L-Arginine and Vitamin C Supplementation May Reduce Fatigue in COPD: Study
Italy: Researchers have found in a new study that among patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure receiving long-term oxygen therapy, adding oral L-arginine plus liposomal vitamin C to a structured pulmonary rehabilitation program was associated with a greater reduction in fatigue compared with placebo.
The findings suggest that this combination may provide an additional benefit for managing fatigue in patients undergoing pulmonary rehabilitation.
The multicentre, randomised, double-blind, placebo-controlled trial was conducted by Mauro Maniscalco, Pulmonary Rehabilitation Unit of Telese Terme Institute, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Campania, Italy, and colleagues. The study was published in the BMJ journal Thorax.
Pulmonary rehabilitation is a key component of non-pharmacological management for COPD, particularly in patients with advanced disease and chronic respiratory failure. However, fatigue can remain a significant and disabling symptom even after rehabilitation. The researchers therefore evaluated whether supplementation with L-arginine and liposomal vitamin C could provide additional benefits when combined with standard rehabilitation.
The study enrolled 98 patients with stable COPD and chronic respiratory failure who were receiving long-term oxygen therapy. Participants were randomly assigned to receive either oral L-arginine plus liposomal vitamin C or placebo while completing a standardised 28-day pulmonary rehabilitation programme.
Fatigue was assessed using the Fatigue Severity Scale (FSS), with repeated measurements analysed using a longitudinal statistical model. The researchers also assessed exercise capacity, muscle strength, respiratory symptoms and health status through measures including the 6-minute walk distance, sit-to-stand test, handgrip strength, COPD Assessment Test and modified Medical Research Council dyspnoea score.
The analysis showed:
- Participants receiving L-arginine plus liposomal vitamin C had a significantly greater reduction in FSS scores than those receiving placebo, with a mean between-group difference of −0.90 points.
- The adjusted treatment-by-time analysis confirmed the difference, showing an adjusted between-group difference of −0.72 points.
- The observed treatment effect exceeded the prespecified minimal clinically important difference of 0.6 points.
- A greater proportion of participants in the intervention group achieved an FSS score below 4 compared with the placebo group (57% versus 36%), although this difference did not reach statistical significance.
- No significant differences were observed between the groups for exercise capacity, muscle strength, COPD-related health status, or dyspnoea.
The findings indicate that adding L-arginine and liposomal vitamin C to pulmonary rehabilitation may specifically help reduce perceived fatigue in patients with advanced COPD and chronic respiratory failure. However, the absence of significant improvements in functional and patient-reported secondary outcomes suggests that the benefit may be limited to fatigue rather than broader rehabilitation outcomes.
The study supports further investigation of nutritional supplementation as an adjunct to pulmonary rehabilitation, particularly for persistent fatigue in patients with severe COPD and chronic respiratory failure.
Reference:
Maniscalco M, Candia C, Fiorentino G, et al. Targeting fatigue in COPD with chronic respiratory failure undergoing pulmonary rehabilitation: a multicentre, randomised, placebo-controlled trial of L-arginine/liposomal vitamin C. Thorax. Published Online First: 18 September 2026. doi: 10.1136/thorax-2026-225106
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