Exercise intolerance

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A 70 year old man with exercise intolerance

Exercise intolerance is a condition where the patient is unable to do physical exercise at the level or for the duration that would be expected of someone in his or her general physical condition, or experiences 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 a primary symptom of chronic diastolic heart failure.[1]

Since there are many possible specific reasons why exercise could be inhibited, this is a rather slippery term. For instance, the patient may experience unusual breathlessness (dyspnea), muscle pain (myalgia), tachypnoea (abnormally rapid breathing), tachycardia (having a heart rate that exceeds the normal range) or increasing muscle weakness while exercising, or may, after exercise, experience severe headache, nausea, dizziness, occasional muscle cramps or extreme fatigue.

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 in it.[2]


Cardiorespiratory Disorders:

  1. cystic fibrosis (CF); 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.[3]
  2. bronchiectasis;
  3. spinal muscular atrophy; symptoms include exercise intolerance, cognitive impairment and fatigue.[4]

Chronic Fatigue Syndrome (CFS):

Post-concussion Syndrome (PCS):

  • exercise intolerance is present in those with PCS however their intolerance to exercise may reduce over time.[6]
  • Individuals with Postconcussion Syndrome (PCS) may also experience a level of exercise intolerance, however there is little known comparatively about exercise intolerance in PSC patients.[7]


Heart Conditions:

  1. cardiac arrhythmia;
  2. aortic valve insufficiency;
  3. pulmonary artery hypertension (PAH); PAH has the following symptoms; dyspnea and fatigue, these systems consequently contribute to exercise intolerance.[8]
  4. asymptomatic atrial septal; In the heart the right ventricular (RV) can have a volume overload which ultimately produces a pressure overload in the RV resulting in exercise intolerance as the RV is no longer able to control high pressure associated with exercise.[9]
  5. Chronic heart failure

Chronic Back Pain/acute back pain:




  1. mitochondrial complex 111; 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.[10]
  2. a complex of Co-enzyme Q10;
  3. several proteins;
  4. Skeletal muscle respiratory chain defect; This can result in serve exercise intolerance which is manifested by the following symptoms of Skeletal muscle respiratory chain defect; muscle fatigue and lactic acidosis.[11]
  • 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.[12]

Cytochrome b mutations[edit]

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.



When exhaustion occurs the body is unable to receive sufficient oxygen causing shortness of breath and dizziness. This means the individual has difficulty performing some aspects of exercise.

Muscle Cramps

Many athletes can also experience muscle pain and cramping. The amount of exertion which produces the cramps however shows the difference between muscle cramps from athletes and muscle cramps from an individual experiencing exercise intolerance. Pain from those experiencing muscle intolerance can occur for several days after exercise.

Insufficient Heart Rate

Heart rate does not rise to the necessary level for the activity being done.


Levels in emotional and mental well being can change due to exercise intolerance, with depression being a common factor associated with exercise intolerance.

Blood Pressure Change

Changes with and individual's blood pressure can occur with exercise intolerance.


Discolouration to the face can indicate abnormal oxygenated blood and being linked with exercise intolerance.[13]


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.[14]

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.[15]


Certain conditions in particular exist where exercise, particularly rehabilitation, may be contraindicated, including:

Other conditions may also preclude exercising under certain conditions. Passive physiotherapy can in some instances be an alternative for some patients unable to safely self-power.


Case 1:

A 22-year-old active male marine presented himself for care after experiencing exercise intolerance for over 4 months. This was preventing him from completing a standard 3 mile run as part of a general fitness test. He reported shortness of breath and fatigue while participating in minimal physical activity. Despite previously taking numerous medications the symptoms did not cease.

After numerous medical examinations the marine was found to have moderate restrictive lung disease, reduced lung capacity and moderate asthma with air trapping.

Treatment was conducted including a diagnostic and staging work-up with bone marrow biopsy and CT of the abdomen. He was also put through chemotherapy with doxorubicin, bleomycin, vinblastine and darcabazine. The treatment estimated a 90% recovery rate. He is expected to return to physical activity and his duties after completion of the chemotherapy.

Case 2:

the case involved a female of 27 years who had a lifelong severe exercise intolerance manifested by muscle fatigue, lactic acidosis, and prominent symptoms of dyspnea and tachycardia. all of which were induced by minimal exercise. She was found to have a skeletal muscle respiratory chain defect characterized by low levels of cytochromes

An Investigation of the pathophysiology the women's exercise response revealed low maximal oxygen uptake (1/3 compared to a normal sedentary women). The findings also showed that impaired oxidative phosphorylation in working muscle disrupted the normal regulation of cardiac output and ventilation rate during exercise.[11]


  1. ^ Dalane W. Kitzman, Leanne Groban (2011). "Exercise Intolerance". National Center for Biotechnology Information. Cardiol Clin. Retrieved 17/04/15.  Check date values in: |accessdate= (help)
  2. ^ Scott Owens, Bernard Gutin (2000). "Exercise Intolerance". Pediatrics in Review. Retrieved 17/04/15.  Check date values in: |accessdate= (help)
  3. ^ Van de Weert-van Leeuwen, Pauline (2013). "Infection, inflammation and exercise in cystic fibrosis". Bio Med Central. doi:10.1186/1465-9921-14-32. Retrieved 2015-04-13. 
  4. ^ Brum, Marisa (2014). "Motor Neuron Syndrome as a New Phenotypic Manifestation of Mutation 9185T>C in Gene MTATP6". Case Rep Neurol Med. doi:10.1155/2014/701761. Retrieved 2015-04-13. 
  5. ^ Leonard, Jason (1/01/2014). "Predictors of post-infectious chronic fatigue syndrome in adolescents". Health Psychology and Behavioural Medicine. doi:10.1080/21642850.2013.869176. Retrieved 2015-04-14.  Check date values in: |date= (help)
  6. ^ Kozlowski, Karl F. (2013). "Exercise Intolerance in Individuals With Postconcussion Syndrome". Journal of athletic training. doi:10.4085/1062-6050-48.5.02. Retrieved 2015-04-14. 
  7. ^ Kozlowski, Karl F; Graham, James (2013). "Exercise Intolerance in Individuals With Postconcussion Syndrome". Journal of Athletic Training (National Athletic Trainers Association) 48 (5): 627–635. doi:10.4085/1062-6050-48.5.02. 
  8. ^ Fowler, Robin (2012). "Exercise Intolerance in Pulmonary Arterial Hypertension". Pulmonary Medicine. doi:10.1155/2012/359204. Retrieved 2015-04-13. 
  9. ^ Geva, Professor Tal (2014). "Atrial septal defects". The Lancet. doi:10.1016/S0140-6736(13)62145-5. Retrieved 2015-04-13. 
  10. ^ Barel, Ortal (2008). "Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ". the American Journal Of Human Genetics. doi:10.1016/j.ajhg.2008.03.020. Retrieved 2014-04-14. 
  11. ^ a b 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. doi:10.1172/JCI114135. Retrieved 2015-04-14. 
  12. ^ Jones, Lee W; Eves, Neil D. "Exercise intolerance in cancer and the role of exercise therapy to reverse dysfunction". linkinghub.elsevier.com. Retrieved 2015-04-13. 
  13. ^ Gregory, John (2013). "Six Signs of Exercise Intolerance". LIVESTRONG.COM. Retrieved 17/04/15.  Check date values in: |accessdate= (help)
  14. ^ Kitzman, Delane W (2005). "Exercise Intolerance". Progress in Cardiovascular Diseases 47 (6): 367–379. doi:10.1016/j.pcad.2005.02.002. 
  15. ^ Casaburi, R (2006). "Combination therapy for exercise intolerance in COPD". Thorax 61 (7): 551–552. doi:10.1136/thx.2006.058511. 





  1. ^ Walters, Dammann, Lynch, Katrina, Gregory, James (2005). "Exercise intolerance in a soldier athlete". Medicine & Science in Sports & Exercise. 
  2. ^ Massie, Wong, Milone, Rami, Lee-Jun, Margherita (2010). "Exercise intolerance due to cytochrome b mutation". Muscle & Nerve. doi:10.1002/mus.21649. 
  3. ^ Quinlivan, Jungbluth, Ros, Heinz (2012). "Myopathic causes of exercise intolerance with rhabdomyolysis". Developmental Medicine & Child Neurology. doi:10.1111/j.1469-8749.2012.04320.x. 
  4. ^ Kitzman, Dalane W (2005). "Exercise intolerance". Progress In Cardiovascular Diseases. doi:10.1016/j.pcad.2005.02.002.