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ntioxidants and Liver Supplements Print E-mail
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The Functions of the Liver
Efficient liver function is extremely important to the overall health of a person and this depends on constant supplies of antioxidant nutrients. If the liver isn't working efficiently and antioxidant defenses are low, the effects can be seen in any cell, tissue or organ in the body. A vast constellation of symptoms can result from impaired liver function that at first glance may seem to have nothing at all to do with the liver.
The liver has a number of important functions, some of the main ones being:
* Detoxification of potentially toxic chemicals from both inside and outside of the body including drugs, alcohol and toxins from intestinal microbes. Accomplished with antioxidant nutrients and enzymes such as glutathione.
* Storage of sugar as 'glycogen' and regulation of blood sugar levels.
* Production and storage of proteins as well as the regulation of many substances involved in protein metabolism.
* Production of bile which aids in the digestion of fats.
* Production of blood proteins, clotting factors and substances important to the production of red blood cells (erythrocytes)
* Regulation of a number of hormones.
* Neutralization of 'free-radicals' by antioxidants. Free radicals are highly reactive oxygen molecules that can damage tissues.
* Storage of vitamins, mainly A, D and B12
As you can see the liver is involved in a wide array of metabolic activities and it requires a large amount of energy and nutrients to accomplish these effectively.
Over the last century the workload of our livers has increased significantly. A vast amount of chemicals are now in everyday use and all of these must be processed and neutralized by the liver. These chemicals come in the form of pharmaceutical drugs, household cleaning products, cosmetic and personal care products and household furnishings and building materials, to name but a few.
Glutathione - The Master Antioxidant
Glutathione is an antioxidant enzyme often referred to as the body's "master antioxidant" due to its central role in protecting the body's cells from free radical damage. Glutathione is composed of the amino acids cysteine, glutamine and glycine and is concentrated in the liver, although it carries out its work throughout the body. This important enzyme is involved in protecting cells from environmental toxins, drugs and alcohol as well as toxins produced by the body itself as a result of normal metabolism. So important to health is glutathione that it's depletion leads to cell death.
Environmental toxins are known to cause depletion of glutathione. Maybe not surprisngly, glutathione deficiency has been implicated in a whole range of chronic degenerative disorders including all of the environmental illnesses covered by this site.
Also of note is the influence glutathione levels have on immune function. Like all cells, immune cells rely up on glutathione for defense against free radicals. Glutathione is also required for the activation of natural killer cells and for many other functions of specific immune cells.
Clearly in this modern age of toxic living it is wise for everybody to be aware of their glutathione status but for environmental illness sufferers it is essential since their levels of this vital detoxifier have almost certainly been compromised already. Fortunately there are a number of natural products that have been shown in clinical studies to raise effective levels of glutathione. These will be discussed in a moment.
The Liver in Environmental Illnesses
The importance of the gut flora in ill health is becoming increasingly obvious as it is implicated as a cause of an increasing number of illnesses. The health of the gut has a substantial impact on the health of the liver as everything absorbed from the intestines passes through the liver so that harmful substances can be detoxified before the rest of the body is exposed to them. In one study by doctors at Biolab UK 61% of sufferers of undiagnosed chronic illnesses with predominant fatigue were found to have overgrowth of both bacteria and yeast in the gut1. As a result of their normal metabolism these micro-organisms produce waste products that in increased amounts can be harmful to the liver and the persons health as a whole. Yeast in particular produce a large amount of ethanol (drinking alcohol) which is highly toxic to the liver, in fact alcohol is the single most toxic substance to liver cells. As well as producing increased amounts of toxic substances for the liver to deal with, yeast or bacterial overgrowth also causes damage to the intestinal lining causing 'leaky gut'. Increased gut permeability results in even more potentially toxic substances from the gut being absorbed to put further stress on the livers detoxification pathways. A study of liver disease in alcoholics found that only the patients with a leaky gut developed cirrhosis of the liver2. This points to the possibility that in people with gut dysbiosis, not only is there chronic ingestion of alcohol but the leaky gut caused by bacterial and/or yeast overgrowth leads to more severe effects on the liver from the alcohol produced. If the liver is overwhelmed by toxins from the gut and from chemicals in everyday use it won't function correctly and may even become damaged and inflamed. As a result, not all toxins entering the liver are detoxified and gain access to the bloodstream to travel anywhere in the body. These toxins and the excess of free radicals (highly reactive forms of oxygen) caused by poor liver function can cause direct damage to tissues and also initiate allergic or auto-immune reactions. Un-neutralized toxins are also expelled into the bile in this situation and can further damage the intestinal lining, setting up a vicious cycle in which gut dysbiosis and leaky gut cause poor liver function which in turn worsens the gut dysbiosis and leaky gut.
As mentioned earlier, the liver requires large amounts of energy and nutrients to function efficiently. If the liver is overwhelmed by toxins, these nutrients can become depleted and the liver will function inefficiently resulting in numerous symptoms and problems throughout the body. Many of these nutrients can be replaced by supplementation, improving the functioning of the liver. There are also a number of herbs and other methods that can heal a damaged liver and improve detoxification functions.
Supplements for the Liver
Herbs
Milk Thistle (Silymarin)
The milk thistle plant contains silymarin and related flavonoids which are some of the most potent liver-protecting substances known. These flavonoids are powerful antioxidants so protect the liver from damaging toxins and free radicals. They also stimulate healing and the production of new liver cells and cause the liver to increase production of glutathione, the bodies most important antioxidant and detoxifying substance. Silymarin has been proven to both protect liver cells and repair existing damage in animals intoxicated with mushroom toxins, medicines, heavy metals or toxic organic solvents3. Human studies have also shown decreased mortality in patients with alcoholic liver damage who are treated with silymarin3. Milk thistle is commonly available in capsule or tincture form and a common dose would be 200mg 2/3 times per day. For hepatitis and cirrhosis doses of 400mg or more 3 times per day are common.
Burdock
Burdock contains a number of nutrients important to liver function. These include vitamins B1, B6 and B12 which are essential for the function of phase 1 liver detoxification's pathways, vitamin E, a powerful antioxidant and sulphur which is essential for a number of important phase 2 liver detoxification pathways in which potent toxins created by phase 1 detoxification are neutralized. Phase 2 pathways requiring sulphur include those utilizing glutathione. Burdock also contains other substances such as arctiin which act to improve liver and gallbladder function.
Dandelion
Clinical studies have shown dandelion extract to have protective effects against lipid peroxidation and free radicals, both damaging products of a poorly functioning liver4. Like burdock, dandelion contains a wealth of nutrients important to liver function, especially the B vitamins. It cleanses the liver and increases the production of bile. Dandelion is often used as a herbal treatment for all liver diseases of the liver including hepatitis, cirrhosis and jaundice.
Nutrients
N-Acetyl-Cysteine (NAC)
Cysteine is a sulphur containing amino acid and is a major component of glutathione (the others being glutamine and glycine). Supplementing cysteine boosts levels of this important 'master antioxidant'. Cysteine is one of the best free radical destroyers and helps to detoxify harmful toxins in the body and also binds to potentially harmful heavy metals, removing them from the body. Clinical studies have shown that pretreatment with NAC before parecetomol overdose protects liver cells and maintains glutathione levels. Treatment after overdose raises glutathione levels to normal and prevents further liver cell damage5. Excessive levels of toxins from the environment and from gut dysbiosis and leaky gut syndrome can lead to depletion of cysteine. This in turn leads to depletion of glutathione and allows free radicals and other toxins to get into the bloodstream un-neutralized, causing damage to tissues. In these instances cysteine levels can be raised by supplementation, indeed any treatment aimed at restoring liver function should include cysteine. The best form to supplement is n-acetyl-cysteine as this has been shown to increase glutathione levels in the body more than cysteine and even glutathione itself. Typical doses are 500-1500mg per day in divided doses.
Taurine
Taurine is a unique amino acid in that it is not incorporated into proteins and enzymes. Instead it is essential for the formation of bile in the liver and acts as a potent detoxifier and antioxidant throughout the body. Alcohol and aldehydes are known to decrease levels of taurine in the liver and it is thought that this is because taurine is used up in protecting liver cells from damage due to these and other toxins. This makes it important for people with gut dysbiosis as bacterial and yeast overgrowths lead to the excessive production of these substances. In one study taurine has been shown to protect against the toxic effects of a chemical called carbon tetrachloride-induced toxicity. In rats exposed to carbon tetrachloride (CCl4), hepatic taurine content decreased significantly 12 and 24 hours after CCl4 administration. When taurine was given to CCl4-exposed rats it was able to protect them from hepatic taurine depletion, suggesting that taurine in the liver may play a critical role in the protection of liver cells against toxins such as CCl46. Similar results have also been found in studies involving human patients with acute hepatitis7. The amount of taurine used in these studies was very high, 4g three times per day, but levels much lower than this are generally believed to be beneficial for less severe liver dysfunction such as that experienced by many environmental illness sufferers. Many doctors and nutritionists recommend 500mg twice a day. Taurine typically comes in 500mg capsules.
Methionine/S-adenosylmethionine (SAMe)
Like cysteine, methionine is a sulphur containing amino acid that is important for detoxification. Both cysteine and taurine can be synthesized in the body from methionine so long as enough vitamin B5 is available. Through this mechanism, methionine can be said to be the starting point for glutathione production, which as already described is the 'master detoxifier' of the body and protects liver cells from the effects of harmful toxins and free radicals. Like cysteine this amino acid is a chelater, binding to heavy metals and removing them from the body before they can build up and cause damage to tissues. Methionine is also important in the metabolism of fats and prevents them building up in the liver which impairs liver function. Typical doses of methionine recommended for liver support are 500-1000mg per day. Doses higher than 2g per day should be viewed with caution, especially when B vitamin deficiencies are present (as they commonly are in environmental illnesses8 as the excess methionine may be converted into homocysteine, a toxic substance implicated in hardening of the arteries and heart disease9. Methionine is typically available in 500mg capsules. When significant liver impairment is present due to the effects of alcohol and related substances studies have shown that a different form of methionine called S-adenosylmethionine (SAMe) needs to be supplemented instead as the livers ability to convert methionine to SAMe is impaired10,11. In fact SAMe is currently one of the most promising treatments being studied for the full spectrum of liver diseases. An effective dosage for severe liver disorders like cirrhosis and chronic hepatitis appears to be in the range of 800-1600mg12, obviously for less severe impairment of liver function as may be seen in environmental illnesses, a significantly lower dose could be helpful. A major drawback of SAMe is its high price. To avoid build of homecysteine when supplementing methionine/SAMe it is advisable to take supplements of Vitamins B12 and B6, folate and possibly trimethyl glycine (TMG)
Arginine
When the liver is functioning poorly ammonia begins to build up. This is especially true when gut dysbiosis is present as an overgrowth of micro-organisms in the gut leads to increased ammonia production as they produce ammonia as a by-product of protein metabolism. Arginine aids liver function by neutralizing ammonia. A typical dose is 500mg per day.
Polyenylphosphatidylcholine (PPC)
PPC supplements supply the body with phosphatidylcholine. This substance is extremely important for the integrity of cell membranes and for supporting detoxification processes. These roles are due to the fact that phosphatidylcholine influences lipid metabolism and cell membranes are composed predominantly of lipids. Currently, along with SAMe, PPC appears to show the most promise of all nutrients tested for the treatment of the whole spectrum of liver disorders. This is borne out by the number of studies investigating its effects and the positive results that are being obtained. In a recent study investigating novel new treatments the investigators studied PPC in detail and found it to be highly effective at treating both cirrhosis and alcoholic hepatitis. They found the beneficial effects to be due to PPC's ability to oppose lipid peroxidation (damage to fats (including cell membranes) due to free radicals) and restore phospholipid levels thus regenerating damaged liver cells13. In diseases of the liver there is an increased production of toxic acetaldehyde and free radicals due to the increased activity of a specific enzyme and multiple studies have shown that this can be effectively opposed by administration of PPC11,14. Finally PPC has been shown to restore depleted SAMe due to alcoholic liver injury. SAMe is required for the synthesis of phosphatidylcholine so supplementing PPC and thus supplying phosphatidylcholine reduces the bodies requirements for SAMe and may allow stores to regenerate. As a result of the increased levels of SAMe, glutathione levels increase in turn and oxidative stress is reduced15. As with SAMe, PPC is unfortunately an expensive supplement.
Alpha Lipoic Acid
Alpha Lipoic Acid is a sulphurous fatty acid that was originally classified as a vitamin until it was discovered that it could be synthesized in the human body. Sometimes referred to as 'thioctic acid' it is often described as the universal antioxidant due to the fact that it is active in both the water and fat based regions of cells unlike other antioxidants like vitamin C which is only water soluble and vitamin E which is only fat soluble. As well as being a particularly powerful antioxidant in its own right, directly neutralizing free radicals, alpha lipoic acid also plays a role in recycling other important antioxidants such as vitamins C and E, glutathione and Coenzyme Q1016. Alpha lipoic acid is said to quench the powerful peroxynitrite radical, an especially dangerous type consisting of both oxygen and nitrogen, according to a recent paper in FEBS Letters (Whiteman M, et al., FEBS Letters, 1996; 379:74-6). Peroxynitrite radicals have been implicated in the development of atherosclerosis, lung disease, chronic inflammation, and various neurological conditions. This 'universal antioxidant' has been shown to be effective in the treatment of a number of serious diseases, most notably diabetes, liver disorders and neuropathies17,18. Alpha lipoic acid comes in 50-600mg capsules or tablets. 600mg per day or more is recommended for liver disorders so well below this level will likely be beneficial to environmental illness sufferers.
B Vitamins
The B vitamins are all essential for healthy liver function. They are required for the formation of a huge number of enzymes including the P450 Cytochrome enzymes which are the basis of the phase 1 liver detoxification pathways. These B vitamin containing enzymes initiate the first part of the detoxification process before glutathione and the other phase 2 enzymes deal with the products of this. When the toxic load on the liver is increased the P450 enzymes tend to become more active which means the requirement for B vitamins increases. It is therefore easy to see how with a constantly increased toxic load from gut derived toxins (gut dysbiosis and leaky gut) and/or environmental exposures can lead to B vitamin deficiencies8. The B vitamins should be taken together as they are synergistic. A capsule form is often sufficient but injections of B12 and folic acid may be necessary as they are not well absorbed, especially in the presence of unhealthy gut flora.
Anti-oxidant Vitamins (A, C, E)
Vitamins A, C and E are all powerful anti-oxidants and are utilized by phase 1 liver detoxification pathways. Recent research shows that vitamins C and E act synergistically to neutralize free radicals with vitamin C scavenging for free radicals in bodily fluids and vitamin E protecting the cell membranes. All of these vitamins help protect the body from environmental toxins and the fat soluble vitamins, A and E , also help protect and repair the intestinal tract thus also protecting the liver indirectly by reducing the severity of leaky gut syndrome. Vitamin E also protects vitamin A from damage by free radicals. Common dosages of these vitamins are 400IU of vitamin E, 10,000IU of vitamin A (more can be toxic to a damaged liver) and any amount up to bowel tolerance of vitamin C is often recommended for people with health problems involving toxicity and oxidative stress as there are no known adverse effects.
Other Supplements
Undenatured Whey
Whey is the liquid part of milk obtained during the cheese making process. It contains a wealth of important nutrients that are easily assimilated by the body. Most important with respect to the liver is its content of the amino acid building blocks for glutathione. Many people believe supplementing whey protein is the best way to raise glutathione levels within the cells. Whether this is the case or not the glutathione increasing ability of whey protein supplements has certainly been proven. In one study, the glutathione levels of HIV patients were shown to increase after taking either of two major brands of whey supplement19. Although whey protein definitely increases glutathione levels considerably it has two major drawbacks. Firstly it is expensive and second it can't be used by people with milk protein allergy, which in the case environmental illness sufferers, is likely to be a large proportion of people.
Raw Liver/Raw Liver Extract
Raw liver or raw liver extract (available in capsules) is a good source of important nutrients required by the liver such as B vitamins (especially B12) and vitamin A. Raw liver extracts have been used for over 100 years and a number of clinical studies conducted mainly in europe in the last century have backed its use20,21. Evidence from these studies suggests that raw liver extract helps liver cells to regenerate and improves detoxification processes by providing the raw materials.
MSM (methylsulfonylmethane)
MSM is a form of organic sulfur and has a wide range of health benefits when taken as a supplement. It is important for liver function as many liver detoxification pathways depend upon sulfur based enzymes. MSM also has the ability to reduce inflammation, this makes it important in environmental illnesses where there is often inflammation of the GI tract and liver due to gut dysbiosis and leaky gut syndrome. Also of importance is the fact that if sufficient MSM is available in the body it forms a protective barrier over mucus membranes. In this way it prevents allergic reactions by trapping allergens such as pollen in the respiratory tract and poorly digested food particles in the intestines. One study using 2600mg of MSM per day found it to be very effective in reducing the symptoms of allergic rhinitis (hayfever) and also commented on its lack of any side effects22. The protective barrier formed by MSM could also potentially inhibit the growth of pathogens such as candida and parasites in the gut.
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