Milk Thistle (Silybum Marianum) Clinical Evidence

Koujan SE, et al. Lower glycemic indices and lipid profiles among type 2 diabetes patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: a triple-blinded randomized controlled clinical trial. 2018 May 15;44:39-44.

Topic:
Does milk thistle help improve blood sugar and cholesterol levels in people with type 2 diabetes?

Background:
Elevated blood sugar and cholesterol often go hand in hand. Can milk thistle help improve these metabolic parameters?

Study Type:
Human clinical intervention trial

Study Design:
Paralleled, randomized, triple-blind, placebo-controlled. Researchers took body measurements and blood samples to analyze for glycemic indices and lipid profiles at baseline and at the end of the study.

Dosage:
140 mg, 3x/day for 45 days

Participants:
140 mg, 3x/day for 45 days

Results:
Silymarin significantly lowered fasting blood sugar by 11.01%, serum insulin by 14.35%, insulin resistance by 25.92%, serum triglyceride by23.7% and, serum triglyceride to high-density lipoprotein (HDL) cholesterol ratio by 27.67%, as compared to placebo. In the treatment group, HDL (good) cholesterol rose by 6.88% and insulin sensitivity by 5.64%, while total cholesterol and LDL (bad) cholesterol fell by 7.93 and 7.15%.

Conclusions:
“Silymarin supplementation may improve the glycemic indices and lipid profiles and T2DM patients. More studies are needed to validate the adjunct use of silymarin for metabolic control of T2DM patients.”

Mirnezami M, et al. The effect of silymarin on liver enzymes in patients taking isotretinoin: a randomized clinical trial. 2020 Mar;33(2):e13236.

Topic:
What is the effect of silymarin on liver enzymes in people taking the acne drug isotretinoin?

Background:
Isotretinoin can cause inflammation of the liver and abnormal liver function. Can milk thistle help?

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind, placebo-controlled. Participants took silymarin or placebo for 30 days. Liver enzymes were measured at baseline and at the end of the study.

Dosage:
140 mg/day for 30 days

Participants:
74 volunteers taking isotretinoin for acne

Results:
At the beginning of the study, there were no significant differences between the treatment and control groups, but at the end, there were significantly lower levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in the treatment group.

Conclusions:
“Livergol prevented liver enzymes from increasing, so it can be used as an effective, low-cost, and low-complication treatment for the problem of increased liver enzymes following the use of isotretinoin.”

Darvishi-Kherzri H, et al. The impact of silymarin on antioxidant and oxidative stress in patients with beta-thalassemia major: a crossover, randomized, controlled trial. 2017 Dec;57:25-35.

Topic:
What is the effect of silymarin on oxidative stress in people with beta-thalassemia?

Background:
Beta-thalassemia is an inherited blood disorder, in which the body’s ability to produce hemoglobin is reduced or completely absent. The disorder is treated with blood transfusions, but this life-saving treatment can lead to iron overload, which in turn causes oxidative stress (OS) and even organ dysfunction. Antioxidants can be used to combat the OS.

Study Type:
Human clinical intervention trial

Study Design:
Crossover, randomized, placebo-controlled. Participants took silymarin or a placebo for a period of 12 weeks. Following a 2-week washout period, the participants switched groups and took silymarin or a placebo again. Researchers measured malondialdehyde (MDA) and protein carbonyl (CO) (which are both markers of oxidative stress), total antioxidant capacity (TAC), and the antioxidant reduced glutathione (GSH) before and after both period of supplementation.

Dosage:
140 mg, 3x/day for 12 weeks

Participants:
82 volunteers with beta-thalassemia

Results:
69 volunteers completed the study. Silymarin significantly reduced serum MDA and CO in all patients by the end of the treatment period. MDA fell from 20.36 to 4.79umol/l in the treatment group, compared to 17.81umol/l in the placebo group, while CO fell from 0.31 to 0.11mM/l in the treatment group, versus 0.24mM/l in the placebo group. Silymarin also significantly increased TAC and GSH. TAC increased from 620.7 to 971.83umol/l in the treatment group, compared to 672.22umol/l in the placebo group. GSH increased from 46.16 to 195.35mM/l in the treatment group, versus 58.52mM/l in the placebo group.

Conclusions:
“Silymarin was effective in decreasing serum OS and enhancing serum antioxidant capacity in patients with beta-thalassemia major. Silymarin given as an adjuvant therapy to standard iron chelators may provide an improvement in the OS measures obtained in these patients, with accompanying benefit.”

Luangchosiri G, et al. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. 2015 Sep 23;15:334.

Topic:
Can silymarin help protect liver health in people taking antituberculosis drugs?

Background:
Drugs are metabolized in the liver and as a result, some kinds of drugs, including those used to treat tuberculosis, can lead to liver injury. Administering silymarin along with these drugs has been promising in animals, but hasn’t yet been studied in humans.

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind, placebo-controlled. Participants took antitubercular drugs and either silymarin or a placebo. At week 4, researchers measured the volunteers’ antioxidant liver enzymes, such as superoxide dismutase (SOD) and glutathione.

Dosage:
140 mg, 3x/day

Participants:
55 volunteers with tuberculosis

Results:
In the treatment group, only 3.7% of participants developed antituberculosis drug-induced liver injury (anti-TB DILI), whereas in the placebo group, 32.1% of participants did. Risk reduction was .28. In other words, in 100 patients, silymarin prevents 28 from developing liver injury. Median levels of ALT (a liver enzyme) at the end of the study were 35 IU/L for the placebo group and 31.5 IU/L for the treatment group. The antioxidant SOD decreased in both groups, but by less in the silymarin group.

Conclusions:
“Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study.”

Gharagozloo M, et al. Combined therapy of silymarin and desferrioxamine in patients with beta-thalassemia major: a randomized double-blind clinical trial. 2009 Jun;23(3):359-65.

Topic:
Is silymarin beneficial in beta-thalassemia patients who are taking desferriosamine for the blood disorder?

Background:
Silymarin, a flavonligan from milk thistle, has strong antioxidant, liver protective, and iron chelating properties. It may be a promising treatment in patients with beta-thalassemia, who require blood transfusions and are at risk of iron overload.

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind, placebo-controlled. Participants taking desferriosamine to reduce excess iron levels, also took silymarin or a placebo for 3 months. Researchers measured alkaline phosphate (a liver enzyme) and glutathione (an antioxidant) at baseline and at the end of the study. They measured ferritin (iron) at those two points and in the middle of the study.

Dosage:
140 mg, 3x/day, for 3 months

Participants:
59 volunteers with beta-thalassemia

Results:
There was significant improvement in alkaline phosphate and glutathione in the treatment group, but no significant difference in iron levels. Researchers speculated that the sample size was not large enough to detect differences in iron levels.

Conclusions:
“This is the first report showing beneficial effects of silymarin in thalassemia patients and suggests that silymarin in combination with desferriosamine can be safely and effectively used in the treatment of iron-loaded patients.”

Müzes G, et al. Effect of silymarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double blind protocol). 1990 Apr 22;131(16):863-66.

Topic:
Does silymarin help repair some of the liver damage characteristic of alcoholic liver disease?

Background:
Silymarin is a compound extracted from milk thistle, an herb traditionally used for liver health, as far back as the first century AD.

Study Type:
Human clinical intervention trial

Study Design:
Double-blind, placebo-controlled. Participants took silymarin or placebo for 6 months. Researchers measured the activity of two antioxidants, superoxide dismutase (SOD) and glutathione peroxidase. They also measured ree-SH groups.

Dosage:
420 mg/day, for 6 months

Participants:
Volunteers with chronic alcoholic liver disease

Results:
At baseline, participants had low levels of SOD activity in red and white blood cells. Silymarin significantly increased this activity, while also increasing glutathione peroxidase activity and serum levels of ree-SH groups. Malondialdehyde (a marker of oxidative stress) also fell in the treatment group. There were no changes in antioxidant defense or lipid peroxidation in the placebo group.

Conclusions:
“These data indirectly suggest that antioxidant, antiperoxidative effects might be important factors in the mechanism of hepatoprotective action of silymarin.”

Szilárd I, Szentgyörgyi D, Demeter I. Protective effect of Legalon in workers exposed to organic solvents. 1988;45(2):249-56.

Topic:
Can silymarin help improve liver function in workers exposed to toxic chemicals?

Background:
Toluene and xylene are hydrocarbons used in solvents. Long-term exposure can lead to liver damage.

Study Type:
Human clinical intervention trial

Study Design:
Controlled. Researchers screened 200 workers exposed to toluene and/or xylene fumes for 5-20 years, and found 49 of them had abnormal liver function, leukocytosis (an increase in white blood cells indicative of an infection), relative lymphocytosis (an increase in white blood cells of over 40%), and/or low platelet counts. Of these 49, 30 received treatment with silymarin for 30 days. At the end of the study, researchers measured levels of the liver enzyme AST and the activity of ALT, another liver enzyme, to assess liver function. They also measured platelet counts and analyzed blood for leukocytosis and relative lymphocytosis.

Participants:
49 workers exposed to toluene and/or xylene fumes, with abnormal liver function

Results:
After treatment, liver function and platelet counts improved significantly. Leukocytosis and relative lymphocytosis showed a non-significant trend toward improvement.

Balouchi S, et al. Serum levels of TGF-beta, IL-10, IL-17, and IL-23 cytokines in beta-thalassemia major patients: the impact of silymarin therapy. 2014 Aug;36(4):271-74.

Topic:
How does silymarin affect immune markers in people with beta-thalassemia?

Background:
Abnormalities in immune markers, particularly cytokines, have been linked to the blood disorder beta-thalassemia.

Study Type:
Human clinical intervention trial

Study Design:
Placebo-controlled. Researchers measured serum levels of TGF-beta, IL-10, IL-17, and IL-23 in beta-thalassemia major patients and in healthy controls. Next the participants with beta-thalassemia took silymarin or a placebo for 6 months and researchers analyzed blood samples for the same immune markers.

Dosage:
420 mg/day, for 6 months

Participants:
49 workers exposed to toluene and/or xylene fumes, with abnormal liver function

Results:
Compared to the healthy controls, participants with beta-thalassemia had elevated levels of TGF-beta and IL-23. After supplementing with silymarin, IL-10 levels fell significantly, compared to baseline.

Conclusions:
“Our data suggest the presence of imbalanced immune condition involving inflammation and immunosuppression in thalassemia patients, which could be modulated to a more effective immune response by silymarin.”

Gharagozloo M, Karimi M, Amirghofran. Immunomodulatory effects of silymarin in patients with B-thalassemia major. 2013 Jun;16(2):243-47.

Topic:
Is silymarin effective in enhancing immune response in patients with beta-thalassemia, when taken with desferrioxamine?

Background:
Desferrioxamine is an iron-reducing drug taken by people with the blood disorder beta-thalassemia.

Study Type:
Human clinical intervention trial

Study Design:
25 participants took both desferrioxamine and silymarin, while 5, who declined the drug, took only silymarin. Researchers analyzed several immune markers before and after supplementation.

Dosage:
420 mg, for 12 weeks

Participants:
30 people with beta-thalassemia

Results:
No differences were observed between the two groups in lymphocyte (white blood cell) subsets, concentration of serum immunoglobins, complement levels, or T-cell proliferation in vitro. In both groups serum levels of TNF-alpha and neopterin decreased significantly, while production of IFNy and IL-4 increased.

Conclusions:
“Silymarin stimulates cell-mediated immune response in beta-thalassemia major, possibly through a direct action on cytokine-producing mononuclear cells. Because of its immunostimulatory, antioxidant and iron-chelating activities, silymarin could be a good candidate in the therapy of chronic iron overload in combination with routine iron chelators in clinical use like desferrioxamine.”

Fallahzadeh MK, et al. Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic patients with overt nephropathy: a randomized, double-blind, placebo-controlled trial. 2012 Dec;60(6):896-903.

Topic:
Can silymarin help people with diabetes-associated kidney disease?

Background:
People with diabetes are prone to nephropathy (kidney disease), with 25% eventually developing the potentially life-threatening condition.

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind, placebo-controlled. Participants took silymarin or a placebo for 3 months. Researchers measured participants’ urinary albumin-creatine ratio (AUCR), as well markers of inflammation (TNF-alpha) and oxidative stress (MDA) at baseline and at the end of the study.

Dosage:
420 mg/day, for 3 months

Participants:
60 volunteers with type 2 diabetes and macroalbuminuria (high levels of albumin) resistant to treatment.

Results:
UACR levels decreased in both groups, but the decline was significantly greater in the silymarin group. Urinary TNF-alpha and MDA also decreased significantly in the silymarin group, as compared to placebo.

Conclusions:
“Silymarin reduces urinary excretion of albumin, TNF-alpha, and MDA in patients with diabetic nephropathy and may be considered as a novel addition to the anti-diabetic nephropathy armamentarium.”

Silymarin, from milk thistle, is an antioxidant and agent of detoxification. It enhances antioxidant enzymes (CAT, SOD, GPX), inhibits expression of eNOS and MARK, activates Nrf2, and inhibits NF-kB to regulate gene expression. It scavenges free radicals in cytoplasm and promotes ribosomal RNA synthesis.

Milk thistle helps detoxify the liver by decreasing levels of glycoproteins, activating phase II detoxifying enzyme GST, stabilizing cell membranes damaged by toxins, impeding the entrance of toxins into liver cells, and by preventing the proliferation of abnormal cells and activating their apoptosis.