TOPLINE

In patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure on 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 than placebo.

METHODOLOGY

• In a randomized controlled trial (July 2024-December 2025) conducted at 10 rehabilitation facilities in Italy, researchers assessed whether adding L-arginine plus liposomal vitamin C to pulmonary rehabilitation could reduce fatigue in patients with COPD and chronic respiratory failure who had been on oxygen therapy for 12 months or longer (n = 98; mean age, 72 years; 52% men).
• Participants were randomly assigned to receive 1.66 g of oral L-arginine plus 500 mg of liposomal vitamin C or matching placebo twice daily alongside a 28-day pulmonary rehabilitation program comprising 22 or more supervised sessions of aerobic, resistance, and flexibility training, with nutritional and psychosocial support.
• The primary endpoint was the change in fatigue severity, assessed using the Fatigue Severity Scale at day 28; a change of ≥ 0.6 points was prespecified as clinically meaningful.
• Changes in the 6-minute walk distance, sit-to-stand test performance, handgrip strength, and dyspnea score were included as secondary outcomes.

TAKEAWAY

• Fatigue scores improved in both the groups at day 28; however, the improvement was significantly greater with L-arginine plus liposomal vitamin C than with placebo (difference, 0.90 points; P = .004), exceeding the prespecified minimal clinically important difference.
• The benefits were consistent even after adjusting for confounding factors.
• The 6-minute walk distance improved by 47.6 m with L-arginine plus liposomal vitamin C vs 36.3 m with placebo (both P < .001); the between-group difference of 11.3 m favored the intervention group but was not statistically significant.  
• Improvements in sit-to-stand performance, handgrip strength, and health-related quality of life and a reduction in dyspnea were observed in both groups, with no significant differences between the groups.

IN PRACTICE

"These findings support the potential role of L-arginine plus liposomal vitamin C as an adjunct to PR [pulmonary rehabilitation], while highlighting the need for cautious interpretation," the authors wrote.

SOURCE

The study was led by Mauro Maniscalco, Istituti Clinici Scientifici Maugeri IRCCS in Telese Terme, Italy. It was published online on September 18, 2026, in Thorax.

LIMITATIONS

Baseline vitamin C levels were not measured, and the intervention lasted only 28 days. The trial primarily focused on fatigue; therefore, it may have missed modest effects on secondary outcomes. The effects of the rehabilitation program alone may have masked any added benefit of the supplement over the relatively limited treatment duration.

DISCLOSURES

The trial was partly funded by Italy's Ministry of Health through its Ricerca Corrente program. Damor Farmaceutici supplied the study product and placebo at no cost. One author reported institutional grants from two pharmaceutical companies and honoraria for talks and educational events from three, including Damor Farmaceutici, the maker of the study product. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.