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.

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 ‘5–2’ 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.

Fat deposition and lipid metabolism are closely related to the morphology, structure and function of mitochondria. The morphology of mitochondria between fusion and fission processes is mainly regulated by protein posttranslational modification. Intermittent fasting (IF) promotes high expression of Sirtuin 3 (Sirt3) and induces mitochondrial fusion in high-fat diet (HFD)-fed mice. However, the mechanism by which Sirt3 participates in mitochondrial protein acetylation during IF to regulate mitochondrial fusion and fission dynamics remains unclear. This article demonstrates that IF promotes mitochondrial fusion and improves mitochondrial function in HFD mouse inguinal white adipose tissue. Proteomic sequencing revealed that IF increased protein deacetylation levels in HFD mice and significantly increased Sirt3 mRNA and protein expression. After transfecting with Sirt3 overexpression or interference vectors into adipocytes, we found that Sirt3 promoted adipocyte mitochondrial fusion and improved mitochondrial function. Furthermore, Sirt3 regulates the JNK-FIS1 pathway by deacetylating malate dehydrogenase 2 (MDH2) to promote mitochondrial fusion. In summary, our study indicates that IF promotes mitochondrial fusion and improves mitochondrial function by upregulating the high expression of Sirt3 in HFD mice, promoting deacetylation of MDH2 and inhibiting the JNK-FIS1 pathway. This research provides theoretical support for studies related to energy limitation and animal lipid metabolism.

This exploratory study investigated the effects of early v. delayed time-restricted eating (TRE) plus caloric restriction (CR) on body weight, body composition and cardiometabolic parameters in adults with overweight and obesity. Adults (20–40 years) were randomised to one of three groups for 8 weeks: early time-restricted eating (eTRE; 08.00–16.00) plus CR, delayed time-restricted eating (dTRE; 12.00–20.00) plus CR or only CR (CR; 08.00–20.00). All groups were prescribed a 25 % energy deficit relative to daily energy requirements. Thirteen participants completed the study in the eTRE and CR groups and eleven in the dTRE group (n 37). After the interventions, there was no significant difference between the three groups for any of the outcomes. Compared with baseline, significant decreases were observed in the body weight (eTRE group: −4·2 kg; 95 % CI, −5·6, −2·7; dTRE group: −4·8 kg; 95 % CI, −5·9, −3·7; CR: −4·0 kg; 95 % CI, −5·9, −2·1), fat mass (eTRE group: −2·9 kg; 95 % CI, −3·9, −1·9; dTRE group: −3·6 kg; 95 % CI, −4·6, −2·5; CR: −3·1 kg; 95 % CI, −4·3, −1·8) and fasting glucose levels (eTRE group: −4 mg/dl; 95 % CI, −8, −1; dTRE group: −2 mg/dl; 95 % CI, −8, 3; CR: −3 mg/dl; 95 % CI, −8, 2). In a free-living setting, TRE with a energetic deficit, regardless of the time of day, promotes similar benefits in weight loss, body composition and cardiometabolic parameters. However, given the exploratory nature of our study, further investigation is needed to confirm these findings.

Eating architecture is a term that describes meal frequency, meal timing and meal size and the daily variation in each of these. The aim of this study was to determine the relationship between components of eating architecture on body fat and markers of glycaemic control in healthy adults at increased risk of type 2 diabetes (T2DM). Participants (n 73, 39 males, age 58·8 (8·1) years, BMI 33·4 (4·4) kg/m2) recorded food intake and wore accelerometers and continuous glucose monitors (CGM) for 7–14 d under free-living conditions. Body fat and glycated Hb (HbA1c) were also measured. The mean and day-to-day variation (calculated as the standard deviation during the monitoring period) of each component of eating architecture were calculated. Multivariable linear regression models were constructed for three separate outcome variables (body fat mass, mean CGM glucose and HbA1c) for each component of eating architecture before and after adjustment for confounders. Higher variability in the time of first meal consumption was associated with increased body fat mass after adjusting for confounders (β = 0·227, 95 % CI: 0·019, 0·434, P = 0·033). Increased variability in the time lag from waking to first meal consumption was also positively associated with increased HbA1c after adjustment (β = 0·285, 95 % CI: 0·040, 0·530, P = 0·023). Low day-to-day variability in first meal consumption was associated with lower body fat and improved glucose control in adults at increased risk of T2DM. Routine consumption of meals may optimise temporal regulation to anticipate and respond appropriately to a glucose challenge.

Menopausal women are susceptible to osteoarthritis(OA) and memory impairment. We hypothesised that Alzheimer’s-like disease(AD) exacerbates OA and that intermittent fasting(IMF) with a high-protein(H-P) diet would enhance memory function and relieve OA symptoms in oestrogen-deficient animals induced AD and OA. The action mechanism was also explored. Ovariectomised Sprague–Dawley rats were fed high-fat(H-F) or H-P diets for 2 weeks, and then they had a hippocampal infusion of β-amyloid(25–35) for 4 weeks to induce AD and an injection of monoidoacetate(MIA) into the articular cartilage to induce OA. Non-AD groups had non-AD symptoms by hippocampal amyloid-β(35–25) infusion. IMF suppressed memory impairment in AD rats, especially those fed H-P diets. Compared with non-AD, AD exacerbated OA symptoms, including swelling, limping, slowed treadmill running speed, and uneven weight distribution in the left leg. The exacerbations were linked to increased inflammation and pain, but IMF and H-P lessened the exacerbation. Lean body mass(LBM) decreased with AD, but H-P protected against LBM loss. Histological examination of the knee joint revealed the degree of the cellular invasion into the middle zone, and the changes in the tidemark plateau were greatest in the AD-AL with H-F, while non-AD-IMF improved the cellular invasion to as much as non-AD-AL. H-P reduced the infiltration into the middle zone of the knee and promoted collagen production. In conclusion, AD exacerbated the articular cartilage deterioration and memory impairment, and IMF with H-P alleviated the memory impairment and osteoarthritic symptoms by decreasing hippocampal amyloid-β deposition and proinflammatory cytokine expressions and by increasing LBM.

It is unknown if time-restricted feeding confers a protective effect on the physical function of older adults. The aim of this study was to assess prolonged nightly fasting in association with performance-based lower-extremity function (LEF) in a large population of community-dwelling older adults. A cross-sectional study was carried out among 1226 individuals ≥64 years from the Seniors-ENRICA-II (Study on Nutrition and Cardiovascular Risk in Spain) cohort. Habitual diet was assessed through a validated diet history. Fasting time was classified into the following categories: ≤9, 10–11 and ≥12 h/d (prolonged nightly fasting). Performance-based LEF was assessed with the Short Physical Performance Battery (SPPB). After adjusting for potential confounders, a longer fasting period was associated with a higher likelihood of impaired LEF (OR for the second and third categories v. ≤ 9 h/d fasting: 2·27 (95 % CI 1·56, 3·33) and 2·70 (95 % CI 1·80, 4·04), respectively; P trend < 0·001). Fasting time showed a significant association with the SPPB subtests balance impairment (OR for highest v. shortest fasting time: 2.48; 95 % CI 1·51, 4·08; P trend = 0·001) and difficulty to rise from a chair (OR 1·47; 95 % CI 1·05, 2·06; P trend = 0·01). The risk associated with ≥12 h fasting among those with the lowest levels of physical activity was three times higher than among those with ≤9 h fasting with the same low level of physical activity. Prolonged nightly fasting was associated with a higher likelihood of impaired LEF, balance impairment, and difficulty to rise from a chair in older adults, especially among those with low levels of physical activity.

Intermittent food restriction (IFR) is used mainly for weight loss; however, its effects on adipose tissue are not known when alternating with an obesogenic diet. To demonstrate its effects on morphological dynamics of fat deposits, female Wistar rats were distributed into groups: standard control (ST-C), with commercial diet; DIO control (DIO-C), with a diet that induces obesity (DIO) during the first and last 15 d, replaced by a standard diet for thirty intermediate days; standard restricted (ST-R), with standard diet during the first and last 15 d, with six cycles of IFR at 50 % of ST-C; and DIO restricted (DIO-R), in DIO during the first and last 15 d, with six cycles of IFR at 50 % of DIO-C. At 105 d of life, white adipose tissue (WAT) and brown adipose tissue (BAT) deposits were collected, weighed and histology performed. The DIO-R group showed higher total food intake (DIO-R 10 768·0 (SEM 357·52) kJ/g v. DIO-C 8868·6 (SEM 249·25) kJ/g, P < 0·0001), energy efficiency during RAI (DIO-R 2·26 (SEM 0·05) g/kJ v. DIO-C 0·70 (SEM 0·03) g/kJ, P < 0·0001) and WAT (DIO-R 5·65 (SEM 0·30) g/100 g v. DIO-C 4·56 (SEM 0·30) g/100 g) than their respective control. Furthermore, IFR groups presented hypertrophy of WAT and BAT, as well as fibrosis in BAT. Thus, IFR can establish prospective resistance to weight loss by favouring changes in adipose tissue morphology, increased energy intake and efficiency. Finally, the DIO diet before and after IFR aggravates the damages caused by the restriction.

Time-restricted feeding (TRF) confers protection against nutritional challenges that predispose obesity and metabolic risks through involvement of circadian locomotor output cycles protein kaput genes and gut microbiome, but the underlying mechanism is not clearly understood. Therefore, the present study examined the effects of TRF on metabolic markers and circadian rhythm associated with gut microbiota in healthy males. Two groups (TRF, n 56; non-TRF, n 24) of male adults were enrolled. The TRF group provided blood at pre-TRF and post-TRF, while non-TRF one time after 25 d of trial. Serum lipid and liver profiles were determined. Real time-PCR was applied for circadian and inflammatory gene expression. The 16S rRNA genes were sequenced on the Illumina Miseq v3 platform to comprehensively catalogue the composition and abundance of bacteria in stool. We showed that TRF ameliorated the serum lipid and liver profiles of the individuals. In the TRF group, gut microbial richness was significantly enhanced, with enrichment of Prevotellaceae and Bacteroideaceae. TRF enhanced circadian gene expression probably by activation of sirtuin-1, which is positively associated with gut microbiome richness. TRF could be a safe remedy for the prevention of metabolic diseases related to dyslipidaemia, as it regulates circadian rhythm associated with gut microbiome modulation.

Studies on the impact of Ramadan diurnal intermittent fasting (RDIF) on the metabolic syndrome (MetS) components among healthy Muslims observing Ramadan month have yielded contradictory results. This comprehensive meta-analysis aimed to obtain a more stable estimate of the effect size of fasting during Ramadan on the MetS components, examine variability among studies, assess the generalisability of reported results and perform subgroup analyses for associated factors. We searched the CINAHL, Cochrane, EBSCOhost, Google Scholar, ProQuest Medical, PubMed/MEDLINE, ScienceDirect, Scopus and Web of Science databases for relevant studies published from 1950 to March 2019. The MetS components analysed were: waist circumference (WC), systolic blood pressure (SBP), fasting plasma/serum glucose (FG), TAG, and HDL-cholesterol. We identified eighty-five studies (4326 participants in total) that were conducted in twenty-three countries between 1982 and 2019. RDIF-induced effect sizes for the MetS components were: small reductions in WC (no. of studies K = 24, N 1557, Hedges’ g = −0·312, 95 % CI −0·387, −0·236), SBP (K = 22, N 1172, Hedges’ g = −0·239, 95 % CI −0·372, −0·106), FG (K = 51, N 2318, Hedges’ g = −0·101, 95 % CI −0·260, 0·004) and TAG (K = 63, N 2862, Hedges’ g = −0·088, 95 % CI −0·171, −0·004) and a small increase in HDL-cholesterol (K = 57, N 2771, Hedges’ g = 0·150, 95 % CI 0·064, 0·236). We concluded that among healthy people, RDIF shows small improvement in the five MetS components: WC, SBP, TAG, FG and HDL.

Intermittent energy restriction (IER) involves short periods of severe energy restriction interspersed with periods of adequate energy intake, and can induce weight loss. Insulin sensitivity is impaired by short-term, complete energy restriction, but the effects of IER are not well known. In randomised order, fourteen lean men (age: 25 (sd 4) years; BMI: 24 (sd 2) kg/m2; body fat: 17 (4) %) consumed 24-h diets providing 100 % (10 441 (sd 812) kJ; energy balance (EB)) or 25 % (2622 (sd 204) kJ; energy restriction (ER)) of estimated energy requirements, followed by an oral glucose tolerance test (OGTT; 75 g of glucose drink) after fasting overnight. Plasma/serum glucose, insulin, NEFA, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and fibroblast growth factor 21 (FGF21) were assessed before and after (0 h) each 24-h dietary intervention, and throughout the 2-h OGTT. Homoeostatic model assessment of insulin resistance (HOMA2-IR) assessed the fasted response and incremental AUC (iAUC) or total AUC (tAUC) were calculated during the OGTT. At 0 h, HOMA2-IR was 23 % lower after ER compared with EB (P<0·05). During the OGTT, serum glucose iAUC (P<0·001), serum insulin iAUC (P<0·05) and plasma NEFA tAUC (P<0·01) were greater during ER, but GLP-1 (P=0·161), GIP (P=0·473) and FGF21 (P=0·497) tAUC were similar between trials. These results demonstrate that severe energy restriction acutely impairs postprandial glycaemic control in lean men, despite reducing HOMA2-IR. Chronic intervention studies are required to elucidate the long-term effects of IER on indices of insulin sensitivity, particularly in the absence of weight loss.

This pilot study explored the feasibility of a moderate time-restricted feeding (TRF) intervention and its effects on adiposity and metabolism. For 10 weeks, a free-living TRF group delayed breakfast and advanced dinner by 1·5 h each. Changes in dietary intake, adiposity and fasting biochemistry (glucose, insulin, lipids) were compared with controls who maintained habitual feeding patterns. Thirteen participants (29 (sem 2) kg/m2) completed the study. The average daily feeding interval was successfully reduced in the TRF group (743 (sem 32) to 517 (sem 22) min/d; P < 0·001; n 7), although questionnaire responses indicated that social eating/drinking opportunities were negatively impacted. TRF participants reduced total daily energy intake (P = 0·019) despite ad libitum food access, with accompanying reductions in adiposity (P = 0·047). There were significant between-group differences in fasting glucose (P = 0·008), albeit driven primarily by an increase among controls. Larger studies can now be designed/powered, based on these novel preliminary qualitative and quantitative data, to ascertain and maximise the long-term sustainability of TRF.

This study was a randomised, double-blind, placebo-controlled cross-over trial examining the effects of β-hydroxy β-methylbutyrate free acid (HMB-FA) supplementation on muscle protein breakdown, cortisol, testosterone and resting energy expenditure (REE) during acute fasting. Conditions consisted of supplementation with 3 g/d HMB-FA or placebo during a 3-d meat-free diet followed by a 24-h fast. Urine was collected before and during the 24-h fast for analysis of 3-methylhistidine:creatinine ratio (3MH:CR). Salivary cortisol, testosterone, their ratio (T:C), and the cortisol awakening response were assessed. ANOVA was used to analyse all dependent variables, and linear mixed models were used to confirm the absence of carryover effects. Eleven participants (six females, five males) completed the study. Urinary HMB concentrations confirmed compliance with supplementation. 3MH:CR was unaffected by fasting and supplementation, but the cortisol awakening response differed between conditions. In both conditions, cortisol increased from awakening to 30 min post-awakening (P=0·01). Cortisol was reduced from 30 to 45 min post-awakening with HMB-FA (−32 %, d=−1·0, P=0·04), but not placebo (PL) (−6 %, d=−0·2, P=0·14). In males, T:C increased from 0 to 24 h of fasting with HMB-FA (+162 %, d=3·0, P=0·001), but not placebo (+13 %, d=0·4, P=0·60), due to reductions in cortisol. REE was higher at 24 h of fasting than 16 h of fasting independent of supplementation (+4·0 %, d=0·3, P=0·04). In conclusion, HMB-FA may affect cortisol responses, but not myofibrillar proteolysis, during acute 24-h fasting.

The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (>70 %) energy restriction (ER) interspersed with normal eating. Studies to date comparing IER to continuous energy restriction (CER) have predominantly measured fasting indices of cardiometabolic risk. This study aimed to compare the effects of IER and CER on postprandial glucose and lipid metabolism following matched weight loss. In all, twenty-seven (thirteen male) overweight/obese participants (46 (sem 3) years, 30·1 (sem 1·0) kg/m2) who were randomised to either an IER intervention (2638 kJ for 2 d/week with an overall ER of 22 (sem 0·3) %, n 15) or a CER intervention (2510 kJ below requirements with overall ER of 23 (sem 0·8) %) completed the study. Postprandial responses to a test meal (over 360 min) and changes in anthropometry (fat mass, fat-free mass, circumferences) were assessed at baseline and upon attainment of 5 % weight loss, following a 7-d period of weight stabilisation. The study found no statistically significant difference in the time to attain a 5 % weight loss between groups (median 59 d (interquartile range (IQR) 41–80) and 73 d (IQR 48–128), respectively, P=0·246), or in body composition (P≥0·437). For postprandial measures, neither diet significantly altered glycaemia (P=0·266), whereas insulinaemia was reduced comparatively (P=0·903). The reduction in C-peptide tended (P=0·057) to be greater following IER (309 128 (sem23 268) to 247781 (sem20 709) pmol×360 min/l) v. CER (297 204 (sem25 112) to 301 655 (sem32 714) pmol×360 min/l). The relative reduction in TAG responses was greater (P=0·045) following IER (106 (sem30) to 68 (sem 15) mmol×360 min/l) compared with CER (117 (sem 43) to 130 (sem 31) mmol×360 min/l). In conclusion, these preliminary findings highlight underlying differences between IER and CER, including a superiority of IER in reducing postprandial lipaemia, which now warrant targeted mechanistic evaluation within larger study cohorts.

The study aimed to examine the effects of diurnal Ramadan fasting (RF) on substrate oxidation, energy production, blood lipids and glucose as well as body composition. Nine healthy Muslim men (fasting (FAST) group) and eight healthy non-practicing men (control (CNT) group) were assessed pre- and post-RF. FAST were additionally assessed at days 10, 20 and 30 of RF in the morning and evening. Body composition was determined by hydrodensitometry, substrate oxidation and energy production by indirect calorimetry, blood metabolic profile by biochemical analyses and energy balance by activity tracker recordings and food log analyses. A significant group×time interaction revealed that chronic RF reduced body mass and adiposity in FAST, without changing lean mass, whereas CNT subjects remained unchanged. In parallel to these findings, a significant main diurnal effect (morning v. evening) of RF on substrate oxidation (a shift towards lipid oxidation) and blood metabolic profile (a decrease in glucose and an increase in total cholesterol and TAG levels, respectively) was observed, which did not vary over the course of the Ramadan. In conclusion, although RF induces diurnal metabolic adjustments (morning v. evening), no carryover effect was observed throughout RF despite the extended daily fasting period (18·0 (sd 0·3) h) and changes in body composition.

Presently, about 12% of the population is 65 years or older and by the year 2030 that figure is expected to reach 21%. In order to promote the well-being of the elderly and to reduce the costs associated with health care demands, increased longevity should be accompanied by ageing attenuation. Energy restriction, which limits the amount of energy consumed to 60–70% of the daily intake, and intermittent fasting, which allows the food to be available ad libitum every other day, extend the life span of mammals and prevent or delay the onset of major age-related diseases, such as cancer, diabetes and cataracts. Recently, we have shown that well-being can be achieved by resetting of the circadian clock and induction of robust catabolic circadian rhythms via timed feeding. In addition, the clock mechanism regulates metabolism and major metabolic proteins are key factors in the core clock mechanism. Therefore, it is necessary to increase our understanding of circadian regulation over metabolism and longevity and to design new therapies based on this regulation. This review will explore the present data in the field of circadian rhythms, ageing and metabolism.