Coadministration of silymarin with iron chelators in transfusion-dependent β-thalassemia patients: a systematic review and meta-analysis for effect on iron overload

ABSTRACT

Background and aim: We conducted a systematic review to apprise the efficacy of silymarin in conjunction with standard iron chelators on iron overload for transfusion-dependent β-thalassemia (TDT) patients.

Methods: We searched PubMed, Web of Science, Scopus, Sciencedirect, the Cochrane Library (the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials (CENTRAL) to 1 May 2020. All randomized controlled trials (RCTs) studies comparing the effect of iron chelators alone versus silymarin plus standard routine treatment on iron burden amid TDT were included in this review. Primary outcomes comprised serum ferritin level (ng/mL), liver iron concentration (LIC Fe/kg dry weight), and total iron binding capacity (TIBC mcg/dL)

Results: Combination therapy of silymarin and iron chelators showed a significant improvement in serum ferritin level in TDT patients, compared to nonsilymarin users [eight studies, n = 477]; weighted mean difference (WMD) −1.79, 95% confidence interval [CI] −2.86 to −0.72, I² 96.1%; P = 0.001. Concurrent treatment with silymarin failed to significantly decrease LIC in TDT patients [two studies, n = 106]; WMD 0.74, 95% CI −1.62 to 3.10, I² 96.6%; P = 0.54.

Conclusion: There is no evidence of the effectiveness of adding silymarin to standard iron chelators to reduce iron load in TDT.

KEYWORDS:

• Thalassemia
• iron-chelators
• iron overload
• silymarin
• legalon
• milk thistle

Article Highlights

• The impact of silymarin alongside standard iron chelators on iron overload amid transfusion dependent β-thalassemia (TDT) patients has not yet been well known.

• Co-administration silymarin with iron chelators is not effective in attenuating iron load in TDT patients.

• The GRADE tools discover that the level of evidence is equal to very low for each outcome, including serum ferritin, LIC and TIBC.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author’s contribution

Searching the database, data extraction phase, and preparing the draft of manuscript were performed by M.Z., M.P., F.T., and A.N. Statistical analysis was executed by H.D.K.H. Moreover, H.D.K.H., M.N., and H.K. were responsible for critical appraisal and reviewing of the manuscript. H.D.K.H. and H.K. edited the final manuscript. All authors contributed in interpretation of data and critical revision of the manuscript for important intellectual content.

Registration and protocol

The protocol of study was prospectively discernable on 19 July 2020 on the first author’s ResearchGate profile (Hadi Darvishi-Khezri, https://www.researchgate.net/publication/343054138) (Appendix 6).

Availability of data, code, and other materials

Data will be available for authors who send their protocol to us.

Supplementary material

Supplemental data for this article can be accessed here.