Reduce Fatigue by Addressing Mitochondrial Dysfunction

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 uniquely positioned to help patients with fatigue, as this model of care examines an individual’s individual life course for underlying causes and helps patients change their lifestyle to promote improved function and quality of life.

Fatigue statistics in the US, while not particularly surprising, illuminate some interesting trends. During 2010-2011, 15.3% of American women and 10.1% of men reported feeling very tired or exhausted in the past three months.¹ Specifically, women aged 18-44 were nearly twice as likely as men of the same age group to report feeling very tired or exhausted.¹ These numbers have only increased over the years. A 2015 YouGov.com poll found that 38% of Americans were poorly rested at least four days a week.² And according to a 2017 National Safety Council survey-based report, 97% of respondents reported at least one risk factor for fatigue.³ The survey found that 43% of Americans do not get enough sleep to mitigate critical risks that can jeopardize safety at work and on the roads, including the ability to think clearly, make informed decisions, and be productive.³

Reports also suggest that one-fifth of primary care visits involve fatigue as a symptom.⁴ Personalized interventions targeting underlying causes may help many patients.

Fatigue may rank as one of the most frustrating symptoms for both patients and providers. One of the key recommendations for patients with fatigue has been exercise,⁴ yet for some patients, that may worsen symptoms. One underlying cause of fatigue is mitochondrial dysfunction, and we now know fatigue is a frequent symptom in mitochondrial disease.⁵ In a survey of patient-perceived fatigue, compared to patients with chronic fatigue syndrome, 32% of mitochondrial disease patients reported severe, limiting fatigue, and 62% reported excessive symptomatic fatigue.⁵

Healthy mitochondrial function is akin to the amount of pressure the foot puts on the gas pedal.⁶

Low levels of the cellular energy currency adenosine triphosphate (ATP) lead to having weak metabolism and feeling “slow”; more ATP allows us to experience life with more energy and vitality. Improving mitochondrial function, or correcting dysfunction, can increase the amount of ATP energy available for use by cells and improve fatigue symptoms.

In a review of research articles on mitochondrial disease, carnitine is the most studied mitochondrial function marker; the most studied enzyme is CoQ10.⁷ Patients with mitochondrial myopathy who received L-carnitine daily for two months enjoyed an increase in their pain tolerance limit and oxygen consumption during constant exercise.⁸ Damage to the mitochondria from peripheral inflammation is also implicated in the fatigue felt by patients with neuroinflammation, chronic fatigue, and some autoimmune conditions.^9,10 Even in healthy individuals, CoQ10 supplementation may reduce the symptoms of physical fatigue.¹¹

In the following video, IFM educator Lisa Portera-Perry, DC, discusses the effects of mitochondrial dysfunction

With 30 years of experience in clinical practice, Dr. Portera-Perry is a passionate advocate of Functional Medicine and its application for patients presenting with a wide variety of structural, neuromuscular, and autoimmune-related chronic illnesses.

A 2012 study suggests that chronic exposure to reduced sleep (less than six hours per day) and insufficient time for recovery sleep could have gradual deleterious effects, leading to alterations in the neuroendocrine, immune, and inflammatory systems.¹² Fatigue is also frequent in patients with diabetes, and this symptom appears to be more prominent in type 2 than type 1 diabetes patients.¹³ Chronic inflammation represents one characteristic of type 2 diabetes that may contribute to fatigue symptoms. In comparison to type 1 diabetic subjects, patients with type 2 diabetes exhibited higher fatigue scores, notably in these dimensions:

General fatigue
Physical fatigue
Reduced activity
Greater levels of inflammatory markers that correlated with indexes of adiposity¹³

Finding the underlying cause of fatigue is a critical part of patient care. From there, clinicians can design individualized treatment plans that address the cause and support the underlying energetic needs of cells, improving the patient’s quality of life. For more information related to the topic of fatigue, please see the following IFM articles:

Treatment options for CFS

Clinician burnout and ways to care for the “self”

Genome-wide changes may result from excessive stress

References

Blackwell D, Clarke TC. QuickStats: percentage of adults who often felt very tired or exhausted in the past 3 months, by sex and age group – National Health Interview Survey, United States, 2010-2011. MMWR Morb Mortal Wkly Rep. 2013;62(14);275. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6214a5.htm
Moore P. Two-fifths of Americans are tired most of the week. YouGov. Published June 2, 2015. Accessed May 30, 2019. https://today.yougov.com/topics/lifestyle/articles-reports/2015/06/02/sleep-and-dreams
43 percent of Americans admit they’re too tired to function at work. Occupational Health & Safety. Published July 27, 2017. Accessed May 31, 2019. https://ohsonline.com/articles/2017/07/27/43-percent-of-americans-admit-they-are-too-tired-to-function-at-work.aspx
Rosenthal TC, Majeroni BA, Pretorius R, Malik K. Fatigue: an overview. Am Fam Physician. 2008;78(10):1173-1179.
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
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
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
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
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
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
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
Faraut B, Boudjeltia KZ, Vanhamme L, Kerkhofs M. Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery. Sleep Med Rev. 2012;16(2):137-149. doi:1016/j.smrv.2011.05.001
Lasselin J, Layé S, Dexpert S, et al. Fatigue symptoms relate to systemic inflammation in patients with type 2 diabetes. Brain Behav Immun. 2012;26(8):1211-1219. doi:1016/j.bbi.2012.03.003

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