Acarbose promotes remission of both early and late dumping syndromes in post-bariatric patients

Objective: Acarbose is a glucosidase inhibitor that slows carbohydrate digestion. It could thus be effective to promote remission of dumping syndrome (DS). Previous studies associating acarbose and late dumping, although not early dumping, have been reported. Herein, we aimed to evaluate the role of acarbose in dumping syndrome prevention and treatment and in resistive exercises resistance in bariatric subjects. Methods: Bariatric patients with DS and complete adherence to diet plan and resistive exercises were included (n=25). Number of early and late episodes, self-referred intensity of each episode, and ability to increase intensity of resistive exercise were evaluated, on a 0-10 scale. Acarbose was administered orally (50 mg) for 6 months, 4-5 times a day before meals. Results: Acarbose administration was associated with a decrease in the number of early (2.18-0.31) and late (2.79-0.12) episodes per week and intensity of each episode (6.10-1.65) and an increase in the ability to perform resistive exercises (3.03-7.12). Complete remission of DS was seen in 21 patients (84%), which persisted for 6 months with the use of acarbose. Conclusion: Acarbose prevented dumping in almost all studied subjects and helped improve exercise capacity.Division of Endocrinology and Metabolism, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SPCorpometria Institute, an Obesity and Endocrinology Center, Brasilia, DF, BrazilDivision of Endocrinology and Metabolism, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, R Pedro de Toledo 781, BR-04039032 Sao Paulo, SP, Brazil.Web of Scienc

Novel insights of overtraining syndrome discovered from the EROS study

BackgroundExcessive training and inadequate recovery could cause ‘overtraining syndrome’ (OTS), which is characterised by underperformance and fatigue. The pathophysiology of OTS is unclear. We aimed to describe novel mechanisms and risk factors associated with OTS, and thereby facilitate its early identification and prevention, from a comprehensive joint qualitative analysis of the findings from all the four arms of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study.MethodsWe compared the types and proportions of behavioural patterns of 67 evaluated parameters of OTS from 51 participants—athletes with OTS (OTS, n=14), healthy athletes (n=25) and healthy non-physically active controls (n=12). We performed overall and pairwise comparisons for statistically significant differences between the three groups (p<0.05).ResultsA total of 44 (65.7%) markers exhibited significant differences between the three groups: 32 (72.7%) showed a loss of the conditioning effect of exercise (‘deconditioning’), 7 (15.9%) showed changes exclusive to OTS, 3 (6.8%) maintained the exercise-induced conditioning effects and 2 (4.5%) revealed an exacerbation of the adaptive changes to exercises.ConclusionOur findings suggest that OTS is likely triggered by multiple factors, not restricted to excessive training, resulted from a chronic energy deprivation, leading to multiple losses in the conditioning processes typically observed in healthy athletes, as a combination of ‘paradoxical deconditioning’ processes, which explains the gradual and marked loss of physical conditioning found in OTS. We, therefore, suggest that the term ‘paradoxical deconditioning syndrome’ better represents the features of this syndrome

Hormonal aspects of overtraining syndrome: a systematic review

Abstract Background Overtraining syndrome (OTS), functional (FOR) and non-functional overreaching (NFOR) are conditions diagnosed in athletes with decreased performance and fatigue, triggered by metabolic, immune, hormonal and other dysfunctions and resulted from an imbalance between training stress and proper recovery. Despite previous descriptions, there is a lack of a review that discloses all hormonal findings in OTS/FOR/NFOR. The aim of this systematic review is to evaluate whether and which roles hormones play in OTS/FOR/NFOR. Methods A systematic search up to June 15th, 2017 was performed in the PUBMED, MEDLINE and Cochrane databases following PRISMA protocol, with the expressions: (1)overtraining, (2)overreaching, (3)overtrained, (4)overreached, or (5)underperformance, and (plus) (a)hormone, (b)hormonal, (c)endocrine, (d)adrenal, (e)cortisol, (f)GH, (g)ACTH, (h)testosterone, (i)IGF-1, (j)TSH, (k)T4, (l)T3, (m)LH, (n)FSH, (o)prolactin, (p) IGFBP-3 and related articles. Results A total of 38 studies were selected. Basal levels of hormones were mostly normal in athletes with OTS/FOR/NFOR compared with healthy athletes. Distinctly, stimulation tests, mainly performed in maximal exercise conditions, showed blunted GH and ACTH responses in OTS/FOR/NFOR athletes, whereas cortisol and plasma catecholamines showed conflicting findings and the other hormones responded normally. Conclusion Basal hormone levels are not good predictor but blunted ACTH and GH responses to stimulation tests may be good predictors of OTS/FOR/NFOR

Adrenal fatigue does not exist: a systematic review

Background: The term "adrenal fatigue" ("AF") has been used by some doctors, healthcare providers, and the general media to describe an alleged condition caused by chronic exposure to stressful situations. Despite this, "AF" has not been recognized by any Endocrinology society, who claim there is no hard evidence for the existence. The aim of this systematic review is to verify whether there is substantiation for "AF". Methods: A systematic search was performed at PUBMED, MEDLINE (Ebsco) and Cochrane databases, from the beginning of the data until April 22nd, 2016. Searched key words were: "adrenal" + "fatigue", "adrenal" + "burnout", "adrenal" + "exhaustion", "hypoadrenia", "burnout" + "cortisol", "fatigue" + "cortisol", "clinical" + "burnout", "cortisol" + "vitalility", "adrenal" + "vitality", and "cortisol" + "exhaustion". Eligibility criteria were: (1) articles written in English, (2) cortisol profile and fatigue or energy status as the primary outcome, (3) performed tests for evaluating the adrenal axis, (4) absence of influence of corticosteroid therapy, and (5) absence of confounding diseases. Type of questionnaire to distinct fatigued subjects, population studied, tests performed of selected studies were analyzed. Results: From 3,470 articles found, 58 studies fulfilled the criteria: 33 were carried in healthy individuals, and 25 in symptomatic patients. The most assessed exams were "Direct Awakening Cortisol" (n = 29), "Cortisol Awakening Response" (n = 27) and "Salivary Cortisol Rhythm" (n = 26). Discussion: We found an almost systematic finding of conflicting results derived from most of the studies methods utilized, regardless of the validation and the quality of performed tests. Some limitations of the review include: (1) heterogeneity of the study design(2) the descriptive nature of most studies(3) the poor quality assessment of fatigue(4) the use of an unsubstantiated methodology in terms of cortisol assessment (not endorsed by endocrinologists)(5) false premises leading to an incorrect sequence of research directionand, (6) inappropriate/invalid conclusions regarding causality and association between different information. Conclusion: This systematic review proves that there is no substantiation that "adrenal fatigue" is an actual medical condition. Therefore, adrenal fatigue is still a myth.[Cadegiani, Flavio A.Kater, Claudio E.] Univ Fed Sao Paulo EPM UNIFESP, Escola Paulista Med, Dept Med, Adrenal & Hypertens Unit,Div Endocrinol & Metab, R Pedro Toledo 781-13th Floor, BR-04039032 Sao Paulo, SP, BrazilUniv Fed Sao Paulo EPM UNIFESP, Escola Paulista Med, Dept Med, Adrenal & Hypertens Unit,Div Endocrinol & Metab, R Pedro Toledo 781-13th Floor, BR-04039032 Sao Paulo, SP, BrazilWeb of Scienc

Hypothalamic-Pituitary-Adrenal (HPA) Axis Functioning in Overtraining Syndrome: Findings from Endocrine and Metabolic Responses on Overtraining Syndrome (EROS)—EROS-HPA Axis

Abstract Background Overtraining syndrome (OTS) results from excessive training load without adequate recovery and leads to decreased performance and fatigue. The pathophysiology of OTS in athletes is not fully understood, which makes accurate diagnosis difficult. Previous studies indicate that alterations in the hypothalamus-pituitary-adrenal (HPA) axis may be responsible for OTS; however, the data is not conclusive. This study aimed to compare, through gold standard and exercise-independent tests, the response of the HPA axis in OTS-affected athletes (OTS group) to healthy physically active subjects (ATL group) and healthy non-active subjects (NCS group). Methods Selected subjects were evaluated for cortisol response to a 250-μg cosyntropin stimulation test (CST), cortisol and adrenocorticotropic hormone (ACTH) responses during an insulin tolerance test (ITT), and salivary cortisol rhythm (SCR). Results A total of 51 subjects were included (OTS, n = 14; ATL, n = 25; and NCS, n = 12). Cortisol response in the CST was similar among the three groups. Conversely, mean cortisol response during an ITT was significantly higher in ATL (21.7 μg/dL; increase = 9.2 μg/dL) compared to OTS (17.9 μg/dL; 6.3 μg/dL) and NCS (16.9 μg/dL; 6.0 μg/dL) (p ≤ 0.001; p = 0.01). Likewise, median ACTH response during an ITT was significantly higher in ATL (91.4 pg/mL; increase = 45.1 pg/mL) compared to OTS (30.3 pg/mL; 9.7 pg/mL) and NCS (51.4 pg/mL; 38.0 pg/mL) (p = 0.006; p = 0.004). For SCR, mean cortisol 30 min after awakening was significantly higher in ATL (500 ng/dL) compared to OTS (323 ng/dL) and NCS (393 ng/dL) (p = 0.004). We identified the following cutoffs that could help exclude or confirm OTS: cortisol level at 30 min after awakening (exclusion = > 530 ng/dL); cortisol response to ITT (exclusion = > 20.5 μg/dL; confirmation =  106 pg/mL or increase > 70 pg/mL; confirmation = < 35 pg/mL and increase < 14.5 pg/mL). Conclusion The findings of the present study showed that healthy athletes disclose adaptions to exercises that helped improve sport-specific performance, whereas this sort of hormonal conditioning was at least partially lost in OTS, which may explain the decrease in performance in OTS

Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial.

Background The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into type II pneumocytes is dependent on a modification of viral spike proteins by transmembrane protease&nbsp;serine 2 (TMPRSS2) expressed on the surface of human cells.&nbsp;TMPRSS2 is regulated by the androgen receptor, hence, SARS-CoV-2 infectivity is indirectly dependent on androgenic status and phenotype.&nbsp;Previously, we have reported that men affected by androgenetic alopecia (AGA) are overrepresented in severe coronavirus disease 2019 (COVID-19). Additionally, we have reported that men taking antiandrogenic drugs, e.g., 5-alpha-reductase inhibitors (5ARis), are less likely to have severe COVID-19.&nbsp;Here we aimed to test whether the androgen receptor antagonist, Proxalutamide, would be a beneficial treatment for subjects with SARS-CoV-2 infection. Methods Male and female subjects were recruited to a double-blinded, randomized, prospective, investigational study of Proxalutamide for the treatment of COVID-19.&nbsp;Mild to moderate, non-hospitalized subjects, who were confirmed positive for SARS-CoV-2, were treated with either Proxalutamide 200 mg/day or placebo. Endpoints for the study were remission time (days) and the percentage of subjects confirmed negative for SARS-CoV-2 on Day 7 after treatment.&nbsp;A negative SARS-CoV-2 test was defined by concentration-time (Ct)&gt;40&nbsp;determined by real-time reverse transcription-polymerase chain reaction (rtPCR). Results Two-hundred thirty-six (2360 subjects were included in the study (108 female, 128 male); 171 were randomized to the Proxalutamide arm and 65 were in the placebo group.&nbsp;On Day 7, SARS-CoV-2 became non-detectable with rtPCR (cT&gt;40) in 82% of the subjects in the Proxalutamide group versus 31% in the placebo group (p &lt; 0.001).&nbsp;The average clinical remission time for patients treated with Proxalutamide was 4.2 ±5.4 days versus 21.8 ±13.0 days in the placebo arm (p &lt; 0.001). Conclusion Proxalutamide significantly accelerated viral clearance on Day 7 in mild to moderate COVID-19 patients versus placebo.&nbsp;Further, the time to clinical remission was significantly reduced in patients treated with Proxalutamide versus placebo