The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial.

Background: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS. Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39-2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34-1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46-1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 µmol/mg protein, [95% CI 0.57-1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment. Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.

Validade do RAST para avaliar o desempenho da potência anaeróbia em relação ao teste Wingate em ciclistas / Validad del RAST para evaluar el rendimiento de potencia anaeróbica en comparación con el test de Wingate en los atletas de ciclismo / Validity of the RAST for evaluating anaerobic power performance as compared to Wingate test in cycling athletes

The validity of the Running-based Anaerobic Sprint Test (RAST) was investigated to evaluate the anaerobic power performance in comparison to Wingate test in cycling athletes. Ten mountain-bike male cyclists (28.0±7.3 years) randomly performed Wingate Test and RAST with two trials each. After several anthropometric measurements, peak power (PP), mean power (MP) and fatigue index (FI) for RAST and Wingate Test were analyzed using Student's paired t-test, Pearson's linear correlation test (r) and Bland and Altman's plots. Results showed that, with the exception of FI (33.8±4.6% vs. 37.8±7.9%; r=0.172), significant differences were detected between the Wingate and RAST tests with regard to PP and MP. Although there was a strong correlation for PP and MP, or rather, 0.831 and 0.714 respectively, agreement of analysis between Wingate and RAST protocols was low. The above suggested that RAST was not appropriate to evaluate the performance of anaerobic power by Wingate test in cycling athletes.

O objetivo foi investigar a validade do teste de RAST (Running-based Anaerobic Sprint Test) em avaliar o desempenho da potência anaeróbia a partir do teste de Wingate em ciclistas treinados. Participaram do estudo 10 ciclistas do sexo masculino (28,0±7,3 anos) da modalidade de Mountain bike. Após a mensuração das variáveis antropométricas, a potência pico (PP), média (PM) e o índice de fadiga (IF) foram determinados randomicamente a partir de dois testes de Wingate e dois testes de RAST. Foram utilizados o teste t independente de Student, a análise de correlação linear de Pearson (r) e o teste de Bland-Altman. Os resultados demonstraram, exceto para o IF (33.8±4.6% vs. 37.8±7.9%; r=0.172), diferenças significativas entre o teste de Wingate e o RAST para PP e PM (W.kg-1 e W). Embora os valores de correlação para a PP e PM (W) tenham sido fortes (0.831 e 0.714, respectivamente) a concordância entre os protocolos de Wingate e RAST foi baixa, sugerindo que o teste de RAST não é válido para avaliar o desempenho da potência anaeróbica a partir do teste de Wingate em ciclistas.

El objetivo fue investigar la validad del teste de RAST (Running-based Anaerobic Sprint Test) en evaluar el desempeño de la potencia anaeróbica través del uso del teste de Wingate en ciclistas trenados. Participaron del estudio 10 ciclistas masculinos (28,0±7,3 años) de la modalidad de Mountain bike. Después de la mensuración de las variables antropométricas, la potencia pico (PP), media (PM) y el índice de fatiga (IF) fueron determinados al acaso a partir de dos testes de Wingate y de dos testes de RAST. Fueron utilizados el test t independiente de Student, el análisis de correlación linear de Pearson (r) y el test de Bland-Altman. Los resultados demostraron, contrariamente al IF (33.8±4.6% vs. 37.8±7.9%; r=0.172), diferencias significativas entre el teste de Wingate y el RAST para PP y PM (W.kg-1 e W). Mismo que los valores de correlación de PP e PM (W) tengan sido fortes (0,831 e 0,714, respectivamente), la concordancia entre los protocolos de Wingate y RAST fue baja, sugiriendo que el teste de RAST no es válido para evaluar el desempeño de la potencia anaeróbica a partir del teste de Wingate en este grupo.