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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.
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; Reasons For Use
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 sulphur 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 catalyse 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 sulphur-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.
Directions
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 glutathione. Methionine, 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.
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Liver Detoxification Phase II Support can help with the following:
KEY | | Likely to help |  | | Highly recommended |
GLOSSARY
Amino Acid (Amino Acids)
An organic acid containing nitrogen chemical building blocks that aid in the production of protein in the body. Eight of the twenty-two known amino acids are considered "essential," and must be obtained from dietary sources because the body can not synthesize them.
Antioxidant (Antioxidants)
A chemical compound that slows or prevents oxygen from reacting with other compounds. Antioxidants are substances that protect cells from oxidative damage caused by molecules called free radicals. These chemicals can damage important parts of cells, such as proteins, membranes, and DNA. Some antioxidants have been shown to have cancer-protecting potential because they neutralize free radicals. Examples include vitamins C and E, beta carotene, the minerals selenium and germanium, superoxide dismutase (SOD), coenzyme Q10, catalase, and some amino acids.
Bacteria (Bacterial, Bacterium)
Microscopic germs. Some bacteria are "harmful" and can cause disease, while other "friendly" bacteria protect the body from harmful invading organisms.
Beta-Carotene (Beta Carotene)
The most abundant of the carotenoids, beta-carotene has strong provitamin A activity and is a stronger antioxidant than vitamin A. It is widely accepted today as a cancer preventative. It is found in leafy green and yellow vegetables, often missing in children's diets. Beta-Carotene is believed to be a superior source of Vitamin A because it is readily converted into a more active form of the substance: your body converts it to Vitamin A as needed.
Bile
A bitter, yellow-green secretion of the liver. Bile is stored in the gallbladder and is released when fat enters the first part of the small intestine (duodenum) in order to aid digestion.
Bioflavonoid (Bioflavonoids, Flavonoid, Flavonoids)
Vitamin P. Any of a group of colored flavones (crystalline compounds) found next to the peel in many fruits. Essential for the stability and absorption of ascorbic acid.
Caffeine
A member of the family of chemicals that are called methyl xanthines. It is variously classified as a stimulant, an addictive substance, a performance-enhancing drug and a slimming aid. Sources of caffeine include drinks, foods and medications. Examples include coffee, tea, cola drinks, the new generation 'energy' drinks, chocolate, and many over-the-counter and prescription medications.
Calcium
The body's most abundant mineral. Its primary function is to help build and maintain bones and teeth. The body also needs calcium to carry nerve signals, keep the heart functioning, contract muscles, clot blood and maintain healthy skin. Calcium helps control blood acid-alkaline balance, plays a role in cell division, muscle growth and iron utilization, activates certain enzymes, and helps transport nutrients through cell membranes. Calcium also forms a cellular cement called ground substance that helps hold cells and tissues together.
Cancer
Refers to the various types of malignant neoplasms that contain cells growing out of control and invading adjacent tissues, which may metastasize to distant tissues.
Carcinogen (Carcinogenic, Carcinogenicity)
Any agent that is cancer-causing.
Choline
A lipotropic substance sometimes included in the vitamin B complex as essential for the metabolism of fats in the body. Precursor to acetylcholine, a major neurotransmitter in the brain. Choline prevents the deposition of fats in the liver and facilitates the movement of fats into the cells. Deficiency leads to cirrhosis of the liver.
Chronic (Chronicity)
Usually referring to chronic illness: Illness extending over a long period of time.
Chronic Fatigue Syndrome (CFS, Chronic Fatigue)
A disorder of unknown cause that lasts for prolonged periods and causes extreme and debilitating exhaustion as well as a wide range of other symptoms such as fever, headache, muscle ache and joint pain, often resembling flu and other viral infections. Also known as Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS), Chronic Epstein-Barr Virus (CEBV), Myalgic Encephalomyelitis (ME), "Yuppy Flu" and other names, it is frequently misdiagnosed as hypochondria, psychosomatic illness, or depression, because routine medical tests do not detect any problems.
Cirrhosis (Liver Cirrhosis)
A long-term disease in which the liver becomes covered with fiber-like tissue. This causes the liver tissue to break down and become filled with fat. All functions of the liver then decrease, including the production of glucose, processing drugs and alcohol, and vitamin absorption. Stomach and bowel function, and the making of hormones are also affected.
Cofactor (Cofactors)
A substance that acts with another substance to bring about certain effects, often a coenzyme.
Cysteine
A nonessential amino acid but may be essential for individuals with certain diseases or nutritional concerns. Cysteine is a sulfur-bearing amino acid with antioxidant properties. It is important for keratin synthesis, a protein found in skin, hair and nails and is a component of coenzyme A and glutathione.
Enzymes (Enzyme)
Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.
Fatty Acids (Fatty Acid)
Chemical chains of carbon, hydrogen, and oxygen atoms that are part of a fat (lipid) and are the major component of triglycerides. Depending on the number and arrangement of these atoms, fatty acids are classified as either saturated, polyunsaturated, or monounsaturated. They are nutritional substances found in nature which include cholesterol, prostaglandins, and stearic, palmitic, linoleic, linolenic, eicosapentanoic (EPA), and decohexanoic acids. Important nutritional lipids include lecithin, choline, gamma-linoleic acid, and inositol.
Fibromyalgia (FMS)
Originally named fibrositis, it is a mysteriously debilitating syndrome that attacks women more often than men. It is not physically damaging to the body in any way, but is characterized by the constant presence of widespread pain that often moves about the body. Fibromyalgia can be so severe that it is often incapacitating.
Free Radical (Free Radicals)
A free radical is an atom or group of atoms that has at least one unpaired electron. Because another element can easily pick up this free electron and cause a chemical reaction, these free radicals can effect dramatic and destructive changes in the body. Free radicals are activated in heated and rancid oils and by radiation in the atmosphere, among other things.
Glutamic Acid
Involved in the synthesis of DNA, glutathione and some amino acids. Helps remove excess ammonia from the body. Interconverted by the body into glutamic acid and gamma-amino-butyric acid (GABA).
Glutamine
A "conditionally essential" amino acid, glutamine is considered to be a brain fuel. Glutamine has been used therapeutically for alcoholism, mild depression and to reduce the craving for sweets. Glutamine is very important in the functioning of the metabolism and muscle maintenance. Glutamine supplementation can help prevent muscle and other tissue breakdown by providing the body with nitrogen and fuel.
Glutathione
A natural sulfur-bearing peptide formed from the linking of three amino acids: glutamic acid, cysteine and glycine. Glutathione acts as an antioxidant and detoxicant and is involved with the selenium-containing enzyme glutathione peroxidase. Glutathione is also involved in amino acid transport across cell membranes and is a powerful free radical scavenger and antioxidant that removes unwanted substances from the body.
Glutathione Peroxidase
A family of antioxidant enzymes containing selenium which are important in the reduction of different hydroperoxides, including hydrogen peroxide which is involved in the irritation of the gastrointestinal tract and increase in perspiration.
Glycine
The simplest amino acid which is a constituent of normal protein and an inhibitory neurotransmitter, used as a dietary supplement. A natural antacid and sweetener, it is involved in the syntheses of DNA, phospholipids and collagen.
Hepatitis
Inflammation of the liver usually resulting in jaundice (yellowing of the skin), loss of appetite, stomach discomfort, abnormal liver function, clay-colored stools, and dark urine. May be caused by a bacterial or viral infection, parasitic infestation, alcohol, drugs, toxins or transfusion of incompatible blood. Can be life-threatening. Severe hepatitis may lead to cirrhosis and chronic liver dysfunction.
Herbs (Herb, Herbal)
Herbs may be used as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, teas should be made with one teaspoon herb per cup of hot water. Steep covered 5 to 10 minutes for leaf or flowers, and 10 to 20 minutes for roots. Tinctures may be used singly or in combination as noted. The high doses of single herbs suggested may be best taken as dried extracts (in capsules), although tinctures (60 drops four times per day) and teas (4 to 6 cups per day) may also be used.
Hormones (Hormone)
Chemical substances secreted by a variety of body organs that are carried by the bloodstream and usually influence cells some distance from the source of production. Hormones signal certain enzymes to perform their functions and, in this way, regulate such body functions as blood sugar levels, insulin levels, the menstrual cycle, and growth. These can be prescription, over-the-counter, synthetic or natural agents. Examples include adrenal hormones such as corticosteroids and aldosterone; glucagon, growth hormone, insulin, testosterone, estrogens, progestins, progesterone, DHEA, melatonin, and thyroid hormones such as thyroxine and calcitonin.
Inositol
Usually considered part of the vitamin B complex. It is thought that along with choline, inositol is necessary for the formation of lecithin within the body. Involved in calcium mobilization.
Liver (Hepatic)
The largest and one of the most complex organs of the body, the liver is responsible for much of the metabolism of fats, proteins and carbohydrates. It is the site of much of the body's detoxification. It is connected very closely with digestion and the regulation of blood sugar, among many other functions. Found behind the ribs on the right side of the abdomen, it has many important functions such as removing harmful material from the blood, making enzymes and bile that help digest food, and converting food into substances needed for life and growth. Hepatic: Pertaining to the liver.
Metabolism (Metabolic, Metabolize, Metabolizes, Metabolizing)
The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds. Also defined as the sum total of changes in an organism in order to achieve a balance (homeostasis): Catabolic burns up, anabolic stores and builds up; the sum of their work is metabolism.
Metabolite (Metabolites)
Any product (foodstuff, intermediate, waste product) of metabolism.
Methionine
Essential amino acid. Dietary source of sulfur and methyl groups. Important for proper growth in infants, nitrogen balance in adults, healthy nails and skin and the synthesis of taurine, cysteine, phosphatidylcholine (lecithin), bile, carnitine and endorphins. It is an antioxidant nutrient and lipotropic agent which promotes the physiological utilization of fat.
Milligram (mg, Milligrams)
0.001 or a thousandth of a gram.
Nausea
Symptoms resulting from an inclination to vomit.
Niacin (B3, B-3, Niacinamide, Vitamin B3)
A coenzyme B-complex vitamin that assists in the breakdown of carbohydrates, fats and proteins. Essential for the health of the skin, nerves, tongue and digestive system. It is found in every cell of the body and is necessary for energy production. Niacin is also needed for DNA formation.
Ounce (Ounces, oz)
Approximately 28 grams.
Protein (Proteins)
Compounds composed of hydrogen, oxygen, and nitrogen present in the body and in foods that form complex combinations of amino acids. Protein is essential for life and is used for growth and repair. Foods that supply the body with protein include animal products, grains, legumes, and vegetables. Proteins from animal sources contain the essential amino acids. Proteins are changed to amino acids in the body.
Steroid (Steroids)
Any of a large number of hormonal substances with a similar basic chemical structure containing a 17-carbon 14-ring system and including the sterols and various hormones and glycosides.
Syndrome
A medical condition characterized by a collection of related symptoms (what the patient feels) and signs (what a doctor can observe or measure).
Taurine
A nonessential amino acid but may be essential for individuals with certain diseases or nutritional concerns. May be needed for the proper development and maintenance of the central nervous system. Taurine's role in bile formation is important for fat metabolism and blood cholesterol control.
Thiamine (B1, B-1, Thiamin, Vitamin B1)
A B-complex vitamin that acts as a coenzyme necessary for the conversion of carbohydrates into glucose, which is burned in the body for energy. It is essential for the functioning of the nervous system.
Trace Element (Trace Elements, Trace Mineral, Trace Minerals)
A mineral or element that is essential, in small amounts, for good health. Nutritionists prefer to call minerals either minerals or trace minerals depending on the amount needed by the body, while analytical chemists prefer to call minerals 'trace elements'.
Vitamin C (Ascorbic Acid)
A water-soluble antioxidant vitamin essential to the body's health. When bound to other nutrients, for example calcium, it would be referred to as "calcium ascorbate". As an antioxidant, it inhibits the formation of nitrosamines (a suspected carcinogen). Vitamin C is important for maintenance of bones, teeth, collagen and blood vessels (capillaries), enhances iron absorption and red blood cell formation, helps in the utilization of carbohydrates and synthesis of fats and proteins, aids in fighting bacterial infections, and interacts with other nutrients. It is present in citrus fruits, tomatoes, berries, potatoes and fresh, green leafy vegetables.
Vitamin E
An essential fat-soluble vitamin. As an antioxidant, helps protect cell membranes, lipoproteins, fats and vitamin A from destructive oxidation. It helps protect red blood cells and is important for the proper function of nerves and muscles. For Vitamin E only, 1mg translates to 1 IU.
Last updated: Nov 14, 2009
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