Biological Aspects of Fatigue: A Narrative Review
Authors: Azevedo Maria Paula Carvalho , Ultramar Rafael Francischetto , Paganini Túlio Novaes , Medeiros Elisa Smith Barbiero , Alves Catarina Bubach Ribeiro , Cabral Hebert Wilson Santos 
Published: December 2023

Introduction: Fatigue is among the most common symptoms in Primary Health-Care and it can be caused by several factors. It is prevailing in the general population and the aggravated condition of fatigue is named Chronic Fatigue Syndrome. This syndrome has a negative impact on the individual’s quality of life and it can lead to functional incapacity. Despite decades of research, Chronic Fatigue Syndrome remains a mysterious disease that needs to be highlighted.
Objective: To describe biological aspects of fatigue regarding its definition, biological origin, the main etiologies of Chronic Fatigue Syndrome and its relation with the circadian cycle, as well as the main methods for measurement, diagnosis, complementary tests and treatment.
Method: It is a narrative review, performed from 2019 to 2022, using the PubMed/MEDLINE database and a manual search for studies referred in selected articles from authors with notorious knowledge and specialized groups in the area. It was performed a combination of several search terms added to Fatigue and Fatigue Syndrome, Chronic through Boolean Operators AND, OR and NOT. Scientific articles that involved studies in humans were included in the research. The articles were available in full version for free, in Portuguese, English and Spanish, with no restriction related to the period of publication. The articles were selected by reading of titles and abstracts. The ones that did not fit the aim of this study were excluded. The remaining articles were read in full and selected according to their relevance and contribution to the topic.
Results: Fatigue can be considered peripheral, physical, mental, intellectual and emotional, but there is no consensus regarding its definition. Its main biological origin is related to cytokines, however, fatigue’s measurement is still mostly conducted by self-reports of affected patients. There is no objective marker consistently associated to fatigue. Regarding Chronic Fatigue Syndrome, its etiology is still not very well-established, but it was observed that genetic, epigenetic, immunological, infectious, psychosocial, psychiatric and neurological factors can contribute to it. Since fatigue is multidimensional and multifactorial, it is important to associate multiple instruments for its investigation. A potent strategy for the measurement of fatigue is using instruments adapted to the realities, extensively tested in different populations considering socio-economic-cultural aspects. These instruments assess the cognitive function in order to measure several variables and when associated they can increase the accuracy of the investigative instruments. The treatments available include cognitive-behavioral therapy, gradual exercises, immunological treatment, corticosteroids and antidepressants, but they do not guarantee a full remission of symptoms in an isolated way.
Conclusion: Even though there are well-defined biological factors it still lacks a precise marker for the measurement of fatigue. Considering fatigue as multidimensional and multifactorial, it is important to associate several instruments for its investigation. The treatments available have shown effectiveness, but they do not guarantee a full remission of symptoms in an isolated way. For this reason, it is necessary a bio-psycho-social care for these patients.