The potential role of creatine in vascular health

Creatine is an organic compound, consumed exogenously in the diet and synthesized endogenously via an intricate inter-organ process. Functioning in conjunction with creatine kinase, creatine has long been known for its pivotal role in cellular energy provision and energy shuttling. In addition to the abundance of evidence supporting the ergogenic benefits of creatine supplementation, recent evidence suggests a far broader application for creatine within various myopathies, neurodegenerative diseases, and other pathologies. Furthermore, creatine has been found to exhibit non-energy related properties, contributing as a possible direct and in-direct antioxidant and eliciting anti-inflammatory effects. In spite of the new clinical success of supplemental creatine, there is little scientific insight into the potential effects of creatine on cardiovascular disease (CVD), the leading cause of mortality. Taking into consideration the non-energy related actions of creatine, highlighted in this review, it can be speculated that creatine supplementation may serve as an adjuvant therapy for the management of vascular health in at-risk populations. This review, therefore, not only aims to summarize the current literature surrounding creatine and vascular health, but to also shed light onto the potential mechanisms in which creatine may be able to serve as a beneficial supplement capable of imparting vascular-protective properties and promoting vascular health

Acute effects of single-bout exercise in adults with type 2 diabetes: a systematic review of randomised controlled trials and controlled crossover trials

Background: Exercise interventions improve type 2 diabetes (T2D). Published randomised control trials and crossover control trials were systematically examined to establish the differences in the effect of single-bout exercise on glucose control and insulin sensitivity in individuals with type 2 diabetes.Methods: Using PRISMA guidelines on three electronic databases, studies that tested the effects of a single bout of exercise on glucose control and insulin sensitivity in T2D were identified. To be included, studies had to meet the PRISMA criteria and contain data on the effects of a single bout of exercise on blood glucose and/or insulin resistance in individuals with T2D.Results: Three of the 205 articles met the inclusion criteria. All of the studies prescribed a single bout of continuous aerobic exercise at 40–60% heart rate reserve (HRR), 60% HRR, or 73% VO2 peak. Aerobic exercise was associated with improved glucose control when  compared with resistance exercise. Continuous aerobic exercise significantly lowered average glucose during the first 24 hours post-exercise. Interval walking decreased mean and maximal blood glucose when compared with that in control.Conclusions: In conclusion, the findings of this review suggest high-intensity interval training to be the most effective form of exercise

Effect of Exercise Training on Microvascular Function in African American and Caucasian Women

African Americans (AA), especially women, exhibit long-standing disparities in cardiovascular disease (CVD) and obesity. The prevalence of endothelial dysfunction, directly linked to hypertension, is considerably greater in AA than Caucasians (C). Vascular smooth muscle function (mediating endothelium-independent vasodilation) is also related to CVD risk factors but is underappreciated because most literature in C suggest endothelium-independent vasodilatory response is resistance to change with disease (hypertension) or exercise training. Furthermore, the regulation of local skeletal muscle blood flow (an important site of peripheral resistance) has not been sufficiently assessed. Microdialysis is the only method that allows monitoring of microvascular blood flow while affecting the local tissue with pharmacological agents in the absence of systemic, or organ level, effects in humans. Microvascular blood flow was assessed by microdialysis in vivo in skeletal muscle before and after 12 weeks of aerobic exercise training in young, obese AA and C women. Our preliminary data suggested that microvascular endothelial function, assessed by percent change in blood flow from basal (Δ Blood Flow) in response to acetylcholine perfusion was improved in both obese AA (n=5) and obese C (n=4) women. Microvascular endothelium-independent blood flow, assessed by percent change in blood flow from baseline (Δ Blood Flow) upon addition of sodium nitroprusside to the perfusate, was improved in AA (n=3) but not in C (n=9) women. Exercise training may improve endothelium-dependent vascular function in both AA and C, but improve endothelium-independent vascular function only in AA. Results of this study have potential to inform preventive interventions including lifestyle and pharmacological approaches designed to reduce disparities in hypertension and end-organ damage

Overexpression of Long-Chain Acyl-CoA Synthetase 5 Increases Fatty Acid Oxidation and Free Radical Formation While Attenuating Insulin Signaling in Primary Human Skeletal Myotubes

In rodent skeletal muscle, acyl-coenzyme A (CoA) synthetase 5 (ACSL-5) is suggested to localize to the mitochondria but its precise function in human skeletal muscle is unknown. The purpose of these studies was to define the role of ACSL-5 in mitochondrial fatty acid metabolism and the potential effects on insulin action in human skeletal muscle cells (HSKMC). Primary myoblasts isolated from vastus lateralis (obese women (body mass index (BMI) = 34.7 ± 3.1 kg/m2)) were transfected with ACSL-5 plasmid DNA or green fluorescent protein (GFP) vector (control), differentiated into myotubes, and harvested (7 days). HSKMC were assayed for complete and incomplete fatty acid oxidation ([1-14C] palmitate) or permeabilized to determine mitochondrial respiratory capacity (basal (non-ADP stimulated state 4), maximal uncoupled (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP)-linked) respiration, and free radical (superoxide) emitting potential). Protein levels of ACSL-5 were 2-fold higher in ACSL-5 overexpressed HSKMC. Both complete and incomplete fatty acid oxidation increased by 2-fold (p < 0.05). In permeabilized HSKMC, ACSL-5 overexpression significantly increased basal and maximal uncoupled respiration (p < 0.05). Unexpectedly, however, elevated ACSL-5 expression increased mitochondrial superoxide production (+30%), which was associated with a significant reduction (p < 0.05) in insulin-stimulated p-Akt and p-AS160 protein levels. We concluded that ACSL-5 in human skeletal muscle functions to increase mitochondrial fatty acid oxidation, but contrary to conventional wisdom, is associated with increased free radical production and reduced insulin signaling

Microvascular Endothelial Dysfunction in Sedentary, Obese Humans Is Mediated by NADPH Oxidase Influence of Exercise Training

Objective—The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results—Young, sedentary men and women were divided into lean (body mass index 18–25; n=14), intermediate (body mass index 28–32.5; n=13), and obese (body mass index 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2 O2 ) and superoxide levels in the vastus lateralis of obese compared with both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase inhibitor, lowered (normalized) H2 O2 and superoxide levels, and reversed microvascular endothelial dysfunction in obese subjects. After 8 weeks of exercise, H2 O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the NADPH oxidase subunits p22phox, p47phox, and p67phox was increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions—This study implicates NADPH oxidase as a source of excessive ROS production in skeletal muscle of obese individuals and links excessive NADPH oxidase–derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these malad

Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation

Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation. J Appl Physiol 106: 1079â 1085, 2009. First published February 5, 2009; doi:10.1152/japplphysiol.91262.2008. The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of 12 miles/wk, 1,200 kcal/wk at 40-55% peak O2 consumption (VO2peak), 200 min exercise/wk], 2) low volume/vigorous intensity (12 miles/wk, 1,200 kcal/wk at 65-80% VO2peak, 125 min/wk), and 3) high volume/vigorous intensity (20 miles/wk, 2,000 kcal/wk at 65-80% VO2peak, 200 min/wk). Insulin sensitivity (intravenous glucose tolerance test, SI) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. SI increased with training compared with the sedentary condition (P less than or equal to 0.05) at 16-24 h with all of the exercise prescriptions. SI decreased to sedentary, pretraining values after 15 days of training cessation in the low-volume/vigorous-intensity group. In contrast, at 15 days SI was significantly elevated compared with sedentary (P less than or equal to 0.05) in the prescriptions utilizing 200 min/wk (low volume/moderate intensity, high volume/vigorous intensity). In the high-volume/vigorous-intensity group, indexes of muscle mitochondrial density followed a pattern paralleling insulin action by being elevated at 15 days compared with pretraining; this trend was not evident in the low-volume/moderateintensity group. These findings suggest that in overweight/obese subjects a relatively chronic persistence of enhanced insulin action may be obtained with endurance-oriented exercise training; this persistence, however, is dependent on the characteristics of the exercise training performed