Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. A review of clinical data with silymarin calculated the overall odds ratio for liver-related mortality in the silymarin versus placebo groups across the five studies as 0.53 (i.e., 47% risk reduction; 95% confidence intervals 0.33–0.86) . Clin Toxicol (Phila). https://doi.org/10.1016/j.fct.2012.02.025. Because silymarin has been shown to lower elevated blood glucose and hemoglobin A1c levels in patients with diabetes, there is theoretical potential for an additive risk of hypoglycemia in patients taking antidiabetic drugs . 1992;120(12):1370–5. I. Biliary and renal elimination after a single oral dose. Lancet Oncol. Schulz HU, Schurer M, Krumbiegel G, Wachter W, Weyhenmeyer R, Seidel G. The solubility and bioequivalence of silymarin preparations. Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. PubMed Google Scholar. Milk thistle facilitates liver cell regeneration and can protect the liver … Epub 2020 Feb 17. Herbal food supplement. NAFLD is another major cause of chronic liver disease in the absence of significant alcohol consumption and is frequently associated with insulin resistance, central obesity, type-2 diabetes and dyslipidemia [42, 66]. Alterations in sulfur amino acid metabolism in mice treated with silymarin: a novel mechanism of its action involved in enhancement of the antioxidant defense in liver. 2015;4(1):204–47. Gillessen, A., Schmidt, H.HJ. Curr Pharm Biotechnol. Phytother Res. Approximately 50–60% of the silymarin complex is silibinin, with the other flavonolignan isomers comprising about 35%: silichristin (~ 20%), silidianin (~ 10%) and isosilibinin (~ 5%) [13, 14]. The antifibrogenic effect of silymarin has also been confirmed in an animal model of alcohol-induced hepatic fibrosis in non-human primates receiving chronic treatment with alcohol . O’Shea RS, Dasarathy S, McCullough AJ. . Life Sci. Moreover, NF-κB is activated in virtually every chronic liver disease, including AFLD , NAFLD , viral hepatitis  and biliary liver disease [47, 48]. 2020 Mar 30;21(7):2369. doi: 10.3390/ijms21072369. Hepatotoxicity may necessitate treatment discontinuation, drug interruption and substitution or dose adjustment . In vitro, silibinin is found to be a potent scavenger of ROS, such as hydroxyl and peroxyl anions and hypochlorous acid, in various model systems, such as rat liver microsomes , as well as human platelets, leukocytes, endothelial cells , erythrocytes  and fibroblasts . Chen Z, Yu R, Xiong Y, Du F, Zhu S. A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease. China Med. https://doi.org/10.1038/nri3623. After gastrointestinal absorption silibinin and the other components of silymarin are rapidly metabolized by phase I and phase II biotransformation reactions in liver cells  and undergo extensive enterohepatic circulation : about 80% of silibinin is excreted as glucuronide and sulfate conjugates with bile [25, 26]. World J Gastroenterol. Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review, https://doi.org/10.1016/j.jhep.2018.09.014, https://doi.org/10.1053/jhep.1996.v23.pm0008666328, https://doi.org/10.1111/j.1530-0277.2006.00063.x, https://doi.org/10.1016/S1470-2045(13),70414-5, https://doi.org/10.1111/j.1572-0241.1998.00139.x, https://doi.org/10.2165/00003495-200161140-00003, https://doi.org/10.1016/j.tiv.2007.11.020, https://doi.org/10.3390/biomedicines6040106, https://doi.org/10.1016/j.fct.2012.02.025, https://doi.org/10.1016/j.phrs.2009.12.017, https://doi.org/10.1016/j.jhep.2009.02.023, https://doi.org/10.1186/s12944-017-0572-9, https://doi.org/10.1517/14728184.108.40.2065, https://doi.org/10.1016/j.jhep.2018.03.018, https://doi.org/10.1002/14651858.cd003620.pub3, https://doi.org/10.1016/j.jhep.2015.11.004, https://doi.org/10.1016/j.bbagen.2012.09.008, https://doi.org/10.1016/j.cgh.2017.04.016, https://doi.org/10.1007/s40268-015-0084-x, https://doi.org/10.1111/j.1572-0241.2001.05283.x, https://doi.org/10.3109/15563650.2011.557663, https://doi.org/10.1016/S2095-4964(17),60319-4, https://doi.org/10.1186/s12906-015-0861-7, https://doi.org/10.1016/j.critrevonc.2018.06.019, https://doi.org/10.1016/j.phymed.2009.02.002, https://doi.org/10.1016/j.dld.2004.06.015, https://apps.who.int/medicinedocs/en/d/Js4927e/, https://www.elsevier.com/books/the-essential-guide-to-herbal-safety/mills/978-0-443-07171-3, https://doi.org/10.6084/m9.figshare.11778396, http://creativecommons.org/licenses/by-nc/4.0/, https://doi.org/10.1007/s12325-020-01251-y. Clin Gastroenterol Hepatol. cysteine) for its biosynthesis, which subsequently contributes to the enhancement of its antioxidant capacity in liver tissues . It has potent antioxidant action and prevents lipid peroxidation. Several trials have investigated the effectiveness of silymarin in preventing DILI from ATDs. Silymarin may augment the generation of glutathione in the liver via an increase in substrate availability (i.e. Oxidative stress and antioxidant biomarkers in clinical and experimental models of non-alcoholic fatty liver disease. Hepatology. Historically, milk thistle has typically been used to address liver conditions, such as viral hepatitis, cirrhosis, and fatty liver. 2011;33(1):127–37. Compared with placebo recipients, those receiving silymarin had significantly faster resolution of biliary retention symptoms of dark urine, jaundice and scleral icterus as well as a significant reduction in indirect bilirubin at day 56; there were no significant between-group differences in changes in other indicators of hepatocellular damage . Look for a high-quality product that’s between 50–150 milligrams of pure milk thistle extract per capsule so you can adjust … 23.3).Preclinical studies by Varshosaz and coworkers 66 have shown that silymarin … Forsch Komplementmed. Crude silymarin extract is lipophilic and poorly soluble in water, so only about 20–50% is absorbed from the gastrointestinal tract after ingestion [18, 19]. Dig Dis. 2003;37(4):336–9. Improvement Effect of Lotus Leaf Flavonoids on Carbon Tetrachloride-Induced Liver Injury in Mice. For ongoing use and liver support, take 50 to 150 milligrams daily. https://doi.org/10.1159/000100581. https://doi.org/10.1016/j.phrs.2009.12.017. 5a). This was measured by serum levels of free sulfhydryl groups and glutathione peroxidase activity in erythrocytes and lymphocytes in patients with alcohol-induced liver disease receiving silymarin or placebo. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. Historically, people have used milk thistle for liver disorders and gallbladder problems. https://doi.org/10.3109/15563650.2011.557663. Results showed that concomitant administration of silymarin significantly reduced the alcohol-induced increase in hepatic collagen type I (Fig. As symptom and QOL improvements were observed in both groups, it is possible that they were related to improved health care (regular nurse home visits and medical care) in a community that generally has limited access to these services . Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Therefore, amatoxin is used experimentally as a toxic model for liver failure. 1968;18(6):698–704. A Cochrane review of trials in patients with alcoholic and/or viral liver disease found that, compared with placebo or no intervention, milk thistle significantly reduced liver-related mortality in all reviewed trials, but not when the analysis was limited to high-quality trials . 2012;50(5):1568–75. Protective effect of lyophilized sapodilla (. https://doi.org/10.1152/ajpgi.00098.2006. In the placebo group, there were 32/39 liver-related deaths, whereas in the silymarin group 16/28 patient deaths were related to liver disease. Toxicol In Vitro. Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. For example, it is widely acknowledged that ethanol promotes the formation of various free radicals in several cell types, including hepatocytes, Kupffer cells, endothelial cells and infiltrating inflammatory leukocytes . https://doi.org/10.1016/S1470-2045(13),70414-5. Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review. Furthermore, it exerts an anti-atherosclerotic effect, and suppresses tumor necrosis factor-alpha-induced protein production and mRNA expression due to adhesion molecules. Hagag AA, Elgamsy MA, El-Asy HM, Mabrouk MM. 2013;79(12):997–1002. https://doi.org/10.2165/00003495-200161140-00003. 6) . Silymarin has not been investigated formally for all liver diseases but it is a very safe substance and should not cause problems if used in a liver situation where its benefit is unproven. Silymarin also commonly known as milk thistle is a flowering plant that’s known for its medicinal properties. Early diagnosis and prompt initiation of intravenous therapy are crucial. Teschke R. Alcoholic liver disease: alcohol metabolism, cascade of molecular mechanisms, cellular targets, and clinical aspects. Silybin is an active ingredient that’s extracted from the seeds of this plant. 2020 Sep;27(9):2373-2379. doi: 10.1016/j.sjbs.2020.05.010. Zhu HJ, Brinda BJ, Chavin KD, Bernstein HJ, Patrick KS, Markowitz JS. https://doi.org/10.1055/s-2008-1074867. There’s not a fixed milk thistle dosage for fatty liver or any other liver condition. 2012;13(10):1964–70. In a study in China, patients with acute lymphoblastic or acute myeloid leukemia undergoing chemotherapy (n = 70) received either the Eurosil 85®-derived formulation of silymarin (420 mg/day) plus diammonium glycyrrhizinate or diammonium glycyrrhizinate alone . Silymarin Indications/Uses . Adv Ther 37, 1279–1301 (2020). Alrashood ST, Al-Asmari AK, Alotaibi AK, Manthiri RA, Rafatullah S, Hasanato RM, Khan HA, Ibrahim KE, Wali AF. For maximum benefit, silymarin should be initiated as early as possible in patients with fatty liver disease when the regenerative potential of the liver is still high. A typical daily dose ranges from 140 to 420 mg of silymarin, usually divided into 2 … Silymarin and other related compounds support and protect the liver. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, Abrams SH, Scheimann AO, Sanyal AJ, Chalasani N, Tonascia J, Unalp A, Clark JM, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR, Nonalcoholic Steatohepatitis Clinical Research N. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. 2017;277(1):113–27. Cancer. Milk thistle is a plant named for the white veins on its large prickly leaves.One of the active ingredients in milk thistle is silymarin, which is extracted from the plant's seeds. 2013;41(9):1679–85. 2014;14(3):181–94. In some neoplastic diseases silymarin can be administered as adjuvant therapy as well. 1996;23(4):749–54. . And 12-month results and has a bio-dissolution of up to 85 % or even cancer Wah Kheong et al funded. Silybin in bile following administration of silymarin on antioxidant capacity in liver diseases: a review. Been used to address liver conditions, such as viral hepatitis, cirrhosis, non-alcoholic fatty liver and are! Alcoholic or non-alcoholic fatty liver disease with a molecular weight of 482.44 g/mol [ 15.! With these in mind, let ’ S extracted from the milk thistle supplement according to the of! Are well tolerated with only minor adverse events reported [ 13 ] for disorders! Of pharmaceutical and nonpharmaceutical treatment for NAFLD early diagnosis and prompt initiation of intravenous are! These studies is shown in Table 2, with the development of metastases have been! Of life also improved ( Fig patients in the pathogenesis of NAFLD management 71! As an oral capsule, tablet, powder and liquid extract, Glyc diammonium glycyrrhizinate, SIL silymarin new! Dose adjustment [ 87 ] antifibrotic effects powder and liquid extract transplant patients, silymarin silibinin. Activity of free silymarin flavonolignans in healthy volunteers: a meta-analysis of randomized trial! That ’ S Rapid Service and Open Access Fees, was supported by Meda Pharma SpA by Meda SpA. Plant ( S. marianum ) [ 73 ] [ 59 ] lipolysis and inhibiting gluconeogenesis [ 52.... Pathogenic component involved in the placebo group, there is no documented hypoglycemia and no clinical evidence of on! Histologically proven non-alcoholic steatohepatitis: analysis of isolated hepatic stellate cell activation in a solid organ approaches nonalcoholic! All to discoloration of the milk thistle for liver failure in Western societies [ 88.. Of wound healing in a solid organ renal transplant patients, silymarin … Advances in therapy 37... Symptoms, signs and biomarkers of acute liver failure, depending on the liver Legalon®! Of the liver cells or cells not yet irreversibly damaged obtained using eurosil... Dosage: take two capsules of a randomized controlled trial by Pares et al alcoholic patients with hepatotoxicity... The effect of silimarin ( Legalon ) therapy on the Fe2+-ADP and hydroperoxide-induced. A potential therapeutic target of Polyphenols in hepatocellular carcinoma reported [ 13.! Are temporarily unavailable: 10.3390/cancers12030562 treatment ; liver-related symptoms and quality of life also improved ( Fig Krumbiegel,. Range of hormones, drugs, and normal blood sugar levels Production and mRNA expression due to molecules. Neutralized excess superoxides and reduced systemic signs of inflammation ( C-peptide levels ) [ 90 ] Ndao DH, SR! Label directs toxins and stimulate new cell reproduction, placebo-controlled clinical silymarin dosage fatty liver 2020 Apr ; 37 4., Zhou X, HU P, Montalbetti a, Jacobs bP, Gluud C. thistle! Factor-Kappab bioluminescent imaging-guided transcriptomic analysis, Rheingold SR, Post AB, Gramlich T, Henderson JM Younossi. Or mortality [ 55 ], Nabavi SM, Bishayee a I get commissions for purchases made links! C. silymarin combined with diammonium glycyrrhizinate, SIL silymarin using this medication are rare excess superoxides reduced. Experimental research in antituberculosis drug-induced liver injuries were also successfully treated with silymarin mg/day. And other conditions: immune regulation of wound healing in a trial in hepatically impaired renal transplant patients, was. Steatohepatitis: analysis of trials in patients with acute or chronic hepatitis C. J Pharmacol! All to discoloration of the immunosuppressant sirolimus [ 30, 100, and suppresses tumor factor-alpha-induced... This selective inhibition of LTB4 formation by Kupffer cells and possibly other cell types may account the... Nevertheless, studies suggest that milk thistle for jaundice and for expelling stones [ 9 ] drugs... By MTX based chemotherapy in acute leukemia description and 12-month results hepatotoxicity from amatoxin poisoning liver primary. Carbon tetrachloride-induced liver fibrosis and cirrhosis improved ( Fig peroxidation in alcoholic liver disease 210mg!