Effects of short-term hypercaloric nutrition on orthostatic tolerance in healthy individuals: a randomized controlled crossover study.

Reduced-caloric intake lowers blood pressure through sympathetic inhibition, and worsens orthostatic tolerance within days. Conversely, hypercaloric nutrition augments sympathetic activity and blood pressure. Because dietary interventions could be applied in patients with syncope, we tested the hypothesis that short-term hypercaloric dieting improves orthostatic tolerance. In a randomized crossover trial, 20 healthy individuals (7 women, 26.7 ± 8 years, 22.6 ± 2 kg/m2) followed a 4-day hypercaloric (25% increase of energy intake by fat) or normocaloric nutritional plan, with a washout period of at least 23 days between interventions. We then performed head-up tilt table testing with incremental lower body negative pressure while recording beat-by-beat blood pressure and heart rate. The primary endpoint was orthostatic tolerance defined as time to presyncope. Time to presyncope during combined head-up tilt and lower body negative pressure did not differ between hypercaloric and normocaloric dieting (median 23.19 versus 23.04 min, ratio of median 1.01, 95% CI of ratio 0.5-1.9). Heart rate, blood pressure, heart rate variability, and blood pressure variability in the supine position and during orthostatic testing did not differ between interventions. We conclude that 4 days of moderate hypercaloric nutrition does not significantly improve orthostatic tolerance in healthy individuals. Nevertheless, given the important interaction between energy balance and cardiovascular autonomic control in the brain, caloric intake deserves more attention as a potential contributor and treatment target for orthostatic intolerance.

Oral fructose intake does not improve exercise, visual, or cognitive performance during acute normobaric hypoxia in healthy humans.

Introduction: The ability to metabolize fructose to bypass the glucose pathway in near-anaerobic conditions appears to contribute to the extreme hypoxia tolerance of the naked-mole rats. Therefore, we hypothesized that exogenous fructose could improve endurance capacity and cognitive performance in humans exposed to hypoxia. Methods: In a randomized, double-blind, crossover study, 26 healthy adults (9 women, 17 men; 28.8 ± 8.1 (SD) years) ingested 75 g fructose, 82.5 g glucose, or placebo during acute hypoxia exposure (13% oxygen in a normobaric hypoxia chamber, corresponding to oxygen partial pressure at altitude of ~3,800 m) on separate days. We measured exercise duration, heart rate, SpO2, blood gasses, and perceived exertion during a 30-min incremental load test followed by Farnsworth-Munsell 100 Hue (FM-100) color vision testing and the unstable tracking task (UTT) to probe eye-hand coordination performance. Results: Exercise duration in hypoxia was 21.13 ± 0.29 (SEM) min on fructose, 21.35 ± 0.29 min on glucose, and 21.35 ± 0.29 min on placebo (p = 0.86). Heart rate responses and perceived exertion did not differ between treatments. Total error score (TES) during the FM-100 was 47.1 ± 8.0 on fructose, 45.6 ± 7.6 on glucose and 53.3 ± 9.6 on placebo (p = 0.35) and root mean square error (RMSE) during the UTT was 15.1 ± 1.0, 15.1 ± 1.0 and 15.3 ± 0.9 (p = 0.87). Discussion: We conclude that oral fructose intake in non-acclimatized healthy humans does not acutely improve exercise performance and cognitive performance during moderate hypoxia. Thus, hypoxia tolerance in naked mole-rats resulting from oxygen-conserving fructose utilization, cannot be easily reproduced in humans.

WISP1 Is a Marker of Systemic and Adipose Tissue Inflammation in Dysmetabolic Subjects With or Without Type 2 Diabetes.

CONTEXT: Wnt1-inducible signaling pathway protein 1 (WISP1) is a novel adipokine participating in adipose tissue (AT) dysfunction; so far, no data on WISP1 in diabetes are available. OBJECTIVES: To evaluate plasma WISP1 in subjects with type 2 diabetes (T2D) and its correlates linked to AT inflammation. DESIGN AND PARTICIPANTS: For this cross-sectional study, 97 consecutive dysmetabolic patients were recruited at the diabetes outpatient clinics of Sapienza University in Rome; 71 of them had T2D, with (n = 35) or without (n = 36) obesity, and 26 were obese patients without diabetes. Twenty-one normal-weight nondiabetic individuals were enrolled as a control group. Study participants underwent clinical workup and blood sampling for metabolic/inflammatory characterization; magnetic resonance imaging (MRI) data on subcutaneous AT and visceral AT (VAT) area, hepatic fat content, and VAT homogeneity were available for most diabetic patients. RESULTS: Plasma WISP1 significantly increased throughout classes of obesity and correlated with greater VAT area, interleukin-8 (IL-8), and lower adiponectin levels, without differing between diabetic and nondiabetic participants. Higher IL-8 was the main determinant of increased WISP1. MRI-assessed VAT inhomogeneity was associated with higher WISP1, IL-8 and C-reactive protein levels, independent of obesity; high WISP1 strongly predicted VAT inhomogeneity (P < 0.001). CONCLUSIONS: WISP1 levels are increased in obese persons and are directly related to adiposity, independent of glycemic status or insulin resistance; moreover, they are strongly associated with increased plasma IL-8 and signal abnormalities of VAT. The overall data add insights to the mechanisms underlying metabolic alterations and may open a scenario for innovative therapeutic approaches for diabetes prevention and care.