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Ever since their introduction a decade ago, stable introns, a type of noncoding (nc)RNAs, are found to be key players in different important cellular processes acting through regulation of gene expression and feedback loops to maintain cellular homeostasis. Despite being commonly regarded as useless byproducts, recent studies in yeast suggested that stable introns are essential for cell survivability under starvation. In Drosophila, we found that a stable intron, sisR‐1, has a direct effect in regulating mitochondrial dynamics during short‐term fasting and subsequently improved overall oocyte quality. We speculated that the beneficial effects implicated by sisR‐1 is through the activation of mitohormesis, an interesting phenomenon in mitochondrial biology. Mitohormesis is suggested to improve health span and lifespan of cells and organisms, but the involvement of ncRNAs is not well‐documented. Here, we discuss the potential role of sisR‐1 and other ncRNAs in activating mitohormesis and the possible applications in improving cellular and organismal health. [ABSTRACT FROM AUTHOR]

Background and Aims: During fasting, bodily homeostasis is maintained due to hepatic production of glucose (gluconeogenesis) and ketone bodies (ketogenesis). The main hormones governing hepatic fuel production are glucagon and glucocorticoids that initiate transcriptional programs aimed at supporting gluconeogenesis and ketogenesis. Methods: Using primary mouse hepatocytes as an ex vivo model, we employed transcriptomic analysis (RNA‐seq), genome‐wide profiling of enhancer dynamics (ChIP‐seq), perturbation experiments (inhibitors, shRNA), hepatic glucose production measurements and computational analyses. Results: We found that in addition to the known metabolic genes transcriptionally induced by glucagon and glucocorticoids, these hormones induce a set of genes encoding transcription factors (TFs) thereby initiating transcriptional cascades. Upon activation by glucocorticoids, the glucocorticoid receptor (GR) induced the genes encoding two TFs: CCAAT/enhancer‐binding protein beta (C/EBPβ) and peroxisome proliferator‐activated receptor alpha (PPARα). We found that the GR‐C/EBPβ cascade mainly serves as a secondary amplifier of primary hormone‐induced gene programs. C/EBPβ augmented gluconeogenic gene expression and hepatic glucose production. Conversely, the GR‐PPARα cascade initiated a secondary transcriptional wave of genes supporting ketogenesis. The cascade led to synergistic induction of ketogenic genes which is dependent on protein synthesis. Genome‐wide analysis of enhancer dynamics revealed numerous enhancers activated by the GR‐PPARα cascade. These enhancers were proximal to ketogenic genes, enriched for the PPARα response element and showed increased PPARα binding. Conclusion: This study reveals abundant transcriptional cascades occurring during fasting. These cascades serve two separated purposes: the amplification of the gluconeogenic transcriptional program and the induction of a gene program aimed at enhancing ketogenesis. [ABSTRACT FROM AUTHOR]

Objective: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100–125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first‐trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first‐ trimester fasting plasma glucose levels, as compared with gestational diabetes, a well‐established risk factor for diabetes, in up to 5‐year follow‐up postpartum. Methods: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post‐delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic‐area under the curve (ROC‐AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status. Results: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut‐off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity. Conclusions: Increased first‐trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first‐trimester fasting plasma glucose has a more pronounced impact on progression to diabetes. Synopsis: First‐trimester fasting plasma glucose levels exceeding 86.5 mg/dL carry at least a comparable risk for type 2 diabetes progression as gestational diabetes, regardless of obesity status. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of small bowel motility disorders is performed by manometric evaluation of the contractile patterns of the small intestine. Conventional intestinal manometry systems include few pressure sensors at relatively long intervals. We have recently shown that high‐resolution jejunal manometry, with multiple closely spaced recording sites, allows the analysis of propagation patterns of intestinal motility in healthy subjects that cannot be detected with conventional manometry. The objective of this pilot study was to explore the feasibility and diagnostic value of high‐resolution intestinal manometry in patients with suspected small bowel dysmotility. Methods: Prospective pilot study evaluating intestinal motility patterns in 16 consecutive patients (16–61 years; 11 women) with severe, chronic digestive symptoms referred for the evaluation of intestinal motility and in 18 healthy controls (21–38 years; 8 women). A 36‐channel high‐resolution manometry catheter was orally placed under radiological guidance in the jejunum. Intestinal motility was continuously recorded for 3 h fasting and 2 h after a 450 kcal meal. The manometric recordings were analyzed in two formats: (a) with the high‐resolution data from 34 channels and (b) showing only the recordings from 5 channels separated by 7 cm intervals, mimicking a conventional manometry recording. Key Results: In the analysis mimicking conventional manometry, abnormal motility criteria were detected in six patients and in no healthy subject [bursts (n = 3), postprandial minute rhythm (n = 1) and myopathic pattern (n = 2)]. These classical dysmotility criteria were also detected by high‐resolution manometry. High‐resolution analysis detected one or more abnormal findings in seven additional patients that were not observed in any healthy subject, specifically: (a) abnormal propagation of Phase III (n = 3); (b) reduced propagated activity during Fasting Phase II (n = 4); (c) increased propagated activity during Fasting Phase II and postprandial phase (n = 1). Conclusions and Inferences: This pilot study suggests that high‐resolution intestinal manometry may improve the sensitivity of conventional manometry in the detection of intestinal motor dysfunction. [ABSTRACT FROM AUTHOR]

A randomized, open‐label, 2‐period, 2‐sequence crossover study was conducted to evaluate the pharmacokinetics and bioequivalence of 2 oral formulations of vildagliptin tablets under both fasting and fed conditions in healthy Chinese subjects. A total of 56 healthy subjects were randomized to receive a single 50‐mg dose of either a generic vildagliptin tablet (T) or the reference formulation (R). The washout period was 3 days. Blood samples were collected up to 24 hours postdosing during each period and analyzed for vildagliptin using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The 90% confidence intervals for the geometric mean ratios (T:R) of maximum serum concentration, area under the serum concentration‐time curve from time 0 to the last measurable concentration, and area under the serum concentration‐time curve from time 0 to infinity were all within the predefined bioequivalence range of 80%‐125%. This indicates that the generic and reference formulations are bioequivalent under both fasting and fed states. All adverse events reported were mild and transient. High‐fat meals delayed absorption and reduced the maximum peak concentration of both formulations; however, they did not affect the overall exposure. Therefore, vildagliptin can be taken without regard to meals. [ABSTRACT FROM AUTHOR]

Objective: The present study objectived to investigate the influence of Ramadan fasting (RF) on olfactory function. Methods: Sixty‐two participants were included in the current prospective study. The odor threshold and identification performances were determined by using the Connecticut Chemosensory Clinical Research Center (CCCRC) test initially (day 0) and on the first and last day (30th) of RF. Body weight (BW)s were measured initially and at the end of the study. The results were analyzed statistically. Results: The average of baseline and last‐day BWs were 78.38 ± 12.96 and 78.36 ± 12.39 kg, respectively. No significant difference was determined in terms of BWs (p =.932, p >.05). In the evaluation of CCCRC test outcomes, significant differences were observed in the scores of butanol thresholds (p =.0001), odor identification (p =.0001), food‐related odors identification (p =.0001), and the number of normosmic individuals (p =.0001) at different times (p <.05). The thresholds scores (p =.0001, p =.0001), the identification scores (p =.0001, p =.0001), food‐related odors identification scores (p =.0001, p =.0002), and the number of normomic individuals (p =.001, p =.001) detected on 30th day were significantly higher than on 0th and 1st days; respectively (p <.05). Additionally, the threshold scores (p =.0001), the identification scores (p =.003), food‐related odors identification scores (p =.007), and the number of normosmic individuals (p =.018) detected on day 1 were significantly higher than on day 0 (p <.05). Conclusion: The current study demonstrated that Ramadan fasting enhances the olfactory detection threshold and odor identification scores, significantly improving the identification of food‐related odors. The results may indicate that Ramadan fasting improves olfactory performance. Level of evidence: Level II. [ABSTRACT FROM AUTHOR]

Summary Circadian disruption, arising from conflict between internal circadian time and behavioural sleep–wake and fasting–feeding rhythms, may contribute to the prevalence of type 2 diabetes mellitus and disease severity. Previous studies have demonstrated a link between irregular breakfast eating and poorer metabolic health. We aimed to further explore the relationships between breakfast habits, circadian misalignment (social jetlag), and metabolic parameters in a cohort of adult participants with type 2 diabetes mellitus. A total of 330 adult participants with type 2 diabetes mellitus attending for routine clinical review completed structured questionnaires to assess habitual sleep timing, chronotype, and social jetlag. Statistical analysis was via inferential groupwise approaches and path analysis to establish interdependencies of effects of social jetlag, chronotype, and breakfast eating regularity on HbA1c. 22.7% of the participants reported eating breakfast five times or fewer a week, and were categorised as irregular breakfast eaters. Compared with those who ate breakfast six or seven times a week, irregular breakfast eaters had significantly higher HbA1c and diastolic blood pressure, were younger and had greater social jetlag. In the path analysis, irregular breakfast eating exerted a direct effect on HbA1c, whilst social jetlag exerted only an indirect effect on HbA1c through breakfast eating regularity. Chronotype did not exert any effect on HbA1c, but did exert an indirect effect on breakfast eating regularity via social jetlag. Our results showed that adult participants with type 2 diabetes mellitus, who ate breakfast irregularly had poorer metabolic health and greater social jetlag. The relationship between social jetlag and glycaemic control appears to be mediated through breakfast eating habits. [ABSTRACT FROM AUTHOR]

Dihydroxyaluminum aminoacetate, heavy magnesium carbonate, and aspirin tablets is a new combined aspirin preparation, each containing aspirin (81 mg), dihydroxyaluminum aminoacetate (11 mg), and heavy magnesium carbonate (22 mg). This study was conducted to evaluate the pharmacokinetic (PK) and bioequivalence in healthy Chinese subjects. This randomized, open‐label, single‐dose, 2‐sequence, and 2‐period crossover study included 78 healthy volunteers (fasting, n = 36; postprandial, n = 42). Blood samples were collected for PK analysis. Aspirin and salicylic acid concentrations in human plasma were determined by liquid chromatography‐tandem mass spectrometry. Safety and tolerability were monitored. There were no significant differences between the test and reference formulations in maximum plasma concentration, area under the plasma concentration‐time curve (AUC) from time 0 to time t, or AUC from time 0 to infinity. The 90% confidence intervals of the test and reference formulations of maximum plasma concentration, AUC from time 0 to time t, and AUC from time 0 to infinity were within the acceptable range (80%‐125%) under fasting and postprandial conditions. All adverse events were mild and no serious adverse events were observed in the study. Both compounds were well tolerated in healthy Chinese volunteers. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)‐ or natural aging‐induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY‐abundant culture medium of osteocytes (OCY‐CM) from osteoarthritic mice possess pro‐inflammatory, pro‐osteoclastic, and pro‐neurite outgrowth effects, while OCY‐CM from the intermittent fasting‐treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM‐induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the comparative effectiveness and safety profiles of generic lenvatinib mesylate capsules and the reference product in a cohort of healthy Chinese individuals. The research design consisted of a randomized, open‐label trial with a single‐dose regimen, 2 crossover periods, and 2 distinct phases involving participants from the Chinese population. A total of 24 individuals were enrolled in the fasting study, with an additional 27 participants included in the postmeal study. Each participant received a single dose of either 4 mg of the reference product or the study product per cycle. The washout period was 14 days between each period. Bioequivalence was assessed through the analysis of geometric mean and ratio of pharmacokinetic parameters, while the safety of both drugs was evaluated by monitoring adverse events (AEs). Following a single oral administration of lenvatinib (4 mg), linear pharmacokinetics were observed. The rate of absorption was found to be significantly faster under fasting conditions (median time to maximum concentration, 2.3‐2.5 hours), while the presence of a high‐fat diet resulted in delayed absorption (median tmax, 5.3‐6.1 hours). Furthermore, the 90% confidence intervals for the reference and test pharmacokinetic parameters under both fasting and postprandial conditions fell within the bioequivalence standard range of 80%‐125%. AEs were reported in 34.78% of cases during fasting and in 48.15% of cases after eating. There was no significant difference in AE rates between the reference and study products. The study determined that both the study product and the reference product were bioequivalent and well tolerated by healthy Chinese participants in both fasting and postprandial conditions. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Fasting headaches frequently occur during the first few days of Ramadan, and treatment is challenging because of fasting.This study aimed to evaluate the effect of extended‐release paracetamol on preventing fasting headaches.A randomized, open‐label clinical trial investigated the efficacy of extended‐release paracetamol at a daily dose of 1330 mg in preventing fasting headache. Adults aged 18 years and older were recruited through the Clinical Trial Unit at the King Saud University Medical City. The eligible participants in the study fasted 13.5 h daily during the first week of Ramadan. Participants in the treatment and control arms were followed up to investigate the occurrence, severity, and timing of headache symptoms via self‐reporting using a standardized headache diary scale with a daily online link or phone call. The primary outcome was the frequency of headache episodes while fasting during the first week of Ramadan.A total of 238 participants were enrolled and randomized. Of these, 173 followed the protocol (80 treated, 93 control) for at least the first day and were included in the analysis. Most participants were young and healthy, with a mean age of 32.2 ± 10.2 years. More men were included in the study (102/173; 59.0%), a small proportion of participants were smokers (31/173; 17.9%), and almost all participants reported being coffee drinkers (165/173; 95.4%); nonetheless, these characteristics were evenly distributed between the two groups in the study. The overall incidence of headache episodes was 33.0% (57/173) on day 1 and decreased to 11.3% (18/159) on day 7. On average over the 7 days, no significant effect was observed for the treatment on the incidence of headache, as the findings from the generalized estimating equation model indicated (β = −0.398, p = 0.084; odds ratio = 0.67, 95% confidence interval [CI] 0.42–1.06). Moreover, there was initially no significant difference in the incidence of headache episodes between the treatment and control groups. However, the treatment group had significantly fewer headache episodes during fasting than the control group on day 3 (4/72 [5.6%] vs. 15/91 [16.5%], p = 0.031; relative risk [RR] = 0.34, 95% CI 0.12–0.97) and day 6 (5/69 [7.2%] vs. 20/90 [22.2%], p = 0.010; RR = 0.33, 95% CI 0.13–0.82). No adverse effects were observed during the study period.No significant differences were observed in the occurrence of fasting headaches between the two groups on most days during the study period. Additional studies are required to address fasting headaches during the first week of Ramadan. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is one of the most prevalent health conditions worldwide, affecting millions of individuals and posing significant public health challenges. Understanding the nature of type 2 diabetes, its causes, symptoms and treatments is crucial for managing and preventing its complications. Many different dietary strategies are used by individuals to treat and manage diabetes. This review provides an overview of popular dietary strategies that have evidence for improving long‐term glycaemic control or achieving diabetes remission, as well as strategies that may be useful to reduce postprandial hyperglycaemia, which may be of use in the prevention of diabetes, but also as strategies for those already diagnosed but trying to manage their condition better. Recent clinical trials have provided evidence that in people living with type 2 diabetes who also live with overweight or obesity, using a total diet replacement weight loss programme results in significant and substantial weight loss, and as a result, many people can achieve remission from their diabetes. There has been considerable interest in whether similar effects can be achieved without reliance on formula foods, using real diet approaches. Reduced or low‐carbohydrate diet approaches hold some promise, with observational or preliminary findings suggesting beneficial effects, but evidence from robust trials or systematic reviews of randomized controlled trials is still lacking. The Mediterranean dietary pattern, low in saturated fat and high in monounsaturated fat, also has some potential, with evidence to suggest some people can lose weight and achieve remission using this approach, which may be easier to adhere to longer term than more intensive total diet replacement and low‐carbohydrate strategies. Plant‐based diets that advocate for the elimination of animal‐based and/or animal‐derived foods have increased in popularity. There is evidence from epidemiological studies that people who follow these diets have a lower risk of developing type 2 diabetes, and evidence from trials and systematic reviews of trials that changing to a dietary pattern lower in animal‐based and animal‐derived foods has benefits on glycaemic control and other markers of cardiovascular disease. While these approaches all provide food or nutrient prescriptions, approaches that incorporate periods of fasting do not provide rules on the types of foods that can or cannot be consumed, but rather provide time windows of when to eat. Evidence suggests that these approaches can be as effective in achieving energy restriction and weight loss as approaches that advocate continuous energy restriction, and there is evidence for benefits on glycaemic control independent of weight loss. Finally, popular dietary strategies that may be useful to use or combine to help prevent postprandial hyperglycaemia include reducing the glycaemic index or glycaemic load of the diet, high‐fibre diets, eating foods in a meal in the order vegetables > protein > carbohydrates, preloading or combining acids such as vinegar or lemon juice with meals and engaging in low‐intensity aerobic exercise immediately after meals. [ABSTRACT FROM AUTHOR]

Aims: Extended fasting–postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting–postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients. Methods: In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF. Results: Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients. Conclusions: AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function. [ABSTRACT FROM AUTHOR]

There are conflicting reports both within the lay media and scientific literature regarding the use and benefit of dietary practices that aim to reduce CHO intake in endurance athletes. This study aimed to determine the prevalence of intentional reduction of CHO intake and fasted training in elite endurance‐based athletes using a semi‐quantitative questionnaire. Bone is a nutritionally modulated tissue; therefore, this study also aimed to explore if these dietary practices are potentially associated with bone injury incidence. The reported reduction of CHO intake was prevalent (28%) with the primary motivation being maintenance or manipulation of body composition. However, discrepancies in athletes' awareness of CHO intake were identified providing a potential avenue of intervention especially within applied practice. The use of fasted training was more prevalent (38%) with athletes using this practice for both body composition manipulation and promoting a desired adaptive response. Forty‐four per cent of participants had suffered a radiographically confirmed bone injury at some point in their career. There was no association between reduction in CHO intake and bone injury incidence; however, the incidence of bone injury was 1.61 times higher in those who currently use fasted training compared to those who have never used it or who have used it in the past. Although a direct causal link between these dietary practices and the incidence of bone injury cannot be drawn, it provides robust justification for future investigations of the potential mechanisms that could explain this finding. Highlights: The self‐reported use of reductions in CHO intake (28%) and fasted training (38%) is prevalent in elite endurance‐based athletes and comparable to previous investigations in this area. Controlling body composition and promoting adaptive responses were common rationales for use.The incidence of bone injury is also high (44%) and there may be some association between bone injury incidence and fasted training. Further controlled experimental studies are required to determine the direct effect of nutritional strategies commonly adopted by endurance athletes on bone metabolism both acutely and chronically.There appears to be a gap in some athlete's knowledge and awareness of CHO rich foods and appropriate consumption of CHO to support endurance training and performance according to current guidelines. Future work should aim to explore and address this area further. [ABSTRACT FROM AUTHOR]

Objective: Fasting for weight control is an under‐studied behaviour implicated in eating disorders. However, little is known about what factors account for its onset and persistence. Method: This study sought to identify risk and maintenance factors for fasting among 1025 women recruited through an eating disorder self‐help platform who completed study measures at baseline and 6 month follow‐up. Univariate and multivariate logistic regressions were performed to test which variables at baseline predicted the onset (vs. stably asymptomatic) and persistence (vs. remission) of fasting at follow‐up. Results: Univariate models showed that higher baseline overvaluation, dissatisfaction, fear of weight gain, generalised and social anxiety, depression, self‐esteem deficits and eating disorder symptoms (inflexible eating rules, driven exercise) predicted greater likelihood of fasting onset. Only fear of weight gain and depressive symptoms remained significant in the multivariate model. Higher baseline overvaluation, fear of weight gain, driven exercise, inflexible eating rules, and depression predicted greater likelihood of fasting persistence in univariate models. An adherence to inflexible eating rules and overvaluation remained significant in the multivariate model. Conclusion: Findings shed new light on factors that may account for the development and maintenance of fasting, which have implications for guiding effective interventions targeting this behaviour. Highlights: Fear of weight gain and depressive symptoms predicted the onset of fasting for weight control at 6 months follow‐up among women who did not report fasting behaviours at baseline.Adherence to inflexible eating rules and overvaluation with weight and shape predicted the persistence of fasting for weight control at follow‐up among women who endorsed fasting at baseline.Findings have clear implications for intervention targets among programs designed to address fasting behaviour. [ABSTRACT FROM AUTHOR]

Organisms subjected to periodic nutrient limitation early in life exhibit improvements in aspects of survival, including resistance to some environmental stressors. Recent findings indicate that forms of periodic fasting, such as intermittent fasting and time‐restricted feeding, can improve starvation resistance. However, it remains unclear to what extent this survival improvement persists across different genetic backgrounds. In this study, we examine fasting‐induced starvation resistance across a broad survey of wild‐derived lineages and document genetic variation within this trait. We adopt a standard dietary intervention and show improvement in starvation resistance within a common laboratory lineage, replicating previous results. Next, we examine fasting‐induced starvation resistance across isofemale lines collected across latitudes and in different seasons, and among inbred lines derived from flies collected on different continents. We discover genetic variation of fasting‐induced starvation resistance and show that fasting improved starvation resistance as often as it worsened starvation resistance. Fasted flies generally showed reduced fat concentration, and their starvation survival varied with sex, season of collection and geographic origin. While specific lineages common to the laboratory can show a specific fasting‐induced phenotype, we show that this result is not consistent across genetic backgrounds, reinforcing the idea that phenotypes observed in historic laboratory strains may not be conserved across a species. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the pharmacokinetics (PKs) and safety of a generic drug, linezolid, compared to those of a reference drug in healthy Chinese subjects under both fasting and fed conditions. This was a randomized, open‐label, 2‐period, 2‐sequence crossover study. The subjects received a single dose of the test or reference drug, linezolid (600 mg), in each period. The PK parameters were calculated using a non‐compartmental method and compared between the 2 drugs. Bioequivalence was analyzed using geometric mean ratios (GMRs) of the 2 formulations and their corresponding 90% confidence intervals (CIs). The safety of the 2 formulations was assessed under both fasting and fed conditions. Forty‐eight subjects completed the study, 24 each in the fasting and feeding groups. The average plasma concentration‐time patterns of linezolid were similar for both medications under both conditions. The GMR and 90% CIs of the maximum plasma concentration and the area under the plasma concentration‐time curve of linezolid were ranged from 0.80 to 1.25. Both drugs were well tolerated with a similar incidence of adverse drug reactions. In conclusion, the PK and safety profiles of the 2 formulations were comparable. Food intake did not influence the PK profiles of linezolid. These results suggest that the test drug can be used as an alternative to reference drugs. [ABSTRACT FROM AUTHOR]

Neuronal senescence is a major risk factor for the development of many neurodegenerative disorders. The mechanisms that drive neurons to senescence remain largely elusive; however, dysregulated mitochondrial physiology seems to play a pivotal role in this process. Consequently, strategies aimed to preserve mitochondrial function may hold promise in mitigating neuronal senescence. For example, dietary restriction has shown to reduce senescence, via a mechanism that still remains far from being totally understood, but that could be at least partially mediated by mitochondria. Here, we address the role of mitochondrial inorganic polyphosphate (polyP) in the intersection between neuronal senescence and dietary restriction. PolyP is highly present in mammalian mitochondria; and its regulatory role in mammalian bioenergetics has already been described by us and others. Our data demonstrate that depletion of mitochondrial polyP exacerbates neuronal senescence, independently of whether dietary restriction is present. However, dietary restriction in polyP‐depleted cells activates AMPK, and it restores some components of mitochondrial physiology, even if this is not sufficient to revert increased senescence. The effects of dietary restriction on polyP levels and AMPK activation are conserved in differentiated SH‐SY5Y cells and brain tissue of male mice. Our results identify polyP as an important component in mitochondrial physiology at the intersection of dietary restriction and senescence, and they highlight the importance of the organelle in this intersection. [ABSTRACT FROM AUTHOR]

Aims: Insulin efsitora alfa (efsitora) is a once‐weekly basal insulin. This review describes the study design and rationale of the efsitora phase 3 Once Weekly (QW) Insulin Therapy (QWINT) clinical development programme, including the five trials, QWINT‐1 through QWINT‐5. Materials and Methods: The five trials included insulin‐naïve adults (QWINT‐1 and ‐2) with type 2 diabetes (T2D), adults with T2D previously treated with basal insulin (QWINT‐3 and ‐4), and QWINT‐5 in adults with type 1 diabetes. All five trials were designed as multicentre, randomized, controlled, open‐label, treat‐to‐target studies to investigate the efficacy and safety of efsitora versus active once‐daily basal insulin comparators (insulin glargine U100 or insulin degludec U100). The primary objective of each trial is to compare the change in HbA1c from baseline to week 26 or 52 between efsitora and the active comparator. The key secondary objectives include change in fasting glucose, insulin dose and continuous glucose monitoring variables, and patient‐reported outcome questionnaires. Conclusions: The QWINT development programme includes a racially and geographically diverse population to provide important information regarding the efficacy and safety of efsitora and its clinical management of people with diabetes. [ABSTRACT FROM AUTHOR]

Movement behaviors within the 24‐h day, including physical activity (PA), sedentary time, and sleep, are associated with cardiometabolic health. We aimed to determine the association between 24‐h movement composition and cardiometabolic health while accounting for sleep efficiency. Altogether, 1134 participants from the Northern Finland Birth Cohort 1986 study, free from prior cardiovascular disease, provided at least 4 days of 24‐h activity and sleep efficiency measured with a wearable ring. Participants' body composition was assessed with bioimpedance, blood pressure, and waist circumference were measured, and lipids and glucose were analyzed from a fasting blood sample. Linear regression models for cardiometabolic outcomes were created with 24‐h movement composition and covariates, including sleep efficiency and behavioral and socioeconomic factors. Isotemporal time reallocations were used to demonstrate the dose‐dependent associations between time use and outcomes. Beneficial associations with the outcomes were detected when sedentary time was reallocated to light PA, moderate‐to‐vigorous PA (MVPA), or sleep. For example, substituting 30 min of sedentary time with MVPA was associated with 7.2% (95% CI from −9.8% to −4.5%) lower visceral fat area, 4.9% (95% CI from −6.5% to −3.3%) lower body fat percentage, 1.6% (95% CI from −2.3% to −0.9%) smaller waist circumference, and 2.4% (95% CI from 1.2% to 3.5%) higher high‐density lipoprotein (HDL) cholesterol after accounting for gender, marital status, education level, employment, smoking, alcohol consumption, and sleep efficiency. Substituting sedentary time with sleep or light PA showed beneficial but smaller differences in adiposity measures and HDL cholesterol. Limiting sedentary time should be encouraged in adulthood. [ABSTRACT FROM AUTHOR]

Atenolol, a cardioselective β1‐blocker, exhibits efficacy in treating cardiovascular diseases. We conducted a single‐center, randomized, open, single‐dose, 2‐preparation, 2‐cycle, 2‐sequence, double‐crossover trial with a 7‐day washout period to investigate the pharmacokinetics, bioequivalence (BE), and safety of test and reference atenolol tablets (25 mg) in healthy Chinese volunteers. Forty‐eight healthy participants were randomized into the fasting and fed arms. After administering a single oral dose of the test or reference formulation (25 mg), plasma atenolol concentrations were measured using liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were obtained from concentration‐time profiles. In total, 23 and 24 individuals were included in the fasting and fed arms, respectively. The mean concentration‐time profiles for both formulations were similar, and Cmax, AUC0‐t, and AUC0‐∞ were within the BE range of 80%‐125%. Thirteen adverse events (AEs) were observed in 7 participants in the fasting arm; 1 withdrew from the trial early owing to an AE. In the fed arm, 20 AEs were observed in 8 participants, and none withdrew from the trial. All adverse reactions were grade I, with no serious AEs or deaths. Therefore, the 2 tablets are bioequivalent in healthy Chinese individuals under fasting and fed conditions, supporting their further clinical development. [ABSTRACT FROM AUTHOR]

Aging is a multifaceted process impacting cells, tissues, organs, and organ systems of the body. Like other systems, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. In the Western world, overnutrition has increased the incidence of obesity (linked with chronic inflammation) which increases the risk of metabolic syndrome, cardiovascular disease, and cancer. Aging is also associated with inflammaging a sterile chronic inflammation that predisposes individuals to age‐associated disease. Genetic manipulation of the nutrient‐sensing pathway, fasting, and calorie restriction (CR) has been shown to increase the lifespan of model organisms. As well in humans, fasting and CR have also been shown to improve different health parameters. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored. Identifying the effect of fasting and CR on the immune system and how it modulates different parameters of immunosenescence could be important in designing pharmacological or nutritional interventions that slow or revert immunosenescence and strengthen the immune system of elderly individuals. Furthermore, clinical intervention can also be planned, by incorporating fasting or CR with medication, chemotherapy, and vaccination regimes. This review discusses age‐associated changes in the immune system and how these changes are modified by fasting and CR which add information on interventions that promote healthy aging and longevity in the growing aging population. [ABSTRACT FROM AUTHOR]

Vitamin A (retinol) is distributed via the blood bound to its specific carrier protein, retinol-binding protein 4 (RBP4). Retinol-loaded RBP4 is secreted into the circulation exclusively from hepatocytes, thereby mobilizing hepatic retinoid stores that represent the major vitamin A reserves in the body. The relevance of extrahepatic retinoid stores for circulating retinol and RBP4 levels that are usually kept within narrow physiological limits is unknown. Here, we show that fasting affects retinoid mobilization in a tissue-specific manner, and that hormone-sensitive lipase (HSL) in adipose tissue is required to maintain serum concentrations of retinol and RBP4 during fasting in mice. We found that extracellular retinol-free apo-RBP4 induces retinol release by adipocytes in an HSL-dependent manner. Consistently, global or adipocyte-specific HSL deficiency leads to an accumulation of retinoids in adipose tissue and a drop of serum retinol and RBP4 during fasting, which affects retinoid-responsive gene expression in eye and kidney and lowers renal retinoid content. These findings establish a novel crosstalk between liver and adipose tissue retinoid stores for the maintenance of systemic vitamin A homeostasis during fasting. Synopsis: Fasting levels of retinol and its transport protein RBP4 in the circulation depend on the presence of HSL in adipocytes, uncovering a crosstalk between adipose tissue and systemic retinoid homeostasis. Fasting reduces hepatic retinyl ester hydrolase activity and induces an accumulation of RBP4 protein in liver in mice. Expression and secretion of RBP4 in hepatocytes are regulated by FOXO1 and cAMP. Global- or adipocyte-specific deletion of hormone-sensitive lipase (HSL) results in reduced circulating retinol and RBP4 levels during fasting. Adipocytes release retinol to extracellular retinol-free apo-RBP4 in an HSL-dependent manner. Adipocyte-specific deletion of HSL affects fasted retinoid homeostasis in peripheral organs like the kidney. Fasting levels of retinol and its transport protein RBP4 in the circulation depend on the presence of HSL in adipocytes, uncovering a crosstalk between adipose tissue and systemic retinoid homeostasis. [ABSTRACT FROM AUTHOR]

Background: Most studies have focused on comparing blood lipid biomarkers between Parkinson's disease (PD) and normal controls (NC). However, further research is necessary to explore the impact of blood lipid levels on motor and cognitive function, as well as the progression of motor dysfunction and cognitive decline over time. Thus, the aim of this study is to investigate the relationship between blood lipid biomarkers and these indicators in individuals with PD. Methods: The cohort study enrolled 157 PD patients and 146 NC from the Tianjin Huanhu Hospital from September 2017 to September 2019. Serum lipid fractions were detected in fasting serum samples. PD patients were followed up at 2 ± 0.6 years for clinical assessment. Results: PD patients exhibited lower serum triglyceride (TG) levels as compared to NC (P = 0.008). PD male patients exhibited lower serum lipoprotein cholesterol(LDL‐C) and total cholesterol (TC) levels than female patients (LDL‐C: P = 0.034; TC: P = 0.019). Serum TG levels correlated significantly with Unified PD Rating Scale III, Hoehn and Yahr stage and Montreal Cognitive Assessment scores in PD patients. Additionally, serum TG levels were associated with follow‐up motor function decline and cognitive decline in adjusted regression models in PD patients. Conclusions: To summarise, the study findings suggest that decreased serum TG levels are significantly associated with greater motor dysfunction, cognitive dysfunction and the greater deterioration of the two indicators. [ABSTRACT FROM AUTHOR]

Objective: Binge‐eating spectrum disorders (BESD) involve large eating episodes accompanied by a sense of loss of control that occur in individuals with body weights spanning the full body mass index (BMI) spectrum. While research links BESD with peripheral inflammation, this literature is limited by underpowered studies and a failure to control for confounding variables that could promote inflammation independent of dysregulated eating, specifically elevated body adiposity and depression. Our study examined plasma interleukin‐6 (IL‐6), a marker of peripheral inflammation, in a sample of women with BESD and non‐eating disorder controls, controlling for BMI, body adiposity, and depression. Method: Participants (N = 94) included women with BESD (n = 73) or no eating disorder (n = 21) who completed structured clinical interviews in a larger study, selected to represent BMI categories ranging from underweight to obese in both groups. Fasting blood samples were processed for plasma IL‐6 concentration via enzyme‐linked immunosorbent assays. In addition to assessing group differences in plasma IL‐6, exploratory analyses examined associations between IL‐6 and biological and clinical markers of BESD. Results: Significantly elevated plasma IL‐6 was found in women with BESD, relative to controls, that was not accounted for by BMI, adiposity, or depression. Plasma IL‐6 was positively correlated with plasma leptin concentration, clinical assessments of eating disorder severity, and participants' largest self‐reported eating episode. Discussion: Peripheral inflammation is specifically linked to presence of dysregulated eating independently from weight, adiposity, and depression in BESD. Future research should probe the potential role of neuroinflammation in altered eating behavior. Public Significance: This study provides the first demonstration that inflammation, characterized by elevated plasma IL‐6 concentration, is uniquely associated with dysregulated eating in a transdiagnostic group of individuals with BESD. A better understanding of whether immune factors contribute to dysregulated eating could help identify novel biological targets for intervention. [ABSTRACT FROM AUTHOR]

This paper examines the effect of religious fasting on truth‐telling using a laboratory experiment in Egypt. While fasting‐induced religiosity may promote truth‐telling, the physiological and psychological changes during fasting, due to alimentary abstention and self‐control exertion, may reduce honesty, especially when fasting is augmented with effort. We examine this question by tracing individual truth‐telling decisions, in the absence and presence of additional effort, both before and during Ramadan. We find that neither effort nor fasting alone affects honesty, but exerting effort while fasting reduces honesty. We provide suggestive evidence on the mechanisms potentially driving this negative effect on honesty. [ABSTRACT FROM AUTHOR]

This study aimed to assess the bioequivalence of 2 avapritinib tablets formulations. A randomized, open‐label, single‐center trial was conducted on fasting, healthy Chinese participants. The study utilized a partial replicated design with 3 sequences and 3 periods. Participants were assigned to 1 of 3 sequences, with each sequence receiving the reference formulation twice and the test formulation once. Plasma samples were collected and analyzed to determine pharmacokinetic parameters. The bioequivalence of the 2 avapritinib formulations was assessed using reference‐scaled average bioequivalence for the maximum plasma concentration (Cmax) and the average bioequivalence analysis for the area under the concentration‐time curve (AUC). Out of 39 participants, 38 completed the study. For Cmax, the 1‐sided 95% upper confidence interval (CI) bound from the scaled approach was −0.035 (<0) and the point estimate value was 0.958, falling inside the acceptance range of 0.8‐1.25. For both the AUC over all concentrations measured (AUC0‐t) and the AUC from time 0 to infinity (AUC0‐inf), the 90% CIs of geometric mean ratios (0.87‐1.01) also met the bioequivalence criteria of 0.8‐1.25. Consequently, the study demonstrated that the 2 avapritinib formulations were bioequivalent under fasting conditions. [ABSTRACT FROM AUTHOR]

Background: This study aims to analyze breast cancer burden attributable to high body mass index (BMI) and high fasting plasma glucose (FPG) in China from 1990 to 2019. Methods: Data were obtained from the Global Burden of Disease (GBD) study 2019. Deaths and disability‐adjusted life years (DALYs) were used for attributable burden, and age‐period‐cohort (APC) model was used to evaluate the independent effects of age, period and birth cohort. Results: In 2019, the age‐standardized mortality and DALY rates of breast cancer attributable to high BMI were 1.107 (95% UI: 0.311, 2.327) and 29.990 (8.384, 60.713) per 100 000, and mortality and DALY rates attributable to high FPG were 0.519 (0.095, 1.226) and 13.662 (2.482, 32.425) per 100 000. From 1990 to 2019, the age‐standardized mortality and DALY rates of breast cancer attributable to high BMI increased by 1.192% and 1.180%, and the trends of high FPG were not statistically significant. The APC results showed that the age effects of high BMI and high FPG‐mortality and DALY rates increased, with the highest rates in the age group over 80 years. The birth cohort effects of high BMI showed "inverted V" shapes, while high FPG showed downward trends. Conclusions: Age was the main reason for the increase of attributable burden, and postmenopausal women were the high‐risk groups. Therefore, targeted prevention measures should be developed to improve postmenopausal women's awareness and effectively reduce the prevalence of obesity and diabetes, thereby reducing the breast cancer burden caused by metabolic factors in China. [ABSTRACT FROM AUTHOR]

Aim: With increasing rates of global obesity and associated health issues, there is an ever‐increasing need for weight management solutions to be more accessible. Mobile applications offer accessible support systems and have the potential to offer a viable and effective weight management solution as an alternative to traditional healthcare models. Objective: To evaluate the effectiveness of the SIMPLE mobile application for time‐restricted eating in achieving weight loss (WL). Methods: User data were analyzed between January 2021 and January 2023. In‐app activity was calculated as the proportion of active days over 12, 26 and 52 weeks. A day is considered active if it contains at least one in‐app action (e.g., logging weight, food, fasting, or physical activity). Users were categorized into four in‐app activity levels: inactive (in‐app activity <33%), medium activity (33%–66%), high activity (66%–99%), and maximal activity (100%). Weight change among in‐app activity groups was assessed at 12, 26, and 52 weeks. Results: Out of 53,482 users, a positive association was found between the use of the SIMPLE app and WL. Active app users lost more weight than their less active counterparts. Active users had a median WL of 4.20%, 5.04%, and 3.86% at 12, 26, and 52 weeks, respectively. A larger percentage of active users—up to 50.26%—achieved clinically significant WL (≥5%) when compared to inactive users. A dose‐response relationship between WL and app usage was found after adjusting for gender, age, and initial Body Mass Index; a 10% increase in app activity correlated with increased WL by 0.43, 0.66 and 0.69 kg at 12, 26, and 52 weeks, respectively. Conclusions: The study demonstrates that the SIMPLE app enables effective WL directly associated with the level of app engagement. Mobile health applications offer an accessible and effective weight management solution and should be considered when supporting adults to lose weight. [ABSTRACT FROM AUTHOR]

Periods of fasting occur for a multitude of reasons in Atlantic salmon aquaculture. Feed withdrawal is widely used prior to transport, parasite treatments, preslaughter and for depuration purposes in recirculating aquaculture systems. Voluntary fasting is a coping response when fish have poor health or are exposed to poor farm environments. Owing to increased attention to animal welfare in aquaculture, concerns have been raised regarding ethical issues when farmed fish are subjected to fasting. However, thorough science‐based recommendations for fasting and feed‐withdrawal regimes have been lacking. The purpose of this review is to provide a synthesis of the various causes for fasting in Atlantic salmon aquaculture and evaluate their associated welfare implications so that guidelines for appropriate practices can be formulated. To interpret impacts, we describe biological responses and tolerance limits to fasting in Atlantic salmon and consider adaptations in the wild. Fry and parr are highly sensitive to feed withdrawal. However, post‐smolts and adults are well‐adapted to endure prolonged fasting without experiencing compromised functionality or health. Here, short periods of feed withdrawal prior to operations should therefore not constitute significant welfare concerns. Serious concerns are instead associated with voluntary fasting that may continue for weeks. We emphasize that environmental extremes that exceed appetite impairing thresholds must be avoided. Additionally, farmed fish should not be subjected to practices that lead to chronic stress that induce cessation of appetite. Diseases or parasites that impair appetite should also be mitigated. Fasting is here a symptom rather than a cause for poor welfare. [ABSTRACT FROM AUTHOR]

Background: Fasting before elective anesthesia care is a standardized practice worldwide. The aim is to decrease the risk of aspiration leading to pulmonary complications such as aspiration pneumonitis during anesthesia care. There are different guidelines for elective preoperative fasting in children. However, there is insufficient literature measuring gastric emptying time after breast milk or formula milk feeding in infants. Objective: This study used gastric ultrasound to determine the gastric emptying time for breast milk and formula milk in children below 6 months of age. We also compared the calculated gastric volumes among breast‐fed and formula milk‐fed based on Schmitz's and Spencer's formula. Materials and methods: This prospective observational study was conducted at a tertiary care center in India between November (2017–2019). A total of 52 infants less than 6 months of age were recruited. The study population was divided into two groups (breast‐fed and formula milk‐fed) of 26 patients each. Ultrasound was used to measure the antral cross‐sectional area of the stomach and to calculate the gastric volume using the two classical formulas (Schmitz and Spencer's). Gastric emptying was reported when the bull's eye appearance of the gastric antrum was seen or when the antral cross‐sectional area was less than 3.07 cm2. Results: The number of breast‐fed children whose antral cross‐sectional was greater than 3.07 cm2 (cut‐off value for aspiration risk) beyond 1 h was 14/26 (53.84%) while none (0) children went beyond 3 h. The number of formula‐fed children whose antral cross‐sectional was greater than 3.07 cm2 beyond 1 h was 17/26 (65.38%) while one child (3.84%) went beyond 3 h. Using Schmitz's formula, mean (SD) gastric emptying times were 0.35 ± 0.68 h (95% CI 0.35 ± 0.185, range 0.165–0.535) for breast‐fed patients and 0.35 ± 0.69 h (95% CI 0.35 ± 0.188, range 0.162–0.538) for formula‐fed patients, and were thus neither clinically nor statistically different (p =.73) Using Spencer's formula, the mean gastric emptying times were 0.12 ± 0.33 h (95% CI 0.12 ± 0.09, range 0.03–0.21) for breast‐fed patients and 0.04 ± 0.20 h (95% CI 0.04 ± 0.05, range −0.01 to 0.09) for formula‐fed patients, and were also neither clinically nor statistically different p =.13. Conclusion: In our series, the gastric emptying times in breast‐fed and formula‐fed infants less than 6 months old were similar. Our results support the fasting guidelines of the European Society of Anaesthesiology and Intensive Care 2022, that is, 3 h for breastfeeding and 4 h for formula milk feeding. In addition, this shows that the Schmitz's and Spencer's formulae used to calculate the gastric volume based on ultrasound measurement of the antral cross‐sectional area are not comparable in infants less than 6 months. [ABSTRACT FROM AUTHOR]

This first‐in‐human study evaluated the safety, tolerability, single‐ and multiple‐dose pharmacokinetic profiles with dietary influence, and pharmacodynamics (PD) of DFV890, an oral NLRP3 inhibitor, in healthy participants. In total, 122 participants were enrolled into a three‐part trial including single and 2‐week multiple ascending oral doses (SAD and MAD, respectively) of DFV890, and were randomized (3:1) to DFV890 or placebo (SAD [3–600 mg] and MAD [fasted: 10–200 mg, once‐daily or fed: 25 and 50 mg, twice‐daily]). DFV890 was generally well‐tolerated. Neither deaths nor serious adverse events were reported. A less than dose‐proportional increase in exposure was observed with the initially used crystalline suspension (3–300 mg); however, an adjusted suspension formulation using spray‐dried dispersion (SDD; 100–600 mg) confirmed dose‐proportional increase in exposure. Relative bioavailability between crystalline suspension and tablets, and food effect were evaluated at 100 mg. Under fasting conditions, Cmax of the tablet yielded 78% compared with the crystalline suspension, and both formulations showed comparable AUC. The fed condition led to a 2.05‐ and 1.49‐fold increase in Cmax and AUC0–last compared with the fasting condition. The median IC50 and IC90 for ex‐vivo lipopolysaccharide‐stimulated interleukin IL‐1β release inhibition (PD) were 61 (90% CI: 50, 70) and 1340 ng/mL (90% CI: 1190, 1490). Crystalline tablets of 100 mg once‐daily or 25 mg twice‐daily were sufficient to maintain ~90% of the IL‐1β release inhibition over 24 h at steady state. Data support dose and formulation selection for further development in diseases, in which an overactivated NLRP3 represents the underlying pathophysiology. [ABSTRACT FROM AUTHOR]

Objective: We investigated how changes in 24‐h respiratory exchange ratio (RER) and substrate oxidation during fasting versus an energy balance condition influence subsequent ad libitum food intake. Methods: Forty‐four healthy, weight‐stable volunteers (30 male and 14 female; mean [SD], age 39.3 [11.0] years; BMI 31.7 [8.3] kg/m2) underwent 24‐h energy expenditure measurements in a respiratory chamber during energy balance (50% carbohydrate, 30% fat, and 20% protein) and 24‐h fasting. Immediately after each chamber stay, participants were allowed 24‐h ad libitum food intake from computerized vending machines. Results: Twenty‐four‐hour RER decreased by 9.4% (95% CI: −10.4% to −8.5%; p < 0.0001) during fasting compared to energy balance, reflecting a decrease in carbohydrate oxidation (mean [SD], −2.6 [0.8] MJ/day; p < 0.0001) and an increase in lipid oxidation (2.3 [0.9] MJ/day; p < 0.0001). Changes in 24‐h RER and carbohydrate oxidation in response to fasting were correlated with the subsequent energy intake such that smaller decreases in fasting 24‐h RER and carbohydrate oxidation, but not lipid oxidation, were associated with greater energy intake after fasting (r = 0.31, p = 0.04; r = 0.40, p = 0.007; and r = −0.27, p = 0.07, respectively). Conclusions: Impaired metabolic flexibility to fasting, reflected by an inability to transition away from carbohydrate oxidation, is linked with increased energy intake. [ABSTRACT FROM AUTHOR]

This article explores the effects of different oral antidiabetic drugs (OADs) on the gut microbiota in patients with type 2 diabetes (T2D). The study found that acarbose and berberine had significant impacts on the gut microbiota, while metformin, vildagliptin, and glipizide did not. The baseline gut microbiota was found to be associated with the response to OAD treatment. However, the study acknowledges that there are variations in the reported gut microbial alterations due to factors such as ethnicity, sample size, and methodology. Further research is needed to fully understand the interactions between OADs and the gut microbiota and their potential impact on drug efficacy. [Extracted from the article]

Physical activity is consistently associated with better health and longer life spans. However, the extent to which length and intensity of exercise across the life course impact health outcomes relative to current activity is undefined. Participants of the Baltimore Longitudinal Study of Aging were asked to categorize their level of physical activity in each decade of life from adolescence to the current decade. In linear mixed effects models, self‐reported past levels of physical activity were significantly associated with activity assessed at study visits in the corresponding decade of life either by questionnaire or accelerometry. A pattern of life course physical activity (LCPA) derived by ranking participants on reported activity intensity across multiple decades was consistent with the trajectories of activity estimated from standard physical activity questionnaires assessed at prior study visits. In multivariable linear regression models LCPA was associated with clinical characteristics, measures of body composition and indicators of physical performance independent of current physical activity. After adjustment for minutes of high intensity exercise, LCPA remained significantly associated with peak VO2, fasting glucose, thigh muscle area and density, abdominal subcutaneous fat, usual gait speed, lower extremity performance, and multimorbidity (all p < 0.01) at the index visit. The observed associations suggest that an estimate of physical activity across decades provides complementary information to information on current activity and reemphasizes the importance of consistently engaging in physical activity over the life course. [ABSTRACT FROM AUTHOR]

To determine the pharmacokinetics (PK), safety, and bioequivalence profiles of 0.5‐g calcium dobesilate capsules in both fasting and fed states for the test drug and reference drug. A randomized‐sequence, single‐dose, open‐label, 2‐period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR202000268‐01). The fasting and fed studies, both involving 24 subjects, were conducted. A single dosage of either the reference or the test preparation was given to each eligible subject in a 1:1 ratio, followed by a 7‐day rest interval before the administration of the alternative formulation. After taking the capsules, plasma samples were taken for 48 hours, and using liquid chromatography‐tandem mass spectrometry, the calcium dobesilate level was determined. The PK parameters evaluated in the study included the maximum serum concentration (Cmax), area under the plasma concentration‐time curve (AUC) from time 0 to the last quantifiable concentration, AUC from time 0 to infinity, half‐life, time to Cmax, and terminal elimination rate constant. In addition, the safety evaluation encompassed monitoring fluctuations in vitals (temperature, pulse, and blood pressure) and laboratory tests (urinalysis, hepatic function, blood biochemistry, and hematology), as well as recording the emergence of adverse events (AEs). The geometric mean ratio (GMR) of the test/reference medications was used to assess bioequivalence by determining if the 90% confidence intervals of the GMR fell within the predefined range of 80%‐125%. AEs were assessed as safety end points. The study included 48 healthy Chinese volunteers (with n = 24 each for the fasting and the fed conditions), and no subjects dropped out for any reason. The differences in the PK metrics for the test and reference drugs for both conditions were insignificant (P >.05). For bioequivalence, irrespective of whether the food was consumed or not, the range of the 90% confidence intervals of the GMR for Cmax, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity was between 80% and 125%. In the experiment, no serious AEs were recorded. Our findings revealed that the calcium dobesilate capsules used as the reference and the test drugs were both bioequivalent. Irrespective of whether the healthy Chinese volunteers consumed food or not, the PK and safety profiles were comparable. [ABSTRACT FROM AUTHOR]

Nutrition profoundly influences the risk for many age‐related diseases. Whether nutrition influences human aging biology directly is less clear. Studies in different animal species indicate that reducing food intake ("caloric restriction" [CR]) can increase lifespan and delay the onset of diseases and the biological hallmarks of aging. Obesity has been described as "accelerated aging" and therefore the lifespan and health benefits generated by CR in both aging and obesity may occur via similar mechanisms. Beyond calorie intake, studies based on nutritional geometry have shown that protein intake and the interaction between dietary protein and carbohydrates influence age‐related health and lifespan. Studies where animals are calorically restricted by providing free access to diluted diets have had less impact on lifespan than those studies where animals are given a reduced aliquot of food each day and are fasting between meals. This has drawn attention to the role of fasting in health and aging, and exploration of the health effects of various fasting regimes. Although definitive human clinical trials of nutrition and aging would need to be unfeasibly long and unrealistically controlled, there is good evidence from animal experiments that some nutritional interventions based on CR, manipulating dietary macronutrients, and fasting can influence aging biology and lifespan. [ABSTRACT FROM AUTHOR]

Objective: Research on the natural course of symptoms of atypical anorexia nervosa (AN) relative to AN and bulimia nervosa (BN) is limited yet needed to inform nosology and improve understanding of atypical AN. This study aimed to 1) characterize trajectories of eating disorder and internalizing (anxiety, depression) symptoms in college students with and without a history of atypical AN, AN, and BN; and 2) compare sex and race/ethnicity distributions across groups. Method: United States college students who participated in Spit for Science™, a prospective cohort study, were classified as having a history of atypical AN (n = 125), AN (n = 160), BN (n = 617), or as non‐eating‐disorder controls (NCs, n = 5876). Generalized and linear mixed‐effects models assessed group differences in eating and internalizing symptom trajectories, and logistic regression compared groups on sex and race/ethnicity distributions. Results: Atypical AN participants demonstrated elevated eating disorder and internalizing symptoms compared to NCs during college, but less severe symptoms than AN and BN participants. Although all eating disorder groups showed signs of improvement in fasting and driven exercise, purging and depression remained elevated. Atypical AN participants showed increasing anxiety and stable binge‐eating trajectories compared to AN and/or BN participants. The atypical AN group comprised significantly more people of color than the AN group. Discussion: Findings underscore that atypical AN is a severe psychiatric disorder. As atypical AN may present as less severe than AN and BN and disproportionately affects people of color, clinicians should be mindful of biases that could delay diagnosis and care. Public Significance: College students with histories of atypical AN, AN, and BN demonstrated improvements in fasting and driven exercise and stable purging and depression levels. Atypical AN students showed worsening anxiety and stable binge‐eating trajectories compared to favorable changes among AN and BN students. A higher percentage of atypical AN (vs. AN) students were people of color. Findings may improve the detection of atypical AN in college students. [ABSTRACT FROM AUTHOR]

Background: Ramadan fasting is an obligatory religious practice for Muslims. However, research data on the effect of Ramadan on idiopathic intracranial hypertension (IIH) symptoms are lacking. This study aimed to study the effect of Ramadan fasting on the severity of headache and visual symptoms and related quality‐of‐life activities. Methods: This prospective cohort study targeted females diagnosed with IIH (n = 102) who were eligible to fast for Ramadan in 2023. The patients were recruited from the Neurology Clinic in Beni‐Suef University Hospital, Egypt. Body mass index (BMI), monthly headache days and intensity of headache attacks, six‐item Headache Impact Test (HIT‐6), and the 25‐item National Eye Institute Visual Function Questionnaire (NEI‐VFQ‐25) scores during Ramadan were compared to those during the (non‐fasting) month of Shaaban, the preceding month to Ramadan. Results: There was a significant increase in the BMI of patients with IIH in Ramadan compared to the (non‐fasting) month of Shaaban, at a median (interquartile range [IQR]) of 30.5 (26.6–35.8) kg/m2 and 30.1 (26.6–35.2) kg/m2, respectively (p = 0.002). The median (IQR) value of monthly headache days was significantly increased during Ramadan in comparison to the (non‐fasting) month of Shaaban, at 20 (11.5–30) vs. 15 (10–25) (p < 0.001). There was a statistically significant worsening in the visual analog scale (VAS) scores (median [IQR] 7 [5–8] vs. 6.5 [5–8]), HIT‐6 scores (median [IQR] 61 [58–67] vs. 59 [53–61.5]), and NEI‐VFQ‐25 total scores (median [IQR] 1312.5 [1238.8–1435] vs 1290 [1165–1417.5]) during Ramadan in comparison to the (non‐fasting) month of Shaaban (p < 0.001 for all comparisons). The change in BMI in Ramadan was positively correlated with the change in monthly headache days (r = 0.24, p = 0.014), VAS (r = 0.20, p = 0.043), HIT‐6 (r = 0.25, p = 0.010) and NEI‐VFQ‐25 scores (r = 0.24, p = 0.016). Conclusion: Ramadan fasting had an aggravating effect on headache, visual symptoms, and related quality‐of‐life activities, which might be attributed to weight gain during this month. Whether proper nutritional management to prevent weight gain during Ramadan may help mitigate this worsening effect is a mission of future studies. Plain Language Summary: Ramadan fasting is a religious practice for Muslims. We studied patients with idiopathic intracranial hypertension (IIH) and found that fasting made headache and visual symptoms worse in patients with IIH and this might be attributed to weight gain during this month. Physicians should discuss the potential effect of fasting during the month of Ramadan with patients who have IIH and provide culturally sensitive nutritional counseling regarding maintaining body weight during this month. [ABSTRACT FROM AUTHOR]

Changes in diet type and nutrient availability can impose significant environmental stress on organisms, potentially compromising physiological functions and reproductive success. In nature, dramatic fluctuations in dietary resources are often observed and adjustments to restore cellular homeostasis are crucial to survive this type of stress. In this study, we exposed male Drosophila melanogaster to two modulated dietary treatments: one without a fasting period before exposure to a high‐fat diet and the other with a 24‐h fasting period. We then investigated mitochondrial metabolism and molecular responses to these treatments. Exposure to a high‐fat diet without a preceding fasting period resulted in disrupted mitochondrial respiration, notably at the level of complex I. On the other hand, a short fasting period before the high‐fat diet maintained mitochondrial respiration. Generally, transcript abundance of genes associated with mitophagy, heat‐shock proteins, mitochondrial biogenesis, and nutrient sensing pathways increased either slightly or significantly following a fasting period and remained stable when flies were subsequently put on a high‐fat diet, whereas a drastic decrease of almost all transcript abundances was observed for all these pathways when flies were exposed directly to a high‐fat diet. Moreover, mitochondrial enzymatic activities showed less variation after the fasting period than the treatment without a fasting period. Overall, our study sheds light on the mechanistic protective effects of fasting prior to a high‐fat diet and highlights the metabolic flexibility of Drosophila mitochondria in response to abrupt dietary changes and have implication for adaptation of species to their changing environment. [ABSTRACT FROM AUTHOR]

The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open‐label, single‐dose, 2‐period, 2‐sequence crossover, single‐center, randomized phase I clinical trial. T and R were considered bioequivalent if the adjusted geometric mean ratios (GMRs) and 90% confidence intervals of the area under the curve (AUC) and maximum concentration (Cmax) were within the range of 0.8‐1.25. Thirty‐five participants completed the trial. The T/R adjusted GMRs (95.7% for Cmax, 98.7% for AUC0→t, 98.8% for AUC0→∞) were within the acceptable bioequivalence range of 80%‐125%. No serious adverse events or suspected or unexpected serious adverse reactions occurred during this trial. The study findings confirmed that generic MH is a well‐tolerated and bioequivalent alternative to innovative products under fasting conditions in healthy Chinese participants. (www.chinadrugtrials.org.cn; registration no. CTR20190356) [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the blood concentration and pharmacokinetic (PK) parameters of 2 formulations under fasting and ed conditions in healthy Chinese volunteers and to evaluate whether the 2 preparations were bioequivalent. This trial screened 170 subjects. Thirteen subjects were assigned to the fasting trial and 18 subjects to the fed trial; 1 subject in the fed trial group was automatically withdrawn for personal reasons. Two cycles had a 14‐day washout period. This clinical study was a bioequivalence study, with PK parameters as end point indicators. The bioequivalence PK parameters were the maximal concentration (Cmax), area under the blood drug concentration‐time curve from 0 to 72 hours (AUC0‐72 h), and the time to peak plasma concentration (tmax) which were determined in human plasma by the liquid chromatography‐tandem mass spectrometry method, and nonatrioventricular model analysis was used to determine Cmax, AUC0‐72 h, tmax, and other PK parameters. The incidence of adverse events was calculated on the basis of System Organ Classification and Preferred Terms. The results showed that the amlodipine besylate tablets met the equivalence range requirements of bioequivalence in the guidelines for human bioavailability and bioequivalence testing under fasting and fed conditions, compared to the fasting test; the tmax of the fed test was almost unchanged; and the Cmax and AUC0‐72 h showed no difference between fasting and fed conditions. It was confirmed that both formulations were well tolerated, and no new safety signals were observed. [ABSTRACT FROM AUTHOR]

Starvation resistance is a life-saving mechanism for many organisms facing food availability fluctuation in the natural environment. Different strategies have been episodically identified for some model organisms, the first of which was the ability to suppress metabolic rate. Among the identified strategies, the ability of planarians to shrink their body under fasting conditions and revert the process after feeding (the growth-degrowth process) represents a fascinating mechanism to face long periods of fasting. The growth-degrowth process is strictly related to the capability of planarians to continuously maintain tissue homeostasis and body proportions even in challenging conditions, thanks to the presence of a population of pluripotent stem cells. Here, we take advantage of several previous studies describing the growth-degrowth process and of recent progress in the understanding of planarian homeostasis mechanisms, to identify tissueselective transcriptional downregulation as a driving strategy for the development of a thrifty phenotype, and the p53 transcription factor as a player in adjusting tissue homeostasis in accordance with food availability. [ABSTRACT FROM AUTHOR]

Objective: Nonresponsive parental feeding practices are associated with poorer appetite self‐regulation in children. It is unknown whether this relationship extends beyond childhood to be prospectively associated with the onset of eating disorder (ED) symptoms in adolescence. This exploratory study therefore investigated prospective associations between early childhood parental feeding practices and adolescent ED symptoms and disordered eating behaviors. Methods: Data were from two population‐based cohorts with harmonized measures: Generation R (Netherlands; n = 4900) and Gemini (UK; n = 2094). Parents self‐reported their pressure to eat, restriction and instrumental feeding (i.e., using food as a reward) at child age 4–5 years. Adolescents self‐reported their compensatory behaviors (e.g., fasting, purging), binge‐eating symptoms, restrained eating, uncontrolled eating, and emotional eating at 12–14 years. Associations between feeding practices and ED symptoms were examined separately in each cohort using generalized linear models. Results: In Gemini, pressure to eat in early childhood was associated with adolescents engaging in compensatory behaviors. In Generation R, parental restriction was associated with adolescents engaging in compensatory behaviors, restrained eating, uncontrolled eating, and emotional eating. Instrumental feeding was associated with uncontrolled eating and emotional eating in Generation R. Discussion: Nonresponsive parental feeding practices were associated with a greater frequency of specific ED symptoms and disordered eating in adolescence, although effect sizes were small and findings were inconsistent between cohorts. Potentially, the cultural and developmental context in which child–parent feeding interactions occur is important for ED symptoms. Further replication studies are required to better understand parents' role in the development and maintenance of ED‐related symptoms. Public Significance: Prospective research examining how early childhood parental feeding practices might contribute to adolescent ED symptoms is limited. In two population‐based cohorts, nonresponsive feeding practices (restriction, instrumental feeding, pressure to eat) predicted increased frequency of some ED symptoms and disordered eating behaviors in adolescence, although associations were small and further replication is required. Findings support the promotion of responsive feeding practices, which may benefit young children's developing relationship with food. [ABSTRACT FROM AUTHOR]

Ketogenic diets (KD) have been used in the treatment of epilepsy in humans for around a century and, more recently, they have been implanted for cancer patients, as well as in the treatment of obesity. This type of diet consists of high‐fat levels, an adequate amount of protein and restricted carbohydrates, or high medium‐chain triglycerides. Recently, the ketogenic diet has gained attention in veterinary medicine and studies were published evaluating the effects of KD in dogs with epilepsy. The objective of this review was to highlight recent studies about the application of KD in dogs and cats, to describe the neurobiochemical mechanisms through which KD improves epilepsy crisis, and their adverse effects. Studies were identified by a systematic review of literature available on PubMed, Embase, and Scopus. All cohort and case‐control studies were included, and all articles were exported to Mendeley® citation manager, and duplicates were automatically removed. Seven articles and three conference abstracts conducted with dogs were included in the present study. There is evidence that the consumption of diets with medium‐chain triglycerides increases the concentration of circulating ketone bodies and improves epilepsy signs, although these diets have higher carbohydrate and lower fat content when compared to the classic KD. [ABSTRACT FROM AUTHOR]

This meta-analysis compared the effectiveness of different energy-restricted diets on body composition, glucose metabolism, and lipid metabolism in overweight and obese populations. Five databases were searched to identify relevant studies in English from inception until July 20, 2023, for randomized controlled trials of at least 2 weeks duration assessing the effects of continuous energy-restricted diets compared with any intermittent energy-restricted diet in obesity adults. The risk of bias was assessed using the Cochrane Risk of Bias Tool version 2.0, while the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to assess the certainty of the evidence. A non-informative prior distribution Bayesian network meta-analysis was conducted. Thirty-eight studies (3039 participants) assessing four energy-restricted diets were included. Three RCTs were at high risk of bias with a very low to moderate certainty of evidence. Combined with pair-wise comparisons and surface under the cumulative ranking curve, alternate-day fasting may be the best energy restriction regimen with the potential to have the most beneficial effects on various aspects of the obesity population. More rigorously designed and long-term follow-up studies are warranted. [ABSTRACT FROM AUTHOR]

Aims: In this study, we assessed the effects of a 12‐week combined aerobic–resistance training and subsequent detraining on Beck Depression Inventory (BDI) score and mediating role of BDNF and also investigated whether exercise‐induced alterations are maintained following a short period of detraining in women with type 2 diabetes (T2D). Materials and Methods: Thirty‐four women with T2D were randomly assigned to experimental or control group (age: 60.6 ± 6.3, body mass index (BMI): 30.2 ± 1.3 kg/m2, HbA1c: 8.09 ± 0.73%). The exercise training comprised of combined aerobic–resistance programme (50%–70% heart rate reserve for aerobic exercise, and 50%–70% 1 repetition maximum for resistance exercise, respectively) performed three sessions per week over 12 weeks. The intervention period was followed by an 8‐week detraining period. Data were collected at baseline and also following exercise intervention and detraining. Data were analysed by linear mixed model at p < 0.05. Results: After 12 weeks of combined exercise training and 8 weeks of detraining, there was a significant difference in BDNF (0.08; 95% confidence interval [CI] = 0.07–0.10; p = 0.001), fasting blood glucose (FBG) (−45.41; CI = −50.83, ‐39.98; p = 0.001), insulin (−6.47; CI = −7.04, −5.9; p = 0.001), HOMA‐IR (−3.76; CI = −4.07, −3.45; p = 0.001) and BDI score (−17.17; CI = −20.29, −14.05; p = 0.001) between the experimental and control group. Multiple mediation analysis indicated that BDNF seems to have a mediating role in exercise‐induced improvement of depression (p = 0.04). After the detraining period, BDI score remained unchanged and it showed a significant increase compared to before the start of training (p = 0.001). Conclusions: It may be concluded that exercise training improves depression that is likely to be explained by increased BDNF concentration in TD2. In spite of decreased BDNF concentration following an 8‐week detraining, depression score was maintained. [ABSTRACT FROM AUTHOR]

This study aimed to restructure beef tallow‐milk‐vegetable oils blends through the chemical and enzymatic interesterifications and to analyze some properties of interesterified lipids including peroxide value, free fatty acid and mono‐di‐triacylglycerol contents, fatty acid profile, and slip melting point. Moreover, the mid‐infrared spectra of the samples were obtained using Fourier transform infrared spectroscopy. The monounsaturated and polyunsaturated fatty acid contents of beef tallow increased by blending and interesterification reactions. The free fatty acid content of the enzymatically interesterified lipids was higher than that of the chemically interesterified fats. The slip melting point of the structured fats decreased after both blending and interesterification. A statistical model showed that infrared spectra combined with analytical data could discriminate the interesterified lipids from binary and ternary blends. It was found out that a 15% milk and 40% vegetable oil ratio in the initial blends yielded as end products which could be an alternative product of butterfat in the bakery industry after chemical interesterification. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of psychotropic medication prescription use in youth has increased over the past several years. Despite recommendations and practice parameters established by the American Diabetes Association‐American Psychiatric Association (ADA‐APA) outlining metabolic monitoring of patients prescribed second‐generation antipsychotic (SGA) medication, monitoring adherence for the pediatric patient population remains inadequate. Aims: This project aimed to improve metabolic monitoring of pediatric patients prescribed SGAs and discharge recommendations for follow‐up monitoring within a small, child, and adolescent psychiatric hospital. Methods: This project compared metabolic monitoring adherence rates pre and postimplementation of a metabolic monitoring organizational policy developed to provide procedural guidance, using ADA‐APA guidelines. Participants included prescribing clinicians (physicians and psychiatric nurse practitioners). Results: Phase 1 chart reviews found no records of fasting blood glucose, fasting lipid profile or waist circumference. Following project implementation, chart review found that fasting blood glucose and fasting lipid profile was recorded in 21 (72.4%) of the charts, and waist circumference was recorded in 18 (62.1%) of the charts for patients prescribed SGA medication. For patients discharged on an SGA, written recommendations for follow‐up metabolic monitoring improved from 13% to 70% (<0.001). Conclusions: Implementing an organizational metabolic monitoring policy and protocol can improve clinician adherence to ADA‐APA guidelines for recording in‐patient monitoring of metabolic parameters and discharge recommendations for pediatric patients prescribed SGA medication. [ABSTRACT FROM AUTHOR]

Aim: To determine whether glucose volume of distribution (VdGLUCOSE) affects the diagnosis of impaired insulin sensitivity (IS) when using an intravenous glucose tolerance test (IVGTT). Methods: Individuals with distinct levels of IS underwent IVGTT after an overnight fast. The prediabetic group (Prediab; n = 33) differed from the healthy group (Healthy; n = 14) in their larger glycosylated hemoglobin (HbA1c of 5.9 ± 0.3 vs. 5.4 ± 0.1%; 41 ± 4 vs. 36 ± 1 mmol/mol; p < 0.001), percent body fat (37 ± 6 vs. 24 ± 3%; p < 0.001) and cardiovascular fitness level (VO2MAX 22 ± 5 vs. 44 ± 5 mL of O2·kg−1·min−1; p < 0.001). Ten minutes after intravenous infusion of the glucose bolus (i.e., 35 g in a 30% solution), VdGLUCOSE was assessed from the increases in plasma glucose concentration. IS was calculated during the next 50 min using the slope of glucose disappearance and the insulin time‐response curve. Results: VdGLUCOSE was higher in Healthy than in Prediab (230 ± 49 vs. 185 ± 21 mL·kg−1; p < 0.001). VdGLUCOSE was a strong predictor of IS (β standardized coefficient 0.362; p = 0.004). VO2MAX was associated with VdGLUCOSE and IS (Pearson r = 0.582 and 0.704, respectively; p < 0.001). However, body fat was inversely associated with VdGLUCOSE and IS (r = −0.548 and −0.555, respectively; p < 0.001). Conclusions: Since fat mass is inversely related to VdGLUCOSE and in turn, VdGLUCOSE affects the calculations of IS, the IV glucose bolus dose should be calculated based on fat‐free mass rather than body weight for a more accurate diagnosis of impaired IS. [ABSTRACT FROM AUTHOR]