Enhancing the Six Phase II Detoxification Pathways by Consuming the Necessary Nutrients

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The detoxification system of the body consists of three phases that process toxins for excretion from the body.  The Phase I detoxification pathway is responsible for breaking fat-soluble toxins down and then sending the metabolites to the Phase II detoxification pathways, which builds new substances from the metabolites by adding molecules to them, which is called conjugation.

The purpose of the addition or conjugation of new substances to the Phase I toxic metabolites is to convert them into water-soluble forms and make them easier to transport, more stable and more functional for the body to excrete.  Once the toxic metabolites are conjugated by Phase II substances, Phase III molecules transport the stable toxins out of the body through the urine and/or bile.

There are 6 Phase II detoxification pathways in the body.  Each conjugation pathway serves a specific purpose of detoxifying certain toxins and requires specific nutrients to function.  These 6 detoxification pathways include:

  • Glutathione conjugation
  • Methylation
  • Sulfation
  • Acylation/Glycation
  • Acetylation
  • Glucuronidation

These 6 conjugation pathways are found primarily in the liver and in various other locations within the body:

Locations of Phase 2 Conjugation Pathways

Conjugation System Location in Body
Acylation/Glycation  conjugation liver, kidney
Glutathione conjugation liver, kidney
Glucuronidation liver, kidney, intestine, lung, skin, prostate, brain
Acetylation liver, lung, spleen, gastric mucosa, RBCs, lymphocytes
Sulfation liver, kidney, intestine
Methylation liver, kidney, lung, CNS

Source:  Liston HL, Markowitz JS, DeVane CL (October 2001). “Drug glucuronidation in clinical psychopharmacology”. J Clin Psychopharmacol 21 (5): 500–15. doi:10.1097/00004714-200110000-00008. PMID 11593076

In order for each conjugation pathways to function properly, they require specific nutrients.  These nutrients are listed in the Table below:

Phase II Conjugation Pathways

Conjugation PathwayFunctionDetoxifiesNutrients to Enhance
Conjugation PathwayFunctionDetoxifiesNutrients to Enhance
Glutathione conjugationGlutathione is an intracellular antioxidant. It is synthesized from the amino acids cysteine, glutamic acid, and glycine. It is synthesized from the amino acids cysteine, glutamic acid, and glycine. Glutathione conjugation is used to eliminate toxins through the lungs, intestines and kidneys, as well as the liver. Exposure to high levels of toxins and heavy metals deplete glutathione faster than it can be replenishedFat soluble toxins: solvents, herbicides, fungicides, hydrocarbons and lipid peroxides. Heavy metals (mercury, cadmium, lead). Nicotine and toxins from tobacco smoke. AlcoholCruciferous vegetables, Vitamin C, Alpha lipoic acid, whey protein, N-Acetyl-Cysteine, Glutamine and methionine, milk thistle
MethylationMethylation conjugates toxins to methyl groups, particularly the amino acid methionineHormones: estrogen, melatonin. Neurotransmitters: Epinephrine and norepinephrine, dopamine, histamine, serotonin. It converts pyridine, sulphites and hypochlorites into compounds excreted through the lungsAmino acid: methionine, B-Vitamins: B12, B6 and Folic acid, Choline, Betaine (TMG), Magnesium, Zinc, SAMe (S-adenosylmethionine)
SulfationConjugates toxins to sulfur compounds. Sulfation requires sulphate and is limited by the amount present in the body. Sulphate may be ingested from food, but is also produced by the action of the enzyme cysteine dioxygenase on the amino acid cysteine. Sulfoxidation, a final stage of methylation, transforms toxic sulfites into sulfateacetaminophen, Food additives: aspartame, Hormones and neurotransmitters: cortisol, thyroid, steroidal, Toxins from intestinal bacteria, Various environmental toxins, XenoestrogensMethionine and cysteine, sulfur rich vegetables, B Vitamins: B1, B2 and B12, Magnesium, Zinc, MSM, N-Acetyl-Cysteine, Indole-3-Carbinol
Amino Acid Conjugation: Acylation/GlycinationAttaching toxins to amino acids glycine, glutamine and tuarine. Attaching toxins to glycine is also known as glycinationBenzoate, Salycilates (aspirin), Toluene (industrial solvent)Protein-rich foods, Amino acids: glycine, taurine, glutamine, arginine, and ornithine
AcetylationAttaches acetyl co-A to toxins. Poor acetylation prolongs the life span of drugs and other toxic chemicals in the body, thus enhancing their toxicityNeurotransmitters: histamine, serotonin, Salicylic acid, PABA, Sulfa drugs, environmental toxins, tobacco smoke, exhaust fumesPantothenic acid (B5), Vitamin C, Thiamine (Vitamin B1)