The Effects of Intravenous Vitamin C on Stress Response Severity in Abdominal Hysterectomy Following Prolonged Fasting Time

Background: Inevitable prolonged fasting time before surgery leads to inflammatory reactions, surgery-related stress response, and consequently unfavorable outcomes; thus, developing strategies to mitigate these consequences is crucial. Objectives: In this study, we evaluated the effect of ascorbic acid on stress response reduction in abdominal hysterectomy following prolonged fasting time. Methods: Eligible women candidates for abdominal hysterectomy following prolonged fasting time were enrolled in the study and divided into 2 groups of vitamin C [group C; 1 g intravenously (IV) before surgery] and placebo (group P). Before induction of anesthesia, C-reactive protein (CRP), mean arterial pressure (MAP), heart rate (HR), and blood sugar (BS) were measured and compared between the 2 groups at 4-point times, 24 and 48 hours immediately after extubation. Results: Finally, the data of 80 patients were included for the final analysis. A statistically significant difference was observed between the 2 groups in terms of CRP and BS values in T1 CRP serum levels; at the end of the study, CRP values were 0.5 ± 0.55 and 0.92 ± 0.69 in groups C and P, respectively (P = 0.012), and BS levels were 124.12 ± 18.11 and 152.0 ± 17.36 in groups C and P, respectively (P = 0.0001). However, this significant difference was not observed at T2 regarding CRP (P = 0.145) and BS (P = 0.135), as well as at T3 regarding CRP (P = 0.282) and BS (P = 0.213). However, according to both CRP and BS values, the trend of changes from T0 to T3 was significant in the 2 groups (P < 0.0001). Hemodynamic parameters were not significantly different between the 2 groups. No adverse event was reported in the 2 groups. Conclusions: We found that ascorbic acid could induce short-term positive effects in abdominal hysterectomy following prolonged fasting time. Obviously, the optimal dosage, timing, and specific cases that benefit the most from this intervention should be investigated.

Overnight fasting affects avoidance learning and relief

Prolonged fasting influences threat and reward processing, two fundamental systems underpinning adaptive behaviors. In animals, overnight fasting sensitizes the mesolimbic-dopaminergic activity governing avoidance, reward, and fear-extinction learning. Despite evidence that overnight fasting may also affect reward and fear learning in humans, effects on human avoidance learning have not been studied yet. Here, we examined the effects of 16h-overnight fasting on instrumental avoidance and relief from threat omission. To this end, 50 healthy women were randomly assigned to a fasting (N=25) or a re-feeding group (N=25) and performed an Avoidance-Relief Task. We found that fasting decreases unnecessary avoidance during signaled safety; this effect was mediated via a reduction in relief pleasantness during signaled absence of threat. A fasting-induced reduction in relief was also found during fear extinction learning. We conclude that fasting optimizes avoidance and safety learning. Future studies should test whether these effects also hold for anxious individuals.

Quality-improvement project to reduce actual fasting times for fluids and solids before induction of anaesthesia

Background Despite well-defined recommendations, prolonged fasting times for clear fluids and solids are still common before elective surgery in adults. Extended fasting times may lead to discomfort, thirst, hunger and physiological dysfunctions. Previous studies have shown that prolonged fasting times are frequently caused by patients being misinformed as well as inadequate implementation of the current guidelines by medical staff. This study aimed to explore how long elective surgery patients fast in a German secondary care hospital before and after the introduction of an educational note for patients and re-training for the medical staff. Methods A total of 1002 patients were enrolled in this prospective, non-randomised interventional study. According to the power calculation, in the first part of the study actual fasting times for clear fluids and solids were documented in 502 consecutive patients, verbally instructed as usual regarding the recommended fasting times for clear fluids (2 h) and solids (6 h). Subsequently, we implemented additionally to the verbal instruction a written educational note for the patients, including the recommended fasting times. Furthermore, the medical staff was re-trained regarding the fasting times using emails, newsletters and employee meetings. Thereafter, another 500 patients were included in the study. We hypothesised, that after these quality improvement procedures, actual fasting times for clear fluids and solids would be more accurate on time. Results Actual fasting times for clear fluids were in the median 11.3 (interquartile range 6.8–14.3; range 1.5–25.5) h pre-intervention, and were significantly reduced to 5.0 (3.0–7.2; 1.5–19.8) h after the intervention (median difference (95%CI) − 5.5 (− 6.0 to − 5.0) h). The actual fasting times for solids also decreased significantly, but only from 14.5 (12.1–17.2; 5.4–48.0) h to 14.0 (12.0–16.3; 5.4–32.0) h after the interventions (median difference (95%CI) − 0.52 (− 1.0 to − 0.07) h). Conclusions The study showed considerably extended actual fasting times in elective adult surgical patients, which were significantly reduced by simple educational/training interventions. However, the actual fasting times still remained considerably longer than defined in recommended guidelines, meaning further process optimisations like obligatory fluid intake in the early morning are necessary to improve patient comfort and safety in future. Trial registration German registry of clinical studies (DRKS-ID: DRKS 00020530, retrospectively registered).

Aging Induces Hepatic Oxidative Stress and Nuclear Proteomic Remodeling in Liver from Wistar Rats

Aging is a continuous, universal, and irreversible process that determines progressive loss of adaptability. The liver is a critical organ that supports digestion, metabolism, immunity, detoxification, vitamin storage, and hormone signaling. Nevertheless, the relationship between aging and the development of liver diseases remains elusive. In fact, although prolonged fasting in adult rodents and humans delays the onset of the disease and increases longevity, whether prolonged fasting could exert adverse effects in old organisms remains incompletely understood. In this work, we aimed to characterize the oxidative stress and nuclear proteome in the liver of 3-month- and 24-month-old male Wistar rats upon 36 h of fasting and its adaptation in response to 30 min of refeeding. To this end, we analyzed the hepatic lipid peroxidation levels (TBARS) and the expression levels of genes associated with fat metabolism and oxidative stress during aging. In addition, to gain a better insight into the molecular and cellular processes that characterize the liver of old rats, the hepatic nuclear proteome was also evaluated by isobaric tag quantitation (iTRAQ) mass spectrometry-based proteomics. In old rats, aging combined with prolonged fasting had great impact on lipid peroxidation in the liver that was associated with a marked downregulation of antioxidant genes (Sod2, Fmo3, and Cyp2C11) compared to young rats. Besides, our proteomic study revealed that RNA splicing is the hepatic nuclear biological process markedly affected by aging and this modification persists upon refeeding. Our results suggest that aged-induced changes in the nuclear proteome could affect processes associated with the adaptative response to refeeding after prolonged fasting, such as those involved in the defense against oxidative stress.

Chronic high fat feeding and prolonged fasting in liver-specific ANGPTL4 knockout mice

Obesity is associated with dyslipidemia, ectopic lipid deposition and insulin resistance. In mice, the global or adipose-specific loss of function of the protein angiopoietin-like 4 (ANGPTL4) leads to decreased plasma triglyceride levels, enhanced adipose triglyceride uptake, and protection from high-fat diet-induced glucose intolerance. ANGPTL4 is also expressed highly in the liver, but the role of liver-derived ANGPTL4 is unclear. The goal of this study was to determine the contribution of hepatocyte ANGPTL4 to triglyceride and glucose homeostasis in mice during a high fat diet challenge. We generated hepatocyte-specific ANGPTL4 deficient (Angptl4LivKO) mice, fed them a 60% kCal/fat diet (HFD) for 6 months, and assessed triglyceride, liver, and glucose metabolic phenotypes. We also explored the effects of prolonged fasting on Angptl4LivKO mice. The loss of hepatocyte-derived Angptl4 led to no major changes in triglyceride partitioning or lipoprotein lipase activity compared to control mice. Interestingly, although there was no difference in fasting plasma triglyceride levels after a 6 h fast, after an 18 h fast normal chow diet fed Angptl4LivKO mice had lower triglyceride levels than control mice. On a HFD, Angptl4LivKO mice initially showed no difference in glucose tolerance and insulin sensitivity, but improved glucose tolerance emerged in these mice after 6 months on HFD. Our data suggest that hepatocyte ANGPTL4 does not directly regulate triglyceride partitioning, but that loss of liver-derived ANGPTL4 may be protective from HFD-induced glucose intolerance and influence plasma TG metabolism during prolonged fasting.

Impact of a Single 36 Hours Prolonged Fasting Period in Adults With Type 1 Diabetes – A Cross-Over Controlled Trial

Prolonged fasting has shown beneficial effects in healthy individuals and in people with chronic diseases. In type 1 diabetes, the effect or even the feasibility of fasting is unclear. We aimed to assess the impact and safety of prolonged fasting in adults with type 1 diabetes. Glycemia was assessed during overnight fasting (12 hours) vs. prolonged fasting (36 hours) via an intermittently-scanned continuous glucose monitoring system. Anthropometric data, metabolic and hormonal markers were compared between both trial arms. After each fasting period, a 75 g oral glucose tolerance test was performed and plasma glucose levels and hormones were assessed. Data were compared via paired t-tests and mixed-model regressions (p ≤ 0.05). Twenty individuals with type 1 diabetes (7 females) with a mean ± SD age of 35 ± 11 years, body mass index (BMI) 24.8 ± 2.8 kg/m2 and HbA1c 54 ± 7 mmol/mol were included. Hypoglycemia/hour (70 mg/dL; &lt;3.9 mmol/L) was similar in both trial arms (12 hrs: 0.07 ± 0.06 vs. 36 hrs: 0.05 ± 0.03, p=0.21). Glycemic excursions during the oral glucose tolerance test were not different after the two fasting periods. Beta-hydroxybutyrate levels were higher after prolonged fasting (p=0.0006). Our study showed that people with type 1 diabetes can safely perform a 36 hours fasting period with a low risk of hypoglycemia and ketoacidosis.Clinical Trial RegistrationDRKS.de, identifier DRKS00016148.

KETONURIAAN EARLY COVID-19 SEVERITY & PROGNOSTIC MARKER? AN OBSERVATIONAL STUDY.

Ketone bodies are insignicant in the blood and urine of normal individuals. Ketoacids become important sources of metabolic energy in circumstances in which the availability of glucose is restricted, as during prolonged fasting, or when the ability to use glucose is greatly diminished, as in decompensated diabetes mellitus or any infective illness like viral or bacterial infection1.It has been found that increased utilization of glucose for CORONA virus replication. Codo et al.1 provided conclusive evidences that glycolytic ux is indispensable for SARS-CoV-2’s impact. Increased utilization of glucose for CORONA virus replication and ux results in diminished availability of glucose and therefore increased production of ketone bodies and its appearance in urine. This study assesses the level of ketonuria and disease severity and use of ketonuria as prognostic marker of COVID infection.

Effect of prolonged starvation on the body preoperatively and the role of carbohydrate loading

Although recent reports discourage preoperative overnight fasting, many clinicians and surgeons still recommend 6-8 hours of overnight preoperative fasting before conducting elective surgeries. On the other hand, recent guidelines from worldwide multiple anesthesiology societies have suggested that overnight fasting should be approached with flexible durations and proper techniques. Many complications can result from prolonged fasting and preoperative starvation as the duration of fasting usually lasts for more than 12 hours secondary to intraoperative surgical delays. In this literature review, the aim was to discuss the current evidence from studies in the literature about the effect of preoperative starvation and the effect of carbohydrate (CHO) loading on the clinical outcomes of patients. We have noticed that gastric aspiration and respiratory damage can be prevented by preoperative fasting. However, this can lead to the development of other complications such as insulin resistance, a fierce immune response and exaggerated release of acute-phase reactants which might lead to severe organ damage and worsened patient’s prognosis. Accordingly, CHO loading should be carefully approached to properly intervene against these cases to enhance the prognosis of the prospective surgeries and the quality of care for patients.