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Background: Time restricted eating (TRE) is a dietary strategy that may improve metabolic health. However, no studies have compared TRE with current practice (CP) in dietetics., Hypothesis: TRE will not be inferior to CP to improve glycaemic control in individuals at risk of type 2 diabetes (T2D)., Methods: This parallel group, randomised, non-inferiority, controlled trial randomised 247 participants by site and glycated haemoglobin (HbA1c) into TRE or CP (1:1) for 12 months. Participants were aged 35-70 years, with a body mass index (BMI) >25 but <45 kg/m 2 , and score ≥15 on the Australian type 2 diabetes risk (AUSDRISK) assessment, without a diagnosis of T2D. Study visits were balanced between groups and all participants received five consultations at 0, 0.5, 1, 2 and 3 months. TRE followed a self-selected 9 h eating window (≥0600 and ≤1900), whereas CP followed Australian dietary guidelines., Outcomes: The primary endpoint is the estimate of group mean difference (TRE vs CP) of HbA1c at 4 months in a covariate linear regression adjusting for stratification factors and sex. Secondary efficacy outcomes at 4 and 12 months are changes in fasting glucose, fasting insulin, HOMA-IR and nocturnal glucose by continuous glucose monitor incremental area under the curve and change in HbA1c at 12 months. Other endpoints are exploratory and will not be adjusted for multiplicity., Conclusions: We will determine whether TRE is an alternate strategy to current practice in dietetics to improve glucose control., Trial Registration: NCT04762251; 21 Feb 2021., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Aim: This qualitative study aimed to explore the experiences of participants who were enrolled in 6-month controlled weight loss interventions with 2-month follow-up to better understand the process of behaviour change and maintenance., Methods: Fifteen participants who completed or dropped out from either a daily energy restriction or intermittent fasting group were recruited using maximum variation purposive sampling. In-depth, semi-structured interviews were conducted at the 2-month follow-up phase. All interviews were transcribed and analysed using thematic analysis, guided by behaviour change models including transtheoretical model, social cognitive theory and integrated model of change., Results: Participants following both diets showed similar behaviour change patterns. Their first motivations were mostly external and relied on 'accountability' to adhere to the diet when initiating the dietary changes. Participants highlighted the importance of frequent reviews and monitoring in assisting their adherence. This feedback system promoted the development of self-efficacy and internalised motivation to encourage an 'ownership'. Participants who transitioned successfully from relying on accountability to take 'ownership' of the intervention were more capable of tackling challenges and tailoring their diet to form a new routine for long-term maintenance., Conclusion: External motivations were key to initiate while internalised motivations were more important to sustain the behaviour change. Health professionals can assist this process through routine monitoring and feedback processes in clinical practice., (© 2023 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Australia.)

Background: The last decade has seen increased research on the relationship between diet and male fertility, but there are no clearly defined nutritional recommendations for men in the preconception period to support clinical fertility outcomes., Objective and Rationale: The purpose of this scoping review is to examine the extent and range of research undertaken to evaluate the effect(s) of diet in the preconception period on male clinical fertility and reproductive outcomes., Search Methods: Four electronic databases (MEDLINE and EMBASE via Ovid, CAB Direct, and CINAHL via EBSCO) were searched from inception to July 2023 for randomized controlled trials (RCTs) and observational studies (prospective/retrospective, case-control, and cross-sectional). Intervention studies in male participants or couples aiming to achieve dietary or nutritional change, or non-intervention studies examining dietary or nutritional components (whole diets, dietary patterns, food groups or individual foods) in the preconception period were included. Controls were defined as any comparison group for RCTs, and any/no comparison for observational studies. Primary outcomes of interest included the effect(s) of male preconception diet on clinical outcomes such as conception (natural or via ART), pregnancy rates and live birth rates. Secondary outcomes included time to conception and sperm parameters., Outcomes: A total of 37 studies were eligible, including one RCT and 36 observational studies (prospective, cross-sectional, and case-control studies; four studies in non-ART populations) published between 2008 and 2023. Eight reported clinical outcomes, 26 reported on secondary outcomes, and three reported on both. The RCT did not assess clinical outcomes but found that tomato juice may benefit sperm motility. In observational studies, some evidence suggested that increasing fish or reducing sugar-sweetened beverages, processed meat or total fat may improve fecundability. Evidence for other clinical outcomes, such as pregnancy rates or live birth rates, showed no relationship with cereals, soy and dairy, and inconsistent relationships with consuming red meat or a 'healthy diet' pattern. For improved sperm parameters, limited evidence supported increasing fish, fats/fatty acids, carbohydrates and dairy, and reducing processed meat, while the evidence for fruits, vegetables, cereals, legumes, eggs, red meat and protein was inconsistent. Healthy diet patterns in general were shown to improve sperm health., Wider Implications: Specific dietary recommendations for improving male fertility are precluded by the lack of reporting on clinical pregnancy outcomes, heterogeneity of the available literature and the paucity of RCTs to determine causation or to rule out reverse causation. There may be some benefit from increasing fish, adopting a healthy dietary pattern, and reducing consumption of sugar-sweetened beverages and processed meat, but it is unclear whether these benefits extend beyond sperm parameters to improve clinical fertility. More studies exploring whole diets rather than singular foods or nutritional components in the context of male fertility are encouraged, particularly by means of RCTs where feasible. Further assessment of core fertility outcomes is warranted and requires careful planning in high-quality prospective studies and RCTs. These studies can lay the groundwork for targeted dietary guidelines and enhance the prospects of successful fertility outcomes for men in the preconception period. Systematic search of preconception diet suggests that increasing fish and reducing sugary drinks, processed meats and total fat may improve male fertility, while consuming healthy diets, fish, fats/fatty acids, carbohydrates and dairy and reducing processed meat can improve sperm health., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Preclinical data show that autophagy delays age-related disease. It has been postulated that age-related disease is-at least in part-caused by an age-related decline in autophagy. However, autophagic flux has never been measured in humans across a spectrum of aging in a physiologically relevant context. To address this critical gap in knowledge, the objective of this cross-sectional observational study was to measure basal autophagic flux in whole blood taken from people at elevated risk of developing type 2 diabetes and correlate it with chronological age. During this study, 119 people were recruited and five people were excluded during sample analysis such that 114 people were included in the final analysis. Basal autophagic flux measured in blood and correlations with parameters such as age, body weight, fat mass, AUSDRISK score, blood pressure, glycated hemoglobin HbA1c, blood glucose and insulin, blood lipids, high-sensitivity C-reactive protein, plasma protein carbonylation, and plasma β-hexosaminidase activity were analysed. Despite general consensus in the literature that autophagy decreases with age, we found that basal autophagic flux increased with age in this human cohort. This is the first study to report measurement of basal autophagic flux in a human cohort and its correlation with age. This increase in basal autophagy could represent a stress response to age-related damage. These data are significant not only for their novelty but also because they will inform future clinical studies and show that measurement of basal autophagic flux in a human cohort is feasible., (© 2023. The Author(s), under exclusive licence to American Aging Association.)

Background: Unripe avocados ( Persea americana ) are naturally enriched in mannoheptulose (MH), which is a candidate caloric restriction mimetic., Objectives: To evaluate the effects of a diet supplement made from unripe avocado on glucose tolerance, and cardiometabolic risk factors in free-living nondiabetic adults with obesity., Methods: In a double-blinded, randomised controlled trial, 60 adults (female n = 47, age 48 ± 13 years, BMI 34.0 ± 2.6 kg/m 2 ) were stratified by sex and randomised to avocado extract (AvX, 10 g finely ground, freeze-dried unripe avocado) or placebo (10 g finely ground cornmeal plus 5% spinach powder) daily, for 12 weeks. The primary outcome was a change in glucose area under the curve (AUC) in response to a 75 g oral glucose tolerance test. A post-hoc analysis was subsequently performed in a subgroup with insulin AUC above the median of baseline values after removal of participants >2 SD from the mean., Results: There were no between-group differences in glucose AUC ( p = 0.678), insulin AUC ( p = 0.091), or cardiovascular outcomes. In the subgroup analysis, insulin AUC was lower in AxV versus placebo ( p = 0.024)., Conclusions: Daily consumption of unripe avocado extract enriched in MH did not alter glucose tolerance or insulin sensitivity in nondiabetic adults with obesity, but the data provided preliminary evidence for a benefit in insulin AUC in a subgroup of participants with elevated baseline postprandial insulin levels.

Intermittent fasting appears an equivalent alternative to calorie restriction (CR) to improve health in humans. However, few trials have considered applying meal timing during the 'fasting' day, which may be a limitation. We developed a novel intermittent fasting plus early time-restricted eating (iTRE) approach. Adults (N = 209, 58 ± 10 years, 34.8 ± 4.7 kg m - 2 ) at increased risk of developing type 2 diabetes were randomized to one of three groups (2:2:1): iTRE (30% energy requirements between 0800 and 1200 hours and followed by a 20-h fasting period on three nonconsecutive days per week, and ad libitum eating on other days); CR (70% of energy requirements daily, without time prescription); or standard care (weight loss booklet). This open-label, parallel group, three-arm randomized controlled trial provided nutritional support to participants in the iTRE and CR arms for 6 months, with an additional 12-month follow-up. The primary outcome was change in glucose area under the curve in response to a mixed-meal tolerance test at month 6 in iTRE versus CR. Glucose tolerance was improved to a greater extent in iTRE compared with CR (-10.10 (95% confidence interval -14.08, -6.11) versus -3.57 (95% confidence interval -7.72, 0.57) mg dl -1  min -1 ; P = 0.03) at month 6, but these differences were lost at month 18. Adverse events were transient and generally mild. Reports of fatigue were higher in iTRE versus CR and standard care, whereas reports of constipation and headache were higher in iTRE and CR versus standard care. In conclusion, incorporating advice for meal timing with prolonged fasting led to greater improvements in postprandial glucose metabolism in adults at increased risk of developing type 2 diabetes. ClinicalTrials.gov identifier NCT03689608 ., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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/m 2 ) 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.

Objective: We sought to examine the effects of 8 wk of time-restricted eating (TRE) on glucose metabolism and the adipose tissue transcriptome during a metabolic ward stay in men with obesity., Methods: In a single-arm, pre-post trial, 15 men (ages 63 ± 4 y, body mass index = 30.5 ± 2.4 kg/m 2 , waist circumference = 113 ± 4 cm) with obesity but no history of diabetes were enrolled and underwent 2 wk of baseline monitoring before they were instructed to eat their regular diets within a contiguous 10-h time frame each day for 8 wk. Metabolic testing was performed at baseline and week 8 during a 35-h metabolic ward stay, during which all food intake was strictly timed and controlled. Identical meal-tolerance tests were performed at breakfast and dinner. Blood glucose, glucoregulatory hormones, and subjective appetite score were measured. Subcutaneous adipose tissue biopsies were performed and the transcriptome was assessed., Results: The primary outcome, plasma glucose area under the curve, was altered by TRE, being unchanged at breakfast but increased at dinner. However, TRE reduced fasting glucose, glycated hemoglobin, body weight, and body fat, and increased glucose-dependent insulinotropic peptide area under the curve at dinner. In subcutaneous adipose tissue, 117 genes were up-regulated and 202 genes down-regulated by TRE. Pathway analysis revealed down-regulation of genes involved in proteasome function and mitochondrial regulation., Conclusions: TRE had a net effect of reducing glycemia and dampening energy-consuming pathways in adipose tissue., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Autophagic flux is a critical cellular process that is vastly under-appreciated in terms of its importance to human health. Preclinical studies have demonstrated that reductions in autophagic flux cause cancer and exacerbate chronic diseases, including heart disease and the pathological hallmarks of dementia. Autophagic flux can be increased by targeting nutrition-related biochemical signaling. To date, translation of this knowledge has been hampered because there has been no way to directly measure autophagic flux in humans. In this study we detail a method whereby human macroautophagic/autophagic flux can be directly measured from human blood samples. We show that whole blood samples can be treated with the lysosomal inhibitor chloroquine, and peripheral blood mononuclear cells isolated from these samples could be used to measure autophagic machinery protein LC3B-II. Blocking of autophagic flux in cells while still in whole blood represents an important advance because it preserves genetic, nutritional, and signaling parameters inherent to the individual. We show this method was reproducible and defined LC3B-II as the best protein to measure autophagic flux in these cells. Finally, we show that this method is relevant to assess intra-individual variation induced by an intervention by manipulating nutrition signaling with an ex vivo treatment of whole blood that comprised leucine and insulin. Significantly, this method will enable the identification of factors that alter autophagic flux in humans, and better aid their translation in the clinic. With further research, it could also be used as a novel biomarker for risk of age-related chronic disease. Abbreviations: AMPK: AMP-activated protein kinase; ACTB: actin beta; ATG5: autophagy related 5; BAF: bafilomycin A 1 ; CQ: chloroquine; DMSO: dimethyl sulfoxide; DPBS: Dulbecco's phosphate-buffered saline; EDTA: ethylenediaminetetraacetic acid; KO: knockout; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP1LC3C/LC3C: microtubule associated protein 1 light chain 3 gamma; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; PBMCs: peripheral blood mononuclear cells; PMNs: polymorphonuclear cells; RPMI: Roswell Park Memorial Institute; SQSTM1: sequestosome 1; TBST: Tris-buffered saline containing 0.1% (v:v) Tween 20; TEM: transmission electron microscopy.

Moderate calorie restriction (CR) has long been recognized to reduce the risk of chronic diseases that are associated with obesity and aging. Intermittent fasting (IF) has recently emerged as a viable alternative to daily CR to reduce risk markers of chronic diseases, such as type 2 diabetes and cardiovascular diseases. The majority of trials have shown that IF provides similar metabolic and weight benefits to CR, although a few suggest that IF maybe superior to CR. The type of fasting protocol that is employed varies widely and could underpin the divergence in study outcomes. This review will discuss the findings of currently available IF versus CR trials, the protocol differences that exist between studies, as well as the gaps that still exist in the field, and finally will highlight upcoming studies that will further our understanding of the metabolic effectiveness of IF diets for metabolic health., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Human trials that compare intermittent fasting (IF) to calorie restriction (CR) with psychological, behavioral and cognition outcomes are limited. We hypothesized that there would be no difference between CR and IF on perceived eating behaviors, mood, sleep quality, quality of life (QOL) and cognition in women with overweight and obesity. In this prespecified secondary analysis of an open-label, single center, parallel assignment, randomized controlled trial, healthy women with overweight or obesity (N = 46, mean [SD] age 50 [9] years, BMI 32.9 [4.4] kg/m 2 ), without a diagnosed eating disorder and who were randomized into 2 weight loss groups (prescribed 70% of calculated energy requirements as IF or CR) were included. Measurements were assessed in both IF and CR groups following a 12-hour overnight fast during baseline and week 8 and additionally following a 24-hour fast in the IF group only at week 8. We observed that IF produced greater weight and body fat loss than CR (P < .001). We did not detect any statistical difference between groups for the change in dietary restraint, disinhibition, hunger, mood, sleep quality, and QOL. An increase in cognitive performance was found in both IF (P = .036) and CR (P = .006) groups in one of the cognitive tasks, but there was no statistical difference between groups. Perceived eating behaviors, mood, sleep quality and cognitive performance were not changed by an acute 24-hour fast within the IF group (all P > .05). IF may be a viable alternative to CR for weight loss, in the short-term, without adversely impacting eating behaviors, mood, sleep quality, QOL or cognition in healthy women with overweight or obesity. However, larger and long term trials are required., Competing Interests: Author Declarations The authors declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Background: Intermittent fasting (IF) is proposed as a viable alternative to moderate calorie restriction (CR) for weight loss and metabolic health, but few long term randomized trials have been conducted. This protocol paper describes the rationale and detailed protocol for DIRECT study (Daily versus Intermittent Restriction of Energy: Controlled Trial to Reduce Diabetes Risk), comparing long term effectiveness of IF versus CR on metabolic health in individuals who are at increased risk of developing type 2 diabetes., Methods: Anticipated 260 non-diabetic men and women aged 35-75 years, BMI 25-50 kg/m 2 with score ≥12 on the Australian Diabetes Risk (AUSDRISK) calculator will be recruited into this open-label, multi-arm, parallel group sequential randomized controlled trial. Participants will be randomized to one of three groups for 18 months: IF (30% of energy needs on fast days), CR (70% of energy needs daily), or standard care (SC) group. All participants will visit the clinic fortnightly for weight assessments during active intervention phase (6 months), followed by a 12-month follow-up phase. IF and CR groups will receive further diet counselling by dietitian. Two primary outcomes are the changes in glycated haemoglobin (HbA1c) and postprandial glucose area under the curve (AUC) at week 24 post-randomization. Secondary outcomes include changes in weight, body composition via dual-energy X-ray absorptiometry, gastro-intestinal hormones, cardiovascular risk factors, and dietary record by a smartphone-based application., Discussion: This study will provide substantial evidence as to whether IF is an effective nutrition intervention for glycaemic control in a population at risk of developing type 2 diabetes., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Health literacy has been reported to have effects on health behavior change and health-related outcomes, but few studies have explored the association between health literacy and frailty. The aim of our study is to investigate the relationships between health literacy and frailty among community-dwelling seniors. This cross-sectional study enrolled 603 community-dwelling older adults (307 women) in residential areas, with a mean age of 70.9 ± 5.82 years. Health literacy was assessed using the Mandarin version of the European Health Literacy Survey Questionnaire. Physical frailty was defined by Fried frailty phenotype. Logistic regression was carried out to determine potential risk factors of frailty. In the multivariate logistic regression model, physical activity (Odds Ratio [OR] 1.47, 95% Confidence Interval [CI] 1.06⁻2.03) and health literacy (sufficient vs. excellent: OR 2.51, 95% CI 1.32⁻4.77) were associated with prefrailty and frailty. In subgroup analysis, pre-frailty and frailty were also negatively associated with health literacy in individuals with 'insufficiently active' (inadequate vs. excellent: OR 5.44, 95% CI 1.6⁻18.45) and 'sufficiently/highly active' physical activity levels (sufficient vs. excellent: OR 2.41, 95% CI 1.07⁻5.42). Therefore, in these community-dwelling elderly adults, health literacy was associated with pre-frailty and frailty regardless of age, gender, socio-economic status, and education level.