The Relationship Between Chronic Fatigue & Mitochondrial Health

Women exercising in the forest with dumbbells to reduce her chronic fatigue and improve her mitochondrial health.
Read Time: 4 minutes

When a patient is fatigued, their quality of life suffers. Morning routines may turn into energy-draining chores, work can become unbearable, and personal relationships might decline. How many of your patients report fatigue? What can be done to help them? Functional medicine is especially well-positioned to help patients with chronic fatigue, as this model of care examines a patient’s health journey to determine underlying causes and personalized lifestyle modifications that support daily function and an improved quality of life.

The global prevalence of general fatigue (lasting less than six months) among adults has been estimated at 20.4%, while prevalence of chronic fatigue (lasting longer than six months) has affected an estimated 10.1% of adults worldwide.1 Specific to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), this condition is a global health issue, with women more often diagnosed than men.2 Between 2021 and 2022, an approximate 3.3 million adults had ME/CFS in the United States, according to results from the National Health Interview Survey.3

Patients experiencing chronic fatigue may suffer a range of symptoms, including heavy exhaustion, problems with sleep, difficulty with thinking and concentration, dizziness, and even pain. In fact, chronic fatigue and chronic pain are often intertwined and may share some common avenues to health restoration. In the following video, Elizabeth Board, MD, IFMCP, discusses the role of mitochondria in chronic fatigue and pain and how supporting this energy-producing organelle may help optimize a patient’s health.

(Video Time: 2 minutes) Dr. Elizabeth Board is a board-certified anesthesiologist and pain medicine physician who practices non-narcotic pain management, acupuncture, and functional medicine full time at her Georgia-based health clinic, Atlanta Functional Medicine.

Fatigue & Mitochondrial Dysfunction

Healthy mitochondria are crucial for optimal energy and vitality, and low levels of the cellular energy currency adenosine triphosphate (ATP) may translate to someone feeling depleted or worn out. While the detailed pathophysiological mechanisms involved in fatigue continue to be explored, mitochondrial dysfunction may contribute to fatigue symptoms, and improving mitochondrial function can increase the amount of ATP energy available for use by cells.4

A 2021 observational study evaluated mitochondrial respiration of peripheral blood mononuclear cells (PBMCs) in older patients (n=45; 75.4 to 77.8 years) with and without fatigue symptoms.5 Compared to those without fatigue, patients with fatigue exhibited more functional limitations, more depressive symptoms, and lower PBMC mitochondrial respiration (i.e., reduced ATP generation).5 Specific to ME/CFS, a 2021 observational study of patients with ME/CFS evaluated fatigue symptoms and PBMC mitochondrial function compared to controls. Patients with ME/CFS showed severe fatigue and altered mitochondrial metabolism, with a decreased ability to fulfill cellular energy demands.6

Supporting Energy With Nutrition

Impaired mitochondrial function may contribute to fatigue symptoms, and targeted nutritional treatments that support mitochondrial processes may benefit health. Anti-inflammatory dietary approaches encourage the consumption of a variety of colorful fruits and vegetables, and the antioxidant and anti-inflammatory benefits from plant-based nutrients, such as polyphenols, may be supportive of mitochondrial biogenesis and function.7,8 In addition, studies suggest that intermittent fasting routines, if appropriate for a patient’s personalized nutrition strategy, may positively impact mitochondrial function, enhancing energy metabolism and overall health.9,10

L-carnitine is one of the key nutrients studied for its role in mitochondrial health, from protecting cellular membranes to assisting in the elimination of toxic metabolites.11 Coenzyme Q10 (CoQ10) is a dietary enzyme that has also been researched for its role in mitochondrial health12 and on fatigue symptoms. A 2021 randomized clinical trial (RCT) studied the effect of a 12-week treatment of CoQ10 (200 mg/day) plus the reduced form of nicotinamide adenine dinucleotide (NADH) (20 mg/day) on perceived fatigue, sleep, and quality of life among ME/CFS patients.13 Compared to placebo, those patients who received the CoQ10/NADH treatment showed significant reductions in cognitive fatigue and overall fatigue scores, as well as improved sleep and health-related quality of life.13

Inadequate nutrition and resulting micronutrient deficiencies may also contribute to mitochondrial dysfunction and fatigue symptoms, especially in older individuals.4 The functional medicine model of care addresses nutrient inadequacies and deficiencies, and therapeutic food plans such as IFM’s Mito Food Plan use nutrition to support mitochondrial function. The Mito Food Plan is characterized as an anti-inflammatory, low-glycemic, gluten-free, low-grain approach to eating that also emphasizes the consumption of high-quality fats. The plan focuses on supporting mitochondrial health through therapeutic foods that improve energy production in the body.


Impaired mitochondrial function may contribute to general and chronic fatigue, and nutrition is one lifestyle approach that may help support mitochondrial and overall health. Functional medicine clinicians are trained to consider the totality of a patient’s health journey and health trajectory to both understand potential root causes of chronic conditions and collaboratively design personalized, dietary treatment plans that improve health outcomes. Learn more about supporting mitochondrial health for a wide range of chronic and neurological conditions and symptoms at IFM’s upcoming Bioenergetics Advanced Practice Module (APM).

Learn More About Mitochondrial Function

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Connecting Mitochondria and Gut Health

Mitochondrial Impairment in Long COVID

Long COVID and the Functional Medicine Approach to Care


  1. Yoon JH, Park NH, Kang YE, Ahn YC, Lee EJ, Son CG. The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis. Front Public Health. 2023;11:1192121. doi:3389/fpubh.2023.1192121
  2. Lim EJ, Ahn YC, Jang ES, Lee SW, Lee SH, Son CG. Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). J Transl Med. 2020;18(1):100. doi:1186/s12967-020-02269-0
  3. Vahratian A, Lin JS, Bertolli J, Unger ER. Myalgic encephalomyelitis/chronic fatigue syndrome in adults: United States, 2021-2022. NCHS Data Brief. 2023;(488):1-8. Accessed April 18, 2024.
  4. Azzolino D, Arosio B, Marzetti E, Calvani R, Cesari M. Nutritional status as a mediator of fatigue and its underlying mechanisms in older people. Nutrients. 2020;12(2):444. doi:3390/nu12020444
  5. Herpich C, Franz K, Klaus S, Müller-Werdan U, Ost M, Norman K. Age-related fatigue is associated with reduced mitochondrial function in peripheral blood mononuclear cells. Exp Gerontol. 2021;144:111177. doi:1016/j.exger.2020.111177
  6. Fernandez-Guerra P, Gonzalez-Ebsen AC, Boonen SE, et al. Bioenergetic and proteomic profiling of immune cells in myalgic encephalomyelitis/chronic fatigue syndrome patients: an exploratory study. Biomolecules. 2021;11(7):961. doi:3390/biom11070961
  7. Chodari L, Dilsiz Aytemir M, Vahedi P, et al. Targeting mitochondrial biogenesis with polyphenol compounds. Oxid Med Cell Longev. 2021;2021:4946711. doi:1155/2021/4946711
  8. Mthembu SXH, Dludla PV, Ziqubu K, et al. The potential role of polyphenols in modulating mitochondrial bioenergetics within the skeletal muscle: a systematic review of preclinical models. Molecules. 2021;26(9):2791. doi:3390/molecules26092791
  9. Lettieri-Barbato D, Cannata SM, Casagrande V, Ciriolo MR, Aquilano K. Time-controlled fasting prevents aging-like mitochondrial changes induced by persistent dietary fat overload in skeletal muscle. PLoS One. 2018;13(5):e0195912. doi:1371/journal.pone.0195912
  10.  Madkour MI, El-Serafi AT, Jahrami HA, et al. Ramadan diurnal intermittent fasting modulates SOD2, TFAM, Nrf2, and sirtuins (SIRT 1, SIRT3) gene expressions in subjects with overweight and obesity. Diabetes Res Clin Pract. 2019;155:107801. doi:1016/j.diabres.2019.107801
  11.  Virmani MA, Cirulli M. The role of L-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. Int J Mol Sci. 2022;23(5):2717. doi:3390/ijms23052717
  12.  Mantle D, Hargreaves IP, Domingo JC, Castro-Marrero J. Mitochondrial dysfunction and coenzyme q10 supplementation in post-viral fatigue syndrome: an overview. Int J Mol Sci. 2024;25(1):574. doi:3390/ijms25010574
  13.  Castro-Marrero J, Segundo MJ, Lacasa M, Martinez-Martinez A, Sentañes RS, Alegre-Martin J. Effect of dietary coenzyme Q10 plus NADH supplementation on fatigue perception and health-related quality of life in individuals with myalgic encephalomyelitis/chronic fatigue syndrome: a prospective, randomized, double-blind, placebo-controlled trial. Nutrients. 2021;13(8):2658. doi:3390/nu13082658

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