Stein GS, Kim JL, Kim YH, Kang MK, Gong JH, Han SJ, Kang YH. Antiosteoclastic Activity of Milk Thistle Extract after Ovariectomy to Suppress Estrogen Deficiency-Induced Osteoporosis. BioMed Research International. 2013;2013:919374. doi:10.1155/2013/919374.

Publication Date: "Published online 2013 May 28."

Peer Reviewed: Yes.

Study Design: "The sham-operated mice served as estrogen controls. The treatment of ovariectomized mice with nontoxic MTE and silibinin improved femoral bone mineral density and serum receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio, an index of osteoclastogenic stimulus."

Methodology: Mice were ovariectomized, fed diets with 10 mg/kg MTE or silibinin, blood and tissue samples collected, serum levels analyzed, bone mineral density measured, histological and immunohistochemical analyses conducted.

Sample Size: "9 mice of each group."

Controls Used: "Sham-operated mice."

Dose Used: "10 mg/kg MTE or 10 mg/kg silibinin once a day for 8 weeks."

Statistical Significance Declared: "Differences were considered significant at P < 0.05."

Adverse Events: Not specifically declared.

Conflict of Interest: Not declared.

Saberi Z, Gorji N, Memariani Z, Moeini R, Shirafkan H, Amiri M. Evaluation of the effect of Silybum marianum extract on menopausal symptoms: A randomized, double-blind placebo-controlled trial. Phytotherapy Research. 2020;34(12):3359-3366. doi:10.1002/ptr.6789

Publication Date: "First published: 06 August 2020"

Peer Reviewed: Yes

Study Design: "randomized, double-blind placebo-controlled trial"

Methodology: "Eighty women were randomly allocated into two equal groups (S. marianum extract [400 mg/d] or placebo capsules). Hot flashes frequency and severity were evaluated in 12 weeks with the Greene Climacteric Scale (GCS) and the Hot Flash Related Daily Interference Scale (HFRDIS)."

Sample Size: "80 participants (Mean age = 52.55, SD = 2.32, range = 44–57) were randomly assigned to the S. marianum extract (n = 40) or placebo (n = 40) groups"

Controls Used: "placebo capsules"

Dose Used: "200 mg of the extract powder (twice per day)"

Statistical Significance Declared: "p < .001"

Adverse Events: "mild gastric pain was reported in two cases in S. marianum group"

Conflict of Interest: Not declared

Oliveira SHP, Moalefshahri R, Javid H, Gheybi F, Fallahnezhad S, Hashemy SI. The Role of Silymarin in Mitigating Inflammation and Cognitive Impairment Induced by Ovariectomy in Wistar Rats. Mediators of Inflammation. 2023;2023:6639533. doi:10.1155/2023/6639533.

Publication Date: "Published online 2013 May 28."

Peer Reviewed: Yes.

Study Design: "Randomized controlled trial."

Methodology: Randomized, double-blind, outpatient clinical trial on 80 postmenopausal women (40–60 years) with symptoms of hot flashes, divided into two parallel experimental and control groups.

Sample Size: "80 postmenopausal women."

Controls Used: "Placebo."

Dose Used: "10 mg/kg/day MTE or 10 mg/kg/day silibinin daily for 8 weeks."

Statistical Significance Declared: "Values in bar graphs not sharing a letter indicate significant difference at P < 0.05."

Adverse Events: "No serious complications were observed but mild gastric pain was reported in two cases in S. marianum group and gastric pain and bloating were reported in three participants in placebo group."

Conflict of Interest: Not declared.

Demirci B, Dost T, Gokalp F, Birincioglu M. Silymarin Improves Vascular Function of Aged Ovariectomized Rats. Phytotherapy Research. 2014;28(6):868-872. doi:10.1002/ptr.5067

Publication Date: "First published: 30 September 2013."

Peer Reviewed: Yes.

Study Design: "Randomized controlled trial."

Methodology: Randomized, double-blind, outpatient clinical trial on 80 postmenopausal women (40–60 years) with symptoms of hot flashes, divided into two parallel experimental and control groups.

Sample Size: "80 postmenopausal women."

Controls Used: "Placebo."

Dose Used: "50 mg/L."

Statistical Significance Declared: "Values in bar graphs not sharing a letter indicate significant difference at P < 0.05."

Adverse Events: "No serious complications were observed but mild gastric pain was reported in two cases in S. marianum group and gastric pain and bloating were reported in three participants in placebo group."

Conflict of Interest: Not declared.

El-Shitany NA, Hegazy S, El-desoky K. Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine. 2010;17(2):116-125. doi:10.1016/j.phymed.2009.05.012

Publication Date: "Date: Feb. 2010"

Peer Reviewed: Yes.

Study Design: "OVX rats were treated chronically (12 weeks) with ethinylestradiol (EE) or SIL."

Methodology: Fifty female rats randomized into five groups, four groups ovariectomized, three treated with SIL, EE, or vehicle for twelve weeks, biochemical markers measured, histopathological examination conducted.

Sample Size: "Twelve-weeks-age fifty virgin female rats (120-150 g) (118[+ or -]5.12)"

Controls Used: "Sham-operated (SHAM)"

Dose Used: "50mg/kg/day"

Statistical Significance Declared: "The level of significance was set at p[less than or equal to]0.05"

Adverse Events: "Uncontrolled SIL intake could endanger women endometrium to become hyperplasic."

Conflict of Interest: Not declared.

Maleki, N., Khosh Ravesh, R., Salehiyeh, S., Faisal Faiz, A., Ebrahimi, M., Sharbati, A., Panji, M., Ajami Khiyavi, H., Safizadeh, F., Abbasi, M., Abazari, O., Norbakhsh, R., & Eskandari, Y. (2022). Comparative effects of estrogen and silibinin on cardiovascular risk biomarkers in ovariectomized rats. *Gene*, 823, 146365. doi:10.1016/j.gene.2022.146365

Publication Date: "Date: Feb. 2024"

Peer Reviewed: Yes.

Study Design: "Longitudinal study."

Methodology: Non-diabetic insulin-resistant women with obesity given silymarin for 12 weeks, no change in habitual diet and physical activity, HOMA-IR, OGTT, and biochemical parameters analyzed before and after treatment.

Sample Size: "Six female patients."

Controls Used: Not explicitly stated.

Dose Used: "One capsule twice daily for twelve weeks."

Statistical Significance Declared: "p < 0.05"

Adverse Events: Not explicitly stated.

Conflict of Interest: "The authors declare no conflicts of interest."

MacDonald-Ramos K, Monroy A, Bobadilla-Bravo M, Cerbón M. Silymarin Reduced Insulin Resistance in Non-Diabetic Women with Obesity.International Journal of Molecular Sciences. 2024; 25(4):2050. https://doi.org/10.3390/ijms25042050

Publication Date: "Published: 8 February 2024"

Peer Reviewed: Yes.

Study Design: "Longitudinal study."

Methodology: Non-diabetic insulin-resistant women with obesity given silymarin for 12 weeks, no change in habitual diet and physical activity, HOMA-IR, OGTT, and biochemical parameters analyzed before and after treatment.

Sample Size: "Six female patients."

Controls Used: Not explicitly stated.

Dose Used: "One capsule twice daily for twelve weeks."

Statistical Significance Declared: "p < 0.05"

Adverse Events: Not explicitly stated.

Conflict of Interest: "The authors declare no conflicts of interest."

Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future.Phytother Res. 2010;24(10):1423-1432. doi:10.1002/ptr.3207

Publication Date: "Published online 7 June 2010"

Peer Reviewed: Yes

Study Design: "randomized controlled trial"

Methodology: "The participants in this study were randomly divided into two parallel experimental and control groups, each of which contained 40 postmenopausal women."

Sample Size: "80 postmenopausal women (40–60 years)"

Controls Used: "The participants in this study were randomly divided into two parallel experimental and control groups."

Dose Used: "The reportedly effective daily doses of silymarin were 420–600 mg."

Statistical Significance Declared: "The total incidence of upper gastrointestinal bleedings (UGBs), both as a co-factor of death and as ‘last data’, were reported in the two largest trials: 4.6% with silymarin vs 9.6% with placebo, and 6.3% vs 13.5% respectively, and showed differences in favor of the active treatment [p = 0.042; odds ratio (OR) 0.44 (95% CI 0.20, 0.97)]"

Adverse Events: "The case reported described an adverse reaction of the MT herbal medication. The symptoms included severe sweating, abdominal cramping, nausea, vomiting, diarrhea and weakness." "Another report described an anaphylactic shock in a 54-year-old man with immediate-type allergy to kiwi fruit."

Conflict of Interest: "The authors have declared that there is no conflict of interest."

Federico A, Dallio M, Loguercio C. Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years.Molecules. 2017;22(2):191. Published 2017 Jan 24. doi:10.3390/molecules22020191

Publication Date: "Accepted: 18 January 2017."

Peer Reviewed: Yes.

Study Design: "randomized double-blind multicentre trial."

Methodology: Randomized double-blind multicentre trial comparing silymarin with placebo in patients with liver cirrhosis.

Sample Size: "103 with placebo (n = 97) enrolled 200 alcoholics."

Controls Used: "placebo."

Dose Used: "silymarin 450 mg/day in three divided doses."

Statistical Significance Declared: "the frequency of complications was lower in the treated patients (p = 0.06)." "p = 0.042; odds ratio (OR) 0.44 (95% CI 0.20, 0.97)."

Adverse Events: "the symptoms included severe sweating, abdominal cramping, nausea, vomiting, diarrhea and weakness." "Another report described an anaphylactic shock."

Conflict of Interest: "The authors declare no conflict of interest."

Galhardi F, Mesquita K, Monserrat JM, Barros DM. Effect of silymarin on biochemical parameters of oxidative stress in aged and young rat brain.Food Chem Toxicol. 2009;47(10):2655-2660. doi:10.1016/j.fct.2009.07.030

Publication Date: "Available online 6 August 2009."

Peer Reviewed: Yes.

Study Design: "The aim of this work was to evaluate the effects of silymarin, employing a standard extract obtained from a reliable source, in oxidative stress parameters in central nervous system."

Methodology: Young and aged male Wistar rats were treated with silymarin at doses of 200 and 400 mg/kg/day for 14 days, brain tissues collected and conserved for subsequent biochemical analyses.

Sample Size: "Young rats n = 5/group, aged rats n = 4/group."

Controls Used: "Vehicle."

Dose Used: "200 and 400 mg/kg/day."

Statistical Significance Declared: "Asterisks indicate significant statistical difference (∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001)."

Adverse Events: Not explicitly stated.

Conflict of Interest: "The authors declare that there are no conflicts of interest."