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The liver is a marvelously sophisticated chemical laboratory, capable of carrying out thousands of chemical transformations on which the body depends. The liver produces important chemicals from scratch, modifies others to allow the body to use them better, and neutralizes an enormous range of toxins. Without a functioning liver, you can't live for very long.
Unfortunately, a number of influences can severely damage the liver. Alcoholism is the most common. Alcohol is a powerful liver toxin that harms the liver in three stages: alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Although the first two stages of injury are usually reversible, alcoholic cirrhosis is not. Generally, more than 10 years of heavy alcohol abuse is required to cause liver cirrhosis. Other causes include hepatitis C infection, primary biliary cirrhosis, and liver damage caused by occupational chemicals and drugs.
A cirrhotic liver is firm and nodular to the touch, and, in advanced cases, is shrunken in size. These changes reflect severe damage to its structure. A high percentage of liver cells have died, and fibrous scar-like tissue permeates the organ.
A cirrhotic liver cannot perform its chemical tasks, leading to wide-ranging impairment of bodily functions, such as the development of jaundice (yellowing of the skin due to unprocessed toxins), mental confusion, emaciation, and skin changes. In addition, the fibrous tissue impedes blood that is supposed to pass through the liver. This leads to abdominal swelling as fluid backs up (ascites), and to bleeding in the esophagus as veins expand to provide an alternative fluid path. Ultimately, coma develops, often triggered by internal bleeding or infection.
Treatments for liver cirrhosis begin with stopping the use of alcohol and all other liver-toxic substances. A number of treatments such as potassium-sparing diuretics can ameliorate symptoms to some extent, but they do not cure the disease.
The liver is too complex for a man-made machine to duplicate its functions, so there is no equivalent of kidney dialysis for liver cirrhosis. Only a liver transplant can help. Unfortunately, this is a very difficult operation, with a high failure rate. In addition, the supply of usable livers is inadequate to meet the need.
Note : Individuals with cirrhosis of the liver should not take any medications, herbs or dietary supplements without first consulting a physician. The liver is in charge of processing many substances taken into the body, and when it is severely damaged, as in liver cirrhosis, ordinarily benign substances may become toxic.
Principal Proposed Natural Treatments
The herb milk thistle might offer various liver-protective benefits. In Europe, it is used to treat viral hepatitis, alcoholic fatty liver, alcoholic hepatitis, liver cirrhosis and drug- or chemical-induced liver toxicity. An intravenous preparation made from milk thistle is used as an antidote for poisoning by the liver-toxic deathcap mushroom, Amanita phalloides. However, the supporting evidence for its use in any of these conditions remains far from definitive.
A double-blind, placebo-controlled study of 170 individuals with alcoholic or non-alcoholic cirrhosis found that in the group treated with milk thistle, the 4-year survival rate was 58% as compared to only 38% in the placebo group.1 This difference was statistically significant.
A double-blind, placebo controlled trial that enrolled 172 individuals with cirrhosis for 4 years also found reductions in mortality, but they just missed the conventional cutoff for statistical significance.2 And a 2-year, double-blind, placebo-controlled study of 200 individuals with alcoholic cirrhosis found no reduction in mortality attributable to the use of milk thistle.3
A 2007 review of published and unpublished studies on milk thistle as a treatment for liver disease concluded that benefits were seen only in low-quality trials, and, even in those, milk thistle did not show more than a slight benefit.51 However, in a 2008 analysis of 19 randomized trials, researchers concluded that milk thistle was significantly more effective at reducing mortality from liver cirrhosis (mostly alcohol-related) compared to placebo, but no more effective at reducing mortality from any cause.54
For more information, including dosage and safety issues, see the full Milk Thistle article.
Other Proposed Natural Treatments TOP
Individuals with liver cirrhosis have difficulty synthesizing the substance S-adenosylmethionine (SAMe) from the amino acid methionine.12,13 For this reason, supplemental SAMe (best known as a treatment for depression and osteoarthritis) has been tried as a treatment for cirrhosis. However, as yet, the evidence that it works is not strong.
A 2-year, double-blind, placebo-controlled trial followed 117 people with alcoholic liver cirrhosis.14 Overall, those given SAMe didn't do significantly better than those given placebo. However, when the results were re-evaluated to eliminate individuals with severe liver cirrhosis, a significant reduction in mortality and liver transplantation was seen with SAMe.
SAMe has also shown a bit of promise for primary biliary cirrhosis, though evidence is not consistent.46
For more information, including dosage and safety issues, see the full SAMe article.
Branched-chain amino acids (BCAAs) are naturally occurring molecules (leucine, isoleucine, and valine) that the body uses to build proteins. Because of how they are metabolized, BCAAs might be helpful for individuals with liver cirrhosis.24,52,53 However, the evidence that BCAAs actually help is not yet conclusive. Furthermore, individuals with cirrhosis of the liver should not increase amino acid or protein intake except under physician supervision.
For more information, including dosage and safety issues, see the full BCAAs article.
Oligomeric Proanthocyanidins TOP
Individuals with cirrhosis are susceptible to internal bleeding. Highly preliminary evidence suggests that oligomeric proanthocyanidins (OPCs) might help prevent this problem.25
OPCs are best documented as a treatment for venous insufficiency (closely related to varicose veins), where they are thought to work in part by stabilizing blood vessels. Individuals with cirrhosis have what amounts to internal varicose veins, caused by the shunting of fluid around the damaged liver. For more information, including dosage and safety issues, see the full OPCs article.
Other Natural Treatments That Might Help TOP
One small study suggests that the supplement carnitine might be helpful for people with hepatic encephalopathy, a life-threatening brain abnormality associated with severe cirrhosis.55Probiotics have also been studied as a possible treatment for hepatic encephalopathy. But, a 2011 review of 7 randomized trials involving 550 people found inconclusive evidence to support the use of probiotics for this condition.57
One study suggests that protein from vegetable sources might be preferable to protein from animal sources for people with liver cirrhosis,28 presumably due to differences in amino acid content.
Preliminary evidence from animal studies suggest that the supplement phosphatidylcholine might help prevent alcoholic liver cirrhosis.29 The supplement ornithine alpha-ketoglutarate (OKG) and related substance ornithine-l-aspartate have shown promise for treating hepatic encephalopathy.40,56
Antioxidants have been proposed for the treatment of primary biliary cirrhosis, based on the theory that free radicals play a role in the disease process. However, despite apparent promise seen in open trials, a double-blind, placebo-controlled study of 61 subjects failed to find that combination of vitamins A, C and E, selenium, methionine and CoQ10 produced any benefit in terms of fatigue or other liver-related symptoms.50
The bones of individuals with biliary cirrhosis often become thin. Taking calcium and vitamin D supplements might help.30,31 Antioxidants such as vitamin C, vitamin E, and lipoic acid have been tried for biliary cirrhosis, with promising results in very preliminary trials.32
Herbs and Supplements to Use Only With Caution TOP
Many natural products have the capacity to harm the liver. Furthermore, because of the generally inadequate regulation of dietary supplements that exists at the time of this writing, there are real risks that herbal products, at the least, may contain liver-toxic contaminants even if the actual herbs listed on the label are safe. For this reason, we recommend that people with liver disease do not use any medicinal herbs except under the supervision of a physician. Here, we list some specific information to aid in your decision-making process.
All forms of vitamin B3 may damage the liver when taken in high doses, including niacin, niacinamide (nicotinamide), and inositol hexaniacinate. (Nutritional supplementation at the standard daily requirement level should not cause a problem.
A great many herbs and supplements have known or suspected liver-toxic properties, including but not limited to:
In addition, herbs that are not liver-toxic in themselves are sometimes adulterated with other herbs of similar appearance that are accidentally harvested in a misapprehension of their identity (for example, germander found in skullcap products). Furthermore, blue-green algae species such as spirulina may at times be contaminated with liver-toxic substances called microcystins, for which no highest safe level is known. Some articles claim that the herb echinacea is potentially liver-toxic, but this concern appears to have been based on a misunderstanding of its constituents. Echinacea contains substances in the pyrrolizidine alkaloid family. However, while many pyrrolizidine alkaloids are liver-toxic, those found in echinacea are not believed to have that property.
Whole valerian contains liver-toxic substances called valepotriates; however, valepotriates are thought to be absent from most commercial valerian products,43 and case reports suggest that even very high doses of valerian do not harm the liver.44,45
References[ + ]
1. Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989;9:105-113.
2. Benda L, Dittrich H, Ferenzi P, et al. The effectiveness of silymarin therapy on the survival rate of patients with liver cirrhosis [translated from German]. Wien Klin Wochenschr. 1980;92:678-683.
3. Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol. 1998;28:615-621.
12. Horowitz JH, Rypins EB, Henderson JM, et al. Evidence for impairment of transsulfuration pathway in cirrhosis. Gastroenterology. 1981;81:668-675.
13. Duce AM, Ortiz P, Cabrero C, et al. S-adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis. Hepatology. 1988;8:65-68.
14. Mato JM, Camara J, Fernandez de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999;30:1081-1089.
24. Marchesini G, Bianchi G, Rossi B, et al. Nutritional treatment with branched-chain amino acids in advanced liver cirrhosis. J Gastroenterol. 2000;35(suppl):7-12.
25. Lesbere FX. Effect of endotelon on the capillary fragility index in a specific group: cirrhotic subjects [in French; English abstract]. Gaz Med Fr. 1983;90:332-337.
26. Liu G-T. Pharmacological actions and clinical use of Fructus schizandrae. Chin Med J. 1989;102:740-749.
27. Matsuzaki Y, Tanaka N, Osuga T. Is taurine effective for treatment of painful muscle cramps in liver cirrhosis? [letter]. Am J Gastroenterol. 1993;88:1466-1467.
28. Okita M, Watanabe A, Nagashima H. A vegetable protein-rich diet for the treatment of liver cirrhosis. Acta Med Okayama. 1985;39:59-65.
29. Lieber CS, Robins SJ, Li J, et al. Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology. 1994;106:152-159.
30. Epstein O, Kato Y, Dick R, et al. Vitamin D, hydroxyapatite, and calcium gluconate in treatment of cortical bone thinning in postmenopausal women with primary biliary cirrhosis. Am J Clin Nutr. 1982;36:426-430.
31. Compston JE, Horton LW, Thompson RP. Treatment of osteomalacia associated with primary biliary cirrhosis with parenteral vitamin D2 or oral 25-hydroxyvitamin D3. Gut. 1979;20:133-136.
32. Watson JP, Jones DE, James OF, et al. Case report: oral antioxidant therapy for the treatment of primary biliary cirrhosis: a pilot study. J Gastroenterol Hepatol. 1999;14:1034-1040.
33. Lucena MI, Andrade RJ, de la Cruz JP, et al. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Int J Clin Pharmacol Ther. 2002;40:2-8.
34. Lang I, et al. Hepatoprotective and immunological effects of antioxidant drugs. Tokai J Exp Clin Med. 1990;15:123-127.
35. Lang I, et al. Immunomodulatory and hepatoprotective effects of in vivo treatment with free radical scavengers. Ital J Gastroenterol. 1990;22:283-287.
36. Lucena MI, Andrade RJ, de la Cruz JP, et al. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Int J Clin Pharmacol Ther. 2002;40:2-8.
37. Leo MA, Aleynik SI, Aleynik MK, et al. Beta-carotene beadlets potentiate hepatotoxicity of alcohol. Am J Clin Nutr. 1997;66:1461-1469.
38. Ni R, Leo MA, Zhao J, Lieber CS. Toxicity of beta-carotene and its exacerbation by acetaldehyde in HepG2 cells. A lcohol. 2001;36:281-285.
39. Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr. 1999;69:1071-1085.
40. Kircheis G, Wettstein M, Dahl S, et al. Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy. Metab Brain Dis. 2002;17:453-462.
41. Mendal JN, Roy BK. Studies with Liv.52 in the treatment of infective hepatitis, chronic active hepatitis and cirrhosis of the liver. Probe. 1983;22:217.
42. de Silva HA, Saparamadu PA, Thabrew MI, et al. Liv.52 in alcoholic liver disease: a prospective, controlled trial. J Ethnopharmacol. 2003;84:47-50.
43. European Scientific Cooperative on Phytotherapy. Valerianae radix. Exeter, UK: ESCOP; 1996-1997:2. Monographs on the Medicinal Uses of Plant Drugs, Fascicule 4.
44. Chan TY, Tang CH, Critchley JA. Poisoning due to an over-the-counter hypnotic, Sleep-Qik (hyoscine, cyproheptadine, valerian). Postgrad Med J. 1995;71:227-228.
45. Chan TY. An assessment of the delayed effects associated with valerian overdose [letter]. Int J Clin Pharmacol Ther. 1998;36:569.
46. Avezov SA, Mansurov FKh. Efficacy of combined administration of ursodeoxycholic acid and hepthral in the treatment of primary biliary cirrhosis] Klin Med (Mosk). 2004;82:46-49,55-58.
47. Malaguarnera M, Pistone G, Elvira R, et al. Effects of L-carnitine in patients with hepatic encephalopathy. World J Gastroenterol. 2006;11:7197-202.
48. Habu D, Shiomi S, Tamori A, et al. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004;292:358-361
49. Huseini HF, Alavian SM, Heshmat R, et al. The efficacy of Liv-52 on liver cirrhotic patients: a randomized, double-blind, placebo-controlled first approach. Phytomedicine. 2005;12:619-624.
50. Prince MI, Mitchison HC, Ashley D, et al. Oral antioxidant supplementation for fatigue associated with primary biliary cirrhosis: results of a multicentre, randomized, placebo-controlled, cross-over trial. Aliment Pharmacol Ther. 2002;17:137-143.
51. Rambaldi A, Jacobs B, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 2007;CD003620.
52. Charlton M. Branched-chain amino Acid enriched supplements as therapy for liver disease. J Nutr. 2005;136:295S-298S.
53. Kobayashi M, Ikeda K, Arase Y, et al. Inhibitory effect of branched-chain amino acid granules on progression of compensated liver cirrhosis due to hepatitis C virus. J Gastroenterol. 2008;43:63-70.
54. Saller R, Brignoli R, Melzer J, et al. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch Komplement Med. 2008;15:9-20.
55. Malaguarnera M, Gargante MP, Cristaldi E, et al. Acetyl-L:-carnitine treatment in minimal hepatic encephalopathy. Dig Dis Sci. 2008 Mar 21.
56. Jiang Q, Jiang XH, Zheng MH, et al. l-Ornithine-l-aspartate in the management of hepatic encephalopathy: A meta-analysis. J Gastroenterol Hepatol. 2008 Sep 24.
57. McGee RG, Bakens A, Wiley K, Riordan SM, Webster AC. Probiotics for patients with hepatic encephalopathy. Cochrane Database Syst Rev. 2011 Nov 9;11:CD008716.
Last reviewed December 2015 by EBSCO CAM Review Board
Last Updated: 12/15/2015