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Foundation for Integrated Medicine
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
• FunctionalizationPhase I
• ConjugationPhase 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