Complex physiology and clinical implications of time-restricted eating.

Time-restricted eating (TRE) is a dietary intervention that limits food consumption to a specific time window each day. The effect of TRE on body weight and physiological functions has been extensively studied in rodent models, which have shown considerable therapeutic effects of TRE and important interactions among time of eating, circadian biology, and metabolic homeostasis. In contrast, it is difficult to make firm conclusions regarding the effect of TRE in people because of the heterogeneity in results, TRE regimens, and study populations. In this review, we 1) provide a background of the history of meal consumption in people and the normal physiology of eating and fasting; 2) discuss the interaction between circadian molecular metabolism and TRE; 3) integrate the results of preclinical and clinical studies that evaluated the effects of TRE on body weight and physiological functions; 4) summarize other time-related dietary interventions that have been studied in people; and 4) identify current gaps in knowledge and provide a framework for future research directions.

Eating Around the Clock: Circadian Rhythms of Eating and Metabolism.

The time of day that we eat is increasingly recognized as contributing as importantly to overall health as the amount or quality of the food we eat. The endogenous circadian clock has evolved to promote intake at optimal times when an organism is intended to be awake and active, but electric lights and abundant food allow eating around the clock with deleterious health outcomes. In this review, we highlight literature pertaining to the effects of food timing on health, beginning with animal models and then translation into human experiments. We emphasize the pitfalls and opportunities that technological advances bring in bettering understanding of eating behaviors and their association with health and disease. There is great promise for restricting the timing of food intake both in clinical interventions and in public health campaigns for improving health via nonpharmacological therapies.

Early time-restricted carbohydrate consumption vs conventional dieting in type 2 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: Early time-restricted carbohydrate consumption (eTRC) is a novel dietary strategy that involves restricting carbohydrate-rich food intake to the morning and early afternoon to align with circadian variations in glucose tolerance. We examined the efficacy, feasibility and safety of eTRC in individuals with type 2 diabetes under free-living conditions. METHODS: In this randomised, parallel-arm, open label, controlled trial, participants with type 2 diabetes and overweight/obesity (age 67.2±7.9 years, 47.8% women, BMI 29.4±3.7 kg/m2, HbA1c 49±5 mmol/mol [6.6±0.5%]) were randomised, using computer-generated random numbers, to a 12 week eTRC diet or a Mediterranean-style control diet with matched energy restriction and macronutrient distribution (50% carbohydrate, 30% fat and 20% protein). The primary outcome was the between-group difference in HbA1c at 12 weeks. Body composition, 14 day flash glucose monitoring and food diary analysis were performed every 4 weeks. Mixed meal tolerance tests with mathematical beta cell function modelling were performed at baseline and after 12 weeks. RESULTS: Twelve (85.7%) participants in the eTRC arm and 11 (84.6%) participants in the control arm completed the study, achieving similar reductions in body weight and fat mass. The two groups experienced comparable improvements in HbA1c (-3 [-6, -0.3] mmol/mol vs -4 [-6, -2] mmol/mol, corresponding to -0.2 [-0.5, 0]% and -0.3 [-0.5, -0.1]%, respectively, p=0.386), fasting plasma glucose, flash glucose monitoring-derived glucose variability and mixed meal tolerance test-derived glucose tolerance, insulin resistance, insulin clearance and plasma glucagon levels, without changes in model-derived beta cell function parameters, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and non-esterified fatty acid levels. The two diets similarly reduced liver function markers and triglyceride levels, being neutral on other cardiometabolic and safety variables. In exploratory analyses, diet-induced changes in body weight and glucometabolic variables were not related to the timing of carbohydrate intake. CONCLUSIONS/INTERPRETATION: The proposed eTRC diet provides a feasible and effective alternative option for glucose and body weight management in individuals with type 2 diabetes, with no additional metabolic benefits compared with conventional dieting. TRIAL REGISTRATION: ClinicalTrials.gov NCT05713058 FUNDING: This study was supported by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the Italian Society of Diabetology (SID).

Time-restricted eating with or without a low-carbohydrate diet improved myocardial status and thyroid function in individuals with metabolic syndrome: secondary analysis of a randomized clinical trial.

BACKGROUND: Obesity and metabolic syndrome (MetS) have become urgent worldwide health problems, predisposing patients to unfavorable myocardial status and thyroid dysfunction. Low-carbohydrate diet (LCD) and time-restricted eating (TRE) have been confirmed to be effective methods for weight management and improving MetS, but their effects on the myocardium and thyroid are unclear. METHODS: We conducted a secondary analysis in a randomized clinical diet-induced weight-loss trial. Participants (N = 169) diagnosed with MetS were randomized to the LCD group, the 8 h TRE group, or the combination of the LCD and TRE group for 3 months. Myocardial enzymes and thyroid function were tested before and after the intervention. Pearson's or Spearman's correlation was assessed between functions of the myocardium and thyroid and cardiometabolic parameters at baseline. RESULTS: A total of 162 participants who began the trial were included in the intention-to-treat (ITT) analysis, and 57 participants who adhered to their assigned protocol were involved in the per-protocol (PP) analysis. Relative to baseline, lactate dehydrogenase, creatine kinase MB, hydroxybutyrate dehydrogenase, and free triiodothyronine (FT3) declined, and free thyroxine (FT4) increased after all 3 interventions (both analyses). Creatine kinase (CK) decreased only in the TRE (- 18 [44] U/L, P < 0.001) and combination (- 22 [64] U/L, P = 0.003) groups (PP analysis). Thyrotropin (- 0.24 [0.83] µIU/mL, P = 0.011) and T3 (- 0.10 ± 0.04 ng/mL, P = 0.011) decreased in the combination group (ITT analysis). T4 (0.82 ± 0.39 µg/dL, P = 0.046), thyroglobulin antibodies (TgAb, 2 [1] %, P = 0.021), and thyroid microsomal antibodies (TMAb, 2 [2] %, P < 0.001) increased, while the T3/T4 ratio (- 0.01 ± 0.01, P = 0.020) decreased only in the TRE group (PP analysis). However, no significant difference between groups was observed in either analysis. At baseline, CK was positively correlated with the visceral fat area. FT3 was positively associated with triglycerides and total cholesterol. FT4 was negatively related to insulin and C-peptide levels. TgAb and TMAb were negatively correlated with the waist-to-hip ratio. CONCLUSIONS: TRE with or without LCD confers remarkable metabolic benefits on myocardial status and thyroid function in subjects with MetS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475822.

The effect of time of eating on cardiometabolic risk in primary and secondary prevention of cardiovascular disease.

Continuous energy restriction is currently considered the first-line dietary therapy for weight loss in individuals with obesity. Recently, interventions which alter the eating window and time of eating occasions have been explored as means to achieve weight loss and other cardiometabolic improvements such as a reduction in blood pressure, glycaemia, lipids and inflammation. It is unknown, however, whether these changes result from unintentional energy restriction or from other mechanisms such as the alignment of nutrient intake with the internal circadian clock. Even less is known regarding the safety and efficacy of these interventions in individuals with established chronic noncommunicable disease states, such as cardiovascular disease. This review examines the effects of interventions which alter both eating window and time of eating occasions on weight and other cardiometabolic risk factors in both healthy participants and those with established cardiovascular disease. We then summarise the state of existing knowledge and explore future directions of study.

Circadian alignment of food intake and glycaemic control by time-restricted eating: A systematic review and meta-analysis.

Daily rhythms of metabolic function are supported by molecular circadian clock systems that are strongly regulated by feeding and fasting. Intermittent fasting diets have been associated with weight loss and improved metabolism. However, the effects of time-restricted eating (TRE) on glycemic parameters are still under debate. In this review, we aim to systematically analyze the effects of TRE on glycemic parameters. We searched on PubMed, EMBASE, and the Cochrane Library for controlled studies in which subjects followed TRE for at least 4 weeks. 20 studies were included in the qualitative systematic review, and 18 studies (n = 1169 subjects) were included in the meta-analysis. Overall, TRE had no significant effect on fasting glucose (Hedges's g = -0.08; 95% CI:-0.31,0.16; p = 0.52), but it did reduce HbA1c levels (Hedges's g = -0.27; 95% CI: -0.47, -0.06; p = 0.01). TRE significantly reduced fasting insulin (Hedges's g = -0.40; 95% CI: -0.73,-0.08; p = 0.01) and showed a tendency to decrease HOMA-IR (Hedges's g = -0.32; 95% CI:-0.66,0.02; p = 0.06). Interestingly, a cumulative analysis showed that the beneficial effects of TRE regarding glucose levels were less apparent as studies with later TRE windows (lTRE) were being included. Indeed, a subgroup analysis of the early TRE (eTRE) studies revealed that fasting glucose was significantly reduced by eTRE (Hedges's g = -0.38; 95% CI:-0.62, -0.14; p < 0.01). Our meta-analysis suggests that TRE can reduce HbA1c and insulin levels, and that timing of food intake is a crucial factor in the metabolic benefit of TRE, as only eTRE is capable of reducing fasting glucose levels in subjects with overweight or obesity.PROSPERO registration number CRD42023405946.

Length of Overnight Fasting and 6-year Weight Change in the Cancer Prevention Study-3.

BACKGROUND: Longer overnight fasting (ONF) is a potential strategy for weight control. Although promising, the evidence from large population-based studies is limited. OBJECTIVES: To examine the association of self-reported ONF duration with 3- and 6-y weight change in the American Cancer Society's Cancer Prevention Study-3 prospective cohort. METHODS: United States adult Cancer Prevention Study-3 participants completed a 24-h validated meal and snack timing and frequency grid (weekday and weekend) in 2015, from which weighted ONF hours were calculated. Participants reported body weight in 2015, 2018, and 2021. Three- and 6-y weight change (kg, and % body weight) were assessed. RESULTS: Among 104,420 mostly female (78.5%) participants aged 52.7 ± 9.5 (standard deviation) y followed for 6 y, a 1-h increase in ONF length was associated with a small but statistically significant reduction in weight gain over 3- and 6-y periods [multivariable-adjusted mean difference in % body weight = -0.02, 95% confidence interval (CI): -0.05, -0.00, P = 0.03 and -0.04, 95% CI: -0.07, -0.01, P < 0.01, respectively]. The mean difference of 6-y % reduction in weight gain was slightly greater among individuals with overweight (-0.05, 95% CI: -0.10, 0.00, P = 0.05) and obesity (-0.06, 95% CI: -0.12, 0.01, P = 0.08) compared with those with healthy body mass index (-0.03, 95% CI:-0.07, 0.01, P = 0.13) or underweight (0.16, 95% CI: -0.04, 0.36, P = 0.13, Pinteraction < 0.0001). Stronger associations were observed among those ≤55 y than 56+ (P < 0.001), and those with higher waist circumference (Pinteraction < 0.0001) but not by sex or earlier/later fasting period. CONCLUSIONS: Longer ONF was associated with slightly lower body weight in adult males and females over 6 y that was stronger among those with overweight or obesity, higher waist circumference, and those aged ≤55 y. The magnitude of weight change, although in the hypothesized direction, suggests that prolonged ONF may have modest impact on weight control over time.

Counting hours or calories? Metabolic regulatory role of time-restricted eating in adults with overweight and obesity: a systematic review and meta-analysis.

Time-restricted eating (TRE) effectively improves healthspan, including controlling obesity and improving metabolic health. To date, few meta-analyses have been conducted to explore the effects of various protocols of TRE in participants with overweight/obesity. PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched up until October 15, 2022. Randomized and non-randomized clinical trials that investigated the effect of TRE on body weight, body composition and cardiometabolic parameters in participants with overweight/obesity were included. Mean differences of changes from the baseline were used for all analyses between the two groups. Prespecified subgroup analyses based on different protocols of TRE were performed. Twenty-three studies were included in the meta-analysis with 1867 participants. TRE interventions led to significant changes in body weight. When energy restriction strategies were conducted in both the TRE and control groups, the weight-loss effect of TRE remained significant. TRE with 4 ∼ 8h feeding window, morning or late eating strategies, led to reduction in body weight and fat mass for at least 8 wk. Hence TRE is a potential and effective approach for weight loss for participants with overweight/obesity. An 8h-TRE intervention with a morning eating strategy for at least eight weeks might be the optimum TRE intervention mode.

The influence of time-restricted eating/feeding on Alzheimer's biomarkers and gut microbiota.

OBJECTIVES: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting approximately 55 million individuals globally. Diagnosis typically occurs in advanced stages, and there are limited options for reversing symptoms. Preventive strategies are, therefore, crucial. Time Restricted Eating (TRE) or Time Restricted Feeding (TRF) is one such strategy. Here we review recent research on AD and TRE/TRF in addition to AD biomarkers and gut microbiota. METHODS: A comprehensive review of recent studies was conducted to assess the impact of TRE/TRF on AD-related outcomes. This includes the analysis of how TRE/TRF influences circadian rhythms, beta-amyloid 42 (Aß42), pro-inflammatory cytokines levels, and gut microbiota composition. RESULTS: TRE/TRF impacts circadian rhythms and can influence cognitive performance as observed in AD. It lowers beta-amyloid 42 deposition in the brain, a key AD biomarker, and reduces pro-ininflammatory cytokines. The gut microbiome has emerged as a modifiable factor in AD treatment. TRE/TRF changes the structure and composition of the gut microbiota, leading to increased diversity and a decrease in harmful bacteria. DISCUSSION: These findings underscore the potential of TRE/TRF as a preventive strategy for AD. By reducing Aß42 plaques, modulating pro-inflammatory cytokines, and altering gut microbiota composition, TRE/TRF may slow the progression of AD. Further research is needed to confirm these effects and to understand the mechanisms involved. This review highlights TRE/TRF as a promising non-pharmacological intervention in the fight against AD.

The association between time-restricted eating and arterial stiffness status in community-dwelling elderly Chinese individuals.

BACKGROUND AND AIMS: Emerging studies indicate that time-restricted eating (TRE) may protect against cardiovascular disease (CVD); however, studies performed in elderly adults are limited. This study aimed to analyze the association of TRE with arterial stiffness (AS) in community-dwelling elderly Chinese individuals. METHODS AND RESULTS: This cross-sectional study recruited 3487 participants aged ≥60 y from Shanghai, China. TRE was determined by calculating the end time of the last meal minus the start time of the first meal of the average day. Participants were then categorized into those with a time-restricted window lasting ≤11 h (TRE) and >11 h (non-TRE). The mean age of the sample was 71.78 ± 5.75 y, and 41.2 % were men. Having a TRE pattern was 72.2 %. In the logistic analysis, TRE was associated with borderline arterial stiffness (OR = 1.419; 95 % CI = 1.077-1.869) and elevated arterial stiffness (OR = 1.699; 95 % CI = 1.276-2.263). In a subgroup analysis, the significance remained in the group at risk of malnutrition (with borderline arterial stiffness: OR = 2.270; 95 % CI = 1.229-4.190; with elevated arterial stiffness: OR = 2.459; 95 % CI = 1.287-4.700), while in well-nourished participants, the association only remained with elevated arterial stiffness (OR = 1.530; 95 % CI = 1.107-2.115) and not with borderline arterial stiffness. CONCLUSIONS: TRE is a risk factor for both borderline and elevated arterial stiffness in community-dwelling Chinese individuals and varies by nutritional status. (Protocol code 2019-WJWXM-04-310108196508064467.).

The effect of observing religious or faith-based fasting on cardiovascular disease risk factors: A systematic review and meta-analysis.

AIMS: Cardiovascular diseases (CVD) are the leading cause of death worldwide. Fasting is common in many religions and is associated with health benefits. This systematic review to compares the impact of different religious fasting practices, on risk of cardiometabolic diseases. DATA SYNTHESIS: The search covered five databases following PRISMA guidelines to identify papers published in English from inception to March 2023 (updated January 2024). Inclusion criteria were healthy adults in observational studies, who engaged in religious fasting practices, studies were included where data on matched non-fasting individuals was available. Outcomes were systolic and diastolic blood pressure, body mass index (BMI), triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and fasting plasma glucose levels. A meta-analysis was conducted, and the review was registered (CRD42022352197). Fourteen studies were met the inclusion criteria with ten studies data being suitable for meta-analysis, reporting on 755 adults participating in fasting practices and 661 non-fasting controls. Religious fasting was associated with a reduction in BMI (-0.40 kg/m2, 95% CI [-0.70, -0.10], p < 0.01). Observance of Ramadan fasting was associated with decreased systolic blood pressure (-3.83  mmHg, 95% CI [-7.44, -0.23], p = 0.04). The observance of Orthodox Christian fasting was associated with a reduction in TC (-0.52 mmoL/l, 95%CI [-0.64, -0.39], p < 0.01). No difference was found for the other outcomes. CONCLUSION: This review found religious fasting practices which were associated with a reduction in some biomarkers of cardiometabolic diseases risk. Further research on other fasting practices is needed due to limited data.

A randomized controlled trial to compare the effects of time-restricted eating versus Mediterranean diet on symptoms and quality of life in bipolar disorder.

BACKGROUND: The primary objective of this randomized controlled trial (RCT) is to establish the effectiveness of time-restricted eating (TRE) compared with the Mediterranean diet for people with bipolar disorder (BD) who have symptoms of sleep disorders or circadian rhythm sleep-wake disruption. This work builds on the growing evidence that TRE has benefits for improving circadian rhythms. TRE and Mediterranean diet guidance will be offered remotely using self-help materials and an app, with coaching support. METHODS: This study is an international RCT to compare the effectiveness of TRE and the Mediterranean diet. Three hundred participants will be recruited primarily via social media. Main inclusion criteria are: receiving treatment for a diagnosis of BD I or II (confirmed via DIAMOND structured diagnostic interview), endorsement of sleep or circadian problems, self-reported eating window of ≥ 12 h, and no current mood episode, acute suicidality, eating disorder, psychosis, alcohol or substance use disorder, or other health conditions that would interfere with or limit the safety of following the dietary guidance. Participants will be asked to complete baseline daily food logging for two weeks and then will be randomly allocated to follow TRE or the Mediterranean diet for 8 weeks, during which time, they will continue to complete daily food logging. Intervention content will be delivered via an app. Symptom severity interviews will be conducted at baseline; mid-intervention (4 weeks after the intervention begins); end of intervention; and at 6, 9, and 15 months post-baseline by phone or videoconference. Self-rated symptom severity and quality of life data will be gathered at those timepoints, as well as at 16 weeks post baseline. To provide a more refined index of whether TRE successfully decreases emotional lability and improves sleep, participants will be asked to complete a sleep diary (core CSD) each morning and complete six mood assessments per day for eight days at baseline and again at mid-intervention. DISCUSSION: The planned research will provide novel and important information on whether TRE is more beneficial than the Mediterranean diet for reducing mood symptoms and improving quality of life in individuals with BD who also experience sleep or circadian problems. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06188754.

Effects of DASH diet with or without time-restricted eating in the management of stage 1 primary hypertension: a randomized controlled trial.

BACKGROUND: Time-restricted eating (TRE), a popular form of intermittent fasting, has shown benefits for improving metabolic diseases and cardiometabolic health. However, the effect of TRE in the regulation of blood pressure in primary hypertension remains unclear. METHODS: A 6-week randomized controlled trial was conducted, in which a total of 74 stage 1 primary hypertensive patients without high-risk were randomly assigned to Dietary Approaches to Stop Hypertension (DASH) group (n = 37) or DASH + TRE group (n = 37). Participants in the DASH + TRE group were instructed to consume their food within an 8-h window. Scientific research platform in We Chat application was used to track participants. The primary outcome was blood pressure. The secondary outcomes included body composition, cardiometabolic risk factors, inflammation-related parameters, urinary Na+ excretion, other clinical variables and safety outcomes. RESULTS: The reduction of systolic blood pressure and diastolic blood pressure were 5.595 ± 4.072 and 5.351 ± 5.643 mm Hg in the DASH group and 8.459 ± 4.260 and 9.459 ± 4.375 mm Hg in the DASH + TRE group. DASH + TRE group improved blood pressure diurnal rhythm. Subjects in DASH + TRE group had decreased extracellular water and increased urinary Na+ excretion. Furthermore, the decrease in blood pressure was associated with a reduction of extracellular water or increase in urinary Na+ excretion. In addition, safety outcomes such as nighttime hunger were also reported. CONCLUSION: Our study demonstrated that 8-h TRE + DASH diet caused a greater decrease in blood pressure in stage 1 primary hypertensive patients than DASH diet. This study may provide novel insights into the benefits of lifestyle modification in the treatment of primary hypertension. TRIAL REGISTRATION: https://www.chictr.org.cn/ (ChiCTR2300069393, registered on March 15, 2023).

Discontinuing semaglutide after weight loss: strategy for weight maintenance and a possible new side effect.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) facilitate weight loss. Weight regain off therapy is concerning. We reported the case of a 35-year-old male prescribed oral semaglutide with 22.7 kg weight loss over 120 days. Herein, we describe the clinical course when discontinuing GLP-1 RA therapy, one approach to maintaining weight loss after discontinuation, and a possible new side effect. At day 120, we continued oral semaglutide 7 mg daily, down from 14 mg, for weight maintenance with subsequent weight regain. We re-increased semaglutide to 14 mg/day with weight re-loss within 1 month and weight maintance for a year. We then discontinued semaglutide; weight loss was maintained for 6 months. The patient reported lactose intolerance ∼13 months before starting semaglutide. During semaglutide therapy, the patient reported worsened lactose intolerance and new gluten intolerance. Food allergy/celiac testing were negative. Intolerances did not improve with semaglutide discontinuation. Six months after semaglutide discontinuation, the patient was diagnosed with small intestinal bacterial overgrowth, possibly worsened by semaglutide. Factors potentially supporting weight maintenance were early drug treatment for new-onset obesity, non-geriatric age, strength training, and diet modification. The case highlights tailoring approaches to maintain weight loss without GLP-1 RAs. Trials are needed to optimize weight maintenance strategies.

Mitochondrial epigenetic modifications and nuclear-mitochondrial communication: A new dimension towards understanding and attenuating the pathogenesis in women with PCOS.

Mitochondrial DNA (mtDNA) epigenetic modifications have recently gained attention in a plethora of complex diseases, including polycystic ovary syndrome (PCOS), a common cause of infertility in women of reproductive age. Herein we discussed mtDNA epigenetic modifications and their impact on nuclear-mitochondrial interactions in general and the latest advances indicating the role of mtDNA methylation in the pathophysiology of PCOS. We highlighted epigenetic changes in nuclear-related mitochondrial genes, including nuclear transcription factors that regulate mitochondrial function and may be involved in the development of PCOS or its related traits. Additionally, therapies targeting mitochondrial epigenetics, including time-restricted eating (TRE), which has been shown to have beneficial effects by improving mitochondrial function and may be mediated by epigenetic modifications, have also been discussed. As PCOS has become a major metabolic disorder and a risk factor for obesity, cardiometabolic disorders, and diabetes, lifestyle/behavior intervention using TRE that reinforces feeding-fasting rhythms without reducing caloric intake may be a promising therapeutic strategy for attenuating the pathogenesis. Furthermore, future perspectives in the area of mitochondrial epigenetics are described.

Missing puzzle pieces of time-restricted-eating (TRE) as a long-term weight-loss strategy in overweight and obese people? A systematic review and meta-analysis of randomized controlled trials.

The efficacy of using time restricted eating (TRE) for weight management and to mitigate metabolic disorders in overweight and obese people remains debatable. This meta-analysis quantified the impact of TRE on weight loss and metabolic health in overweight and obese people. The pooled results were subjected to a random-effects modeling using Hartung-Knapp-Sidik-Jonkman (HKSJ) method. Additionally, subgroup analysis was conducted based on study types, randomized controlled trials (RCTs) vs. non-randomized studies of interventions (NRSIs). Pooled results showed that subjects on TRE regimen (> 4 weeks) achieved a significant weight loss in comparison with unrestricted time regimen (weighted mean difference: -2.32%; 95% CI: -3.50, -1.14%; p < 0.01); however, weight loss was mainly attributed to the loss of lean mass rather than fat mass. The magnitude of weight loss was inversely correlated with daily fasting duration in RCTs. TRE significantly decreased the diastolic blood pressure and fasting insulin. An increase of low-density lipoprotein cholesterol (LDL-C) was observed in the TRE group. Favorable effect of TRE was observed on glucose metabolism but not on lipid profiles independent of weight loss. Hence TRE shall be administered with caution to overweight and obese people who have comorbidities such as dyslipidemia and sarcopenia.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1974335.

Does intermittent fasting impact mental disorders? A systematic review with meta-analysis.

Accumulating evidence supports the benefits of intermittent fasting (IF) as a dietary strategy for cardiometabolic health and weight control. However, little is known about the potential implications of IF on mental disorders. The aim of this review was to synthesize evidence regarding the effects of IF on mental disorders (depression, anxiety, and mood state) in the general population. We conducted a systematic search in five databases from inception to January 2022. Randomized and nonrandomized clinical trials (RCTs/nonRCTs) were included. A random effects method was used to pool standardized mean differences (SMDs) and 95% CIs. A total of 14 studies involving 562 individuals were included, of which 8 were RCTs and 6 were nonRCTs. IF showed a moderate and positive effect on depression scores when compared to control groups (SMD: 0.41; 95%CI: 0.05 to 0.76; I2=45%; n = 4). Conversely, within-group analyses did not show any significant effect of IF on anxiety (SMD: 0.10; 95%CI: -0.09 to 0.30; I2=0%; n = 5) or mood state (SMD: 0.14; 95%CI: -0.09 to 0.37; I2=59%; n = 7). IF modalities did not negatively impact mental disorders in the general population. In fact, IF showed a positive influence on diminishing depression scores, and did not modify anxiety or mood.

Rationale and design of IMPACT-women: a randomised controlled trial of the effect of time-restricted eating, healthy eating and reduced sedentary behaviour on metabolic health during chemotherapy for early-stage breast cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

Intermittent fasting and bone health: a bone of contention?

Intermittent fasting (IF) is a promising strategy for weight loss and improving metabolic health, but its effects on bone health are less clear. This review aims to summarise and critically evaluate the preclinical and clinical evidence on IF regimens (the 5:2 diet, alternate-day fasting (ADF) and time-restricted eating (TRE)/time-restricted feeding and bone health outcomes. Animal studies have utilised IF alongside other dietary practices known to elicit detrimental effects on bone health and/or in models mimicking specific conditions; thus, findings from these studies are difficult to apply to humans. While limited in scope, observational studies suggest a link between some IF practices (e.g. breakfast omission) and compromised bone health, although lack of control for confounding factors makes these data difficult to interpret. Interventional studies suggest that TRE regimens practised up to 6 months do not adversely affect bone outcomes and may even slightly protect against bone loss during modest weight loss (< 5 % of baseline body weight). Most studies on ADF have shown no adverse effects on bone outcomes, while no studies on the '5­2' diet have reported bone outcomes. Available interventional studies are limited by their short duration, small and diverse population samples, assessment of total body bone mass exclusively (by dual-energy X-ray absorptiometry) and inadequate control of factors that may affect bone outcomes, making the interpretation of existing data challenging. Further research is required to better characterise bone responses to various IF approaches using well-controlled protocols of sufficient duration, adequately powered to assess changes in bone outcomes and designed to include clinically relevant bone assessments.

Association between time-restricted eating and non-alcoholic fatty liver disease in a nationwide cross-sectional study.

The association between time-restricted eating (TRE) and the risk of non-alcoholic fatty liver disease (NAFLD) is less studied. Moreover, whether the association is independent of physical exercise or diet quality or quantity is uncertain. In this nationwide cross-sectional study of 3813 participants, the timing of food intakes was recorded by 24-h recalls; NAFLD was defined through vibration-controlled transient elastography in the absence of other causes of chronic liver disease. OR and 95 % CI were estimated using logistic regression. Participants with daily eating window of ≤ 8 h had lower odds of NAFLD (OR = 0·70, 95 % CI: 0·52, 0·93), compared with those with ≥ 10 h window. Early (05.00-15.00) and late TRE (11.00-21.00) showed inverse associations with NAFLD prevalence without statistical heterogeneity (Pheterogeneity = 0·649) with OR of 0·73 (95 % CI: 0·36, 1·47) and 0·61 (95 % CI: 0·44, 0·84), respectively. Such inverse association seemed stronger in participants with lower energy intake (OR = 0·58, 95 % CI: 0·38, 0·89, Pinteraction = 0·020). There are no statistical differences in the TRE-NAFLD associations according to physical activity (Pinteraction = 0·390) or diet quality (Pinteraction = 0·110). TRE might be associated with lower likelihood of NAFLD. Such inverse association is independent of physical activity and diet quality and appears stronger in individuals consuming lower energy. Given the potential misclassification of TRE based on one- or two-day recall in the analysis, epidemiological studies with validated methods for measuring the habitual timing of dietary intake are warranted.