Nutritional Interventions for Patients with Intermittent Claudication: Mechanisms, Clinical Implications, and the...

Peripheral arterial disease (PAD) is a common atherosclerotic condition affecting over 200 million people worldwide, and supervised exercise therapy remains the best-supported first-line treatment for claudication. However, real-world adherence to exercise programs is persistently low, largely because the ischemic leg pain that exercise is intended to treat is itself a primary barrier to participation. This narrative review synthesizes the mechanistic rationale and clinical trial evidence for five classes of nutritional intervention proposed as potential adjuncts to exercise in patients with intermittent claudication: omega-3 fatty acids/fish oil, L-arginine and other nitric oxide precursors, carnitine derivatives, antioxidant vitamins, and dietary nitrate (beetroot juice and related sodium nitrate/nitrite forms). Across these categories, mechanistic rationale is generally strong, but clinical translation to improved walking distance is inconsistent and depends heavily on route of administration, dose, and combination with exercise. Carnitine derivatives, particularly propionyl-L-carnitine, showed relatively consistent walking-distance improvement, though evidence remains limited and further confirmatory studies are needed. Dietary nitrate showed benefit primarily when combined with supervised exercise, suggesting potential as an adjunct rather than a standalone therapy, particularly for patients with limited exercise tolerance. L-arginine, despite a compelling mechanistic rationale, showed no benefit in the best-powered trial available. Antioxidant vitamins demonstrated route-dependent effects, with acute intravenous administration showing more promise than chronic oral supplementation. Overall, nutritional interventions for patients with intermittent claudication represent mechanistically diverse approaches with markedly uneven supporting evidence. Further well-designed, adequately powered trials are needed to clarify their efficacy, safety, and place alongside exercise in clinical practice.