The impact of silymarin on antioxidant and oxidative status in patients with ß-thalassemia major: A crossover, randomized controlled trial.

BACKGROUND & AIMS: Blood transfusion therapy is lifesaving for individuals with ß-thalassemia major (ß-TM). Iron burden following blood transfusion is the main cause of oxidative stress (OS) and organ dysfunction in these patients. The aim of this study was to evaluate the effects of silymarin on serum antioxidant and oxidative status in patients with ß-TM. METHODS: A crossover, randomized controlled trial was performed on 82 thalassemia patients. In two periods of 12 weeks, patients received 420mg silymarin (divided into three equal 140-mg daily doses) and placebo. The washout period between the two phases was two weeks. Serum malondialdehyde (MDA), protein carbonyl (CO), total antioxidant capacity (TAC), and reduced glutathione (GSH) were measured before and after both periods. RESULTS: Sixty-nine patients completed the study. Mean serum MDA and protein CO significantly decreased in all patients with ß-TM after three months of treatment with silymarin. At the end of the study, serum MDA decreased from 20.36±20.11 to 4.79±4.71µmol/l (compared to 17.81±16.05µmol/l after administration of placebo), and protein CO dropped from 0.31±0.28 to 0.11±0.09mM/l (compared to 0.24±0.17mM/l with placebo). Additional laboratory parameters (such as serum TAC and plasma GSH) were also significantly elevated after therapy with silymarin. At the end of the study, serum TAC increased in all patients from 620.7±202.64 to 971.83±328.16µmol FeSO4/l (compared to 672.22±206.88µmol FeSO4/l with placebo), and GSH increased from 46.16±41.68 to 195.35±210.98nM/l (compared to 58.52±48.95nM/l with placebo). The treatment effect of silymarin was measured using a mixed-effects model of variance analysis for changes in MDA, protein CO, TAC, and GSH, with significant effects being demonstrated for each laboratory parameter (P<0.001, P=0.002, P<0.001, and P<0.001, respectively). CONCLUSIONS: Silymarin was effective in decreasing serum OS and enhancing serum antioxidant capability in patients with ß-thalassemia major. Silymarin given as an adjuvant therapy to standard iron chelators may provide an improvement in the OS measurements obtained in these patients, with accompanying benefit.