Why should ME/CFS-patients be cautious with physical exercise?
Who risks decline after a forced reconditioning program?
Most ME/CFS-patients have chronically activated immune systems, as is the case in Rheumatoid Arthritis patients. This problem is not detected in routine laboratory tests because these are mainly indicators for inflammation and do not reveal an altered 'innate immunity'. Nevertheless, there are laboratory tests available which indicate the presence of these maladjustments and which worsen under the influence of physical exertion. The parameters are: hCRP (high sensitivity CRP), elastase (index of immune activity), NO (nitric oxide) and presence in the serum of DNA, RNA, LPS (lipopolysaccharides), and/or antibodies for bowel bacteria in the blood.
If ME/CFS-patients are systematically examined for these markers, one finds that the majority of them have one or more abnormal values, and it is therefore probable that they will have a slow recovery after physical exercise. Furthermore, patients will sometimes feel worse after exertion because the underlying anomalies continue to become worse as a consequence of the physical exertion.
The case of nitric oxide (NO) is interesting. As a result of disruption in normal bowel flora in these patients, there is sometimes an increased NO-production by these bacteria. Also, due to an activated nonspecific immune system, the enzyme iNOS is responsible for higher NO-values in the serum. This, among other things, is responsible for a lowered blood pressure because it expands the larger blood vessels. As a result, the peripheral blood vessels must contract, which causes a maladapted circulation in different parts of the body.
Nitric monoxide, or simply NO, plays an important role in physical exertion. An acceleration of the heartbeat causes the blood flow to increase. As a response to this, endothelial cells trigger a number of processes to raise the production of NO. This leads to several processes which raise NO-production and activity and keep it going: the eNOS (endothelial enzyme that stimulates NO-production) becomes more active and there is a drop in the inactivation of NO caused by a decrease in production of free oxygen radicals and by activation of the anti-oxidizing ESA. NO is toxic for natural killer cells and T-cells because they lose their ability to function if there is too much NO circulating. This is one of the reasons why ME/CFS-patients easily become ill after they have engaged in physical activity.
Sports is beneficial to healthy individuals because NO has a protective impact against arteriosclerosis and bacterial infections. However, an excess of NO is detrimental and patients should be advised that physical exertion has been shown to lead to a build up of NO in people suffering from ME/CFS. Furthermore, these patients show exercise intolerance because the blood supply cannot adapt to the increased exercise-induced demand for oxygen in the tissues.
The case of NO is just one of the many imbalanced systems which create exercise intolerance and/or delayed recovery. Typically, an ME/CFS-patient of the Rheumatoid Arthritis type will have a much lower exercise capacity 24 hours after undergoing an exercise test till exhaustion. Also, a lot of patients do not reach their target heart rate when they are pushed to perform an exercise test, due to muscle weakness or pain in the lower extremities. This muscle weakness is a result of the binding of NO to the ryanodine receptors in the muscles. The pain is a result of maladapted blood flow in the muscles of the same extremities, which results in a premature accumulation of lactic acid. A portion of the NO will oxidize: NO + O2 -> ONOO - (peroxynitrate). This is a very strong free radical which damages cell membranes.
What can we learn from this?
ME/CFS-patients must never be forced to do compulsory exercise; they must listen to their bodies and not to other people who think they know better but are not familiar with the biology of these disorders.
Physical exercise must be adapted to the individual, based on the severity and consequences of the illness. Therefore, the individual patient evaluation should be extensive, specific and adapted to the disorder.Leo Trower
References:
Ito et al. Cell.Immunol. 1996 : 174 ; 13
Englebienne & De Meirleir 2002 - book (291 pages) - CRC press
Mihylova et al. Neuro.Endocrinol.Letters 2007 : 11 ; 28
Connolly et al. J.Appl.Physiol. 2004 : 97 ; 1461
Sobko et al. Free Radical Biology & Medicine 2006 : 41 ; 985
VanNess et al. J. Chronic Fatigue Syndrome 2007 : 14(2) ; 77
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