Tests for CFS and ME



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Introduction - Types of Tests

Hair Mineral Analysis Test

Live Blood Microscopy and Dried Layer Blood Test
     Live Blood Microscopy
     Dried Layer Test
     Increased Inflammation
     Digestive Function and Nutritional Reserve
     Immune Function and Reserve

Laboratory Tests - Saliva, Blood, Urine and Stool
     Amino Acid and Organic Acid Tests
     Mitochondrial Function Tests
     Hormone and Neurotransmitter Tests
     Liver Function Tests
     Toxicity Tests
     Oxidative Stress and Damage Tests
     DNA and RNA Related Tests
     Virus Tests
     Dysbiosis Tests
     Intracellular Bacteria and Protozoa Blood Tests (Lyme)
     General Pathology Tests for Essential Fatty Acids, Vitamins and Co-Factors
     Immunology Testing
     Chemical Sensitivity Tests
     Food Allergy & Intolerance Tests

Laboratory Testing Considerations

Laboratory Links
     UK Laboratories
     Mainland Europe Laboratories
     US Laboratories
     Australian Laboratories

Neurophysiological Tests
     Autonomic Profiling and Quantitative Inotropic Fatigability Test (QIFT)
     Transcutaneous Gases Test
     2,3-BiPhosphoGlycerate (2,3-BPG) and BPG Mutase Test
     Vascular Endothelial Growth Factor (VEGF) Test

Basal Body Temperature Measurement

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Introduction - Types of Tests:

Please see below for a number of tests that can be performed to get an accurate picture of the root causes of CFS and other related illnesses. This is not a comprehensive list but a reasonable cross section of pertinent tests from reputable laboratories. It is highly unlikely in most cases that one single test will be enough to identify all root causes initially. In some cases a few exploratory tests are required to point one in the right direction for what additional tests are required, so the identification phase may require a series of short steps. Equally it is not necessary to perform all of the below tests, and there is clearly some overlap between some of the tests. In some instances, equivalent tests from more than one laboratory are listed, for comparison purposes. Ultimately it is up to your consultant to recommend what tests should be performed. If your current consultant is not aware of some of these tests, it may be prudent to discuss them with him. Familiarising yourself with the scope of the available tests and the associated explanations will help you to become familiar with what diagnostic tools are available and indeed shed some light on the possible mechanics of your condition. If your consultant is unwilling to request any of these types of tests, then it may be as well to find another or to contact any of the laboratories for a recommendation of a consultant in your area that uses that particular laboratory.

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Hair Mineral Analysis Test:

Hair mineral analysis tests are inexpensive and will show any mineral/vitamin deficiencies you have, and also any levels of toxic metals etc. I would recommend a healthy person to do this every 5 years anyway, let alone someone with CFS, who I think should do it every 3-6 months, to monitor progress. You can get it done at a health food shop, or send off a sample of hair with your credit card number to a lab. So you do not even need to leave the house to do this! A hair mineral analysis is a rather crude test, and only gives information about certain kinds of vitamin deficiency (not B-Vitamins as such), and will tell you very little about hormonal function, protein digestion, and amino acid balance. However, it is a great starting point, and really quite fascinating to view the charts. This test should really be done straight away, and not 6 or 9 months into treatment when your doctor is in the mood.

The picture above is just for illustrative purposes. Hairs are not examined under a microscope but a hair sample is placed into a solvent and metal elements are extracted with a solvent and various processing, the solvent is then removed, and the elements are analysed using inductively coupled plasma mass spectroscopy (ICP-MS).

I recommend the Hair Elements test (for 16 Toxic Metals and 23 Essential Nutrients) by Doctor's Data in the USA (even for people based in Europe) which seems to provide the widest cross section of elements and the most accurate laboratory equipment. Doctor's Data Hair Elements report includes the following potentially toxic elements: Aluminium, Antimony, Arsenic, Beryllium, Bismuth, Cadmium, Lead, Mercury, Platinum, Thallium, Thorium, Uranium, Nickel, Silver, Tin and Titanium. Doctor's Data Hair Elements report includes the following essential and other elements: Calcium, Magnesium, Sodium, Potassium, Copper, Zinc, Manganese, Chromium, Vanadium, Molybdenum, Boron, Iodine, Lithium, Phosphorus, Selenium, Strontium, Sulfur, Barium, Cobalt, Iron, Germanium, Rubidium and Zirconium. Doctor's Data also provides a Hair Toxic Element Exposure Profile testing for 31 toxic metals only. In general, the Hair Elements profile is probably the most useful. A sample report can be viewed at the link below.

http://www.doctorsdata.com/repository.asp?id=1270

The hair mineral analysis test shows those levels of nutrient and toxic metals that are present in the hair folicles and tissues around the hair folicles (and mobile) at the time the hair is formed. Please note that hair does not grow immediately at the surface of the skin but is formed a short distance below the surface of the skin. In addition, one has to wait until one has sufficient length of hair to actually cut/shave off (e.g. a minimum of 3-4mm), and so the hair mineral analysis provides a historical picture or snap shot (a couple of months old) as opposed to a current snap shot or view.

The hair mineral analysis will only reveal levels of nutritional minerals and toxic metals that were present in the hair folicles and surrounding tissues. It will not give you an indication of heavy metal build up elsewhere in the body, for example in the fat tissues or alimentary canal. It may therefore not be representative of your cumulative toxic metal build up in the body. It will also not tell you anything about your cell membrane health and the amount of toxins that are physically on your cell membranes. It will say nothing about toxins other than heavy metals, for example, organic chemical toxins.

The hair mineral analysis test does not also reveal the source of toxic metals, and in some instances it may come from a coating around the hair (e.g. from the air, shampoo etc) rather than inside the hair (i.e. from the tissues of the body). However, relative proportions of different toxic and nutrient metals is usually a good guide in determining if the toxic metal results indeed derive from the tissues of the body.

Despite its limitations, a hair mineral analysis test is still a very useful tool. Different types of hair analyses are routinely used in police forensics and also archeology to determine DNA, age, sex, diet and many other characteristics. Please see the Nutritional Deficiencies page for information on a parallel procedure for identifying magnesium cellular levels/requirements.

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Live Blood Microscopy and Dried Layer Blood Test:

 
Live Blood Microscopy (LdBM):

Live Blood Microscopy (a.k.a. live blood screening, unchanged live blood test, dark field microscopy or phase contrast) is a procedure where a few drops of blood are collected from one's finger and put onto a slide base plate and covered with a transparent cover plate. The slide is viewed under a microscope under 1000 times magnification, with the view projected onto a TV screen or monitor.

This is an excellent way of getting an overview of what is happening in the body on many levels (not all). Individual red blood cells can be viewed, and their general healthiness, shape, stickiness etc, indicating fatty acid deficiencies/imbalances, levels of dehydration/inflammation and so on. The level of activity of white blood cells can also be viewed here (in their role of gulping up harmful micro-organisms - sluggish white blood cells suggests a low immune system efficiency). Also, foreign organisms such as bacteria, yeast spores, parasites and parasite eggs can be seen at this level of magnification. This gives a qualitative indication of the level of infestation, rather than an accurate quantitative result. Please see the section on Harmful Micro-Organisms on the Digestive Disorders page for pictures and detail.

For example, the slide below on the left shows clumping of red blood cells. They work less efficiently in oxygen transport than healthy red blood cells would. This is perhaps reflective of a fatty acid imbalance (of course there are many factors to consider and it depends on the individual case), inflammation, oxidative damage and/or dehydration.

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Dried Layer (Blood) Test (DLT):

Dried Layer Test (a.k.a. Clotting Profile or Dry Layer Oxidative Stress Test (OST)) is a way of analysing the properties of clotting blood at a much lower level of magnification, and what happens what the blood on the slide dries out. This can provide different types of information to the Live Blood Microscopy described above. The Dry Layer Test can be performed in a number of different ways, but usually by the analysis of eight magnified dried layers of a drop of capillary blood that has set on your finger for half a minute. The layers of blood are allowed to dry out, and the layers of blood go through a natural centrifugal spinning action as the blood coagulates. The blood is then examined at a low magnification under a microscope, the results being displayed on a TV screen or monitor. A picture of a DLT slide is shown below.

Quoted from Biomdx web site:

www.oralchelation.com/LifeGlowBasic/technical/p59.htm

'Blood is an interesting indicator of health and where free radicals are concerned, their activity impacts blood morphology. Putting it very simply, when free radicals attack cells, damage is done. The stuff that lies between cells and holds them together is the interstitium, or extra cellular matrix. Through free radical attack, cells get damaged, enzyme activity is altered, and the extra cellular matrix around the cells becomes compromised. Water soluble fragments of this matrix get into the blood stream and then alters the blood clotting cascade. With that done, we find that blood does not coagulate perfectly. This is one mechanism for altering a "normal" blood pattern. Reading the dry layers of blood is like reading an ink blot. It can be very revealing as to the overall state of one's health. Blood from a healthy person will be uniform in coagulation, and tightly connected. From an individual with health problems and excess free radical activity, the dry layer blood profile will be disconnected, showing puddles of white (known as polymerized protein puddles). The more ill the patient with free radical/oxidative stress, the more disconnected is the dried layer of blood.

The blood of a healthy individual is inter-connected with black connecting lines. The black interconnecting lines is a fibrin network. This is fibrinogen, one of the protein constituents of the blood. The red in-between the black lines are the red blood cells. The image to the right is of an individual who has cancer. The blood fails to coagulate completely and has many white areas. These are the polymerized protein puddles and they reflect oxidative stress. They represent the degradation of the body's extra cellular matrix from free radical activity. Since free radical activity has been implicated in nearly all disease processes, this test can be used as a quick reference to gauge the severity and extent of one's health problems.'

The location, size and shape of the free-radical and toxin-caused white polymerized protein puddles (white patches on the blood slide) as seen on color TV or using a magnifying glass can indicate dozens of inflammatory problems and degenerative diseases. The clotting profile provides information about white blood cell activation/immune system health, detoxification overload, and general digestive system health. A dark thin border around a large central white patch usually indicates over-detoxification, for example. A wider, slighly darker area around the central white patch may indicate digestive impairment, for example.

These two tests are usually performed at the same sitting, and it would be unusual to do one without the other.

So all in all, microscopic blood analyses are a very good set of tests to have performed, and a prelude to further more sophisticated tests, should they be required. There are numerous consultants/doctors of naturopathic medicine who can perform this test for you. As you are treated, you will need to follow up and have repeated live blood microscopies/screenings performed to evaluate your progress. Of course, you are relying on your individual practitioner's skill, knowledge and attentiveness to spot patterns and individual micro-organisms in the blood, so interpretating a blood microscopy is very much practitioner dependent. A practitioner may be highly skilled, average, below average or awful!

Below is a list of observations and their potential significance, courtesy of Integrative Health Solutions. This is for illustrative purposes and you do not need to fully understand all of these unless you want to! This list may however be useful to refer back to once you are more familiar with the individual topics. It is of course the job of your consultant to perform the blood microscopy and also to interpret the results.

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Increased Inflammation:

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Digestive Function and Nutritional Reserve:

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Immune System Function and Reserve:

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Saliva, Blood, Urine and Stool Tests:

Depending on how you initially respond to treatment and the details of your case history, you may well require additional tests. Additional tests can include some of these listed below. Like or related tests have been grouped together where possible.

Laboratory Testing Considerations:

Clearly every type of test has its limitations and requires interpretation by a skilled medical practitioner:

Hair analysis provides information on the toxic elements and nutrients that are able to be absorbed from the hair folicle into the hair fibres themselves. Hair folicle nutrient and toxic element levels do not necessarily correlate to those found in other tissues and the blood stream and provide historical data (like the rings in tree bark) rather than a snap shot of the time of sample collection.

Urine tests provide indirect information about what was once in the blood, e.g. amino acids and wasted minerals and vitamins, (although the blood may contain amino acids and nutrients that do not appear (in the same concentrations or at all) in the urine). Urine is also tainted with other waste products. Urine amino acid levels are usually representative of the blood levels and reflect dietary uptake and metabolism, as well as excretion of these amino acids. However, a number of factors must be taken into consideration, as the urine levels may not necessarily correspond directly to the blood or tissue levels. For example, abnormal renal clearance, loss of urine during the collection period, decay or spoilage of the urine sample, and the presence of blood in the urine could cause the sample to be unrepresentative. However, the possibility of such problems can be judged from analytical measurements (metabolic markers for urine representativeness.)

Blood tests are better, and provide a snap shot of what nutrients or toxic elements are in the blood or the state of the blood cells. Blood tests do not necessarily provide information about the tissues or fat cells, where many toxins may accumulate.

It should be remembered that certain compounds do not cross the blood-brain barrier effectively (e.g. Choline), and so whilst they may be present in high concentrations in the rest of the body (e.g. as the neurotransmitter Acetyl-Choline), the levels of these compounds in the brain, and those made from these compounds, can be quite low. In addition, some compounds are only produced intracellularly and tend not to be circulated around the body, and any dietary intake may be directly absorbed and utilised, and so are hard to measure directly through blood or urine analysis (e.g. L-Carnitine). Also, hormone tests, whether performed through saliva, blood or urine, do not always reflect the cellular levels if the cells are absorbing the hormones as quickly as they are being produced.

A biopsy can provide a full picture of what is actually going on in the tissues themselves (e.g. a fat biopsy), although taking a biopsy is a rather drastic measure, and clearly only certain bodily parts or tissues are conducive to biopsy in live specimens!

In the case of toxicity, and neurotoxins in particular, one can gauge to a reasonable extent what is going on by looking at the blood (as described above). In addition, by following detoxification protocols such as taking additional phospholipids and FIR saunas, one can gauge oneself how much more is necessary and how many more toxins there are in the tissues and bones by simply continuing the regime and increasing the dosage/duration over time and observing the symptoms (if any). So one can indirectly 'measure' toxicity without having to use the scalpel. In any case, the information one might gain from a fat biopsy would only tell you to continue the detoxification protocol in any case.

Minerals levels are difficult to measure in a meaningful manner. Each sample for each specific mineral ideally needs to be a different source, e.g. red blood cell magnesium levels; or white blood cell zinc levels. Most mineral tests test for a variety of mineral sources from one place, which does not tell you anything necessarily about the mineral levels in the critical places where those minerals are most heavily utilised. In addition, one's mineral levels according to a particular type of test may be considered to be 'normal' for the population as a whole, but you could still have abnormal organic and amino metabolite results even though your levels were ÒnormalÓ. This is why in many cases, deducing what mineral and vitamin levels are inadequate or deficient based on the metabolic by-products that collect in the urine (e.g. amino acids or organic acids) may be a useful diagnostic tool. Measurement of these by-products in the blood and saliva is also possible. For example, I had had a hair mineral analysis test performed, and it showed that Magnesium levels were virtually normal (in the hair). But an amino acid profile showed that Asparagine was very low indicating that Magnesium was deficient in the tissues.

For this reason, muscle testing, or Applied Kinesiological Testing, may be used in conjunction with laboratory tests, to partially offset the inherent problems and weakness of each specific test, and also to further clarify the picture or corroborate the results.

Your consultant should advise what is necessary. It is entirely up to their discretion as to the general order of tests, and some may recommend some of the above tests ahead/instead of a hair mineral analysis or live blood microscopy. The above list is be no means comprehensive and one should refer to the respective laboratory's web site for a full list of tests offered. Some tests will be highly relevant in your case and others much less so.

Some of the CFS information or support group web sites on the links page may also list some tests. Some of these are listed below.

The NHS web site provides a list of forms of allergy testing.

http://www.nhs.uk/Livewell/Allergies/Pages/Whichallergytest.aspx

Which? magazine in the UK has claimed that the IgG (antibody) blood analyses conducted by YorkTest Laboratories and Cambridge Nutritional Sciences produced significantly different results for the same blood sample, and as such claims that food allergy testing is often an unproven science.

The Environmental Illness Resource's web site shown below also contains a brief summary of many of the above tests.

www.ei-resource.org/labtests.asp Dr Sarah Myhill, who has been working with CFS patients since the 1980s, has a list of tests that she uses with her patients on her web site - including BioLab, The Doctor's Laboratory, Genova Diagnostics, Acumen and many others.

www.drmyhill.co.uk/tests.cfm

BeatCFSandFMS.org's web site features a series of tests that 'George' had performed between 1998 and 1999. Some of the nested links no longer work and some of the tests and laboratories have changed, but the pages are interesting for illustrative purposes.

www.beatcfsandfms.org/html/GeorgesTests.html

www.beatcfsandfms.org/html/GeorgesTests_M_.html

Further tests will be added to this Identification page over time. Thank you for your patience.

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Laboratory Links:

Web sites to the above laboratories can be found on below. Do not feel that you have to stick to local laboratories, as it is quite common to submit samples from UK or mainland Europe patients to US laboratories, for example. Many large laboratories have agents in each respective country that handle and forward the samples onto the main lab, or are licensed and approved to carry out the testing locally. The above list is by no means comprehensive, but contains some of the tests that my associates and I have found useful. Please visit each laboratory's web site for a complete list of tests offered and for high level technical information. In particular, I highly rate Genova Diagnostics, Doctor's Data, The Doctor's Laboratory (TDL) and Acumen. Please familiarise yourself with the laboratory's test pages and the scope of each relevant test. This will give you a good feel for what can be done and what potential paths you may go down in the course of your treatment.  

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Neurophysiological Tests:

The following mainly Neurophysiological tests of Autonomic Function are conducted by Dr Peter Julu of Breakspear Medical Group, based at Breakspear Hospital in Hemel Hempstead in the UK. These tests are part of his own research work into CFS, ME and Fibromyalgia and the neurological system. They are however quite expensive and may provide perhaps more benefit for research than the patient's immediate practical benefit, given their descriptive nature, at the patient's expense. Related topics about cardiac and oxygenation functions can be found on the Cardiac page.

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Autonomic Profiling and Quantitative Inotropic Fatigability Test (QIFT) [Breakspear Medical Group]

The Quantitative Inotropic Fatigability Test (QIFT) is a test to measure a set of cardiovascular reflexes controlled in the brainstem, and both parasympathetic (rest and digest) function and sympathic (fight or flight) function, with a view to identifying any possible dysautonomia, Any abnormalities, such as Abnormal Spontaneous Brainstem Activation, issues with maintenance of blood pressure (baroreflex function), cardiac arrhythmia and/or thermoregulation problems can be detected, which may be a contributary factor for some of the fatigue, cardiac and oxygenation problems in those with CFS, ME or Fibromyalgia.

The QIFT test is useful in that it provides physiological and neurological evidence of the problems in inotropic function, fatigability and baroreflex failure, as opposed to examining biochemical tests or evidence or even psychological explanations or factors. The QIFT test is described below, and also on Breakspear Medical Group's web site here.

The tests of the QIFT are designed to stimulate the receptors of the autonomic system either directly or indirectly, to produce a set of unconscious cardiovascular reflexes that can be measured. The tests of the QIFT include a set of standardised exercises or manoeuvres optimised to stimulate the receptors or direct manipulation of the receptors themselves, in order to examine the autonomic nervous system. Standardisation allows comparison with the normal level/quality of cardiovascular reflex expected. These receptors are also known as target-organs and are located in 4 main areas: the brainstem, the large blood vessels including the heart, deep inside the body and in the skin (superficial).

The patient should only sip water during the test. It is advisable to be hydrated prior to the commencement of the test, but not excessively so, because it is not really possible to visit the toilet for the first 90 minue or 2 hour phase of the test as one is hooked up to various pieces of equipment. Being strongly in need of the toilet during the test may also affect the results as it involves increased muscular effort, even during rest.

The patient should desist from the consumption of caffeine prior to the commencement of the test, as it will increase the patient's heart beat. The polyphenols in black and green tea are also inotropic substances, that strengthen the heart's action (during exercise), and so may affect the test results also (which may show up as a higher than normal inotropic response during the isometric exercise). The consumption of green or black tea, or supplements containing these extracts, prior to the assessment or even within a day or so or the assessment. In general, however, one should note that inotropic response tends to be lower in those with CFS.

The QIFT test lasts approximately 2.5 hours and is held in a laboratory at 24C. The test is performed in two halves, which are described below.

Transcutaneous Gases Test [BreakSpear Medical Group]

The balance between carbon dioxide and oxygen in the soft tissues of the body is critical to normal cellular functioning. Too much CO2 in the blood and cells may result in acidosis (contributing to fatigue) and too little CO2 in alkalosis (stimulating abnormal responses from the brainstem). Low levels of oxygen in the tissues can result in hypoxia and all round fatigue. Low oxygenation levels may stem from incorrect breathing techniques but more frequently the problem lies in oxygen transport and perfusion.

Pulse Oximeters are routinely used in hospitals to measure a patient's haemoglobin oxygen saturation levels in the Red Blood Cells. These are small and inexpensive devices that use Infrared light and are placed over the finger. However, they tell us nothing about how much oxygen is actually getting out of the blood and into the tissues where it is needed, i.e. the oxygen perfusion, nor does it tell us anything about the amount of haemoglobin in the blood, nor relative levels of carbon dioxide. In CFS patients it is not infrequently noted that blood oxygen levels are high but tissue oxygen levels are low.

http://en.wikipedia.org/wiki/Pulse_oximeter

It is difficult to measure the oxygen and carbon dioxide levels inside the tissues themselves, however it is much easier to measure the amount of O2 and CO2 that moves through the tissues and out through the skin. This can be measured using sensors placed on the various parts of the skin on the body. These readings are directly proportional to the partial pressures of oxygen and carbon dioxide found in the peripheral tissues, also known as the Nutritive Circulation. This is the essence of the Transcutaneous Gases test.

Each sensor has two membranes, one sensitive to CO2 only and the other membrane sensitive to O2 only. A small plastic cup is applied to the skin next to the liver, where the skin is generally warm. The cup is filled with a special fluid that readily dissolves both oxygen and carbon dioxide. The sensor with the two membranes is then screwed firmly into the cup. Oxygen and carbon dioxide escape from the skin and dissolve into the fluid. The dissolved gases are then detected by the sensor. CO2 is detected by the change in the pH (hydrogen ion concentration). O2 is detected by its magnetic property which increases with its concentration. Both O2 and CO2 concentrations can be measured simultaneously in real-time and in a healthy individual these concentrations mirror the concentration in the capillary blood. This concentration is similar to mixed arterial and venous blood.

The Transcutaneous Gases test can be conducted in isolation, with the patient lying on his back, resting and with the patient taking deep breaths. However the test is usually conducted in conjunction with the (first half of the) QIFT test, described above, being run simultaneously, i.e. the O2 and CO2 values being recorded during all of the exercises and body positions of the QIFT test, the results being viewed/displayed/recorded in parallel to the cardiac readings, to provide a much clearer overall picture of what is going on in the body.

O2 levels are intended to be greater when one is sitting up or standing up, as opposed to reclining in the supine position - to reflect levels of cellular activity, energy expenditure, relative alertness and also the blood pressure requirements of the respective postures. An excessive drop in what is effectively tissue O2 levels, particularly evident in dysautonomia cases, when lying down, is evidence of poor oxygen diffusion and perhaps also poor BP and HR regulation.

During exercise, O2 levels are also meant to immediately increase. In some patients, the O2 levels are slow to increase, but do eventually reach the levels required. This may be experienced in the initial phase of the exercise being particularly hard but getting easier once the body's O2 levels have caught up with requirements/expenditure. However, there may be other issues present, including mitochondrial inefficiency, meaning that after the brief period of exercise, the patient ends up exhausted in any case.

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2,3-BiPhosphoGlycerate (2,3-BPG) and BPG Mutase Test [Breakspear Medical Group]

This is a quantitative blood test for 2,3-BiPhosphoGlycerate (2,3-BPG) and the BPG Mutase (BPGM) enzyme. These two compounds are examined briefly below.

2,3-BiPhosphoGlycerate (2,3-BPG or BPG for short), a.k.a. 2,3-DiPhosphoGlycerate (2,3-DPG), is the chemical compound that encourages the release of partially deoxygenated hemoglobin (deoxyhemoglobin), to ensure as much oxygen is released from the red blood cells (RBCs) as possible. 2,3-BPG shifts the equilibrium of haemoglobin to the deoxy-state. 2,3-BPG binds with high affinity to haemoglobin, displacing and releasing some of the remaining oxygen from the semi-deoxygenated RBCs, which then passes out of the capillaries and into the surrounding cells. 2,3-BPG selectively binds to the deoxyhemoglobin, making it harder for oxygen to bind with the hemoglobin and more likely to be released to the surrounding tissues.

2,3-BPG is generated from inside Red Blood Cells. Bisphosphoglycerate mutase (BPGM) is an enzyme responsible for the catalytic synthesis of 2,3-BPG from 1,3-BPG. BPGM has also both mutase and a phosphatase function which are less pronounced that its effect as a catalyst in 2-3-BPG synthesis. BPGM is unique to erythrocytes (Red Blood Cells or RBCs) and placental cells,i.e. those cells that contain haemoglobin. 1,3-BPG is an intermediate formed in Glycolysis (the metabolic process of converting glucose in pyruvate (examined on the Food Intolerance page with respect to Fructose metabolism and Fructose intolerance).

2,3-BPG levels are not altered dynamically as the blood circulates around the body (from the lungs to the tissues), but tend to be fairly constant in a given individual, depending on physiological adaptation. High levels of 2,3-DPG create a decreased affinity for O2 in the hemoglobin, and shift the Oxygen-Hemoglobin Dissociation Curve to the right so that a higher partial pressure of O2 is required to achieve the same level of O2 saturation in the Hemoglobin. However, higher 2,3-BPG levels also ensure that hemoglobin loses more of the O2 that it is carrying at the capillaries (i.e. when hemoglobin is in the deoxy-state). Conversely, lower 2,3-BPG levels result in an increased affinity for O2 in the hemoglobin, i.e. a leftward shift in the Oxygen-Hemoglobin Dissociation Curve, and lower partial pressure of O2 required to achieve the same level of O2 saturation in the Hemoglobin, but that there is less tissue perfusion and delivery of O2 to the tissues as less of the RBC's Oxygen i delivered in the capillaries (i.e. more is retained).

Low 2,3-BPG levels are usually observed in patients with Septic Shock and Hypophosphatemia, the latter which can be caused by respiratory alkalosis (in the RBCs). However, Dr Peter Julu theorises that low 2,3-BPG levels in some CFS patients may also result in similar patterns of low oxygen perfusion into the tissues, and may mean that the enzyme BPG mutase may not be functioning inefficiently (i.e. not producing enough 2,3-BPG) or there is not enough 1,3-BPG available (from Glycolysis), despite sufficient oxygen levels in the red blood cells. This can set the body up for an oxygen-deficient state (i.e. anoxia). Some parallels could be drawn between Hypophosphatemia and CFS in that in both conditions, a lack of ATP (a source of phosphate) could be a contributary factor.

Elevated 2,3-BPG levels may indicate that tissue anoxia has been present for a significant period of time and that the body is trying to compensate (with higher levels of BPG mutase). This would presumably signify an improvement in oxygen diffusion but a decrease in overall oxygen saturation (higher partial pressures of O2 being required).

Please see the Cardiac and Oxygenation Insufficiency page for more information.

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Vascular Endothelial Growth Factor (VEGF) Test [Breakspear Medical Group]

Besides low 2,3-BPG levels above, another possible reason for low tissue oxygenation levels could be the clogging up of the basement membrane on the outside of the capillaries with immunoglobulins, from excessive allergic responses. One of the body's responses to this anoxic (oxygen deficient) tissue environment and poor circulation and/or oxygen transport capability is for capillaries to 'bud' to produce additional capillaries to try to increase the local circulation of blood around the tissues, in order to encourage more oxygen to be released into the tissues (in combination with attempts to boost 2,3-BPG levels, which is often not possible). This 'capillary budding' involves a compound known as Vascular Endothelial Growth Factor (VEGF). VEGF is a chemical signal produced by cells to instigate the growth of new capillaries around them.

http://en.wikipedia.org/wiki/Vascular_endothelial_growth_factor

'Vascular endothelial growth factor (VEGF) a sub-family of growth factors, more specifically of platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis (the de novo formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature).'

The VEGF blood test is used to measure the VEGF levels to determine whether capillary 'budding' is taking place, which would be one indicator of an anoxic or low oxygen environment.

Please see the Cardiac and Oxygenation Insufficiency page for more information.

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Basal Body Temperature Measurement:

Basal (waking) body temperature can provide a good indication of endocrine system health, and can be one of many way of identifying issues and measuring one's progress during treatment. The sensor of an electronic thermometer can be placed deep in the arm pit upon the moment of waking in the morning and held there (bring your upper arm onto your side to hold it in there and to keep maximum contact area) until a final peak temperature is reached, which can take up to 5 minutes (alternatively you can insert a regular thermometer into your rectum if you prefer!) Take readings every day for a couple of weeks. Use a chart (a graph) where temperature is on the vertical axis (e.g. 94.0F - 99.0F or 34.5C to 37.2C). Each 'square' or unit on the vertical axis should correspond to a tenth of a degree. This axis does not have to reach zero ;-) unless you have want to be frozen for medical research! The horizontal axis is the date, each square represents a day. Notice any changes in your dietary or supplement/treatment regime and the effect they have on your basal body temperature. The optimal basal temperature can be in the range 97.6F to 98.2F or 36.5C to 36.8C.

A consistently low basal body temperature is usually indicative of hypothyroidism (low thyroid function). An unstable basal body temperature is usually indicative of adrenal dysfunction and low adrenal gland activity. Unstable and low temperatures usually indicates both low adrenal and thyroid activity. Please note that measuring basal body temperature is different from measuring daytime body temperature, which is usually higher (as the metabolic rate increases slightly when we are awake), with its optimal range in a healthy person at around 98.6F to 98.8F or 37.0C to 37.1C. See the Hormonal Dysfunction page for more information.


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