Liver Degenerative Disease

Natural Therapies
Scientific literature reports the results of research using natural or alternative treatments for liver conditions. Note that the vast majority of natural or alternative treatments act by having an antioxidant effect. As with almost all disease processes, research has demonstrated that good antioxidant levels are necessary for optimum health and to protect us from the physical assaults of trauma and disease. Some of the therapies listed in the following section also act by having an effect on the immune system (an immune-modulating effect). Other therapies have anti-inflammatory benefits. Additionally, some agents act by having both antioxidant mechanisms and immune modulating mechanisms.

For the liver to continue to perform essential functions, even when damaged, a healthy intake of vitamins, minerals, and essential trace elements from dietary sources such as fruits and vegetables is important. However, few people can consistently include enough fruits and vegetables in their daily diets to protect them from degenerative conditions, especially those related to age-related diseases; toxic agents; carcinogens; inflammatory agents; free-radical damage; and immune suppression. As an adjunct to maintaining a healthy diet, supplements can:

1. Maintain healthy metabolic functioning
2. Neutralize free-radical damage
3. Increase levels of glutathione, the liver's natural antioxidant
4. Detoxify the liver

Supplements that Maintain Metabolic Health
Vitamin B complex. The vitamin B complex is a group of vitamins (B1, thiamine; B2, riboflavin; B3, niacin; B5, pantothenic acid; B6, pyridoxine; and B12, cyanocobalamin) that differ from each other in structure and the effect they have on the human body. The B vitamins play a vital role in numerous essential activities including enzyme activities (thiamine, riboflavin, niacin, pantothenic acid, pyridoxine). These enzyme activities also have many roles and are involved in the metabolism of carbohydrates and fats; functioning of the nervous and digestive systems; and production of red blood cells. The B vitamins have a synergistic effect with each other (AMA 1989). They are found in large quantities in the human liver as well as in many foods and yeast.

Folic acid. Folic acid is an important member of the B-complex family, important for reducing harmful levels of homocysteine, a sulfur-containing amino acid, known to be a major culprit in heart disease. The liver uses folic acid to facilitate healthy methylation patterns that are essential components of enzymatic detoxification. Decreased folate (folic acid) is also associated with increased levels of lipoperoxidases, that is, an indicator of increased oxidative stress. Therefore, folic acid is potentially beneficial if there is ongoing oxidative damage (Chern et al. 2001).

Choline. Another of the B complex vitamins is choline, essential for the use of fats in the body. It comprises a large part of acetylcholine (a nerve signal carrier). Choline also stops fats from being deposited in the liver and helps move fats into the cells. Deficiency of choline can lead to degenerative diseases such as cirrhosis with associated conditions such as bleeding, kidney damage, hypertension (high blood pressure), cholesterolemia (high blood levels of cholesterol), atherosclerosis (cholesterol deposits in blood vessels), and arteriosclerosis (hardening of the arteries) (Glanze 1996).

Acetyl-L-carnitine. Acetyl-L-carnitine has been shown to convert some hepatic parameters to more youthful levels. Acetyl-L-carnitine is the biologically active form of the amino acid L-carnitine that has been shown to protect cells throughout the body from age-related degeneration. By facilitating the youthful transport of fatty acids into the cell mitochondria, acetyl-L-carnitine facilitates conversion of dietary fats to energy and muscle. Acetyl-L-carnitine has also been shown to regenerate nerves (Fernandez et al. 1997), to provide protection against glutamate and ammonia induced toxicity to the brain (Rao et al. 1999), and to reverse the effects of heart aging in animals (Paradies et al. 1999).

Antioxidants that Reduce Free-Radical Damage
Vitamin C. Vitamin C is a potent antioxidant that is found naturally in many fruits and vegetables. According to Garg et al. (2000), vitamin C has protective effects against liver oxidative damage, particularly when used in combination with vitamin E. Researchers have found inadequate levels of vitamin C in patients with degenerative diseases. Garg et al. (2000) found that supplementation in rats lowered plasma and liver lipid peroxidation, normalized plasma vitamin C levels, and raised vitamin E above normal levels.

Vitamin E. Vitamin E protects the lipid membrane from oxidative damage. Adequate levels of vitamin E also protect cholesterol from oxidative damage. Oxidized cholesterol damages arteries and contributes to atherosclerosis (Mydlik et al. 2002). Hepatocytes incorporate vitamin E into lipoproteins, which then transport it to various tissues in the body.

Coenzyme Q10 (CoQ10). CoQ10 is an antioxidant that is protective for a liver that has been damaged by ischemia (reduced blood flow) (Genova et al. 1999). CoQ10 is also an important component of healthy metabolism. It protects the mitochondria and cell membrane from oxidative damage and helps generate ATP, the energy source for cells. CoQ10 is absorbed by the lymphatic system and distributed throughout the body. Japanese researchers studied the effects of the toxic drug hydrazine on liver cells. Hydrazine caused remarkable increases in intracellular levels of reactive oxygen species in hepatocytes, which were suppressed by CoQ10 (Teranishi et al. 1999).

N-acetyl-cysteine (NAC). N-acetyl-cysteine is an amino acid that acts as an antioxidant or free-radical scavenger. Most scientific articles related to liver protection with NAC emphasize this effect. NAC is frequently used in medical settings to treat liver toxicity associated with ingesting Tylenol (also poisonous mushrooms) (Hazai et al. 2001; Attri et al. 2001).

Alpha-lipoic acid (ALA). Alpha-lipoic acid is an antioxidant that has been shown to decrease the amount of hepatic fibrosis associated with liver injury. Both of these mechanisms suggest it has promise for cirrhosis. Because alpha-lipoic acid is fat soluble, it can penetrate the cell membrane to exert therapeutic action. It has been shown to effectively scavenge harmful free radicals, chelate toxic heavy metals, and help to prevent mutated gene expression (Biewenga et al. 1997). Another of its most beneficial functions is to enhance the effects of other essential antioxidants including glutathione, which is vital to the health of the liver (Lykkesfeld 1998; Khanna et al. 1999).

Selenium. Selenium is a trace element that acts by several mechanisms, including detoxifying liver enzymes, exerting anti-inflammatory effects, and providing antioxidant defense. The presence of selenium helps induce and maintain the glutathione antioxidant system (Sakaguchi 2000).

Zinc. Zinc is an essential dietary nutrient and is used in numerous drugs and preparations that are protective. Zinc helps remove copper from the body and is used as an adjuvant treatment in Wilson's disease (Brewer et al. 1999).

Protecting and Improving Liver Function
S-adenosylmethionine (SAMe). SAMe is a methylation agent (a methyl group donor) and is necessary for the synthesis of glutathione. Medical studies have shown that SAMe has beneficial antioxidant effects on the liver and other tissues, particularly in protecting and restoring liver cell function destroyed by the hepatitis C virus. SAMe decreases the production of liver collagen, which leads to the formation of fibrous tissue (Deulofeu et al. 2000). SAMe is found naturally in every cell of the body. It is synthesized from a combination of the amino acid L-methionine, folic acid, vitamin B12, and trimethylglycine, provided all these ingredients are present and performing (Anon. 2002).

Phosphatidylcholine (PC). Phosphatidylcholine is a type of fat that is part of cell membranes. PC is one of the most important substances for liver protection and health and is a primary constituent of cell membranes. PC acts by several mechanisms: exerting potent antioxidant effects; inhibiting the tendency of stellate cells to progress to cirrhosis; decreasing apoptotic death of liver cells and thereby prolonging the life of liver cells; stabilizing the cell membrane, thus improving the integrity and function of the liver cell; and exerting an antifibrotic effect related to the breakdown of collagen (not only slowing the progression of fibrosis, but also encouraging regression of existing fibrosis) (Ma 1996; Lieber 1999; Pniachik 1999; Wolf 2001). A special form of PC called polyenylphosphatidylcholine has been shown to prevent the early changes in the damaged liver from occurring before the actual development of cirrhosis (Navender 1997).

Silymarin. Silymarin, (also known as milk thistle or Silybum marinum) is a member of the aster family (Asteraceae). The active extract of milk thistle is silymarin (Bosisio et al. 1992), a mixture of flavolignans, including silydianin, silychristine, and silybin, with silybin being the most biologically active. Silymarin has proven to be one of the most potent liver-protecting substances known. Its main routes of protection appear to be the prevention of free-radical damage, stabilization of plasma membranes, and stimulation of new liver cell production. It has also been shown to inhibit lipid peroxidation and to prevent glutathione depletion induced by alcohol and other liver toxins, even increasing total glutathione levels in the liver by 35% over controls (Valenzuela et al. 1989). Early studies show that silymarin has the ability to stimulate protein synthesis, resulting in production of new liver cells to replace older, damaged ones (Sonnenbichler et al. 1986a; 1986b). Studies also demonstrate the benefits of silymarin for protection from numerous toxic chemicals.

Branched-chain amino acids. Branched-chain amino acids (leucine, isoleucine, and valine) are considered to be essential amino acids because humans cannot survive unless these amino acids are present in the diet. Branched chain amino acids (BCAAs) are needed for the maintenance of muscle tissue and appear to preserve muscle stores of glycogen (stored form of carbohydrates that can be converted into energy). Dietary sources of BCAAs are dairy products and red meat. Whey protein and egg protein supplements are other sources. Most diets provide the daily requirement of BCAAs for healthy people. However, in cases of physical stress, we have increased energy requirements, in particular persons with cirrhosis. Studies on alcoholic cirrhosis patients have shown benefits from supplementing valine, leucine, and isoleucine. These branched-chain amino acids can enhance protein synthesis in liver and muscle cells, help restore liver function, and prevent chronic encephalopathy (Shimazu 1990; Chalasani et al. 1996) In studies, BCAAs have also been shown to have therapeutic value in adults with cirrhosis of the liver. According to the researchers, BCAAs seem to be the preferred substrate to meet this requirement (Kato et al. 1998).

SUMMARY

If you already have a degenerative liver condition, or have symptoms of liver disease, consult a qualified physician who is experienced in treating liver disease and who will coordinate your treatment. Supplementation with antioxidants, branched-chain amino acids, and all of the B complex of vitamins except B3 (niacin) has been shown to have protective qualities and to be beneficial for the liver. The following are important in preventing liver disease and for providing beneficial supportive effects.

1. The B vitamins are essential for healthy metabolic functioning. Working individually and synergistically, they facilitate energy release and the manufacture of new cells.
   • B1 (thiamine), 500 mg
   • B2 (riboflavin), 75 mg
   • B5 (pantothenic acid), 1500 mg
   • B6 (pyridoxine), 200 mg
   • B12 (cobalamin), sublingual methylcobalamin is recommended for better absorption, one 5-mg lozenge 1-5 times daily
   • Folic acid, 800 mcg daily
   • Vitamin B3 (niacin) should be avoided by people with liver conditions as it disrupts healthy methylation patterns.
2. Choline helps reduce the amount of fat deposited in the liver, 1500 mg daily.
3. Acetyl-L-carnitine will help to maintain mitochondrial health, take 2 daily doses of 1000 mg.
4. Antioxidants afford protection to the liver from the damaging effects of free radicals produced from environmental toxins.
   • Take at least 2500 mg of vitamin C daily.
   • Vitamin E (400 IU of D-alpha tocopheryl succinate and 200 mg of gamma tocopherol daily provide broad-spectrum antioxidant protection).
   • CoQ10 protects the mitochondria from oxidative damage and provides cellular energy, 100-300 mg daily.
   • N-acetyl-cysteine (NAC) enhances the production of glutathione and has protective benefits for the liver from toxins. Take 600 mg daily.
   • Alpha-lipoic acid can dramatically increase glutathione levels inside of cells. Suggested dose is 250 mg 2-3 times a day.
   • The trace mineral selenium has shown antioxidant protection in the liver. Zinc is often deficient in the cirrhotic liver and acts as a chelator in removing copper from the system. Take selenium, 200 mcg daily, and zinc, 30-85 mg daily.
5. Several supplements can benefit a damaged or diseased liver:
   • S-adenosylmethionine (SAMe) is needed to synthesize glutathione and has restored liver function from damage due to hepatitis C. The suggested dose of SAMe is 400 mg 3 times daily. Do not take SAMe on an empty stomach.
   • Polyenylphosphatidylcholine (PPC) has been shown to prevent the development of fibrosis and cirrhosis and to prevent lipid peroxidation and associated liver damage from alcohol consumption. PPC is sold as a drug in Europe. A product called HepatoPro (formerly GastroPro) is one of the few American dietary supplements to provide pharmaceutical-grade polyenylphosphatidylcholine. Take two to three 900-mg capsules daily.
   • Silymarin extract from milk thistle can raise glutathione levels and has shown multi-faceted protective benefits to the liver. The most active flavonoid in silymarin is silibinin. A product called Silibinin Plus is formulated to provide the same silibinin extract used in European prescription drugs. One 325-mg capsule taken twice daily is recommended for healthy people. Patients with liver disease may take up to 6 capsules daily.
   • Branched-chain amino acids can enhance protein synthesis in the liver and are particularly beneficial in alcoholic cirrhosis. The suggested dose is 2-4 capsules daily between meals with fruit juice or before eating. Each capsule should contain 300 mg of leucine, 150 mg of isoleucine, and 150 mg of valine.

For more informatiON

More information on conventional therapies is available by contacting the American Liver Foundation, (800) 223-0179.

Product availabiliTY

HepatoPro (formerly GastroPro) (polyenylphosphatidylcholine), Silibinin Plus, branched-chain amino acids, choline capsules, B vitamins, SAMe, vitamin C, vitamin E (tocopheryl succinate and gamma tocopherol), selenium, zinc, coenzyme Q10, acetyl-L-carnitine, alpha-lipoic acid, and N-acetyl-cysteine (NAC) may be ordered by calling (800) 544-4440 or by ordering online.