Detoxification

Leo Galland M.D.

Foundation for Integrated Medicine

Foundation for Integrated Medicine

OUR BODIES DETOXIFY

• Exogenous, foreign substances • Endogenous, internally created substances

Foundation for Integrated Medicine

ENDOGENOUS SUBSTANCES

• Gut toxins – bacteria – parasites – yeast • Hormones • Bile acids • Metabolic intermediates Foundation for Integrated Medicine

EXOGENOUS SUBSTANCES

• Xenobiotics – herbicides – pesticides • Air pollutants – auto exhaust – tobacco smoke • Pharmaceuticals Foundation for Integrated Medicine

DETOXIFICATION TRANSFORMS MOLECULES

• Functionalization

Phase I

• Conjugation

Phase II Foundation for Integrated Medicine

MAJOR SITES OF ENZYMATIC DETOXIFICATION

• Liver – most important organ • Lung, intestine, kidney & skin – demonstrable detox capability Foundation for Integrated Medicine

LIVER DETOXIFICATION

• PHASE ONE: OXYGENATION • PHASE TWO: CONJUGATION Foundation for Integrated Medicine

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

Foundation for Integrated Medicine

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

PHASE ONE INDUCERS

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

PHASE ONE INHIBITORS

• grapefruit (naringenin) • turmeric (curcumin) • capsicum (capsaicin) • cloves (eugenol) • onions (quercetin) Foundation for Integrated Medicine

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

PHASE TWO:CONJUGATION

• sulfate • amino acids: glycine, taurine, glutamine, ornithine, arginine • glutathione • methylation • glucuronic acid Foundation for Integrated Medicine

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

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

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

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

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

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

ANTIOXIDANT PROTECTION

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

Foundation for Integrated Medicine

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

CLASSES OF FLAVONOIDS

• Glycosides – rutin, hesperidin • Aglycones – flavonols (quercetin) – anthocyanidins (catechin) • Proanthocyanidins – dimers, trimers of anthocyanidins • Tannins – polymeric anthocyanidins Foundation for Integrated Medicine

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

Foundation for Integrated Medicine

Foundation for Integrated Medicine

Foundation for Integrated Medicine

Foundation for Integrated Medicine

Foundation for Integrated Medicine

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

THE INTESTINES AND DETOXIFICATION

• absorption and excretion of toxins • second largest volume of detox enzymes • intestinal toxicity stresses the liver Foundation for Integrated Medicine

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

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

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