L-Arginine Supplementation and Metabolism in Asthma

Abstract

l-Arginine, the amino acid substrate for nitric oxide synthase, has been tested as a therapeutic intervention in a variety of chronic diseases and is commonly used as a nutritional supplement. In this study, we hypothesized that a subset of moderate to severe persistent asthma patients would benefit from supplementation with l-arginine by transiently increasing nitric oxide levels, resulting in bronchodilation and a reduction in inflammation. The pilot study consisted of a 3 month randomized, double-blind, placebo-controlled trial of l-arginine (0.05 g/kg twice daily) in patients with moderate to severe asthma. We measured spirometry, exhaled breath nitric oxide, serum arginine metabolites, questionnaire scores, daily medication use and PEFR with the primary endpoint being the number of minor exacerbations at three months. Interim analysis of the 20 subjects showed no difference in the number of exacerbations, exhaled nitric oxide levels or lung function between groups, though participants in the l-arginine group had higher serum l-arginine at day 60 (2.0 ± 0.6 × 10−3 vs. 1.1 ± 0.2 × 10−3 μmol/L, p < 0.05), ornithine at day 30 (2.4 ± 0.9 vs. 1.2 ± 0.3 μmol/L serum, p < 0.05) and ADMA at day 30 (6.0 ± 1.5 × 10−1 vs. 2.6 ± 0.6 × 10−1 μmol/L serum, p < 0.05) on average compared to the placebo group. The study was terminated prematurely. Supplementing asthma subjects with l-arginine increases plasma levels; whether subgroups might benefit from such supplementation requires further study.

Glucagon-like peptide 1: A potential anti-inflammatory pathway in obesity-related asthma

“…Furthermore, it can undergo methylation and generate asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor. Dysregulation of arginine metabolism occurs in obesity, metabolic syndrome, and asthma, resulting in depletion of L-arginine through increased ADMA production and arginase activity (Kenyon et al, 2011; Linderholm et al, 2014). …”

Arginine and Asthma

“…Other studies using murine asthma models found that arginine supplementation amplified the asthmatic inflammatory response [68,69] while a small study of 14 patients with asthma found that pretreatment with oral L-arginine (50 mg/kg) had no significant influence on AHR to histamine [70]. The same dose given twice a day for 3 months to 15 patients completing a randomized placebo-controlled trial had no impact on number of exacerbations, exhaled NO levels or lung function compared to placebo in patients studied with moderate to severe persistent asthma [71].…”

Competitive metabolism of L -arginine: arginase as a therapeutic target in asthma

“…Some asthmatic subjects boost exhaled NO levels, while others have a significant increase in the downstream products of arginase, as measured in serum. Furthermore, supplementation in asthmatic patients may cause short term increases in plasma ADMA[105], which may result from increased efflux of intracellular ADMA into the plasma compartment. While the strategy of L -arginine supplementation is appealing because it is inexpensive and readily available, it will be important to discover a biomarker or NOS/arginase genotype that predicts some response to therapy.…”