Article: silymarin dosage fatty liver
December 22, 2020 | Uncategorized
2015;8(3):4320–7. Epub 2020 Feb 17. https://doi.org/10.1016/j.dld.2004.06.015. Silymarin preconditioning protected insulin resistant rats from liver ischemia-reperfusion injury: role of endogenous H2S. Results showed that concomitant administration of silymarin significantly reduced the alcohol-induced increase in hepatic collagen type I (Fig. Dehmlow C, Murawski N, de Groot H. Scavenging of reactive oxygen species and inhibition of arachidonic acid metabolism by silibinin in human cells. Wenfeng Z, Yakun W, Di M, Jianping G, Chuanxin W, Chun H. Kupffer cells: increasingly significant role in nonalcoholic fatty liver disease. In this case, a 57-year-old woman required hospitalization after experiencing intermittent sweating, nausea, colicky pain, diarrhea, vomiting, weakness and collapse [100]. Silymarin helps in treating hepatic dysfunction. Effect of silimarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double blind protocol). Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in adult patients with NASH, but only at a very high dosage (533.6 mg/day for 96 weeks) [81]. 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. J Hepatol. 2010;3:85–91. The standard dose of milk thistle is based on its silymarin content, 70 to 210mg three times daily. Ha HL, Shin HJ, Feitelson MA, Yu DY. 2001;61(14):2035–63. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. cysteine) for its biosynthesis, which subsequently contributes to the enhancement of its antioxidant capacity in liver tissues [3]. Drug Metab Dispos. 1) [16]. Arzneimittelforschung. 1996;23(4):749–54. DILI was measured according to the 1990 Paris International Consensus Conference classification of liver injury. In a rat model of NAFLD, silibinin ameliorated insulin resistance by reducing visceral obesity, enhancing lipolysis and inhibiting gluconeogenesis [52]. 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]. Am J Physiol Gastrointest Liver Physiol. Most of the published clinical research on silymarin has used this standardized pharmaceutical preparation. CAS J Surg Res. One reported effect of milk thistle is that it can boost breast … Cancer. 2012;55(6):2005–23. van Pelt JF, Verslype C, Crabbe T, Zaman Z, Fevery J. Of the 170 patients with cirrhosis, 87 were treated with silymarin 420 mg/day (alcoholic: 47, non-alcoholic: 40), and 83 received placebo (alcoholic: 45, non-alcoholic: 38) for at least 24 months, with a median observation period of 41 months. Lucena MI, Andrade RJ, de la Cruz JP, Rodriguez-Mendizabal M, Blanco E, Sanchez de la Cuesta F. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. https://doi.org/10.1055/s-0032-1328704. https://doi.org/10.4084/MJHID.2016.043. Belongs to the class of drugs used in liver therapy. BMC Complement Altern Med. Using the most bioavailable form of milk thistle or silybin, studies have shown the usual dosage to be 420 mg in three divided doses. 2008 Dec 21;149(51):2413-8. doi: 10.1556/OH.2008.28519. Dig Liver Dis. … https://doi.org/10.1002/ptr.3207. The mechanism of action by which silymarin produces these clinical effects is attributed to its antioxidant activity. https://doi.org/10.1517/14728222.12.3.265. Twelve-month follow-up data were available for 141 patients. The impact of silymarin in these studies is shown in Table 2, with the study by Ferenci et al. SH: sulfhydryl; GSH-Px: glutathione peroxidase. Silybum marianum (milk thistle) has been safely used for centuries as a natural herbal medicine for the treatment of liver disorders. Part B of figure reproduced with permission from Wah Kheong et al. The study authors indicate that the liver's primary role predisposes individuals who develop NAFLD to other systemic metabolic disorders. https://doi.org/10.1055/s-2008-1074867. Most of the clinical research on silymarin has used this formulation. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. CAS In addition to reducing membrane peroxidation, silymarin also significantly reduced levels of glycosylated hemoglobin and insulin requirements (Fig. In another trial in patients with chronic hepatitis C, 177 Egyptian patients received either the commercial (Eurosil 85®) formulation of silymarin (125 mg) or a low-dose multivitamin supplement three times a day [99]. Furthermore, it exerts an anti-atherosclerotic effect, and suppresses tumor necrosis factor-alpha-induced protein production and mRNA expression due to adhesion molecules. Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM. The silymarin exerts membrane-stabilizing and antioxidant activity, it promotes hepatocyte regeneration; furthermore it reduces the inflammatory reaction, and inhibits the fibrogenesis in the liver. Dig Dis. 2020 Apr;37(4):1279-1301. doi: 10.1007/s12325-020-01251-y. A double-blind controlled study. J Hepatol. Chen Z, Yu R, Xiong Y, Du F, Zhu S. A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease. https://doi.org/10.1007/s40268-015-0084-x. Belongs to the class of drugs used in liver therapy. Eurosil 85® is a proprietary formulation developed to maximize the oral bioavailability of silymarin. Am J Gastroenterol. https://doi.org/10.1038/nri3623. A lab study showed that silymarin may increase glutathione content in the liver … Gastroenterol Clin Biol. Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Alcoholic liver disease. https://doi.org/10.1042/CS20090549. In chronic liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver diseases, drug- and chemical-induced hepatic toxicity), the antioxidant medicines such as silymarin can have beneficial effect. https://doi.org/10.1056/NEJMra1208937. 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. https://doi.org/10.3109/15563650.2011.557663. However, silymarin (140 mg, 3 times a day) did not alter the pharmacokinetics of a single 10-mg dose of rosuvastatin in a study in healthy males [30]. Results of systematic reviews of clinical trials of silymarin show a low incidence of adverse events (< 4%, slightly lower than with placebo) and no treatment-related serious adverse events [13, 65, 100] or deaths [13, 100]. Exp Clin Gastroenterol. Hepatology. Silymarin isolated from the milk thistle (Silybum marianum) is arguably the most commonly used medication for various liver diseases. Reproduced with permission from Gillessen et al. a Liver function parameters (all comparisons P < 0.001 baseline vs. 4 months); b signs and symptoms of liver disease; c: quality of life. Primary human hepatocytes are protected against prolonged and repeated exposure to ethanol by silibinin-dihemisuccinate. French LK, Hendrickson RG, Horowitz BZ. Phytomedicine. It Can Boost Breast Milk Production. https://doi.org/10.1177/0091270009347475. Four studies examined the impact of silymarin on clinical outcomes such as mortality [55, 57, 58, 60], and two of these trials had survival as the primary clinical endpoint [55, 57]. Zhu HJ, Brinda BJ, Chavin KD, Bernstein HJ, Patrick KS, Markowitz JS. N Engl J Med. Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver. Fengyun C. Silymarin combined with diammonium glycyrrhizinate for prevention and treatment of liver injury induced by chemotherapy in acute leukemia. Regulatory Classification. Article © 2020 Springer Nature Switzerland AG. I. Biliary and renal elimination after a single oral dose. Silymarin 200 mg taken orally three times/day in combination with conventional treatment Dosage Considerations – Should be Given as Follows: There are no dosage considerations for use of … Insulin resistance and oxidative stress are the major pathogenetic mechanisms leading the hepatic cell injury in these patients. Approximately 20% of patients with NAFLD (simple steatosis) will go on to develop the more severe form known as non-alcoholic steatohepatitis (NASH) [70]. 5a). Studies on elimination of silymarin in cholecystectomized patients. Several trials have investigated the effectiveness of silymarin in preventing DILI from ATDs. Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review. Clin Gastroenterol Hepatol. A double-blind comparative study in 116 patients. 1968;18(6):698–704. Wu JW, Lin LC, Hung SC, Lin CH, Chi CW, Tsai TH. Burden of liver diseases in the world. 2011;49(2):128–9. The most commonly reported adverse events (> 1 event per person week) were abdominal colic/discomfort (3.6 events per person week for silymarin vs. 3.2 for multivitamins), fatigue (3.5 vs. 4.4), headache (3.3 vs. 3.8) and diarrhea (1.4 vs. 1.7 events per person week). Form. Silymarin from milk thistle formulated into a cream (Leviaderm) prevented skin damage from radiotherapy in one trial of over 100 breast cancer patients . Major Probl Clin Surg. Most clinical data discussed in this review have been obtained using the Legalon® formulation. Lazzeroni M, Petrangolini G, Legarreta Iriberri JA, Pascual Avellana J, Tost Robusté D, Cagnacci S, Macis D, Aristarco V, Bonanni B, Morazzoni P, Johansson H, Riva A. Molecules. Milk Thistle is a herb that contains a few active ingredients collectively referred to as Silymarins. Lorenz D, Lucker PW, Mennicke WH, Wetzelsberger N. Pharmacokinetic studies with silymarin in human serum and bile. Drugs. It also holds free radicals in check. A typical daily dose ranges from 140 to 420 mg of silymarin, usually divided into 2 or 3 doses. Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. Alcohol Alcohol. 1980;38(3):227–37. https://doi.org/10.1001/jama.2011.520. https://doi.org/10.1016/j.fct.2012.02.025. Baskaran UL, Sabina EP. Moreover, in patients with diabetes and alcoholic cirrhosis, silymarin was also able to improve glycemic parameters. Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. Nevertheless, studies suggest silymarin may have a role as supportive treatment for patients with acute or chronic hepatitis [97,98,99]. Please enable it to take advantage of the complete set of features! Results of a randomized, double-blind, placebo-controlled clinical study. 1995;45(1):61–4. Silymarin protects liver cells by a number of mechanisms. In this study, the 4-year survival rate was significantly higher (58% vs. 39%) in silymarin recipients than placebo recipients (P = 0.036) [55]. 3) [63]. Does Milk Thistle Work for Fatty Liver? 1996 July 25. A number of silymarin formulations are available, including Legalon®, which contains the Eurosil 85® formulation that has high oral bioavailability and well-characterized pharmacokinetic and pharmacodynamic properties. Non-Rx Presentation/Packing . Teschke R. Alcoholic liver disease: alcohol metabolism, cascade of molecular mechanisms, cellular targets, and clinical aspects. Silymarin isolated from the milk thistle (Silybum marianum) is arguably the most commonly used medication for various liver diseases. However, there is no documented hypoglycemia and no clinical evidence of this additive effect. PubMed 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. CAS Its medicinal properties were mentioned in the writings of the Greek physician and botanist Dioscorides (40–90 AD), who recommended it as a treatment for snakebite [8, 9]. There is increasing evidence that demonstrates the overall inhibition by silymarin of inflammatory mediators such as NF-κB and inflammatory metabolites (e.g., prostaglandin E2 [PGE2] and leukotriene B4 [LTB4]) [49]. This ingredient is combined with other vitamins and used to prepare commercial medications like … Symptoms of hepatitis also range from nothing at all to discoloration of the skin, diarrhea, abdominal pain, and more. Look for a high-quality product that’s between 50–150 milligrams of pure milk thistle extract per capsule so you can adjust the amount you are taking depending on your needs. Therefore, the lack of an effect of silymarin on survival in three of the four studies with death as an outcome [57, 58, 60] may have been because the trials were underpowered, not long enough or included too many patients with severe/advanced disease to be able to demonstrate an impact on mortality. Prophylactic therapy of silymarin (milk thistle) on antituberculosis drug-induced liver injury: a meta-analysis of randomized controlled trials. Glutathione is the most abundant cellular antioxidant that protects hepatocytes against the toxic effects of ROS [77, 78]. A small March 2013 study published in the World Journal of Hepatology found that patients who took oral silymarin supplements twice a day for six months saw an improvement in … Use at such high dosage over a prolonged period has raised concerns about the long-term safety of vitamin E, particularly in patients with NAFLD who have not yet progressed to NASH [71]. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published. All authors contributed equally to this paper related to the conception, literature review and analysis, drafting and critical revision and editing, and final approval of the final version. Ore A, Akinloye OA. NF-κB is an important transcriptional regulator of the inflammatory response and plays an essential role in regulating inflammatory signaling pathways in the liver [43]. Silymarin also commonly known as milk thistle is a flowering plant that’s known for its medicinal properties. 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 [65]. You can stay on milk thistle indefinitely, although this is not generally recommended. PubMed A typical daily dose ranges from 140 to 420 mg of silymarin, usually divided into 2 … Mushroom poisoning-from diarrhea to liver transplantation. Therefore, amatoxin is used experimentally as a toxic model for liver failure. To date, the combination of dietary modifications and increased physical activity remains the mainstay of NAFLD management [71]. Various doses (0, 30, 100, and 300 mg/kg/d) of silymarin were p.o. It has potent antioxidant action and prevents lipid peroxidation. [Silymarin in the treatment of chronic liver diseases: past and future]. Changes in alcoholic liver disease and diabetes parameters in patients with diabetes and alcoholic liver disease receiving standard treatment alone (untreated) or with concomitant silymarin (treated) [59]. 2013;46(3):270–7. Reproduced with permission from Lieber et al. 2010;28(1):267–73. This ingredient … Chemo chemotherapy, DILI drug-induced liver injury, Glyc diammonium glycyrrhizinate, Sil silymarin. Alrashood ST, Al-Asmari AK, Alotaibi AK, Manthiri RA, Rafatullah S, Hasanato RM, Khan HA, Ibrahim KE, Wali AF. In numerous clinical studies, silymarin has been shown to have positive effects in treating virtually every type of liver disease including cirrhosis, hepatitis, jaundice, and chemical- or alcohol-induced fatty liver. Taken orally three times/day in combination with conventional treatment hepatitis are found affect! Wu SL, Ho TY this, anti-inflammatory properties, anti-inflammatory properties, antifibrotic effects and applications RJ Ahmed. 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