Detoxification is the process of conversion of a “lipophilic”, fat-soluble substance to a “hydrophilic”, water-soluble substance to be excreted. Detoxification takes place at two major sites: the intestinal mucosal wall and, more significantly, the liver

It is estimated that up to 25% of people in the US suffer from heavy metal poisoning. Also, many gut-derived microbial toxins have been implicated in a wide variety of diseases, including liver diseases, Crohn’s disease, ulcerative colitis, thyroid disease, psoriasis, SLE, pancreatitis, allergies, asthma, and immune disorders. Moreover, up to 90% of all cancers are thought to be due to the effects of environmental carcinogens not eliminated properly by the liver

Liver detoxification is a complex process that can be divided into 4 main phases:

1. Blood filtration: when working properly, the liver clears 99% of the bacteria and other toxins during the first pass. However, when the liver is damaged, the passage of toxins increases by over a factor of 10!!

2. Bile excretion: the liver’s second detoxification process involves the synthesis and secretion of bile. Bile serves as a carrier in which many toxic substances are dumped into the intestines. In the intestines, the bile and its toxic load are absorbed by “Dietary fibers” and excreted. However, a diet low in fiber results in inadequate binding and reabsorption of the toxins. Moreover, this problem is magnified when bacteria in the intestine modify these toxins to more damaging forms because of improper elimination

3. Phase I detoxification: phase I detoxification reaction works by producing an “active site” on the toxin by the help of oxygen. phase I detoxification reaction is composed of multiple processes like oxidation, reduction, and hydrolysis of metabolites into toxic intermediate substrates”, preparing these metabolites to phase II detoxification. These reactions are performed by a family of enzymes collectively known as “Cytochrome P450 enzymes”. The products of cytochrome P450 partially are “carcinogenic”!!  

4. Phase II detoxification: phase II detoxification adds a water-soluble substance (conjugate) to the active site produced in phase I to make the substance water soluble. Phase II detoxification typically is involves detoxification of phase I toxic metabolites converting them into “Non-toxic wastes” through many processes (e.g., glucuronidation, glutathione conjugation). This conjugation reaction either “neutralizes” the toxin or makes the toxin more easily excreted through the urine or bile. Six phase II detoxification pathways are defined, and in order to work, these enzyme systems need nutrients both for their activation and to provide the small molecules they add to the toxins

* The six phase II detoxification pathways are:

A. Glutathione conjugation: the toxic intermediate from phase I detox is conjugated with “glutathione”, a tripeptide composed of three amino-acids: cysteine, glutamic acid, and glycine. Glutathione conjugation produces water-soluble products which are excreted via the kidneys. Smoking depletes glutathione from the body due to continuous detox

B. Amino acid conjugation: this system uses several amino acids (glycine, taurine, glutamine, arginine, & ornithine) to combine with and neutralize toxins. Of these, “glycine” is the most commonly utilized in phase II amino acid detoxification. Failure of this system causes: hepatitis, chronic arthritis, and hypothyroidism

C. Methylation: methylation involves conjugating “Methyl groups” to toxins. Most of the methyl groups used for detoxification comes from “S-adenosylmethionine - SAM”. SAM is synthesized from the amino acid “Methionine”, a process which requires the nutrients choline, vitamin B12, and folic acid. SAM is “able to inactivate estrogens”, supporting the use of methionine in conditions of estrogen excess. Methionine is a major source of numerous sulfur-containing compounds, including the amino acids cysteine and taurine

D. Sulfation: sulfation is the process of conjugating toxins with “Sulfur-containing” compounds. Sulfation is very important in the detoxifications of many medications (e.g., acetaminophens), hormones (e.g., estrogen, thyroid), neurotransmitters (e.g., glutamate), food additives, and dysbiosis endotoxins

E. Acetylation: conjugation of toxins with “acetyl-CoA” is the primary method by which the body eliminates sulfa drugs. This system appears to be especially sensitive to genetic variation, with those having a poor acetylation system being far more susceptible to sulfa drugs and other antibiotics

F. Glucuronidation: is a process of combining of “glucuronic acid” with toxins, which requires the enzyme, UDP-glucuronyl transferase (UDPGT). Many of the commonly prescribed drugs are detoxified through this pathway. It also helps to detoxify aspirin, menthol, vanillin (synthetic vanilla), food additives such as benzoates, and some hormones. Patients with Gilbert’s syndrome have defective glucuronidation pathway


Selected references

1. Bennett P et al. Textbook of functional medicine.  2010; Institute of Functional Medicine Publication; 1st edition

2. Baker SM. Detoxification and Healing: The Key to Optimal Health. 2003; McGraw-Hill Education; 2nd edition