Exercise intolerance

Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass.[1] 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
EKG of a 70-year-old man with exercise intolerance
SpecialtyCardiology, pulmonology, vascular medicine/vascular surgery/phlebology, rheumatology, orthopedics, neurosurgery, neurology; exercise physiology, physical therapy/physiotherapy
SymptomsDyspnea, chest pain, other pains, fatigue
DurationVariable
CausesVarious
Risk factorsMultiple, including sedentary lifestyle and low baseline physical activity

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.[2]

Signs and symptoms

Exercise in this context means physical activity, not specifically exercise in a fitness program. For example, a person with exercise intolerance after a heart attack may not be able to sustain the amount of physical activity needed to walk through a grocery store or to cook a meal. In a person who does not tolerate exercise well, physical activity may cause unusual breathlessness (dyspnea), muscle pain (myalgia), tachypnoea (abnormally rapid breathing), tachycardia (having a faster heart rate than normal) or increasing muscle weakness; or exercise might result in severe headache, nausea, dizziness, occasional muscle cramps or extreme fatigue, which would make it intolerable.

The three most common reasons people give for being unable to tolerate a normal amount of exercise or physical activity are:

Causes

Neurological disorders

Respiratory disorders
  • 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.[4]
  • Bronchiectasis

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.[8]
  • Individuals with postconcussion syndrome may also experience a level of exercise intolerance, however there is little known comparatively about exercise intolerance in PCS patients.[9]

Heart conditions

Musculoskeletal disorders
  • Spinal muscular atrophy: symptoms include exercise intolerance, cognitive impairment and fatigue.[13]
  • Rhabdomyolysis: a condition in which muscle degrades, releasing intracellular muscle content into the blood as reflected by elevated blood levels of creatine kinase.[14] Exercise tolerance is significantly compromised.[15]

Mutations
  • 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.[16]
  • A complex of Coenzyme Q10:
  • Skeletal muscle respiratory chain defect (electron transport chain [ETC]): 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.[17]
  • 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 temporary exercise intolerance.[18]
  • Riboflavin-responsive exercise intolerance caused by mutations of the SLC25A32 gene

Cytochrome b mutations

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 fabrication 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.

Intracranial hypertension

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.

General physical problems

A person who is not physically fit due to a sedentary lifestyle may find that vigorous exercise is unpleasant.

Diagnosis

Objective tests for exercise intolerance normally involve performing some exercise. Common tests include stair climbing, walking for six minutes, a shuttle-walk test, a cardiac stress test, and the cardiopulmonary exercise test (CPET).[3] In the six-minute walk test, the goal is to see how far the person can walk, with approximately 600 meters being a reasonable outcome for an average person without exercise intolerance.[3] The CPET test measures exercise capacity and help determine whether the cause of exercise intolerance is due to heart disease or to other causes.[3] People who experience significant fatigue before reaching the anaerobic threshold usually have a non-cardiac cause for exercise intolerance.[3]

Additionally, testing for exercise-induced asthma may be appropriate.[3]

Treatment

Exercise is key for many people with heart disease or back pain, and a variety of specific exercise techniques are available for both groups.

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.[19]

Research on individuals with 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.[20]

Hazards

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.

See also

References
  1. Vissing, John (2016-04-13). "Exercise intolerance and myoglobinuria". In Lisak, Robert P.; Truong, Daniel D.; Carroll, William M.; Bhidayasiri, Roongroj (eds.). International Neurology. John Wiley & Sons. p. 516. ISBN 978-1-118-77735-0.
  2. Scott Owens, Bernard Gutin (2000). "Exercise Intolerance". Pediatrics in Review. 21 (1): 6–9. doi:10.1542/pir.21-1-6. PMID 10617757. S2CID 39545913. Retrieved 2015-04-17.
  3. Kalathiveetil, Sujith (2006). "Exercise Testing". In Shifren, Adrian (ed.). The Washington Manual Pulmonary Medicine Subspecialty Consult. Lippincott Williams & Wilkins. ISBN 978-0-7817-4376-1.
  4. 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.
  5. Brown, Abigail; Jason, Leonard A (2020). "Meta-analysis investigating post-exertional malaise between patients and controls". Journal of Health Psychology. 25 (13–14): 2053–2071. doi:10.1177/1359105318784161. PMC 7440642. PMID 29974812.
  6. "Comments Post-exertional malaise in ME/CFS: Medical Research Council announces new neuroimaging research". ME Association. 16 October 2015. Retrieved 23 September 2017.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Fowler, Robin (2012). "Exercise Intolerance in Pulmonary Arterial Hypertension". Pulmonary Medicine. June: 359204. doi:10.1155/2012/359204. PMC 3377355. PMID 22737582.
  12. Geva, Professor Tal (2014). "Atrial septal defects". The Lancet. 383 (9932): 1921–1932. doi:10.1016/S0140-6736(13)62145-5. PMID 24725467. S2CID 205971022.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. Kitzman, Delane W (2005). "Exercise Intolerance". Progress in Cardiovascular Diseases. 47 (6): 367–379. doi:10.1016/j.pcad.2005.02.002. PMID 16115516.
  20. 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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