Clinical Studies

Clinical Implications Of Silymarin In Liver Health

Study Focus:

  • Sylimarin in non-alcoholic fatty liver disease
  • Safety and efficacy of Silymarin on symptoms, signs and biomarkers of acute hepatitis
  • Efficacy of Silymarin in preventing hepatotoxicity from anti-tuberculosis drugs with Samarin(R) in a double-blind placebo controlled study
  • Hepatoprotective effect of Silymarin in individuals chronically exposed to hydrogen sulfide; modulating influce of TNF- cytokine genetic polymorphism

Silymarinin Non-Alcoholic Fatty Liver

A randomized, double-blind, placebo-controlled trial in 99 adults with biopsy-proven non-alcoholic steatohepatitis (NASH) and a nonalcoholic fatty liver disease (NAFLD) activity score (NAS) of 4 or more. Patients were randomly assigned to groups given silymarin(SM) (700mg(n=49) or placebo(PB) (n=50) three times daily for 48 weeks. After 48-week period, biopsies were repeated.

Changes in Liver Profile and Fibro Scan Measurement,
Intention-To-Treat Analysis

NOTE: The p-value were calculated using paired t test for change within group and independent t test for change between groups.
ALT, alanine aminotransferase; APRI, aspartate aminotransferase to platelet ratio index: AST, aspartate aminotransferase; FIB-4, fibrosis 4; GGT, gamma glutamyl transpeptidase;

A significantly higher proportion of patients in the SM group had reductions in fibrosis based on histology (reductions of 1 point or more; 22.4%) than did the PB group (6.0%;p=0.023), and based on liver stiffness measurements (decrease of 30% or more; 24.2%) than did the PB group (2.3%; p=0.02). The SM group also had significant reductions in mean APRI (reduction of 0.14, p=0.011 compared to baseline.), and NAFLD fibrosis score (reduction of 0.30, p <.001 compared with baseline these changes were not observed in the pb group of p=".154;" increase and reduction respectively there was no significant difference between groups number adverse events. events that occurred attributed to silymarin.> Ref. Kheong CW et al. A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis. Clinical Gastroenterology and Hepatology 2017;15:1940–1949.

Proven Efficacy Of Silymarin In Non-Alcoholic Fatty Liver Disease


AIM: This study was undertaken to evaluate the hepatic effects of silymarin(SM) on non-alcoholic fatty liver disease (NAFLD).

METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before SM treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment.

RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of SM. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P <0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. These results indicate that SM appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis.
Ref. Cacciapuoti F. et al. Silymarin in non-alcoholic fatty liver disease. World J Hepatol 2013 March27;5(3):109-113.

Silymarin for Liver Disease

L. Abenavoli, N. Milic, in Liver Pathophysiology, 2017
Nonalcoholic Fatty Liver Disease

In a randomized placebo-controlled trial, silymarin reduced significantly the levels of ALT and aspartate aminotransferase (AST). Namely, after 25 NAFLD patients were administered with 140 mg silymarin each day for 2 months, compared to 25 patients treated with placebo, the liver function of the treated group was significantly improved and the drop in ALT and AST was from 103 to 41 IU/mL and from 53 to 20 IU/day, respectively, while the placebo did not cause any significant change in the aminotransferase levels (Hajaghamohammadi et al., 2008). These findings were confirmed in another randomized placebo-controlled study conducted on 100 patients diagnosed with NAFLD and treated with silymarin versus placebo in a 6-month period. The normalization of ALT values was detected in 32% cases after 3 months of therapy and in 52% cases after 6 months of therapy with 140 mg silymarin a day, which is significant in comparison with the placebo results. The levels of AST below 40 IU/mL (normal value) were detected in 46% and 62% cases after 3 and 6 months of silymarin administration, respectively, and reported as statistically significant results when compared with the AST levels in the placebo group (Hashemi et al., 2009). Silymarin, in a dosage of 210 mg/day, demonstrated its therapeutic effect in the treatment of NASH, the progressive form of NAFLD. After being applied in 33 NASH patients for 8 weeks, silymarin decreased the AST and ALT levels with a statistical significance, compared to ones measured in 31 patients receiving a placebo (Solhi et al., 2014). Furthermore, silymarin seems to be as efficient as vitamin E in the reduction of liver aminotransferases. The combination of silibinin with vitamin E is even more effective in the therapy of NAFLD. In a randomized placebo-controlled double-blind research in Italy, 179 NAFLD patients (36 positive on HCV) were enrolled and 138 patients finished the study after 12-month treatment. Half the patients were treated with 2 pills/day of Realsil (one piece contained 94 mg of silybin, 194 mg of phosphatidylcholine, and 90 mg of vitamin E), and half with a placebo. The rate of the patients, who reached the normalization of AST, ALT, and GGT plasma levels, was significant in the treated versus the placebo group. Over the time, the liver inflammation and ballooning were improved in the group which received therapy while liver fibrosis and mean score for liver steatosis severity were significantly reduced. The body mass index (BMI) normalized in 15% of the treated patients compared to only 2.1% of the patients in the placebo group. Finally, the treatment showed a metabolic effect as the blood glucose level and insulinemia were significantly lowered (Loguercio et al., 2007, 2012). These data are in line with a subsequent study which combined silymarin with vitamin E, l-glutatione, lmethionine, and l-cysteine as a medication for the NAFLD patients. In that randomized study, 72 patients were registered with lowered AST, ALT, and GGT levels and decreased levels of TNF-α after 6 months of the treatment. The hepatic steatosis severity was restricted according to the ultrasonographic findings (Cacciapuoti et al., 2013). Compared to the insulin sensitizers, pioglitazone and metformin, silymarin was clinically proven not to be less effective. On the contrary, it is equally beneficial as pioglitazone and significantly more potent than metformin. After 66 patients diagnosed with NAFLD were enrolled in the research, a third was treated with 15 mg pioglitazone, another third with 500 mg metformin, and the rest with 140 mg silymarin per day for 2 months. The levels of liver aminotransferases were reduced, the lipid status was lowered, and the insulin and glucose parameters were improved in all three groups (Hajiaghamohammadi et al., 2012). This therapeutic equivalence of silymarin with the insulin sensitizers can be attributed to its metabolic activity. Recently our group has shown in a randomized study, the ability of Realsil, to improve not only ltrasonographic stage of liver steatosis, but also transaminase levels, anthropometric parameters, lipid and glycemic metabolisms (Abenavoli et al., 2015).

Samarin® Clinical Study in Drug-Induced Hepatitis

A double-blind randomized placebo controlled trial of Samarin® for the prevention of antituberculosis drug- induced liver injury in 55 patients with newly diagnosed pulmonary tuberculosis.

Patients were randomly assigned to receive either placebo(PB) or SM(Samarin®) 140 mg three times daily.

The outcomes of interest were the maximum liver enzymes (ALT levels) and the development of antituberculosis drug- induced liver injury (antiTB-DILI) at week 4 after treatment with standard antiTB drugs (isoniazid, rifampicin, pyrazinamide and ethambutol)


  • Median (IQR) of ALT levels at week 4 in the PB and SM group were35.0 (15,415)IU/L and 31.5(20,184)IU/L respectively (p=0.455) ,i.e., no statistical difference between the two groups
  • The incidences of antiTB-DILI at week 4 were 3.7% and 32.1% in the SM and PB group respectively. Risk reduction was 0.28 (0.10-0.47) or 28 patients will be prevented from antiTB-DILI among 100 treated patients. An estimated number need to treat(NTT) was 3.5(95%CI:2.11,2.37) which could be interpreted that 1 in 4 patients treated with SM will be prevented from antiTB-DILI
  • There were similarly mild adverse effects in both groups.
    Ref. Luangchosiri C. et al. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC complementary and alternative Medicine 2015;15:334

Other Clinical Studies And Reviews Of Silymarin Medicinal Implications (2012-2018)

“A randomized double, placebo-controlled trial of 99 consecutive adults with biopsy-proven NASH and NAFLD activity score(NAS) of 4 or more…A significant higher proportion of patients in the silymarin group had reductions in fibrosis based on histology (reduction of 1point or more; 22.4%) than did the placebo group.(6.0%;P=.023) and based on liver stiffness measurements (decrease of 39% or more ;24.2%) than did the placebo group (2.3%; P= .002)”.

Clinical Gastroenterology and Hepatology 2017;15:1940-1949

“A systemic review with meta-analysis of randomized and controlled clinical trails … The trials with adult and elderly patients of both sexes, with liver diseases who took oral silymarin supplementation.. In the meta-analysis, the results indicated a reduction of 0.26IU/ml (95%CI:-0.46-0.07,P=0.007) at the level of ALT and 0.53IU/ml(95%CI:-0.74-0.32,P=0.000 at the serum levels of AST after using the silymarin,….”

World J Gastroenterol 2017 July 21; 23(27):5004-5017

“Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation”.

Molecules 2017,22,191;doi:10.3390/molecules22020191

“SM is the extract of Silybum marianum (milk thistle) and contains a complex mixture of 7 flavonolignan and a flavonoid. Among all ingredients silybinin is the most relevant one with the most important biological effects. The current study was a randomized to receive either 700mg of SM orally or placebo for 48 weeks. The majority of patients included in the trial had type2 diabetesmellitus(T2DM) and central obesity, the 2 most relevant comorbidities in NASH …. In conclusion, this study showed the antifibrotic benefits of silymarin in NASH This study underlined the safety and tolerability of silymarin, which therefore may be a potential future therapy …..”

Clinical Gastroenterology and Hepatology 2017; 15,:1863-1865

“Silymarin has long been used as a hepatoprotective remedy. Chronic toxicity studies in rodents have Confirmed that silymarin has a very low toxicity. These data support its history as a safe medication in hepatic diseases”.

Clinical Phytoscience (2016) 2:7 DOI 10.1186/s40816-016-0019-2

“We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increase apoptotis compared to single compound treated cells …..”

Journal of Cancer 2016; 7(10):1250-1257.dpi:10.7150/jca. 15690

“A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury”

BMC Complementary & Alternative Medicine (2015) 15:334DOI 10.1186/s2906-015-0861-7

“ The clinical-trial study was conducted on 64 patients with NASH who were randomly divided as case group (33) and control group(31).. Patients in the case group received 210mg/day silymarin orally for 8 weeks and those in the control group received placebo. Results.. Serum concentrations of ALT were 91.3±21.3 NS 38.4±11.8 in case group before and after the study respectively, whiles the figures were 84.6±23.3 and 52.3±29 in the control group (P=0.026). The same trend was seen for AST (P=0.038). Conclusion: the patients who had taken silymarin experienced more notable fall in hepatic enzymes.”

Claspian J Intern Med 2014; 5 (1):9-12

“We genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQ01,mEPxH1, GSTT1) and inflammation (TNF-α) and TGF-ß1… Results: a significant reduction of blood AST, ALT and ALP was observed after 30days of consumption (p <0.001)”.

Journal of Pharmaceutical Sciences 2013; 21:28

“ This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). .. Conclusion: the obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lower.

World J Hepatol 2013; March 27;5(3):109-113

“The active substance in milk thristle, silymarin, is a complex mixture of flavonolignan. Silymarin’s primary constituents are the flavonolignan isomers: silybins A and B (also called silibinin), isosilybin A and B, silychristin, silydianin and their flavonoid precursor, taxifolin” “Milk thristle fruit and seeds have been used for >2000 years as a treatment for liver and biliary disorders”

NIH, June 19, 2017.

“Silymarin antagonizes the progression of NAFLD, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction----different therapeutic targets involved in the process that leads to NAFLD onset and worsening– --and has a high safety profile. In this regard, silymarin is probably one of the most promising molecules, usable in NAFLD therapy, given the necessity of a long-term treatment”

Molecules 2017,22,191;doi:10.3390/molecules22020191

Sylimarin hepatoprotective activity include antioxidant and anti-inflammatory activities, cell permeability regulator and membrane stabilizer, stimulation of liver regeneration and inhibition of deposition of collagen fibers, which may lead to fibrosis” “Available standardized products should contain at least 70% silymarin”

Journal of the Evidence –Based Complimentary &Alternative Medicine 2015;20(4):292-301

“Several recent randomized clinical studies have demonstrated that silymarin versus placebo significantly contributes to amelioration of the liver condition affected by NAFLD since it reduces steatosis severity, liver ballooning and fibrosis, followed by lowered aminotransferase levels in both short and long lasting therapies” “Phase III trials have confirmed silymarin to be currently the best medication for the NAFLD patients”

Rev Recent Clin Trials 2014;9(3):195-203

“Silymarin antagonizes the progression of NAFLD, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction----different therapeutic targets involved in the process that leads to NAFLD onset and worsening– --and has a high safety profile. In this regard, silymarin is probably one of the most promising molecules, usable in NAFLD therapy, given the necessity of a long-term treatment”

Molecules 2017,22,191;doi:10.3390/molecules22020191

“A preliminary report showing that silymarin 420 mg/day reduced the 4-years risk of mortality in patients with cirrhosis”

Nutrients 2018;10,1153;doi:10.3390/nu10091153

“A meta-analysis (PRISMA) of 8 RCTs involved 587 NAFLD patients found silymarin to have positive efficacy in reducing transaminase levels. Silymarin can be encouraging and considerable phytotherapy for NAFLD patients”


A multicenter randomized double-blind phase III study conducted in 179 patients with histological diagnosis of NAFLD /NASH, the administration of silybin combined with phosphatidylcholine and vitamin E for 12 months determined the normalization of transaminase, a significant reduction of gamma-glutamyl transferase levels and a significant decrease of liver steatosis measured with both ultrasound scan and a second liver biopsy

Free Radical Biology and Medicine 2012; 52(9):1658-1665

“Sixty six patients with NAFLD were assigned randomly to pioglitazone 15mg/day (n+22) or metformin 500mg/day (n=22) or silymarin 140 mg /day(n=22) for 2 months. Changes in AST and ALT in silymarin group were demonstrated more than the other groups”


The Investigative And Clinical Studies Conducted On Silymarin Show:

  • “Functional Triad” of silymarin allows for antagonizing the onset/progression of the damage responsible for the progression of hepatitis to cirrhosis and liver cancer.[1]
  • Silymarin is an “antidote” against toxins in the liver.[2]
  • Silymarin (Brand used: Samarin) reduced incidences of anti-TB drug-induced liver injury.[3]
  • Silymarin stimulates detoxification pathway/liver tissue regeneration and possibly increase the efficacy of certain chemotherapy agents. [4]
  • Silymarin significantly reduced fibrosis using several means of measurements, when compared to placebo in a 48-week study.[5]
  • Silymarin has positive efficacy to reduce liver enzymes (liver damage) in nonalcoholic fatty liver disease.[6]

Despite great scientific interest in the therapeutic actions of Silymarin, the number of clinical trials is small and thus clinical evidence is currently insufficient or inconclusive.


[1] Molecules 2017, 22, 191; doi:10.3390/molecules22020191

[2] Clin Drug Invest 2002; 22 (1): 51-65

[3] BMC Complementary and Alternative Medicine 2015;15:334 DOI


[4] (originally published by the National Cancer institute)

[5] Clin Gastroenterol hepatol 2017;15(12):1940-1949

[6] Medicine(Baltimore)2017;96(49):e9061.doi:10.1097:MD0000000000009061