Testing

(Add tests list including those relevant to possible causes and cofactors)

From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment' <a href="https://sites.google.com/site/cfstestingandtreatmentroadmap/home">https://sites.google.com/site/cfstestingandtreatmentroadmap/home</a>
When a test is performed for a microbe, we want to know not only whether you have it in your body, but more importantly, whether it is active or not. In chronic infections, the level of activity of a microbe can be gauged to a certain extent by the amount of IgG and IgM antibodies your body produces in response to that microbe. 

Alternative methods of testing for the presence of pathogens in the body include: PCR (polymerase chain reaction) and viral culture. Viral culture is usually the gold standard by which other viral detection methods are judged. 

Empirical testing. While it is always better to test for pathogens or health conditions before using treatments, because some tests are expensive, not available in all countries, or might not always be reliable or sensitive enough to detect certain pathogens, you may choose to bypass the test and go straight to treatment (if the treatment well tolerated and safe). This is known as empirical testing: using a treatment itself as a test for a pathogen or health condition. Empirical testing makes the assumption that if you get better on the treatment, you may well have the pathogen or the health condition that the treatment targets. 
*

While not everyone with ME/CFS shows signs of infection, many do. Several pieces of evidence support a theory that some ME/CFS is caused at least in part by a virus:

Enterovirus connection
In a 2007 study, people with ME/CFS were four times more likely than healthy people to have evidence of enteroviruses in their stomach tissues. Enteroviruses cause stomach infections, and symptoms of ME/CFS frequently start after that kind of illness.

Rnase L
Your body uses the enzyme Rnase L to kill viruses that are attacking your cells, and ME/CFS patients frequently have high Rnase L activity.

Natural Killer (NK) Cells and T Cells
NK & T cells in your immune system attack virus-infected cells, and people with ME/CFS frequently have impaired NK and T cell functions and numbers, suggesting chronic immune activity may be exhausting and depleting them.

Antibodies
People with ME/CFS typically have high levels of antibodies to many infection-causing organisms that cause fatigue and other ME/CFS symptoms. These organisms include those that cause candida (yeast), human herpesvirus type 6 (HHV-6), measles, parvovirus, and Epstein-Barr. Researchers have not been able to show that any of these is a significant cause of ME/CFS.

Post-illness onset
Up to 80 percent of ME/CFS cases start suddenly after a flu-like condition.

Cluster outbreaks
While the CDC has not confirmed most cluster outbreaks, reports of multiple people in the same household, workplace, and community developing ME/CFS at the same time are not unheard of.

Some researchers suggest that changes in normally harmless bacteria in the intestine may play a role in the development of ME/CFS.

However, some evidence seems to run counter to the viral-cause theory. ME/CFS doesn't appear to spread through direct content, people with it don't appear contagious, and -- in spite of well-designed studies -- researchers have not been able to link ME/CFS with any specific infections.

A Note on XMRV

In 2009, researchers from the Whittemore Peterson Institute (WPI) published a study in the journal Science that suggested a link between XMRV, a newly discovered retrovirus, and ME/CFS. They found XMRV in about 67% of blood samples from ME/CFS patients. They also detected it in 3% of healthy controls.

However, subsequent studies failed to confirm the link, including a large study involving the WPI's primary researcher. Other studies suggested means by which contamination may have created false positives in the original study. By late 2011, the XMRV theory had been all-but abandoned.

Firstly exclude macroscopical pathology

Most patients, by the time they get to see me, have had all the routine tests done. These tests just test for macroscopic pathology such as major organ failure (anaemia, heart disease, cancer, liver failure, kidney failure and some gut problems). They do not test for minor organ failures (such as partial thyroid gland failure, partial adrenal gland failure, mild liver damage, poor ability to detox). None of these tests look for poor function of the brain or brain damage, nutritional tests are often absent or limited, hormone tests are usually incomplete and there are virtually no tests of micropathological function.

Having said that, there are often mild abnormalities in standard tests which have not been picked up on by the GP or consultant, but which are clinically important for the CFS sufferer. Results are given by a figure and there should also be a reference range next to this figure – that tells you if you are inside or outside the reference range. This reference range often varies from one lab to another.

The basic tests that most doctors do for their patients with chronic fatigue are:

▪ Haematology (full blood count – red cells, white cells and platelets)

▪ Inflammation in the blood – ESR, C reactive protein, plasma viscosity.

▪ Biochemistry (liver and kidney function)

▪ Blood sugar level

▪ Urine testing (for infection or kidney damage)

▪ Faecal occult bloods (looking for bleeding from the gut)

▪ Thyroid stimulating hormone (only looks for primary thyroid failure – most thyroid problems in CFS are secondary to poor pituitary function)

▪ Ferritin (iron), B12, folic acid and calcium

▪ Perhaps a serum magnesium – which is a completely useless test! This is because serum levels are maintained at the expense of levels inside cells. A serum magnesium is just an ITU (Intensive Therapy Unit) test!

▪ Autoantibody tests for autoimmunity.

Common abnormalities that can be shown by routine tests

The mild abnormalities I always look for in CFS in the above tests are:

▪ Low or low normal white cell count – can be a sign of poor immune function which most commonly is secondary to nutritional deficiencies, such as low zinc, low magnesium, low B vitamins, low essential fatty acids.

▪ Low or low normal platelet count – can be a sign of toxic stress

▪ Low MCV (mean corpuscular volume) suggesting iron or copper deficiency. Low iron is suggestive of HYPOCHLORHYDRIA, in which case other mineral deficiencies are also likely.

▪ High MCV suggesting B12, folic acid or HYPOTHYROIDISM

▪ A high blood sugar or a low blood sugar suggests there may be a tendency to HYPOGLYCAEMIA (a pre-diabetic tendency). A normal blood sugar tells you very little! Normal ranges of blood glucose have been changed because so many people now have carbohydrate intolerance. A normal blood sugar should be between 4-6mmol/l. High blood sugar is now associated with toxic stress because chemicals cause insulin resistance.

▪ Low potassium. Potassium varies according to diet! Low potassium means there is a lack of vegetables in the diet. Bananas may be rich in potassium but they are high glycaemic index, so beware!

▪ High normal bilirubin – may be Gilbert’s syndrome suggesting poor ability to detoxify.

▪ High normal or abnormal liver enzymes – suggesting liver damage, usually from chemicals, or poor nutritional status.

▪ High urea or creatinine suggesting dehydration

▪ Low urea or creatinine suggesting low protein diet

▪ Low glomerular filtration rate suggesting poor kidney function – could be due to allergy or toxic damage but may indicated poor mitochondrial function.

▪ A TSH tells you very little about thyroid status! It is essential to see the actual level of thyroid hormones in the blood.

▪ Low levels of B12 can be due to HYPOCHLORHYDRIA or MALABSORPTION

▪ High uric acid can point to poor ANTIOXIDANT status. See GOUT.

▪ Raised cholesterol could mean low levels of vitamin D or hypothyroidism.

▪ Low levels of calcium likely to mean low levels of vitamin D.

The routine tests which I nearly always do initially and which have important implications for management

<ol>

<li>Mitochondrial function profile (p. 17 ) – this is a batch of tests to identify the mitochondrial problem. This test has important implication for treatment; this test includes:</li>

</ol>

<ul>

<li>ATP profiles – looks at levels of ATP, how well energy is released from ATP, the rate of production of ATP from ADP and movement of ATP and ADP across mitochondrial membranes (translocator protein function - could be blocked by toxins or pH changes). Also gives us an objective measure of the level of disability.</li>

<li>Plasma cell-free DNA – a measurement of cell damage and antioxidant status in CFS</li>

<li>Red cell NAD levels – a measure of the efficiency of Kreb’s citric acid cycle. Levels can be corrected with niacinamide 500mgs daily and acetyl L carnitine.</li>

<li>Co-enzyme Q10 levels – the most important antioxidant inside mitochondria. In CFS levels are nearly always deficient</li>

<li>Superoxide dismutase – three types measured, indicates levels of zinc, copper and manganese, also gene studies to give an indication of toxic damage. SODase is a major antioxidant in all cells.</li>

<li>Red cell magnesium – done as part of the ATP profile or can be done separately.</li>

<li>Glutathione and glutathione peroxidase (also indicates selenium status).</li>

</ul>

<li>Thyroid function profile (free T4, Free T3 and TSH).</li>

</ol>

More esoteric tests which have implications for management

▪ Microrespirometry - looks in detail at ADP to ATP conversion (see sample result on p. 20

▪ Further investigation of poor translocator protein function Translocator protein studies (p.21)

▪ Cardiolipin studies looks at the structure of mitochondrial membranes (p. 22 )

▪ Calcium studies – calcium levels inside cells often too high.

▪ Adrenal stress profile – salivary levels of cortisol and DHEA over 24 hours

▪ Salivary Melatonin levels – it is common to get poor melatonin production and therefore poor sleep in CFS. This is a further reflection of the inadequate HPA axis in CFS.

▪ Lactate dehydrogenase studies – if there is evidence of cell damage, this indicates where the damage is coming from eg liver or muscle.

▪ Red cell Carbonic anhydrase – indicates hyperventilation

When gut symptoms suggest tests

▪ Gut fermentation test – to look for evidence of fermentation by bacteria or yeast. Irritable bowel syndrome may be caused by food allergy or gut dysbiosis. Low levels of short chain fatty acids can mean insufficient probiotics in the gut.

▪ Salivary VEGF test for hypochlorhydria – if there are symptoms of poor digestion or “too much acid”.

▪ Urine hydrogen sulphide test – some people ferment food to produce hydrogen sulphide and this can inhibit mitochondrial function. See HYDROGEN SULPHIDE AND CFS, FERMENTATION IN THE GUT AND CFS

▪ Parasitology at the London School of Hygiene and Tropical Medicine – detects worms, amoebae, giardia, blastocystis hominis.

▪ Comprehensive Digestive Stool Analysis – ability to digest and gut flora. Parasitology can also be done as part of this test.

▪ Short chain polypeptides – if the result is abnormal, it suggests leaky gut syndrome.

▪ Early morning Short chain fatty acids and/or tests of Fructose intolerance – indicate a tendency to HYPOGLYCAEMIA

Looking for toxic stress

▪ Fat biopsy for pesticides and/or for volatile organic compounds (VOCs). A fat biopsy is very easy to do – easier than a blood test! A green needle and 10ml syringe is used – the green needle is pushed into buttock fat, suction applied with the syringe, then needle withdrawn. The amount of fat inside the bore of the needle is sufficient to do the test.

▪ Sauna sweat test.

▪ Kelmer test (urine test) for mercury load – anybody with mercury fillings will have mercury on board – the question is how much? How hard does one have to work to get rid?

▪ Translocator protein studies.

▪ DNA adducts – looks to see if toxins have stuck onto DNA – if so, this is a pre-cancerous condition. This is a useful test to work out how much damage has been done to the body as a result of toxic stress and therefore how much work has to be put into a detox regime. If abnormal then it should be repeated following a detox regime to make sure there are improvements.

Looking for sensitivity to chemicals

▪ Lymphocyte sensitivity test for chemicals, heavy metals, silicones, VOCs. This is helpful if you suspect that you are reacting to one/some/all of those substances, in other words you are sensitive to them. I often use this where there is a silicone implant to help decide if it should be removed. Where there is sensitivity, there will be toxicity, and vice versa. Indeed, multiple chemical sensitivity is usually triggered by toxicity

More recently John McLaren-Howard has developed similar tests to diagnose electrical sensitivity

Evidence of damage to cells

▪ Plasma cell-free DNA – this is nearly always abnormal in CFS and can be for any one of the following reasons:

<ul>

<li>There is poor antioxidant status (see Co-enzyme Q10, SODase),</li>

<li>There is ongoing toxic stress (such as from pesticides, volatile organic compounds, heavy metals etc),</li>

<li>There is immune activation (as for example in acute infection),</li>

<li>There is very poor mitochondrial function (see mitochondrial function) score but the patient is forced to do some muscular activity just in order to live.</li>

<li>The patient is not pacing well – i.e. pushing too hard and this is resulting in cell damage. However some people who are very disabled have no choice – just the energy required to exist will cause tissue damage. So people with the worst mitochondrial function score often have high cell free DNAs even though they are doing almost nothing</li>

</ul>

This can be investigated further with LDH studies, which tells us where the damage is coming from.

Tests not worth doing either because the result is worthless or the test is unreliable

▪ Tests for food allergy – at best these are 70% accurate.

▪ B12 – occasionally picks up pernicious anaemia, but regardless of the level I almost routinely prescribe injections to improve fatigue syndromes. B12 provides “instant” antioxidant cover. It has no toxicity. I like to see blood levels above 2000 (at this levels many GPs recommend stopping treatment!).

▪ Hair analysis – does not reliably detect heavy metal toxicity and can be very misleading with trace elements. Useless for allergies.

There is no point doing the tests I list below before starting nutritional supplements. This is because deficiencies are pandemic

▪ B vitamin profile

▪ Red cell Magnesium

▪ Essential fatty acids

▪ Vitamins A, C and E

▪ Vitamin D3 levels (a bit expensive!)

There is no point doing a test unless it has implications for management – either one needs the test to make the diagnosis or to determine management options. Always ask this question when requesting a test or it is money wasted!

Tests ask very specific questions – there are literally hundreds of tests available, it is a case of picking the right one dependent on the symptoms and signs. If your doctor does not ask the right questions with his tests, then the results will not be relevant to recovery.

Where there are symptoms pertaining to a specific area such as the gut, tests need to be done to exclude ulcer disease, gall bladder disease, cancer and so on.

My general principle for tests of nutritional status is that I always advise sufferers to continue with their usual nutritional supplement programme when doing a test of nutritional status. This way I can assess if the current nutritional regime is adequate or not. I simply need to know what the patient is taking when interpreting such tests of nutritional status.

In CFS the problem is micro-pathology (intracellular, immune and biochemical problems), i.e. problems inside cells and on cell membranes. This is why standard medical tests do not come up with abnormalities.

A vital test in chronic fatigue syndrome

The central problem of chronic fatigue syndrome is mitochondrial failure resulting in poor production of ATP. ATP is the currency of energy in the body and if the production of this is impaired then all cellular processes will go slow. It is not good enough to measure absolute levels of ATP in cells since this will simply reflect how well rested the sufferer is. The perfect test is to measure the rate at which ATP is recycled in cells and this test has now been developed by the brilliant medical biochemist Dr John McLaren-Howard. He calls it “ATP profiles”. It is a test of mitochondrial function.

Not only does this test measure the rate at which ATP is made, it also looks at where the problem lies. Part A measures levels of ATP in the cell. Release of energy from ATP is a magnesium dependent process and the first part of the test studies this aspect (I refer to this aspect of the test as Part A– this corresponds to the labels in Figure 3 below).

The second aspect of the test (Part B) measures the efficiency with which ATP is made from ADP in the mitochondrion. If this is abnormal then this could be as a result of magnesium deficiency, of low levels of Co-enzyme Q10, low levels of vitamin B3 (NAD) or of acetyl L-carnitine. It is also possible that ADP to ATP conversion is blocked and this is also seen on this part of the test.

The third possibility is that the protein which transports ATP and ADP across mitochondrial membranes is impaired and this is also measured (Part C).

Acetyl-L-carnitine

Fue

CoQ10

Part C– crossing mitochondrial membrane Part A – ATPlevels

ATP

Mitochondrion

NAD

Magnesium

ADP

Energy

Oxygen

Part B - ADPto ATPconversion

Figure 3

The joy of the ATP profiles test is that we now have an objective test of chronic fatigue syndrome which clearly shows this illness has a physical basis. This test clearly shows that cognitive behaviour therapy, graded exercise and anti-depressants are irrelevant in addressing the root cause of this illness.

To get the full picture I recommend combining this test with measuring levels of the front line anti- oxidants Co-enzyme Q10, Superoxide dismutase (SODase), and glutathione peroxidase together with NAD (a functional test of vit B3 levels) and L-carnitine. See ANTIOXIDANTS

Cell-free DNA is very useful because it measures tissue damage. When cells are damaged and die, they release their contents into the blood stream – cell-free DNA measures the extent of this damage. I believe this equates to how ill one feels – or malaise. The levels which come back are similar to those from patients recovering from major infections, trauma, surgery or chemotherapy – so this test puts CFS firmly in the realms of major organic pathology. Where there is tissue damage, the immune system is activated for healing and repair – this requires energy and can produce distressing symptoms such as PAIN and INFLAMMATION.

SODase is an important antioxidant which mops up the free radicals produced in all the inefficient chemical reactions in the cells. Dr McLaren-Howard also looks at the genes which code for the different types of SODase! It is common to find blockage or polymorphisms typical of toxic stress. See INFLAMMATION.

Dr McLaren-Howard has recently developed a serum L-carnitine test and made it available in September 2009. I have now included it in the Mitochondrial Function Profile.

In fact, all of these above blood tests have now been combined as a Mitochondrial function profile and can be ordered from my practice – see details below p. To order any test123.

One other important co-factor in the production of energy in cells is D-ribose. It is used up so quickly by cells that measuring levels is unhelpful, but low levels of ATP imply low levels of D- ribose. .

Therefore, the cost of the Mitochondrial function profile, which will now include the mitochondrial function studies (ATP profiles), levels of Co-enzyme Q10, glutathione peroxidase, zinc copper SODase, manganese SODase and extracellular SODase together with NAD levels, cell- free DNA and L-carnitine is £225, plus £70 for the letter of interpretation to the GP.

John McLaren-Howard now has specialist equipment to refine these tests further, particularly in respect of oxidative phosphorylation. See Practical Details p. 123 should you wish to order this test

<ul>

<li>Testing

<ul>

<li>(Add tests list including those relevant to possible causes and cofactors)</li>

<li>From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment' https://sites.google.com/site/cfstestingandtreatmentroadmap/home When a test is performed for a microbe, we want to know not only whether you have it in your body, but more importantly, whether it is active or not. In chronic infections, the level of activity of a microbe can be gauged to a certain extent by the amount of IgG and IgM antibodies your body produces in response to that microbe. Alternative methods of testing for the presence of pathogens in the body include: PCR (polymerase chain reaction) and viral culture. Viral culture is usually the gold standard by which other viral detection methods are judged.   Empirical testing. While it is always better to test for pathogens or health conditions before using treatments, because some tests are expensive, not available in all countries, or might not always be reliable or sensitive enough to detect certain pathogens, you may choose to bypass the test and go straight to treatment (if the treatment well tolerated and safe). This is known as empirical testing: using a treatment itself as a test for a pathogen or health condition. Empirical testing makes the assumption that if you get better on the treatment, you may well have the pathogen or the health condition that the treatment targets.  *</li>

<li>While not everyone with ME/CFS shows signs of infection, many do. Several pieces of evidence support a theory that some ME/CFS is caused at least in part by a virus:</li>

<li>Enterovirus connection In a 2007 study, people with ME/CFS were four times more likely than healthy people to have evidence of enteroviruses in their stomach tissues. Enteroviruses cause stomach infections, and symptoms of ME/CFS frequently start after that kind of illness.</li>

<li>Rnase L Your body uses the enzyme Rnase L to kill viruses that are attacking your cells, and ME/CFS patients frequently have high Rnase L activity.</li>

<li>Natural Killer (NK) Cells and T Cells NK & T cells in your immune system attack virus-infected cells, and people with ME/CFS frequently have impaired NK and T cell functions and numbers, suggesting chronic immune activity may be exhausting and depleting them.</li>

<li>Antibodies People with ME/CFS typically have high levels of antibodies to many infection-causing organisms that cause fatigue and other ME/CFS symptoms. These organisms include those that cause candida (yeast), human herpesvirus type 6 (HHV-6), measles, parvovirus, and Epstein-Barr. Researchers have not been able to show that any of these is a significant cause of ME/CFS.</li>

<li>Post-illness onset Up to 80 percent of ME/CFS cases start suddenly after a flu-like condition.</li>

<li>Cluster outbreaks While the CDC has not confirmed most cluster outbreaks, reports of multiple people in the same household, workplace, and community developing ME/CFS at the same time are not unheard of.</li>

<li>Some researchers suggest that changes in normally harmless bacteria in the intestine may play a role in the development of ME/CFS.</li>

<li>However, some evidence seems to run counter to the viral-cause theory. ME/CFS doesn't appear to spread through direct content, people with it don't appear contagious, and -- in spite of well-designed studies -- researchers have not been able to link ME/CFS with any specific infections.</li>

<li>In 2009, researchers from the Whittemore Peterson Institute (WPI) published a study in the journal Science that suggested a link between XMRV, a newly discovered retrovirus, and ME/CFS. They found XMRV in about 67% of blood samples from ME/CFS patients. They also detected it in 3% of healthy controls.</li>

<li>However, subsequent studies failed to confirm the link, including a large study involving the WPI's primary researcher. Other studies suggested means by which contamination may have created false positives in the original study. By late 2011, the XMRV theory had been all-but abandoned.</li>

<li>Firstly exclude macroscopical pathology</li>

<li>Most patients, by the time they get to see me, have had all the routine tests done. These tests just test for macroscopic pathology such as major organ failure (anaemia, heart disease, cancer, liver failure, kidney failure and some gut problems). They do not test for minor organ failures (such as partial thyroid gland failure, partial adrenal gland failure, mild liver damage, poor ability to detox). None of these tests look for poor function of the brain or brain damage, nutritional tests are often absent or limited, hormone tests are usually incomplete and there are virtually no tests of micropathological function.</li>

<li>- Having said that, there are often mild abnormalities in standard tests which have not been picked up on by the GP or consultant, but which are clinically important for the CFS sufferer. Results are given by a figure and there should also be a reference range next to this figure that tells you if you are inside or outside the reference range. This reference range often varies from one lab to another.</li>

<li>The basic tests that most doctors do for their patients with chronic fatigue are:</li>

<li>- ▪ Haematology (full blood count red cells, white cells and platelets)</li>

<li>- ▪ Inflammation in the blood ESR, C reactive protein, plasma viscosity.</li>

<li>▪ Biochemistry (liver and kidney function)</li>

<li>▪ Blood sugar level</li>

<li>▪ Urine testing (for infection or kidney damage)</li>

<li>▪ Faecal occult bloods (looking for bleeding from the gut)</li>

<li>- ▪ Thyroid stimulating hormone (only looks for primary thyroid failure most thyroid problems in CFS are secondary to poor pituitary function)</li>

<li>▪ Ferritin (iron), B12, folic acid and calcium</li>

<li>- ▪ Perhaps a serum magnesium which is a completely useless test! This is because serum levels are maintained at the expense of levels inside cells. A serum magnesium is just an ITU (Intensive Therapy Unit) test!</li>

<li>▪ Autoantibody tests for autoimmunity.</li>

<li>Common abnormalities that can be shown by routine tests</li>

<li>The mild abnormalities I always look for in CFS in the above tests are:</li>

<li>- ▪ Low or low normal white cell count can be a sign of poor immune function which most commonly is secondary to nutritional deficiencies, such as low zinc, low magnesium, low B vitamins, low essential fatty acids.</li>

<li>- ▪ Low or low normal platelet count can be a sign of toxic stress</li>

<li>▪ Low MCV (mean corpuscular volume) suggesting iron or copper deficiency. Low iron is suggestive of HYPOCHLORHYDRIA, in which case other mineral deficiencies are also likely.</li>

<li>▪ High MCV suggesting B12, folic acid or HYPOTHYROIDISM</li>

<li>▪ A high blood sugar or a low blood sugar suggests there may be a tendency to HYPOGLYCAEMIA (a pre-diabetic tendency). A normal blood sugar tells you very little! Normal ranges of blood glucose have been changed because so many people now have carbohydrate intolerance. A normal blood sugar should be between 4-6mmol/l. High blood sugar is now associated with toxic stress because chemicals cause insulin resistance.</li>

<li>▪ Low potassium. Potassium varies according to diet! Low potassium means there is a lack of vegetables in the diet. Bananas may be rich in potassium but they are high glycaemic index, so beware!</li>

<li>- ▪ High normal bilirubin may be Gilbert s syndrome suggesting poor ability to detoxify.</li>

<li>- ▪ High normal or abnormal liver enzymes suggesting liver damage, usually from chemicals, or poor nutritional status.</li>

<li>▪ High urea or creatinine suggesting dehydration</li>

<li>▪ Low urea or creatinine suggesting low protein diet</li>

<li>- ▪ Low glomerular filtration rate suggesting poor kidney function could be due to allergy or toxic damage but may indicated poor mitochondrial function.</li>

<li>▪ A TSH tells you very little about thyroid status! It is essential to see the actual level of thyroid hormones in the blood.</li>

<li>▪ Low levels of B12 can be due to HYPOCHLORHYDRIA or MALABSORPTION</li>

<li>▪ High uric acid can point to poor ANTIOXIDANT status. See GOUT.</li>

<li>▪ Raised cholesterol could mean low levels of vitamin D or hypothyroidism.</li>

<li>▪ Low levels of calcium likely to mean low levels of vitamin D.</li>

<li>The routine tests which I nearly always do initially and which have important implications for management</li>

<li>- Mitochondrial function profile (p. 17 ) this is a batch of tests to identify the mitochondrial problem. This test has important implication for treatment; this test includes:</li>

<li>- ATP profiles looks at levels of ATP, how well energy is released from ATP, the rate of production of ATP from ADP and movement of ATP and ADP across mitochondrial membranes (translocator protein function - could be blocked by toxins or pH changes). Also gives us an objective measure of the level of disability.</li>

<li>- Plasma cell-free DNA a measurement of cell damage and antioxidant status in CFS</li>

<li>- Red cell NAD levels a measure of the efficiency of Kreb s citric acid cycle. Levels can be corrected with niacinamide 500mgs daily and acetyl L carnitine.</li>

<li>- Co-enzyme Q10 levels the most important antioxidant inside mitochondria. In CFS levels are nearly always deficient</li>

<li>- Superoxide dismutase three types measured, indicates levels of zinc, copper and manganese, also gene studies to give an indication of toxic damage. SODase is a major antioxidant in all cells.</li>

<li>- Red cell magnesium done as part of the ATP profile or can be done separately.</li>

<li>Glutathione and glutathione peroxidase (also indicates selenium status).</li>

<li>Thyroid function profile (free T4, Free T3 and TSH).</li>

<li>More esoteric tests which have implications for management</li>

<li>▪ Microrespirometry - looks in detail at ADP to ATP conversion (see sample result on p. 20</li>

<li>▪ Further investigation of poor translocator protein function Translocator protein studies (p.21)</li>

<li>▪ Cardiolipin studies looks at the structure of mitochondrial membranes (p. 22 )</li>

<li>- ▪ Calcium studies calcium levels inside cells often too high.</li>

<li>- ▪ Adrenal stress profile salivary levels of cortisol and DHEA over 24 hours</li>

<li>- ▪ Salivary Melatonin levels it is common to get poor melatonin production and therefore poor sleep in CFS. This is a further reflection of the inadequate HPA axis in CFS.</li>

<li>- ▪ Lactate dehydrogenase studies if there is evidence of cell damage, this indicates where the damage is coming from eg liver or muscle.</li>

<li>- ▪ Red cell Carbonic anhydrase indicates hyperventilation</li>

<li>When gut symptoms suggest tests</li>

<li>- ▪ Gut fermentation test to look for evidence of fermentation by bacteria or yeast. Irritable bowel syndrome may be caused by food allergy or gut dysbiosis. Low levels of short chain fatty acids can mean insufficient probiotics in the gut.</li>

<li>- ▪ Salivary VEGF test for hypochlorhydria if there are symptoms of poor digestion or  too much acid .</li>

<li>- ▪ Urine hydrogen sulphide test some people ferment food to produce hydrogen sulphide and this can inhibit mitochondrial function. See HYDROGEN SULPHIDE AND CFS, FERMENTATION IN THE GUT AND CFS</li>

<li>- ▪ Parasitology at the London School of Hygiene and Tropical Medicine detects worms, amoebae, giardia, blastocystis hominis.</li>

<li>- ▪ Comprehensive Digestive Stool Analysis ability to digest and gut flora. Parasitology can also be done as part of this test.</li>

<li>- ▪ Short chain polypeptides if the result is abnormal, it suggests leaky gut syndrome.</li>

<li>- ▪ Early morning Short chain fatty acids and/or tests of Fructose intolerance indicate a tendency to HYPOGLYCAEMIA</li>

<li>Looking for toxic stress</li>

<li>- ▪ Fat biopsy for pesticides and/or for volatile organic compounds (VOCs). A fat biopsy is very easy to do easier than a blood test! A green needle and 10ml syringe is used   the green needle is pushed into buttock fat, suction applied with the syringe, then needle withdrawn. The amount of fat inside the bore of the needle is sufficient to do the test.</li>

<li>▪ Sauna sweat test.</li>

<li>- ▪ Kelmer test (urine test) for mercury load anybody with mercury fillings will have mercury on board   the question is how much? How hard does one have to work to get rid?</li>

<li>▪ Translocator protein studies.</li>

<li>- ▪ DNA adducts looks to see if toxins have stuck onto DNA   if so, this is a pre-cancerous condition. This is a useful test to work out how much damage has been done to the body as a result of toxic stress and therefore how much work has to be put into a detox regime. If abnormal then it should be repeated following a detox regime to make sure there are improvements.</li>

<li>Looking for sensitivity to chemicals</li>

<li>▪ Lymphocyte sensitivity test for chemicals, heavy metals, silicones, VOCs. This is helpful if you suspect that you are reacting to one/some/all of those substances, in other words you are sensitive to them. I often use this where there is a silicone implant to help decide if it should be removed. Where there is sensitivity, there will be toxicity, and vice versa. Indeed, multiple chemical sensitivity is usually triggered by toxicity</li>

<li>More recently John McLaren-Howard has developed similar tests to diagnose electrical sensitivity</li>

<li>Evidence of damage to cells</li>

<li>- ▪ Plasma cell-free DNA this is nearly always abnormal in CFS and can be for any one of the following reasons:</li>

<li>There is poor antioxidant status (see Co-enzyme Q10, SODase),</li>

<li>There is ongoing toxic stress (such as from pesticides, volatile organic compounds, heavy metals etc),</li>

<li>There is immune activation (as for example in acute infection),</li>

<li>There is very poor mitochondrial function (see mitochondrial function) score but the patient is forced to do some muscular activity just in order to live.</li>

<li>- The patient is not pacing well e. pushing too hard and this is resulting in cell damage. However some people who are very disabled have no choice   just the energy required to exist will cause tissue damage. So people with the worst mitochondrial function score often have high cell free DNAs even though they are doing almost nothing</li>

<li>This can be investigated further with LDH studies, which tells us where the damage is coming from.</li>

<li>Tests not worth doing either because the result is worthless or the test is unreliable</li>

<li>- ▪ Tests for food allergy at best these are 70% accurate.</li>

<li>- ▪ B12 occasionally picks up pernicious anaemia, but regardless of the level I almost routinely prescribe injections to improve fatigue syndromes. B12 provides  instant  antioxidant cover. It has no toxicity. I like to see blood levels above 2000 (at this levels many GPs recommend stopping treatment!).</li>

<li>- ▪ Hair analysis does not reliably detect heavy metal toxicity and can be very misleading with trace elements. Useless for allergies.</li>

<li>There is no point doing the tests I list below before starting nutritional supplements. This is because deficiencies are pandemic</li>

<li>▪ B vitamin profile</li>

<li>▪ Red cell Magnesium</li>

<li>▪ Essential fatty acids</li>

<li>▪ Vitamins A, C and E</li>

<li>▪ Vitamin D3 levels (a bit expensive!)</li>

<li>- There is no point doing a test unless it has implications for management either one needs the test to make the diagnosis or to determine management options. Always ask this question when requesting a test or it is money wasted!</li>

<li>- Tests ask very specific questions there are literally hundreds of tests available, it is a case of picking the right one dependent on the symptoms and signs. If your doctor does not ask the right questions with his tests, then the results will not be relevant to recovery.</li>

<li>Where there are symptoms pertaining to a specific area such as the gut, tests need to be done to exclude ulcer disease, gall bladder disease, cancer and so on.</li>

<li>My general principle for tests of nutritional status is that I always advise sufferers to continue with their usual nutritional supplement programme when doing a test of nutritional status. This way I can assess if the current nutritional regime is adequate or not. I simply need to know what the patient is taking when interpreting such tests of nutritional status.</li>

<li>In CFS the problem is micro-pathology (intracellular, immune and biochemical problems), i.e. problems inside cells and on cell membranes. This is why standard medical tests do not come up with abnormalities.</li>

<li>A vital test in chronic fatigue syndrome</li>

<li>The central problem of chronic fatigue syndrome is mitochondrial failure resulting in poor production of ATP. ATP is the currency of energy in the body and if the production of this is impaired then all cellular processes will go slow. It is not good enough to measure absolute levels of ATP in cells since this will simply reflect how well rested the sufferer is. The perfect test is to measure the rate at which ATP is recycled in cells and this test has now been developed by the brilliant medical biochemist Dr John McLaren-Howard. He calls it ATP profiles . It is a test of mitochondrial function.</li>

<li>Not only does this test measure the rate at which ATP is made, it also looks at where the problem lies. Part A measures levels of ATP in the cell. Release of energy from ATP is a magnesium dependent process and the first part of the test studies this aspect (I refer to this aspect of the test as Part A this corresponds to the labels in Figure 3 below).</li>

<li>The second aspect of the test (Part B) measures the efficiency with which ATP is made from ADP in the mitochondrion. If this is abnormal then this could be as a result of magnesium deficiency, of low levels of Co-enzyme Q10, low levels of vitamin B3 (NAD) or of acetyl L-carnitine. It is also possible that ADP to ATP conversion is blocked and this is also seen on this part of the test.</li>

<li>The third possibility is that the protein which transports ATP and ADP across mitochondrial membranes is impaired and this is also measured (Part C).</li>

<li>Acetyl-L-carnitine</li>

<li>- Part C crossing mitochondrial membrane Part A   ATPlevels</li>

<li>Mitochondrion</li>

<li>Magnesium</li>

<li>Energy</li>

<li>Oxygen</li>

<li>Part B - ADPto ATPconversion</li>

<li>Figure 3</li>

<li>The joy of the ATP profiles test is that we now have an objective test of chronic fatigue syndrome which clearly shows this illness has a physical basis. This test clearly shows that cognitive behaviour therapy, graded exercise and anti-depressants are irrelevant in addressing the root cause of this illness.</li>

<li>To get the full picture I recommend combining this test with measuring levels of the front line anti- oxidants Co-enzyme Q10, Superoxide dismutase (SODase), and glutathione peroxidase together with NAD (a functional test of vit B3 levels) and L-carnitine. See ANTIOXIDANTS</li>

<li>- Cell-free DNA is very useful because it measures tissue damage. When cells are damaged and die, they release their contents into the blood stream cell-free DNA measures the extent of this damage. I believe this equates to how ill one feels   or malaise. The levels which come back are similar to those from patients recovering from major infections, trauma, surgery or chemotherapy   so this test puts CFS firmly in the realms of major organic pathology. Where there is tissue damage, the immune system is activated for healing and repair   this requires energy and can produce distressing symptoms such as PAIN and INFLAMMATION.</li>

<li>SODase is an important antioxidant which mops up the free radicals produced in all the inefficient chemical reactions in the cells. Dr McLaren-Howard also looks at the genes which code for the different types of SODase! It is common to find blockage or polymorphisms typical of toxic stress. See INFLAMMATION.</li>

<li>Dr McLaren-Howard has recently developed a serum L-carnitine test and made it available in September 2009. I have now included it in the Mitochondrial Function Profile.</li>

<li>- In fact, all of these above blood tests have now been combined as a Mitochondrial function profile and can be ordered from my practice see details below p. To order any test123.</li>

<li>One other important co-factor in the production of energy in cells is D-ribose. It is used up so quickly by cells that measuring levels is unhelpful, but low levels of ATP imply low levels of D- ribose. .</li>

<li>Therefore, the cost of the Mitochondrial function profile, which will now include the mitochondrial function studies (ATP profiles), levels of Co-enzyme Q10, glutathione peroxidase, zinc copper SODase, manganese SODase and extracellular SODase together with NAD levels, cell- free DNA and L-carnitine is 225, plus  70 for the letter of interpretation to the GP.</li>

<li>John McLaren-Howard now has specialist equipment to refine these tests further, particularly in respect of oxidative phosphorylation. See Practical Details p. 123 should you wish to order this test</li>

<li>Allergy Testing</li>

<li>Amino Acids Asparagine, Glutamine, Serine</li>

<li>Antioxidants</li>

<li>Some ME/CFS patients show evidence of decreased adenosine triphosphate ATP production.

<ul>

<li>- Examples of some test resultsATP profilesThis patient has low levels of ATP (1), low magnesium (2), poor conversion of ADP to ATP (3) with blockage of the active sites (4) together with poor translocator protein function (5) no wonder there is severe fatigue!</li>

</ul>

</li>

<li>A closer look at oxidative phosphorylation with micro-respirometry studies chart</li>

<li>A closer look at translocator protein studies chart

<ul>

<li>- Cardiolipin Studies a closer look at mitochondrial membranes chart</li>

</ul>

</li>

<li>Anti-oxidant studies chart</li>

<li>Biotoxins (Lyme and mold)</li>

<li>Cardiac abnormalities</li>

<li>From: 'Heart Problems in Chronic Fatigue Syndrome, Cardiac abnormalities linked to unexplained fatigue' https://www.verywell.com/heart-abnormalities-in-chronic-fatigue-syndrome-716011

<ul>

</ul>

</li>

<li>Chronic fatigue syndrome (CFS) — also referred to as myalgic encephalopathy, or ME/CFS — is a medical condition characterized by persistent fatigue and other symptoms which limit a person's ability to carry out normal, everyday tasks. ME/CFS is not well understood and is believed to be caused by a combination of psychological, genetic, and biological factors.

<ul>

</ul>

</li>

<li>In recent years, researchers have noticed that, in addition to the symptoms of exhaustion, people with ME/CFS have higher rates of heart abnormalities than the general population.

<ul>

</ul>

</li>

<li>While it is often difficult to connect cause with effect, there are many in the research community who believe that this association is more than incidental.

<ul>

</ul>

</li>

<li>Types of Heart Abnormalities

<ul>

</ul>

</li>

<li>One foundational study conducted in 2006 reported that persons with ME/CFS who died of heart failure did so at a mean age of 58.7 years compared to 83.7 years for those without ME/CFS. While no one can know for sure which factors may have contributed to this result, studies like this have long suggested that ME/CFS is inherently linked to insufficient heart function.

<ul>

</ul>

</li>

<li>And the abnormalities don't stop there. Other investigators have noted similar high rates of heart irregularities, including:

<ul>

</ul>

</li>

<li>a lack of nocturnal heart rate variability (meaning the heart fails to slow as expected during sleep)

<ul>

</ul>

</li>

<li>a small left ventricle (the chamber of the heart that pumps blood to the rest of the body)

<ul>

</ul>

</li>

<li>postural tachycardia (a condition where the heart rate speed up, often unevenly, when a person rises)

<ul>

</ul>

</li>

<li>short QT interval (a genetic disorder which affects the electrical system of the heart and causes palpitations or sudden loss of consciousness)

<ul>

</ul>

</li>

<li>abnormally low blood volumes

<ul>

</ul>

</li>

<li>These irregularities may, in fact, explain some of the key symptoms of ME/CFS. They also suggest that people living with ME/CFS may need to work harder to maintain good heart health than persons in the general population.

<ul>

</ul>

</li>

<li>Low Heart Rate Variability

<ul>

</ul>

</li>

<li>A study conducted in 2011 looked into sleep patterns in people with ME/CFS in order to better understand why unrefreshing sleep is commonly reported in this group. What they found, surprisingly, was that people with ME/CFS had little variation in their heart rate from day to night, a condition known as low heart rate variability (HRV).

<ul>

</ul>

</li>

<li>To understand this, if you feel your pulse and then breathe in and out slowly, you'll notice that your heart rate changes slightly, speeding up when you breathe in and slowing down when you breathe out. That's heart rate variability.

<ul>

</ul>

</li>

<li>A low nocturnal HRV suggests that there's a problem with the nerve signals that regulate the pacemaker of the heart (called the sinus node). This is in line with thinking that ME/CFS may be caused, at least in part, by flaws in a person's autonomic nervous system (the system which regulates involuntary functions such as breathing, digestion, and heart rate).

<ul>

</ul>

</li>

<li>Small Left Ventricle

<ul>

</ul>

</li>

<li>A 2011 study found that some people with ME/CFS have a smaller left ventricle, the chamber of the heart responsible for pumping blood to the rest of the body. As a result of this, persons will invariably experience symptoms of what is called orthostatic intolerance (OI).

<ul>

</ul>

</li>

<li>Normally, when we get up from a seated or lying position, our blood pressure will rise briefly to counter gravity and keep the blood flowing to the brain. With OI, this doesn't happen, and a person will end up feeling dizzy or fainting whenever he or she rises. This physiological anomaly could explain why minimal exertion tends to wear out a person with ME/CFS more than others.

<ul>

</ul>

</li>

<li>Postural Tachycardia

<ul>

</ul>

</li>

<li>Postural tachycardia is similar to OI except that it involves the pulse rate rather than the blood pressure. Tachycardia is the medical term for an abnormally rapid heart rate. Postural tachycardia simply means your heart rate speeds up abnormally whenever you rise, resulting in dizziness or even fainting.

<ul>

</ul>

</li>

<li>Postural tachycardia is commonly seen in people with ME/CFS, running at three times the rate of the general population.

<ul>

</ul>

</li>

<li>Short QT Interval

<ul>

</ul>

</li>

<li>A QT interval is a term used to describe the space between certain up-and-down beats on an electrocardiogram (ECG) readout. A short QT interval means that your heart is beating normally but has less chance to recover after a heartbeat. A short QT interval is typically considered a genetic disorder and is associated with the increased risk of sudden cardiac death. While rare in the general population, a short QT interval is frequently seen in persons with ME/CFS.

<ul>

</ul>

</li>

<li>Abnormally Low Blood Volume

<ul>

</ul>

</li>

<li>Two studies conducted in 2009 and 2010 reported that persons with ME/CFS had lower blood volumes than the general population. Moreover, the severity of ME/CFS directly corresponded with a decrease in blood volume, meaning those who were less able to function had far less blood than those who were. Many scientists now believe that low blood volume contributes to many of the symptoms of ME/CFS simply by depriving cells of the oxygen needed to produce energy.

<ul>

</ul>

</li>

<li>What the Research Tells Us

<ul>

</ul>

</li>

<li>While the studies suggest that abnormalities of the heart and nervous system contribute to the high rates of cardiac failure in people with ME/CFS, they shouldn't suggest that they are the only factors. Other things, such as weight and sedentary lifestyle, may contribute as much or even more.

<ul>

</ul>

</li>

<li>In the end, most of these studies are small and isolated and need far more investigation to considered conclusive. What they should highlight, however, is the increased need to monitor the cardiac health of people living with ME/CFS. This is especially true for those with severe symptoms as well as anyone who has risk factors for cardiac disease (including smoking, obesity, and a lack of exercise).

<ul>

</ul>

</li>

<li>What is becoming increasingly clear is that ME/CFS is not "all in your head." If living with ME/CFS, treat it as would any other medical condition by looking not only at the illness itself but at its impacts on your overall good health.

<ul>

</ul>

</li>

<li>Sources:

<ul>

</ul>

</li>

<li>Hurwitz, B., et. al. "Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function." 2009; 118(2):125-35.

<ul>

</ul>

</li>

<li>Jason LA, et. al. Health care for women international. 2006 Aug;27(7):615-26. Causes of death among patients with chronic fatigue syndrome.

<ul>

</ul>

</li>

<li>Miwa, K. and Fujita, M. "Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome." Clinical Cardiology. 2011; 34(12):782-6.

<ul>

</ul>

</li>

<li>Naschitz J., et. al. "Shortened QT interval: a distinctive feature of the dysautonomia of chronic fatigue syndrome." European Journal of Internal Medicine. 2006; 39(4):389-94.

<ul>

</ul>

</li>

<li>Rahman K., et. al. "Sleep-wake behavior in chronic fatigue syndrome." Sleep. 2011; 34(5):671-</li>

<li>Cardiovascular Testing (Good and Bad Cholesterol)</li>

<li>Changes from Head Injury</li>

<li>From: Phoenix rising user 'MishMash' http://forums.phoenixrising.me/index.php?threads/head-injury-and-hypopituitarism.22717/

<ul>

</ul>

</li>

<li>Head injuries can cause collapse or damage to the pituitary gland. Which can be seen in a scan (sometimes). This usually correlates, but not always, to symptoms of low pituitary function.

<ul>

</ul>

</li>

<li>But the number of people who have collapsed pituitary gland, and hence low pituitary function, due to accidents, head injuries is tiny compared to the number who get it idiopathically. Collapsed, or disappearing, pituitary gland is known as "empty sella syndrome," because the gland sits naturally in a bone cavity called "the sella."

<ul>

</ul>

</li>

<li>ESS is very common among CFS patients BTW. Before he left, Cort did an interesting feature on this for PR. A number of members posted they had ESS. Cort himself said the radiologist noted that his pituitary gland had disaappeared. One of the things he was recommending as a CFS spokesman was further research into this.

<ul>

</ul>

</li>

<li>The chances for getting ESS go up markedly as age increases. Intracranial hypertension (too much brain fluid pressure) is usually cited as the reason for young people getting it. Too much brain fluid pressure has been associated with connective tissue weakness (or Ehlers-Danlos) since the cerebral ducts are weak and floppy, and get kinked and clogged easily. So the fluid just keeps building up in your cranium. Which leads to lower blood flow to the brain, if the theory is correct.

<ul>

</ul>

</li>

<li>Some people go as far as putting in shunts. I've done quite a bit of research on this, and the shunts rarely result in reduction in symptoms, from what I've read. The doctor at "prettyill.com" has recommended taking diuretics to reduce cerebral brain fluid amounts; hence reducing pressure on the brains, and lowering frequency of headaches.</li>

<li>Chronic infections</li>

<li>Cytokines</li>

<li>from: Cytokine signature associated with disease severity in chronic fatigue syndrome patients | PNAS</li>

<li>Although only two cytokines were found to be different (TGF- higher and resistin lower) in ME/CFS patients compared with controls, 17 cytokines correlated with ME/CFS severity. Thirteen of these cytokines are proinflammatory and may contribute to many of the symptoms these patients experience for several years. Only CXCL9 (MIG) inversely correlated with fatigue duration.</li>

<li>The average pMFI of two cytokines was found to be significantly different in ME/CFS patients and in healthy controls. TGF- (P = 0.0052) was elevated in ME/CFS patients, and resistin (P = 0.0052) was lower (Table 2). In addition, three cytokines were significantly different in cases and controls when stratified by severity, as shown in Fig. 1 (red brackets). The average pMFI of IL-13 was significantly higher in the severe group (P = 0.0250) than in controls; leptin was significantly lower in the mild group (P = 0.0495), and resistin was significantly lower in the mild (P = 0.0370) and severe (P = 0.0208) groups (Table 3).</li>

<li>Overall, 17 cytokines were found to have a statistically significant upward linear trend across the sequence of mild, moderate, and severe ME/CFS severity: CCL11 (P = 0.0069), CXCL1 (P = 0.0266), CXCL10 (P = 0.0100), G-CSF (P = 0.0110), GM-CSF (P = 0.0063), IFN- (P = 0.0101), IL-4 (P = 0.0103), IL-5 (P = 0.0073), IL-7 (P = 0.0063), IL-12p70 (P = 0.0069), IL-13 (P = 0.0069), IL-17F (P = 0.0103), leptin (P = 0.0100), leukemia inhibitory factor (LIF) (P = 0.0100), nerve growth factor (NGF) (P = 0.0069), stem cell factor (SCF) (P= 0.0145), and TGF-  (P = 0.0367) (Fig. 2 and Table 4). Intercellular adhesion molecule 1 (ICAM1) and resistin exhibited a statistically significant, nonlinear, inverted trend (P = 0.0334 for each) (Fig. 1).</li>

<li>Analysis of ME/CFS Cases by Fatigue Duration.</li>

<li>In Spearman correlation analyses, before controlling for potentially confounding variables, several cytokines were found to correlate inversely with fatigue duration: Growth related oncogene- (GRO-  or CXCL1), IFN- , IL-1 , IL-1RA, IL-2, IL-8, IL-15, TGF- , and TGF-  (SI Appendix, SI Materials and Methods and Table S1). Following correction for age, nonspecific binding, race, and sex, only one cytokine, CXCL9 (monokine induced by interferon- , MIG), was found to correlate inversely with fatigue duration (unadjusted for multiple comparisons, P = 0.0123) (SI Appendix, Table S1). Although the inclusion of fatigue duration as an additional covariate was expected to result in a loss of statistical power, regression analysis by both disease severity and fatigue duration revealed that the upward linear trend across disease severity remained statistically significant for CCL11, CXCL10, G-CSF, GM-CSF, IFN- , IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, LIF, NGF, ICAM1, and resistin. The findings by severity for CXCL1, SCF, and TGF-  shifted slightly above the threshold for statistical significance (CXCL1, adjusted P = 0.0536; SCF, adjusted P = 0.0531; TGF- , adjusted P = 0.0797), possibly because of variance inflation (18) by the independent covariate of fatigue duration. Only CXCL9 and IL-1  inversely correlated with fatigue duration but lost statistical significance after correction for multiple comparisons (SI Appendix, Table S2). We also compared mean cytokine levels in cases with  3-y fatigue duration (n = 30) and those with >3-y fatigue duration (n = 156), as per Hornig et al. (17). We did not find any cytokine to be significantly different between these two groups (SI Appendix, Table S3).</li>

<li>Enzymes</li>

<li>Heavy Metals and voc</li>

<li>Conventional testing for heavy metals consists of drawing blood to see what s in the blood stream. The problem is that heavy metals will only appear in the bloodstream if there was an acute exposure within the last week. For example, if you broke a thermometer and had your blood tested two days later, mercury would likely be found in your bloodstream. This kind of testing is not accurate for determining the effects of a lifetime chronic metals. The target of heavy metals is not the blood stream. That means that if you grew up in a home with leaded pipes but were not exposed to lead in the last week, a standard blood test for lead would come up negative but there would still be lead stored up in your body (and specifically your bones). Standard blood tests miss the heavy metals that are being stored in your body. of exposure or exposure to heavy</li>

<li>Hair analysis is another testing method that practitioners use. However, while hair analysis has some accuracy for minerals, it is not useful for detecting heavy metals. Also, some practitioners muscle test for heavy metals. I caution against this type of testing for heavy metals. I am not against muscle testing in general, but it is not useful regarding heavy metals. For instance, mercury has a high affinity for brain tissue (specifically the hypothalamus and pituitary gland). When someone is muscle testing they are challenging the nervous system, including the brain. Since mercury is a neurotoxin that targets the brain, the accuracy of muscle testing would be impacted by any mercury present in the brain at the time of testing. I think of mercury as the heavy metal of deception. My wife had a blood test and a hair analysis for heavy metals that came back negative. She was also muscle tested and heavy metals were shown to not be a major issue. Those results were inaccurate and it caused more suffering until someone told us how to properly test for heavy metals.</li>

<li>The best test that is currently available is a heavy metal urine challenge test. When being given this test, you take a true heavy metal chelator like DMPS, DMSA, or EDTA and your urine is then collected to be analyzed. The chelator pulls heavy metals out of the body through the liver, kidneys, and urine. In this test, the urine is sent in and inspected for the presence and amount of twenty different heavy metals. There are very specific instructions needed for this test to make sure it is performed correctly and to ensure that it doesn t cause the individual any harm. Go to a trusted health professional with experience in testing and treating heavy metal toxicity to have this test properly administered.</li>

<li>Hormones</li>

<li>Hypoglycaemia</li>

<li>Lyme Disease Testing (see Appendix Lymes)</li>

<li>Male & Female Sex Hormone Testing</li>

<li>Metabolites Choline, Inositol, Carnitine</li>

<li>Methylation Testing</li>

<li>Mitochondrial Function</li>

<li>Neurally mediated hypotension (NMH)</li>

<li>A form of low blood pressure called neurally mediated hypotension (NMH) is common in people with ME/CFS. It's caused by an abnormal interaction between the heart and the brain, even though both organs are normal and healthy. Also called the fainting reflex, NMH can cause dizziness and fainting and is sometimes diagnosed by what's called a tilt table test.</li>

<li>Some people with diagnosed NMH take a low-blood-pressure medication called Florinef (fludrocortisone), while others take the high blood-pressure medication Tenormin (atenolol). If you're on Tenormin, you'll probably need to be watched for low blood pressure and may be advised to increase your salt and water intake.</li>

<li>NK cells</li>

<li>Other</li>

<li>Carbohydrate Metabolism Fatty Acids Alpha Lipoic Acid, Coenzyme Q10, Cysteine, Glutathione, Selenium, Vitamin E, Total Antioxidant Function, Chromium, Fructose Sensitivity, GlucoseInsulin Metabolism, Oleic Acid</li>

<li>Other suspects</li>

<li>Use the following as a check list to make sure these possibilities have at least been considered:</li>

<li>Some chronic infections need specialist treatment in their own right, such as hepatitis B and C and HIV infection.</li>

<li>Gut dysbiosis. See Fermentation in the gut and CFS.</li>

<li>Helicobacter pylori: a blood test for helicobacter pylori antibodies is now available at most district general hospitals so your GP should be able to do this. H pylori infection can also be tested for by a helicobacter pylori breath test. Indeed, if you have had eradication therapy for H pylori, then this is the follow-up test to see if eradication has worked (antibody levels remain positive for many months after).</li>

<li>Urinary tract infections can be tested for using the multistix urine testing kit (this can be ordered through my online sales website at Sales at Dr Myhill for packs of 25 Multistix). This looks for a range of abnormalities. If there is infection, expect to see positives for protein, nitrites and/or leucocytes. Positive results need treatment with antibiotics. I usually start with a "best guess" antibiotic such as trimethoprim. But a full sample of urine (mid stream urine microscopy and culture) should also be sent off to ascertain which bacteria are there and to which antibiotic it is sensitive. See Irritable Bladder Syndrome.</li>

<li>Pelvic inflammatory disease and prostatitis. If you want to be tested, please contact my office and I shall refer you to The Doctors' Laboratory for an appropriate test. The usual ordering process as in Ordering Tests will apply.</li>

<li>The available blood tests are as follows, with the possible reasons for getting them done:</li>

<li>Amoebic antibodies. If illness started with gastroenteritis when living in an area of poor sanitation. Treatable with drugs.</li>

<li>Borrelia antibodies (Lyme's disease). Contact with ticks from sheep or deer. I honestly do not know the best way to diagnose and treat this problem! The tests are not reliable neither to my mind is the treatment!</li>

<li>Brucella antibodies: Usually acquired in parts of Europe, Middle East, Central and South America.</li>

<li>Chlamydia antibodies . Chlamydia is a group of bugs also called mycoplasma, the smallest known free living organisms. They cause a variety of diseases including pneumonia, but the commonest problem associated with fatigue is sexually transmitted disease - pelvic inflammatory disease in women and prostatitis in men. Men may have no symptoms of infection. Sexually transmitted diseases are the commonest chronic infections in UK. Chlamydia may also be responsible for: Gulf War syndrome mycoplasma incognito - difficult to test for and treat.</li>

<li>Psittacosis (from parrots) and ornithosis (from birds) - rare</li>

<li>Echinococcus (tapeworm) antibody. Tapeworms are usually acquired from dogs.</li>

<li>Enteroviral antibody screen (coxsackie virus, adenovirus, polio virus and echo virus). These common viral infections may cause no illness at all, gastroenteritis or 'flu-like symptoms. There is no specific treatment for these infections.</li>

<li>Epstein-Barr virus screen. This is the cause of glandular fever, a common trigger of CFS. Indeed, it has been estimated that over 20% of people getting glandular fever never fully recover their previous energy levels. No specific treatment for this viral infection.</li>

<li>Helicobacter antibody. The bacteria helicobacter pylori lives in the stomach. The stomach tries to get rid of it by producing extra acid. This extra acid production can cause problems such as duodenal ulcer, gastric ulcer, gastritis and oesophagitis, which present with symptoms of indigestion, acidity and heartburn.</li>

<li>Hepatitis A antibodies (Total)- HAV. This causes a mild, non serious jaundice. No specific treatment for this virus.</li>

<li>Hepatitis B core antibody HBcAB</li>

<li>Hepatitis B e antibody HbeAb. Hepatitis B is a nasty chronic infection which can certainly cause fatigue. No specific treatment for this virus.</li>

<li>Hepatitis B surface antibody (post vaccination check) to see if vaccination has been effective.</li>

<li>Hepatitis C antibody HCV. Hepatitis C is a nasty chronic infection which can certainly cause fatigue. No specific treatment for this virus.</li>

<li>Hepatitis D (Delta) - usually found with the other hepatitis viruses.</li>

<li>Hepatitis E antibody (IgG)</li>

<li>Herpes I and II combined IgG antibody test. HSV I causes cold sores and is very common with over half the population testing positive. HSV II is sexually transmitted and is one cause of genital warts (they can also be caused by papovaviruses). In women warts are risk factor for cervical cancer. Both HSV I and II are sensitive to anti-virals such as acyclovir.</li>

<li>HIV antibodies HIV1 and 2. This website does not offer HIV testing. This has to be done at specialist clinics.</li>

<li>Leishmania antibody. Leishmania is a tropical disease transmitted by sandfly bites.</li>

<li>Leptospira antibody. This causes hepatitis, acquired from rat's urine, treatable with penicillin.</li>

<li>Malaria antibodies. Malaria should be suspected in any person with 'flu like illness recently returning from a malarial area, regardless of whether or not they have taken malaria prophylaxis. I don't know if malaria does cause CFS, but I don't see why it could not be a trigger.</li>

<li>Measles antibodies. A viral infection and trigger of CFS. Vaccination also produces antibodies.</li>

<li>Mumps antibodies. A viral infection and trigger of CFS. Vaccination also produces antibodies.</li>

<li>Mycoplasma antibodies. See chlamydia, above.</li>

<li>Mycoplasma incognito. For information about this infection, see Nancy and Garth Nicholson's website www.immed.org.</li>

<li>Parvovirus antibodies. Causes "slapped cheek" in children. Can cause arthritis in women. No treatment for this viral infection.</li>

<li>Rubella IgG. A viral infection and trigger of CFS. Vaccination also produces antibodies.</li>

<li>Salmonella antibodies. There are many strains of salmonella, one of which is typhoid. They are one cause of food poisoning.</li>

<li>Schistosoma antibodies. Schistosomiasis is a tropical disease acquired through paddling in infected water. Treatable.</li>

<li>Toxoplasma antibodies Total. A protozoal infection acquired from cats. May cause low grade fever and swollen lymph nodes. Difficult to treat.</li>

<li>TPHA & VDRL. This is a test for syphilis, which is now very rare since this spirochete is very sensitive to penicillin. All pregnant women are routinely tested for this disease.</li>

<li>Positive results and treatment</li>

<li>A positive antibody test means that there has been exposure at some time in the past to that particular infection, it does not necessarily mean there is active infection now. For helicobacter pylori, breath testing will indicate active current infection. I would normally treat a positive test for chlamydia since this is resistant to commonly used antibiotics. For other infections ultra sensitive tests looking for DNA from the offending organism can be done (PCR tests) but I very rarely do them. Please e-mail my office if you have a particular query. (See How to contact us) The point about any infection is that the diagnosis is both a clinical and a laboratory one - furthermore, lab tests are fallible!</li>

<li>Furthermore, positive results do not mean a cure is round the corner. The problem with CFS is that the immune system is not working properly. This may be why the infection was picked up in the first place. Any antifungals and antibiotics to treat these conditions only give a percentage kill, furthermore there is likely to be an allergic element with inappropriate immune reactions getting in the way. Again see Inflammation and Antioxidants - poor anti-oxidant status is a disease amplifying problem! This essentially is my approach to treating any of the above problems - ie put the immune system in as fit a state as possible so it can sort things out!</li>

<li>Related Tests</li>

<li>Helicobacter Pylori breath test</li>

<li>Comprehensive Digestive Stool Analysis with parasitology</li>

<li>Related Articles

<ul>

<li>- Chronic infection Life is an arms race   how to tackle with natural remedies</li>

</ul>

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<li>Urine analysis</li>

<li>External Links</li>

<li>The Doctors' Laboratory offer a range of testing for STD. You can see a list of their profile tests here</li>

<li>References Nancy and Garth Nicholson, Sarah Myhill Limited :: Registered in England and Wales :: Registration No. 4545198 Registered Office: Upper Weston, Llangunllo, Knighton, Powys, Wales LD7 1SL, UK. Tel 01547 550331 | Fax 01547 550339</li>

<li>The Digestive Tract (Digestion Testing)</li>

<li>Thyroid and Adrenals</li>

<li>A lab test for identifying adrenal fatigue is a saliva test. It s important to take samples of the saliva at different times of the day in order to establish the true cortisol rhythm and DHEA levels. Samples are taken in the morning (6am-8am), midday (12pm-1pm), late afternoon (4pm-5pm) and nighttime (10pm-midnight). Cortisol should be at the highest in the morning and the lowest at night.</li>

<li>Taking your body temperature when you wake up in the morning and finding that your temperature is below 97.8 degrees Fahrenheit can help to detect adrenal and/or thyroid problems</li>

<li>Please note that adrenal fatigue (exhaustion) has three different stages before it reaches failure. People in stage one of adrenal fatigue have a high amount of cortisol overall and at least one cortisol reading that is higher than it should be. An overall high count and a spike at an inappropriate time of the day indicates there is a problem. Cortisol must be kept under control because it eats muscle when at an excessively high level.</li>

<li>Stage two of adrenal fatigue is commonly misdiagnosed and can even go undiagnosed entirely. This primarily happens because a person s total cortisol level is normal in stage two! The key indicators in this stage are the DHEA level and a low level of cortisol in the morning, midday, or afternoon. The trouble with properly identifying adrenal fatigue in stage two is that cortisol levels are often normal at night and the overall reading usually averages in the normal range as well. Again, cortisol should be at the highest in the morning and lowest at night. If a client is experiencing low cortisol levels when it should be at its peak, there is a problem.</li>

<li>Stage three of adrenal fatigue is the easiest to identify. The DHEA level is low and most cortisol levels are borderline low or low throughout the day. And of course, the total cortisol level is low as well. Low nighttime cortisol is a major marker for late stage three adrenal fatigue.</li>

<li>There are some tests that can be taken at home which tell you if adrenal fatigue is part of your problem. For example, go into an indoor room that is away from the natural sunlight (a room with no windows or, at the very least, with the shades lowered) with a small flashlight. Shine the light at a 45-degree angle towards your eye and you will see your pupil shrink (the pupil is the black center of your eye). The light of the flashlight will cause the pupil to shrink and it should remain constricted while the light is being pointed at your eye. You likely have adrenal problems if you see your pupil pulsing (alternating between being bigger and smaller). While this simple test shouldn t replace an actual diagnosis, it does point to what could be the source of your issues and it would be something to further investigate with a health professional.</li>

<li>Another test is I recommend involves an electronic blood pressure cuff (the Omron® blood pressure cuff can be purchased online for around $50-60). Place the blood pressure cuff on your arm as you normally would when measuring your blood pressure but lay down on your back for 5-10 minutes before taking the measurement. Have someone write down what the measurement is. Then stand up as fast as you can, take your blood pressure again, and write down that number. You are looking for the difference in blood pressure numbers between lying down and standing. This is called an orthostatic measurement.</li>

<li>To illustrate, let s say someone s measurement is 120/80 when laying down and jumps to 130/85 immediately after standing. That s good! The body naturally increases blood pressure when standing because gravity places more demands on our bodies. It is normal and healthy to see both the systolic rate (the top number) and the diastolic rate (the bottom number) increase 5-10 mmHg when going from laying down to standing. What if the rate doesn t go up? For example, let s say a person s lying down blood pressure rate is 120/80 but it goes down to 110/80 immediately after standing. That s bad. When this occurs, I often find the person has adrenal dysfunction and toxicity issues. Similarly, people who become light headed or dizzy when rising from a lying or sitting position also tend to have adrenal dysfunction and toxicity issues.</li>

<li>Conventional practitioners generally determine if a patient has thyroid problems by testing their TSH level. What I find interesting is that TSH (thyroid stimulating hormone) is not even manufactured by the thyroid! It s actually manufactured by the pituitary gland and is meant to communicate with the thyroid. Low TSH indicates hyperthyroidism (overactive) and high TSH suggests hypothyroidism (low functioning).</li>

<li>Conventional testing says that normal  values for TSH are typically .5 to 5  /mL. I believe that is too big of a range. I would not use the conventional bell curve that is used to determine the  normal range.  Instead, I recommend all practitioners and those who suspect they have thyroid dysfunction to use the optimal values that are between 1.8 and 3  /mL. The bell curve used to show the  normal  range is established by sick people! Think about it: who has their TSH tested? People who are displaying symptoms of having a dysfunctioning thyroid! To be on the edges of what is considered normal in that group is not optimal.</li>

<li>Like I said earlier, TSH communicates and works with the thyroid. The pituitary gland in the brain releases TSH which then stimulates the thyroid gland. The thyroid gland then produces its T4 hormone (and a small amount of T3), which is then converted to the T3 hormone primarily in the liver. T3 is the active form of the thyroid hormone and is the most important.</li>

<li>To take it to another level, there is a difference between Total T4 and Total T3 vs. Free T4 and Free T3. The body s cells can only use the free forms of the hormone and Free T3 is the most important. Your body uses proteins to transport T4 & T3 hormones in the blood stream. Your body breaks up the proteins and allows the T3 to be absorbed at the cellular level (which makes it Free T3).</li>

<li>T4 is converted to T3 primarily in the liver and this is typically a problem for most people with hypothyroidism. During times of stress the body converts T4 into Reverse T3 (RT3) instead of T3. This is a normal process that typically is very short lived. When the body is under extreme physical, chemical and/or emotional stress this conversion of T4 into Reverse T3 becomes chronic and is very dangerous.</li>

<li>The leading cause of hypothyroidism is caused by an autoimmune condition called Hashimoto s Disease, which was the first to be recognized as an autoimmune condition in 1912. Hashimoto s Disease causes the body to attack its own thyroid gland tissues. Testing thyroid antibody levels (TPO and TG) reveal this problem. The most common symptom of the disease is feeling worse even with thyroid replacement hormone treatment. Another symptom is when lab tests show both hypothyroid and hyperthyroid levels at different times.58 When diagnosing a client with potential thyroid problems I always recommend a complete thyroid panel that includes at least: TSH, Free T4, Free T3, Reverse T3 and Thyroid Antibodies. Depending on what is found in the lab tests, there are different protocols we could follow to heal the thyroid.</li>

<li>Most doctors don t run Reverse T3 or Antibody testing because their treatment would be the same regardless of the results. They typically give a prescription synthroid (or generic Levothyroxine), which is a T4 hormone replacement. If the patient is seeing an alternative medicine practitioner they will typically be switched to Armour thyroid, which is a bio-identical T3/T4 hormone from pigs, not just T4. A recent issue that has emerged is that the manufacturers of Armour thyroid are reducing their production costs by adding gluten as a filler. If you need a bio-identical T3/T4 hormone, I recommend that you find a compound pharmacy to specifically make it for you and eliminate the gluten filler because research has shown a correlation between gluten intolerance and Hashimoto s</li>

<li>Vitamin and Mineral Deficiency</li>

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Testing

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