Liver Degenerative Disease
Conventional Medical Therapy
Liver damage caused by degenerative conditions is irreversible. There are no commonly accepted, effective, conventional drug therapy regimes to prevent or reverse liver damage. Treatment primarily consists of identifying the underlying cause(s), determining possible steps to slow or stop progression of degeneration, and manage symptoms. One causal factor is alcohol: stopping alcohol intake will help stop progression. Ending the use of hepatotoxic drugs and removing sources of environmental toxins will also stop progression. The possible presence of metabolic diseases (eg, hemochromatosis, Wilson's disease) should be investigated. Identifying the presence of hepatitis viruses is essential. Because obesity plays an important role in fatty liver, attention to weight control is essential.
Conventional drug therapies can include:
- Colchicine. Colchicine, a generic drug used to treat gout, also inhibits collagen (a protein in the body the makes up scar tissue) and has produced some improvement in liver function and patient survival (Nidus 1999).
- Corticosteroids. Corticosteroids reduce inflammation and have been helpful in improving liver function and symptoms; however, they have potentially serious side effects (Glanze 1996). If taking a corticosteroid, measures must be taken to monitor adverse side effects such as edema, hypertension, diabetes mellitus, osteoporosis, and ulcers.
- Malotilate. Malotilate (a drug developed in Japan) prevents damage to liver cells (and cirrhosis) induced in laboratory animals. It has been shown by several researchers to prevent induced liver damage, accumulation of collagen, and morphologic changes (such as accumulation of inflammatory cells and fibrosis and to reduce ethanol induced lesions) (Takase 1989; Mirossay 1996; Ryhanen 1996).
- Alpha interferon (Intron A) and ribavirin (Rebetol and Virazole). Alpha interferon and ribavirin are antiviral drugs used in treating hepatitis viruses. These drugs are a mainstay for some persons (NIDA 2002). However, some patients are not responsive, experience relapse after the antiviral drugs are discontinued, or have great difficulty handling the side effects (Strickland 2002). Newer alpha interferon drugs are pegylated, meaning they contain polyethylene glycol combined with interferon. PEG-Intron was approved by the FDA in January 2001 for once-weekly therapy for the hepatitis C virus. Another drug, PEGASYS was approved by the FDA in October 2002 as therapy for treating the hepatitis C virus.
- Gene therapy. Gene therapy as a treatment option is the subject of research, but even if research indicates that gene therapy appears feasible, human trials are years away.
Itching is a very troublesome symptom for patients with liver disease. It is also a very difficult symptom to manage for physicians. The reason why patients with liver disease itch is not understood. One thought is that certain substances accumulate in the blood as a result of liver disease and cause itching. The nature of these substances is under investigation, but some evidence suggests that normal substances found in blood plasma (eg, endogenous opioids known as enkaphalins) for some unknown reason cause itching in liver disease patients. Itching/scratching studies have also shown that some patients manifest scratching in a 24-hour rhythm (circadian), suggesting that neurotransmitters in the brain may cause itching (Bergasa 2002). At this time, the followin treatment is available for itching secondary to liver disease:
- Cholestyramine (taken with food) and Naltrexone can help relieve itching (Nidus 1999). High doses of Naltrexone are toxic for the liver, but low doses appear to be safe.
Phototherapy (light therapy) has been helpful in reducing itching (Nidus 1999).
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 from physical assaults of trauma and disease. Some 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 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:
- Maintain healthy metabolic functioning
- Neutralize free-radical damage
- Increase levels of glutathione, the liver's natural antioxidant
- Detoxify the liver
Supplements that Maintain Metabolic Health
Vitamin B complex. 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 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, an important member of the B-complex family, reduces harmful levels of homocysteine (ie, 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 (ie, an indicator of increased oxidative stress). Therefore, folic acid is potentially beneficial if there is ongoing oxidative damage (Chern 2001).
Choline. Another B complex vitamin 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. Choline deficiency can lead to degenerative diseases such as cirrhosis with associated conditions such as bleeding, kidney damage, hypertension (high blood pressure), hypercholesterolemia (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 1997), provide protection against glutamate and ammonia induced toxicity to the brain (Rao 1999), and reverse the effects of heart aging in animals (Paradies 1999).
Antioxidants that Reduce Free-Radical Damage
Vitamin C. Vitamin C is a potent antioxidant found naturally in many fruits and vegetables. 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. They noted that supplementation in rats lowered plasma and liver lipid peroxidation, normalized plasma vitamin C levels, and raised vitamin E above normal levels (Garg 2000).
Vitamin E. Vitamin E protects the lipid membrane from oxidative damage. Adequate vitamin E levels also protect cholesterol from oxidative damage. Oxidized cholesterol damages arteries and contributes to atherosclerosis (Mydlik 2002). Hepatocytes incorporate vitamin E into lipoproteins, which then transport it to various tissues in the body.
Coenzyme Q10. Coenzyme Q10 (CoQ10) is an antioxidant that is protective for a liver that has been damaged by ischemia (reduced blood flow) (Genova 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 1999).
N-acetyl-cysteine. N-acetyl-cysteine (NAC) 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 2001; Attri 2001).
Lipoic acid. Alpha-lipoic acid is an antioxidant 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 prevent mutated gene expression (Biewenga 1997). Another of its most beneficial functions is enhancing the effects of other essential antioxidants including glutathione, which is vital to a healthy liver (Lykkesfeld 1998; Khanna 1999). Alpha lipoic acid consists of two different forms (isomers) that have vastly different properties. The “R” form is the biologically active component (native to the body) that is responsible for lipoic acid’s phenomenal antioxidant effect. The “S” form is produced from chemical manufacture and is not very biologically active. Alpha lipoic acid supplements consist of the “R” and “S” form in a 50/50 ratio. That means a 100 mg alpha lipoic acid supplement is providing 50 mg of the biologically active “R” form. The human body normally produces and uses R-lipoic acid, the active form.
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 used in numerous protective drugs and preparations. Zinc helps remove copper from the body and is used as an adjuvant treatment in Wilson's disease (Brewer 1999).
Schisandra and melon pulp concentrate. As the body loses its natural primary antioxidant mechanisms, it accumulates lipid peroxidation products, and liver mitochondria begin to fail. Purified extract from a non-GMO Cucumis melo melon has been found to be rich in superoxide dismutase (SOD), the first enzyme in the body's mitochondrial oxidant protection system (Vouldoukis 2004; Lester 2009). Melon-derived SOD quickly converts primary free oxygen radicals into hydrogen peroxide. That hydrogen peroxide must be rapidly converted into water to complete the mitochondrial oxidant detoxification process. That task is handled by a second liver-protective agent, an extract of the Chinese vine Schisandra chinensis.
Protecting and Improving Liver Function
S-adenosylmethionine. S-adenosylmethionine(SAMe), a methylation agent (a methyl group donor), 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 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. Phosphatidylcholine is a type of fat that is part of cell membranes. Phosphatidylcholine, one of the most important substances for liver protection and health, is a primary constituent of cell membranes. Phosphatidylcholine 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 phosphatidylcholine called polyenylphosphatidylcholine (PPC) 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 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. 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 prevent glutathione depletion induced by alcohol and other liver toxins, even increasing total glutathione levels in the liver by 35% over controls (Valenzuela 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 1986a,b). 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 their 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, energy requirements increase (in persons with cirrhosis, in particular). 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 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 1998).