How N-Acetylcysteine Supplementation Affects Redox Regulation, Especially at Mitohormesis and Sarcohormesis Level: Current Perspective

Abstract

Exercise frequently alters the metabolic processes of oxidative metabolism in athletes, including exposure to extreme reactive oxygen species impairing exercise performance. Therefore, both researchers and athletes have been consistently investigating the possible strategies to improve metabolic adaptations to exercise-induced oxidative stress. N-acetylcysteine (NAC) has been applied as a therapeutic agent in treating many diseases in humans due to its precursory role in the production of hepatic glutathione, a natural antioxidant. Several studies have investigated NAC’s possible therapeutic role in oxidative metabolism and adaptive response to exercise in the athletic population. However, still conflicting questions regarding NAC supplementation need to be clarified. This narrative review aims to re-evaluate the metabolic effects of NAC on exercise-induced oxidative stress and adaptive response developed by athletes against the exercise, especially mitohormetic and sarcohormetic response.

Blood oxidative stress biomarkers in women: influence of oral contraception, exercise, and N-acetylcysteine

“…Previous research in men has reported an increase in total glutathione after intravenous NAC supplementation (Medved et al 2003 ) or that it remains stable after oral supplementation (Matuszczak et al 2005 ), and this may be due to equivalent changes in the reduced to oxidised glutathione ratio (Ferreira et al 2011 ; Matuszczak et al 2005 ). Our finding of a reduction in total glutathione during exercise may represent sex differences during exercise or a translation of NAC into specific pro-oxidants that were quenched by glutathione (Devrim-Lanpir et al 2021 ; Karimi et al 2016 ). For example, thiols were elevated in the plasma from acute NAC ingestion, which may have resulted in mixed disulphide formation.…”

The effects of N‐acetylcysteine on recovery biomarkers: A systematic review and meta‐analysis of controlled trials

“…NAC has been considered a powerful antioxidant and glutathione precursor playing a crucial role in a variety of fields including athletic performance, respiratory complications, poisonings, infections, and cardiovascular diseases (Devrim‐Lanpir et al, 2021; Zarei et al, 2020). According to the available literature, there are some doubts about NAC side effects.…”

“…However, other performance parameters such as lactate, pH, VO 2 , CK-MB, and CK were not assessed by the authors (Rhodes & Braakhuis, 2017). Also, a more recent narrative review presented the NAC effects on exercise-induced oxidative stress (EIOS) and athletes' adaptive responses (Devrim-Lanpir et al, 2021). To our knowledge, no study has attempted to run a systematic review and meta-analysis on NAC and recovery parameters (lactate, pH, VO 2 , CK, and CPK).…”

“…An imbalance between the generation of reactive oxygen species (ROS) and the availability of antioxidants induces oxidative stress which can lead to damage of biomolecules, contributing to the activation of inflammation signaling cascades (Farhangi et al, 2020). The increased level of oxidative stress, not only in patients but also in healthy and trained athletes, triggers inflammatory responses that may lead to the imbalance in levels of lactate, the potential of hydrogen (pH), oxygen consumption (VO 2 ), creatine kinase‐muscle brain (CK‐MB), and creatine kinase (CK) (Ammar & Abdou, 2020; Devrim‐Lanpir et al, 2021; Sakelliou et al, 2016; Song et al, 2015). A high level of oxidative stress exerts its negative effects on recovery by destroying cellular proteins and lipids in mitochondria (Kavyani et al, 2021), contractile myocytes (Scott K. Powers et al, 2011), and more gravely affecting various cellular signal cascades linked to cellular function adaptability and homeostasis (S. K. Powers et al, 2016).…”

Oxidative Stress in Skeletal Muscle

“…The review by Devrim-Lanpir et al [ 2 ] focuses on the induced effects of using N-acetylcysteine (NAC) due to its precursor role in the production of hepatic glutathione, a natural antioxidant that can significantly modulate exercise-induced oxidative stress. In the various studies considered by the authors, a possible therapeutic role for NAC in oxidative metabolism and the adaptive response to exercise is not always clear-cut.…”