Detoxification Pathways. Theory and Application to Practice

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1 Detoxification Pathways Theory and Application to Practice 1

2 Detoxification Pathways Failure to detoxify Accumulation of Toxins Detoxification mechanism Importance to practitioner Phase 1 Biotransformation Phase 2 Conjugation Phase 3 Elimination Summary Application to practice 2

3 Failure to Detoxify symptoms Headache Muscle and joint pain Fatigue Irritability, Depression Mental confusion Flu like symptoms Allergic reactions (Hileman 1991) Gastrointestinal tract irregularities Cardiovascular irregularities 3

4 Failure to Detoxify conditions Inflammatory conditions (Rooney 1990) Rheumatoid Arthritis (Smith 1985) Parkinson s (Steventon et al 1990) Alzheimer s (Steventon et al 1989) Cancer (Heerdt et al 1995) CFS / ME (Racciatti et al 2001) 4

5 Accumulation of Toxins TOXIC BURDEN depends on Genetics Age Lifestyle diet, exercise, stress Environment 5

6 EXOTOXINS Drugs recreational, pharmaceutical Pesticides Industrial chemicals Food additives Environmental pollutants Cigarette smoke, car exhaust, barbecue fumes 6

7 ENDOTOXINS Intestinal bacteria Products of normal metabolism Free radicals Many substances become more harmful to the body as they pass through the detoxification process 7

8 The Process of Detoxification Natural Barriers Skin, Lungs, Gastrointestinal tract Rooney et al (1990) associate leaky gut syndrome with inflammatory joint disease Allison et al (1992) cite increased permeability to be due to imbalance of intestinal flora, use of NSAIDs, asprin 8

9 Processing and Eliminating Waste Liver Most intensive site of detoxification Intestines Second most intensive site Kidneys Blood and Bile 9

10 Importance of Detoxification Increasing exposure to foreign chemicals Increasing Stress Use of processed and nutrient poor foods Increasing access to and use of pharmaceutical drugs 10

11 Three Phases of Detoxification Phase 1 Biotransformation Introduces oxygen to form a reactive site Phase 2 Conjugation Adds water soluble group to reactive site Phase 3 Elimination Actively eliminates conjugates from the cell 11

12 Phase 1 Bioactivation Oxidation: substrates are amines, alcohols, aldehydes Hydroxylation: major pathway for cholesterol and endogenous estrogens Reduction: substrates are aldehydes and ketones 12

13 Phase 1 Bioactivation Introduction of oxygen into molecule by Cytochromes P 450 Enzymes / oxidases which are present in the liver, intestines, skin, lymphocytes, placenta and which catalyse reactions Over ten groups of CYP450 are present in humans Each enzyme may transform up to 20 toxins 13

14 Phase 1 Bioactivation Activity induced / accelerated by: Medications (e.g. epilepsy drugs) Xenobiotics pesticides, organophosphates, paint fumes Alcohol Tobacco, charcoaled meat both are active inducers of phase 1, with no phase 2 stimulation Natural substances hypericin, indole 3 carbinol (brassicas) 14

15 Phase 1 Bioactivation Activity inhibited by: Grapefruit juice (quercitin) Seville orange Turmeric (curcumin) Pomegranate (ellagic acid) Green tea (catechins) Milk thistle (silymarin) Watercress Hypothyroidism 15

16 Phase 1 Bioactivation Dietary co factors to support Phase 1 Niacin and other B Vitamins Antioxidants Vitamin C (Anderson & Kappas 1991) Bioflavanoids Zinc, Magnesium, Copper Molybdenum (Anderson & Kappas 1991) 16

17 Phase 2 Conjugation 35 genes control production of enzymes Glutathione conjugation Glucoronidation Methylation Sulfation Acetylation Amino acid conjugation 17

18 Glutathione conjugation (Phase2) Substrates: Benzopyrene (car exhaust, smoke, barbecue) Penicillin Paracetamol Heavy metals Bacterial toxins Fatty peroxides Alcohol Steroids 18

19 Glutathione conjugation (Phase 2) Inducers, co factors, conjugation moitetes: Glutamine, glutamate, glycine Cysteine, Methionine Indole 3 carbinol (flavanoid rosemary) Curcumin, ellagic acid Sulforophane (brassicas and horseradish) Vitamins B2,3,6,12, Se, Zn, Mg, Cu Inhibitors Co factor deficiencies 19

20 Glucoronidation (Phase 2) Substrates: Asprin, paracetamol Propranalol, benzodiazapenes Nitrosomes Carcinogens (Amdur et al 1991) Steroid hormones Serum estrogen (Heerdt et al 1995) 20

21 Glucoronidation (Phase 2) Inducers, co factors: Glutamine Fe, Mg, Vits B3, B6 D Limonene (esp lemon) Cynarin (globe artichoke) Fish oil Calcium D Glucarate S-adenosyl methionine (SAM) Obesity Inhibitors: Silymarin Fast (lack of glucose) Oxidative stress Hypothyroidism Gilbert s syndrome 21

22 Other Phase 2 pathways Methylation Substrates: Estrogens, heavy metals Inducers: Choline, inositol, methionine Co factors: SAM, magnesium, B vitamins Sulfation Substrates: Paracetamol, estrogen Inducers: Sulpher amino acids Co factors: Vitamin A, protein, sulphates 22

23 Amino acid conjugation (Phase 2) IMPORTANT AMINO ACIDS Glycine Taurine Glutamine Cysteine Arginine Ornithine 23

24 Phase 2 Conjugation Supportive: Watercress Green tea Phytoestrogens D Limonene Magnesium B Vitamins Carnitine (ATP) Complex carbohydrates Inhibitive: Alcohol High fructose intake Smoking Fasting Simple sugars Deficiency of co factors 24

25 Application for the Practitioner Individuality of Client Need for cell energy (ATP) Improve gut barrier Minimise exposure to toxins Support Cytochrome P450 activity (phase 1) Protect cell membranes against damage Stabilise blood sugar levels Co factors for phase 2 Elimination from cell and body 25

26 References Allison MC et al 1992 gastrointestinal damage associated with the use of non steroidal and anti inflammatory drugs N Eng J of Med327: Amdur MO et al 1991 The basic science of poisons N.Y. McGraw -Hill Anderson KE and Kappas A 1991 Dietary regulation of cytochrome P450 Annu Rev Nutr:11: Heerdt AS, Young CW, Borgen PI. Calcium glucarate as a chemopreventative agent in breast cancer Israel Journal of Medical Sciences (2-3),101-5 Hileman B Multiple Chemical Sensitivity C&EN July 22, 1991; Racciatti D et al 2001 Chronic fatigue syndrome following a toxic exposure Sci Total Environ 270(1-3) Rooney PJ 1990 A short review of the relationship between intestinal permeability and inflammatory joint disease Clinical and Experimental Rheumatology 12: Smith MD 1985 Abnormal bowel permeability in ankylosing spondylitis and rheumatoid arthritis J Rheumatol 12: Steventon GB et al 1989 Xenobiotic metabolism in Parkinson s disease Neurology39: Steventon GB et al 1990 Xenobiotic metabolism in Alzheimer s disease Neurology40:

27 Bibliography Hall DC 2001 Nutritional influences on estrogen metabolism Applied Nutritional Science Reports Advanced Met451 1/01 Nutrition Publications Inc Seeley RS, Stephens TD, Tate P 2006 Anatomy and Physiology New York, McGraw - Hill 27

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