L-glutamine is an FDA-approved treatment for sickle cell disease. One study explored the potential benefits and mechanism of action of L-glutamine in sickle cell disease patients.
Leukocytosis is common in sickle cell disease (SCD) in the absence of infection and is a predictor for increased risk of stroke, acute chest syndrome, and mortality.
Oral L-glutamine received approval by the Food and Drug Administration (FDA) as a new treatment for both adults and children with SCD in July 2017. Even though a large trial of oral glutamine showed that it reduced the acute complications of SCD in adults and children 5 years and older, the mechanism of action of L-glutamine is not entirely understood.
In a trial to investigate the potential mechanism of L-glutamine in SCD treatment, researchers used BAX (pro-apoptotic marker) and LC3-II/LC3-I (autophagy marker) as indicators to measure active intrinsic cell death of leukocytes. BAX is an established indicator for active intrinsic cell death. LC3-II is needed for autophagocyte maturation and transport and is used as a marker of autophagic activity.
At baseline and two, four, six, and eight weeks after oral glutamine therapy, blood cells were taken from SCD patients and healthy controls to examine leukocytes. Prior to glutamine therapy, SCD leukocytes had 2-fold higher levels of BAX and LC3-I than controls. After 8 weeks of glutamine supplementation, BAX expression increased by 300%. The LC3-II/LC3-I ratio also increased significantly as LC3-I protein levels decreased while LC3-II levels increased by 70%.
Because both BAX and the LC3-II/LC3-I ratio increased in parallel with L-glutamine treatment, cell death may play a role in glutamine treatment, which could alleviate pathologic leukocytosis in SCD. Further research is warranted to verify this discovery.
Source
Walter, P. B., Hohman, L. S., Rokeby, A., Lum, J. J., Hagar, R., Lavrisha, L., . . . Morris, C. R. (2022). The effects of glutamine supplementation on markers of apoptosis and autophagy in sickle cell disease peripheral blood mononuclear cells. Complement Ther Med, 70, 102856. doi:10.1016/j.ctim.2022.102856
