Evaluation of an Antioxidant and Anti-inflammatory Cocktail Against Human Hypoactivity-Induced Skeletal Muscle Deconditioning.

Michele Salanova,Dieter Blottner,Bernard J Jasmin,Coralie Arc-Chagnaud,Mari-Carmen Gomez-Cabrera,Angèle Chopard,Rémi Roumanille,Stéphane Blanc,Pierre Delobel,Thomas Brioche,José Viña,Rémi Demangel,Allan F Pagano,Théo Fovet,Guillaume Py

doi:10.3389/fphys.2020.00071

Abstract

Understanding the molecular pathways involved in the loss of skeletal muscle mass and function induced by muscle disuse is a crucial issue in the context of spaceflight as well as in the clinical field, and development of efficient countermeasures is needed. Recent studies have reported the importance of redox balance dysregulation as a major mechanism leading to muscle wasting. Our study aimed to evaluate the effects of an antioxidant/anti-inflammatory cocktail (741 mg of polyphenols, 138 mg of vitamin E, 80 μg of selenium, and 2.1 g of omega-3) in the prevention of muscle deconditioning induced by long-term inactivity. The study consisted of 60 days of hypoactivity using the head-down bed rest (HDBR) model. Twenty healthy men were recruited; half of them received a daily antioxidant/anti-inflammatory supplementation, whereas the other half received a placebo. Muscle biopsies were collected from the vastus lateralis muscles before and after bedrest and 10 days after remobilization. After 2 months of HDBR, all subjects presented muscle deconditioning characterized by a loss of muscle strength and an atrophy of muscle fibers, which was not prevented by cocktail supplementation. Our results regarding muscle oxidative damage, mitochondrial content, and protein balance actors refuted the potential protection of the cocktail during long-term inactivity and showed a disturbance of essential signaling pathways (protein balance and mitochondriogenesis) during the remobilization period. This study demonstrated the ineffectiveness of our cocktail supplementation and underlines the complexity of redox balance mechanisms. It raises interrogations regarding the appropriate nutritional intervention to fight against muscle deconditioning.

Highlights

Skeletal muscle is a plastic tissue able to adapt to intrinsic and environmental stresses (Harridge, 2007)
Torques measured in the ankle extension and flexion modes were equal at baseline in the two groups and significantly decreased after bedrest in both groups (−16 and −25% for the placebo group and −22 and −25% for the cocktail group, in flexion and extension mode, respectively; Figure 2B). These results demonstrated that 2 months of bedrest induced a significant loss of lower limb muscle strength, which was not prevented by cocktail supplementation
In aerospace applications, understanding muscle deconditioning mechanisms induced by microgravity environments constitutes an essential issue

Summary

Introduction

Skeletal muscle is a plastic tissue able to adapt to intrinsic and environmental stresses (Harridge, 2007). While physical exercise and training reinforce our muscles, in contrast, situations of hypoactivity such as immobilization, sedentary lifestyle, or microgravity environments lead to skeletal muscle deconditioning. In this context, space agencies must always work on the optimization of countermeasures, especially in astronaut training programs and supplementation to preserve their work capacity and health. It translates mainly to a loss of muscle mass and myofiber atrophy, largely induced by a dysregulation of protein balance signaling pathways (Kandarian and Stevenson, 2002; Glass, 2005; Degens and Alway, 2006; Ventadour and Attaix, 2006). Alteration of some actors of the oxidative system (mitochondria and enzymes) contributes to the shift toward a glycolytic profile to the detriment of the oxidative one (Widrick et al, 1999; Fitts et al, 2010)

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