What are the causes of fatigue?

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Last updated: March 5, 2025View editorial policy

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From the Guidelines

Fatigue is a complex and multifaceted symptom that can be caused by a variety of biological, psychological, and social factors, and its management should be tailored to the individual's specific needs and preferences, as recommended by the 2023 EULAR guidelines 1. The causes of fatigue can be diverse and include underlying medical conditions such as anemia, thyroid disorders, sleep apnea, or depression, as well as lifestyle factors like poor sleep quality, lack of physical activity, and unhealthy nutrition habits. Some key factors that contribute to fatigue include:

  • Immune system dysfunction, which may involve the production of pro-inflammatory cytokines and other mediators that can induce fatigue, as suggested by research on cancer-related fatigue 1
  • Central and autonomic nervous system dysfunction, which can affect the regulation of fatigue perception and energy homeostasis
  • Neuroendocrine system dysfunction, which can impact the balance of hormones that regulate energy and motivation
  • Sleep disturbances, which are prevalent in up to 75% of patients with cancer and can significantly contribute to fatigue, as noted in the NCCN clinical practice guidelines for cancer-related fatigue 1
  • Emotional distress, including depression and anxiety, which can be both a cause and a consequence of fatigue
  • Physical inactivity and deconditioning, which can lead to decreased cardiovascular function and reduced energy levels
  • Nutritional deficiencies and poor dietary habits, which can impair energy production and exacerbate fatigue To address fatigue, it is essential to identify and treat any underlying medical conditions, as well as to implement lifestyle modifications that promote healthy sleep habits, regular physical activity, and balanced nutrition. The most effective approach to managing fatigue is a multifaceted one that incorporates patient-centered care, shared decision-making, and tailored interventions, as recommended by the American Society of Clinical Oncology clinical practice guideline adaptation for screening, assessment, and management of fatigue in adult survivors of cancer 1.

From the Research

Causes of Fatigue

The causes of fatigue are multifaceted and can be attributed to various factors, including:

  • Age, gender, physical condition, type of food, latency to last meal, mental status, psychological conditions, personality type, life experience, and health status of an individual 2
  • Underlying diseases, such as cancer, neurological disorders, and sleep disorders 3, 4, 5
  • Decompression of already known conditions, depression, excessive psychosocial stress, anemia, and other organic causes 4
  • Nutrition and dietary intake, including insufficient energy and protein consumption, which can lead to catabolism of body fat and muscles, disrupt homeostatic balance, and cause fatigue 6
  • Inflammation and mitochondrial dysfunction, which can be triggered by malnutrition and other factors 6

Classification of Fatigue

Fatigue can be classified as:

  • Acute or chronic 2
  • A symptom or a measurable and quantifiable dimension, also known as fatigability 2
  • A condition occurring at rest or under exercise or stress, as physiologic reaction or pathologic condition, as spontaneous phenomenon or triggerable state, as resistant or irresistant to preconditioning, training, or attitude, as prominent or collateral experience, and as accessible or inaccessible to any type of treatment or intervention 2

Prevalence of Fatigue

Fatigue is a highly prevalent condition, affecting:

  • 10-20% of all consultations with a primary care physician 4
  • A significant proportion of cancer patients, with fatigue being a major obstacle to maintaining normal daily activities and quality of life 3
  • Individuals with neurological diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson disease, traumatic brain injury, stroke, and bleeding, as well as neuromuscular disorders 2, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Fatigue in healthy and diseased individuals.

The American journal of hospice & palliative care, 2014

Research

Fatigue in older persons: the role of nutrition.

The Proceedings of the Nutrition Society, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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