Detoxification

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

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Detoxification