Exercise

Evidence for graded exercise

Main article: Graded exercise therapy

Physiological effects of exercise

Exercise causes a variety of temporary physiological changes in healthy people.

Immune system

In healthy people, exercise induces a variety of temporary changes to immune markers. Immediately after exercise, natural killer cell activity is decreased and Leukotriene B4 (LTB4) increase, along with the LTB4/PGE2 ratio. Exercise elevates levels of prostaglandin E2 (PGE2) for up to five days.

Neurotransmitters

Acetylcholine, an important neurotransmitter that regulates immune response and muscle strength, decreases during exercise.

Effects of exercise in Chronic Fatigue Syndrome

Post Exertional Malaise

Post-exertional worsening of symptoms, VanNess et al 2010.png

PEM chart from the 2015 Institute of Medicine report

ME patients who exercise are likely to experience Post-exertional malaise which is a worsening of symptoms following physical, mental, emotional or sensory exertion.

Read the main page: Post-exertional malaise.

Pain threshold

Pain thresholds drop in people with CFS (as per the Fukuda criteria) after graded exercise, whereas in healthy controls, pain thresholds rise. This phenomenon is attributed by the study researchers to a dysfunction of the central anti-nociceptive mechanism in CFS patients.

Microbiome

A small study of ten CFS patients found significant changes in the composition of the microbiome and increased bacterial translocation (movement from the intestine into the bloodstream following exercise. In the blood, the study found increased Clostridium fifteen minutes after exercise and increased Bacilli 48 hours later.

Musculature

Exercise has also been found to induce both early and excessive lactic acid formation in the muscles with reduced intracellular concentrations of ATP and acceleration of glycolysis. Several studies have found abnormal increases in plasma lactate following short period of moderate exercise that cannot be explained by deconditioning.

There is evidence of loss of capacity to recover from acidosis on repeat exercise.

There is evidence of abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells in ME/CFS patients.

There is evidence of abnormalities in pH handling by peripheral muscle, and possible evidence of an increased acidosis and lactate accumulation.

Gene expression

Gene expression changes following moderate exercise (Light et al, 2011)

There is evidence of increased gene expression following muscular exertion.

A 2011 study found that moderate exercise in CFS increased the expression of 13 genes (sensory, adrenergic and 1 cytokine) for 48 hours, and the increases correlated with fatigue and pain levels. (see graph at right)

Second day exercise test

File:Oxidative impairment.png

Oxidative impairment on the second day of a two-day CPET, VanNess et al 2007

The seminal study on the response by CFS patients to a 2-day cardiopulmonary exercise test was published by Mark VanNess, Christopher Snell & Staci Stevens in 2007: "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise" A repeat study in 2013 confirmed these results.

In a confirmation study, Doctor Betsy Keller found that patients could not repeat their performance on a second cardiopulmonary exercise test performed a day after the first.

A review by Nijs et al. found that multiple studies showed reduced peak heart rate, reduced endurance, reduced peak work rate, reduced peak oxygen uptake, lower blood lactate values, and an increased respiratory exchange ratio; see 'Oxidative impairment', below.

Read the main page: Two-day cardiopulmonary exercise testing.

Oxidative impairment

DeBecker et al (2000) and VanNess et al (2003) found low VO2 during exercise testing; Fulle et al (2000) demonstrated oxidative damage to DNA.; and Wong et al (1992) showed defects in oxidative metabolism and poor recovery of ATP after exercise.

Notable quotations

Mark VanNess

Our studies clearly show that dynamic exercise like walking or jogging exacerbates symptoms associated with ME/CFS

Paul Cheney

The whole idea that you can take a disease like this and exercise your way to health is foolishness. It is insane

The most important thing about exercise is not to have (patients with ME / CFS) do aerobic exercise. I believe that even progressive aerobic exercise is counter-productive. If you have a defect in mitochondrial function and you push the mitochondria by exercise, you kill the DNA

(Lecture in Orlando, Florida, International Congress of Bioenergetic Medicine, 5th-7th February 1999).

Peter Behan

There is "... general agreement that (ME’s) distinguishing characteristic is severe muscle fatigability, made worse by exercise. It becomes apparent that any kind of muscle exercise can cause patients to be almost incapacitated (and) the patient is usually confined to bed."

Peter Behan (1988 Crit Rev Neurobiol: 1988:4:2:157-178)

MS Riley et al

Patients with the chronic fatigue syndrome have reduced aerobic work capacity compared with normal subjects and patients with the irritable bowel syndrome. They also have an altered perception of their degree of exertion and their premorbid level of physical activity.

Examples of clinical recommendations

While there has been no research on physical therapy alternatives to graded exercise, and many patients find it harmful, many clinicians recommend some exercise or strength training for patients who are able, tending to apply this to non-severely affected patients.

Dr Sarah Myhill

Dr Myhill recommends patients who are well enough engage in strength training, specifically Body by Science created by Dr Doug McGuff and John Little. "If muscle strength is correctly developed, this automatically translates into cardiovascular fitness and increased numbers of mitochondria". Dr Myhill has a page on her web site detailing her recommendations.

Dr. Lucinda Bateman

Dr Bateman encourages her patients to find a way to exercise: "we try to focus on maintaining or improving muscle strength, flexibility and also bit of cardiovascular exercise". She discusses exercise and gene expression in an interview.

Dr. Nancy Klimas

Dr Klimas recommends patients engage in exercise or movement without exceeding a certain heart rate, a proxy for an individual's anaerobic threshold, as established by a VO2 max test. She also recommends alternating periods of exercise and rest. She says that exercise tends to be better tolerated when performed in a horizontal position, like recumbent bicycling or swimming.

Dr. Ritchie Shoemaker

See YouTube video regarding resuming exercise gradually for mold illness aka CIRS patients.

Workwell Foundation

Workwell Foundation, which specialises in two-day cardiopulmonary exercise testing (CPET), recommends short periods (eg: 30 seconds) of analeptic exercise, with periods of rest which are 3-6 times longer than the period of exercise. The amount of exercise that the individual undertakes should be guided by VO2 max testing (or a safe heart rate threshold (generally 60% of maximum heart rate)), and the use of a heart rate monitor (both during exercise and to help with pacing) is recommended to ensure that the individual doesn't exceed their capacity. The Foundation also advises against aerobic exercise for people with ME/CFS.

This approach to exercise differs from Graded Exercise Therapy (GET) in several important ways:

• There is no claim that the exercise program will cure the condition. The aim is to increase functional strength and flexibility, and to improve quality of life, whilst not exacerbating the condition
• This program is based on a deep understanding of Post-exertional malaise (PEM), and the importance of staying within the energy envelope in order to not trigger PEM
• There is a recognition that any approach to exercise with people with ME/CFS must be carefully tailored to the individual. There is no one-size fits all
• This approach utilises objective measures such as VO2 max testing and heart rate monitoring to guide the level of activity suitable for the individual

United States Centers for Disease Control

The Centers for Disease Control in the United States recommends patients perform strength and conditioning exercise.

UK NICE Guidelines

British patient Sally Burch has written about the The UK National Institute for Health and Care Excellence (NICE) guidelines on maintaining a lower heart rate.

Talks & Interviews

• 2016, Dr. Mark Van Ness, "Expanding Physical Capability in ME/CFS" Part 1 (of 2) (Mark VanNess)
• 2016, Dr. Mark Van Ness, "Expanding Physical Capability in ME/CFS" Part 2 (of 2) (Mark VanNess)
• 2015, 72. Gene-expression and exercise / Gen-expressie en inspanning – dr. Lucinda Bateman (Lucinda Bateman, Science for Patients)
• 2014, Mark VanNess 'Exercise and ME/CFS' at Bristol Watershed. Part One (Mark VanNess)
• 2013, CFS gene expression after exercise (part 1) (Lucinda Bateman)
• 2012, Clinical exercise testing in CFS/ME research and treatment (Christopher Snell)
• 2012, MECFS Alert Episode 32: Staci Stevens, Director of the Pacific Fatigue Lab (Staci Stevens, ME/CFS Alert)
• 2012, Top 10 Things You Should Know About Post-Exertional Relapse (Staci Stevens)
• 2010, Slide presentation to CFSAC (Staci Stevens, CFSAC)
• 2009, Staci Steven speaking to CFSAC meeting (Staci Stevens)

Studies

• 2016, Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis
• 2016, Cochrane meta-analysis
• 2011, PACE trial

Learn more

• 2016, Neuromuscular Strain in ME/CFS – Research Study Conclusion
• 2016, Australian metabolomics study of young women with ME/CFS (CCC)
• 2016, Review Article: Understanding Muscle Dysfunction in Chronic Fatigue Syndrome
• 2016, Lost in Translation - The ME-Polio Connection and the Dangers of Exercise
• 2015, Exercise alteration of the CFS Microbiome
• 2015, Dr VanNess on recent press reports (Mark VanNess, January)
• 2015, Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome
• 2014, ME/CFS and Exercise: VO2 Max Testing with Nancy Klimas M.D. PREVIEW (this is a preview of a pay-per-view video)
• 2014, ME/CFS and Exercise: The VO2 Max Based Exercise Program, A Personal View (Dan Moricoli)
• 2014, Sufferers of chronic fatigue, fibromyalgia have hope in new diagnostic tool
• 2011, Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case–control study (ME Research UK)

See also

• Two-day cardiopulmonary exercise testing
• Graded exercise therapy
• Muscle fatigability
• Mitochondria
• Deconditioning
• Post-exertional malaise
• Body by Science

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

National Academy of Medicine (NAM) - An American non-profit, non-governmental organization which provides expert advice to governmental agencies on issues relating to biomedical science, medicine and health. Formerly known as the Institute of Medicine (IOM).

microbiome The full collection of microscopic organisms (especially bacteria and fungi) which are present in a particular environment, particularly inside the human body.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

two-day cardiopulmonary exercise test (CPET) - A diagnostic test which involves testing an ME/CFS patient exercising on an exercise machine, while monitoring their respiration, especially oxygen consumption. This test is repeated the following day in order to confirm the patient's inability to replicate the first-day performance. This test is thought to be the most objective way to detect post-exertional malaise.

two-day cardiopulmonary exercise test (CPET) - A diagnostic test which involves testing an ME/CFS patient exercising on an exercise machine, while monitoring their respiration, especially oxygen consumption. This test is repeated the following day in order to confirm the patient's inability to replicate the first-day performance. This test is thought to be the most objective way to detect post-exertional malaise.

two-day cardiopulmonary exercise test (CPET) - A diagnostic test which involves testing an ME/CFS patient exercising on an exercise machine, while monitoring their respiration, especially oxygen consumption. This test is repeated the following day in order to confirm the patient's inability to replicate the first-day performance. This test is thought to be the most objective way to detect post-exertional malaise.

heart rate (HR) - the number of times the heart beats within a certain time period, usually a minute

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

VO2 Max (VO2max) - the maximum amount of oxygen the body can utilize during a specified period of usually intense exercise (Volume of O2 Maximal)

heart rate monitor (HRM) - A device that measures your heart rate (pulse rate). Heart rate monitors may come as a chest strap, wrist strap, smartwatch, or even as a mobile phone app. Heart rate monitors are often used by ME/CFS patients to pace their exertion, in order to avoid post-exertional malaise (PEM). For more information, see pacing with a heart rate monitor.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

NICE guidelines Clinical guidelines used in the UK.

Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) - Chronic Fatigue and Immune Dysfunction Syndrome is another term for Chronic Fatigue Syndrome, but one which emphasizes the immunological aspects of the disease. Popular in the 1990s, this term has apparently fallen into disuse.