What is fatigue?

Fatigue is a subjective feeling of tiredness, weakness, or lack of energy that can vary in severity and duration. It is a common symptom experienced by many people at some point in their lives and can be temporary or chronic. Fatigue can affect physical, mental, and emotional well-being and may interfere with daily activities, work performance, and quality of life.


What is the relationship between fatigue and oxidative stress?

The relationship between fatigue and oxidative stress is complex and bidirectional, with each influencing the other in various physiological and pathological conditions. Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses, leading to cellular damage and dysfunction. Fatigue, on the other hand, is a subjective feeling of tiredness, weakness, or lack of energy that can result from various physical, psychological, and environmental factors.


Several mechanisms underlie the relationship between fatigue and oxidative stress:


  • Mitochondrial Dysfunction: Oxidative stress can impair mitochondrial function, particularly in cells with high energy demands such as muscle cells and neurons. Mitochondria are the primary producers of cellular energy (ATP) through oxidative phosphorylation, and they are also a major source of reactive oxygen species (ROS). Mitochondrial dysfunction leads to decreased ATP production, increased ROS generation, and oxidative damage to cellular components, contributing to fatigue and reduced energy levels.


  • Inflammation: Oxidative stress and inflammation are closely interconnected processes that can contribute to fatigue. Chronic inflammation stimulates the production of ROS by immune cells, leading to oxidative stress and tissue damage. In turn, oxidative stress can activate inflammatory pathways and exacerbate inflammation, creating a cycle of oxidative stress and inflammation that contributes to fatigue and fatigue-related symptoms. Chronic inflammatory conditions such as autoimmune diseases, chronic infections, and metabolic disorders are often associated with both fatigue and oxidative stress.


  • Neurotransmitter Imbalance: Oxidative stress can affect neurotransmitter systems in the brain, including serotonin, dopamine, and norepinephrine, which play key roles in regulating mood, motivation, and energy levels. Imbalances in neurotransmitter levels are implicated in the pathogenesis of fatigue and mood disorders such as depression and anxiety. Oxidative stress may disrupt neurotransmitter synthesis, release, and signaling pathways, contributing to fatigue and fatigue-related symptoms.


  • Cellular Damage and Dysfunction: Oxidative stress can damage cellular components such as lipids, proteins, and DNA, leading to cellular dysfunction and impaired cellular processes. ROS can directly affect cellular signaling pathways, gene expression, and protein function, disrupting normal cellular homeostasis and contributing to fatigue. Oxidative damage to muscle cells, neurons, and other tissues can impair their function and contribute to fatigue and reduced physical and cognitive performance.


  • Antioxidant Defenses: Chronic fatigue and conditions associated with oxidative stress may be characterized by dysregulation of antioxidant defenses. Antioxidants play a crucial role in neutralizing ROS and protecting cells from oxidative damage. Reduced antioxidant capacity or increased ROS production can tip the balance toward oxidative stress and contribute to fatigue. Supporting antioxidant defenses through dietary antioxidants, supplementation, or lifestyle modifications may help mitigate oxidative stress and alleviate fatigue symptoms in some individuals.


Overall, the relationship between fatigue and oxidative stress involves complex interactions between cellular pathways, inflammatory processes, neurotransmitter systems, and antioxidant defenses.