Introduction

Sickle cell disease (SCD) is a blood disorder that is genetic and can lead to cyclical occurrences of vaso-occlusive crises (VOCs). Hydroxyurea is the current standard of treatment, although emerging novel therapies like L-glutamine have shown potential in reducing the frequency of VOCs. This meta-analysis aims to evaluate the safety and efficacy of L-glutamine in reducing VOCs while also improving secondary outcomes.

Methodology

Studies were obtained from PubMed, Cochrane, Scopus, Web of Science, EMBASE, CINDAHL, and CNKI. The primary outcome was VOC frequency and reduction in pain, while the secondary outcomes included hematologic parameters, patient-reported quality of life, hospitalization rates, and biomarkers. A random effect model meta-analysis was performed using R version 3.4.3 (R Core Team)

Results

We included three studies comprising a total of 352 patients. The L-Glutamine group showed a significant reduction in hospitalization rates (MD -0.72 95% CI: -1.26 to – 0.18, p = 0.009, I2 = 0.0%) and VOC frequency (MD -0.75; 95% CI: -1.41 to -0.09, p = 0.02, I² = 58.2%). However, serious adverse events were noted in all studies, without any significant differences between the two groups (RR 1.09; 95% CI: 0.93 to 1.29, p = 0.14, I² = 0.0%). Heterogeneity was moderate to high for VOC outcomes but low for hospitalization and adverse events.

Conclusion

Our findings suggest that L-glutamine can reduce VOCs and hospitalization rates in SCD patients, potentially being used as an adjunctive therapeutic. However, due to the limited sample size in existing studies there remains a need for large-scale and long-term RCTs to confirm is safety and efficacy. Such studies would provide more definitive evidence to support its use in clinical practice.

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2025
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