Metabolomic Signature as a Predictor of Liver Disease Events in Patients With HIV/HCV Coinfection.

BACKGROUND: Advanced liver disease due to hepatitis C virus (HCV) is a leading cause of human immunodeficiency virus (HIV)-related morbidity and mortality. There remains a need to develop noninvasive predictors of clinical outcomes in persons with HIV/HCV coinfection. METHODS: We conducted a nested case-control study in 126 patients with HIV/HCV and utilized multiple quantitative metabolomic assays to identify a prognostic profile that predicts end-stage liver disease (ESLD) events including ascites, hepatic encephalopathy, hepatocellular carcinoma, esophageal variceal bleed, and spontaneous bacterial peritonitis. Each analyte class was included in predictive modeling, and area under the receiver operator characteristic curves (AUC) and accuracy were determined. RESULTS: The baseline model including demographic and clinical data had an AUC of 0.79. Three models (baseline plus amino acids, lipid metabolites, or all combined metabolites) had very good accuracy (AUC, 0.84-0.89) in differentiating patients at risk of developing an ESLD complication up to 2 years in advance. The all combined metabolites model had sensitivity 0.70, specificity 0.85, positive likelihood ratio 4.78, and negative likelihood ratio 0.35. CONCLUSIONS: We report that quantification of a novel set of metabolites may allow earlier identification of patients with HIV/HCV who have the greatest risk of developing ESLD clinical events.

Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation.

To determine the effects of a mushroom blend containing Cordyceps militaris on high-intensity exercise after 1 and 3 weeks of supplementation. Twenty-eight individuals (Mean ± standard deviation [SD]; Age = 22.7 ± 4.1 yrs; Height = 175.4 ± 8.7 cm; Weight = 71.6 ± 12.0 kg) participated in this randomized, repeated measures, double-blind, placebo-controlled design. Maximal oxygen consumption (VO2max), time to exhaustion (TTE), and ventilatory threshold (VT) were measured during a maximal graded exercise test on a cycle ergometer. Relative peak power output (RPP), average power output (AvgP), and percent drop (%drop) were recorded during a 3 minute maximal cycle test with resistance at 4.5% body weight. Subjects consumed 4 g·d-1 mushroom blend (MR) or maltodextrin (PL) for 1 week. Ten volunteers supplemented for an additional 2 weeks. Exercise tests were separated by at least 48 hours and repeated following supplementation periods. One week of supplementation elicited no significant time × treatment interaction for VO2max (p = 0.364), VT (p = 0.514), TTE (p = 0.540), RPP (p = 0.134), AvgP (p = 0.398), or %drop (p = 0.823). After 3 weeks, VO2max significantly improved (p = 0.042) in MR (+4.8 ml·kg-1·min-1), but not PL (+0.9 ml·kg-1·min-1). Analysis of 95% confidence intervals revealed significant improvements in TTE after 1- (+28.1 s) and 3 weeks (+69.8 s) in MR, but not PL, with additional improvements in VO2max (+4.8 ml·kg-1·min-1) and VT (+0.7 l·min-1) after 3 weeks. Acute supplementation with a Cordyceps militaris containing mushroom blend may improve tolerance to high-intensity exercise; greater benefits may be elicited with consistent chronic supplementation.

Metabolic characterization of overweight and obese adults.

OBJECTIVES: Traditional evaluations of metabolic health may overlook underlying dysfunction in individuals who show no signs of insulin resistance or dyslipidemia. The purpose of this study was to characterize metabolic health in overweight and obese adults using traditional and non-traditional cardiometabolic variables. A secondary purpose was to evaluate differences between overweight/obese and male/female cohorts, respectively. METHODS: Forty-nine overweight and obese adults (Mean ± SD; Age = 35.0 ± 8.9 yrs; Body mass index = 33.6 ± 5.2 kg·m-2; Percent body fat [%fat] = 36.7 ± 7.9%) were characterized. Body composition (fat mass [FM], lean mass [LM], %fat) was calculated using a 4-compartment model; visceral adipose tissue (VAT) was quantified using B-mode ultrasound. Resting metabolic rate (RMR) and respiratory exchange ratio (RER) were evaluated using indirect calorimetry. Fasted blood and saliva samples were analyzed for total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides (TRG), glucose (GLUC), insulin, leptin, estradiol, and cortisol. RESULTS: The prevalence of individuals with two or more cardiometabolic risk factors increased from 13%, using traditional risk factors (GLUC, TRG, HDL), to 80% when non-traditional metabolic factors (VAT, LM, RMR, RER, TC, LDL, HOMA-IR) were considered. Between overweight/obese, there were no significant differences in %fat (p = 0.152), VAT (p = 0.959), RER (p = 0.493), lipids/GLUC (p > 0.05), insulin (p = 0.143), leptin (p = 0.053), or cortisol (p = 0.063); obese had higher FM, LM, RMR, and estradiol (p < 0.01). Males had greater LM, RMR, and TRG (p < 0.01); females had greater %fat, and leptin (p < 0.001). There were no significant sex differences in RER, estradiol, insulin, or cortisol (p > 0.05). CONCLUSIONS: Evaluating metabolic health beyond BMI and traditional cardiometabolic risk factors can give significant insights into metabolic status. Due to high variability in metabolic health in overweight and obese adults and inherent sex differences, implementation of body composition and visceral fat measures in the clinical setting can improve early identification and approaches to disease prevention.