Hompes Method. Practitioner Training Level II. Spring 2014 Class. Lesson Twelve Part Three Organic Acids & Lipid Peroxides

Transcription

1 Hompes Method Practitioner Training Level II Spring 2014 Class Lesson Twelve Part Three Organic Acids & Lipid Peroxides Health for the People Ltd not for reuse without expressed permission Hompes Method is a trading name of Health For The People Ltt Registered in England & Wales Company # VAT #

2 Organic Acids - Introduction In the previous lesson we looked at a number of different test options for detoxification capacity: Complete blood count Detoxification capacity test (caffeine, aspirin, acetaminophen) UBAS Hepatic detox profile Creatinine clearance Genetic polymorphisms

3 Organic Acids - Introduction To do all these tests individually would be inconvenient for the majority of clients and patients, especially on top of GI testing, etc. Organic acids testing is an effective alternative and carries a couple of major advantages: It requires a single sample It helps to identify many other metabolic imbalances

4 Organic Acids - Introduction We ll be covering organic acids testing in great detail over the coming weeks, but for now let s focus on the direct markers of toxicity and oxidative stress.

5 What Are Organic Acids? Organic acids are metabolic intermediates produced in pathways of central energy production, detoxification, neurotransmitter breakdown, and intestinal microbial activity. Accumulation of specific organic acids in urine often signals a metabolic inhibition or block. This abnormality may be due to a nutrient deficiency, an inherited enzyme deficit, toxic build-up, or drug effect.

6 What Are Organic Acids? Assessing organic acids provides a view into the body's cellular metabolic processes and the efficiency of metabolic function. Identifying metabolic blocks or problems with detoxification, gut dysbiosis, or oxidative stress that can be treated nutritionally allows for individual tailoring of interventions.

7 What Are Organic Acids? Identifying metabolic blocks that can be treated nutritionally allows individual tailoring of interventions in order to maximize client/patient responses and lead to improved outcomes.

8 Detoxification and Organic Acids Organic acids can provide an excellent indication of whether your client or patient s detox system is overwhelmed. It provides indicators of acute toxic exposure, nutritional insufficiency, amino acid metabolism and liver/kidney overload. It also provides markers for oxidative stress, inflammation and gut issues. When these are present, it s common to see challenges and overload of the detox pathways.

9 Detoxification and Organic Acids Metametrix Interpretive Guide

10 Detoxification and Organic Acids Metametrix Interpretive Guide

11 Detoxification and Organic Acids

12 Detoxification Markers and Organic Acids

13 Detox Markers - 2-Methylhippurate Urinary excretion of 2-methylhippurate is a sensitive and specific marker for xylene exposure which increases oxidative stress. Xylene is a common solvent present in household and workplace air, exhaust fumes, etc. It s pretty ubiquitous new paint, spray paint, new carpet, new cars, dry cleaning fluid, cleaning solvents, paint thinners, building products, fuel and exhaust fumes, etc.

14 Detox Markers - 2-Methylhippurate Xylene is oxidized in a Phase 1 detoxification reaction to 2- methylbenzoate; then in Phase II (glycine conjugation) it becomes 2-methylhippurate.

15 Detox Markers - 2-Methylhippurate If 2-methylhippurate comes back elevated, you know a person has ongoing exposure to (at least) xylene and probably other chemicals. It may also indicate insufficient glycine levels for detoxifying xylene, etc.

16 Detox Markers - Orotate Ammonia is a by-product of normal metabolism. It is detoxified through the urea cycle, which takes place in both the liver and kidneys. Excess ammonia is very toxic and can cause significant symptoms. Elevated urine orotate indicates ammonia toxicity.

17 Detox Markers - Orotate Orotate levels increase in the urine when urea cycle capacity is exceeded and is a very sensitive marker to anything that increases ammonia in liver:

18 Detox Markers - Orotate Possible causes of high orotate: High meat intake Dysbiosis Arginine deficiency (arginine is the key nutrient for detoxification) Possible need for magnesium Long term oral glutamine supplementation above 10 gm/day (rare)

19 Detox Markers - Glucarate Glucarate is an indicator of overall hepatic (liver) detoxification demand phase I and glucoronidation. High urinary glucarate suggests above normal exposure to pesticides, herbicides, fungicides, petrochemicals, alcohol, pharmaceutical compounds, or toxins produced in the gastrointestinal tract.

20 Detox Markers - Glucarate Elevated glucarate levels can indicate intestinal dysbiosis and exposure to: Fungal toxins Alcohol Food additives Drugs Pesticides, herbicides, fungicides Petrochemicals PAH Nitrosamines

21 Detox Markers- a-hydroxybutyrate (AHB) AHB is a marker of hepatic glutathione synthesis. GSH is an important antioxidant that helps protect against reactive oxygen species such as free radicals. GSH is constantly used up in the removal of toxic molecules and prevention of oxidative damage. AHB is a by-product from the process in which the body forms more glutathione.

22 Detox Markers- a-hydroxybutyrate (AHB) When that process is running at high rates, α- hydroxybutyrate excretion is increased If α-hydroxybutyrate is elevated then glutathione support may be recommended.

23 Detox Markers- a-hydroxybutyrate (a-hbd) The activity of α-hbd on the second day after a myocardial infarction is a marker for estimates of infarct size and a measure of reperfusion effectiveness. The intense energy demand of cardiac muscle is likely the reason for such high concentrations of α-hbd in that tissue, because α-hb strongly inhibits mitochondrial energy metabolism as measured by CO 2 production.

24 Detox Markers- a-hydroxybutyrate (AHB) Smoking, poor diet, and lack of exercise significantly inhibit the activity of α-hbd, suggesting that urinary elevation of α-hydroxy-butyrate may be related to these factors. High α-hydroxybutyrate is also found during phases of increased lymphocyte destruction in infectious diseases such as measles.

25 Detox Markers - Pyroglutamate Pyroglutamate elevates in urine when glutathione is being used up rapidly or when there is not enough methionine, glycine or cysteine for glutathione production.

26 Detox Markers - Pyroglutamate Glutathione is constantly used up in the removal of toxic molecules and prevention of oxidative damage. AHB is a by-product from the process in which the body forms more glutathione. When that process is running at high rates, AHB excretion is increased. Elevated levels of the marker pyroglutamate also reveal that glutathione is being lost at a high rate.

27 Detox Markers - Sulfate Elevated sulfate can indicate increased Phase II detoxification or inorganic sulfate intake. Low urinary sulfate is an indication that total body glutathione is low due to chronic demand and sulfur-containing amino acids are needed.

28 Detox Markers - Sulfate Since both pyroglutamate and sulfate are markers of sulfur compound depletion, explanation of the interpretation of various combinations of abnormalities is needed. Severe depletion of organic sulfur sources will cause simultaneous high pyroglutamate and low sulfate excretion.

29 Detox Markers - Sulfate High pyroglutamate with normal sulfate indicates inadequate organic sulfur sources for production of cysteine required for glutathione synthesis. Only organic sulfur in the form of compounds such as N- acetylcysteine or methionine will restore normal glutathione levels.

30 Detox Markers - Sulfate Normal pyroglutamate with low sulfate levels can occur in individuals with impaired sulfate activation. In these cases, rapid replenishment of hepatic sulfate may be accomplished with either sulfur donors like N-acetylcysteine or inorganic sulfate such as sodium sulfate.

31 Detoxification Markers - Sample Report 1

32 Detoxification Markers - Sample Report 2

33 Detoxification Markers - Sample Report 3

34 Detox Markers - Methylation In simple terms, methylation is a process in which certain chemicals called methyl groups are added to various constituents of proteins, DNA and other molecules. These are needed to keep them in good working condition.

35 Detox Markers - Methylation Methylation is a primary method of removing toxins in the phase 2 liver detoxification. With adequate methylation, we can detoxify with greater ease but without it, the body s ability to detoxify is undermined.

36 Detox Markers - Methylation An important methylation process is when it is applied to homocysteine, which is what remains when the amino acid methionine is used to methylate protein and DNA. Homocysteine needs to be methylated to convert it back to methionine. If this process does not happen, it s a big problem. As with everything, methylation must be balanced. Too much can be as bad as too little.

37 Detox Markers - Methylation There are four cornerstones to the methylation cycle and on each cornerstone sit four molecules: Homocysteine Methionine S-adenosylmethionine (SAMe) S-adenosylhomocysteine

38 Detox Markers - Methylation Each of these molecules leads into the next one by means of enzymes. The important co-factors that allow this to happen are the B vitamins such as folic acid, vitamin B 12 and vitamin B 6. In converting from S-adenosyl methionine into S-adenosyl homocysteine, a methyl group is given up and this can then be used to stick on to other molecules - hence the name, the methylation cycle.

39 Detox Markers - Methylation There are three groups of compounds that are helpful in methylation with varying levels of efficacy. They are: B Vitamins, B 6, B 12 and folic acid Tri-methyl-glycine TMG SAMe.

40 Detox Markers - Methylation

41 Detox Markers - Methylation Poor methylation, leading to increased levels of homocysteine is implicated in: Heart disease and stroke Higher levels of oxidized LDL cholesterol Dementia and Alzheimer s Liver Disease Depression Aging in general

42 Detox Markers - Methylation There are two methylation cofactor markers in organic acids testing methylmalonate (B 12 ) and formiminoglutamate (FIGLU folic acid). When elevated, these markers can indicate insufficiencies in methylation pathways, which can have a dramatic impact on detoxification, amongst pother body functions.

43 Detox Markers - Methylation We ll discuss the B 12, folic acid and B 6 markers in other organic acid lessons as pattern analysis is required to understand different marker combinations.

44 Methylation Sample Report 1

45 Methylation Sample Report 2

46 Methylation Sample Report 3

47 Detox Markers - Dysbiosis Recall from lesson 6C, that the organic acids profiles assess certain compounds that indicate the overgrowth of bacteria, parasites and Candida. By definition, these must also be considered markers of detoxification stress. Remember that all blood draining the gut goes directly to the liver.

48 Detox Markers - Dysbiosis The relevant markers are: Benzoate Hippurate Phenylacetate Phenylproprionate P-hydroxybenzoate P-hydroxyphenylacetate Indican Tricarballyate D-lactate 3,4-dihydroxyphenylproprionate D-arabinitol

49 Detox Markers Oxidative Stress One of the mechanisms by which toxins exert their influence on metabolism is by causing oxidative stress. We ll cover this topic in greater detail elsewhere in the course. For now, let s look at two key organic acid markers for oxidative stress.

50 Detox Markers Oxidative Stress P-Hydroxyphenyllactate (HPLA) is a metabolite of tyrosine and a marker of cell turnover. It may be useful for studying disorders of tyrosine metabolism, including inborn errors of metabolism, and liver disease. Elevated HPLA is associated with tumor growth and leukemia. HPLA is also a marker of hepatic encephalopathy in patients with hepatic cirrhosis.

51 Detox Markers Oxidative Stress HPLA is an important regulator of normal and malignant cell growth, and it appears to mediate the cancer promoting effects of estrogen. Thus, high urinary HPLA signals an increased tissue growth response that may be associated with neoplastic disease or increased growth of normal tissue.

52 Detox Markers Oxidative Stress Elevated levels of HPLA result in a dramatic decrease of ascorbic acid (vitamin C) concentration in the liver, adrenal glands, and blood. High doses of ascorbic acid (100 mg/kg body weight daily) were shown to arrest or significantly inhibit the excretion of HPLA in patients with hemoblastoses and nephroblastoma.

53 Detox Markers Oxidative Stress When considering oxidative stress and explaining it to clients I find it helpful to imagine a pinball machine. You fire off the pinball and off it goes, bouncing around everywhere in a completely uncontrolled fashion. It bumps into things and causes damage (oxidative damage).

54 Detox Markers Oxidative Stress Sustained inflammatory responses cause increased production of reactive oxygen species (ROS). When local antioxidant protection fails to keep reactive oxygen species in check, there are molecular consequences for every class of structural molecule.

55 Detox Markers Oxidative Stress 8-Hydroxy-2 -deoxyguanosine (8-OHdG) is a product of oxidative damage to DNA. It is recognized as a useful marker in estimating DNA damage induced by oxidative stress. Oxidative DNA damage is common in various forms of chronic liver disease,suggesting a link between chronic inflammation and hepatocarcinogenesis.

56 Detox Markers Oxidative Stress Why would the liver be chronically inflamed? Bad foods Bad bugs Bad toxins Plus inadequate levels of antioxidants, amino acids and other protective nutrients.

57 Detox Markers Oxidative Stress The antioxidant protection in young children was evaluated by urinary 8-OHdG. 8-OHdG formation is sufficiently sensitive to reveal even mild chronic effects of ROS. The association of cancer with chronic psychological stress and perceived overwork may be via the formation of 8-OHdG.

58 Detox Markers Oxidative Stress Increases in 8-OHdG with cigarette smoking is associated with aging and enhancement of oxidative damage in human lung tissues. 8-OHdG levels rise with age in adults with mild hypercholesterolemia or/and mild hypertension.

59 Detox Markers Oxidative Stress Lower levels of antioxidants may predispose to oxidative stress, which is manifested by higher levels of 8-OHdG. Levels of 8-OHdG were significantly higher in atherosclerotic patients and vitamin C levels were significantly lower. This oxidative stress may promote and worsen atherosclerosis.

60 Detox Markers Oxidative Stress Exposure to organochlorines does not result in elevated 8-OHdG, indicating that the genotropic effects of this compound are exerted through mechanisms other than ROS formation. A similar conclusion may be reached regarding moderate alcohol consumption, which seems to have the overall effect of reducing DNA damage, as shown by the decrease in 8-OHdG levels.

61 Detox Markers Oxidative Stress Diabetics tend to have higher urinary 8-OHdG excretion than healthy controls and the levels are related to the severity of tubulointerstitial lesions. Oxidative stress may contribute to the progression of tubulointerstitial injury in patients with diabetic nephropathy.

62 Oxidative Stress Sample Result 1 66 year old female; presence of heavy metals and high porphyrins also identified.

63 Oxidative Stress Sample Result 2 Female, 70 years old chronic oral inflammation and digestive problems.

64 Lipid Peroxides Lipid peroxides are the products of chemical damage done by oxygen free radicals to the polyunsaturated fatty acids of cell membranes. They cause a variety of toxic effects at the cellular level and their formation is considered a pathological process in biological systems. Their formation can be repressed by antioxidants, such as vitamins C and E.

65 Lipid Peroxides Biohealth Diagnostics (101 or urine): The level of lipid peroxides is an index of cell / organelle membrane damage caused by free radicals. Membrane proteins, membrane lipids and cholesterol can be damaged due to an insufficiency of antioxidants to deal with the level of oxidative stress/free radicals.

66 Lipid Peroxides Metametrix (TBARS serum) Lipid peroxides are the products of chemical damage done by oxygen free radicals to the polyunsaturated fatty acids of cell membranes. Using a blood test (plasma analysis), the total thiobarbituric acid-reactive substances (TBARS) can be measured, providing an index of lipid peroxidation.

67 Organic Acids - Summary As you can see, organic acids is a phenomenal test for examining a person s detoxification status because it contains such a wide variety of useful markers. The inclusion of gut dysbiosis, oxidative stress and methylation markers over and above the six liver / ammonia markers is convenient and offers outstanding value for money in my opinion.

68 Organic Acids Disclaimer Important note: the organic acids test does not replace comprehensive liver tests for cases of advanced liver disease.

69 Thank you! As always, thanks a million for tuning in. In Lesson twelve, part four, we ll look at the specific testing to evaluate oestrogen metabolism, which is yet another important consideration in toxicity and detoxification.