Phase II Detoxification Flashcards
Phase II
A variety of chemical reactions which add functional groups to reactive toxins to make them safe to be released into the blood or bile for excretion via the kidneys or bowel:
*There are six primary phase II detoxification pathways, which are all highly dependent on the necessary substrates to carry out their function. Amino acids are of central importance.
Glucuronidation
Enzyme: UDP-Glucuronosyltransferases
Detoxifies: Oestrogens, NSAIDs, morphine, hydrocarbons.
Inhibited by: Aspirin, smoking, contraceptive pill, fluoride.
Requires: Glucuronic acid (e.g., from apples, alfalfa, broccoli).
Enhanced by: Citrus peel, brassica vegetables, turmeric.
Sulfation
Enzyme: Sulphotransferases (SULT)
Detoxifies: Steroid hormones (e.g., oestrogen), food additives, industrial chemicals.
Inhibited by: NSAIDs, tartrazine, molybdenum deficiency.
Requires: Sulphur-containing amino acids (esp. cysteine and methionine, Sulphur-rich foods (brassica veg; onion, garlic). Molybdenum (legumes, leafy veg, whole grains).
Acetylation
Enzyme: N-acetyl transferases (NAT)
Detoxifies: Smoke, HAAs, halides, histamine, sulphonamides
Inhibited by: Vitamin B and C deficiency.
Enhanced by: Vitamins B1, B5, vitamin C, butyric acid (SCFA).
Methylation
Enzyme: Methyltransferases e.g., COMT
Detoxifies: Steroid hormones incl. oestrogens, dopamine, adrenaline, noradrenaline. Arsenic and urea.
Inhibited by: B12 and folate deficiency; a high sucrose diet can inhibit enzymes such as COMT.
Enhanced by: Methionine, betaine, choline, vitamins B2, B6, B12, folate, magnesium.
Amino acid conjugation
Enzyme: Amino acid transferases
Detoxifies: Xenobiotics, drugs (e.g., aspirin and statins).
Inhibited by: Low protein diet.
Enhanced by: Glycine primarily (legumes, seaweed, cauliflower, bone broth, meat, fish, eggs), taurine, glutamine, arginine.
Glutathione conjugation
Enzyme: Glutathione S-transferases (GST)
Detoxifies: Xenobiotics, paracetamol, heavy metals (esp.mercury).
Requires: Glycine, glutamine and cysteine for formation of glutathione.
Inhibited by: Selenium, B6, zinc, glutathione deficiency.
Enhanced by: Brassica veg (especially broccoli sprouts), turmeric, citrus peel, alpha-lipoic acid.
Nrf2 (nuclear factor erythroid 2)
- The transcription factor, Nrf2(nuclear factor erythroid 2) is key to regulating the body’s detoxification and antioxidant system:
– Induction of Nrf2 increases endogenous antioxidants to protect against reactive intermediates, and promotes phase II pathways.
– Nrf2 induction is considered protective against various oxidative stress-related conditions such as cancer, kidney dysfunction, neurological disease, and cardiovascular disease.
Phyochemical that regulate Nrf2 activity
Curcumin(turmeric)
Broccoli constituents
Garlic
Epicatechins(e.g., green tea) Lycopene(tomatoes)
Resveratrol(e.g., red grapes)
Isoflavones (legumes, alfalfa sprouts)
Rosemary
Blueberry
Pomegranate
Naringenin (grapefruit)
Glutathione
A crucial antioxidant that protects against reactive metabolites from phase I and is essential for glutathione conjugation in phase II
* Cysteine is the rate-limiting amino acid for glutathione synthesis (sources include legumes, sunflower seeds, eggs, chicken).
* Glutathione is critical to mitochondrial protection.
* Low levels of glutathione have been associated with neurodegenerative diseases, autoimmunity, CVD, liver diseases, and pulmonary diseases such as COPD.
* Glutathione binds and transports mercury out of cells and out of the brain across the blood-brain barrier.
How to increase glutathione levels
- Decrease depletion (decrease oxidative stress): Decrease toxic load, optimise melatonin (sleep hygiene, vitamin B6 etc.), alpha-lipoic acid.
- Milk thistle (silymarin).
- NAC (also binds to methyl Hg) —300–1000 mg x 2 daily.
- Liposomal glutathione.
- Resveratrol(e.g., red grapes, berries).
- Cruciferous vegetables (glucosinolates boost glutathione).
- Cordyceps mushroom.
Phase II SNPs
Glutathione (GSTM1):
* Genes: GSTM1 is the most active member of the GST family and is responsible for the removal of xenobiotics, carcinogens and products of oxidative stress.
* SNPs: An ‘absent’ gene is common, resulting in reduced capacity for liver detoxification.
* Recommendations:
– Focus on minimising toxic load, e.g., stop smoking, eat organic.
– ↑ antioxidants(‘rainbow of colour’).
– ↑ cruciferous vegetables (for the sulforaphane) and alliums.
– Milk thistle, NAC, alpha-lipoic acid, selenium.
Phase III
The removal and excretion phase where detoxified products are pumped into blood or bile for elimination:
* This involves over 350 antiporter proteins (ATP-dependent pumps) that work on specific substrates.
Inducing Phase III
‒ Fasting(e.g., intermittent / vegetable broth).
‒ Being in a lipolytic state allows toxins stored in fat cells to be mobilised and eliminated.
‒ Fasts and calorie restriction should be short term (5–10 days) and toxin elimination should be supported with practices such as saunas.
Supporting Phase III
- Certain very high dose isolated phytonutrients appear to inhibit phase III —notably curcumin and epicatechins (in green tea).
– However, turmeric and green tea are highly valuable to detoxification and antioxidant processes.
– Focus on dietary inclusion and use of whole plant preparations. - Good hydration is essential, helping with elimination.
- Bile production and flow can be supported with choleretic and cholagogue herbs. Dandelion root and globe artichoke leaf provide both actions and are also mild diuretics. Burdock root (e.g., tea) is a cholagogue
