Detoxification of toxins, both endotoxins and exotoxins, occurs in the liver. Endotoxins are the end products of metabolism and those toxins produced by bacteria and viruses. Exotoxins include chemicals, such as all forms of drugs, sulphites, MSG, food additives, agrochemicals and radiation. Once detoxified, the waste products are eliminated from the body through the bile and into the faeces, through the kidneys as urine and through the skin as sweat.
There are two phases of detoxification, known as Phase 1 and Phase 2:
Is catalysed by cytochrome P450 enzymes (found in the cell membrane of hepatocytes). It involves the conversion of toxic chemicals to less harmful ones by one or more of the following:Oxidation involves the introduction of OH and involves mixed function oxidases, monooxygenases and cytochrome P450. Enzymes also include alcohol dehydrogenase, which convert alcohol to aldehydes, and ketones and aldehyde dehydrogenases that convert aldehydes to carboxylic acids.
Reduction involves reductase enzymes that can reduce aldehyde and ketone groups.
Hydrolysis enzymes that involve the introduction of water. Enzymes include esterases, peptidases and amidases.
Between 50-100 enzymes make up the cytochrome P450 system, each enzyme detoxifying certain types of chemicals although some enzymes overlap their activity. If the liver is overloaded with toxins, the Cytochrome P450 enzyme may become “induced” or upregulated, resulting in high levels of free radicals. If these are not metabolised by Phase 2 conjugation, there may be resultant damage to cellular DNA and RNA. Caffeine, alcohol, organophosphate pesticides, dioxins, cigarette smoke, sulphonamide drugs, excess oestrogens and other steroid hormones (and even saturated fats) may induce or overactivate CYP450.
Cofactors for CYP450 include vitamins B1, B2, B3, B6, B9 (folic acid), B12, vitamins C and E, beta-carotene, magnesium, glutathione and broccoli.
Some substances can inhibit Phase 1 enzymes:
As a general guide, if coffee stops a person sleeping, cytochrome P450 function may be impaired; if lots of coffee has no affect on sleep, then cytochrome P450 may be upregulated or overactive. People may also experience intolerance to perfumes and environmental chemicals and not be able to detoxify alcohol easily.
Also, Phase 1 detoxification enzymes decrease with age, so sensitivity to chemicals, alcohol or coffee may develop later in life where they were absent before.
Is also known as the conjugation pathway. This phase also involves detoxifying fat-soluble toxic compounds, but does so by adding certain chemical groups to that compound to make them less toxic and water soluble. There are 6-8 conjugation pathways:Glucuronidation pathway involves the enzyme glucuronyl transferase for conjugating alcohols, phenols and carboxylic acids. Nutrients required are magnesium, B vitamins and glucuronic acid. The glucuronidation pathway removes steroid hormones such as oestrogen, progesterone and thyroxine, fatty acid derivatives, bilirubin and bile salts. Aspirin, diazepam, morphine and vanillin (synthetic vanilla) are detoxified through this pathway, also fungal toxins.
Sulphation pathway involves sulphotransferase enzymes for conjugating phenols, alcohols and amines. Nutrients required include B6, P5P, B9, B12, MSM, cysteine, magnesium, taurine. The sulphation pathway detoxifies neurotransmitters, steroid hormones, paracetamol and other xenobiotic substances.
Amino acid conjugation (glycine conjugation) involves carboxylic acids in conjugation. Nutrients include glycine and glycine cofactors including folic acid, manganese, B2, and B6 as P-5-P. Benzoates and salicylates are detoxified through the glycine pathway. Sodium benzoate is a common food preservative.
Glutathione conjugation involves the enzyme glutathione-S-transferase conjugating organic and inorganic chemical compounds, and heavy metals including mercury, lead and arsenic. Lack of glutathione transferase decreases the ability to detoxify alcohol. Nutrients include all precursors to glutathione production including cysteine, glycine and glutamic acid, EPA and vitamin B6. Glutathion-S-transferase can be depleted by excess drugs, toxins or fasting.
Acetylation involves the enzyme N. acetyltransferase for detoxifying sulphonamides. Nutrients required include acetyl-CoA, molybdenum, vitamins B2 and B3.
Methylation (and sulphoxidation) involves methyltransferase enzymes for detoxifying phenol, thiol and amino groups. Nutrients required include methionine, B6, P-5-P, B9, B12, MSM, magnesium, choline, betaine.
If there is a toxic overload in the body, toxins may be stored as fat in fatty organs such as the brain, which can disrupt function.
Metabolics Nutrient Phase 1 & 2 contains nutrients known to be necessary to support both the Phase 1 and Phase 2 liver detoxification enzymes and we recommend it is taken with Metabolics Artichoke (see Heart Health) for its glucuronic acid content.