L-Arginine and Vitamin C reduce fatigue in COPD patients, trial finds
- Oral L-arginine combined with liposomal vitamin C significantly reduces fatigue in patients with chronic obstructive pulmonary disease who require long-term oxygen therapy, according to a clinical trial published...
- The multicenter, randomized controlled trial was coordinated by the IRCCS Maugeri medical institute and conducted across 10 rehabilitation facilities in Italy between July 2024 and December 2025, Medscape...
- Participants in the trial were randomly assigned to receive either 1.66 grams of oral L-arginine plus 500 milligrams of liposomal vitamin C, or a matching placebo, taken twice...
Oral L-arginine combined with liposomal vitamin C significantly reduces fatigue in patients with chronic obstructive pulmonary disease who require long-term oxygen therapy, according to a clinical trial published on September 18, 2026, in the journal Thorax. Researchers found that adding the supplement to a 28-day pulmonary rehabilitation program lowered fatigue severity scores by 27 percent, compared to a 10 percent reduction observed in patients receiving a placebo.
The multicenter, randomized controlled trial was coordinated by the IRCCS Maugeri medical institute and conducted across 10 rehabilitation facilities in Italy between July 2024 and December 2025, Medscape reported. The study included 98 participants with a mean age of 72 years, of whom 52 percent were men. All participants had chronic respiratory failure and had been on long-term oxygen therapy for at least 12 months.
Participants in the trial were randomly assigned to receive either 1.66 grams of oral L-arginine plus 500 milligrams of liposomal vitamin C, or a matching placebo, taken twice daily, Medscape reported. The intervention ran alongside a structured 28-day pulmonary rehabilitation program that included at least 22 supervised sessions of aerobic, resistance, and flexibility training, alongside nutritional and psychosocial support. ad-hoc-news.de noted that the primary focus of the analysis was the quantification of exhaustion symptoms using standardized measurement tools.
The primary endpoint was the change in fatigue severity at day 28, assessed using the Fatigue Severity Scale, with a change of 0.6 points or greater prespecified as clinically meaningful. Secondary outcomes evaluated by the researchers included the 6-minute walk distance, sit-to-stand test performance, handgrip strength, and dyspnea scores.
Significant Fatigue Reductions on the Fatigue Severity Scale
Fatigue scores improved in both study groups by day 28, but the improvement was significantly greater in the group receiving L-arginine and liposomal vitamin C, according to Medscape. The between-group difference of 0.90 points on the Fatigue Severity Scale favored the supplement group and exceeded the prespecified minimal clinically important difference.
When examining clinical thresholds, ad-hoc-news.de reported that approximately 60 percent of patients in the supplement group reached a status where clinically relevant fatigue was no longer detected following the 28-day intervention. Furthermore, the trial data showed that these benefits persisted even after researchers adjusted for potential confounding factors.
Secondary Functional Outcomes and Trial Limitations
Regarding secondary functional outcomes, Medscape reported that the 6-minute walk distance increased by 47.6 meters in the L-arginine and liposomal vitamin C group, compared to 36.3 meters in the placebo group. While this 11.3-meter difference favored the intervention group, it was not statistically significant. Improvements in sit-to-stand performance, handgrip strength, health-related quality of life, and reductions in dyspnea occurred across both groups without significant differences between them.
The study authors, led by Mauro Maniscalco at Istituti Clinici Scientifici Maugeri IRCCS in Telese Terme, Italy, acknowledged several limitations in their published findings. The trial did not assess baseline vitamin C levels, the intervention lasted for only 28 days, and the study was primarily powered to evaluate the primary outcome rather than modest secondary effects. The researchers noted that the effects of the rehabilitation program alone may have masked additional benefits from the supplement over the relatively short intervention period.
Future Evaluation of Mikronährstoffkonzepte in Pulmonary Rehabilitation
Systemic exhaustion in advanced chronic obstructive pulmonary disease frequently limits patient participation in movement therapies and restricts training success during rehabilitation, ad-hoc-news.de reported. The observed reduction in fatigue scores indicates that supporting sauerstoffpflichtige patients with Arginin and liposomal vitamin C could improve how they respond to structured rehabilitation programs.
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.
Mauro Maniscalco et al., Thorax
Funding for the trial was provided in part by Italy’s Ministry of Health through its Ricerca Corrente program, while Damor Farmaceutici supplied the study product and placebo at no cost. Treatment facilities and clinical researchers must now determine whether longer intervention periods will clarify the impact of these micronutrient concepts on secondary functional measures in chronic respiratory care.