Among children and adults with sickle cell anemia, the median number of pain crises over 48 weeks was lower among those who received oral therapy with l-glutamine, administered alone or with hydroxyurea, than among those who received placebo, with or without hydroxyurea. (Funded by Emmaus Medical; ClinicalTrials.gov number, NCT01179217 .).

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Previously, we demonstrated that there is an increased utilization of glutamine by intact sickle red blood cells (RBC) in conjunction with nicotinamide adenine dinucleotide (NAD) metabolism in vitro. In this report, we describe the in vivo effect of L-glutamine supple-mentation on total NAD, nicotinamide adenine dinucleotide reduced (NADH), and NAD redox potential of sickle RBC. Seven adult sickle cell anemia patients participated in this study. The exclusion criteria were pregnancy, previous or current use of hydroxyurea, and transfusion within 3 months of initiation of the study. After proper consent, L-glutamine was started at a dose of 30 g/day administered orally. Fasting blood samples were drawn at baseline and after 4 weeks of therapy by routine phlebotomy for evaluation of RBC total NAD and NADH levels. We found significant changes in both the NADH level and NAD redox potential (ratio of NADH to NAD + + NADH). NAD redox potential increased from 47.2 ± 3.7% to 62.1 ± 11.8% (P < 0.01). The NADH level increased from 47.5 ± 6.3 to 72.1 ± 15.1 nmol/ml RBC (P < 0.01). The total NAD level demonstrated an upward trend (from 101.2 ± 16 to 116.4 ± 14.7 nmol/ml RBC) but this was not statistically significant. Our data show that oral L-glutamine can significantly increase the NAD redox potential and NADH level in sickle RBC. These changes may decrease oxidative susceptibility of sickle RBC and result in clinical benefit. Am.