June 2009
Laboratory Testing in Chronic Fatigue Syndrome/ME
30th June 2009
CFS, also known as ME, is a complex health condition which can take many years to diagnose and has a profound effect on quality of life for many people. The Sussex and Kent ME/CFS Society estimates that there are over 12000 adults and children affected by CFS/ME in Sussex and Kent alone1. The exact aetiology of CFS/ME is still unknown. It is a multi-factorial condition and pathways to illness may be different for each individual. Nutritional Therapy can help individuals alleviate the symptoms of CFS/ME by ensuring the food and nutrients they take in provide the raw materials the body needs to return to function. The use of laboratory tests as part of a thorough nutritional assessment can help develop targeted programmes which address the specific biochemical and functional imbalances for each individual increasing the effectiveness of the nutritional programmes.
Definitions and Diagnosis
Chronic Fatigue Syndrome(CFS) also known as Myalgic Encephalomyelitis (ME), is one of the ‘overlapping syndromes’: a multi faceted condition of unknown aetiology which often displays many of the signs and symptoms of other chronic conditions such as Multiple Chemical Sensitivity 2. It is characterised by long term debilitating fatigue and other symptoms which have a profound effect on an individual’s ability to function. Use of the terms CFS and ME is in itself a subject of much debate nationally and internationally; this debate is described well elsewhere 2. For the purposes of this review the terms will be used interchangeably or abbreviated to CFS/ME.
The most commonly used definition of CFS/ME within the research literature is that of the U.S. based Centers for Disease Control and Prevention 3 which requires persistent or relapsing fatigue for 6 months or more with specific onset and accompanied by at least four of a set of additionally specified symptoms such as, low grade fever, muscle pain, sleep disturbance, cognitive dysfunction and recurrent headache. In the UK the National Institute for Clinical Excellence definition is similar though less rigid and requires symptoms to have persisted for 4 months in an adult, 3 months in a child 4.
The exact aetiology of CFS/ME is still unknown. It is a multi-factorial condition and pathways to illness may be different for each individual. From recent research it seems likely that genetic susceptibility and hereditary factors may be important antecedents in the development of CFS/ME 5,6 Studies have identified potentially relevant gene polymorphisms relating to T-Cell activation (immune system); neuronal function (nervous system) and mitochondrial function (cell energy production) in people with CFS/ME 7-9. It is however increasingly believed that the actual expression of these genes can be influenced thorough environmental and nutritional factors10 .Put simply, just because someone has a genetic vulnerability it is not inevitable that this will always be expressed.
Important Areas to Consider in CFS/ME and Related Tests
Immunity, Infections, Mitochondrial Dysfunction and Oxidative Stress
There is a vast CFS/ME research base focusing on identifying a specific infectious agent yet there is ample evidence that many people exposed to the same agents do not go on to develop CFS/ME. Genes suggestive of genetic susceptibility to viral infections have been found in CFS/ME patients including EBV, enterovirus (EIF4G1) and other viral infections (EIF4G1, EB12)9 and a high percentage of CFS/ME onset follows a period of acute viral infection 11. Despite numerous studies a single viral cause has not been substantiated suggesting that the immune competence of the individual and interplay of other triggers and mediators is more important than the specific infection itself.
A chronic immune response in CFS/ME, whatever it's initial cause, may lead to mitochondrial dysfunction as a result of oxidative stress. Mitochondria are ‘the powerhouses of the cells’ and the site of the majority of energy production through ATP.Damaged or dysfunctional mitochondria would inevitably have a detrimental impact on energy production in all cells resulting in acute fatigue and retarded functioning in most cells of the body contributing to the wide numbers of symptoms seen in many with CFS/ME. Bell has called this hypothesis “Cellular hypoxia and Neuro-Immune Fatigue” 12.
The mitochondria require vitamin and mineral co-factors in order to produce energy through a complex pathway. Problems with the metabolic pathways leading to energy production which may benefit from specific nutrient support can be investigated through laboratory tests which also include other key areas of function. One test which can be particularly useful as a first line strategy is the Metabolic Analysis Profile:
Metabolic Analysis Profile (Organic Acids)
Metabolic Analysis assesses metabolites found in urine urine in order to evaluate four critical areas of metabolism:
- cellular energy production
- gastrointestinal function
- neurotransmitter processing
- amino acid/organic acid balance as influenced by vitamin/mineral availability.
Taken together and following careful analysis,these markers can provide a comprehensive picture of key body systems which may be in need of support. The level of information provided from this just one simple test often negates the need for further tests.
Digestive Function and Allergens
IgA and IgM antibodies to a number of enterobacteria have been found in some CFS/ME patients. The presence of these antibodies is suggestive of increased gut permeability (sometimes referred to as ‘leaky gut’) which could lead to the chronic activation of the immune system and inflammation13. Increased gut permeability can be caused by a number of factors already implicated in CFS/ME such as infections, stress, toxic exposure and inflammation.
A potential link between increased gut permeability and CFS/ME is further evidenced by a number of studies which have identified a high prevalence of Irritable Bowel Syndrome (IBS) in CFS/ME patients14-16. Further to this, imbalances have been found in the gut flora of CFS/ME patients suggesting that dysbiosis may be prevalent. Dysbiosis is likely to add to the inflammatory response and immune imbalance. Investigation of digestive function and the status of the gut flora may be important as part of nutritional assessment.
In animal models cytokines (messenger molecules) released in response to infection have been linked to increases in Blood Brain Barrier Permeability (BBBP)17 which could lead to neurotoxicity and ‘molecular mimicry’ type effects of opiod-like peptides. Whilst evidence is limited at this stage, if the same effect occurs in humans, foods such as gluten and dairy could contribute to some of the neurological symptoms associated with CFS . The investigation of the impact of casein from dairy products and gluten from wheat, barley, rye and to an extent oats may be a useful approach for some.
Tests used to investigate digestive function and potential allergens/intolerances are as follows:
Comprehensive Digestive Stool Analysis
This test considers a wider range of markers in relation to digestive function including inflammatory markers,the balance of gut bacteria, digestive enzyme function and absorption of nutrients. For those with signficant digestive issues, this may be the test of choice and the nutritional programme may focus on restoration of gut as first priority - without a well functioning gut, the body is unable to take in vital nutrients needed for all of the major functions in the body.
Intestinal Permeability Test
Exposure to toxins and other environmental stressors can lead to the formation of extended 'gaps' in the membrane of the intestine in the gut. This is sometimes known as 'leaky gut'. As we as being associated with a number of other symptoms and conditions, a gut which is too permeable can lead to symptoms (such as pain in the joints) and undermine the absorption of important vitamins needed for energy production. If intestinal permeability is found to be an issue, the nutritional programme may focus on restoration of gut function as a first line strategy- without a well functioning gut, the body is unable to take in vital nutrients needed for all of the major functions in the body.
Food Allergy Tests
Gluten, dairy and a number of other foods are common allergens and may contribute to symptoms in some people. Subject to clinical history and symptoms, tests for food intolerances may also be part of a screening approach.
Hormonal balance
CFS/ME is more prevalent in the female population suggesting a possible role for oestrogen as an immune modulator in some people. 18 Kerr’s large genetic study in CFS/ME patients has suggested that an oestrogen receptor polymorphism (ESR2) may be significant in CFS/ME patients 9. Oestrogen is thought by some to play a central role in immune mediated disease 19 and problems related to the immune system are common for many people who have CFS/ME. Where clinical history and symptoms suggest oestrogen may be a significant mediator for an individual the following test may be useful:
Detoxification Profile
The liver is involved in the neutralisation and excretion of toxins and 'used up' metabolic products, including oestrogens, into soluble and safe by-products which can then be eliminated via the urine or bile.This test looks at the functioning of the pathways for detoxification within the liver.It includes examination of the sulphation pathway which is a route for the removal of oestrogens.The profile may also identify other pathways which have become compromised due to toxic exposure. If detoxification pathways are compromised in some way, specific nutritional strategies to promote a return to function can be implemented as part of the nutritional programme.
Hypothalamus –pituitary adrenal (HPA) axis
Some research studies suggest that alterations in the HPA axis and problems relating to cortisol and the stress response may be related to some of the symptoms of CFS/ME 20. Recent research suggest that these alterations in the stress response hormone systems may be due to many factors and could also occur purely as a consequence of the illness 21,22. Whether a cause or a consequence, the hormonal stress response may impact on energy production and clinical information from lab tests may be very relevant in devising an effective nutritional programme:
Adrenal Stress Index
This test looks at the status of key hormones involved in the stress response including cortisol and DHEA. A more comprehensive version of this test which includes an important gut immune marker, Secretory IgA, may be useful for individuals where the immune system and gut health appear to be compromised. Where stress hormones are depleted or where activity is very high, specific nutrients, and sometimes adaptogenic herbs, can be incorporated into the programme to support adrenal function and enable the individual to manage stress.
Toxic exposure
There is some evidence that CFS/ME has arisen in later life for some people following toxic exposure to pesticides, solvents, heavy metals and xenoestrogens 23-25. Exposure to toxins such as cadmium from cigarette smoking can lead to a shift in the immune system to a Th2 response 26 which is consistent with other research relating to immune activation in CFS/ME. Toxic exposure may also influence nutritional depletion, increased intestinal and other membrane permeability and dysbiosis. Where toxic exposure appears clinically relevant, the following tets may be important in informing the nutritional programme:
Detoxification Profile
As already noted,the liver is involved in the neutralisation and excretion of toxins and 'used-up' metabolic products into soluble and safe by-products that can then be eliminated via the urine or bile.This profile looks at the functioning of the pathways for detoxification within the liver. The test includes examination of major Phase I and Phase II liver detoxification pathways. If particular detoxification pathways are compromised specific nutritional strategies to promote a return to function can be implemented as part of the nutritional programme alongside reducing toxic inputs to the body from known food allergens and environmental sources
Conclusion
CFS/ME is a complex condition and has a profound affect on quality of life for many people. Given the complexity of the illness, laboratory testing can be a key tool in identifiying the most important triggers and mediators for each individual, aiding the development of targeted and effective programmes based on biochemical individuality. Detailed clinical assessment involves consideration of each person's own history and symptoms in order to identify and recommend the first choice of tests for each person's unique needs.
References
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