Liver Detoxification Phase
II Support

Liver Detoxification Phase II Support: Overview

The liver is one of the most important organs in the body when it comes to detoxifying or getting rid of foreign substances or toxins, especially from the gut.  The liver plays a key role in most metabolic processes, especially detoxification.

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The liver detoxifies harmful substances by a complex series of chemical reactions.  The role of these various enzyme activities in the liver is to convert fat-soluble toxins into water-soluble substances that can be excreted in the urine or the bile depending on the particular characteristics of the end product.

Many of the toxic chemicals that enter the body are fat-soluble, which means they dissolve only in fatty or oily solutions and not in water.  This makes them difficult for the body to excrete.  Fat-soluble chemicals have a high affinity for fat tissues and cell membranes, which are composed of fatty acids and proteins.  In these fatty tissues of the body, toxins may be stored for years, being released during times of exercise, stress or fasting.  During the release of these toxins, several symptoms such as headaches, poor memory, stomach pain, nausea, fatigue, dizziness and palpitations can occur.

Function; Why it is Recommended

Simply speaking, the body's natural liver detoxification process involves two steps; Phase 1 and Phase 2.  A toxin initially enters Phase 1, the P-450 cytochrome system, and is reduced to smaller fragments.  These fragments then progress to Phase 2, where they are bound to molecules such as glutathione, glycine and sulfate.  This process creates a new non-toxic molecule that can be excreted in the bile, urine or stool.

In effect, Phase 1 either directly neutralizes a toxin, or modifies the toxic chemical to form activated intermediates which are then neutralized by one of more of the several Phase 2 enzyme systems.  In Phase 1, a toxic chemical is converted into a less harmful chemical.  This is achieved by various chemical reactions (such as oxidation, reduction and hydrolysis), and during this process free radicals are produced which, if excessive, can damage the liver cells.  Antioxidants reduce the damage caused by these free radicals.  If antioxidants are lacking and toxin exposure is high, toxic chemicals become far more dangerous.  Some may be converted from relatively harmless substances into potentially carcinogenic substances.

One or both detoxification phases can be inefficient or overloaded.  A particularly damaging combination in an ill person is an excessive overload of toxins coming into Phase 1, with an inefficient Phase 2.  In some cases this combination is believed to be the cause of marked environmental sensitivities, drug intolerances and interactions that characterize many chronic fatigue and fibromyalgia patients.

Patients with underactive Phase 1 detoxification will experience an intolerance to caffeine, perfumes and other environmental chemicals, and an increased risk for liver disease, while those with an overactive system will be relatively unaffected by caffeine drinks.  Caffeine is an example of a chemical directly neutralized by Phase 1.  One way of objectively determining the activity of Phase 1 is to measure how efficiently a person detoxifies caffeine.  Using this test, a surprising fivefold difference in the detoxification rates of apparently healthy adult has been noted.

Substances that activate Phase I detoxification:

  • Drugs: alcohol; nicotine in cigarette smoke; Phenobarbital; sulfonamides; steroids
  • Foods: cabbage, broccoli, and brussels sprouts; charcoal-broiled meats; high-protein diet; oranges and tangerines (but not grapefruits)
  • Nutrients: niacin; vitamin B1; vitamin C
  • Herbs: caraway and dill seeds
  • Environmental toxins: carbon tetrachloride; exhaust fumes; paint fumes; dioxin; pesticides

Grapefruit juice, which contains naringenin, slows down Phase I enzyme activity.  It decreases the rate of elimination of drugs from the blood and has been found to substantially alter their clinical activity and toxicity.  Eight ounces of grapefruit juice contains enough of the flavonoid naringenin to decrease cytochrome P450 activity by a remarkable 30%.

Phase II Detoxification
This is called the conjugation pathway, whereby the liver cells add another substance (eg.  cysteine, glycine or a sulfur molecule) to a toxic chemical or drug, to render it less harmful.  This makes the toxin or drug water-soluble, so it can then be excreted from the body via watery fluids such as bile or urine.  Individual xenobiotics and metabolites usually follow one or two distinct pathways.  There are essentially six phase II detoxification pathways:

  • Glutathione conjugation
  • Amino acid conjugation
  • Methylation
  • Sulfation
  • Acetylation
  • Glucuronidation

The conjugation molecules are acted upon by specific enzymes to catalyze the reaction step.  Through conjugation, the liver is able to turn drugs, hormones and various toxins into excretable substances.  For efficient Phase Two detoxification, the liver cells require sulfur-containing amino acids such as taurine and cysteine.  The nutrients glycine, glutamine, choline and inositol are also required for efficient phase two detoxification.

The rate at which Phase 1 produces activated intermediates must be balanced by the rate at which Phase 2 finishes its processing.  People with a very active Phase 1 detoxification system coupled with slow or inactive Phase 2 enzymes are termed pathological detoxifiers.  These people suffer unusually severe toxic reactions to environmental poisons.  A liver detoxification test can pinpoint exactly how efficiently your liver is carrying out the detoxification process and if you are a pathological detoxifier.

An imbalance between Phase I and Phase II can also occur when a person is exposed to large amounts of toxins or exposed to toxins for a long period of time.  In these situations, the critical nutrients needed for Phase II detoxification are depleted, which allows the highly toxic activated intermediates to build up.

Proper functioning of the liver's detoxification systems is especially important for the prevention of cancer.  Up to 90% of all cancers are thought to be due to the effects of environmental carcinogens, such as those in cigarette smoke, food, water, and air, combined with deficiencies of the nutrients the body needs for proper functioning of the detoxification and immune systems.

The level of exposure to environmental carcinogens varies widely, as does the efficiency of the detoxification enzymes, particularly Phase 2.  High levels of exposure to carcinogens coupled with slow detoxification enzymes significantly increases susceptibility to cancer.

When optimum nutrition is provided, the liver operates efficiently.  Many (and perhaps most) people do not eat the right kinds of foods to provide the liver with everything it needs for the elimination of the extra toxins that the body is exposed to daily.  If nutrition is compromised through poor dietary and lifestyle habits, this will impede detoxification processes, and other organs will suffer as the body retains these toxins.

When working properly, the liver clears 99% of the bacteria and other toxins during the first pass.  However, when the liver is damaged, such as in alcoholics, the passage of toxins increases by over a factor of 10.

The liver's Phase 2 detoxification process involves the synthesis and secretion of bile.  Each day the liver manufactures approximately 1 quart of bile, which 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 fiber and excreted.  However, a diet low in fiber results in inadequate binding and reabsorption of the toxins.  This problem is magnified when bacteria in the intestine modify these toxins to more damaging forms.


If a patient is very ill with severe toxic symptoms, hepatic detoxification must be performed very slowly and gradually.  It is always preferable first to reduce toxin exposure and any liver inflammation.  In addition, leaky gut syndrome should be addressed and repaired prior to any liver detoxification.

An efficient liver detoxification system is vital to health and in order to support this process it is essential that many key nutrients are included in the diet.  Vitamins and minerals – particularly the B vitamins – play a major role, acting as cofactors for many enzyme systems including those of liver detoxification, therefore ensuring a plentiful supply of the B-complex group of vitamins is of prime importance for optimum detoxification.

Liver Detoxification Support can be achieved through both nutritional means and botanical medicines.

Nutritional factors – including antioxidant vitamins such as vitamin C, beta-carotene, and vitamin E – are obviously important in protecting the liver from damage as well as helping in the detoxification mechanisms.  However, even simple nutrients like the B-vitamins, calcium, and trace minerals are critical in the elimination of heavy metals and other toxic compounds from the body.  The lipotropic agents, choline, betaine, methionine, vitamin B6, folic acid, and vitamin B12, are useful as they promote the flow of fat and bile to and from the liver.  Lipotropic formulas have been used for a wide variety of conditions by nutrition-oriented physicians including a number of liver disorders such as hepatitis, cirrhosis, and chemical-induced liver disease.  Lipotropic formulas appear to increase the levels of SAM and glutathioneMethionine, choline, and betaine have been shown to increase the levels of SAM.

Depletion of vitamin C may impair the detoxification process; vitamin C also prevents free radical formation.  Vitamin E and selenium are cofactors for glutathione peroxidase activity as well as being powerful antioxidants in themselves.  Other nutrients which play vital roles in the Phase II pathway include amino acids glycine, cysteine, glutamine, methionine, taurine, glutamic acid and aspartic acid.

Botanical medicines include a long list of plants which exert beneficial effects on liver function.  However, the most impressive research has been done on silymarin, the flavonoids extracted from milk thistle (silybum marianum).  These compounds exert a substantial effect on protecting the liver from damage as well as enhancing detoxification processes.  Silymarin prevents damage to the liver through several mechanisms: by acting as an antioxidant, by increasing the synthesis of glutathione and by increasing the rate of liver tissue regeneration.  Silymarin is many times more potent in antioxidant activity than vitamin E and vitamin C.  The protective effect of silymarin against liver damage has been demonstrated in numerous experimental studies.  Silymarin has been shown to protect the liver from the damage produced by such liver-toxic chemicals as carbon tetrachloride, amanita toxin, galactosamine, and praseodymium nitrate.

One of the key mechanisms by which silymarin enhances detoxification is by preventing the depletion of glutathione.  Silymarin not only prevents the depletion of glutathione induced by alcohol and other toxic chemicals, but has been shown to increase the level of glutathione of the liver by up to 35%, even in normal individuals.  In human studies, silymarin has been shown to have positive effects in treating liver diseases of various kinds, including cirrhosis, chronic hepatitis, fatty infiltration of the liver, and inflammation of the bile duct.  The standard dosage for silymarin is 70-210 mg three times/day.

Curcumin, the compound that gives turmeric its yellow color, is interesting because it inhibits Phase I while stimulating Phase II.  This effect can be very useful in preventing certain types of cancer.  Curcumin has been found to inhibit carcinogens such as benzopyrene (found in charcoal-broiled meat) from inducing cancer in several animal models.  It appears that the curcumin exerts its anti-carcinogenic activity by lowering the activation of carcinogens while increasing the detoxification of those that are activated.  Curcumin has also been shown to directly inhibit the growth of cancer cells.

Expected Outcome

As patients improve clinically, serial testing of their liver detoxification capacity shows corresponding improvement.

On This Page

Liver Detoxification Phase II Support:

Liver Detoxification Phase II Support can help with the following:


Environmental Illness / MCS

Reducing the body burden of chemicals can be enhanced by maximizing Phase II liver detoxification pathways with selected nutrients.

Organ Health

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