[HTML][HTML] l-Arginine supplementation in severe asthma
SY Liao, MR Showalter, AL Linderholm, L Franzi… - JCI insight, 2020 - ncbi.nlm.nih.gov
JCI insight, 2020•ncbi.nlm.nih.gov
BACKGROUND Dysregulation of l-arginine metabolism has been proposed to occur in
patients with severe asthma. The effects of l-arginine supplementation on l-arginine
metabolite profiles in these patients are unknown. We hypothesized that individuals with
severe asthma with low fractional exhaled nitric oxide (FeNO) would have fewer
exacerbations with the addition of l-arginine to their standard asthma medications compared
with placebo and would demonstrate the greatest changes in metabolite profiles. METHODS …
patients with severe asthma. The effects of l-arginine supplementation on l-arginine
metabolite profiles in these patients are unknown. We hypothesized that individuals with
severe asthma with low fractional exhaled nitric oxide (FeNO) would have fewer
exacerbations with the addition of l-arginine to their standard asthma medications compared
with placebo and would demonstrate the greatest changes in metabolite profiles. METHODS …
Abstract
BACKGROUND
Dysregulation of l-arginine metabolism has been proposed to occur in patients with severe asthma. The effects of l-arginine supplementation on l-arginine metabolite profiles in these patients are unknown. We hypothesized that individuals with severe asthma with low fractional exhaled nitric oxide (FeNO) would have fewer exacerbations with the addition of l-arginine to their standard asthma medications compared with placebo and would demonstrate the greatest changes in metabolite profiles.
METHODS
Participants were enrolled in a single-center, crossover, double-blind l-arginine intervention trial at UCD. Subjects received placebo or l-arginine, dosed orally at 0.05 mg/kg (ideal body weight) twice daily. The primary end point 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= 0.005 and P= 2.51× 10–9, respectively). Higher AAI was associated with lower exacerbation events. The eicosanoid prostaglandin H 2 (PGH 2) and N α-acetyl-l-arginine were found to be good predictors for differentiating clinical responders and nonresponders.
CONCLUSIONS
There was no statistically significant decrease in asthma exacerbations in the overall cohort with l-arginine intervention. PGH 2, N α-acetyl-l-arginine, and the AAI could serve as predictive biomarkers in future clinical trials that intervene in the arginine metabolome.
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