Efficacy and safety of l-glutamine for reducing complications in sickle cell disease: A systematic review and meta-analysis original article

V Vaidarshi Abbagoni (1Montefiore Medical Center/Albert Einstein College of Medicine/MJHS, Hospice and Palliative Care, Bronx, United States) A Ajay Kumar (Ames National Laboratory) B Barbara Lopez (3University of Carabobo, Venezuela, Carabobo, Venezuela) K Khaled MahmoudAli (4Ilia State University, Tbilisi, Georgia, Tbilisi, Georgia) R Rakan Fawwaz (4Ilia State University, Tbilisi, Georgia, Tbilisi, Georgia) K Krishna Veena (5Tbilisi State Medical University, Tbilisi, Georgia, Tbilisi, Georgia) I Ibrahim Sallam (4Ilia State University, Tbilisi, Georgia, Tbilisi, Georgia) K Koussay Gharbi (4Ilia State University, Tbilisi, Georgia, Tbilisi, Georgia) M Mohamed Khalil (1Versiti Blood Research Institute, Milwaukee, United States) S Shreya Shambhavi (7Rutgers health / Community Medical Center, Jersey, United States) E Ernesto Calderon Martinez (The University of Texas, Ciudad de Mexico, Mexico) V Victor Arruarana (9Brookdale University Medical Center, New york, United States)

Abstract

Abstract 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.

Article Details

Journal Blood
Volume / Issue Vol. 146, Issue Supplement 1
Published November 03, 2025
Pages 6510-6510
ISSN 0006-4971
Publisher Elsevier BV

Journal Info

Blood

Elsevier BV

ISSN: 0006-4971 Health Sciences

Authors (12)

V

Vaidarshi Abbagoni

1Montefiore Medical Center/Albert Einstein College of Medicine/MJHS, Hospice and Palliative Care, Bronx, United States

A

Ajay Kumar

Ames National Laboratory

B

Barbara Lopez

3University of Carabobo, Venezuela, Carabobo, Venezuela

K

Khaled MahmoudAli

4Ilia State University, Tbilisi, Georgia, Tbilisi, Georgia

R

Rakan Fawwaz

4Ilia State University, Tbilisi, Georgia, Tbilisi, Georgia

K

Krishna Veena

5Tbilisi State Medical University, Tbilisi, Georgia, Tbilisi, Georgia

I

Ibrahim Sallam

4Ilia State University, Tbilisi, Georgia, Tbilisi, Georgia

K

Koussay Gharbi

4Ilia State University, Tbilisi, Georgia, Tbilisi, Georgia

M

Mohamed Khalil

1Versiti Blood Research Institute, Milwaukee, United States

S

Shreya Shambhavi

7Rutgers health / Community Medical Center, Jersey, United States

E

Ernesto Calderon Martinez

The University of Texas, Ciudad de Mexico, Mexico

V

Victor Arruarana

9Brookdale University Medical Center, New york, United States