Acupuncture or auricular electro-acupuncture as adjuncts to lifestyle interventions for weight management in PCOS: protocol for a randomised controlled feasibility study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent women's health condition with reproductive, metabolic, and psychological manifestations. Weight loss can improve these symptoms and is a key goal; however, many women find this difficult to achieve. Acupuncture is a Chinese medical treatment that involves insertion of very fine metal needles into specific areas of the body and has been shown to be efficacious for weight loss in non-PCOS populations. However, few studies have been conducted in women with PCOS. A variant of acupuncture, auricular electro-acupuncture (AEA), may have beneficial effects on sympathetic tone, which is associated with insulin resistance, obesity and PCOS. METHODS: This prospective three-arm open label parallel randomised controlled trial will assess feasibility and acceptability of acupuncture and/or AEA for weight loss in women with PCOS. We will enrol 39 women from the community aged between 18 and 45 years, with physician diagnosis of PCOS according to the Rotterdam criteria: body mass index (BMI) between 25 and 40 kg/m2. Women will be randomly allocated to receive one of three treatments for 12 weeks duration: body electro-acupuncture + lifestyle interventions, AEA + lifestyle interventions, or lifestyle interventions alone. The lifestyle intervention in this study is telephone-based health coaching (between 4 and 13 phone calls, depending on individual need), provided by the Get Healthy Service. Primary outcomes of the study are feasibility and acceptability of trial methods as determined by recruitment and retention rates, adherence, acceptability, credibility, and safety. Secondary outcomes include anthropometric (body weight, BMI, waist and hip circumference), metabolic (glucose tolerance and insulin sensitivity obtained from a 2-h 75 g oral glucose tolerance test with area under the curve insulin calculated using the trapezoid rule), reproductive (androgen levels, menstrual cyclicity, clinical hyperandrogenism using the Ferriman-Gallwey scoring system), autonomic (heart rate variability, blood pressure), lifestyle (physical activity levels, diet quality, weight self-efficacy), quality of life, and psychological (depression and anxiety symptoms, internal health locus of control). DISCUSSION: This study addresses the feasibility and acceptability of novel interventions to treat overweight/obesity in PCOS. Study findings have the potential to generate a new understanding of the role of acupuncture and auricular acupuncture in weight management. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, 8/6/18 ACTRN12618000975291.

Attempting to Compensate for Reduced Neuronal Nitric Oxide Synthase Protein with Nitrate Supplementation Cannot Overcome Metabolic Dysfunction but Rather Has Detrimental Effects in Dystrophin-Deficient mdx Muscle.

Duchenne muscular dystrophy arises from the loss of dystrophin and is characterized by calcium dysregulation, muscular atrophy, and metabolic dysfunction. The secondary reduction of neuronal nitric oxide synthase (nNOS) from the sarcolemma reduces NO production and bioavailability. As NO modulates glucose uptake, metabolism, and mitochondrial bioenergetics, we investigated whether an 8-week nitrate supplementation regimen could overcome metabolic dysfunction in the mdx mouse. Dystrophin-positive control (C57BL/10) and dystrophin-deficient mdx mice were supplemented with sodium nitrate (85 mg/l) in drinking water. Following the supplementation period, extensor digitorum longus and soleus were excised and radioactive glucose uptake was measured at rest (basal) and during contraction. Gastrocnemius was excised and mitochondrial respiration was measured using the Oroboros Oxygraph. Tibialis anterior was analyzed immunohistochemically for the presence of dystrophin, nNOS, nitrotyrosine, IgG and CD45+ cells, and histologically to assess areas of damage and regeneration. Glucose uptake in the basal and contracting states was normal in unsupplemented mdx muscles but was reduced following nitrate supplementation in mdx muscles only. The mitochondrial utilization of substrates was also impaired in mdx gastrocnemius during phosphorylating and maximal uncoupled respiration, and nitrate could not improve respiration in mdx muscle. Although nitrate supplementation reduced mitochondrial hydrogen peroxide emission, it induced mitochondrial uncoupling in red gastrocnemius, increased muscle fiber peroxynitrite (nitrotyrosine), and promoted skeletal muscle damage. Our novel data suggest that despite lower nNOS protein expression and likely lower NO production in mdx muscle, enhancing NO production with nitrate supplementation in these mice has detrimental effects on skeletal muscle. This may have important relevance for those with DMD.

A Combination of Amino Acids and Caffeine Enhances Sprint Running Capacity in a Hot, Hypoxic Environment.

Heat and hypoxia exacerbate central nervous system (CNS) fatigue. We therefore investigated whether essential amino acid (EAA) and caffeine ingestion attenuates CNS fatigue in a simulated team sport-specific running protocol in a hot, hypoxic environment. Subelite male team sport athletes (n = 8) performed a repeat sprint running protocol on a nonmotorized treadmill in an extreme environment on 4 separate occasions. Participants ingested one of four supplements: a double placebo, 3 mg.kg-1 body mass of caffeine + placebo, 2 x 7 g EAA (Musashi Create)+placebo, or caffeine + EAA before each exercise session using a randomized, double-blind crossover design. Electromyography (EMG) activity and quadriceps evoked responses to magnetic stimulation were assessed from the dominant leg at preexercise, halftime, and postexercise. Central activation ratio (CAR) was used to quantify completeness of quadriceps activation. Oxygenation of the prefrontal cortex was measured via near-infrared spectroscopy. Mean sprint work was higher (M = 174 J, 95% CI [23, 324], p < .05, d = 0.30; effect size, likely beneficial) in the caffeine + EAA condition versus EAAs alone. The decline in EMG activity was less (M = 13%, 95% CI [0, 26]; p < .01, d = 0.58, likely beneficial) in caffeine + EAA versus EAA alone. Similarly, the pre- to postexercise decrement in CAR was significantly less (M = -2.7%, 95% CI [0.4, 5.4]; p < .05, d = 0.50, likely beneficial) when caffeine + EAA were ingested compared with placebo. Cerebral oxygenation was lower (M = -5.6%, 95% CI [1.0, 10.1]; p < .01, d = 0.60, very likely beneficial) in the caffeine + EAA condition compared with LNAA alone. Co-ingestion of caffeine and EAA appears to maintain muscle activation and central drive, with a small improvement in running performance.

Vitamin D in polycystic ovary syndrome: Relationship to obesity and insulin resistance.

SCOPE: Polycystic ovary syndrome (PCOS) is underpinned by insulin resistance (IR). In PCOS, the relationships between vitamin D, adiposity, and IR are unclear. We aim to explore these relationships in lean and overweight women with PCOS. METHODS AND RESULTS: This is a cross-sectional study conducted in a tertiary medical center. Participants included 42 women with PCOS and 34 controls without PCOS. Vitamin D and metabolic markers were measured. Detailed body composition and gold standard hyperinsulinemic euglycemic clamps were performed. The main outcome measures were plasma levels of vitamin D, adiposity measures, and glucose infusion rate. Vitamin D levels were lower in overweight women with PCOS compared with overweight controls (31.6 and 46.1 nmol/L, respectively, p = 0.01). Vitamin D was not associated with IR after adjustment for confounders; however, there was a significant interaction between PCOS and percentage body fat. Further analysis by PCOS status revealed that vitamin D was associated with IR in the PCOS group (ß coefficient 2.1, 95% CI 0.2-4.0, p = 0.03), but not in the non-PCOS group. CONCLUSION: Vitamin D is associated with IR in women with PCOS, but not in controls. Large intervention studies are needed to determine if vitamin D supplementation can improve IR in PCOS.

N-acetylcysteine alters substrate metabolism during high-intensity cycle exercise in well-trained humans.

We investigated the effects of N-acetylcysteine (NAC) on metabolism during fixed work rate high-intensity interval exercise (HIIE) and self-paced 10-min time-trial (TT10) performance. Nine well-trained male cyclists (V̇O2peak, 69.4 ± 5.8 mL · kg(-1) · min(-1); peak power output (PPO), 385 ± 43 W; mean ± SD) participated in a double-blind, repeated-measures, randomised crossover trial. Two trials (NAC supplementation and placebo) were performed 7 days apart consisting of 6 × 5 min HIIE bouts at 82% PPO (316 ± 40 W) separated by 1 min at 100 W, and then after 2 min of recovery at 100 W, TT10 was performed. Expired gases, venous blood, and electromyographic (EMG) data were collected. NAC did not influence blood glutathione but decreased lipid peroxidation compared with the placebo (P < 0.05). Fat oxidation was elevated with NAC compared with the placebo during HIIE bouts 5 and 6 (9.9 ± 8.9 vs. 3.9 ± 4.8 µmol · kg(-1) · min(-1); P < 0.05), as was blood glucose throughout HIIE (4.3 ± 0.6 vs. 3.8 ± 0.6 mmol · L(-1); P < 0.05). Blood lactate was lower with NAC after TT10 (3.3 ± 1.3 vs. 4.2 ± 1.3 mmol · L(-1); P < 0.05). Median EMG frequency of the vastus lateralis was lower with NAC during HIIE (79 ± 10 vs. 85 ± 10 Hz; P < 0.05), but not TT10 (82 ± 11 Hz). Finally, NAC decreased mean power output 4.9% ± 6.6% (effect size = -0.3 ± 0.4, mean ± 90% CI) during TT10 (305 ± 57 W vs. 319 ± 45 W). These data suggest that NAC alters substrate metabolism and muscle fibre type recruitment during HIIE, which is detrimental to time-trial performance.

Effects of high-dose large neutral amino acid supplementation on exercise, motor skill, and mental performance in Australian Rules Football players.

This study investigated the effects of high-dose large neutral amino acid (LNAA) supplementation on attenuating fatigue-induced decrements in exercise and motor skill performance in Australian Rules Football (ARF) players. Fifteen subelite ARF players participated in 3 testing sessions separated by 7 days. Players completed an initial control trial involving a reactive motor skills test (RMST) and a reactive agility test (RAT) carried out before and after fatiguing exercise. In the subsequent experimental trials, players ingested a serotonin-depleting or protein control (PC) LNAA mixture 3 h before testing, allocated in a double-blind randomized cross-over design. Blood samples were taken at presupplementation and pre- and postexercise for analysis of plasma amino acid, insulin, and metabolite concentrations. The effect of the LNAA was established as the difference in the change in the mean RMST and RAT test scores among the depleting, PC, and baseline (BL) trials. Mean overall repetition time of the RAT was moderately improved by -5.2% ± 3.4% (mean ± 90% confidence limits; effect size -0.45 ± 0.28) after ingestion of the serotonin-depleting mixture compared with the BL trial. Serotonin-depleting and PC supplements had a divergent effect on mean repetition time after fatiguing exercise in RMST: depleting serotonin elicited a small improvement (-3.0% ± 2.7%) in motor skill performance in contrast to a small decrement (2.4% ± 2.7%) after ingestion of the PC mixture, when compared to the BL. High-dose serotonin-"depleting" LNAA supplementation given 3 h prior to intermittent high-intensity exercise improved reactive motor skill and agility performance in ARF players.