Search Results (56)

The impact of prolonged fasting on human oxidative stress (OS) levels and antioxidant defence mechanisms remains poorly understood. The aim of this current study was to investigate the redox response to a 6-day fast in a cohort of healthy men. Twenty-six participants were randomly allocated to a 6-day complete fasting or a control trial. Sympathetic activity, substrate oxidation, redox status, blood glucose, ketones, and testosterone concentrations were assessed. Throughout the fasting period, ketone concentration and fat oxidation increased, and carbohydrate oxidation and glucose and testosterone concentrations decreased. Heart rate increased on fasting days 2 and 4 and returned to the pre-fasting level on fasting day 6. Malondialdehyde (MDA) concentration increased after fasting days 4 and 6, and this increase was accompanied by an increase in the total antioxidant capacity (TAC), but the TAC/MDA ratio remained constant. Notably, all fasting-evoked changes returned to the baseline values after resumption of the regular diet. Thus, prolonged fasting activated both antioxidant defence and OS, but the redox balance was maintained. Consistent with this response, ketone concentration and sympathetic nervous system activity increased, and testosterone concentration decreased. These variables returned to the pre-fasting state after resumption of the usual eating habits. Full article

Fasting–feeding timing is a crucial pattern implicated in the regulation of daily circadian rhythms. The interplay between sleep and meal timing underscores the importance of maintaining circadian alignment in order to avoid creating a metabolic environment conducive to carcinogenesis following the molecular and systemic disruption of metabolic performance and immune function. The chronicity of such a condition may support the initiation and progression of cancer through a variety of mechanisms, including increased oxidative stress, immune suppression, and the activation of proliferative signaling pathways. This review aims to summarize current evidence from human studies and provide an overview of the potential mechanisms underscoring the role of chrononutrition (including time-restricted eating) on cancer risk. Current evidence shows that the morning chronotype, suggesting an alignment between physiological circadian rhythms and eating timing, is associated with a lower risk of cancer. Also, early time-restricted eating and prolonged nighttime fasting were also associated with a lower risk of cancer. The current evidence suggests that the chronotype influences cancer risk through cell cycle regulation, the modulation of metabolic pathways and inflammation, and gut microbiota fluctuations. In conclusion, although there are no clear guidelines on this matter, emerging evidence supports the hypothesis that the role of time-related eating (i.e., time/calorie-restricted feeding and intermittent/periodic fasting) could potentially lead to a reduced risk of cancer. Full article

Background/Objectives: Despite standard preoperative fasting guidelines, residual gastric content can persist in some patients, increasing the risk of aspiration pneumonitis. Multiple patient-specific factors may predict gastric content retention, but their predictive accuracy is limited. We hypothesized that ultrasound would more reliably identify residual gastric content compared to a comprehensive questionnaire and aimed to determine the most practical approach for risk assessment in elective surgical patients. Methods: We conducted a prospective, observational study in adult patients scheduled for elective surgery at a single center. All participants adhered to an 8 h fasting period. The primary outcome was the incidence of a “full stomach” on ultrasound. Secondary outcomes included the Perlas risk classification, comparisons of established volume estimation formulas, correlations with self-reported fasting duration, agreement between questionnaire-based predictions and ultrasound findings, and the time efficiency of each method. Multivariable logistic regression and Cohen’s kappa were used for analyses. Results: Data from 404 patients were analyzed. Despite prolonged fasting, 16.3% had a full stomach by ultrasound, suggesting incomplete gastric emptying. Early satiety and cholelithiasis significantly predicted a full stomach; prolonged fasting duration and female sex were protective. Questionnaire-based predictions demonstrated fair agreement with ultrasound (kappa = 0.327). The Michiko formula often yielded negative volumes, highlighting limitations in volume estimations. Ultrasound examination (3 min median) was faster than questionnaire completion (5 min). Conclusions: Ultrasound accurately detects residual gastric content, outperforming questionnaire-based assessments. Integrating it into routine preoperative evaluation may improve patient safety, although research is needed to refine volume estimation formulas and expand feasibility for patients with positioning limitations. Full article

Importance: Although prolonged fasting has become increasingly popular, the favourable biological adaptations and possible adverse effects in humans have yet to be fully elucidated. Objective: To investigate the effects of a three-day water-only fasting, with or without exercise-induced glycogen depletion, on autophagy activation and the molecular pathways involved in cellular damage accumulation and repair in healthy humans. Design: A randomised, single-centre, two-period, two-sequence crossover trial. The primary outcome is autophagic activity, assessed as flux in peripheral blood mononuclear cells (PBMCs) measured in the context of whole blood. Secondary outcomes include changes in body composition, heart rate variability, endothelial function, and genomic, epigenomic, metabolomic, proteomic, and metagenomic adaptations to fasting in plasma, platelets, urine, stools, and PBMCs. Detailed profiling of circulating immune cell populations and their functional states will be assessed by flow cytometry. Setting: All clinical investigations will be undertaken at the Charles Perkins Centre Royal Prince Alfred Hospital clinic, University of Sydney, Australia. Participants: Twenty-four individuals aged 18 to 70 years, with a BMI of 20–40 kg/m², free of major health conditions other than obesity. Discussion: While autophagic flux induction through fasting has garnered interest, there is a notable lack of human studies on this topic. This trial aims to provide the most detailed and integrated analysis of how three days of prolonged water-only fasting, combined with glycogen-depleting exercise, affects autophagy activation and other crucial metabolic and molecular pathways linked to cellular, metabolic, and immune health. Insights from this study may pave the way for safe and effective strategies to induce autophagy, offering potential preventive interventions for a range of chronic conditions. Full article

Background: Exogenous melatonin, a nutraceutical for maintaining a healthy sleep–wake cycle and managing sleep disorders, requires large, repeated doses due to its low bioavailability and short half-life. This necessitates the development of a sustained-release formulation with a longer half-life and sustained plasma concentration. Therefore, exogenous novel 5 mg sustained-release melatonin capsules (Melatonin-SR, test product) were formulated. Methods: This open-label cross-over study compared the pharmacokinetics (maximum concentration [C_max], time to reach C_max [T_max], area under the curve [AUC], and elimination half-life [t_1/2]) and the safety of Melatonin-SR with 5 mg immediate-release melatonin capsules (Melatonin-IR, reference product) after single-dose oral administration in healthy fasting adults. Results: Sixteen participants (aged 18–45 years) were randomized (1:1) to receive either Melatonin-SR or Melatonin-IR in two periods with a 7-day washout period. Melatonin-SR reported a lower C_max (11,446.87 pg/mL) compared to Melatonin-IR (22,786.30 pg/mL). The mean T_max of Melatonin-SR and Melatonin-IR was 1.26 h and 0.87 h, respectively. The mean t_1/2 of Melatonin-SR (5.10 h) was prolonged by five-fold compared to Melatonin-IR (1.01 h). One adverse event (vomiting) was reported following the administration of the Melatonin-IR. Conclusions: Melatonin-SR resulted in higher and sustained plasma melatonin concentrations for an extended period and was well-tolerated. Hence, Melatonin-SR may be a promising nutraceutical for maintaining healthy sleep. Full article

Tadalafil (TD) has poor water solubility but is well absorbed without affecting food intake when administered orally. Owing to patient adherence and therapeutic characteristics, a TD-loaded orodispersible film (TDF) is preferable. However, the mechanistic role of dietary status on the clinical pharmacokinetic analysis of TDF in human volunteers should be investigated because the gastrointestinal environment varies periodically according to meal intervals, although commercial 20 mg TD-loaded tablets (TD-TAB, Cialis^® tablet) may be taken with or without food. TDF was prepared by dispersing TD in an aqueous solution and polyethylene glycol 400 to ensure good dispersibility of the TD particles. In the fasting state, each T/R of Cmax and AUC between TD-TAB and TDF showed bioequivalence with 0.936–1.105 and 1.012–1.153, respectively, and dissolution rates in 1000 mL water containing 0.5% SLS were equivalent. In contrast, TDF was not bioequivalent to TD-TAB under the fed conditions by the C_max T/R of 0.610–0.798. The increased dissolution rate of TDF via the micronization of drug particles and the reduced viscosity of the second meal content did not significantly affect the bioequivalence. Interestingly, an increase in second meal intake time from 4 h to 6 h resulted in the bioequivalence by the Cmax T/R of 0.851–0.998 of TD-TAB and TDF. The predictive diffusion direction model for physical digestion of TD-TAB and TDF in the stomach after the first and second meal intake was successfully simulated using computational fluid dynamics modeling, accounting for the delayed drug diffusion of TDF caused by prolonged digestion of stomach contents under postprandial conditions. Full article

(1) Background: The benefits of weight management are widely recognized, and prolonged fasting duration has become a common method for weight control. The suitability of time-restricted eating (TRE) for elderly individuals remains controversial. This study aims to examine the correlation between fasting duration and mortality within a nationally representative cohort of elderly individuals in the United States. (2) Methods: Data were extracted from a prospective cohort study conducted as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Participants aged over 60 with complete data on dietary intake and mortality follow-up information were included. Fasting duration was assessed using two 24 h dietary recalls. All the participants were categorized into fasting duration quartiles. Mortality outcomes were ascertained through the National Death Index. Cox proportional hazards regression models were utilized to analyze the association between fasting duration and mortality. (3) Results: The final analysis included 10,561 elderly participants (mean age 69.89, 45.58% male). Individuals with the longest fasting duration (over 12.38 h) had a significantly higher risk of CVD mortality compared to those with a normal fasting duration (10.58–12.38 h). This elevated CVD mortality risk was particularly pronounced in males, individuals over 70 years old, and non-shift workers. A non-linear relationship was observed between fasting duration and all-cause mortality and CVD mortality. (4) Conclusions: Prolonged fasting periods are associated with a higher risk of CVD mortality in the elderly population, although this correlation is not evident for all-cause, cancer, or other-cause mortality. A fasting duration of 11.49 h correlates with the lowest mortality risk. Additionally, elderly individuals with the shortest fasting duration exhibit elevated hazard ratios for both cancer and other-cause mortality. As with any health intervention, clinicians should exercise caution when recommending a fasting regimen that is personalized to the health condition of people who are older. Further research through randomized controlled trials should be conducted to comprehensively investigate the impact of TRE on mortality. Full article

Fibromyalgia syndrome (FMS) is a common chronic pain disorder and often occurs as a concomitant disease in rheumatological diseases. Managing FMS takes a complex approach and often involves various non-pharmacological therapies. Fasting interventions have not been in the focus of research until recently, but preliminary data have shown effects on short- and medium-term pain as well as on physical and psychosomatic outcomes in different chronic pain disorders. This single-arm observational study investigated the effects of prolonged fasting (3–12 days, <600 kcal/d) embedded in a multimodal treatment setting on inpatients with FMS. Patients who were treated at the Department of Internal Medicine and Nature-Based Therapies of the Immanuel Hospital Berlin, Germany, between 02/2018 and 12/2020 answered questionnaires at hospital admission (V0) and discharge (V1), and then again three (V2), six (V3), and 12 (V4) months later. Selected routine blood and anthropometric parameters were also assessed during the inpatient stay. A total of 176 patients with FMS were included in the study. The Fibromyalgia Impact Questionnaire (FIQ) total score dropped by 13.7 ± 13.9 (p < 0.001) by V1, suggesting an improvement in subjective disease impact. Pain (NRS: reduction by 1.1 ± 2.5 in V1, p < 0.001) and quality of life (WHO-5: +4.9 ± 12.3 in V1, p < 0.001) improved, with a sustainable effect across follow-up visits. In contrast, mindfulness (MAAS: +0.3 ± 0.7 in V1, p < 0.001), anxiety (HADS-A: reduction by 2.9 ± 3.5 in V1, p < 0.0001), and depression (HADS-D: reduction by 2.7 ± 3.0 in V1, p < 0.0001) improved during inpatient treatment, without longer-lasting effects thereafter. During the study period, no serious adverse events were reported. The results suggest that patients with FMS can profit from a prolonged therapeutic fasting intervention integrated into a complex multimodal inpatient treatment in terms of quality of life, pain, and disease-specific functional parameters. ClinicalTrials.gov Identifier: NCT03785197. Full article

Weather has significant impact on plant growth and development. It is important to analyze the influence of changing climate conditions on the expression of plant agronomic characters. Two flax varieties were grown from 1987 to 2018 in the Northwest of Russia. Weather conditions and their influence on flax agronomic characters were analyzed using the variance and correlations analyses. Significant influence of conditions of a particular year on the manifestation of all evaluated characters was revealed. Starting from June, high temperatures accelerate plant development at all stages. Prolongation of the germination-flowering period is most important for improving fiber productivity, while fast ripening in hot weather after flowering is preferable for the formation of high-quality fiber. Such data give a possibility to predict the yield amount and quality. The use of weather conditions data also makes possible a comparison of the results obtained in different years. The suggested method of classifying meteorological conditions of a year can be used in other genebanks for systematizing and analyzing the results of crop evaluation in the field. The correlation analysis revealed 3 correlated pleiades, namely (1) of productivity, (2) of fiber quality and yield, and (3) of the growing season phase durations, the sums of active temperatures and precipitation during each period. The great influence of growing conditions on the economically valuable traits indicates the necessity of searching for genotypes with stable character manifestations for breeding new varieties with stable yields and good fiber quality. Full article

Fish can tolerate prolonged periods of fasting more easily than endothermic organisms. However, these fasting periods are associated with pronounced lipid and protein catabolism and body weight loss. We evaluated the use of body reserves, growth performance, and the histology of the intestines and muscles of Colossoma macropomum subjected to prolonged fasting for 45 days and refeeding for 14 days. We used 66 juvenile C. macropomum (71.78 ± 10.75 g) distributed in 10 tanks of 100 L in a recirculating aquaculture system (RAS) and kept 6 fish in a separate tank, considered the basal group. The fish were divided into two groups: fed (continuously fed for 59 days) and fasted/refed (subjected to fasting for 45 days and subsequently refed for 14 days). The tambaqui juveniles showed the mobilization of their body reserves during 45 days of fasting but with a large deficit in their growth performance. The 14-day refeeding period was sufficient for fish to restore their energy but insufficient for recovering most growth parameters. Full article

Background: Malnutrition is usual in patients referred for endoscopic gastrostomy (PEG). Refeeding syndrome is rarely observed in PEG-fed patients, which could possibly be associated with reduced absorption induced by prolonged starvation. Objective: In patients submitted to PEG after a significant period of fasting, the present study aims to: 1. evaluate the histological/ultrastructural initial changes in the intestinal mucosa, potentially associated with reduced absorption, and 2. assess if these changes could reverse with enteral refeeding. Methods: The present study is an observational, prospective, controlled study. Adult patients with ingestion below 50% of daily needs for at least one month and/or diagnosis of malnutrition were enrolled. Duodenal biopsies were taken at baseline and after 3–6 months of PEG feeding, which then underwent histological/ultrastructural analysis. Random healthy individuals were used as controls. Results: A total of 30 patients (16 men/14 women) aged 67.1 ± 13.5 years were included. Malnutrition was found in 40% of patients. Approximately 14 patients completed follow-up during both periods (46.7%). At baseline: duodenal mucosal atrophy was evident in three patients (10%); the median villi length (MVL) was 0.4 mm (0.25–0.6 mm), with it being shorter than the controls, which was 0.6 mm (0.4–0.7 mm) (p = 0.006); ultrastructural changes included focal shortening, bending, and disruption of enterocyte microvilli, the presence of citoplasmatic autophagic vacuoles, dilation and vesiculation of the smooth endoplasmic reticulum, and the presence of dilated intercellular spaces with basement membrane detachment. After refeeding, most patients displayed normal histology (92.9%) and increase MVL (p < 0.001), ultrastructural changes disappeared, and enterocytes resumed a normal appearance, although retaining scarce, small, dense bodies in apical regions from the evolution of previous autophagy. Conclusions: Prolonged fasting induces histological and ultrastructural changes in the intestinal mucosa that may reflect impaired absorption in the early post-PEG period. These changes were reverted after refeeding with enteral nutrition. Full article

Despite the advancements in evidence-based medicine, many hospitals still maintain high rates of patients undergoing prolonged preoperative fasting. The goal of this study is to determine the prevalence of prolonged fasting time among patients undergoing elective surgeries at a Brazilian university hospital and its associations with clinical and sociodemographic variables. This cross-sectional study was conducted between May and November 2019 and included patients of all ages undergoing elective surgeries. Out of the 293 patients analyzed, 64.2% were male, with ages ranging from 1 to 85 years, and 93.9% were classified as ASA I or II. The prevalence of preoperative fasting exceeding 8 h was 89.4%. An average fasting time exceeding 11 h was observed across all age groups. Patients who underwent procedures in the afternoon had an average fasting time that was 24% longer than those in the morning period (14.9 vs. 12 h, p < 0.001). Surgery time (r = 0.134, p < 0.03) and anesthesia times (r = 0.121, p < 0.04) demonstrated a weak correlation with fasting time. Despite the international consensus on preoperative fasting time, our study demonstrated low adherence to current recommendations. Therefore, healthcare professionals should ensure the comprehension of fasting guidelines, and further studies should aim to identify effective solutions to mitigate prolonged fasting. Full article

Across the globe, obesity is a significant concern for public health, a disease characterized by excessive accumulation of body fat, with a negative impact on health. Time-restricted feeding (TRF), in which food accessibility is restricted to a variable period of 8–10 h, especially in the active phase, inducing a prolonged fasting period, is a strategy with potential effects in preventing obesity. Evidence in preclinical studies demonstrated that TRF attenuates the impacts of metabolic disturbances related to high-fat diet feeding in rodents. Through these discoveries, there has been growing interest in revealing the effects associated with TRF in preventing obesity and its comorbidities, as well as investigating its effects in humans. Although TRF is a promising alternative to reduce the impact of obesity, it is necessary to investigate the results on skeletal muscle tissue. Muscle tissue is important for body energy expenditure; however, caloric restriction can negatively impact protein turnover and induce loss of muscle mass, influencing the basal metabolic rate and weight loss. This mini review examined the scientific literature exploring the effects of time-restricted feeding (TRF) on muscle mass. Although still incipient, the findings related to TRF applied to obese individuals highlight the importance of carrying out dietary control, as well as the consumption and fractionation of proteins, to maintain a balanced protein turnover and, consequently, muscle mass. Full article

Background and Objectives: This study aimed to investigate the causes of continuous deep fluctuations in the absolute lymphocyte count (ALC) in an untreated patient with Chronic Lymphocytic Leukemia (CLL), who has had a favorable prognosis since the time of diagnosis. Up until now, the patient has voluntarily chosen to adopt a predominantly vegetarian and fruitarian diet, along with prolonged periods of total fasting (ranging from 4 to 39 days) each year. Materials and Methods: For this purpose, we decided to analyze the whole transcriptome profiling of peripheral blood (PB) CD19+ cells from the patient (#1) at different time-points vs. the same cells of five other untreated CLL patients who followed a varied diet. Consequently, the CLL patients were categorized as follows: the 1st group comprised patient #1 at 20 different time-points (16 time-points during nutrition and 4 time-points during fasting), whereas the 2nd group included only one time point for each of the patients (#2, #3, #4, #5, and #6) as they followed a varied diet. We performed microarray experiments using a powerful tool, the Affymetrix Human Clariom™ D Pico Assay, to generate high-fidelity biomarker signatures. Statistical analysis was employed to identify differentially expressed genes and to perform sample clustering. Results: The lymphocytosis trend in patient #1 showed recurring fluctuations since the time of diagnosis. Interestingly, we observed that approximately 4–6 weeks after the conclusion of fasting periods, the absolute lymphocyte count was reduced by about half. The gene expression profiling analysis revealed that nine genes were statistically differently expressed between the 1st group and the 2nd group. Specifically, IGLC3, RPS26, CHPT1, and PCDH9 were under expressed in the 1st group compared to the 2nd group of CLL patients. Conversely, IGHV3-43, IGKV3D-20, PLEKHA1, CYBB, and GABRB2 were over-expressed in the 1st group when compared to the 2nd group of CLL patients. Furthermore, clustering analysis validated that all the samples from patient #1 clustered together, showing clear separation from the samples of the other CLL patients. Conclusions: This study unveiled a small gene expression signature consisting of nine genes that distinguished an untreated CLL patient who followed prolonged periods of total fasting, maintaining a gradual growth trend of lymphocytosis, compared to five untreated CLL patients with a varied diet. Future investigations focusing on patient #1 could potentially shed light on the role of prolonged periodic fasting and the implication of this specific gene signature in sustaining the lymphocytosis trend and the favorable course of the disease. Full article

Natural alkaloid galantamine is widely used for the treatment of mild to moderate Alzheimer’s dementia. Galantamine hydrobromide (GH) is available as fast-release tablets, extended-release capsules, and oral solutions. However, its oral delivery can cause some unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. Intranasal administration is one possible way to avoid such unwanted effects. In this work, chitosan-based nanoparticles (NPs) were studied as potential GH delivery vehicles for nasal application. The NPs were synthesized via ionic gelation and studied using dynamic light scattering (DLS) as well as by spectroscopic and thermal methods. The GH-loaded chitosan–alginate complex particles were also prepared as a way to modify the release of GH. The high loading efficiency of the GH was confirmed for both types of particles, at 67% for the GH-loaded chitosan NPs and 70% for the complex chitosan/alginate GH-loaded particles. The mean particle size of the GH-loaded chitosan NPs was about 240 nm, while the sodium alginate coated chitosan particles loaded with GH were expectedly bigger, with a mean particle size of ~286 nm. GH release profiles in PBS at 37 °C were obtained for both types of NPs, and it was found that the GH-loaded chitosan NPs allowed the prolonged release of the incorporated drug for a period of 8 h, while the complex GH-loaded chitosan/alginate NPs released the incorporated GH faster. The stability of the prepared GH-loaded NPs was also demonstrated after 1 year of storage at 5 °C ± 3 °C. Full article