Abstract

We have demonstrated previously that oral L-glutamine administration can improve NAD redox potential in sickle red blood cells (RBC) and decrease the endothelial adhesion rate of sickle RBC. Additionally, preliminary results showed that L-glutamine therapy improved the exercise endurance of sickle cell anemia patients. Following up on this study, minute ventilation and work rate were evaluated. After proper consent, 6 homozygous sickle cell anemia volunteers participated in this two-part study. The first part was incremental work rate testing where the work rate was increased incrementally. The second part was the constant work rate test, in which 80% of the maximum work rate of the incremental test was utilized. Patients were observed for changes in ventilation. These tests were conducted at baseline and after 8 to 12 weeks of therapy with oral L-glutamine at 30 grams a day. There were 6 patients who completed the incremental work rate test and 4 patients who completed the constant work rate test, respectively, at baseline and after treatment. Two of the patients withdrew prior to the completion of the follow-up testing. The results were as follows: On the incremental test, there was an upward trend in peak work rate with an average of 3.5 ± 8.7 watts/min (88.7 ± 25.6 vs. 91.5 ± 21.7; ρ> 0.05). Minute ventilation (VE) showed an average improvement of −4.8 ± 3.9 liters/min (61.2 ± 9.8 vs. 56.4 ± 9.9; ρ value of 0.05). The improved ventilation may be secondary to increased pulmonary blood flow inferring an increased cardiovascular oxygen delivery. On the constant work rate test, there was significant increase in exercise duration with an average of 1.4 ± 0.8 minutes (5.9 ± 1.6 vs. 7.3 ± 1.1; ρ< 0.05). The minute ventilation (VE) showed an average decrease of −11.0 ± 11.6 liters/min (66.5 ± 24.9 vs. 55.5 ± 14.5; ρ> 0.05). This could be indicative of improved oxygen delivery to the exercising musculature despite the absence of a preparatory exercise training program. The data confirm our preliminary report suggesting that L-glutamine therapy improves the exercise endurance of sickle cell anemia patients.

TestMean + SDρ value
PrePostPaired Δ(two-tailed t-test)
Incremental Work Rate     
Peak Work Rate (watts/min) 88.7 ± 25.6 91.5 ± 21.7 3.5 ± 8.7 0.37 
VE (liters/minute) 61.2 ± 9.8 56.4 ± 9.9 −c4.8 ± 3.9 0.05 
Constant Work Rate     
−Duration (minutes) 5.9 ± 1.6 7.3 ± 1.1 1.4 ± 0.8 0.04 
−VE (liters/minute) 66.5 ± 24.9 55.5 ± 14.5 −11.0 ± 11.6 0.15 
TestMean + SDρ value
PrePostPaired Δ(two-tailed t-test)
Incremental Work Rate     
Peak Work Rate (watts/min) 88.7 ± 25.6 91.5 ± 21.7 3.5 ± 8.7 0.37 
VE (liters/minute) 61.2 ± 9.8 56.4 ± 9.9 −c4.8 ± 3.9 0.05 
Constant Work Rate     
−Duration (minutes) 5.9 ± 1.6 7.3 ± 1.1 1.4 ± 0.8 0.04 
−VE (liters/minute) 66.5 ± 24.9 55.5 ± 14.5 −11.0 ± 11.6 0.15 

Author notes

Disclosure:Employment: Yutaka Niihara, MD is an officer of Emmaus Medical, Inc. which is developing treatment for sickle cell disease. Ownership Interests: Yutaka Niihara, MD and Kouichi Tanaka, MD have ownership interests of Emmaus Medical, Inc. Research Funding: FDA Office of Orphan Products Development Grant.