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Digestive Function and Nutritional Reserve:

• Complex aggregates of cellular and foreign detritus may indicate an increase in intestinal permeability, i.e. Leaky Gut Syndrome (LGS).


• Increased level of bacteria observed in the blood serum (i.e. blood plasma - yellow liquid - with clotting factors removed) - perhaps suggests increased intestinal permeability (LGS).


• Central darkening of fibrin may indicate inadequate digestive capability, e.g. low stomach acid production, diminished pancreatic enzyme production, bacterial overgrowth of small intestine and/or dysbiosis.


• Diffuse deterioration of the fibrin net integrity in the first two drops of blood may indicate protein malnutrition or absorption, or a functional deficiency of oestrogen, testosterone or the growth hormone DHEA.


• Large red blood cells (Macrocytes) suggest possible Vitamin B12 or Folic Acid deficiency.


• An increase in nuclear segmentation of neutrophils (white blood cells) suggests a functional deficiency of folic acid.


• Small red blood cells (Microcytes) suggests a possible Iron deficiency.


• Scallop-shaped red blood cells suggests membrane changes and possible deficiencies of Omega-3 or Omega 6 Essential Fatty Acids (EFAs) or Carnitine.


• Early crenation or shrivelling of red blood cells may indicate the need for increased levels of antioxidants and glutathione.


• Peripheral dispersed outer edge of blood clot may indicate an increased functional need for additional Vitamin C and other anti-oxidants.


• Striae radiating form the centre of the clot may indicate inadequate functional levels of Magnesium, Calcium or other essential minerals, and a metabolic acidosis of the matrix space and biological terrain.


• Peripheral black ring present in the blood clots may suggest and increased risk of heavy metal toxicity and/or an overwhelmed detoxification capacity.


• The separation of denatured red blood cells away from the blood clot, forming a kind of 'chemical sensitivity halo' may indicate environmental or chemical hypersensitivity (e.g. Multiple Chemical Sensitivity (MCS).


• The localised breakdown of fibrin in a circular-linear pattern may indicate a functional thyroid imbalance.


• Pinpoints of soluble fibrin deposits, seen centrally, may suggest increased adrenal stress and a decreased adrenal adaptation to stress.

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Immune System Function and Reserve:

• White blood cell count either markedly increased or reduced - would recommend a full blood count test to investigate further.


• Neutrophil (type of white blood cell) motility (spontaneous motion) reduced may suggest a sluggish immune responsiveness and possible deficiency of either the amino acid Taurine and/or Vitamin A.


• Lymphocyte (type of white blood cell) activation observed - may indicate chronic viral infection and ongoing antiviral immune system activation.


• Increased levels of bacteria observed in blood serum - occult infections should be excluded, e.g. Leaky Gut Syndrome (LGS), Dysbiosis, Dental Infections, Cystitis, Prostatitis and/or Upper Respiratory Tract Infection.


• Parasitic protozoa seen in the blood serum suggest an ongoing infection.


• Black 'bulges' in the blood clot sample may suggest an increased probability of parasitic infection.


• Fungal spores observed in the blood serum may suggest an ongoing infection of Candida and/or other yeast species.


• Fungal hyphae seen in the blood serum indicate a more aggressive form of Candida albicans overgrowth. A hypha (plural hyphae) is a long, branching filamentous cell of a fungus, and also of unrelated Actinobacteria.[1] In fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium.


• Multiple soluble fibrin deposits observed peripherally may suggest an ongoing immune system activation.


• Liver spicules observedin the blood plasma may indicate an increased detoxification burden (overloaded liver) or impaired liver function. Spicules are skeletal structures that occur in most sponges. They provide structural support and deter predators.


• Spirochetes (spiralling bacteria) may indicate dental, gum and/or periodontal infection (supporting structures of teeth) - a visit to the dentist is recommended!

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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.

 
Amino Acid and Organic Acid Tests:



• Bloodspot Amino Acid Assay [Metametrix]
  
  The Bloodspot Amino Acid Assay is available for 11 or 20 amino acids, and is a blood test using a blood spot sample taken from the finger. The 11 test includes: Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Taurine, Threonine, Tryptophan and Valine. A 30 day amino acid powder supplementation recommendation is also provided with the test results, containing relative proportions and amounts of a variety of amino acids, amino precursors and B-vitamins. Click here for more information about the blood spot, blood plasma and urine tests for amino acid analysis.



• Amino Acid Analysis Profile [Genova Diagnostics]
  
  This is a urine test examining amino acid conversion capability (including Homocysteine levels and implied methylation capability - subject to reagent availability - check with Genova Diagnostics) - to determine the essential amino acid levels critical for synthesis of enzymes, homrones, neurotransmitters, stomach acid, muscle, bone etc.; maldigestion and malabsorption of proteins; the nitrogen balance in the body; kidney function; adequate detoxification of excess nitrogen; function deficiencies of essential minerals, vitamins and co-factors (e.g. B-Vitamins such as B12, Folic Acid, P5P, and reserve of Antioxidants such as A, C and E) and mineral deficiencies (e.g. Magnesium).
  
  An information sheet on this test can be viewed by clicking here. A sample report can be viewed by clicking here. Interpretation guidelines can be viewed by clicking here.
  
  This test is also available in combination with the Metabolic Analysis Profile below in a test called Optimal Nutrition Evaluation. A complete analyte list can be seen from this page. Click here to read a sample report.
  
  Quoting from the ONE test report:
  
  'Analytes characteristic of cellular energy and mitochondrial function:
  These markers are metabolites from four important biochemical pathways in the body, all of which significantly impact the production and availability of energy at the cellular levl: glycoloysis, the citric acid acid (Krebs cycle) and both beta-oxidation and omega-oxidation of fatty acids. These analytes provide unique insight into macronutrient catabolism, and mitochondrial function in cells. Abnormal levels may be associated with fatigue, malaise, myalgia, headache, muscle weakness, myopathy, hypotonia, or acid-based imbalance. This test is intended to be a diagnostic aid for acquired disorders in these pathways. It is not intended for diagnosis of inborn errors of organic acid metabolism, as this would require extensive molecular genetics testing. However significantly abnormal findings could be consistent with such inborn errors. If significant abnormalities persist after removal of toxics, supplementation of appropriate nutrients, dietary and hormonal adjustments, and correction of intestinal dysbiosis or infection, it is suggested that the patient be referred to a medical center with capabilities for diagnosis and treatment of congenital metabolic defects.
  
  Cofactor-Dependent and Metabolites from amino acid catabolism:
  These analytes are formed from essential and protein amino acids via amino group transfer or by other enzymatic transformations. Many are sensitive to vitamin functions as coenyzmes and to minerals as enzyme activators. Excesses or deficiencies may lead to various conditions depending upon the particular metabolic imbalance, including fatigue, headaches, myalgias, metabolic acidoses, dietary intolerances, neurological problems and cognitive disorders.'



• Metabolic Analysis Profile [Genova Diagnostics]
  
  Also known as an Organic Acids Profile. This is a urine test examining the organic acids involved in the Krebs Cycle , i.e. energy production (mitochondrial dysfunction) and hormonal production. It can measure whether nutrients are being catabolised to energy efficiently; if mitochondrial energy production is impaired or not; whether there is excessive oxidative stress in the body; if functional deficiencies of vitamins and minerals are present (as above); whether intestinal malabsorption is present; if there is an excess of bacterial or yeast growth in the gut (by their byproducts); if detoxification capacity is impaired; and whether critical neurotransmitters are being in sufficient quantities for the brain, gut and one's adrenal function.
  
  An information sheet on this test can be viewed by clicking here. A sample report can be viewed by clicking here. Interpretation guidelines can be viewed by clicking here.
  
  As mentioned above, the Metabolic Analysis Profile is also available in combination with the Amino Acid Analysis Profile in a test called Optimal Nutrition Evaluation (ONE).
 


Mitochondrial Function Tests:



• Metabolic Analysis Profile [Genova Diagnostics]
  
  See Amino Acid section above for description.
  
  Please note that this type of test does not actually provide any information about the state of the mitochondrial membranes, if any unwanted compounds or partial detoxification products or viruses are clogging them up, or provide any quantitative measurement of mitochondrial efficiency, which the two mitochondrial tests described below do.



• Mitochondrial Membrane - Translocator Protein (TL) Study [Acumen]
  
  This is a largely qualitative white cell blood test examining energy production capacity (mitochondrial dysfunction), to establish the numbers of mitochondria, clumping, membrane structure, binding, pH and Calcium levels at the outer membrane, essential elements associated with mitochondrial function (K, Mg, Zn) and the presence of unwanted substances that can interfere with mitochondrial function (e.g. heavy metals, PCBs, toxic organic compounds and partial detoxification products like glutathione conjugates and peptide complexes (e.g. the body's detoxification molecule bondeds with a toxic organic chemical compound or a drug like antiobiotics) - these latter substances contribute to a condition known as Neurotoxic Membrane Syndrome. Although a membrane test, it is really concerned with toxin accumulation and measurement.
  
  Blood samples should ideally be analysed within 4 hours of collection, as the test is concerned with live blood cells. However, many doctors deem that the test result is ok as long as it is performed within a maximum of 72 hours after collection. This test includes Phase-contrast and dark field microscopy, and explores the mitochondrial membrane and the TL site using a series of specific and group-specific fluorescence probes.
  
  Parameters examined include: essential elements associated with mt-membranes (K, Mg, Zn), pH at the outer mitochondrial membrane, Ca2+ at the outer mitochondrial membrane, mitochondrial membrane binding of proteins, lipids, esterases and other substances bound. Other substances bound include detection of:
  
  
  • Glutathione conjugates
  
  
  • Organic Sulphate conjugates
  
  
  • Peptide complexes
  
  
  • Lactic acid & keto-acids
  
  
  • malondialdehyde - a naturally occurring lipid peroxidation product - whose levels may be elevated in those individuals with significant (endogenous) free radical damage of the mitochondrial (mainly phospholipid-based) membranes.
  
  
  • Chlorinated pesticides
  
  
  • Pentachlorphenol (PCP)
  
  
  • Polychlorinated Biphenyls (PCBs)
  
  
  • Polybrominated Biphenyls (PBBs)
  
  
  • Dichlorobenzene
  
  
  • Organophosphates (inc. OP pesticides)
  
  
  • Toxic metals
  
  
  • DNA/RNA (probably of viral origin)
  
  
  • Others
  
  
  Info: Translocator Protein (TL) scavenges ADP from the cytoplasm and returns ATP from re-conversion with 'new' ATP from oxidative phosphorylation. TL can be blocked by zenobiotics and/or partial detoxification products. The site is also extremely pH sensitive and can be affected by local or general acidosis, including the organic acid accumulation from over-dependence on anaerobic metabolism. the efficiency of TL can also be compromised by increased intracellular Calcium or reduced intracellular Magnesium.
  
  Any unidentified compounds (e.g. glutathione conjugates of a drug or chemical, or other) which are detected in the above test can be further isolated and identified with an additional procedure. This technique uses ATR (attenuated total reflection) Fourier Transform InfraRed spectral analysis using, for example, a Thermo Avatar Nicolet 330/370 Fourier Transform Infrared Spectrometer with horizontal ATR. An absorbance vs wavelength chart for each compound provides a unique spectroscopy graph (a signature) which can be used to correctly identify the compound on the mitochondrial membrane.
  
  Please note that mitochondrial function tests based on organic acid profiles (in the urine for example) provide no information on the state of the mitochondrial membranes and indeed if they are congested or not, and what with. One's organic 'Krebs' cycle acids may appear 'normal' but mitochondrial function may be significantly impaired (e.g. ADP to ATP recovery). Of course this TL Study does not provide any information on which parts of the Krebs cycle and associated cofactors are deficient or a bottleneck, unlike organic acid based mitochondrial profiles, which actually examine these parameters.



• Malondialdehyde [Laboratoire de Biologie Medicale]:
  
  This quantitative urine test by LdBM measures the level of urinary Malondialdehyde (MDA), a byproduct of lipid peroxidation by free radicals, in particular mitochondrial membranes. The presence of elevated MDA in the urine suggests evidence of excessive oxidative damage to mitochondrial membrane lipids and hence an oxidative stress problem. It is not a direct measurement of mitochondrial function, but a measurement of its impairment by oxidative stress.



• F2-Alpha Isoprostane [Laboratoire de Biologie Medicale]
  
  F2-Alpha Isoprostane (a.k.a. 8-iso-PGF2 alpha) is a marker for oxidative damage of the lipid component of cell membranes. It is a downstream oxidation product of membrane oxidation. Isoprostanes as prostaglandin-like compounds created from the free radical attack of esterified of the Omega 6 Essential Fatty Acid (EFA) known as Arachidonic Acid (ARA) inside the membrane phospholipid. It is of course a very different molecule to a prostaglandin which is a lipid compound produced enyzmatically by the body using cyclooxygenase (Cox1-2) from EFAs and which has nothing to do with free radical attack on cell membranes.
  
  Isoprostanes in general are valuable markers in clinical biology as they are found in all biological fluids and tissues and are stable in vivo and ex vivo. There are 10 times more isoprostanes in atherosclerotic plaque compared with normal vascular tissue. They are also only dependent on their production (in this case free radical attack) rather than metabolism or excretion without intraindividual variability. There are many studies validating Isoprostanes as the most accurate and reliable indicator of oxidative stress in vitro and in vivo.
  
  It is not a direct measurement of mitochondrial function, but a measurement of its impairment by oxidative stress.



• ATP Profile [Acumen]
  
  This is a quantitative blood test measuring energy production (mitochondrial dyfunction). Includes ATP (Adenosine Triphosphate) studies on neutrophils (ATP of whole cells - with excess Mg added; with endogenous Mg only (readings in nmol/million cells); and the ATP/ATP(Mg) ratio. The test also includes ADP to ATP conversion efficiency (whole cells) - including ATP(Mg) as before, ATP(Mg) - inhibitor present, and ATP(Mg) - inhibitor removed; and ADP to ATP efficiency. Finally it includes ADP-ATP Translocator (TL) (mitochondria, not whole cells) including TL 'out' and TL 'in' (in ATP pmol/million cells). A paper regarding this test, research study data (from January 2009) and a sample report can be found in the PDF document here. Please note that mitochondrial function tests based on organic acid profiles (in the urine for example) may not always provide an indication of how well or poorly mitochondrial function is actually performing, as this test can. One's organic 'Krebs' cycle acids may appear 'normal' but mitochondrial function may be significantly impaired (e.g. ADP to ATP recovery). Of course the ATP profile does not provide any information on which parts of the Krebs cycle and associated cofactors are deficient or a bottleneck, unlike organic acid based mitochondrial profiles, which actually examine these parameters.



• Superoxide Dismutase (SOD) Studies [Acumen]
  
  This is a quantitative test to estbaablish the levels of various forms of SOD, the body's most important antioxidant that is involved in cellular respiration, in the Red Blood Cells (RBCs). It examines the in-vitro efficiency of the patient's different forms of RBC SOD when the neutrophil superoxide (a powerful oxidising agent and byproduct of respiration) production is maximally stimulated. As discussed on the Nutritional Deficiencies page, general cell protection from damage by superoxide is provided by intracellular Zinc:Copper SOD (Zn/Cu-SOD). Mitochondria are protected by manganese-dependent SOD (Mn-SOD). Extracellular SOD (EC-SOD - another type of Zn/Cu SODase) protects the nitric oxide pathways that relax vascular smoother muscle tissue. For each form of SOD, genetic variations are known, and mutations and polymorphisms can occur during excessive oxidative stress placed on the DNA. DNA adducts can chemically block these genes however.



• Methylation Panel - Red Blood Cell (RBC) and Blood Plasma [Breakspear Medical Group]
  
  These are two separate blood tests, often performed together, to determine the levels of key amino acids in the blood plasma, levels of sulphate, B-vitamins associated with energy production, TMG, enzymes associated with energy production and antioxidant protection (respiration), levels of Folic acid and Thiamin derivatives and also remnants of ATP/ADP/AMP in the blood. These profiles are therefore concerned with methylation and to some extentmitochondrial function.
  
  The RBC test measures the levels of cellular enzymes including:
  
  
  • Glutamate oxaloacetate transaminase (GOT)
  • Glutathione peroxidase (GP)
  • Glutathione reductase (GR)
  • Superoxide dismutase (SOD)
  • Catalase

The Plasma test measures the following plasma levels of:

• Amino Acids - Serine, Taurine, Glycine, Methionine, Cystathionine, Cysteine.


• Sulphate - Total Sulphate (serum/plasma), Free Sulphate (Serum/Plasma).


• Folic Acid Derivatives - 5-Methyl-THF (5MTHF), 10-Formyl-THF (10-FTHF), 5-Formyl-THF (5-FTHF), THF.


• Active Vitamin B2 derivaties - FMN in plasma, FAD in plasma.


• Active Vitamin B3 - NADPH


• Homocysteine Factors - Total Homocysteine, Trimethyl glycine (TMG), Dimethyl glycine (DMG)

 


Hormone and Neurotransmitter Tests:



• NeuroEndocrine Expanded Profile [NeuroScience]
  
  This test uses a urine sample to assess the levels of a variety of Neurotransmitters, Amino Acids and Hormones, including Estradiol, Estrone, Progesterone, Testosterone, Dihydrotestosterone, DHEA, Cortisol x4, Epinephrine, Norepinephrine, Dopamine, DOPAC, Serotonin, 5-HIAA, Glycine, Taurine, GABA, Glutamate, PEA, Histamine, Creatinine. Test information can be found here.



• Analysis of Brain Chemistry (Comprehensive) [Neurolab]
  
  This is a quantitative urine test to establish the relative levels of the neurotransmitters, the levels of neurotransmitter metabolites, levels of neurotransmitter precursors, additional neuroactive substances and neurotoxins and false neurotransmitters. The neurotransmitters measured include Adrenaline (A), Noradrenaline (NA), Dopamine (DA), Serotonin (5-HT), Gamma-Amminobutyric Acid (GABA) and Acetylcholine. The neurotransmitter metabolites are the products of neurotransmitter utilisation, i.e. their deactivation. The patterns of the respective metabolites therefore provide us with information about the activities of these neurotransmitters. Neurotransmitter precursors are the compounds from which the body manufacturers the neurotransmitters, either directly or indirectly. Various neuroactive substances are also evaluated as they are involved in different aspects of nervous system functioning. Finally, the harmful effects of various substances, i.e. neurotoxins and substances which mimmick the effects of neurotransmitters, are taken into consideration as a possible explanation as to why certain neurotransmitters are outside their reference range.



• Adrenocortex Stress Profile [Genova Diagnostics]
  
  This is a saliva test to measure the levels of the DHEA growth hormone and Cortisol adrenal stress hormone. Further information about the test can be reviewed by clicking here. An Interpretation Guide can be viewed by clicking here. A sample report can be viewed by clicking here.



• Complete Male Hormones [Genova Diagnostics]
  
  This test uses a urine sample to analyze key adrenal and androgen steroid hormones, providing a broad overview of hormone balance. Click here for further information. Click here for a sample report. Click here for the Interpretation Guide (of the old test). A Complete Hormones test is also available for female hormones, amongst numerous other urinary hormone tests.



• Comprehensive Thyroid Assessment [Genova Diagnostics]
  
  This test analyzes blood serum levels of TSH, free T4, free T3, reverse T3, anti-TG antibodies, and anti-TPO antibodies to assess central and peripheral thyroid function, as well as thyroid auto-immunity. For further information, click here. For a sample report, click here.

 


Liver Function Tests:



• Hepatic Detox Profile [Doctor's Data]
  
  This urine test is designed to establish liver health and liver function, and how the liver is handling exposure to (toxic) chemicals.



• Functional Liver Detoxification Profile [ARL Pathology]
  
  The FLDP is a serum blood test that measures the enzymatic detoxification capability of the liver. Further information can be see here. A sample report can be seen by clicking here.



• Short-Chain Fatty Acids (SCFAs) in Blood Plasma [Acumen]
  
  This quantitative blood test is a measure of the Acetate, Propionate and Butyrate - Short-Chain Fatty Acids (SCFAs) - in blood plasma. SCFAs are produced in the colon by the bacterial fermentation of dietary fibre, which helps to keep down the stool pH to suppress dysbiotic and pathogenic microogranism overgrowth.
  
  However, greatly elevated levels of these SCFAs is an indicator of Fructose Malabsorption. Unabsorbed fructose osmotically reduces the absorption of water and is metabolised by the normal colonic bacteria to SCFAs and the gases Hydrogen, Carbon Dioxide and Methoane. These SCFAs and gases are absorbed into the bloodstream, and thus elevated SCFA levels can be observed in the blood plasma.
  
  The reverse pattern is observed in the case of Hereditary Fructose Intolerance (HFI) and other genetic liver enzyme deficiencies of the Fructose metabolic pathway. HFI is a genetic condition whereby a liver enzyme deficiency prevents normal fructose metabolism and gluconeogenesis occurring in the liver. Inhibition of gluconeogenesis results in lactic acidosis as the cells underogo anaerobic respiration in the absence of glucose (i.e. Hypoglycaemia). The liver may try to compensate by producing glucose from the SCFAs Acetate, Propionate and Butyrate that are produced by the bacterial fermentation of dietary fibre. Rapid depletion of SCFAs in blood plasma is associated with HFI and can be detected with this blood test.
  
  The SCFA blood sample is taken 3 hours after food was last consumed. The Fructose-6-Phosphate test is usually performed in parallel to see if excessive Fructose intake is implicated in any way.



• Uric Acid in Blood Plasma [Breakspear Medical Group]
  
  This is a quantitative blood test to measure the Uric acid levels in the blood plasma, as an indicator of Hereditary Fructose Intolerance (HFI). Please see the Food Allergy page for more information.



• Lymphocyte Proliferation Test for Fructose [Breakspear Medical Group]
  
  This is a qualitative blood test to measure the ratio of white blood cell (lymphocyte) growth on a low glucose medium compared to that on a low glucose/high fructose medium. Values below the reference for low glucose only reflect a metabolic intolerance to excess fructose. Please see the Food Allergy page for more information.

 

Toxicity Tests:



• Porphyrins [Laboratoire de Biologie Medicale]
  
  This is a quantitative urine test for the levels of the different Urinary Porphyrin. Porphyrins are intermediary compounds in the production of Heme, and the respective enzymes involved with converting one form of Porphyrin to another are particularly sensitive to the presence of heavy metals or certain organic chemical toxins. Presence of these foreign toxins can inhibit the enzymes involved in these intemediary steps, thereby resulting in elevated levels of these intermediary products in the urine; and consequently too little Heme being produced. As this pathway is particularly sensitive to toxicity, it is a particularly good indicator of toxicity. In other words, the Urinary Porphyrins can provide us with information about the extent of heavy metal toxicity in the body and the extent to which it is interfering with normal bodily biochemical processes. It thus differs from a urine test or blood test for heavy metal levels as it provides us with direct information about the problems the current heavy metal levels are causing in the body, which is arguably what is really important.
  
  The levels of the following Porphyrins are measured.
  
  
  • Uroporphyrins I & III (a.k.a. uP)
  
  
  • Heptacarboxyporphyrin (a.k.a. 7-Carboxyporphyrin, 7cxP or 7cP)
  
  
  • Hexacarboxyporphyrin (a.k.a. 6-Carboxyporphyrin, 6cxP or 6cP)
  
  
  • Pentacarboxyporphyrin (a.k.a. 5-Carboxyporphyrin, 5cxP or 5cP)
  
  
  • Precoproporphyrin (a.k.a. PrCP or pcP)
  
  
  • Coproporphyrins I & III (a.k.a. cP)

  The absolute levels and also the relative ratios of the different Porphyrins in the urine can provide us with information about what kind of heavy metal or other toxin is causing the problem in the Heme biosynthesis pathway, and thus assist in the determination of chelation strategy.
  
  The absolute levels of these porphyrins and also the relative ratios can provide us with information on the following toxins.
  
  
  • Aluminium (Al)
  
  
  • Arsenic (As)
  
  
  • Lead (Pb)
  
  
  • Mercury (Hg)
  
  
  • Xenobiotics, chiefly organic chemicals including Polychlorinated Biphenyl (PCB)

  Please see the Heavy Metal Toxicity section on the Effects of Toxicity page for more information about the role of Porphyrins and Heme, and test result interpretation.
  
  This Porphyrins test can be performed in isolation or in a combined test entitled 'Autism Panel' which also includes tests for urinary markers for cellular immuno-inflammation, DNA and RNA oxidative damage and lipid membrane oxidative damage.
  
  The Metametrix laboratory in the USA also offers a similar Porphyrins profile.



• Toxic Elements in Urine Scan [Biolab]
  
  This is a quantative urine test for establishing levels of toxic elements (toxic/unsafe at all levels) and some nutritional and trace elements that are toxic at high levels. This may be performed either by collecting a 'typical' set of urine samples over a 24 hour period (i.e. a measure of the metals that are present in the blood), or the method described below (provoked metals) which is better.



• The Provoked Urine Metals Test [Doctor's Data]
  
  This quantitative urine test is perhaps more reflective of the toxic metals that are present in the tissues. The test is also known as the Oral DMSA Challenge Test (pre & post). It works on the basis of comparing heavy metal urine levels, with and without a significant dose of a synthetic chelating agent (e.g. Thorne Research Captomer (DMSA)), to indirectly infer what the body's current heavy metal burden is. The chelating agent encourages the release of heavy metals from the tissues, fat cells and cell membranes, and measuring the levels of heavy metals in the urine, above the individual's 'normal' or 'expected' levels.
  
  On the day of the test, one fasts for the first few hours. One collects the first urine of the day (which is representative of the level of heavy metals without any 'provocation or chelation', and then one takes a 'standard' provocation dose of DMSA (or DMPS) for one's weight (essentially one's calculated daily dosage but consumed all in one go rather than split up during the day into smaller doses as one would normally do when doing a chelation programme).
  
  After taking the chelating agent, one collects one's urine for the next 6 hours, taking a sample of that 6 hour urine at the end (noting the total volume collected). This second sample is thus representative of the 'provoked' level of heavy metals excreted from the body in one's urine and their rate of excretion from the body's tissues given a fixed amount of DMSA input; and it is an indirect measurement of the amount of specific heavy metals in the body's tissues that are released into the blood by DMSA.
  
  The picture is quite complicated, because some tissue compartments release heavy metal toxins slower than others, even in the presence of a chelating agent, and some tissue compartments may be not accessible by certain types of chelating agent (i.e. DMSA cannot cross the blood-brain barrier to release heavy metals from the brain tissue, which is why it is used in conjunction with Lipoic Acid). The test is therefore measuring heavy metal release from the tissues in the body except for the brain.
  
  In addition, the provoked urine graph profile is dependent on the chelating abilities of the chelating agent with each heavy metal being measured in the urine. That is to say, DMSA is a better chelating of Mercury than say Lead, although it is still a good chelator of Lead. Thus if concentrations of these two heavy metals in the readily chelated and accessible tissue compartments are roughly the same, the actual concentrations observed in the urine (i.e. removed from the body by the chelating agent) may not be exactly equivalent. The test therefore requires a little interpretation. It is a useful guide, but one must take into account the properties of the exact provoking chelating agent in question.
  
  It should be noted that for those that have very high lymphocyte sensitivities to certain heavy metals, or have a huge amount in their system, a 'standard' dosage for their weight of the chelating agent may well be way too much, and may result in their becoming ill for a few days, in which case there is way more 'provocation' than is actually required. Anyone who has experience of chelation will know that the dosages can vary by 60x, according to how much chelation one has performed, and in some cases, by 1000x. There is not really such a thing as a universal comfortable standard dosage in chelation. The sensitivity to the dosage will depend on the individual of course. It is likely that one will feel slightly tired afterwards, as one is taking a full day's dosage in one go, and also going without food for a couple of hours too, so one's blood sugar levels may be low.
  
  Please see the Detoxification page for more information.
  
  A list of heavy metals tested for is detailed below.
  
  
  • Aluminium
  • Antimony
  • Arsenic
  • Beryllium
  • Bismuth
  • Cadmium
  • Lead
  • Mercury
  • Nickel
  • Platinum
  • Thallium
  • Thorium
  • Tin
  • Tungsten
  • Uranium

  Click here for a sample report.



• Screen for Pesticides and Related Substances in Fat Cells [Acumen]
  
  This quantitative test is a test for various forms of toxins, principally pesticides and other organic toxins, in the adipose tissue or fat cells, which store and hold the fat deposits in the fatty areas of the body. It is essentially a fat biopsy, but because such a small sample is required, it can be extracted with a syringe, usually in the buttock area and does not leave scarring. The following substances are tested for.
  
  
  • Organochlorine group - including Aldrin, Dieldrin, Toxaphenek DDT, DE, DDD and HCB.
  
  
  • Lindane - a.k.a. Gamma-HexaChloroCycloHexane (gamma-HCH), gammaxene or Gammalin (not included in above Organochlorine group) and other isomers of Benzene Hydrochloride (BHC).
  
  
  • Chlorinated Phenols group - penta- and tri-chlorophenols with other chlorophenols if present.
  
  
  • Chlorinated Benzenes - para-dichlorobenzene is the most commonly used.
  
  
  • PolyChlorinated Biphenyls (PCBs) - banned in 'open' use but still used in 'enclosed applications'.
  
  
  • Polybrominated Biphenyls (PBBs) - found in flame retardant plastics, textiles and foams.
  
  
  • Carbamates group, inc. Bendiocarb and Carbaryl.
  
  
  • Naphthols group - including Alpha-Naphthol (Carbaryl metabolite).
  
  
  • Organophosphate group
  
  
  • Organo-metal complex - usually methyl or ethyl complexes of heavy metals

  
  
• DNA Adducts (genomic DNA from Leucocytes) [Acumen]
  
  This qualitative test examines the DNA of White Blood Cells (WBCs, a.k.a. Leucocytes) and looks for the presence of organic toxin compounds attached to specific genes; and indeed their general concentration in the blood (from their representation in WBCs. It also measures the levels of DNA-associated Zinc, and whether this is within the normal reference ranges, or whether it has been displaced.
  
  The Genomic DNA from Leucoctyes is analysed using gas-liquid chromatography to detect for the group-presence of organic chemicals. It is also analysed using atomic emission to detect for the presence of toxic metals. Specific adducts are measured using a variety of techniques. Any abnormal proteins are selectively precipitated out, where possible, for further investigation by immuno-assay procedures and polarisation microscopy. If possible, the location of the adducted (added/attached) chemical on the DNA protein molecule, which may tell us whether it is associated with a specific gene or control factor.
  
  Al types of adducts are detected and identified. Some of the most 'commonly' occurring adducts that are found with this test (in a variety of patient profiles) are listed below.
  
  Organic Chemicals or Groups Adducts include:
  
  
  • Amines - general
  • Diamino componds
  • Diazo compounds
  • Nitrosamines
  • Pentachlorophenol (PCP) and other fungicide-type Chlorinated Phenols
  • Bacteriocide-type Chlorinated Phenols
  • Para-Dichlorobenzene
  • Other Halogenated Benzene compounds
  • Vinyl halide
  • Acrylamide
  • Malondiadehyde (lipid peroxidation product)
  • Other Aldehydes
  • Aflatoxin / Mitotoxins
  • Lindane (and other BHCs)
  • Toxaphene
  • Other Organochlorine compounds
  • Tetrachlorvinphos
  • Other Organophosphates
  • Organophosphate metabolites
  • Phthalates
  • Abnormal proteins
  • Abnormal peptides

  Toxic Metal Adducts include:
  
  
  • Aluminium
  • Antimony
  • Arsenic
  • Barium
  • Cadmium
  • Chromium
  • Cobalt
  • Copper
  • Lead
  • Manganese
  • Mercury
  • Nickel
  • Platinum
  • Rhodium
  • Silver
  • Strontium
  • Thallium
  • Tin
  • Titanium

  
  
• Mitochondrial Membrane - Translocator Protein (TL) Study [Acumen]
  
  This is strictly speaking a chiefly quantitative mitochondrial function blood test, but it also defines any chemical compounds (i.e. most likely toxins) present on the white cell mitochondrial membranes, clogged them up, which may impact mitochondrial function and hence cellular energy availability. The chemicals present at TL sites are specified and measured qualitatively. For more information on this test, please see the Amino Acid and Mitochondrial Function Tests section above.



• Memory Lymphocyte Immunostimulation Assay (MELISA) test - Metals [MELISA/LADR]
  
  The MELISA test is a qualitative white cell blood test to test for heavy metal sensitivity. White blood cells (lymphocytes) from whole blood are isolated and tested against allergens chosen accordingly to the patient's anamnesis, dental and occupational history. The blood is incubated for five days and the lymphocyte reaction is measured by two separate technologies: one based on the uptake of radioisotope by dividing lymphocytes; the other by evaluation by microscopy. The level of reactivity is measured as a Stimulation Index (SI). A value over 3 indicates a positive reaction to a given allergen. The results are presented with a graph. More information can be found be clicking here.



• Lymphocyte Chemical Sensitivity - Electrical Sensitivity [Acumen]
  
  This is a quantitative white blood cell blood test to test for heavy metal and organic toxin sensitivity in the immune system. It is a type of Lymphocyte Proliferation Test (LPT). Parameters include Metabisulphite, Salicylate, Benzoate, Formaldehyde, Petrol exhaust fumes, Natural Gas, Nickel, Titanium, Mercury (Inorganic), Mercury (Organic), Diamino compounds and Pentachlorophenol. When sensitized lymphocytes are exposed to a small amounts of an 'allergen', one of the responses includes the rapid passage of Calcium into the cells. This loss of cellular integrity and subsequent influx of Calcium can result in Calcium attaching to the proteins in the cell, leaving insoluble Calcium deposits, and leading to consequent cell death. Rapid absorption of Calcium into the Lymphocytes under test is measured quantitatively using a Calcium-sensitive fluorescent probe pre-loaded into the lymphocytes. A number of lymphocytes are measured in this way. The effect of the 'allergen' is also noted when the lymphocyte is exposed to an AC electrical field, which tends to amplify the effect in particularly sensitive individuals. Any result over 100 nmol/l of Calcium in the lymphocyte for a particular parameter is deemed to be a sign of lymphocyte sensitivity to that parameter. A result indicating a lymphocyte sensitivity/allergy to a particular parameter may also indicate a possible historical or present elevated level of that toxin in the body. Either way, if the lymphocytes are sensitive to a particular toxin, then the body will react very badly to its presence even if levels are much lower than for the next individual who does not have a problem with that toxin - although no levels of such toxins in the body are of course preferable. In other words, the test may highlight that certain levels are too much for you, rather than absolute statements of 'high' or 'low' levels of such toxins and their physiological impact on the body. This test is broadly similar to the MELISA test, but it is quantitative rather than qualitative, although the range of metals tested is perhaps somewhat wider in the MELISA test.



• Visual Contrast Sensitivity (VCS) Test [Stereo Optical Co. Inc.]
  
  This is a qualitative test to establish lipid status (and potentially Neurotoxic Membrane Syndrome). This is a test that can be done yourself at home. This test is recommended by Ian Solley, although I have no experience of it and cannot comment as to its effectiveness or acceptance in the medical community. It was formerly marketed by E-Lyte, but is now handled by Stereo Optical Co. Inc.



• Total Care - Heavy Metal Screen Test [Nissen Medica]
  
  This is a qualitative, home test kit to establish the approximate levels of heavy metal ions (Cadmium, Mercury, Nickel and Lead) in one's urine. Results are obtained in around 3 minutes. It gives a general combined concentration level. It also measures Zinc, Copper, Cobalt and Manganese, so it is recommended to avoid supplementation of these 24-36 hours prior. The test is also marketed by Detoxpeople.eu.

http://www.nissenmedica.com/pages/products/heavy_metal/
 


Oxidative Stress and Damage Tests:



• 8-Oxo-2-Deoxyguanosine & 8-Oxo-Guanosine [Laboratoire de Biologie Medicale]
  
  8-Oxo-2-Deoxyguanosine (a.k.a. 8-OHdG) is a DNA oxidative damage marker, a byproduct of the oxidation of DNA by free radicals or Reactive Oxidative Species (ROS).
  
  8-Oxo-Guanosine (a.k.a. 8-OHG) is a cytoplasmic RNA oxidative damage marker, a byproduct of the oxidation of RNA by free radicals or Reactive Oxidative Species (ROS).
  
  Cellular concentrations of both purines 8-OHdG and 8-OHG are a direct measurement or indication of oxidative stress in the body as a whole. Oxidative stress may come from excessive free radical formation by the presence of heavy metals, or it may be related to excessive cellular immune activation response and inflammation (Neopterin production) or indeed from free radicals escaping damaged mitochondrial membranes, etc. Both of these DNA and RNA oxidative damage markers can be measured in this quantitative urine test by LdBM in France.
  
  DNA damage is one of the key mechanisms in the ageing process and the development of cardio-vascular diseases and cancer. RNA oxidation is an early prominent feature of the main brain neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Senile Dementia (SD), Amyotrophic Lateral Sclerosis (ALS) and Multiple System Atrophy (MSA).
  
  The following additional purines nucleoside (nucleic acid constituent) concentrations are measured.
  • Guanosine
  • Hypoxanthine (Hx)
  • Xanthine (Xa)
  • Inosine (Ino)

  The following ratios are also calculated.

  • Hx/Urate
  • Xa/Urate
  • Ino/Urate
  • Hx/Ino



• F2-Alpha Isoprostane [Laboratoire de Biologie Medicale]
  
  F2-Alpha Isoprostane (a.k.a. 8-iso-PGF2 alpha) is a marker for oxidative damage of the lipid component of cell membranes. It is a downstream oxidation product of membrane oxidation. Isoprostanes as prostaglandin-like compounds created from the free radical attack of esterified of the Omega 6 Essential Fatty Acid (EFA) known as Arachidonic Acid (ARA) inside the membrane phospholipid. It is of course a very different molecule to a prostaglandin which is a lipid compound produced enyzmatically by the body using cyclooxygenase (Cox1-2) from EFAs and which has nothing to do with free radical attack on cell membranes.
  
  Isoprostanes in general are valuable markers in clinical biology as they are found in all biological fluids and tissues and are stable in vivo and ex vivo. There are 10 times more isoprostanes in atherosclerotic plaque compared with normal vascular tissue. They are also only dependent on their production (in this case free radical attack) rather than metabolism or excretion without intraindividual variability. There are many studies validating Isoprostanes as the most accurate and reliable indicator of oxidative stress in vitro and in vivo.



• Malondialdehyde [Laboratoire de Biologie Medicale]:
  
  This quantitative urine test by LdBM measures the level of urinary Malondialdehyde (MDA), a byproduct of lipid peroxidation by free radicals, in particular mitochondrial membranes. The presence of elevated MDA in the urine suggests evidence of excessive oxidative damage to mitochondrial membrane lipids and hence an oxidative stress problem.



• Mitochondrial Membrane - Translocator Protein (TL) Study [Acumen]
  
  This is strictly speaking a quantitative mitochondrial function blood test, but it also provides information on the general state of the mitochondrial membranes, in terms of any partial detoxification products or toxins attached to them, effectively reducing their permeability; and indeed if there are any signs of oxidised lipid byproducts attached to the mitochondrial membranes, such as the aldehyde derivatives, Malondialdehyde (MDA) and Crotonaldehyde. The presence of these latter compounds provides us with evidence of oxidative damage of the mitochondrial membrane lipids, and thus an oxidative stress problem. For more information on this test, please see the Amino Acid and Mitochondrial Function Tests section above.



• Metabolic Analysis Profile [Genova Diagnostics]
  
  See Amino Acid and Mitochondrial sections above for more information.

 


DNA and RNA Related Tests:



• DNA Adducts (genomic DNA from Leucocytes) [Acumen]
  
  This qualitative test examines the DNA of White Blood Cells (WBCs, a.k.a. Leucocytes) and looks for the presence of organic toxin compounds attached to specific genes; and indeed their general concentration in the blood (from their representation in WBCs. It also measures the levels of DNA-associated Zinc, and whether this is within the normal reference ranges, or whether it has been displaced.
  
  Please see the Toxicity Tests section above for more information.



• 8-Oxo-2-Deoxyguanosine & 8-Oxo-Guanosine [Laboratoire de Biologie Medicale]
  
  [SeeOxidative Stress and Damage Tests tests section above]



• Gene Test for Gluten Sensitivity/Celiac Sprue [Enterolab]
  
  Enterolab offers genetic testing to ascertain one's predisposition to gluten intolerance - to identify the presence of the responsible HLA-DQ:
  
  
  • Gene Test for Gluten Sensitivity/Celiac Sprue - HLA-DQ testing from swab of inside of mouth - to detect for presence of one or more genes associated with (predisposition to) gluten sensitivity, celiac sprue and other autoimmune syndromes. This test detects the presence of the locus type HLA-DQB1*0201.

  Please see the Food Allergy Testing section for more information on genetic testing for Celiac Disease.



• DNA Technology [Australian Biologics]
  
  DNA Testing uses Polymerase Chain Reaction (PCR) technology to detect the present of certain pathogenic and opportunistic microorganisms, including Mycoplasma species and beta-hemolytic streptococcal infections, present in the Red (RBCs) and White Blood Cells (WBCs) in the blood stream. DNA for PCR analysis is extracted from both RBC and WBC blood components, not just from WBC nuclei.
  
  Please see the Live Blood Microscopy section for a qualitative method for identifying these types of intracellular bacterial infection, and also the Dysbiosis section for other tests for detecting the presence of bacterial overgrowth in general.

 


Virus Tests:



• Cell-Free DNA in Blood Plasma [Acumen]
  
  This is a quantitative test to establish the levels of free DNA present in the blood plasma (i.e. not tied into the nuclei inside blood cells), i.e. of viral origin. Most of the cell-free DNA present in blood plasma is associated with cell degradation. Some of course may be of viral origin. Very low levels are present in healthy individuals and increases are often associated with serious illnesses such as malignancy, stroke, auto-immune diseases, severe infections and indeed CFS. In studies on 87 CFS patients, positive results were found in 93% of those with CFS duration of 4 months to 4 years. In those with a CFS duration of 14 years, 75% had positive results.



• See US Laboratories section below for more tests.
  
  
  

Dysbiosis / Pathogenic Microorganism Tests:



• Comprehensive Stool Analysis / Parasitology x 1 [Doctor's Data]
  
  This is a qualitative stool test to establish a range of information pertaining to one's stool. A frozen stool sample is submitted along with two other stool samples using various preservative liquids. The physical nature of the stool can be examined, and also microbes can be cultured from the stool samples and then tested antimicrobial agents to determine which antimicrobial agents they are sensitive to and which they are resistant to. This can provide useful treatment guidelines to practitioners who do not use any forms of muscle testing etc.
  
  Parameters include:
  
  
  • Microbiology - examines the proliferation of beneficial flora species, such as Bifidobacterium, E. coli species (spp for short), Lactobacillus spp and Enterococcus spp. Also examined are non-pathogenic bacterial species that are out of balance (i.e. found in too high numbers); and also dysbiotic flora and the extent of their proliferation.
  
  
  • Mycology (Yeast) Culture is also examined, to see which yeast species are in normal amounts and if any are dysbiotic.
  
  
  • Parasitology/Microscopy (Trichrome Stain & Concentration) tests also test for the presence of Giardia Lamblia and Cryptosporidium by ELISA/EIA (Enzyme Immunoassay).
  
  
  • Campylobacter jejuni - pathogenic bacteria that frequential causes diarrheal disease. Presence detected.
  
  
  • Digestion/Absorption - Elastase, Fat stain, muscle fibres, vegetable fibres, carbohydrate fibres.
  
  
  • Inflammation - Lysozyme, lactoferrin, WBC, mucus.
  
  
  • Immunology - sIgA - Secretory IgA.
  
  
  • Short Chain Fatty Acids - Acetate, Propionate, Butyrate, Valerate.
  
  
  • Intestinal Health Markers - RBC, pH, Occult Blood, Yeast (Candida albicans).
  
  
  • Macroscopic Appearance - Colour (expected - brown), consistency (expected - formed/soft).
  
  
  • Bacterial Susceptibilities - To test a pathogenic or dysbiotic species (if present) with the following antimicrobial agents. Prescriptive agents tested - Amoxicillin, Ampicillin, Augmentin, Ciprofloxacin, Trimeth-sulpha. Natural agents tested - Berberine, Black Walnut, Caprylic Acid, Cat's Claw, Citrus Seed Extract, Goldenseal, Oregano, Uva Ursi.
  
  
  • Yeast Susceptibilities - To test a pathogenic or dysbiotic species (if present) with the following antimicrobial agents. Prescriptive agents tested - Fluconazole, Itraconazole, Ketoconazole, Nystatin. Natural agents tested - Berberine, Caprylic Acid, Goldenseal, Oregano, Tanalbit, Undecylenic Acid, Uva Ursi.
  
  
  
• Comprehensive Digestive Stool Analysis (CDSA) 2.0 plus Parasitology [Genova Diagnostics]
  
  This is a semi-quantiative stool test for various digestive, dysbiosis and parasite markers. Stool samples are collected over a 3 day period, the first two days being samples for parasite testing (small amounts) - this allows increased Optimisezed Parasite Recovery (OPR) by combining samples compared with a single collection. As with the Doctor's Data test, a number of antimicrobial agents are tested for effectiveness, but this time only with any yeast overgrowth. I am not entirely sure which profile is better, the Genova or DD. One omission from the GDX test is measurement of Enterococcus sp. There are some minor differences as you can see below.
  
  Parameters include:
  
  
  • Digestion/Absorption - Pancreatic Elastase 1, Putrefactive SCFAs (e.g. Branched Chain Fatty Acids or BCFAs)
  
  
  • Gut Immunology - Eosinophil Protein X (indicative of IgE-mediated inflammation and tissue damage) and Calprotectin (a neutrophilic marker for GI inflammation).
  
  
  • Metabolic (activity of mainly commensal bacteria) - Beneficial SCFAs (produced by fermenting soluble fibre), n-Butyrate (an SCFA) and stool pH; also levels of Secondary Bile Acid (Bile Acids deconjugated by commensal bacteria) inc. Lithocholic acid (LCA), Deoxycholic acid (DCA) and the LCA/DCA Ratio.
  
  
  • Bacteriology - Beneficial Bacteria (Lactobacillus sp., Escherichia coli and Bifidobacterium), Additional Bacteria (gamma haemolytic Streptococcus, alpha haemolytic Streptococcus, and Bacillus sp.) and also Mycology (e.g. yeasts) inc. Saccharomyces cerevisiae. These are qualitatively categorised from 0+ to 4+. Beneficial bacteria should be ideally 2+ or over, and 4+ suggests fully recovered flora. Mycology, i.e. those organisms present in low numbers, may become pathogens and cause a local infection (via bloodstream) if GI mucosal lining is disrupted. The Additional and Mycology categorised further as NG (No Growth), NP (Non-Pathogen), PP (Potential Pathogen) and P (Pathogen) - which may be dependent on their numbers.
  
  
  • Additional Tests - for pathogenic bacterial strains inc. Shiga toxin E.coli (STEC) and Camphylobacter sp. inc. jejuni.
  
  
  • Azole Antifungals - e.g. for Saccharomyces cerevisiae inc. Fluconazole, Itraconazole and Ketoconazole - and respective susceptibility (susceptible (S), intermediate susceptibility (I) and resistance (R) - with a numerical score in the respective category).
  
  
  • Non-absorbed Antifungals - Nystatin (rated graphically between low and high inhibition - inhibition being the level of reduction in organism growth by the agent in question)
  
  
  • Natural Antifungals - Berberine, Caprylic Acid, Garlic, Undecylenic Acid, Plant Tannins and Uva-Ursi (rated as above, inhibition).
  
  
  • Parasitology - Cryptosporidium, Giardia lamblia and Entamoeba histolytica/dispar. GDX report that 22% of stool samples submitted contain parasites.
  
  
  
• GI Stool Effects Profile [Metametrix]
  
  The GI Stool Effects Profile (a.k.a. Microbial DNA Ecology Profile and Microbial Sensitivity Profile) is a quantitative stool test. It can quantify the number of different major harmful microbes in one's stool including protozoan parasites, yeast/fungi, pathogenic bacteria and Mycoplasma. Click here for a sample report and here for more information.



• DNA Technology [Australian Biologics]
  
  DNA Testing uses Polymerase Chain Reaction (PCR) technology to detect the present of certain pathogenic and opportunistic microorganisms, including Mycoplasma species and beta-hemolytic streptococcal infections, present in the Red (RBCs) and White Blood Cells (WBCs) in the blood stream. DNA for PCR analysis is extracted from both RBC and WBC blood components, not just from WBC nuclei.
  
  Please see the Live Blood Microscopy section for a qualitative method for identifying these types of intracellular bacterial infection.



• D-Lactate Test [Biolab]
  
  Commensal Streptococcus and Enterococcus bacteria ferment fibre to produce lactic acid. The two isomers of Lactic acid produced are L-Lactate and D-Lactate. Humans (and mammals in general) only produce L-lactate as part of anaerobic respiration and only possess the enzymes Lactate Dehydrogenase (LDH) for metabolising L-Lactate in any significant quantity. Mammals do not possess the D-Lactate Dehyrogenase enzyme in any significant quantity, and this is generally only found in plants and bacteria.
  
  In humans, the two LDH enzymes act on L-Lactate to convert it into Pyruvate (and vice versa). One of these enzymes e.g. in Glycolysis in the NAD(P) dependent L-Lactate Dehydrogenase enzyme (EC.1.1.2.3). The other LDH enzyme is a Cytochrome c-enzyme found in the liver (EC.1.1.1.27). Mammals including humans however can metabolise D-Lactate using the D-alpha-hydroxy acid dehydrogenase enzyme found in the mitochondria (at 20% of the rate of a proper D-Lactate Dehydrogenase enzyme as found in plants).
  
  http://en.wikipedia.org/wiki/Lactate_dehydrogenase
  
  If excessive conmensal Streptococcus and Enterococcus fermentation in the GI tract occurs, then D-Lactate levels tend to rise in th body, and acidosis (a drop in blood pH) occurs - known as D-Lactic Acidosis. D-Lactate can accumulate in the mitochondria and inhibit their proper function. The body then has two main methods available to eliminate D-Lactate are renal excretion (i.e. whatever is in the fluid filtered off by the kidneys into urine) and via faeces (excreting the D-Lactate remaining in the stool) - which is not particularly efficient in clearing the D-Lactate, especially if it is being produced continually in the GI tract. Recent studies however have claimed to show that humans do actually possess the D-Lactate Dehydrogenase enzyme on the inner mitochondrial membrane. Studies from the 1920s showed that D-Lactate was poorly metabolised compared with L-Lactate, whereas studies from the 1980-90s found that D-Lactate was actually readily metabolised, although most academic and medical sources still quote the 1920s results as fact. The area is still hotly debated.
  
  D-Lactic Acidosis is rare in general terms and usually only occurs in the case of short bowel syndrome in humans (malabsorption disorder caused by surgical removal of the small intestine) and children with gastroenteritis. It can of course occur in patients who have markedly poor digestion with a large proportion of undigested carbohydrate in the GI tract. In animals, it can occur through excessive grain consumption by ruminants (e.g. cattle, goat, sheep etc.) or in cases of diarrhea in calves.
  
  Biolab's blood plasma test for D-Lactate is described in the pdf document below.
  
  www.biolab.co.uk/docs/dlactate.pdf



• Organix Dysbiosis Profile - Urine [Metametrix]
  
  This quantitative test of organic acids is targeted towards those produced by dysbiotic bacteria and yeasts, and includes D-Lactate amongst other parameters.
  
  http://www.metametrix.com/test-menu/profiles/organic-acids/organix-dysbiosis
  
  Please see the Bacterial page for more information on D-Lactate.



• Candida IgG & Candida IgM [Cambridge Nutritional Sciencies]
  
  This is a qualitative blood test for IgG and IgM antibodies that react with Candida species. For more information, click here.



• Candia5 Rapid Candida (Self) Test [Return2Health]
  
  Candia5 is a qualitative home finger-prick test for the detection of IgG antibodies in whole blood serum that react with purified Candida antigens.
  
  http://www.return2health.net/candia-5-candida-test-kit.html#panel_info



• Neurotoxic Metabolite Test (NMT) [Protea biopharma]
  
  The Neurotoxic Metabolite Test Kit is a qualitative home urine test kit that measures the presence of abnormal levels of metabolites in the uring, related to the production of Hydrogen Sulphide (H2S) - known as Hydrogen Sulfide in the US! The body naturally produces some H2S, and it plays a part in normal physiological functions, but an excess in production may be extremely detrimental in terms of reduced oxygen circulation and impaired mitochondrial function. Overproduction is thought to result from metabolic dysfunctions as well as from the overgrowth of certain pathogenic bacterial species. A test request/order form can be requested from Protea biopharma. This test has been recently introduced (in June 2009) and is presented as a test for CFS and ME, although it may relate only to a subset of patients, and is only really an initial indicator - as many more tests would be required to ascertain exactly what is going on in the body in other respects. The NMT Test Kit should be refrigerated if to be stored for any length of time.

 


Intracellular Bacteria and Protozoa Blood Tests (Lyme):



• Memory Lymphocyte Immunostimulation Assay (MELISA) test - Borrelia [MELISA/LADR]
  
  The MELISA test is a qualitative white cell blood test to test for Borrelia bacteria species sensitivity. Borrelia are the predomainant bacteria associated with Lyme Disease, acquired from tick bites from infected ticks. White blood cells (lymphocytes) from whole blood are isolated and tested against Borrelia-derived peptide antigens (not actual whole, live Borrelia bacteria). This test is considered by LADR as being more reliable an indicator of Lyme Disease than either ELISA or Western Blot tests.
  
  The peptides are derived from the following Borrelia species:
  
  
  • Borrelia afzelii
  • Borrelia burgdorferi sensu strico
  • Borrelia garinii

These peptides include:

• r-OspC
• r-p41-intern-1
• r-p41-intern-2
• r-p41-intern-3
• r-p100
• r-Peptide Mix (OspA/V1sE)
• Full Ag Lysate

The blood is incubated for five days and the lymphocyte reaction is measured by two separate technologies: one based on the uptake of radioisotope by dividing lymphocytes; the other by evaluation by microscopy. The level of reactivity is measured as a Stimulation Index (SI). A value over 3 indicates a positive reaction to a given allergen, and two or more scores of 3+ are indicative of a Borrelia infection. Cytotoxicity of the Borrelia peptide antigens is measured against the isolated lymphocytes. More information can be found be clicking here.



• See US Laboratories section below for more tests.
  
  
 

General Pathology Tests for Essential Fatty Acids, Vitamins and Co-Factors:



• Essential Fatty Acids [Biolab]
  
  This is a quantitative red cell blood test to establish to exact levels of each EFA (omega 3 and omega 6) and also non-EFA fatty acids, and to note that they in the correct ranges and relative ratios.



• Niacin Status (vitamin B3) [Acumen]
  
  This is a quantitative blood test to establish red blod cell levels of active B3 (NAD).



• Functional (Blood) Test for B3 [Biolab]
  
  This is a quantitative blood test to establish levels of Vitamin B3.



• Functional (Blood) Tests for B1, B2 and B6 [Biolab]
  
  This test measures the B1 (ETK activation), B2 (EGR activation) and B6 (EGOT activation). Results expressed as IU/gHb.



• Functional (Blood) Test for Biotin [Biolab]
  
  This test establishes the blood levels of Biotin (Vitamin H or B7). The Biotin test measures levels of two acids, 3-hydroxyisovaleric acid and 4-hydroxyisovaleric acid. A high level of 3 (i.e. over 6.7 micro mol/l) in the presence of normal levels of 2 (i.e. 2-19 micro mol/l) indicates a biotin deficiency. Biotin is not measured directly.



• Functional (Blood) Test - MMA (B12) [Biolab]
  
  This quantitative blood test establishes the blood levels of Vitamin B12.



• Direct Measurement (Blood) - Coenzyme Q10 (serum) [Biolab]
  
  This is a blood serum test to measure the levels of Coenzyme Q10, a metabolite in mitochondrial function and energy production.



• Biochemistry Pathology Report [Biolab]
  
  This is a quantitative blood test to establish levels of key amino acids, glucose, cholesterol, and specific nutritional elements.



• Haematology & Biochemistry with Electrolytes Pathology Report [Doctor's Laboratory]
  
  This is a quantitative blood test to establish levels of key nutritional metal elements, amino acids, enzymes, glucose, cholesterol, and various physical blood parameters. A low platelet and lymphocyte count can indicate either insufficient nutrition (or nutrients reaching the blood stream) or either the presence of toxins or a virus. An elevated Eosinophil (white cell) count may indicate the presence of parasites.

 


Immunology Tests:



• Immunology Profile Pathology Report [Doctor's Laboratory]
  
  This is a quantitative blood test to establish a variety of immunology and special pathology parameters.



• Urinary Pterins [Laboratoire de Biologie Medicale]

The Urinary Pterins Test as its name suggests is a quantitative urine test for three types of Pterin. These are markers of neuroinflammation and cellular immune system response and inflammation. The test is a.k.a. Urinary Neopterine Profile.

Neopterin is a sensitive marker of cellular mediated immunity. Reduced levels reflect cellular immunity weakening. Increased levels are positively correlated with infectious, inflammatory, immune system dysfunction or neoplastic disease evolution. Excessive Neopterin may indeed impact the Nitric Oxide pathway in the body (e.g. excessive peroxynitrite formation and oxidative stress). Neopterin is generally regarded as a useful index of inflammation response associated with immune activation.

Tetrahydrobiopterin (BH4) is the cellular protection or antidote to Neopterin. It helps to alleviate the oxidative damage caused by Neopterin induced immune activation. When BH4 is oxidised, by Neopterin, it forms Biopterin (a.k.a. Oxidised Biopterin or 'Box'). Biopterin is the coenzyme oxidised degradation product of Tetrahydrobiopterin (BH4).

If Neopterin is constantly increased, then there is a possibility that BH4 levels are inadequate. The extent of differential between these two Pterins could be considered to be an index of deleterious consequences of cellular inflammation. Decreased Biopterin relative to Neopterin might suggest inadequate antidote protection capability and increased oxidative damage caused by immune activation (in addition to the original cause of the immune system activation). Too much Oxidised Biopterin (Box) relative to BH4 might suggest an inability to recycle the Box back to BH4 and also inadequate total Biopterin to deal with the amount of Neopterin.

Please see the Immunity page for more information on Pterins.

The parameters measured in the Urinary Pterins Test are:


• Neopterine (NEO)
• 
  
• Oxidised Biopterin (a.k.a. Biopterin or Box)


• Tetrahydrobiopterin (a.k.a. Reduced Biopterin or BH4)

The following ratios are also calculated to compare the amount of Neopterin to the amount of reduced and oxidised Biopterin:


• Total Biopterin to Neopterin ratio: (BH4 + Box)/Neopterin
• Tetrahydrobiopterin to Nepterin ratio: BH4/Neopterin
• Tetrahydrobiopterin to Oxidised Biopterin: BH4/Box



• See US Laboratories section below for more tests.

 


Chemical Sensitivity Tests:



• Lymphocyte Chemical Sensitivity - Electrical Sensitivity [Acumen]
  
  This is a quantitative test to detect lymphocyte sensitivity to a variety of organic toxins and heavy metals. For more information, please see the test description in the Liver Function and Toxicity test section above.



• MELISA Test [MELISA]
  
  This is a qualitative test to detect lymphocyte sensitivity to a variety of heavy metals. For more information, please see the test description in the Liver Function and Toxicity test section above.



• Immunology Testing [Breakspear Medical Group]
  
  This is a semi-quantitative programme of skin testing for an allergic response to a small number of mainly organic chemical compounds. Please see the section below on Immunology Testing for more information.

 


Food Allergy and Intolerance Tests:



• Lactose, Lactulose and Sucrose Breath Test [Breakspear Medical Group]
  
  This is a quantitative breath test to determine whether specific food intolerances exist, specifically Lactose (or Lactulose) Intolerance and Fructose Malabsorption, by measuring the Hydrogen concentration in the breath.
  
  In patients where these sugars are not either properly digested (in the case of Lactose on account of a 'deficiency' in the Lactase enzyme) nor absorbed (in the case of Fructose), these sugars will largely pass through the digestive tract and be fermented by bacteria, into Short Chain Fatty Acids (SCFAs) such as Butyric acid, Propionic acid and Acetic Acid, but also the gases hydrogen, carbon dioxide and methane. Only bacterial fermentation of carbohydrates produces these byproducts in the colon, primarily by anaerobic bacteria. A proportion of these gases will be absorbed into the blood stream from the GI tract, and are transported by the heart to the lungs. Here a proportion of these gases passes through the alveolar membrane and is expelled out of the lungs where the Hydrogen concentration can be measured.
  
  The patient is required to avoid any complex (slow digesting) carbohydrates for 24 hours prior to the test (including beans, bran etc.) and also to fast from 12am on the night before the test. The reason for this is explained below.
  
  At the start of the test, the patient's Hydrogen breath level is measured by having him blow into a Hydrogen meter, in order to establish a baseline H2 breath level. The patient immediately then consumes a small, measured amount of either Lactose, Lactulose or Sucrose, stirred in a glass of water (depending on what type of intolerance/malabsorption is being tested for). The patient is then monitored every 20 minutes and at each interval the patient breathes into a Hydrogen gas meter. This is continued for 2 hours. This concludes the test.
  
  If at any point during the test the patient's breath level of Hydrogen goes up significantly, the specific condition can be diagnosed. If there is little change in the H2 breath level, then the diagnosis is negative (i.e. the patient is not intolerant to that particular type of sugar.)
  
  Sucrose is used in order to test for Fructose Malabsorption as Sucrose is broken down by Sucrase in the digestive tract into Glucose and Fructose.
  
  Measuring Hydrogen levels is also an indicator of whether an individual has been eating or fasting during the testing period.
  
  
  • For non-fasting individuals, the H2 breath level is high early in the morning. H2 accumulates in the blood on account of reduced motility during sleep, and food is exposed to bacterial fermentation for longer. Reduced breathing rates (hypoventilation) during sleep also decreases the amount expelled through the lungs and thus the blood concentration and alveolar air concentration can creep up. H2 breath levels tend to fall during early afternoon, then increases again during mid-afternoon, after the carbohydrates consumed at lunchtime have reached the colon. H2 breath levels gradually decrease thereafter, until after one's dinner in the evening.
  
  
  • For fasting individuals, H2 breath levels fall gradually during the entire day, which is why the Lactose, Lactulose and Sucrose Breath Test is performed in controlled conditions, the patient having fasted prior and only consuming a controlled amount of a specific sugar type, in order to monitor the effects.
  
  It is beneficial to measure both methane and hydrogen levels in order to gain a full picture, but it is not strictly necessary. Methanogenic bacteria convert hydrogen to methane in the colon (small intestine). When disaccharides (i.e. lactose, sucrose) are metabolised/fermented by bacteria, one of three processes can occur: Hydrogen is produced; Methane is produced or both Hydrogen and Methane are produced. However, in an individual who is not able to digest/absorb Lactose or Sucrose effectively, the H2 levels will generally spike enormously compared to a person who is able to digest/absorb these sugars effectively; however measuring both gases will of course increase the accuracy of the test.



• Red Blood Cell Fructose-6-Phosphate (F6P) [Acumen]
  
  This quantitative blood test is a measure of the Fructose-6-Phosphate in one's blood. It is used to detect for an excessive level of Fructose intake and also any potential problems associated with Glycolysis (the conversion of Glucose into Pyruvate). This method of Fructose usage is found mainly in the muscle cells (as opposed to Liver cells that produce Fructose-1-Phosphate).
  
  Fructose-6-Phosphate (F6P) is produced from Fructose, and is utilised in the Glycolysis pathway, to produce Pyruvate from Glucose. Excessive Fructose intake leads to high F6P levels in the cells. If the Fructose availability far exceeds the Glucose supply, then metabolic issues arise as the control mechanisms that apply to Glucose are essentially bypassed or lifted. Excessive fructose intake tends to inhibit Glycolysis and Gluconeogensis, albeit in a slightly different manner to Hereditary Fructose Intolerance (HFI), a hereditary deficiency in the liver enzyme Aldolase-B that is involved in Fructose Metabolism. Please note that this is not a blood test for Fructose-1-Phosphate (F1P), levels of which tend to build up in HFI patients.
  
  Excessive Fructose intake can also deplete Short-Chain Essential Fatty Acids even before blood sugar levels drop significantly. The liver uses the SCFAs Acetate, Proprionate and Butyrate for the production of Glucose to try to avert Hypoglycaemia.
  
  The liver converts Fructose into Glucose in a series of enzymatically controlled steps known as Glycolysis. If any of the enzymes involved in Glycolysis are deficient, then the liver is no longer able to produce Glucose from Fructose and one of the intermediary products where the bottleneck is will build up to dangerous levels. In the case of HFI, a deficiency in the Aldolase-B enzyme means that its substrate, Fructose-6-Phosphate, builds up in the liver and kidneys and has a variety of adverse effects on the body. The Fructose-6-Phosphate (F6P) levels can be detected in the blood. The blood sample is taken 3 hours after food was last consumed. A high red cell Fructose-6-Phosphate reading is indicative of either Hereditary Fructose Intolerance or excessive Fructose intake. Both problems stress the same pathways. A concurrent SCFA test detailed below is also recommended in order to demonstrate any tendency towards Hypoglycaemia and LDH isoenzymes will show a shift to the liver pattern if Fructose-1-Phosphate levels build up (c/f HFI) and also inhibit Glycolysis and/or Gluconeogenesis.
  
  According to Acumen, F6P it is a good integrating measure is unlikely to have huge hour-to-hour or day-to-day variation, unlike F1P levels that tend to vary a great deal throughout the day and which are much more recent-diet-dependent.



• Short-Chain Fatty Acids (SCFAs) in Blood Plasma [Acumen]
  
  Please see Liver Function tests section above for description.



• Uric Acid in Blood Plasma [Breakspear Medical Group]
  
  This is a quantitative blood test to measure the Uric acid levels in the blood plasma, as an indicator of Hereditary Fructose Intolerance (HFI). Please see the Food Allergy page for more information.



• Lymphocyte Proliferation Test for Fructose [Breakspear Medical Group]
  
  This is a qualitative blood test to measure the ratio of white blood cell (lymphocyte) growth on a low glucose medium compared to that on a low glucose/high fructose medium. Values below the reference for low glucose only reflect a metabolic intolerance to excess fructose. Please see the Food Allergy page for more information.



• Food Scan 113 Food Intolerance Test [YorkTest Laboratories]
  
  This is an arguably semi-quantitative blood test for immune system mediated Food Intolerances, specifically IgG-mediated. Its purpose is to examine the levels of Immunoglobulin/antibody IgG that correspond to a variety of food types (113 in total). Food intolerance is where the body does not produce sufficient enzymes of a specific type to digest certain food types, resulting in very slow digestion of these foods, which can 'rot' in the digestive tract. The Food Scan 113 does NOT measure IgE reactions to any of these food types which typically represent classical allergic food responses (e.g. skin rashes, shortness of breath etc.) Food allergies are usually well known by the patient, whereas food intolerances can often go unnoticed, but manifest themselves as general gut complaints such as Irritable Bowel Syndrome (IBS). One can be intolerant of a particular food type but not allergic to it, or allergic but not intolerant to it.
  
  Food Scan 113 is a pin prick test and can be performed at home; and ordered directly from the YorkTest Laboratories web site without necessarily a practitioner referral. It is the only food intolerance test endorsed by Allergy UK (to date). A small blood sample is collected and tested against a list of 113 food items, and the immune system response graded between 0 and 4 (integer rating only). A complete list of food items/parameters tested can be seen here. A sample report can be found http://www.yorktest.com/downloads/FoodScan_113_example_result.pdf. A vegetarian version, excluding all the meat products, is also available, at the same price, covering 113 items/parameters, called 'Vegetarian FoodScan Food Intolerance Test'. The YorkTest allergy tests are merely a diagnostic tool to formulate an elimination diet to avoid those foods that provoke an allergic reaction (at the time of testing), and not to actually 'treat' one's food allergies per se.



• Food Detectve & FoodPrint [Cambridge Nutritional Sciences]
  
  This is a semi-quantitative blood test for immune system mediated Food Intolerances, specifically IgG-mediated. Two profiles are Food Detective and FoodPrint.
  
  
• Gluten, Dietary Yeast, Cow's Milk, Chicken Egg and Soy Sensitivity Tests [EnteroLab]
  
  This is a set of quantitative stool tests to examine the number of IgA antibodies in the colon produced in response to historical consumption of the above food types (if eaten regularly within last 1-2 years). IgA is a protective antibody/immunoglobulin and those with food intolerances tend to have very low levels of this antibody corresponding to a particular food type they have an intolerance to. Low IgA levels generally then correspond to higher levels of Lymphocyte activity in response to the presence of these food types, causing the symptoms of gut/bodily inflammation and food intolerance. Antibody test values range from a positive value of 10 to as high as 350 units. The average positive value is approximately 45 units.
  
  IgA Sensivity Stool Tests include:
  
  
  • Gluten Sensitivity - Fecal anti-gliadin IgA antibody
  
  
  • Cow's Milk Protein (Casein) Sensitivity - Fecal anti-casein IgA antibody
  
  
  • Chicken Egg (Ovalbumin) Protein Sensitivity - Fecal anti-ovalbumin IgA antibody
  
  
  • Dietary Yeast Sensitivity - Fecal anti-Saccharomyces cerevisiae IgA antibody
  
  
  • Soy Sensitivity - Fecal anti-Soy Protein IgA antibody
  
  
  • Tissue Transglutaminase Sensitivity - Fecal anti-tissue transglutaminase IgA antibody. A measure of the reaction of the body's immune system response to the tissue transglutaminase enzyme produced by the body when Gliadin/Gluten is ingested (c/f mechanism of Celiac Disease)

  Other Sensitivity Stool Tests include:
  
  
  • Acute/Chronic Colitis - tests for Lactoferrin protein emitted from the inflammatory White Blood Cells called Neutrophils
  
  
  • Intestinal Malabsorption/Intestinal Damage - Quantitative fecal fat microscopy - a measure of malabsorption of dietary nutrients caused by damage of small intestine and/or lack of enzyme production by pancreas.

  Enterolab also offers genetic testing to ascertain one's predisposition to gluten intolerance - to identify the presence of the responsible HLA-DQ gene.
  
  
  • Gene Test for Gluten Sensitivity/Celiac Sprue - HLA-DQ testing from swab of inside of mouth - to detect for presence of one or more genes associated with (predisposition to) gluten sensitivity, celiac sprue and other autoimmune syndromes. This test detects the presence of the locus type HLA-DQB1*0201.
    
    Please see the Food Allergy Testing section for more information on genetic testing for Celiac Disease.

  All of the above tests can be ordered in two panels, the 'Gluten Sensitivity Stool and Gene Panel Complete' and the 'Egg, Yeast and Soy Sensitivity Stool Panel'.


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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.  

UK Laboratories:

Doctor's Laboratory in London can arrange for various blood tests inc. Melisa test for heavy metals etc.
www.tdLdBMthology.com

Biolab Medical Unit (UK) are a medical referral laboratory specialising in nutritional and environmental medicine, in Weymouth Street in London. On their web site, they have a referral list of medical doctors specialising in nutritional and environmental medicine, and allergy testing.
www.biolab.co.uk
www.biolab.co.uk/tests.html
www.biolab.co.uk/reflist.html

Acumen is a laboratory set up by Biolab's retired laboratory director Dr John McLaren Howard. He performs the Translocator (TL) Protein Study and ATP Profile. For those who live outside the UK and wish to order these tests, the blood sample can be couriered direct (in sealed tube, in plastic bag, with cooling packet and absorbent material, in padded envelope etc. to arrive maximum 72 hours from when the sample is taken.) Acumen Laboratory has no web site currently but can be contacted directly via email at acumenlab//////at//////hotmail.co.uk or telephone on +44 (0)7707 877175. Postal address is Acumen, PO Box 129, Tiverton, Devon EX16 0AJ.

Individual WellBeing Diagnostic Laboratories (IWDL) is the new European parter for the US laboratory Genova Diagnostics.
www.iwdl.co.uk

Diagnostic Services Limited in High Peak provide independent pathology services and were formerly the UK agents for Genova Diagnostics (US Laboratory).Their contact telephone number is 0800 298 6280, email: info@diagnosticservices.co.uk.

Neuro-Lab Limited is a laboratory run by Dr Galkina-Taylor, based in Bournemouth, Dorset. It specialises in neurological assays.
www.neuro-lab.com

YorkTest Laboratories Limited are a laboratory specialising in food allergy testing.
www.yorktest.com

Cambridge Nutritional Sciencies Ltd (CNS) are providers of various Food Intolerance blood tests as well as other blood tests.
http://www.cambnutri.com

The Diagnostic Clinic are a diagnostic laboratory offering a range of medical services and also a range of supplements. Nurses currently used by Nutrition Associates for PLX and B12 injections etc. Also offer Live Blood Analysis.
www.thediagnosticclinic.com

Lab21 Healthcare are a diagnostic and clinical biochemistry laboratory based in Cambridge offering a range of tests, including blood and saliva tests (for hormones).
www.lab21.com/healthcare/index.php

Bionetics are a UK based laboratory for hair mineral analysis. No doctor's referral is necessary. Have not tried them as yet.
www.bionetics.co.uk

Lab Tests Online is an internet resource listing different types of test for a variety of different conditions. It is not a laboratory. It is by no means comprehensive, but may supplement the tests described on MedicalInsider.
http://labtestsonline.org

Institut Europeen de la Prevention Personnalisee (I.E.P.P.) provides diagnostic and predictive genetic susceptibility testing.
www.i-e-p-p.org

Nutrition Geeks are a supplier of professional nutritional supplments such as Design for Health, and also Clinical Laboratory Services. They are also the UK representative for Metametrix in the USA.
www.nutritiongeeks.co.uk

Breakspear Medical Group in the UK. Their web site is shown below, including a link to view a pdf file on the causes and treatments for 'CFS/ME'. Breakspear Hospital is a private licensed day patient unit, dedicated to the treatment of allergy and environmental illness located in Hemel Hempstead, Hertfordshire. They offer various pathology testing services, in conjunction with consultations with specialists based at the hospital. Prices are somewhat high. A list of pathology tests can also be found below. Other tests include 2,3-BPG and BPG mutase tests (oxygen transport), transcutaneous gases test, VEGF test (formation of new budded capillaries, and also resulting elevated Nitric Oxide and Peroxynitrite levels), and QIFT (Quantitative Inotropic Fatigability Test) test (of heart function). Please see the Cardiac page for more information pertaining to this area.
www.breakspearmedical.com/files/chronic.html
www.breakspearmedical.com/files/documents/ChronicFatigueweb.pdf
www.breakspearmedical.com/files/pathology.html

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Mainland Europe Laboratories:

Laboratoire de Biologie Medicale (formerly known as Laboratoire Philippe Auguste) in Paris, France offers a variety of test panels such as tests for evidence of toxicity (Polyphyrins), oxidative stress (80HdG & 80HG), Mitochondrial Membrane Damage (F2-Alpha-Isoprostane), and cellular immune response and inflammation (Pterins).
www.labbio.net

R.E.D. Laboratories in Belgium offer a variety of viral and bacterial tests, and many others, including tests for XMRV, MLV, HHV-6, HHV-7, Cytomegalovirus, Epstein-Barr Virus, Mycoplasma and Chlamydia Pneumoniae, stool analysis, oxidative stress markers, etc.
http://www.redlabs.be

The MELISA test web site (a test of the immune system response to the presence of different heavy metals) is shown below. The MELISA web site contains a list of agents and laboratories that can submit blood samples on your behalf for the MELISA test. The actual MELISA Diagnostics Research Laboratory is based in Belgium.
www.melisa.org

Micro Trace Minerals are a German based laboratory for hair mineral analysis. They offer a variety of profiles for element analysis, including those a comprehensive radioactive isotope profile. The nutritional valency 1 elements Sodium and Potassium, and also Phosphorus, however are not currently included in hair analysis tests. Staff are very helpful and are multi-lingual. No doctor's referral is strictly necessary.
www.microtrace.de

Protea biopharma, a company run by Prof. Kenny de Meirleir, has in June 2009 launched the Neurotoxic Metabolite Test (NMT), a test to detect elevated Hydrogen Sulphide/Sulfide (H2S) levels based on abnormal level of certain metabolites in the urine. Please see the Identification page for more information. Please see the Viruses page for more information about Kenny de Meirlier and his work on RNaseL.
www.proteabiopharma.com/page/diagnostics.php
www.proteabiopharma.com

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US Laboratories:

Genova Diagnostics (formerly known as The Great Smokies Laboratory) is an excellent resource for a wide variety of blood/urine/faecal tests, such as Amino Acid Analysis Profile and Metabolic Analysis Profile. The site contains detailed information, sample reports and interpretation guidelines for a wide variety of test types. It also contains a contact form for information about practitioners in your area that use Genova. Genova also have local agents in many countries across the world who conduct the testing on their behalf and are fully approved.
www.gdx.net/home
Genova Diagnostics do not have a page that lists all available tests as such, but offers search pages to find the test you are looking for. Click here to search for Profile Name or here to search for tests under Disease or Condition.

Doctor's Data is a great laboratory with high tech equipment for performing hair analyses, amongst other tests.
www.doctorsdata.com
http://www.doctorsdata.com/tests_assessments_info.asp

EnteroLab is a laboratory that provides gluten intolerance testing.
www.enterolab.com

IGeneX in Palo Alto, California, is a laboratory specialising in Tick-Bourne Disease testing, i.e. Lyme Disease and Lyme Co-Infections - they offer a unique extended Western Blot test, as well as IFA, PCR and FISH tests. All the tests on their requisition form marked as antibody tests are IFA if not otherwise specified. Results are faxed or posted to practitioner only (not emailed). Do not answer technical questions about tests from patients.
www.igenex.com

Fry Laboratories in Scottsdale, Arizona, founded by Dr Stephen Fry, MS, MD, specialise in Lyme and Co-Infection Tick-Bourne Disease Testing, and offer IFA serology tests (antibody tests) and Molecular Diagnstic Tests (PCR DNA tests). They also offer PCR testing for Protomyxzoa rheumatica (FL1953), a lipid-loving, biofilm-forming protozoan that is transmitted by mosquito bites in certain regions of the US - an organism discovered by Dr Fry. Global prevalence is undetermined at this time. Toxoplasma and Coxiella PCR and IFA tests are also offered.
They also offer microscopic tests , which are able to detect bacterial or protozoan biofilms and a wide variety of organisms:
- Stained Smear MMG (Modified May- GrŸndwald Stain a.k.a. Special Stains test) to detect blood borne infections and is best suited for the detection of very small and intracellular bacteria etc. The MMG test includes a photograph and report;
- Traditional Giemsa - smear test used to confirm blood-borne infections found on Stained Smear MMG using a thin and thick smear preparation. This test is performed automatically as part of the Stained Smear MMG.
- Fluorescent DNA Stain (a.k.a. Advanced Stains test), a unique cutting edge test using highly specific DNA dyes to aid in visualising infections and blood-borne biofilm communities - including a photograph and report.
- Oragnismal Enrichment - test utilising an enrichment protocol to produce a higher yield of detectable parasitic infections and biofilm structures. Included as part of the Fluorescent DNA Stain test.
These microscopic tests have a greater accuracy, sensitivity and reliability than standard live blood microscopies that are routinely performed by naturopaths. Fry labs are very helpful in answering technical questions about their tests from patients (that does not constitute medical advice). (
http://www.frylabs.com/

Spiro Stat Technologies, based in Lubbock, Texas, specialise in Lyme Disease and Co-Infection PCR testing, as well as Fungi testing. They have a comprehensive list of organisms in their database and are able to test for multiple geni and species concurrently. They recommend taking multiple blood samples from different locations to increase likelihood of successful detection. .
http://www.spirostat.com/

Advanced Laboratory Services, in Sharon Hill, PA, offer Spirochete/Borrelia culture tests, as opposed to antibody, lymphocyte or DNA/RNA testing for Borrelia. Spirochetes are cultured from patient's blood samples, if present. Currently only offer tests to North American residents because of shipping delays overseas.Joe Burrascano is on the board of directors and consulted with the lab to assist in the creation of their culture test.
http://www.advanced-lab.com/

UNEVX Clinical Laboratory, in the medical campus of the University of Nevada in Reno, was founded by Dr Sanford H. Barksy, M.D., and is wholly owned by the Whitemore Peterson Institute (WPI). The lab is engaged in clinical trials as well as offering diagnostic testing services. Tests include Immune Profiles, Human Herpes Infection Profile (EBV, CMV, HHV6, HHV7), Cykokine profiles, Mycoplasma (hominis, penumoniae, fermentans) PCR, Chlamydia pneumoniae (Cpn) PCR, Heavy Metals Sensitivity Test (HELP), Intestinal Dysbiosis Profile (Immunobilan) etc. Samples are only accepted from within the USA however (international samples not accepted).
http://unevx.com/

EMSL Analytical have a series of laboratories in the USA. They offer a wide variety of lab services, including microbiological tests such as the ERMI test (the EPA's Environmental Relative Moldiness Index) which is a mold test for one's home (using dust collected from vacuum cleaner).
http://www.emsl.com

LabCorp (Laboratory Corporation of America) offer a variety of genetic testing services including HLA Testing, including PCR testing for HLA DR Genes (Human Keukocyte Antigens) - to determine one's level of susceptibility to biotoxins (from mold or other infections such as Borrelia etc.) To determine if one is multisusceptible, mould susceptible, prescence of Borrelia or Post-Lyme Syndrome, Dinoflagellates, Multiple Antibiotic Resistant Staph Epidermis (MARCoNS), low risk mould or no recognised significance. LabCorp also offer MSH testing, an indicator of biotoxin exposure.
http://www.labcorp.com
https://www.labcorp.com/wps/portal/dna/hla

Quest Diagnostics USA offer a huge variety of tests, including MMP9, VEGF, Leptin tests which can be markers of biotoxin exposure.
http://www.questdiagnostics.com

Richie Shoemaker, MD offers the Visual Contrast Sensitivity or VCS APTitude test for biotoxin illness - either on line or as a hardcopy home test kit - from his web site Surviving Mold. His web site also offers (paid for) treatment guidelines, books and resources for physicians.
http://www.survivingmold.com/

Stereo Optical Co. Inc. in the USA provides the Visual Contrast Sensitivity Test (VCS) kit as well as a variety of other visual tests.
www.stereooptical.com/html/contrast-sensitivity.html

Metametrix Clinical Laboratory's web site is shown below.
www.metametrix.com/content/Home/Main
www.metametrix.com/content/DirectoryOfServices/Main

NeuroScience in the USA offer a wide array of Neurological, Endocrine and Immunological tests, and work with practitioners to provide Targeted Amino Acid Terhapy (TAAT) programmes designed to address the spectrum of neurotransmitter and hormone imbalances. They are able to provide contact details of doctors and practitioners in your area that work with their laboratory.
www.neurorelief.com

Hemex Laboratories specialise in blood coagulation tests, e.g. ISAC (Immuno Solid-phase Allergen Chip) test, usually in conjunction with hypercoagulation through viral infection.
www.hemex.com

The Holtorg Medical Group, Inc., the Center for Hormone Imbalance, Hypothyroidism and Fatigue is located in Torrance, CA. They offer in house hormone testing at their laboratory.
http://hormoneandlongevitycenter.com

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Australian Laboratories:

ARL Pathology offer a number of tests, including the Functional Liver Detoxification Profile (FLDP):
www.arlaus.com.au
www.arlaus.com.au/sub.php?page=tests
www.arlaus.com.au/clinical_guides/FLDP%20Guide.pdf

Australian Biologics offer a variety of blood tests for Mycoplasma DNA testing, food sensitivity testing, chemical sensitivity testing and much more. Click on Testing Services on the left on their home page for more information.
www.australianbiologics.com.au/

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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.

• Oxygenation, Breathing, Heart Rate and Blood Pressure Tests
  
  The first half of the QIFT test consists of direct measurement of continuous breathing movements, pulse (heart rate or HR), the ECG R-R intervals (the elapsed time between two consecutive R waves in the electrocardiogram - each wave representing a heart beat), systolic blood pressure (SBP), diastolic blood pressure (DBP) - and tissue O2 and CO2 levels if conducted alongside the Transcutaneous Gases test described below) - in conjunction with a number of 'exercises' or manipulations of the autonomic nervous system.
  
  The patient is monitored using a small finger appliance, a number of sensor pads placed around the thorax and a special belt around the chest is used to monitor continuous breathing movements.
  
  An electrocardiogram, a thoracic interpretation of electrical activity of the heart over time, is monitored continuously throughout the duration of the autonomic examination - using the the Neuroscope method, created by Medifit Instruments Ltd. Whilst the neurologist examines the data as the test goes on, the data is also saved (with appropriate electronic markers placed into the data to signify the different phases of the test) so it can be examined in further detail after the event. Interpretation of test data is based on a normal range of values and patterns that have been obtained using standardised procedures to minimise unnecessary variances.
  
  The body is monitored in a variety of bodily positions, each posture or change in posture, and the response of the heart, has a clinical significance. The body undergoes a variety of physiological changes and adaptations, instigated by various receptors in the body, following posture changes, to properly regulate our blood pressure, heat rate and physiological requirements.
  
  
  • Supine Position -reclining horizontally
  
  
  • Head tilted backwards
  
  
  • Sitting up straight
  
  
  • Standing up

A change in the mean SBP of more than 25mmHg suggests orthostatic instability (a.k.a. orthostasis or postural cardiac instability), often associated with poor inotropic (strengthening of cardiac muscle action) response. Whilst orthostatic hypotension may not be present, other forms of orthostatic maladaptation may be present, including poor BP stability.

A sustained drop in DBP by 10mmHg or more within 3 minutes of having assumed an erect posture in comparison with the level in a horizontal posture, is an indication of orthostatic hypotension (a.k.a. postural hypotension - a sudden drop of blood pressure when a person stands up, a 'head rush'). When a healthy person stands up, the blood pressure increases hugely momentarily, but then drops down again 'like a stone' to a normal level. This reflex is designed to preserve blood flow into the brain and to maintain consciousness. An example of very poor control of BP when standing up, would follow the usual pattern of a big increase in BP followed by a sharp drop in BP, but then a period of oscillation of BP, fluctuating, until it eventually settles down.

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.

The presence of tachypnoea, abnormally rapid breathing, can be detected on the screen with data fed from the breathing belt.

Various exercises are performed, to test specific types of cardiac response, either parasympathetic or sympathetic.

The first segment of exercises are measures of parasympathetic function (rest and digest), with the exception of the third exercise which affects both parasympathic and sympathetic functions. Vagal tone, a.k.a. parasympathetic nervous system tone, is the effect producedon the heart when only the parasympathetic (rest and digest) nerve fibres (carried in the Vagus nerve - follows the jugular vein) are controlling the heart rate. The parasympathetic nerve fibres slow the heart rate down from approximately 70bpm to 60bpm. Vagal tone is measured according to a medical scale known as the Linear Vagal Scale (LVS).

• Deep Breathing Exercise - this is a 10 second cycle of deep inhalations and exhalations. This strengthens the parasympathetic nerve signals to slow the heart rate down. The above parameters are measured before, during and after the deep breath. It is used to stimulate the target-organs inside the brain stem to produce a measurable cardiovascular reflex, in this case, a drop in heart rate. During deep breathing we expect to see a significant rise in O2 levels and a significant drop in CO2 levels. A late and slight change in these gas levels in the deep breathing exercise is seen as a sign of poor gas diffusion in the tissues.

The second segment of exercises are primarily measures of sympathetic function (fight or flight response) and also parasympathetic function (rest and digest). These tests are designed to stimulate a variety of target-organs. The carotid massage exercise stimulates the parasympathetic function whereas the Sustained Isometric Exercise abolishes the parasympathetic function.

• Carotid Massage - Manual manipulation of the carotid artery in the throat by the neurologist. This artery is pressed by by the neurologist's finger for a specified number of seconds. One side of the neck is 'massaged' in this manner at a time. The massaging is the direct stimulation of the target-organs in the jugular vein. Carotid massage influences both sympathetic and parasympathetic mechanisms. Cartotid massage has a cardioinhibitory effect, a brainstem response that can be measured in the form of increased cardiac vagal tone (decreased heart rate), i.e. a measurement of cardiodepressor function. Carotid massage is also used to elicit a vasodepressor effect (on baroreflex function) measured as a decrease in SBP, but little change in HR. This response occurs due to vasodilation, probably as a result of a withdrawal of sympathetic nervous system tone. For example, there may be a normal cardiodepressor effect but failure of the vasodepressor effect of the carotid reflex.


• Sustained Isometric Exercise - performed using a stiff hand gripper pressed together in one hand for 3 minutes. One arm is exercised at a time, which a short break in between. Recordings in the third minute of the isometric exercise are compared with rest levels immediately prior to commencing the exercise in the same posture (for each of the two parts of the exercise - i.e. for each arm). This sustained isometric exercise is used to abolish the parasympathetic tone in order to assess the sympathetic tone, i.e. to withdraw/abolish the parasympathetic negative feedback control on the cardiovascular system so that the sympathetic cardioaccelerator function in the cardiac muscle and sympathetic vasoconstrictor response (and general level of control) of the blood vessels in the skeletal muscles can be assessed. The presence of central gain of the baroreflex system (i.e. excessive baroreflex response (BP increase) to exercise) can be assessed (if present). The mixture of sympathetic and parasympathetic target-organs can be assessed independently. These target-organs are located in the large blood vessels including the heart and also deep inside the body. HR (R-R interval) is used as a measure of sympathetic activity in the heart muscle. The gradient of the rise in DBP rise in the ejection phase of the cardiac cycle is used an an index of beat-to-beat left ventricular inotropic function. Sustained exercise involves the adrenaline pathway. This test is a useful measure of inotropic response during sustained exercise, which may be inadequate or even higher than normal. Any inotropic substances consumed prior to the test or indeed recently, e.g. black or green tea, may well give a falsely elevated inotropic response during this isometric exercise test, as discussed above.

The third segment of exercises are primarily measures of sympathetic function (fight or flight response). These tests are designed to stimulate the target-organs deep inside the body.

• Single Respiratory Gasp - this induces sympathetic Emotional Sudomotor Function (ESF) effects, shown by changes in skin response, e.g. sweating of the palms of hands and soles of feet. This can be measured by the Galvanic Skin Response (GSR), a measure of measuring electrical resistance of the skin between two points (on the palm of the hand usually). This test is optional and was not performed with me.


• Valsalva manoeuvre - performed by blowing against a high resistance tube at an even rate for a predefined length of time. The subject sits upright, without moving his legs, whilst leaning forwards slightly. This ejects blood out of the heart over a period of around 10 seconds by greatly increasing intrathoracic pressure, thereby impeding venous return of blood into the right atrium. The Valsalva manoeuvre tells us what the body is doing to compensate for the insufficient blood returning to the heart when the intrathoracic pressure is raised. The major organs of the abdomen constrict in order to push blood back into the thorax.
  
  The three phases of the Valsalva manoeuvre are described below. All 3 phases occur whilst the patient is blowing against an obstruction or resistance. The return to more cardiac and circulatory function occurs after the Valsalva manoeuvre has been stopped (i.e. after Phase IIi has ended).
  
  
  • Phase I - there is an initial rise in BP on account of the pressure on the great blood vessels in the thorax.
  
  
  • Phase IIe - the early, sharp drop in SBP and DBP on account of a sustained reduction in the venous return of blood caused by the positive intra-thoracid pressure.
  
  
  • Phase IIi is the recovery of both the SBP and DBP (bounce back of BP) against the positive intrathoracic pressure being applied by the Valsalva manoeuvre. This rise in BP is caused by the sympathetic mobilisation of a reserved volume of blood ('auto-transfusion') from the splanchic vascular bed, stimulated by the crisis of reduced blood volume in the heart. The Inferior Vena Cava (IVC) - the large vein that carries de-oxygenated blood from the lower half of the body into the right atrium of the heart) -carries more than 2/3rds of the venous return, but venous return from the lower limbs is dependent largely on the muscle pump effect. If the BP rises too high, it is an indication of the adrenaline system being too active (potentially an allergic response).

The standardised Valsalva manoeuvre is therefore use to mechanically reduce the volume of blood returning to the heart so that the sympathetically mediated reflex 'auto-transfusion' can be initiated and examined in a controlled manner. The Valsalva manoeuvre allows us therefore to assess the sympathetic adrenergic function in the splanchnic vascular bed - to assess the BP responses in each part of the Valsalva manoeuvre and afterwards when normal venous blood flow to the heart returns. Adrenergic function describes those receptors that are the targets of catecholamines, the stress hormones. The splanchic nerves are those of the organs of the thorax or abdomen. The pulmonary vascular bed describes the blood vessels of the lungs. Phase IIi is a measure of the splanchnic sympathetic tone of the deep organs of the sympathetic division of the autonomic nervous system, which may be normal, or perhaps raised, for example. If raised, it may be an indicator of increased immuen activity in the patient and often consistent with the presence of ASBAs and may cause dysmotility (abnormal or uncoordinated muscle movement of peristalsis) in the gut.

If the legs are not moved during the Valsalva manoeuvre, which are a large reservoir of blood volume, then one can specifically measure the compensatory mechanism in the abdomen (a.k.a. 'reflex autotransfusion' (Keele, et al., 1982) - i.e. a reflex to give oneself one's own blood). In Phase IIi, the reserves of blood in the organs of the splanchic bed are employed to provide an emergency venous flow of blood to the heart. These organs contain the wider blood vessels of the liver, spleen and kidney, that are used for filtering blood and thus contain a large amount of blood that can be utilised for other purposes in an emergency. These organs squeeze the blood out which is the pushed back into the heart as venous blood return, causing the SBP and DBP to rise again.

The patient leans forwards slightly in order to exclude any possible contribution to the blood flow from the vasoconstrction of muscle-pump effect in the lower limbs to the recovery of the SBP and DBP, allowing the neurologist to assess the splanchnic sympathetic adrenergic function selectively.

The gradient of BP rise during the ejection of blood from the heart provides us with information about the function of the heart ventricles (i.e. inotropic function - the alteration of the force or energy of cardiac muscular contractions). The longest ECG R-R interval occurs after the Valsalva manoeuvre, in contrast to the shortest R-R interval during the Valsalva manoeuvre.

As well as examining the abnormalities in blood pressure, breathing, heart rate and oxygenation level maintenance and patterns, and which body positions or exercises they are particularly unstable or abnormal, it is possible to infer the extent of Abnormal Spontaneous Brainstem Activation (ASBAs), which is manifested as sporadic and random fluctuations in blood pressure and pulse rate. The brainstem controls all the involuntary body functions (breathing and heart rate.) Severe abnormalities in BP and HR maintenance can have a huge impact on fatigability and energy levels.


• Cold Water Challenge
  
  The second half of the QIFT involves the assessment of Thermoregulatory Vasomotor Function (TVF) in the skin using a cold water challenge. This measures the effects of temperature on the skin and the regulation of corresponding blood vessels in all four limbs. It could be considered part of the sympathetic (fight or flight) response of the body. The cold challenge is used to specifically elicit the thermoregulatory vasoconstrictor reflex of the sympathetic system from the target-organs in the skin. Whilst only the extremities of the four limbs are monitored, it could be assumed that whatever pattern is observed in the extremities in terms of thermoregulation also applies to a large extent in the core of the body. TVF can be manifested in a number of ways, for example poor management of body temperature, temperature sensitivity (e.g. to wind or drafts) etc.
  
  Waterproof sensors (attached to a four channel laser Doppler flow meter (by Moor Instruments Ltd) are used to measure skin blood flow are placed on the extremities of all four limbs, i.e. the backs of the hands and feet. The effect on the blood flow in all 4 limbs are monitored during the test.
  
  
  • The right hand is first immersed in warm water (40C) for 2 minutes to maximise vasodilation
  • It is then immediately plunged into a tub of cold water (10C) for 2 minutes to evoke vasoconstruction
  • The cooled hand is then immediately reimmersed in the warm water (40C) for 2 minutes (i.e. re-warming)
  • After a couple of minutes break the experiment is repeated on the other hand (the left hand)

A normal response is a simultaneous decrease in blood flow to all 4 limbs when only one hand is rapidly cooled (the cooling phase), and a simultaneous return to baseline in all 4 limbs upon warming the hand in question (the re-warming phase). Abnormalities in thermoregulation (i.e. TVF) can be identified in this manner, which may include little or no response upon cooling or rewarming, or even the opposite expected response (i.e. increase in blood circulation when it should be decreasing, etc.).

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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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