Exercise intolerance

Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at what would be considered to be the normally expected level or duration. It also includes experiences of unusually severe post-exercise pain, fatigue, nausea, vomiting or other negative effects. Exercise intolerance is not a disease or syndrome in and of itself, but can result from various disorders.

Exercise intolerance
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EKG of a 70-year-old man with exercise intolerance

In most cases, the specific reason that exercise is not tolerated is of considerable significance when trying to isolate the cause down to a specific disease. Dysfunctions involving the pulmonary, cardiovascular or neuromuscular systems have been frequently found to be associated with exercise intolerance, with behavioural causes also playing a part.[1]


Neurological disordersEdit

Respiratory disordersEdit

  • Cystic fibrosis: CF can cause skeletal muscle atrophy, however more commonly it can cause exercise intolerance. The exercise intolerance is associated with reduced pulmonary function that is the origin of CF.[2]
  • Bronchiectasis

Chronic fatigue syndromeEdit

  • Orthostatic intolerance (OI) occurs in CFS. OI includes exercise intolerance as one of the main symptoms. It also includes fatigue, nausea, headaches, cognitive problems and visual disturbances as other less major symptoms.[3]

Post-concussion syndromeEdit

  • Exercise intolerance is present in those with PCS however their intolerance to exercise may reduce over time.[4]
  • Individuals with postconcussion syndrome may also experience a level of exercise intolerance, however there is little known comparatively about exercise intolerance in PCS patients.[5]

Heart conditionsEdit

Musculoskeletal disordersEdit

  • Spinal muscular atrophy: symptoms include exercise intolerance, cognitive impairment and fatigue.[9]
  • Rhabdomyolysis: a condition in which muscle degrades, releasing intracellular muscle content into the blood as reflected by elevated blood levels of creatine kinase.[10] Exercise tolerance is significantly compromised.[11]


  • Mitochondrial complex III: Currently it is suggested that there are 27 different mutations identified in cytochrome b (mitochondrial complex III is one of those mutations). This mutation can often lead to skeletal muscle weakness and as a result exercise intolerance.[12]
  • a complex of Coenzyme Q10:
  • Skeletal muscle respiratory chain defect: This can result in severe exercise intolerance which is manifested by the following symptoms of Skeletal muscle respiratory chain defect; muscle fatigue and lactic acidosis.[13]
  • Exercise tolerance reflects the combined capacity of components in the oxygen cascade to supply adequate oxygen for ATP resynthesis. In individuals with diseases such as cancer, certain therapies can affect one or more components of this cascade and therefore reduce the body's ability to utilise or deliver oxygen, leading to exercise intolerance.[14]

Cytochrome b mutationsEdit

Cytochrome b mutations can frequently cause isolated exercise intolerance and myopathy and in some cases multisystem disorders. The mitochondrial respiratory chain complex III catalyses electron transfer to cytochrome c. Complex III is embedded in the inner membrane of the mitochondria and consists of 11 subunits. Cytochrome b is encoded by the mitochondrial DNA which differs from all other subunits which are encoded in the nucleus. Cytochrome b plays a major part in the correct fabricating and function of complex III.

This mutation occurred in an 18-year-old man who had experienced exercise intolerance for most of his adolescence. Symptoms included extreme fatigue, nausea, a decline in physical activity ability and myalgia.[citation needed]

Intracranial hypertensionEdit

Individuals with elevated levels of cerebrospinal fluid can experience increased head pain, throbbing, pulsatile tinnitus, nausea and vomiting, faintness and weakness and even loss of consciousness after exercise or exertion.


Exercise is key for many heart and back patients, and a variety of specific exercise techniques are available for both groups. Some exercise specialists are trained in modifications specific to these patients[who?].

In individuals with heart failure and normal EF (ejection fraction), including aortic distensibility, blood pressure, LV diastolic compliance and skeletal muscle function, aerobic exercise has the potential to improve exercise tolerance. A variety of pharmacological interventions such as verapamil, enalapril, angiotensin receptor antagonism, and aldosterone antagonism could potentially improve exercise tolerance in these individuals as well.[15]

Research on individuals suffering from Chronic obstructive pulmonary disease (COPD), has found a number of effective therapies in relation to exercise intolerance. These include:

  1. Oxygen Supplementation
    • Reduces carotid body drive and slows respiration at a given level of exercise.
  2. Treatment with bronchodilators
    • Clinically useful improvements in expiratory airflow, allows fuller exhalation in a given period of time, reduces dynamic hyperinflation, and prolongs exercise tolerance.
  3. Heliox (79% Helium, 21% oxygen)
    • Heliox has a lower density than air.
    • Breathing heliox lowers expiratory airflow resistance, decreases dynamic hyperinflation, and prolongs exercise tolerance.
  4. High intensity rehabilitative exercise training
    • Increasing the fitness of muscles decreases the amount of lactic acid released at any given level of exercise.
    • Since lactic acid stimulates respiration, after rehabilitative training exercising, ventilation is lower, respiration is slowed, and dynamic hyperinflation is reduced.

A combination of these therapies (Combined therapies), have shown the potential to improve exercise tolerance as well.[16]


Certain conditions exist where exercise may be contraindicated or should be performed under the direction of an experienced and licensed medical professional acting within his or her scope of practice. These conditions include:

The above list does not include all potential contraindications or precautions to exercise. Although it has not been shown to promote improved muscle strength, passive range-of-motion exercise is sometimes used to prevent skin breakdown and prevent contractures in patients unable to safely self-power.


  1. ^ Scott Owens, Bernard Gutin (2000). "Exercise Intolerance". Pediatrics in Review. 21 (1): 6–9. doi:10.1542/pir.21-1-6. PMID 10617757. Retrieved 2015-04-17.
  2. ^ Van de Weert-van Leeuwen, Pauline (2013). "Infection, inflammation and exercise in cystic fibrosis". Respiratory Research. 14: 32. doi:10.1186/1465-9921-14-32. PMC 3599254. PMID 23497303.
  3. ^ Leonard, Jason (2014-01-01). "Predictors of post-infectious chronic fatigue syndrome in adolescents". Health Psychology and Behavioural Medicine. 2 (1): 41–51. doi:10.1080/21642850.2013.869176. PMC 3956649. PMID 24660116.
  4. ^ Kozlowski, Karl F. (2013). "Exercise Intolerance in Individuals With Postconcussion Syndrome". Journal of Athletic Training. 48 (5): 627–35. doi:10.4085/1062-6050-48.5.02. PMC 3784364. PMID 23952041.
  5. ^ Kozlowski, Karl F; Graham, James (2013). "Exercise Intolerance in Individuals With Postconcussion Syndrome". Journal of Athletic Training. 48 (5): 627–635. doi:10.4085/1062-6050-48.5.02. PMC 3784364. PMID 23952041.
  6. ^ Dalane W. Kitzman, Leanne Groban (2011). "Exercise Intolerance". Cardiology Clinics. 29 (3): 461–77. doi:10.1016/j.ccl.2011.06.002. PMC 3694583. PMID 21803233.
  7. ^ Fowler, Robin (2012). "Exercise Intolerance in Pulmonary Arterial Hypertension". Pulmonary Medicine. June: 359204. doi:10.1155/2012/359204. PMC 3377355. PMID 22737582.
  8. ^ Geva, Professor Tal (2014). "Atrial septal defects". The Lancet. 383 (9932): 1921–1932. doi:10.1016/S0140-6736(13)62145-5. PMID 24725467.
  9. ^ Brum, Marisa (2014). "Motor Neuron Syndrome as a New Phenotypic Manifestation of Mutation 9185T>C in Gene MTATP6". Case Rep Neurol Med. 2014: 701761. doi:10.1155/2014/701761. PMC 4274829. PMID 25548692.
  10. ^ Chavez, L. O.; Leon, M; Einav, S; Varon, J (2016). "Beyond muscle destruction: A systematic review of rhabdomyolysis for clinical practice". Critical Care. 20 (1): 135. doi:10.1186/s13054-016-1314-5. PMC 4908773. PMID 27301374.
  11. ^ Quinlivan, R; Jungbluth, H (2012). "Myopathic causes of exercise intolerance with rhabdomyolysis". Developmental Medicine and Child Neurology. 54 (10): 886–91. doi:10.1111/j.1469-8749.2012.04320.x. PMID 22616958.
  12. ^ Barel, Ortal (2008). "Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ". The American Journal of Human Genetics. 82 (5): 1211–6. doi:10.1016/j.ajhg.2008.03.020. PMC 2427202. PMID 18439546.
  13. ^ Haller, R.G (1989). "Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency". The Journal of Clinical Investigation. 84 (1): 155–61. doi:10.1172/JCI114135. PMC 303965. PMID 2544623.
  14. ^ Jones, Lee W.; Eves, Neil D.; Haykowsky, Mark; Freedland, Stephen J.; MacKey, John R. (2009). "Exercise intolerance in cancer and the role of exercise therapy to reverse dysfunction". The Lancet Oncology. 10 (6): 598–605. doi:10.1016/S1470-2045(09)70031-2. PMID 19482248.
  15. ^ Kitzman, Delane W (2005). "Exercise Intolerance". Progress in Cardiovascular Diseases. 47 (6): 367–379. doi:10.1016/j.pcad.2005.02.002. PMID 16115516.
  16. ^ Casaburi, R (2006). "Combination therapy for exercise intolerance in COPD". Thorax. 61 (7): 551–552. doi:10.1136/thx.2006.058511. PMC 2104677. PMID 16807386.

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