KORN KURATED RESEARCH

The Role of Mitochondrial Dysfunction in Chronic Fatigue and Long COVID

Research shows that mitochondrial dysfunction plays a fundamental role in mental illness, chronic pain, fatigue, and post-infectious syndromes like Long COVID. Dysfunction arises from multiple types of exposures that damage mitochondria with excessive exposure to oxidative stressors.

Those of you who follow my work know my passion for supporting mitochondria for mental health and the ways in which psychotropic medications can depress mitochondrial respiration. Yes! Even mitochondria do their moment-to-moment pranayama! 

What are Mitochondria?

Mitochondria play a vital role in cellular energy production and overall cellular health. Mitochondrial dysfunction can be due to genetic, environmental, nutritional medication, or age-related influences. These changes disrupt neuronal energy, increase oxidative stress, and promote inflammation.

The first publication of this research post is an example of what happens when multiple studies are reviewed, with multiple designs and methods compared, in order to ascertain an outcome: Results end up being "clear as mud", and the authors correctly call for better-designed standardized studies. 

However, research needs to reflect bioindividual needs as well. In spite of the mixed conclusions from the first article, clinical observation and plenty of research evidence clearly show that mitochondrial dysfunction is involved in mental illness, chronic pain, fatigue, and post-infectious syndromes like Long COVID. The general agreement focuses on the numerous types of exposure that damage mitochondria and lead to excessive oxidative stress.  

The second article explores the role of mitochondrial dysfunction in Long COVID, and potential therapeutic strategies aimed at improving mitochondrial function. It highlights lifestyle changes, exercise, and dietary interventions while stressing the importance of continued research and collaborative efforts to advance our understanding and treatment of Long COVID.

The final article of this post draws links between fatigue, serotonin, and hypothyroidism, suggesting the use of the amino acid L- Carnitine, known for its benefits in mitochondrial support, may play a role in improving outcomes.

How to Support Your Mitochondria?

Eating foods associated with the colors of the Brainbow, like plant polyphenols and polyunsaturated fatty acids, improves mitochondrial metabolism and biogenesis and reduces oxidative stress.

Mitochondria relies on B vitamins, Coenzyme Q10, and magnesium to start. Photobiomodulation also supports mitochondrial function. High-intensity Interval training boosts mitochondria, and reducing exposure to blue lights, which can damage retina-rich mitochondria, is another action to take. 

Tags: mitochondria, mitochondrial dysfunction, chronic fatigue, oxidative stress, long COVID

Interested in Learning More?

• Book(s): Rhythms of Recovery
• Book(s): The Brainbow Blueprint

Referenced Research Publications

Journal of Translational Medicine
2020, July 29
DOI: 10.1186/s12967-020-02452-3

A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease

Abstract

Background: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) present with a constellation of symptoms including debilitating fatigue that is unrelieved by rest. The pathomechanisms underlying this illness are not fully understood and the search for a biomarker continues, mitochondrial aberrations have been suggested as a possible candidate. The aim of this systematic review is to collate and appraise current literature on mitochondrial changes in ME/CFS/SEID patients compared to healthy controls.

Methods: Embase, PubMed, Scopus and Medline (EBSCO host) were systematically searched for articles assessing mitochondrial changes in ME/CFS/SEID patients compared to healthy controls published between January 1995 and February 2020. The list of articles was further refined using specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.

Results: Nineteen studies were included in this review. The included studies investigated mitochondrial structural and functional differences in ME/CFS/SEID patients compared with healthy controls. Outcomes addressed by the papers include changes in mitochondrial structure, deoxyribonucleic acid/ribonucleic acid, respiratory function, metabolites, and coenzymes.

Conclusion: Based on the included articles in the review it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID.

Keywords: Chronic Fatigue Syndrome; Energy metabolism; Mitochondria; Myalgic Encephalomyelitis; Systemic Exertion Intolerance Disease.

Reference

Holden, S., Maksoud, R., Eaton-Fitch, N., Cabanas, H., Staines, D., & Marshall-Gradisnik, S. (2020). A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease. Journal of translational medicine, 18(1), 290. https://doi.org/10.1186/s12967-020-02452-3

GeroScience
2024, April 26
DOI: 10.1007/s11357-024-01165-5

Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches

Abstract

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced the medical community to the phenomenon of long COVID, a condition characterized by persistent symptoms following the resolution of the acute phase of infection. Among the myriad of symptoms reported by long COVID sufferers, chronic fatigue, cognitive disturbances, and exercise intolerance are predominant, suggesting systemic alterations beyond the initial viral pathology. Emerging evidence has pointed to mitochondrial dysfunction as a potential underpinning mechanism contributing to the persistence and diversity of long COVID symptoms. This review aims to synthesize current findings related to mitochondrial dysfunction in long COVID, exploring its implications for cellular energy deficits, oxidative stress, immune dysregulation, metabolic disturbances, and endothelial dysfunction. Through a comprehensive analysis of the literature, we highlight the significance of mitochondrial health in the pathophysiology of long COVID, drawing parallels with similar clinical syndromes linked to post-infectious states in other diseases where mitochondrial impairment has been implicated. We discuss potential therapeutic strategies targeting mitochondrial function, including pharmacological interventions, lifestyle modifications, exercise, and dietary approaches, and emphasize the need for further research and collaborative efforts to advance our understanding and management of long COVID. This review underscores the critical role of mitochondrial dysfunction in long COVID and calls for a multidisciplinary approach to address the gaps in our knowledge and treatment options for those affected by this condition.

Keywords: Chronic fatigue; Long COVID; Metabolic disturbances; Mitochondrial dysfunction; Oxidative stress; Post-infectious syndromes; Therapeutic strategies.

Reference

Molnar, T., Lehoczki, A., Fekete, M., Varnai, R., Zavori, L., Erdo-Bonyar, S., Simon, D., Berki, T., Csecsei, P., & Ezer, E. (2024). Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches. GeroScience, 10.1007/s11357-024-01165-5. Advance online publication. https://doi.org/10.1007/s11357-024-01165-5

Frontiers in endocrinology
2024, March 05
DOI: 10.3389/fendo.2024.1358404

Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome

Abstract

Background: Fatigue of unknown origin is a hallmark symptom in chronic fatigue syndrome (CFS) and is also found in 20% of hypothyroidism patients despite appropriate levothyroxine treatment. Here, we suggest that in these disorders, peripheral serotonin levels are low, and elevating them to normal range with L-carnitine is accompanied with reduced fatigue.

Methods: We conducted a retrospective analysis of follow-up clinical data (CFS N=12; hypothyroidism with fatigue N=40) where serum serotonin and fatigue levels were compared before vs. after 7 weeks of oral L-carnitine supplementation.

Results: After L-carnitine, serotonin increased (8-fold in CFS, Sig. = 0.002, 6-fold in hypothyroidism, Sig. < 0.001) whereas fatigue decreased (2-fold in both CFS and hypothyroidism, Sig. = 0.002 for CFS, Sig. < 0.001 for hypothyroidism). There was a negative correlation between serotonin level and fatigue (for CFS, rho = -0.49 before and -0.67 after L-carnitine; for hypothyroidism, rho = -0.24 before and -0.83 after L-carnitine).

Conclusions: These findings suggest a new link between low peripheral serotonin, L-carnitine, and fatigue.

Keywords: L-carnitine; chronic fatigue syndrome (CFS); fatigue; hypothyroidism; mitochondria; myalgic encephalomyelitis (ME); peripheral serotonin; systemic exertion intolerance disease (SEID).

Reference

Raij, T., & Raij, K. (2024). Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome. Frontiers in endocrinology, 15, 1358404. https://doi.org/10.3389/fendo.2024.1358404

Nutrients
2022, July 28
DOI: 10.3390/nu14153112

The Potential of the Mediterranean Diet to Improve Mitochondrial Function in Experimental Models of Obesity and Metabolic Syndrome

Abstract

The abnormal expansion of body fat paves the way for several metabolic abnormalities including overweight, obesity, and diabetes, which ultimately cluster under the umbrella of metabolic syndrome (MetS). Patients with MetS are at an increased risk of cardiovascular disease, morbidity, and mortality. The coexistence of distinct metabolic abnormalities is associated with the release of pro-inflammatory adipocytokines, as components of low-to-medium grade systemic inflammation and increased oxidative stress. Adopting healthy lifestyles, by using appropriate dietary regimens, contributes to the prevention and treatment of MetS. Metabolic abnormalities can influence the function and energetic capacity of mitochondria, as observed in many obesity-related cardio-metabolic disorders. There are preclinical studies both in cellular and animal models, as well as clinical studies, dealing with distinct nutrients of the Mediterranean diet (MD) and dysfunctional mitochondria in obesity and MetS. The term “Mitochondria nutrients” has been adopted in recent years, and it depicts the adequate nutrients to keep proper mitochondrial function. Different experimental models show that components of the MD, including polyphenols, plant-derived compounds, and polyunsaturated fatty acids, can improve mitochondrial metabolism, biogenesis, and antioxidant capacity. Such effects are valuable to counteract the mitochondrial dysfunction associated with obesity-related abnormalities and can represent the beneficial feature of polyphenols-enriched olive oil, vegetables, nuts, fish, and plant-based foods, as the main components of the MD. Thus, developing mitochondria-targeting nutrients and natural agents for MetS treatment and/or prevention is a logical strategy to decrease the burden of disease and medications at a later stage. In this comprehensive review, we discuss the effects of the MD and its bioactive components on improving mitochondrial structure and activity.

Keywords: obesity, mitochondria, Mediterranean diet, metabolic syndrome, plant-based foods, polyphenols, polyunsaturated fatty acids

Reference

Khalil, M., Shanmugam, H., Abdallah, H., John Britto, J. S., Galerati, I., Gómez-Ambrosi, J., Frühbeck, G., & Portincasa, P. (2022). The Potential of the Mediterranean Diet to Improve Mitochondrial Function in Experimental Models of Obesity and Metabolic Syndrome. Nutrients, 14(15), 3112. https://doi.org/10.3390/nu14153112