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Detoxification

Detoxification. Leo Galland M.D. Foundation for Integrated Medicine. OUR BODIES DETOXIFY. Exogenous, foreign substances Endogenous, internally created substances. ENDOGENOUS SUBSTANCES. Gut toxins bacteria parasites yeast Hormones Bile acids Metabolic intermediates.

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Detoxification

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  1. Detoxification Leo Galland M.D. Foundation for Integrated Medicine Foundation for Integrated Medicine

  2. OUR BODIES DETOXIFY • Exogenous, foreign substances • Endogenous, internally created substances Foundation for Integrated Medicine

  3. ENDOGENOUS SUBSTANCES • Gut toxins • bacteria • parasites • yeast • Hormones • Bile acids • Metabolic intermediates Foundation for Integrated Medicine

  4. EXOGENOUS SUBSTANCES • Xenobiotics • herbicides • pesticides • Air pollutants • auto exhaust • tobacco smoke • Pharmaceuticals Foundation for Integrated Medicine

  5. DETOXIFICATION TRANSFORMS MOLECULES • Functionalization Phase I • Conjugation Phase II Foundation for Integrated Medicine

  6. MAJOR SITES OF ENZYMATIC DETOXIFICATION • Liver • most important organ • Lung, intestine, kidney & skin • demonstrable detox capability Foundation for Integrated Medicine

  7. LIVER DETOXIFICATION • PHASE ONE: OXYGENATION • PHASE TWO: CONJUGATION Foundation for Integrated Medicine

  8. PHASE ONE ENZYMES • Cytochrome P450 system (20-30 enzymes) • Use oxygen to alter molecules • By-products include free oxygen radicals • End products may be more dangerous than the initial chemicals Foundation for Integrated Medicine

  9. Foundation for Integrated Medicine

  10. PHASE ONE ACTIVITY • Increased in tobacco smokers • Increased or decreased by medications • Increased by char-broiled meats and high intake of alcohol, BHT or vegetable oils • Variably influenced by phytochemicals, especially flavonoids • Decreased in vegans Foundation for Integrated Medicine

  11. PHASE ONE INDUCERS • cabbage, broccoli, brussel sprouts (indole-3-carbinol) • oranges and tangerines (limonene) • caraway and dill seeds (limonene) Foundation for Integrated Medicine

  12. PHASE ONE INHIBITORS • grapefruit (naringenin) • turmeric (curcumin) • capsicum (capsaicin) • cloves (eugenol) • onions (quercetin) Foundation for Integrated Medicine

  13. ZINC DEFICIENCY DISRUPTS PHASE ONE ACTIVITY, SHIFTING ENZYME PATTERNS TO INCREASE THE PRODUCTION OF CANCER PROMOTERS Foundation for Integrated Medicine

  14. PHASE TWO:CONJUGATION • sulfate • amino acids: glycine, taurine, glutamine, ornithine, arginine • glutathione • methylation • glucuronic acid Foundation for Integrated Medicine

  15. PHASE TWO INHIBITION • nutritional deficiency • toxin exposures that exhaust supplies of substrates or co-factors • example: acetaminophen, alcohol and low protein intake deplete glutathione, which is needed for acetaminophen detoxification Foundation for Integrated Medicine

  16. PHASE TWO STIMULATION • cabbage, broccoli, cauliflower, brussel sprouts, kale (glucosinolates) • garlic oil, rosemary, soy • citrus peel, dill and caraway oils (limonene) • curcumin • S-adenosyl methionine (SAM) • milk thistle (silymarins) Foundation for Integrated Medicine

  17. Glucosinolates Must Be Hydrolyzed by the Enzyme Myrosinase • Glucosinolates (>70 types) are separated from myrosinase in plants, not sprouts • Crushing the plant before cooking liberates the active phytochemical • Sulforaphane releases nuclear respiratory factor-2 (Nrf2), induces glutathione S-transferase Foundation for Integrated Medicine

  18. Glucosinolates Must Be Hydrolyzed by the Enzyme Myrosinase • Indole-3-carbinol is converted to diindolyl methane (DIM) by acid conjugation in the stomach • DIM stimulates CYPA1/1A2, which alters estrone metabolism to reduce estrogenic activity and inhibit growth of breast cancers Foundation for Integrated Medicine

  19. PHASE TWO GENETICS • Genetic variation in the activity of different Phase two enzymes in the liver, brain or intestines may account for disease susceptibility: • colon cancer • breast cancer • Parkinson’s disease Foundation for Integrated Medicine

  20. ANTIOXIDANT BENEFITS • protect DNA and cell or organelle membranes from free radical damage • elevate levels of glutathione • stimulate immune responses • increase activity of tumor suppressor genes • inhibit activity of enzymes needed for tumor growth Foundation for Integrated Medicine

  21. ANTIOXIDANT PROTECTION • vitamins E and C • carotenoids (carotene, lycopene, lutein) • flavonoids • selenium • glutathione • lipoic acid Foundation for Integrated Medicine

  22. Foundation for Integrated Medicine

  23. PLANT FUNCTIONS OF FLAVONOIDS • Production stimulated by lack of light • Stress: microbes, heavy metals, ozone, sulfur dioxide, pH changes • Inhibit photo-oxidation and microbial growth Foundation for Integrated Medicine

  24. CLASSES OF FLAVONOIDS • Glycosides • rutin, hesperidin • Aglycones • flavonols (quercetin) • anthocyanidins (catechin) • Proanthocyanidins • dimers, trimers of anthocyanidins • Tannins • polymeric anthocyanidins Foundation for Integrated Medicine

  25. FLAVONOID EFFECTS ON MAMMALIAN CELLS • Potent anti-oxidants • quench free radicals • chelate transition metals • Inhibit oxygenases: PG synthetase • 5-lipoxygenase • Alter activity of ION pumps Foundation for Integrated Medicine

  26. Foundation for Integrated Medicine

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  31. METHYLATION • protects DNA from mutation • depends upon methionine (SAM), folic acid, vitamin B12 • enhanced by dimethylglycine (DMG), choline, betaine • CAVEAT: methylation inactivates genes; aberrant methylation may inactivate tumor suppressor genes Foundation for Integrated Medicine

  32. THE INTESTINES AND DETOXIFICATION • absorption and excretion of toxins • second largest volume of detox enzymes • intestinal toxicity stresses the liver Foundation for Integrated Medicine

  33. DETOXIFYING AGENTS • dietary fiber (beans, grains) • antioxidants (vegetables, seeds, fruit) • Phase Two inducers (crucifers) • glutathione enhancers (selenium...) • methylation enhancers (folic acid...) • spices (turmeric, rosemary) • herbs (milk thistle, Ginkgo biloba) Foundation for Integrated Medicine

  34. AB, 6 year old girl with psoriasis • Prior to age 3: infantile colic, rarely ill • Age 3: otitis media associated with guttate psoriasis, treated with steroids and dovenex • Naturopath: avoid junk food, use flax oil and primrose oil progressively worse • On a 50% fruit and vegetable diet, nightshade free dramatic improvement, leaving few tiny patches on arms Foundation for Integrated Medicine

  35. AB, 6 year old girl with psoriasis • Her psoriasis controlling diet -Breakfast: Granola, soy milk, water -Lunch: Whole wheat bread, tuna, cheese, almond butter, fruit conserves, water -Dinner: Chicken, salmon, noodles, brown rice, salad, vegetables -Snacks: fruits and vegetables Foundation for Integrated Medicine

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