L-arginine supplementation in severe asthma.
What this study found
No significant reduction in moderate asthma exacerbations with l-arginine in the overall cohort (primary endpoint; P=0.41). In the low-FeNO subgroup, l-arginine was associated with a 0.45 L (0.12% predicted) increase in FVC versus the high-FeNO subgroup (interaction P=0.02; group difference P<0.001). FeNO rose more in the low-FeNO group on l-arginine. Baseline metabolites PGH2 and Nα-acetyl-L-arginine predicted treatment response; higher arginine availability index (AAI) correlated with fewer exacerbations and higher FeNO. A subset of 28 with complete data included 8 responders (≥33%…
- Study & population
- Single-center, randomized, double-blind, placebo-controlled, crossover trial at UC Davis.
- Intervention
- Oral l-arginine 0.05 g/kg ideal body weight twice daily; 12 weeks per treatment period.
- Key limitation
- Small, single-center crossover trial; potential carryover and period effects; metabolomics results were semiquantitative and not validated in a replication cohort; limited generalizability.
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Open PDFOriginal abstract
BACKGROUND Dysregulation of L-arginine metabolism has been proposed to occur in severe asthma patients. The effects of L-arginine supplementation on L-arginine metabolite profiles in these patients is unknown. We hypothesized that severe asthmatics with low fractional exhaled nitric oxide (FeNO) would have fewer asthma exacerbations with the addition of L-arginine to their standard asthma medications compared to placebo and would demonstrate the greatest changes in metabolite profiles. METHODS Participants were enrolled in a single-center, cross-over, double-blinded, L-arginine intervention trial at the University of California-Davis (NCT01841281). Subjects received placebo or L-arginine, dosed orally at 0.05mg/kg (ideal body weight) twice daily. The primary endpoint was moderate asthma exacerbations. Longitudinal plasma metabolite levels were measured using mass spectrometry. A linear mixed-effect model with subject-specific intercepts was used for testing treatment effects. RESULTS A cohort of 50 subjects was included in the final analysis. L-arginine did not significantly decrease asthma exacerbations in the overall cohort. Higher citrulline levels and a lower arginine availability index (AAI) were associated with higher FeNO (P-value = 0.005 and 2.51 x 10-9 respectively). Higher AAI was associated with lower exacerbation events. The eicosanoid prostaglandin H2 (PGH2) and Nα-Acetyl-L-arginine were found to be good predictors for differentiating clinical responders and non-responders. CONCLUSIONS There was no statistically significant decrease in asthma exacerbations in the overall cohort with L-arginine intervention. PGH2, Nα-Acetyl-L-arginine and the AAI could serve as predictive biomarkers in future clinical trials that intervene in the arginine metabolome.