L-glutamine reduces pain crises and other common events associated with sickle cell disease

Data from a phase III study in patients with sickle cell disease (SCD) demonstrated that a treatment with prescription grade L-glutamine provides clinical benefit over placebo by reducing the frequency of painful crises and hospitalization. In addition to this L-glutamine reduced the incidence of acute chest syndrome (ACS), delayed the time to the first crises and reduced the duration of hospital stay. Of note, unlike more intense regimens for SCD that require infusions and regular monitoring, L-glutamine forms a simple oral alternative, making it particularly interesting.

SCD is a chronic condition with few treatment options available. The most commonly utilized treatment consists of oral hydroxyurea, but because of its potential severe side effects, it is not feasible in all patients. Increased oxidant stress plays a major part in the pathophysiology of sickle cell disease. It can lead to disturbance of cell membranes, exposure of adhesion molecules and damage to the contents of the sickle red blood cells. Nicotinamide adenine dinucleotide (NAD). is an important physiological antioxidant in RBC and in SCD, the red blood cell NAD redox potential is significantly compromised. As such, glutamine, a precursor for NAD, could potentially improve this NAD redox potential. A multi-center phase II, placebo-controlled trial in patients with SCD utilizing oral prescription grade L-glutamine resulted in a trend for a decrease in the incidence of painful crises at 24 weeks and a statistically significant decrease in hospitalization during the same time period in the L-glutamine group without increased adverse events. Based on these results, a large multicenter phase III clinical trial was undertaken to evaluate the efficacy and safety of prescription grade L-glutamine therapy in patients with SCD.

This phase III study evaluated the use of pharmaceutical-grade L-glutamine as a new, daily oral treatment option for SCD based upon the theory that it may reduce oxidative stress and therefore decrease the red blood cell “sickling” associated with the disease. In total 230 patients were randomized to receive daily L-glutamine (152 patients) or placebo (78 patients) for 48 weeks, after which treatment levels were tapered to zero over 3 weeks and a final evaluation visit was made 2 weeks after the last dose. The primary endpoint of the trial was the number of sickle cell crises, while secondary objectives included rates of hospitalization and adverse events. Additional analyses looked at the cumulative hospital days, the incidence of ACS, a severe complication of SCD, and the time to the first crisis.

Researchers observed that patients who received L-glutamine experienced fewer painful crises (3 vs. 4 events respectively; p= 0.008). The median time to the first crisis was 54 days in placebo group and 87 days in treatment group (p= 0.010). Treated patients were also less likely to be hospitalized for their condition (2 vs. 3 events during the study period) and spent less time in the hospital for these events (6.5 vs. 11 days, p= 0.022) than those receiving placebo. Importantly, the percentage of patients experiencing ACS was less than half among the L-glutamine group compared to the placebo group (11.9% vs. 26.9%; p= 0.006). The treatment was well tolerated, as safety profiles were similar among the treatment and placebo groups.

These phase III data support the use of L-glutamine in SCD patients, as it appears to safely reduce the most common events associated with the disease. Interestingly, oral L-glutamine is easy to administer and does not require special monitoring, unlike more intense regimens for SCD.


Niihara Y, Koh H, Tran L, et al. A Phase 3 Study of L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß-Thalassemia. Presented at ASH 2014; Abstract #86.

Speaker Yutaka Niihara


Yutaka Niihara, MD, PhD,
David Geffen School of Medicine at University of California, Los Angeles, CA, USA


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