Impact of L-arginine and liposomal vitamin C supplementation on quality of life and daily life activities in patients with COPD: a randomized, multicenter, single blind, placebo-controlled trial (ILDA study)

Objective: Chronic Obstructive Pulmonary Disease (COPD) patients experience limitations in activities of daily living (ADL) despite optimal inhaled treatment. L-arginine depletion is associated with poor exercise performance. Our aim was to assess whether oral L-arginine supplementation improves dyspnea and ADL in COPD patients. Design and Methods: Randomized, multicenter, single blind, placebo-controlled study (NCT05412160). Stable COPD patients received L-arginine (1.66 g) plus liposomal vitamin C (500 mg) twice daily or placebo for 4 weeks. At baseline (T0) and after treatment (T1) lung function, six minutes walking test (6MWT), dyspnea and ADL perfomance, evaluated through: COPD assessment test (CAT), self-administered chronic respiratory questionnaire (CRQ-SA), Clinical COPD Questionnaire 24 h and 7 days (CCQ) and London Chest Activity of Daily Living Scale (LCADL) -were assessed. The primary endpoint was CRQ score change compared with placebo. Results: 150 patients were enrolled (67 % males, median FEV1 57 %predicted), with 76 receiving L-arginine. Baseline characteristics and questionnaire scores were balanced between arms. At T1, L-arginine patients demonstrated significant improvements compared to placebo in CRQ total score (median (IQR) 3.5 (0.0;6.75); P = 0.006), CRQ dyspnea domain (3.0 (0.0;6.0); P < 0.001); LCADL total score (-1.0 (-3.0;0.0); P = 0.005); LCADL housework (-1.0 (-3.0;0.0); P < 0.001) and LCADL free time (0.0 (-1.0;0.0); P = 0.003). More L-arginine patients reached the minimal clinically important difference (MCID) in CRQ dyspnea and total LCADL. Baseline CRQ dyspnea<20 (OR (95 %CI): 4.296 (2.051–8.999); P < 0.001) and a LCADL score<27 (7.126 (2.729–18.609); P < 0.001) predicted MCID response. Conclusion: Oral supplementation with L-arginine added to inhaled therapy appears to improve dyspnea and ADL in COPD.