Table 2.
Randomized Clinical trials not included in the published meta-analysis studies, investigating the impact of silibinin/silymarin on classical cardiovascular risk factors.
| Reference | Cohorts | Study Design | Outcomes-Variables |
|---|---|---|---|
| Ebrahimpour Koujan, et al., 2015 [92] | 40 pts, T2DM | RCT; Intervention group (20 pts): 140 mg Silymarin orally, 3 times/day, for 45 d Control group (20 pts): placebo |
↑ SOD, ↑ GPX, ↑ TAC, ↓ hs-CRP, ↓ MDA |
| Ebrahimpour-Koujan, et al., 2018 [93] | 40 pts, T2DM, dyslipidemia | RCT; Intervention group (20 pts): 140 mg Silymarin orally, 3 times/day, for 45 d Control group (20 pts): placebo |
↓ FBS, ↓ insulin, ↓ HOMA-IR, ↑ QUICKI, ↓ TG, ↓ TChol, ↑ HDL-C, ↓ LDL-C |
| Hussain SA, et al., 2007 [94] | 51 pts, T2DM | RCT; Group A (18 pts): 200 mg/day Silymarin orally + 10 mg/day oral glibenclamide for 120 d Group B (20 pts): placebo + 10 mg/d oral glibenclamide, for 120 d Group C (control) (21 pts): 10 mg/d glibenclamide |
↓ FBG, ↓ HbA1c, ↓ insulin, ↓ LDL-C, ↓ TG, ↓ TChol, ↓ SGOT, ↓ SGPT, ↓ weight, ↓ SBP ↓ DBP |
| Khalili, et al., 2017 [95] | 60 pts, T2DM | RCT; Intervention group (30 pts): 200 mg Silymarin orally, 3 times/day, for 90 d Control group (30 pts): placebo |
↓ FBG, ↓ HbA1c, ↓ TG, ↓ TChol, ↔ LDL-C, ↔ HDL-C, ↔ SBP, ↔ DBP, ↔ AST, ↔ ALT, ↔ ALP, ↔ BUN, ↔ Creatinine |
| Huseini HF, et al., 2006 [96] | 51 pts, T2DM | RCT; Intervention group (25 pts): 200 mg silymarin orally 3 times/day, for 120 d Control group (26 pts): placebo |
↓ FBG, ↓ HbA1c, ↓ BMI |
| Velussi M., et al., 1997 [97] | 60 pts, insulin-treated DM, liver cirrhosis | Randomized, open, controlled study; Intervention group (30 pts): standard therapy + 200 mg Silymarin orally, 3 times/day, for 360 d Control group (30 pts): standard therapy |
↓ FBG, ↓ glucosuria, ↓ HbA1c, ↓ insulin, ↓ MDA, ↓ C-peptide, ↔ γGT, ↔ ALP ↔ creatinine, ↔ bilirubin, ↔ microalbuminuria, ↓ AST, ↓ ALT, ↓ TChol, ↑ HDL-C, ↑ TG |
| Federico A, et al., 2019 [99] | 90 pts with NAFLD and 60 healthy participants | Prospective study; Intervention group (NAFLD, 60 pts): 1 capsule 2 times/day, for 180 d [capsules: silybin-phospholipid complex (303 mg) of, vitamin D (10 mg), vitamin E (15 mg)]. Control group (NAFLD, 30 pts): no drug Healthy group (60 pts): no drug | ↔ BMI, ↔ weight, ↓ ALT, ↓ γGT, ↔AST, ↓ insulin, ↓ HOMA-IR, ↑ vitamin D, ↓ degree of steatosis ↔ FBG, ↔ TG, ↔ TChol, ↔ LDL-C, ↔ Ferritin |
| Cerletti C, et al., 2020 [100] | RCT, 126 pts, NAFLD | RCT; Intervention group (62 pts): 2 capsules, once a day, for 90 d [capsules: mixture of active ingredients, 70% DHA (250 mg), phosphatidylcholine (150 mg), silymarin (75 mg), choline bitartrate (35 mg), curcumin (35 mg) and D-α-tocopherol (10 mg)] Control group (64 pts): placebo |
↓ AST, ↑ HDL, ↑ LDL, ↑ TChol, ↑ FBG, ↔ weight, ↔ BMI, ↔ waist circumference |
| Sciacqua A, et al., 2019 [102] | 50 pts, Hypertension | Pilot, single arm, interventional, longitudinal study. Dose: 3 g Silibinin, twice a day (Silibinin conjugated to vit E and phosphatidylcholine–oral solution) |
↓ TChol, ↓ TG, ↑ HDL-C, ↓insulin, ↓ FBG, ↓ HOMA-IR, ↑IGF-1, ↑ eGFR, ↓ CRP, ↓ UA, ↓liver enzymes, ↓ SBP, ↓ Pulmonary pressure |
| Alkuraishy, et al., 2012 [103] | 20 pts, Dyslipidemia | RCT; Intervention group (10 pts): 600 mg silymarin orally, once/day, for 14 d Control group (10 pts): placebo |
↓ TChol, ↓ TG, ↑ HDL-C, ↓ LDL-C, ↓ VLDL |
| Altaei T, et al., 2012 [104] | 102, CABG | Prospective study; Intervention group (50 pts): 140 mg silymarin orally, 3 times/day, 3 d before surgery Control group (52 pts): no drug | ↓ cytokine concentrations (IL-6, IL-1a, TNF-a), ↓ CRP, ↑ GSH, ↑ TEAC, ↓ MDA |
| Roozbeh J, et al., 2011 [105] | 80, ESRD, DM, Hypertension | Prospective study; Group 1 (20 pts): 140 mg silymarin, orally, 3 times/day, for 90 d Group 2 (20 pts): vitamin E 400 IU/day, for 90 dGroup 3 (20 pts): 140 mg silymarin, orally, 3 times/day + vit E 400 IU/day, for 90 d Group 4, control (20 pts): no drug |
↑ GPX, ↓ MDA, ↑ mean hemoglobin (all three treatment groups VS control) |
| Firuzi O, et al., 2016 [106] | 60, ESRD | RCT; Intervention group (28 pts): 140 mg silymarin orally, 4 times/day, for 60 d Control group (22 pts): placebo |
↓ FRAP, ↑ Hemoglobin, ↑ serum albumin, ↔ creatinine, ↔ iPF2a |
| Voroneanu L, et al., 2017 [107] | 102, T2DM, Proteinuria, (ischemic heart disease) | RCT; Intervention group (51 pts): 150 mg silymarin, orally, 3 times/day, for 2 years (720 d) Control group (51 pts): placebo |
↔ mortality ↔ progression of CKD indefinite effect on eGFR and proteinuria |
Key: ALP, Alkaline phosphatase; ALT, Alanine transaminase; AST, Aspartate transaminase; BMI, Body mass index; BUN, blood urea nitrogen; d, days; DBP, diastolic blood pressure; DM, diabetes mellitus; eGFR, estimated Glomerular filtration rate; ESRD, End-stage renal disease; FBG, Free blood glucose; FRAP, Ferric Reducing Antioxidant Power; GPX, Glutathione peroxidase; GSH, Blood Glutathione; HbA1c, Haemoglobin A1c; HDL-C, High-density lipoprotein Cholesterol; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; hs-CRP, high-sensitivity C-reactive protein; IGF-1, Insulin-like growth factor 1; iPF2a, 8-iso-prostaglandin F2a; LDL-C, Low-density lipoprotein Cholesterol; MDA, Malondialdehyde; NAFLD, Non-Alcoholic Fatty Liver Disease; pts, patients; QUICKI, quantitative insulin sensitivity check index; RCT, randomized control trial; SBP, systolic blood pressure; SOD, superoxide dismutase; TAC, total antioxidant capacity; TEAC, Plasma trolox equivalent antioxidant capacity; TChol, Total cholesterol; TG, Triglycerides; TGFβ, Transforming growth factor beta; TNF-a, tumour necrosis factor-a; UA, uric acid; UACR, Urinary albumin-creatinine ratio; VLDL-C, Very-low-density lipoprotein cholesterol; γGT, gamma-glutamyl transpeptidase; ↓, decrease; ↑, increase; ↔, significant change.