|CRDAMC Homepage | CRDAMC Library Phone #: (254) 288-8366 | CRDAMC Library Fax #: (254) 288-8368|
Liver Disease, General
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.
However, this last function of the liver, neutralizing toxins, is also the organ’s Achilles’ heel. The process of rendering toxins harmless to the body at large may bring harm to the liver itself.
Alcohol is the most common chemical responsible for toxic damage to the liver, causing fatty liver, alcoholic hepatitis, and, potentially, cirrhosis of the liver. Exposure to industrial chemicals may harm the liver. Many prescription medications may damage the liver as well, including cholesterol-lowering drugs in the statin family and high-dose niacin (also used to reduce cholesterol levels.) The over-the-counter drug acetaminophen (Tylenol) is highly toxic to the liver when taken to excess. Finally, numerous natural herbs and supplements contain chemicals that may cause or accelerate harm to the liver. (See Herbs and Supplements to Use Only With Caution below.)
Chemicals aren’t the only source of harm to the liver. Viruses may infect it, causing viral hepatitis; hepatitis C, in particular, may become chronic and gradually destroy the liver. In addition, during pregnancy, the liver may become backed up with bile, a condition called cholestasis of pregnancy.
Conventional treatment of liver disease depends on the source of the problem. People who abuse alcohol will at the very least avoid further liver damage by stopping alcohol use, and, in cases short of liver cirrhosis, full liver recovery may be expected. When drugs are at fault, it may be possible to switch to a different drug.
Conventional treatment of liver injury caused by chronic viral hepatitis involves sophisticated immune-regulating therapies, which have become fairly successful. In extreme cases of liver injury, a liver transplant may be necessary.
Principal Proposed Natural Treatments
Natural treatments for alcoholic hepatitis, cirrhosis, and viral hepatitis are each discussed in their own articles. In this article, we discuss natural treatments for other forms of liver disease. In addition, we address the herbs and supplements that may harm the liver and that, therefore, should not be taken by people who already have liver disease.
The herb milk thistle has shown promise for a wide variety of liver conditions, and for this reason it is often said to have general liver protective properties.
Some evidence suggests benefit for viral hepatitis (especially chronic hepatitis), cirrhosis of the liver, alcoholic hepatitis, and liver toxicity caused by industrial chemicals, mushroom poisons, and medications.1-25 However, as yet the evidence that milk thistle really works remains incomplete and contradictory.
For example, a double-blind, placebo-controlled study performed in 1981 followed 106 Finnish soldiers with alcoholic liver disease over a period of 4 weeks.18 The treated group showed a significant decrease in elevated liver enzymes and improvement in liver histology (appearance of cells under a microscope), as evaluated by biopsy in 29 subjects.
Two similar studies provided essentially equivalent results.9,11 However, a 3-month, randomized, double-blind study of 116 people showed little to no additional benefit, perhaps because most participants reduced their alcohol consumption and almost half stopped drinking entirely.20 Another study found no benefit in 72 patients followed for 15 months.7
Study results similarly conflict on whether milk thistle is helpful in liver cirrhosis.
In a double-blind, placebo-controlled study of 170 people with alcoholic or non-alcoholic cirrhosis, researchers found that the 4-year survival rate was 58% in the group treated with milk thistle as compared to only 38% in the placebo group.10 This difference was statistically significant.
A double-blind, placebo-controlled trial that enrolled 172 people with cirrhosis for 4 years also found reductions in mortality, but they just missed the conventional cutoff for statistical significance.4 Yet another study, a 2-year, double-blind, placebo-controlled trial of 200 people with alcoholic cirrhosis, found no reduction in mortality attributable to the use of milk thistle.1
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.56
Milk thistle is also used in a vague condition known as minor hepatic insufficiency, or "sluggish liver."26 This term is mostly used by European physicians and American naturopathic practitioners—conventional physicians in America don't recognize it. Symptoms are supposed to include aching under the ribs, fatigue, unhealthy skin appearance, general malaise, constipation, premenstrual syndrome, chemical sensitivities, and allergies.
For more information, including dosage and safety issues, see the full Milk Thistle article.
The body manufactures S-adenosylmethionine (SAMe) for use in converting certain chemicals to other chemicals (specifically, through the processes of transmethylation and transsulfuration). Some evidence suggests that SAMe taken as an oral supplement may have value in the treatment of various liver diseases, including chronic viral hepatitis, liver cirrhosis, jaundice of pregnancy, and liver toxicity caused by drugs or chemicals.27-31,51-54
Perhaps the best evidence regards cholestasis (backup of bile in the liver) caused by serious liver disease. In a 2-week, double-blind study of 220 people with cholestasis, use of SAMe (1,600 mg daily) significantly improved liver-related symptoms as compared to placebo.28 Most participants in this study had chronic viral hepatitis.
Another large study evaluated the potential benefits of SAMe for the treatment of people with alcoholic liver cirrhosis.27 This 2-year, double-blind, placebo-controlled study of 117 people failed to find SAMe helpful for the group as a whole. However, in a subgroup of those with less advanced disease, treatment with SAMe appeared to reduce the number of people who needed a liver transplant, or who died.
Gilbert’s syndrome is an unexplained but harmless condition in which levels of bilirubin rise in the body, causing an alarming yellowing of the skin (jaundice). Weak evidence hints that SAMe may help reduce bilirubin levels in this condition.32
For more information, including dosage and safety issues, see the full SAMe article.
Other Proposed Natural Treatments TOP
Probiotics have been studied as possible treatment for liver disease. In one such study, 84 adults (aged 18-65) with liver disease ( cirrhosis or hepatitis) were randomized to receive yogurt (1 cup, 3 times daily) with or without the probiotics B. bifidus, L. acidophilus, L. bulgaricus, and S. thermophilus.58 After 2 weeks, the people in the probiotics group experienced an improvement in their symptoms, including less debilitation and better appetite. Chronic liver disease with cirrhosis can lead to a potentially life-threatening brain abnormality, called hepatic encephalopathy. A 2011 review of 7 randomized trials involving 550 people found inconclusive evidence to support the use of probiotics as a treatment for this condition.59
One double-blind study found evidence that a beverage made from sweet potato could improve measures of liver function in people with mild hepatitis of unspecified cause.55
Very preliminary evidence suggests that the supplement betaine (trimethylglycine, or TMG—not to be confused with betaine hydrochloride) may be helpful for treating fatty liver caused by alcohol and other causes, and also for protecting the liver from toxins in general.33-37
Green tea has long been considered to play a protective role against liver disease. However, the evidence to date is unconvincing.57
Numerous other herbs and supplements have shown a bit of promise in test tube studies for protecting the liver, including:
Hundreds of others are included on this list. However, it is a long way from test tube studies to effects in people, and none of these treatments should be regarded as having proven or even probable liver-protective properties.
Herbs and Supplements to Use Only With Caution TOP
Many natural products have the capacity to harm the liver. Furthermore, due to the generally inadequate regulation of dietary supplements that exists at the time of this writing, there are real risks that herbal products, at 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.
High doses of the supplements beta-carotene and vitamin A are thought to accelerate the progression of alcoholic liver disease in people who abuse alcohol.46,47 (Nutritional supplementation at the standard daily requirement level should not cause a problem.)
All forms of vitamin B3, including niacin, niacinamide (nicotinamide), and inositol hexaniacinate, may damage the liver when taken in high doses. (Again, 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: chaparral, coltsfoot, corydalis, comfrey, germander, germanium (a mineral), greater celandine, green tea extracts (despite its proposed benefits), kava , kombucha, mistletoe, noni, pennyroyal, pokeroot, sassafras, and various herbs and minerals used in traditional Chinese herbal medicine.
In addition, herbs that are not toxic to the liver 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 toxic to the liver, 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 toxic to the liver, 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,48 and case reports suggest that even very high doses of valerian do not harm the liver.49,50
References[ + ]
1. 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.
2. Albrecht M, Frerick H, Kuhn U, et al. Therapy of toxic liver pathologies with Legalon [in German]. Z Klin Med. 1992;47:87-92.
3. Allain H, Schuck S, Lebreton S, et al. Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 1999;10:181-185.
4. Benda L, Dittrich H, Ferenzi P, et al. The influence of therapy with silymarin on the survival rate of patients with liver cirrhosis [translated from German]. Wien Klin Wochenschr. 1980;92:678-683.
5. Berenguer J, Carrasco D. Double-blind trial of silymarin vs. placebo in the treatment of chronic hepatitis. Munch Med Wochenschr. 1977;119:240-260.
6. Bode JC, Schmidt U, Durr HK. Silymarin for the treatment of acute viral hepatitis? Report of a controlled trial [translated from German]. Med Klin. 1977;72:513-518.
7. Bunout D, Hirsch SB, Petermann MT, et al. Controlled study of the effect of silymarin on alcoholic liver disease [translated from Spanish]. Rev Med Chil. 1992;120:1370-1375.
8. Buzzelli G, Moscarella S, Giusti A, et al. A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB 1016) in chronic active hepatitis. Int J Clin Pharmacol Ther Toxicol. 1993;31:456-460.
9. Feher J, Desk G, Muzes G, et al. Liver protective action of silymarin therapy in chronic alcoholic liver diseases [in Hungarian]. Orv Hetil. 1989;130:2723-2727.
10. 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.
11. Fintelmann V, Albert A. Proof of the therapeutic efficacy of LegalonW for toxic liver illnesses in a double-blind trial [translated from German]. Therapiewoche. 1980;30:5589-5594.
12. Lang I, et al. Hepatoprotective and immunological effects of antioxidant drugs. Tokai J Exp Clin Med. 1990;15:123-127.
13. Lang I, et al. Immunomodulatory and hepatoprotective effects of in vivo treatment with free radical scavengers. Ital J Gastroenterol. 1990;22:283-287.
14. Lirussi F, Okolicsanyi L. Cytoprotection in the nineties: Experience with ursodeoxycholic acid and silymarin in chronic liver disease. Acta Physiol Hung. 1992;80:363-367.
15. 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.
16. Magliulo E, Gagliardi B, Fiori GP. Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres [translated from German]. Med Klin. 1978;73:1060-1065.
17. Palasciano G, Portincasa P, Palmieri V, et al. The effect of silymarin on plasma levels of malon-dialdehyde in patients receiving long-term treatment with psychotropic drugs. Curr Ther Res. 1994;55:537-545.
18. Salmi HA, Sarna S. Effect of silymarin on chemical, functional and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol. 1982;17:517-521.
19. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-Verlag; 1998:215-218.
20. Trinchet JC, Coste T, Levy VG, et al. Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients [translated from French]. Gastroenterol Clin Biol. 1989;13:120-124.
21. Muriel P, Garciapina T, Perez-Alvarez V, et al. Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J Appl Toxicol. 1992;12:439-442.
22. Paulova J, Dvorak M, Kolouch F, et al. Verification of the hepatoprotective and therapeutic effect of silymarin in experimental liver injury with tetrachloromethane in dogs. Vet Med (Praha). 1990;35:629-635.
23. Tuchweber B, Sieck R, Trost W. Prevention of silybin of phalloidin-induced acute hepatotoxicity. Toxicol Appl Pharmacol. 1979;51:265-275.
24. Boari C, Montanari FM, Galletti GP, et al. Toxic occupational liver diseases. Therapeutic effects of silymarin. Minerva Med. 1981;72:2679-2688.
25. Szilard S, Szentogyorgyi D, Demeter I. Protective effect of Legalon in workers exposed to organic solvents. Acta Med Hung. 1988;45:249-256.
26. Giannola C, Buogo F, Forestiere G, et al. A two-center study on the effects of silymarin in pregnant women and adult patients with so-called minor hepatic insufficiency. Clin Ther. 1985;114:129-135.
27. Mato JM, Camara J, Fernandez de Paz J, et al. S-adenosylmethionine in alcoholic cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999;30:1081-1089.
28. Frezza M, Surrenti C, Manzillo G, et al. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Gastroenterology. 1990;99:211-215.
29. Frezza M, Pozzato G, Pison G, et al. S-adenosylmethionine counteracts oral contraceptive hepatotoxicity in women. Am J Med Sci. 1987;293:234-238.
30. Frezza M, Pozzato G, Chiesa L, et al. Reversal of intrahepatic cholestasis of pregnancy in women after high dose S-adenosyl-L-methionine administration. Hepatology. 1984;4:274-278.
31. Nicastri P, Diaferia A, Tartagni M, et al. A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy. Br J Obstet Gynaecol. 1998;105:1205-1207.
32. Bombardieri G, Milani A, Bernardi L, et al. Effects of S-adenosyl-methionine (SAMe) in the treatment of Gilbert’s syndrome. Curr Ther Res. 1985;37:580-585.
33. Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol and the liver: a review. Alcohol. 1996;13:395-398.
34. Barak AJ, Beckenhauer HC, Junnila M, et al. Dietary betaine promotes generation of hepatic S-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration. Alcohol Clin Exp Res. 1993;17:552-555.
35. Murakami T, Nagamura Y, Hirano K. The recovering effect of betaine on carbon tetrachloride-induced liver injury. J Nutr Sci Vitaminol. 1998;44:249-255.
36. Kanbak G, Inal M, Baycu C. Ethanol-induced hepatotoxicity and protective effect of betaine. Cell Biochem Funct. 2001;19:281-285.
37. Abdelmalek MF, Angulo P, Jorgensen RA, et al. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol. 2001;96:2711-2717.
38. Thyagarajan SP, Subramanian S, Thirunalasundar T, et al. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Lancet. 1988;2:764-766.
39. Berk L, de Man RA, Schalm SW, et al. Beneficial effects of Phyllanthus amarus for chronic hepatitis B, not confirmed. J Hepatol. 1991;12:405-406.
40. Calixto JB, Santos AR, Cechinel Filho V, et al. A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential. Med Res Rev. 1998;18:225-258.
41. Leelarasamee A, Trakulsomboon S, Maunwongyathi P, et al. Failure of Phyllanthus amarus to eradicate hepatitis B surface antigen from symptomless carriers. Lancet. 1990;335:1600-1601.
42. Thyagarajan SP, Jayaram S, Valliammai T, et al. Phyllanthus amarus and hepatitis B. Lancet. 1990;336:949-950.
43. Thamlikitkul V, Wasuwat S, Kanchanapee P. Efficacy of Phyllanthus amarus for eradication of hepatitis B virus in chronic carriers. J Med Assoc Thai. 1991;74:381-385.
44. Doshi JC, Vaidya AB, Antarkar DS, et al. A two-stage clinical trial of Phyllanthus amarus in hepatitis B carriers: failure to eradicate the surface antigen. Indian J Gastroenterol. 1994;13:7-8.
45. Milne A, Hopkirk N, Lucas CR, et al. Failure of New Zealand hepatitis B carriers to respond to Phyllanthus amarus. N Z Med J. 1994;107:243.
46. Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr. 1999;69:1071-1085.
47. Ni R, Leo MA, Zhao J, Lieber CS. Toxicity of beta-carotene and its exacerbation by acetaldehyde in HepG2 cells. Alcohol. 2001;36:281-285.
48. European Scientific Cooperative on Phytotherapy. Valerianae radix. Exeter, UK: ESCOP; 1996-1997:2. Monographs on the Medicinal Uses of Plant Drugs, Fascicule 4.
49. 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.
50. Chan TY. An assessment of the delayed effects associated with valerian overdose [letter]. Int J Clin Pharmacol Ther. 1998;36:569.
51. Binder T, Salaj P, Zima T, et al. Ursodeoxycholic acid, S-adenosyl-L-methionine and their combinations in the treatment of gestational intrahepatic cholestasis (ICP)] Ceska Gynekol. 2006;71:92-98.
52. Burrows RF, Clavisi O, Burrows E. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2001;CD000493.
53. Roncaglia N, Locatelli A, Arreghini A, et al. A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis. BJOG. 2003;111:17-21.
54. Avezov SA, Mansurova FKh. Efficacy of combined use of ursodeoxycholic acid and heptral in the treatment of primary biliary cirrhosis. Klin Med (Mosk). 2004;82:46-49,55-58.
55. Suda I, Ishikawa F, Hatakeyama M, et al. Intake of purple sweet potato beverage effects on serum hepatic biomarker levels of healthy adult men with borderline hepatitis. Eur J Clin Nutr. 2007 Feb 14. [Epub ahead of print]
56. 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.
57. Jin X, Zheng RH, Li YM. Green tea consumption and liver disease: a systematic review. Liver Int. 2008 May 14.
58. Liu JE, Zhang Y, Zhang J, Dong PL, Chen M, Duan ZP. Probiotic yogurt effects on intestinal flora of patients with chronic liver disease. Nurs Res. 2010;59(6):426-432.
59. 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