Vitamins that may be helpful
Large amounts of S-adenosylmethionine (SAMe) may improve survival and liver function in
alcoholic liver cirrhosis. A double-blind trial found that 1,200 mg of SAMe per day for two
years significantly decreased the overall death rate and the need for liver transplantation in
people with alcoholic liver cirrhosis, particularly in those with less advanced liver
disease.11 Preliminary trials suggest that lower amounts of SAMe (180 mg per day in
one trial12 and 800 mg per day in another13 ) may improve liver function
in people with liver cirrhosis. SAMe supplementation has been shown to reverse the depletion
of glutathione, an important antioxidant
required for liver function.14 It has also been shown to aid in the resolution of
blocked bile flow (cholestasis), a common complication of liver cirrhosis.15
In addition to protein deficiency as discussed above, liver cirrhosis is characterized by
low blood levels of branched-chain amino acids
(BCAAs) in relation to other amino
acids.17 This imbalance may contribute to the development of PSE.18
BCAA supplementation could be a way to correct this problem, as well as to provide a source of
needed protein, but its effectiveness is unclear.19 BCAAs (isoleucine, leucine, and
valine) represent a good protein source for people with cirrhosis because they are less likely
to induce PSE. A controlled study of protein-intolerant people with cirrhosis showed that BCAA
supplementation corrected abnormal protein metabolism about as well as an equivalent amount of
dietary protein without inducing PSE as frequently.20 In a small double-blind
trial, people with liver cirrhosis taking 5 grams per day of BCAAs had significant improvement
in their ability to process protein.21
However, treatment trials using BCAAs alone or in solutions containing other amino acids in
people with cirrhosis and PSE have reported conflicting results.22 23
24 25 It may be that certain people with liver cirrhosis can benefit
from supplementation with BCAAs while others cannot, for reasons that are
unclear.26 In a double-blind trial, people with liver cirrhosis and PSE received
0.24 grams per 2.2 pounds body weight (approximately 16–17 grams per day) of BCAAs for
15 days, after which most experienced significant improvement in brain function, mental
status, and protein metabolism. Those who continued taking BCAAs for three months also had
mild improvement in liver function tests.27
Therapeutic effects of oral BCAAs have also been shown in children with liver
failure28 and in adults with cirrhosis of the liver without PSE.29
Overall, it appears that BCAA supplementation does not always help in cirrhosis, but some
people with and without PSE may benefit. A qualified doctor must closely supervise such BCAA
In a study of people with cirrhosis, supplementing with 10 grams of fermentable fiber per day (containing equal parts of beta-glucan,
inulin, pectin, and resistant starch) for 30 days resulted in an improvement in liver
function.30 The impaired brain function that often accompanies cirrhosis of the
liver (hepatic encephalopathy) also improved.
Phosphatidylcholine (PC) breaks down scar
tissue in the liver and may be able to reverse tissue changes that cause
cirrhosis.31 In animal studies, PC has been repeatedly shown to prevent or reverse
the progression of alcohol-induced cirrhosis,32 33 34 but
this has not yet been demonstrated in humans. In a controlled trial, Czech researchers found
that PC supplementation (900 mg per day for four months) improved liver function in people
Alcoholic liver cirrhosis is associated with
zinc deficiency.36 37 In a double-blind trial, zinc acetate
supplementation (200 mg three times daily, providing a total of 215 mg of elemental zinc per
day), given to cirrhosis patients for seven days, significantly improved portal-systemic
encephalopathy (PSE).38 A second trial achieved similar results after three months
of treatment.39 People with cirrhosis sometimes have impaired taste function, and
it has been suggested that zinc deficiency may be the cause of this abnormality. Although one
study demonstrated that taste problems in cirrhosis are due to the disease process itself and
not to zinc deficiency,40 a double-blind trial showed that 200 mg three times per
day of zinc sulfate (providing 135 mg of elemental zinc per day) for six weeks significantly
improved taste function in people with alcoholic liver cirrhosis.41 A doctor should
supervise long-term supplementation of zinc in these amounts.
People with cirrhosis have decreased secretion of bile acids.42 Supplementation
with bile acids (such as ursodeoxycholic acid and tauroursodeoxycholic acid) may improve the
composition of bile and delay disease progression in primary biliary cirrhosis (PBC). In one
trial, people with PBC were followed for five to nine years. Those who took 13–15 mg per
2.2 pounds body weight of ursodeoxycholic acid (about 900–1200 mg) per day had improved
liver function tests and significantly delayed progression to cirrhosis.43 Several
other trials have confirmed that bile acids improve liver function in people with
PBC.44 45 46 47 48 Commercial
supplements of bile acids are available as ox bile concentrates. However, these ox bile
preparations contain other types of bile acids than those used in PBC research. The
effectiveness and appropriate amount of ox bile concentrates in the treatment of PBC is
L-ornithine-L-aspartate (OA) is a
nutritional supplement that has been investigated as a treatment for cirrhosis and hepatic
encephalopathy. In a double-blind trial, participants taking 18 grams of OA for 14 days had
significant improvements in liver function, mental status, and brain function.49
Similar benefits have also been demonstrated using injections of OA.50
L-carnitine injections have been used to
improve circulation to the liver in people with cirrhosis,52 but trials of the oral
supplement are lacking.
Vitamin E has been shown to decrease damage
in cirrhotic livers and may reduce immune abnormalities that contribute to the development of
the disease.53 However, a study reported that supplementation of 500 IU per day of
vitamin E for one year failed to influence laboratory tests, liver function, survival or
hospitalization rates in people with alcoholic cirrhosis.54 Further clinical trials
are needed to determine if any benefits may be expected from vitamin E supplementation in
people with liver cirrhosis.
Selenium levels have been found to be low
in people with liver cirrhosis55 and the need for antioxidants has been found to be
increased.56 A small, preliminary trial suggested that 100 mcg per day of selenium
may improve liver function in people with alcoholic cirrhosis.57 Larger,
double-blind trials of selenium in people with liver cirrhosis are needed.
People with primary biliary cirrhosis are at increased risk of bone loss. In a preliminary
trial, supplementation with 0.5 micrograms of calcitriol (a prescription form of vitamin D) twice daily for 12 months prevented a loss
in bone mineral density.58 Whether regular vitamin D might also prevent bone loss
in people with PBC is unknown.
Are there any side effects or interactions?
Refer to the individual supplement for information about any side effects or interactions.
1. Beers MH, Berkow R (eds). The Merck Manual, 17th ed.
Whitehouse Station, NJ: Merck and Co., Inc., 1999, 372–4.
2. Lochs H, Plauth M. Liver cirrhosis: rationale and modalities for
nutritional support—the European Society of Parenteral and Enteral Nutrition consensus
and beyond. Curr Opin Clin Nutr Metab Care 1999;2:345–9.
3. Lieber CS. Nutrition in liver disorders. In: Shils ME, Olson JA, Shike
M, Ross AC (eds). Modern Nutrition in Health and Disease, 9th ed. Baltimore, MD:
Williams and Wilkins, 1999, 1179–80.
4. Rodriguez-Moreno F, Gonzalez-Reimers E, Santolaria-Fernandez F, et al.
Zinc, copper, manganese, and iron in chronic alcoholic liver disease. Alcohol
5. Gibbs K, Walshe JM. Studies with radioactive copper (64 Cu and 67 Cu);
the incorporation of radioactive copper into caeruloplasmin in Wilson’s disease and in
primary biliary cirrhosis. Clin Sci 1971;41:189–202.
6. Lieber CS. Nutrition in liver disorders. In: Shils ME, Olson JA, Shike
M, Ross AC (eds). Modern Nutrition in Health and Disease, 9th ed. Baltimore, MD:
Williams and Wilkins, 1999:1179–80.
7. Halsted CH. Alcohol: medical and nutritional effects. In Ziegler EE,
Filer LJ (eds). Present Knowledge in Nutrition, 7th ed. ILSI Press, Washington, DC,
8. Roggin GM, Iber FL, Kater RM, Tabon F. Malabsorption in the chronic
alcoholic. Johns Hopkins Med J 1969;125:321–30.
9. Roggin GM, Iber FL, Linscheer WG. Intraluminal fat digestion in the
chronic alcoholic. Gut 1972;13:107–11.
10. Luca A, Garcia-Pagan JC, Bosch J, et al. Effects of ethanol
consumption on hepatic hemodynamics in patients with alcoholic cirrhosis.
11. 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;30:1081–9.
12. Miglio F, Stefanini GF, Corazza GR, et al. Double-blind studies of
the therapeutic action of S-Adenosylmethionine (SAMe) in oral administration, in liver
cirrhosis and other chronic hepatitides. Minerva Med 1975;66:1595–9 [In
13. Gorbakov VV, Galik VP, Kirillov SM. Experience in heptral treatment
of diffuse liver diseases. Ter Arkh 1998;70:82–6 [in Russian].
14. Loguercio C, Nardi G, Argenzio F, et al. Effect of
S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in
alcoholic patients with and without liver disease. Alcohol Alcohol
15. Frezza M, Centini G, Cammareri G, et al. S-adenosylmethionine for the
treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial.
Hepatogastroenterology 1990;37 Suppl 2:122–5.
16. 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;99:211–5.
17. Lieber CS. Nutrition in liver disorders. In: Shils ME, Olson JA,
Shike M, Ross AC (eds). Modern Nutrition in Health and Disease, 9th ed. Baltimore,
MD: Williams and Wilkins, 1999, 1179–80.
18. Beers MH, Berkow R (eds). The Merck Manual, 17th ed.
Whitehouse Station, NJ: Merck and Co., Inc., 1999, 362–4.
19. Nompleggi DJ, Bonkovsky HL. Nutritional supplementation in chronic
liver disease: an analytical review. Hepatology 1994;19:518–33 [review].
20. Horst D, Grace ND, Conn HO, et al. Comparison of dietary protein with
an oral, branched chain-enriched amino acid supplement in chronic portal-systemic
encephalopathy: a randomized controlled trial. Hepatology 1984;4:279–87.
21. Okita M, Watanabe A, Nagashima H. Treatment of liver cirrhosis with
branched chain amino acid-supplemented diet. Gastroenterol Jpn
22. Maddrey WC. Branched chain amino acid therapy in liver disease. J
Am Coll Nutr 1985;4:639–50 [review].
23. Wahren J, Denis J, Desurmont P, et al. Is intravenous administration
of branched chain amino acids effective in the treatment of hepatic encephalopathy? A
multicenter study. Hepatology 1983;3:475–80.
24. Egberts E-H, Schomerus H, Hamster W, Jürgens P. Branched chain
amino acids in the treatment of latent portosystemic encephalopathy. A doublel-blind
placebo-controlled crossover study. Gastroenterology 1985;88:887–95.
25. Muto Y, Sato S, Watanabe A, et al. Effects of oral branched-chain
amino acid granules on event-free survival in patients with liver cirrhosis. Clin
Gastroenterol Hepatol 2005;3:705–13.
26. Dioguardi FS, Brigatti M, Dell’Oca M, et al. Effects of chronic
oral branched-chain amino acid supplementation in a subpopulation of cirrhotics. Clin
Physiol Biochem 1990;8:101–7.
27. Marchesini G, Dioguardi FS, Bianchi GP, et al. Long-term oral
branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized
double-blind casein-controlled trial. The Italian Multicenter Study Group. J Hepatol
28. Chin SE, Shepherd RW, Thomas BJ, et al. Nutritional support in
children with end-stage liver disease: a randomized crossover trial of a branched-chain amino
acid supplement. Am J Clin Nutr 1992;56:158–63.
29. Kato M, Miwa Y, Tajika M, et al. Preferential use of branched-chain
amino acids as an energy substrate in patients with liver cirrhosis. Internal Med
30. Liu Q, Duan ZP, Ha DK, et al. Synbiotic modulation of gut flora:
effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology
31. Ma X, Zhao J, Lieber CS. Polyenylphosphatidylcholine attenuates
non-alcoholic hepatic fibrosis and accelerates its regression. J Hepatol
32. Lieber CS, Robins SJ, Leo MA. Hepatic phosphatidylethanolamine
methyltransferase activity is decreased by ethanol and increased by phosphatidylcholine.
Alcohol Clin Exp Res 1994;18:592–5.
33. Lieber CS, Robins SJ, Li J, et al. Phosphatidylcholine protects
against fibrosis and cirrhosis in the baboon. Gastroenterology
34. Lieber CS, DeCarli LM, Mak KM, et al. Attenuation of alcohol-induced
hepatic fibrosis by polyunsaturated lecithin. Hepatology 1990;12:1390–8.
35. Fassati P, Horejsi J, Fassati M, et al. Essential choline
phospholipids and their effect on HBsAg and selected biochemical tests in cirrhosis of the
liver. Cas Lek Cesk 1981 22;120:56–60 [in Czech].
36. Taniguchi S, Kaneto K, Hamada T. Acquired zinc deficiency associated
with alcoholic liver cirrhosis. Int J Dermatol 1995;34:651–2.
37. Scholmerich J, Lohle E, Kottgen E, Gerok W. Zinc and vitamin A
deficiency in liver cirrhosis. Hepatogastroenterology 1983;30:119–25.
38. Reding P, Duchateau J, Bataille C. Oral zinc supplementation improves
hepatic encephalopathy. Results of a randomised controlled trial. Lancet
39. Marchesini G, Fabbri A, Bianchi G, et al. Zinc supplementation and
amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology
40. Sturniolo GC, D’Inca R, Parisi G, et al. Taste alterations in
liver cirrhosis: are they related to zinc deficiency? J Trace Elem Electrolytes Health
41. Weismann K, Christensen E, Dreyer V. Zinc supplementation in
alcoholic cirrhosis. A double-blind clinical trial. Acta Med Scand
42. Vlahcevic ZR, Miller JR, Farrar JT, Swell L. Kinetics and pool size
of primary bile acids in man. Gastroenterology 1971;61:85–90.
43. Angulo P, Batts KP, Therneau TM, et al. Long-term ursodeoxycholic
acid delays histological progression in primary biliary cirrhosis. Hepatology
44. Larghi A, Crosignani A, Battezzati PM, et al. Ursodeoxycholic and
tauro-ursodeoxycholic acids for the treatment of primary biliary cirrhosis: a pilot crossover
study. Aliment Pharmacol Ther. 1997;11:409–14.
45. Crosignani A, Battezzati PM, Setchell KD, et al. Tauroursodeoxycholic
acid for treatment of primary biliary cirrhosis. A dose-response study. Dig Dis Sci
46. Setchell KD, Rodrigues CM, Podda M, Crosignani A. Metabolism of
orally administered tauroursodeoxycholic acid in patients with primary biliary cirrhosis.
47. Ferri F, Bernocchi P, Fedeli S. Taurodeoxycholic acid in the
treatment of primary biliary cirrhosis. A controlled study in comparison to ursodeoxycholic
acid. Clin Ter 1993;143:321–6 [in Italian].
48. Pares A, Caballeria L, Rodes J, et al. Long-term effects of
ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled
multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the
Liver. J Hepatol 2000;32:561–6.
49. Stauch S, Kircheis G, Adler G, et al. Oral L-ornithine-L-aspartate
therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study.
J Hepatol 1998;28:856–64.
50. Kircheis G, Nilius R, Held C, et al. Therapeutic efficacy of
L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy:
results of a placebo-controlled, double-blind study. Hepatology
51. Staedt U, Leweling H, Gladisch R, et al. Effects of ornithine
aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind,
randomized study using a four-fold crossover design. J Hepatol
52. Pugliese D, Sabba C, Ettorre G et al. Acute systemic and splanchnic
haemodynamic effects of l-carnitine in patients with cirrhosis. Drugs Exp Clin Res
53. Ferro D, Basili S, Practico D, et al. Vitamin E reduces monocyte
tissue factor expression in cirrhotic patients. Blood 1999;93:2945–50.
54. de la Maza MP, Petermann M, Bunout D, Hirsch S. Effects of long-term
vitamin E supplementation in alcoholic cirrhotics. J Am Coll Nutr
55. Burk RF, Early DS, Hill KE, et al. Plasma selenium in patients with
cirrhosis. Hepatology 1998;27:794–8.
56. Feher J, Lengyel G, Blazovics A. Oxidative stress in the liver and
biliary tract diseases. Scand J Gastroenterol Suppl 1998;228:38–46.
57. Van Gossum A, Neve J. Low selenium status in alcoholic cirrhosis is
correlated with aminopyrine breath test. Preliminary effects of selenium supplementation.
Biol Trace Elem Res 1995;47:201–7.
58. Shiomi S, Masaki K, Habu D, et al. Calcitriol for bone loss in
patients with primary biliary cirrhosis. J Gastroenterol 1999;34:241–5.
59. Yamamoto M, Oka H, Kanno T, et al. Controlled prospective trial to
evaluate sho-saiko-to for the prevention of hepatotcellular carcinoma in patients with
cirrhosis of the liver. Gan To Kagaku Ryoho (Jpn J Cancer Chemother)
1989;16:1519–24 [in Japanese].
60. Kumada T, et al. Effect of shakuyaku-kanzo-to (Tsumura TJ-68) on
muscle cramps accompanying cirrhosis in a placebo-controlled double-blind parallel study.
J Clin Ther Med 1999;15:499–523.
61. 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.
62. Salmi HA, Sarna S. Effect of silymarin on chemical, functional and
morphological alterations of the liver. A double-blind controlled study. Scand J
63. Feher J, Deak G, Muzes G, et al. Liver-protective action of silymarin
therapy in chronic alcoholic liver diseases. Orv Hetil 1989;130:2723–7 [in
64. Muzes G, Deak G, Lang I, et al. Effect of silymarin (Legalon) therapy
on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double
blind protocol.) Orv Hetil 1990:131:863–6 [in Hungarian].
65. Velussi M, Cernigoi AM, De Monte A, et al. Long-term (12 months)
treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous
insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol
66. Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled
trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol
67. Velussi M, Cernogoi AM, De Monte A, et al. Long-term (12 months)
treatment with an antioxidant drug (silymarin) is effective on hyperinsulinemia, exogenous
insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatology
68. Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic
patients with cirrhosis of the liver: results of a double-blind, randomized and multicenter
trial. J Hepatol 1998;28:731–3.