Assessment of the effectiveness and safety of two-month oral supplementation with L-arginine depending on the type of lipid metabolism disorder in patients with atherosclerotic lower limb ischemia.

2025-10-01
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 76(5)
- M Micker
- N Balcer-Dymel
- M Czerwonka
- B Madej
- E Swiecka
- P A Kolodziejski
- E Pruszynska-Oszmalek
- Z Checinska-Maciejewska
- H Krauss
- A Rekas-Dudziak

PubMed: 41364169
DOI: 10.26402/jpp.2025.5.05

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 100
Population: 100 patients (62 men and 38 women) over 50 years of age with Fontaine stage II ischemia
Methods: A randomized study; oral L-arginine at a dose of 6 g/day for 30 and 60 days
Blinding: Open-label
Duration: 30 and 60 days
Funding: Unclear

Large Human Trial

Lower limb arterial disease is among the most common vascular disorders, with its incidence rising significantly in aging populations, thus posing a major social and healthcare challenge. Currently, L-arginine is considered by vascular surgery experts as a compound with therapeutic potential in intermittent claudication, though its clinical efficacy remains insufficiently confirmed. The aim of this study was to evaluate the efficacy and safety of oral L-arginine supplementation in patients with atherosclerotic lower limb ischemia, with particular regard to lipid metabolism disorders. A randomized study included 100 patients (62 men and 38 women) over 50 years of age with Fontaine stage II ischemia. The study group received oral L-arginine at a dose of 6 g/day for 30 and 60 days. Clinical parameters were assessed, including the ankle-brachial index (ABI) and pain-free walking distance (PFWD), along with oxidative stress markers (serum nitric oxide (NO) concentration, total antioxidant status (TAS)) and lipid profile (total, HDL, and LDL cholesterol, and triglycerides). In both study and control groups, subgroups with hypertriglyceridemia, hypercholesterolemia, and mixed hyperlipidemia were additionally identified. Evaluations were performed at baseline, day 30, and day 60. After 30 and 60 days, significant increases in NO and TAS levels (p<0.001), as well as extended PFWD (p<0.001), were observed across all subgroups receiving L-arginine compared with controls. No significant effects were observed on ABI (right or left) or on cholesterol and triglyceride concentrations. These findings support the potential role of L-arginine as a supportive therapy in the management of atherosclerotic complications, particularly by improving oxidative balance and exercise tolerance.

Research Insights

L-Arginine→Improved Ankle-Brachial Index
No significant effects were observed on ABI (right or left) ...
Effect
Neutral
Effect size
Small
Dose
6 g/day
L-Arginine→Improved Pain-Free Walking Distance
After 30 and 60 days, significant increases in ... extended PFWD (p<0.001) were observed across all subgroups receiving L-arginine compared with controls.
Effect
Beneficial
Effect size
Moderate
Dose
6 g/day
L-Arginine→Increased Antioxidant Enzyme Levels
After 30 and 60 days, significant increases in ... TAS levels (p<0.001) were observed across all subgroups receiving L-arginine compared with controls.
Effect
Beneficial
Effect size
Moderate
Dose
6 g/day
L-Arginine→Increased HDL Cholesterol Levels
No significant effects were observed on ... cholesterol ... concentrations.
Effect
Neutral
Effect size
Small
Dose
6 g/day
L-Arginine→Increased Serum Nitric Oxide Level
After 30 and 60 days, significant increases in NO ... levels (p<0.001) were observed across all subgroups receiving L-arginine compared with controls.
Effect
Beneficial
Effect size
Moderate
Dose
6 g/day
L-Arginine→Reduced Low-Density Lipoprotein Level
No significant effects were observed on ... cholesterol ... concentrations.
Effect
Neutral
Effect size
Small
Dose
6 g/day
L-Arginine→Reduced Total Cholesterol Levels
No significant effects were observed on ... cholesterol ... concentrations.
Effect
Neutral
Effect size
Small
Dose
6 g/day
L-Arginine→Reduced Triglyceride Levels
No significant effects were observed on ... triglyceride ... concentrations.
Effect
Neutral
Effect size
Small
Dose
6 g/day

Adverse Events Reported

L-Arginine→Overall tolerability
No significant effects were observed on ABI (right or left) or on cholesterol and triglyceride concentrations.
Finding
Reported