Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21.

Dietary restriction promotes resistance to surgical stress in multiple organisms. Counterintuitively, current medical protocols recommend short-term carbohydrate-rich drinks (carbohydrate loading) prior to surgery, part of a multimodal perioperative care pathway designed to enhance surgical recovery. Despite widespread clinical use, preclinical and mechanistic studies on carbohydrate loading in surgical contexts are lacking. Here we demonstrate in ad libitum-fed mice that liquid carbohydrate loading for one week drives reductions in solid food intake, while nearly doubling total caloric intake. Similarly, in humans, simple carbohydrate intake is inversely correlated with dietary protein intake. Carbohydrate loading-induced protein dilution increases expression of hepatic fibroblast growth factor 21 (FGF21) independent of caloric intake, resulting in protection in two models of surgical stress: renal and hepatic ischemia-reperfusion injury. The protection is consistent across male, female, and aged mice. In vivo, amino acid add-back or genetic FGF21 deletion blocks carbohydrate loading-mediated protection from ischemia-reperfusion injury. Finally, carbohydrate loading induction of FGF21 is associated with the induction of the canonical integrated stress response (ATF3/4, NF-kB), and oxidative metabolism (PPARγ). Together, these data support carbohydrate loading drinks prior to surgery and reveal an essential role of protein dilution via FGF21.

Improved physical performance of elite soccer players based on GPS results after 4 days of carbohydrate loading followed by 3 days of low carbohydrate diet.

BACKGROUND: Carbohydrate loading is an established sports nutrition strategy for endur- 16 ance exercise performance. We tested if carbohydrate loading could improve the performance of 17 elite soccer players under ecologically valid circumstances using Global Positioning System (GPS) data. METHODS: Twenty-two adult Iran Premier league soccer players were divided into a carbohydrate-loading group (CLG) and Control group (CG). The carbohydrate loading group restricted carbohydrate intake for three days to 1.5 g/kg/d while increasing exercise intensity. From days four to seven, exercise intensity was decreased and carbohydrate intake was considerably increased up to 7.5 g/kg/d on the day of the match, during which performance was analyzed using GPS data. The control group performed the same exercise training but maintained their habitual carbohydrate intake of 5-6 g/kg/d. The data were analyzed using a univariate ANCOVA with baseline data from a pre-intervention match as the control variable. RESULTS: The carbohydrate loading team scored significantly higher on running distance, maximum speed and the number of top and repeated sprints; the carbohydrate loading group scored significantly lower on player load, metabolic power and running imbalance compared to the control team during their match. CONCLUSIONS: Our findings suggest carbohydrate loading enabled elite soccer players to achieve greater running outputs with greater metabolic efficiency and lower fatigue compared to their habitual diets.

High-fat, high-sucrose, and combined high-fat/high-sucrose diets effects in oxidative stress and inflammation in male rats under presence or absence of obesity.

The study examines the influence of three types of hypercaloric diets on metabolic parameters, inflammatory markers, and oxidative stress in experimental model. Male Wistar rats (n = 40) were randomized in control (C), high-sucrose (HS), high-fat (HF), and high-fat with sucrose (HFHS) for 20 weeks. Nutritional, metabolic, hormonal, and biochemical profiles, as well as histological analysis of adipose and hepatic tissues were performed. Inflammation and oxidative stress were determined. HF model caused obesity and comorbidities as glucose intolerance and arterial hypertension. In relation to hormonal and biochemical parameters, there was no significant difference between the groups. All groups showed increased deposition of fat droplets in the hepatic tissue, even though adipocyte areas were similar. Biomarkers of oxidative stress in serum and adipose tissues were similar among the groups. HF model was effective in triggering associated obesity and comorbidities in male rats, but all hypercaloric diets were unable to promote oxidative stress and inflammation.

Effects of Preoperative Oral Carbohydrate Loading on Neutrophil/Lymphocyte Ratio and Postoperative Complications following Colorectal Cancer Surgery: A Randomized Controlled Study.

INTRODUCTION: Preoperative carbohydrate oral (CHO) drinks attenuate the surgical stress response; however, the effects of CHO supplementation on the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory and immunology-based predictor remain unclear. This study evaluated the effects of preoperative CHO loading on NLR values and complications following open colorectal surgery compared with a conventional fasting protocol. METHODS: Sixty eligible participants having planned for routine and open colorectal cancer surgery from May 2020 to January 2022 were prospectively and randomly allocated to either the control (fasting) group, whose members discontinued oral intake beginning the midnight before surgery, or the intervention (CHO) group, whose members consumed a CHO solution the night before surgery and 2 h prior to anaesthesia. NLR was assessed at 06:00 h before surgery (baseline) and at 06:00 h on postoperative days 1, 3, and 5. The incidence and severity of postoperative complications were assessed by Clavien-Dindo Classification up to postoperative day 30. All data were analysed using descriptive statistics. RESULTS: Postoperative NLR and delta NLR values were significantly higher in controls (p < 0.001; p < 0.001). Control group participants also demonstrated grade IV (n = 5; 16.7%, p < 0.01) and grade V (n = 1; 3.3%, p < 0.313) postoperative complications. There were no major postoperative complications in the CHO group. CONCLUSION: Preoperative CHO consumption reduced postoperative NLR values and the incidence and severity of postoperative complications following open colorectal surgery, compared with a preoperative fasting protocol. Preoperative carbohydrate loading may improve recovery following colorectal cancer surgery.

An analysis of enhanced recovery pathways for bariatric surgery-preoperative fasting, carbohydrate loading, and aspiration risk: a position statement from the International Society for the Perioperative Care of Patients with Obesity.

Enhanced recovery pathways (ERPs) and recommendations have become widely accepted for metabolic and bariatric surgery, including recommendations for preoperative carbohydrate loading and duration of fasting status. There is still a lack of consensus regarding such protocols and the underlying issues of gastric emptying time, resting gastric volume and pH, and risk of aspiration in patients with severe obesity and in patients undergoing bariatric surgery. The goal of this position statement by the International Society for the Perioperative Care of Patients with Obesity (ISPCOP) is to provide an analysis of available data on preoperative fasting and loading with oral complex clear carbohydrate drinks as well its potential effects on perioperative risk of aspiration in the context of Enhanced Recovery Pathways for Metabolic and Bariatric Surgery (ERAMBS).

Carbohydrate Loading and Aspiration Risk in Bariatric Patients: Safety in Preoperative Enhanced Recovery Protocols.

BACKGROUND: Enhanced recovery protocols have been developed to improve perioperative outcomes; however, there is ongoing concern for aspiration with recent oral intake in patients with obesity, who may be predisposed to impaired gastrointestinal motility and greater gastric volumes. We aim to study the safety of a 300-mL preoperative carbohydrate-loading drink preceding bariatric surgery. STUDY DESIGN: Data were collected prospectively from patients undergoing primary bariatric surgery. All bariatric patients at our institution are prescribed a proton pump inhibitor for 4 weeks before surgery and undergo a screening preoperative esophagogastroduodenoscopy (EGD) before surgery with a traditional 8-hour fast (NOCARB), followed by an intraoperative day-of-operation EGD with carbohydrate loading (CARB) 2 to 4 hours before incision. Gastric volumes and pH are measured after being endoscopically suctioned via direct visualization during both settings. RESULTS: We identified 203 patients: 94 patients (46.3%) in the CARB group and 109 patients (53.7%) in the NOCARB group. The patients were 82.3% female with a mean age of 42.8 years and average BMI of 41.7 kg/m 2 . There was no difference in gastric volume between NOCARB and CARB (17.0 vs 16.1 mL, p = 0.59). The NOCARB group had lower pH values than the CARB group (2.8 vs 3.8, p = 0.001). Subset analysis of 23 patients who had measurements on both screening and intraoperative EGD revealed lower gastric volumes in CARB patients (13.3 vs 18.3, p < 0.0001). CONCLUSIONS: When included in an enhanced recovery protocol, proton pump inhibitor use and preoperative carbohydrate loading 2 to 4 hours before bariatric surgery does not increase aspiration risk based on gastric volumes and pH and should be strongly considered in all eligible bariatric patients.

Pilot study on the impact of a carbohydrate loading drink on postprandial glycemic responses and gastric emptying in adults with prediabetes and type 2 diabetes mellitus.

BACKGROUND: Preoperative carbohydrate (CHO) loading improves patient outcomes but is not extensively studied in individuals with diabetes mellitus (DM), resulting in limited professional recommendations. This study examined postprandial glycemic responses and gastric emptying rates following consumption of a CHO drink in adults with and without DM. METHODS: A single-arm, nonrandomized pilot trial was conducted in adults without DM (non-DM) (47.5 ± 2.5 years), with pre-DM (55.8 ± 3.0 years), and with type 2 DM (56.2 ± 2.5 years). Following an overnight fast, participants consumed a 50 g CHO drink followed by 1.5 g liquid paracetamol. Venous blood samples were collected at baseline (ie, t = 0 min) and 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min for plasma glucose and serum insulin and paracetamol concentrations to assess gastric emptying. RESULTS: Participants with DM were older and had a higher body mass index than non-DM participants (31.2 ± 0.9 vs 28.2 ± 0.9). Fasting glucose and hemoglobin A1c levels differed significantly across groups (non-DM: 95.4 ± 3.6 mg/dl and 5.2% ± 0.1%; pre-DM: 111.6 ± 3.6 mg/dl and 5.8% ± 0.1%; DM: 167.4 ± 3.6 mg/dl and 7.2% ± 0.1%). Compared with the non-DM group, DM had increased glucose responses at 30-180 min. Glucose returned to baseline at 150 min in the non-DM and pre-DM groups compared with 210 min in the DM group. Paracetamol concentrations were not significantly different between the non-DM and DM groups. CONCLUSION: Blood glucose returned to baseline within ~2.5 h in non-DM and pre-DM groups and ~3.5 h in participants with DM following ingestion of a CHO drink. No consistent differences in gastric emptying rates were observed between participants with and without DM.

Preexercise High-Fat Meal Following Carbohydrate Loading Attenuates Glycogen Utilization During Endurance Exercise in Male Recreational Runners.

ABSTRACT: Iwayama, K, Tanabe, Y, Yajima, K, Tanji, F, Onishi, T, and Takahashi, H. Preexercise high-fat meal following carbohydrate loading attenuates glycogen utilization during endurance exercise in male recreational runners. J Strength Cond Res 37(3): 661-668, 2023-This study aimed to investigate whether one preexercise high-fat meal can increase glycogen conservation during endurance exercise, as compared with one preexercise high-carbohydrate meal. Ten young male recreational runners (22.0 ± 0.6 years; 171.3 ± 0.9 cm; 58.3 ± 1.9 kg; maximal oxygen uptake [V̇ o2 max], 62.0 ± 1.6 ml·kg -1 ·min -1 ) completed 2 exercise trials after high-carbohydrate loading: eating a high-carbohydrate (CHO; 7% protein, 13% fat, 80% carbohydrate) meal or eating a high-fat (FAT; 7% protein, 42% fat, 52% carbohydrate) meal 3.5 hours before exercise. The order of the 2 trials was randomized, and the interval between trials was at least 1 week. The experimental exercise consisted of running on a treadmill for 60 minutes at 95% of each subject's lactate threshold. Muscle and liver glycogen content were assessed using noninvasive carbon magnetic resonance spectroscopy before the experimental meal as well as before and after exercise; respiratory gases were measured continuously during exercise. The respiratory exchange ratio during exercise was statistically lower in the FAT trial than in the CHO trial ( p < 0.01). In addition, muscle ( p < 0.05) and liver ( p < 0.05) glycogen utilization during exercise was less in the FAT trial than in the CHO trial. Therefore, one high-fat meal following carbohydrate loading reduced muscle and liver glycogen use during the 60-minute exercise. These results suggest that this dietary approach may be applied as a strategy to optimize energy utilization during endurance exercise.

The Role of High-Fructose Diet in Liver Function of Rodent Models: A Systematic Review of Molecular Analysis.

The present systematic review of animal studies on long-term fructose intake in rodents revealed a significant decrease in the activities of antioxidant enzymes due to a fructose-rich diet. The reduced activity of these enzymes led to an increase in oxidative stress, which can cause liver damage in rodents. Of eight studies analyzed, 5 (62.5%) and 1 (12.5%) used male and female rats, respectively, while 2 studies (25%) used female mice. Moreover, half of the studies used HFCS, but the other half employed fructose in the diet. Hence, it is essential to monitor dietary habits to ensure public health and nutrition research outcomes.

Preoperative carbohydrate loading before colorectal surgery: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Preoperative carbohydrate loading has been introduced as a component of many enhanced recovery after surgery programs. Evaluation of current evidence for preoperative carbohydrate loading in colorectal surgery has never been synthesized. METHODS: MEDLINE, Embase, and CENTRAL were searched until May 2021. Randomized controlled trials (RCTs) comparing patients undergoing colorectal surgery with and without preoperative carbohydrate loading were included. Primary outcomes were changes in blood insulin and glucose levels. A pairwise meta-analysis was performed using inverse variance random effects. RESULTS: The search yielded 3656 citations, from which 12 RCTs were included. In total, 387 patients given preoperative carbohydrate loading (47.2% female, age: 62.0 years) and 371 patients in control groups (49.4% female, age: 61.1 years) were included. There was no statistical difference for blood glucose and insulin levels between both patient groups. Patients receiving preoperative carbohydrate loading experienced a shorter time to first flatus (SMD: - 0.48 days, 95% CI: - 0.84 to - 0.12, p = 0.008) and stool (SMD: - 0.50 days, 95% CI: - 0.86 to - 0.14, p = 0.007). Additionally, length of stay was shorter in the preoperative carbohydrate loading group (SMD: - 0.51 days, 95% CI: - 0.88 to - 0.14, p = 0.007). There was no difference in postoperative morbidity and patient well-being between both groups. CONCLUSIONS: Preoperative carbohydrate loading does not significantly impact postoperative glycemic control in patients undergoing colorectal surgery; however, it may be associated with a shorter length of stay and faster return of bowel function. It merits consideration for inclusion within colorectal enhanced recovery after surgery protocols.

Effect of pre-operative carbohydrate loading on aspiration risk evaluated with ultrasonography in type 2 diabetes patients: a prospective observational pilot study.

Owing to concerns about delayed gastric emptying or hyperglycemia, evidence is lacking regarding whether pre-operative carbohydrate loading can be routinely administered to patients with type 2 diabetes. The objective of this study was to determine the aspiration risk and gastric volume after pre-operative carbohydrate loading in patients with type 2 diabetes. A prospective, single-center, observational cohort study. The study was conducted at a tertiary teaching hospital in Seoul, Korea, from May 2020 to May 2021. Patients (n = 49) with type 2 diabetes underwent elective noncardiac surgery. All patients were administered carbohydrate loading two hours before surgery. Once in the operating room, they underwent gastric ultrasonography to determine gastric volume. The anesthesiologists monitored the patients' glucose concentrations during and after surgery. The primary outcome was the predicted risk of aspiration. The secondary outcomes were gastric volume, antral grade, satisfaction score, and perioperative glucose profile. Forty-nine patients were analyzed. All patients had a low risk of aspiration after carbohydrate loading, as follows: 33 (67.3%) patients classified as antral grade 0 and 16 (32.7%) patients classified as antral grade 1. The median time from carbohydrate drink ingestion to ultrasound examination was 120 min (IQR 115-139). After carbohydrate loading, the median gastric volume in the right-lateral position after carbohydrate loading was 2.64 ml (IQR 0.00-32.05). The mean glucose concentrations (SD) were 134 (24) mg/dl, 159 (37) mg/dl, 150 (32) mg/dl, and 165 (36) mg/dl at baseline, after induction, 30 min after surgery, and in the post anesthesia care unit, respectively. The median satisfaction score of the patients was 5 (IQR 4-5). Pre-operative carbohydrate loading may be feasible for patients with type 2 diabetes and without complications.Trial registration: ClinicalTrials.gov (NCT04456166). Registered on 2 July 2020.

The effect of pre-operative carbohydrate loading in femur fracture: a randomized controlled trial.

BACKGROUND: Femur fracture is a major burden among elderly people, leading patients to be bedridden for a long time in the hospital. The body is more likely to be in a catabolic state as a result of the prolonged fasting period required for surgery, leading to an increase in insulin resistance. Pre-operative carbohydrate loading has been shown to improve postoperative outcomes in several countries. The study aimed to evaluate the effect of pre-operative carbohydrate loading in femur fracture surgery. METHODS: This study was single-center, hospital-based, open-label, parallel-group randomized controlled trial conducted between August 2020 and November 2021. A total of 66 participants, aged 50 years and above having femur fractures planned for surgery were included in this study and assigned to the control (n = 33) and study (n = 33) groups through computer-generated random numbers. The control group was kept fasting from midnight to the next morning as in existence while the study group was intervened with carbohydrate loading according to the Enhanced Recovery After Surgery (ERAS) protocol. The pre-operative nutritional status was identified and the postoperative outcomes were measured using the Visual Analogue Score (VAS), Cumulative Ambulatory Score (CAS), and Modified Barthel Index (MBI) scoring systems. Statistical analyses were performed using the Chi-square test and the Student's two-sample t-test to compare the outcomes between the two groups. RESULTS: All the participants completed the study. There was a significant reduction in the average postoperative pain in the carbohydrate loading group (VAS: 4.8 (SD ± 1.8), 95% CI: 4.7-5.4) as compared to the control group (VAS: 6.1 (SD ± 2.1), 95% CI: 5.3-6.8). The average CAS showed a significant improvement in regaining the mobility function of participants in the study group (CAS: 8.1 (SD ± 2.8), 95% CI: 7.1-9.1) than that of the control group (CAS: 6.8 (SD ± 2.8), 95% CI: 5.8-7.8). The mean MBI score of the participants at the time of discharge from the hospital was higher in the study group (MBI:13.1 (SD ± 2.3), 95% CI: 12.2-13.9) compared to the control group (MBI: 11.8 (SD ± 3.1), 95% CI:10.6-12.9). Similarly, the length of hospital stay after surgery had decreased in the study group than in the control group. CONCLUSIONS: The uptake of carbohydrate loading showed reduced post-operative pain, enhanced functional mobility, and decreased length of hospital stay. This study warrants larger trials to show the effect of pre-operative carbohydrate loading in a clinical setting. TRIAL REGISTRATION: NCT04838366, first registered on 09/042021 ( https://clinicaltrials.gov/ct2/show/NCT04838366 ).

The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases.

Central and peripheral serotonin (5-hydroxytryptamine, 5-HT) regulate feeding signals for energy metabolism. Disruption of central 5-HT signaling via 5-HT2C receptors (5-HT2CRs) induces leptin-independent hyperphagia in mice, leading to late-onset obesity, insulin resistance, and impaired glucose tolerance. 5-HT2CR mutant mice are more responsive than wild-type mice to a high-fat diet, exhibiting earlier-onset obesity and type 2 diabetes. High-fat and high-carbohydrate diets increase plasma 5-HT and fibroblast growth factor-21 (FGF21) levels. Plasma 5-HT and FGF21 levels are increased in rodents and humans with obesity, type 2 diabetes, and non-alcohol fatty liver diseases (NAFLD). The increases in plasma FGF21 and hepatic FGF21 expression precede hyperinsulinemia, insulin resistance, hyperglycemia, and weight gain in mice fed a high-fat diet. Nutritional, pharmacologic, or genetic inhibition of peripheral 5-HT synthesis via tryptophan hydroxylase 1 (Tph1) decreases hepatic FGF21 expression and plasma FGF21 levels in mice. Thus, perturbing central 5-HT signaling via 5-HT2CRs alters feeding behavior. Increased energy intake via a high-fat diet and/or high-carbohydrate diet can upregulate gut-derived 5-HT synthesis via Tph1. Peripheral 5-HT upregulates hepatic FGF21 expression and plasma FGF21 levels, leading to metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and NAFLD. The 5-HT network in the brain-gut-liver axis regulates feeding signals and may be involved in the development and/or prevention of metabolic diseases.

Preoperative carbohydrate loading before elective abdominal surgery: A systematic review and network meta-analysis of phase II/III randomized controlled trials.

BACKGROUND & AIMS: The preoperative use of carbohydrate loading (CHO) is recommended in patients undergoing abdominal surgery, even if the advantages remain debatable. The aim was to evaluate the CHO benefits in patients undergoing abdominal surgery. METHODS: A systematic search of randomized clinical trials was made. A frequentist random-effects network meta-analysis was carried out, reporting the surface under the cumulative ranking (SUCRA). The primary endpoint regarded the morbidity rate. The secondary endpoints were aspiration/regurgitation rates, the length of stay (LOS), the rate of postoperative nausea and vomiting (PONV), the changes (Δ) in insulin sensitivity or resistance, and the postoperative C- reactive protein (CRP) values. RESULTS: CHO loading and water administration had a similar probability of being the approach with a lower morbidity rate (SUCRA = 62.4% and 64.7%). CHO and clear water also had a similar chance of avoiding the PONV (SUCRA of 80.8% and 77%). The aspiration regurgitation rate was not relevant in non-fasting patients (0.06%). CHO administration was associated with the shorter hospitalization (SUCRA 86.9%), with the best metabolic profile (SUCRA values for insulin resistance and sensitivity were 81.1% and 76%). CHO enriched was the best approach for postoperative CRP values. Preoperative fasting was the worst approach for morbidity, PONV, insulin resistance and sensitivity, and CRP (SUCRA values of 32.1%, 21.7%, 10.2%, 3.2%, and 2.0%). CONCLUSION: Both preoperative CHO loading and clear water use were superior to the fasting about morbidity. CHO drinks use could provide specific advantages, reduce the PONV rate, and improve carbohydrate homeostasis, inflammatory pathway, and hospitalization.

Postoperative Dietary Intake Achievement: A Secondary Analysis of a Randomized Controlled Trial.

Sufficient postoperative dietary intake is crucial for ensuring a better surgical outcome. This study aimed to investigate the postoperative dietary intake achievement and predictors of postoperative dietary intake among gynecologic cancer patients. A total of 118 participants were included in this secondary analysis. Postoperative dietary data was pooled and re-classified into early postoperative dietary intake achievement (EDIA) (daily energy intake (DEI) ≥ 75% from the estimated energy requirement (EER)) and delay dietary intake achievement (DDIA) (DEI < 75% EER) There was a significant difference in postoperative changes in weight (p = 0.002), muscle mass (p = 0.018), and handgrip strength (p = 0.010) between the groups. Postoperative daily energy and protein intake in the EDIA was significantly greater than DDIA from operation day to discharged (p = 0.000 and p = 0.036). Four significant independent postoperative dietary intake predictors were found: preoperative whey protein-infused carbohydrate loading (p = 0.000), postoperative nausea vomiting (p = 0.001), age (p = 0.010), and time to tolerate clear fluid (p = 0.016). The multilinear regression model significantly predicted postoperative dietary intake, F (4, 116) = 68.013, p = 0.000, adj. R2 = 0.698. With the four predictors' recognition, the integration of a more specific and comprehensive dietitian-led supportive care with individualized nutrition intervention ought to be considered to promote functional recovery.