND: Dietary modifications are crucial for managing newly diagnosed type 2 diabetes mellitus (T2DM) and preventing its health complications, but many patients fail to achieve clinical goals with diet alone. We sought to evaluate the clinical effects of a personalized postprandial-targeting (PPT) diet on glycemic control and metabolic health in individuals with newly diagnosed T2DM as compared to the commonly recommended Mediterranean-style (MED) diet. METHODS: We enrolled 23 adults with newly diagnosed T2DM (aged 53.5 ± 8.9 years, 48% males) for a randomized crossover trial of two 2-week-long dietary interventions. Participants were blinded to their assignment to one of the two sequence groups: either PPT-MED or MED-PPT diets. The PPT diet relies on a machine learning algorithm that integrates clinical and microbiome features to predict personal postprandial glucose responses (PPGR). We further evaluated the long-term effects of PPT diet on glycemic control and metabolic health by an additional 6-month PPT intervention (n = 16). Participants were connected to continuous glucose monitoring (CGM) throughout the study and self-recorded dietary intake using a smartphone application. RESULTS: In the crossover intervention, the PPT diet lead to significant lower levels of CGM-based measures as compared to the MED diet, including average PPGR (mean difference between diets, - 19.8 ± 16.3 mg/dl × h, p < 0.001), mean glucose (mean difference between diets, - 7.8 ± 5.5 mg/dl, p < 0.001), and daily time of glucose levels > 140 mg/dl (mean difference between diets, - 2.42 ± 1.7 h/day, p < 0.001). Blood fructosamine also decreased significantly more during PPT compared to MED intervention (mean change difference between diets, - 16.4 ± 37 μmol/dl, p < 0.0001). At the end of 6 months, the PPT intervention leads to significant improvements in multiple metabolic health parameters, among them HbA1c (mean ± SD, - 0.39 ± 0.48%, p < 0.001), fasting glucose (- 16.4 ± 24.2 mg/dl, p = 0.02) and triglycerides (- 49 ± 46 mg/dl, p < 0.001). Importantly, 61% of the participants exhibited diabetes remission, as measured by HbA1c < 6.5%. Finally, some clinical improvements were significantly associated with gut microbiome changes per person. CONCLUSION: In this crossover trial in subjects with newly diagnosed T2DM, a PPT diet improved CGM-based glycemic measures significantly more than a Mediterranean-style MED diet. Additional 6-month PPT intervention further improved glycemic control and metabolic health parameters, supporting the clinical efficacy of this approach. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01892956.
Effect of intermittent fasting and refeeding on insulin action in healthy men
Nils Halberg, Morten Gaarden Henriksen, Nathalie Söderhamn +4 more · Journal of Applied Physiology · 2005 · 256 citations
Insulin resistance is currently a major health problem. This may be because of a marked decrease in daily physical activity during recent decades combined with constant food abundance. This lifestyle collides with our genome, which was most likely selected in the late Paleolithic era (50,000-10,000 BC) by criteria that favored survival in an environment characterized by fluctuations between periods of feast and famine. The theory of thrifty genes states that these fluctuations are required for optimal metabolic function. We mimicked the fluctuations in eight healthy young men [25.0 +/- 0.1 yr (mean +/- SE); body mass index: 25.7 +/- 0.4 kg/m(2)] by subjecting them to intermittent fasting every second day for 20 h for 15 days. Euglycemic hyperinsulinemic (40 mU.min(-1).m(-2)) clamps were performed before and after the intervention period. Subjects maintained body weight (86.4 +/- 2.3 kg; coefficient of variation: 0.8 +/- 0.1%). Plasma free fatty acid and beta-hydroxybutyrate concentrations were 347 +/- 18 and 0.06 +/- 0.02 mM, respectively, after overnight fast but increased (P < 0.05) to 423 +/- 86 and 0.10 +/- 0.04 mM after 20-h fasting, confirming that the subjects were fasting. Insulin-mediated whole body glucose uptake rates increased from 6.3 +/- 0.6 to 7.3 +/- 0.3 mg.kg(-1).min(-1) (P = 0.03), and insulin-induced inhibition of adipose tissue lipolysis was more prominent after than before the intervention (P = 0.05). After the 20-h fasting periods, plasma adiponectin was increased compared with the basal levels before and after the intervention (5,922 +/- 991 vs. 3,860 +/- 784 ng/ml, P = 0.02). This experiment is the first in humans to show that intermittent fasting increases insulin-mediated glucose uptake rates, and the findings are compatible with the thrifty gene concept.
Heekyung Chung, Winjet Chou, Dorothy D. Sears +3 more · Metabolism · 2016 · 147 citations
Relationship between screen time and metabolic syndrome in adolescents
Amy E. Mark, Ian Janssen · Journal of Public Health · 2008 · 271 citations
BACKGROUND: The primary objective was to determine the dose-response relation between screen time (television + computer) and the metabolic syndrome (MetS) in adolescents. METHODS: The study sample included 1803 adolescents (12-19 years) from the 1999-04 US National Health and Nutrition Examination Surveys. Average daily screen time (combined television, computer and video game use) was self-reported. MetS was defined according to adolescent criteria linked to the adult criteria of the National Cholesterol Education Program (> or =3 of high triglycerides, high fasting glucose, high waist circumference, high blood pressure and low HDL cholesterol). RESULTS: After adjustment for relevant covariates, the odds ratios (95% confidence intervals) for MetS increased in a dose-response manner (P(trend) < 0.01) across < or =1 h/day (1.00, referent), 2 h/day (1.21, 0.54-2.73), 3 h/day (2.16, 0.99-4.74), 4 h/day (1.73, 0.72-4.17) and > or =5 h/day (3.07, 1.48-6.34) screen time categories. Physical activity had a minimal impact on the relation between screen time and MetS. CONCLUSIONS: Screen time was associated with an increased likelihood of MetS in a dose-dependent manner independent of physical activity. These findings suggest that lifestyle-based public health interventions for youth should include a specific component aimed at reducing screen time.
Metabolic Syndrome and Its Association with Diet and Physical Activity in US Adolescents
Yang Pan, Charlotte Pratt · Journal of the American Dietetic Association · 2008 · 254 citations
Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function
Grant D. Brinkworth · Archives of Internal Medicine · 2009 · 205 citations
BACKGROUND: Very low-carbohydrate (LC) diets are often used to promote weight loss, but the long-term effects on psychological function remain unknown. METHODS: A total of 106 overweight and obese participants (mean [SE] age, 50.0 [0.8] years; mean [SE] body mass index [calculated as weight in kilograms divided by height in meters squared], 33.7 [0.4]) were randomly assigned either to an energy-restricted (approximately 1433-1672 kcal [to convert to kilojoules, multiply by 4.186]), planned isocaloric, very low-carbohydrate, high-fat (LC) diet or to a high-carbohydrate, low-fat (LF) diet for 1 year. Changes in body weight, psychological mood and well-being (Profile of Mood States, Beck Depression Inventory, and Spielberger State Anxiety Inventory scores), and cognitive functioning (working memory and speed of processing) were assessed. RESULTS: By 1 year, the overall mean (SE) weight loss was 13.7 (1.8) kg, with no significant difference between groups (P = .26). Over the course of the study, there were significant time x diet interactions for Spielberger State Anxiety Inventory, Beck Depression Inventory, and Profile of Mood States scores for total mood disturbance, anger-hostility, confusion-bewilderment, and depression-dejection (P < .05) as a result of greater improvements in these psychological mood states for the LF diet compared with the LC diet. Working memory improved by 1 year (P < .001 for time), but speed of processing remained largely unchanged, with no effect of diet composition on either cognitive domain. CONCLUSIONS: Over 1 year, there was a favorable effect of an energy-restricted LF diet compared with an isocaloric LC diet on mood state and affect in overweight and obese individuals. Both diets had similar effects on working memory and speed of processing. Trial Registration anzctr.org.au Identifier: 12606000203550.
Kazeminasab F, Sharafifard F, Bahrami Kerchi A +5 more · Nutrients · 2025 · 2 citations
Jin X, Deng Y, Zhang W +2 more · Crit Rev Food Sci Nutr · 2025 · 4 citations
Jahrami H, Ammar A, Glenn JM +3 more · Nutr Rev · 2025 · 6 citations
Mohamed Cheikh, Omar Hammouda, Nawel Gaamouri +5 more · Chronobiology International · 2018 · 50 citations
The present study aimed to explore the effects of a single 10-mg dose of melatonin (MEL) administration after exhaustive late-evening exercise on sleep quality and quantity, and short-term physical and cognitive performances in healthy teenagers. Ten male adolescent athletes (mean ± SD, age = 15.4 ± 0.3 years, body-mass = 60.68 ± 5.7 kg, height = 167.9 ± 6.9 cm and BMI = 21.21 ± 2.5) performed two test sessions separated by at least one week. During each session, participants completed the Yo-Yo intermittent-recovery-test level-1 (YYIRT-1) at ~20:00 h. Then, sleep polysomnography was recorded from 22:15 min to 07:00 h, after a double blind randomized order administration of a single 10-mg tablet of MEL (MEL-10 mg) or Placebo (PLA). The following morning, Hooper wellness index was administered and the participants performed the Choice Reaction Time (CRT) test, the Zazzo test and some short-term physical exercises (YYIRT-1, vertical and horizontal Jumps (VJ; HJ), Hand grip strength (HG), and five-jump test (5-JT)). Evening total distance covered in the YYIRT-1 did not change during the two conditions (p > 0.05). Total sleep time (Δ = 24.55 mn; p < 0.001), sleep efficiency (Δ = 4.47%; p < 0.001), stage-3 sleep (N3 sleep) (Δ = 1.73%; p < 0.05) and rapid-eye-movement sleep (Δ = 2.15%; p < 0.001) were significantly higher with MEL in comparison with PLA. Moreover, sleep-onset-latency (Δ = -8.45mn; p < 0.001), total time of nocturnal awakenings after sleep-onset (NA) (Δ = -11 mn; p < 0.001), stage-1 sleep (N1 sleep) (Δ = -1.7%; p < 0.001) and stage-2 sleep (N2 sleep) (Δ = -1.9%; p < 0.05) durations were lower with MEL. The Hooper index showed a better subjective sleep quality, a decrease of the subjective perception of fatigue and a reduced level of muscle soreness with MEL. Moreover, MEL improved speed and performance but not inaccuracy during the Zazzo test. CRT was faster with MEL. Morning YYIRT-1 (Δ = 82 m; p < 0.001) and 5-JT (Δ = 0.08 m; p < 0.05) performances were significantly higher with MEL in comparison with PLA. In contrast, HG, VJ and HJ performances did not change during the two conditions (p > 0.05). The administration of a single dose of MEL-10 mg after strenuous late-evening exercise improved sleep quality and quantity, selective attention, subjective assessment of the general wellness state, and some short-term physical performances the following morning in healthy teenagers.
Patikorn C, Roubal K, Veettil SK +6 more · JAMA Netw Open · 2021 · 271 citations
Couto-Alfonso S, Cenit MC, Sanz-Pérez CM +1 more · Nutrients · 2026 · 0 citations
Guo J, Zhang N, Chen J +1 more · Front Nutr · 2025 · 1 citations
This meta-analysis found that combining Intermittent Hypoxia Training (IHT) and Intermittent Fasting (IF) can lead to significant weight loss (average 6.3 kg) and improvements in memory and attention in adults with obesity, offering a promising non-drug strategy for those looking to improve metabolic and cognitive health through lifestyle changes.
Read the breakdown →Frampton J, Edinburgh RM, Ogden HB +2 more · Int J Obes (Lond) · 2022 · 18 citations
Exercising in a fasted state without eating immediately afterwards appears to acutely reduce your total calorie intake over 24 hours, but it also makes you feel significantly hungrier and slightly lowers the total calories you burn, presenting a trade-off for those focused on short-term energy balance.
Read the breakdown →Anderson KC, Zieff G, Paterson C +3 more · Peptides · 2021 · 17 citations
Acute exercise consistently lowers pre-meal ghrelin levels in healthy adults, with higher intensity exercise leading to greater suppression, suggesting a potential strategy to influence appetite-regulating hormones.
Read the breakdown →Trabelsi K, Ammar A, Boukhris O +10 more · Br J Sports Med · 2024 · 11 citations
Effect of Time-Restricted Eating on Sleep Quality and Body Composition: A Systematic Review.
de Sousa BA, Silva ACQ, Ferreira MLA +2 more · Nutr Rev · 2025 · 2 citations
Khan H, Kunutsor SK, Kauhanen J +5 more · J Card Fail · 2014 · 0 citations
Lauche R, Fathi I, Saddat C +6 more · Int J Behav Med · 2025 · 11 citations
Kang J, Ratamess NA, Faigenbaum AD +5 more · J Am Nutr Assoc · 2022 · 42 citations
Yeary KHK, Johnson D, Harris N +8 more · J Acad Nutr Diet · 2025 · 3 citations
Guevara-Cruz M, Hernández-Gómez KG, Condado-Huerta C +15 more · Clin Nutr · 2024 · 35 citations
Hegedus E, Vu MH, Salvy SJ +5 more · J Acad Nutr Diet · 2024 · 19 citations
Fang Y, de Mutsert R, Gijbels A +7 more · Cardiovasc Diabetol · 2026 · 0 citations
Bahr LS, Bellmann-Strobl J, Koppold DA +12 more · BMC Nutr · 2025 · 6 citations
Bartholomew CL, Muhlestein JB, May HT +10 more · Eur Heart J Open · 2021 · 34 citations
Stable cognitive performance while adapting to intermittent fasting: A randomised controlled trial.
Bamberg C, Reichenberger J, Blechert J · J Health Psychol · 2026 · 0 citations
Teong XT, Liu K, Hutchison AT +6 more · Obes Res Clin Pract · 2020 · 10 citations
Sadeghian M, Hosseini SA, Zare Javid A +2 more · Obes Surg · 2021 · 34 citations
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