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Since one-fifth of primary care visits involve fatigue as a symptom,1 personalized interventions targeting underlying causes can help many patients. Over one third of Americans (37%) report short sleep duration and fatigue.2,3 One of the key recommendations for patients with fatigue has been exercise,1 yet for some patients, that may worsen symptoms. Fatigue may rank as one of the most frustrating symptoms for both patients and providers. One underlying cause of fatigue that is getting attention is mitochondrial dysfunction, and we now know fatigue is a frequent symptom in mitochondrial disease.4 In a survey of patient-perceived fatigue, compared to patients with myalgic encephalopathy/CFS, 32% of mitochondrial disease patients reported severe, limiting fatigue and 62% reported excessive symptomatic fatigue.4

Healthy mitochondrial function is akin to the amount of pressure the foot puts on the gas pedal.5 Low levels of adenosine triphosphate (ATP) lead to having weak metabolism and feeling “slow”; more ATP allows us to experience life with more energy and vitality.

In a review of research articles on mitochondrial disease, carnitine is the most studied mitochondrial function marker; the most studied enzyme is CoQ10.6 Patients with mitochondrial myopathy who received L-carnitine daily for two months enjoyed an increase in their pain tolerance limit and oxygen consumption at constant exercise rate.7 Damage to the mitochondria from peripheral inflammation is also implicated in the fatigue felt by patients with neuroinflammation, chronic fatigue, and some autoimmune conditions.8,9 Even in healthy individuals, CoQ10 supplementation reduces the symptoms of physical fatigue.10

In the following video, Lisa Portera-Perry, DC, discusses the effects of mitochondrial dysfunction on the brain:



  1. Rosenthal TC, Majeroni BA, Pretorius R, Malik K. Fatigue: an overview. Am Fam Physician. 2008;78(10):1173-1179.
  2. Ricci JA, Chee E, Lorandeau AL, Berger J. Fatigue in the U.S. workforce: prevalence and implications for lost productive work time. J Occup Environ Med. 2007;49(1):1-10. doi:1097/01.jom.0000249782.60321.2a.
  3. Yong LC, Li J, Calvert GM. Sleep-related problems in the US working population: prevalence and association with shiftwork status. Occup Environ Med. 2017;74(2):93-104. doi:1136/oemed-2016-103638.
  4. Gormon GS, Elson JL, Newman J, et al. Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease. Neuromuscul Disord. 2015;25(7):563-566. doi:1016/j.nmd.2015.03.001.
  5. Gellerich FN, Gizatullina Z, Gainutdinov T, et al. The control of brain mitochondrial energization by cytosolic calcium: the mitochondrial gas pedal. IUBMB Life. 2013;65(3);180-190. doi:1002/iub.1131.
  6. Filler K, Lyon D, Bennett J, et al. Association of mitochondrial dysfunction and fatigue: a review of the literature. BBA Clin. 2014;1:12-23. doi:1016/j.bbacli.2014.04.001.
  7. Gimenes AC, Bravo DM, Nápolis LM, et al. Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy. Braz J Med Biol Res. 2015;48(4):354-362. doi:1590/1414-431X20143467.
  8. Morris G, Berk M, Walder K, Maes M. Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses. BMC Med. 2015;13:28. doi:1186/s12916-014-0259-2.
  9. Morris G, Berk M. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med. 2015;13:68. doi:1186/s12916-015-0310-y.
  10. Mizuno K, Tanaka M, Nozaki S, et al. Antifatigue effects of coenzyme Q10 during physical fatigue. Nutrition. 2008;24(4):293-299. doi:1016/j.nut.2007.12.007.