foundation for integrated medicine detoxification leo galland m.d. foundation for integrated...

Foundation for Integrated Medicine

Detoxification

Leo Galland M.D.



OUR BODIES DETOXIFY

• Exogenous, foreign substances

• Endogenous, internally created substances


ENDOGENOUS SUBSTANCES

• Gut toxins– bacteria– parasites– yeast

• Hormones• Bile acids• Metabolic intermediates


EXOGENOUS SUBSTANCES

• Xenobiotics– herbicides– pesticides

• Air pollutants– auto exhaust– tobacco smoke

• Pharmaceuticals


DETOXIFICATION TRANSFORMS MOLECULES

• FunctionalizationPhase I

• ConjugationPhase II


MAJOR SITES OF ENZYMATIC DETOXIFICATION

• Liver

– most important organ

• Lung, intestine, kidney & skin

– demonstrable detox capability


LIVER DETOXIFICATION

• PHASE ONE: OXYGENATION

• PHASE TWO: CONJUGATION


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


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


PHASE ONE INDUCERS

• cabbage, broccoli, brussel sprouts (indole-3-carbinol)

• oranges and tangerines (limonene)

• caraway and dill seeds (limonene)


PHASE ONE INHIBITORS

• grapefruit (naringenin)

• turmeric (curcumin)

• capsicum (capsaicin)

• cloves (eugenol)

• onions (quercetin)


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


PHASE TWO:CONJUGATION

• sulfate

• amino acids: glycine, taurine, glutamine, ornithine, arginine

• glutathione

• methylation

• glucuronic acid


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


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)


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


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


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


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


ANTIOXIDANT PROTECTION

• vitamins E and C

• carotenoids (carotene, lycopene, lutein)

• flavonoids

• selenium

• glutathione

• lipoic acid


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


CLASSES OF FLAVONOIDS

• Glycosides– rutin, hesperidin

• Aglycones– flavonols (quercetin)– anthocyanidins (catechin)

• Proanthocyanidins– dimers, trimers of anthocyanidins

• Tannins– polymeric anthocyanidins


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


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


THE INTESTINES AND DETOXIFICATION

• absorption and excretion of toxins

• second largest volume of detox enzymes

• intestinal toxicity stresses the liver


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)


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


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 detoxification leo galland m.d. foundation for integrated...

Documents

integrated medicine

conjugation slide

conjugation phase

created substances slide

oxygenation phase

dill seeds limonene

acid conjugation

enzyme myrosinase indole