During Phase I, a family of enzymes commonly referred to as the cytochrome P450 system, reduces, oxidizes, and hydrolyze toxins, a process known as functionalization. The intermediate metabolites so produced are then further transformed during Phase II by other specialized enzymes in the liver. Following Phase II, the biotransformed substances are then able to be eliminated in the urine and feces.

Proper detoxification is dependent upon adequate levels of supporting nutrients, including protein, carbohydrates, fat, antioxidants, and other factors. These dietary factors alter the efficiency of liver detoxification as well as the manifestation of secondary symptoms resulting from the detoxification process.

Cytochrome P450 enzymes require adequate dietary protein in order to actively detoxify xenobiotic chemicals. Restriction of dietary protein in laboratory animals has been shown to increase the toxicity of certain pesticides and other carcinogens.[3] High carbohydrate intake may reduce the efficiency of the cytochrome P450 enzymes.[4] This effect is particularly prominent with the use of common table sugar, as opposed to other polyglucose sources. A diet higher in protein and lower in carbohydrates seems to provide optimal activation of the cytochrome P450 family of enzymes.5 Proper sources of both mono and polyunsaturated fatty acids also optimize the activity of the cytochrome P450 enzymes.[6] Free radicals produced during Phase I can be quenched by antioxidants such as vitamins C and E, as well as flavonoids and the mineral selenium. A high intake of pure water also enhances the elimination of toxins along the detoxification pathways.

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In addition to the above-named nutrients necessary for efficient and effective detoxification, other substances (cofactors) are required.[7] These include the amino acids methionine, cysteine and N-acetylcysteine; vitamins such as carotenoids, vitamins C and E; and the minerals copper, iron, magnesium, selenium and zinc. The following is a more comprehensive list of nutrients required for effective detoxification:[8]

One of the most important protective substances synthesized by the body is glutathione, also referred to as GSH. Consisting of the three amino acids cysteine, glycine, and glutamate (glutamic acid), glutathione is a water-phase molecule present in all human cells. The presence of this substance is a sensitive indicator of a cell’s overall state of health and may ultimately prove to be the single most accurate indicator of cellular health.[9] Conversely, its intracellular depletion ultimately results in cellular death.[10] Glutathione plays a role in many diverse biological processes including cell maturation, enzyme catalysis, intermediary metabolism, protein synthesis, receptor action, and trans-membrane transport.[11] It is most abundant in the liver, and is also significantly present in the spleen, red blood cells, lens of the eye, kidneys and leukocytes.[12]

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One of the major functions of glutathione is its role as a master antioxidant, fighting damaging free radicals. As such, it exerts a direct and powerful effect as an immune system enhancer, radioprotective agent, and detoxifier. Free radicals including superoxide, peroxide, the hydroxyl radical, and others threaten the integrity of cells, tissues and organs including critical bodily constituents such as DNA, RNA, enzymes, and other proteinaceous structures.[13] The body’s trillions of cells face the continual challenge of neutralizing free radical reactions before they lead to cell impairment or destruction. As described previously, an impressive body of evidence indicates that free radical damage is a principal contributor to progressive loss of organ function (aging), as well as maladies such as allergies, Alzheimer’s disease, arteriosclerosis, asthma, cancer, cataracts, coronary artery disease, diabetes, immune dysfunction, Parkinson’s disease, and stroke.

As one of the body’s master antioxidants, glutathione is effective against free radical oxidation that can occur as the result of burns; cigarette smoke; dietary deficiencies of GSH precursors and enzyme cofactors; environmental toxins; heavy metals; household and industrial chemicals; inflammation; pesticides; pharmaceutical drugs; septic shock; strenuous exercise; surgery; ultraviolet (sun) and x-radiation (sun and medical); and viral and bacterial infection.[14] In addition to its significant antioxidant capability, glutathione also assists in the restoration of other antioxidants that have been oxidized.[15] The many forms of free radicals against which glutathione has been shown effective include 1) hydroxyl radical, 2) secondary radicals, 3) radical centers on DNA, 4) DNA peroxyl radicals, and 5) lipid peroxidases.[16]

The immune system is the body’s front-line defense against all forms of illness. A healthy immune system is able to ward off most challenges by infective microbes including bacteria, viruses, fungi, yeasts, and parasites. The immune cells, as is the case with other cells as well, depend upon glutathione to grow and proliferate. Adequate levels of glutathione are required by both T and B lymphocytes to differentiate. Intracellular glutathione is also necessary for T-cell proliferation and other T-cell functions, activation of T “killer cells,” and metabolism of interleukin-2.[17] Experimental depletion of glutathione has been shown to inhibit immune cell functions, and its intracellular levels in lymphocytes have been shown to be the determining factor of the magnitude of the immune system’s capacity.[18] The ability of lymphocytes to combat oxidative damage is a function of their capacity to regenerate intracellular levels of glutathione.[19] Treatment methods and dietary supplements which replenish cellular glutathione are therefore expected to optimize the immune system’s capability.

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Detoxification is the process whereby the body rids itself of poisonous substances such as xenobiotic chemicals present within the body. Because up to 75% of detoxification activity takes place in the liver, glutathione is the cornerstone of the detoxification process. About 70% of the total dietary intake of glutathione is used in the liver where it is stored and exported to other organs.[20] There is also a high concentration of glutathione in the lower regions of the lungs where it aids in neutralizing inhaled toxins such as cigarette smoke and also free radicals produced by activated immune cells within the lungs.[21] The kidneys and intestines, where significant detoxification takes place, also have high levels of glutathione. Its free radical scavenging ability is the key to its systemic detoxification activity at the molecular, cellular and tissue levels.[22]