Iron‐chelating effect of silymarin in patients with β‐thalassemia major: A crossover randomised control trial

Abstract

This study aimed to determine the potential iron-chelating effects of silymarin in patients with β-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with β-thalassemia major.

Therapeutic potential of silymarin as a natural iron‐chelating agent in β‐thalassemia intermedia

“…We found that ferritin levels were significantly decreased in β‐TI patients after 3 and 6 months of silymarin therapy. This finding is consistent with previous studies that reported iron‐chelating effect of silymarin in combination with desferrioxamine or deferiprone 5‐8 . Additionally, the iron‐chelating potential of silybin, a major bioactive component of silymarin flavonolignan complex, has previously been reported in patients with hereditary hemochromatosis 9 …”

“…Many studies have shown a positive association between serum ferritin levels and liver iron concentration. We and others have previously shown that a combination of silymarin and desferoxamine improves liver and cardiac function in β‐thalassemia major patients 5,10 …”

“…This finding is consistent with previous studies that reported iron‐chelating effect of silymarin in combination with desferrioxamine or deferiprone. 5 , 6 , 7 , 8 Additionally, the iron‐chelating potential of silybin, a major bioactive component of silymarin flavonolignan complex, has previously been reported in patients with hereditary hemochromatosis. 9 Many studies have shown a positive association between serum ferritin levels and liver iron concentration.…”

“… 4 We and others previously reported that combined treatment with silymarin and conventional iron chelators are safe and effective for reducing the iron overload in β‐thalassemia major patients. 5 , 6 , 7 , 8 However, it is still unclear whether silymarin monotherapy would be an effective iron‐chelating agent for the treatment of iron‐overload disorders. In this study, we evaluated the iron‐chelating effect of silymarin regimen alone in a group of β‐TI patients, who refused the conventional iron‐chelating treatments.…”

Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases

“…The possible antioxidant mechanisms of silymarin include (a) prevention of free radical formation via inhibition of reactive oxygen species (ROS)‐producing enzymes; (b) direct scavenging of free radicals actions; (c) ion chelation (Fe and Cu) in the intestine; (d) promotion of the synthesis of protective molecules (e.g., heat shock proteins, thioredoxin, and sirtuins) that provide protection against stressful stimuli (Surai, ); and (e) activation of antioxidant enzymes such as superoxide dismutase and nonenzymatic pathways, mainly via Nrf2 activation. For example, it has been reported that silymarin markedly increases the expression of superoxide dismutase in the patients with nonalcoholic steatohepatitis (Milosević, Milanović, Abenavoli, & Milić, ; Stiuso et al, ) and decreases the oxidative stress in the β‐thalassemia patients (Darvishi‐Khezri et al, ).…”