Inorganic nitrate supplementation enhances functional capacity and lower-limb microvascular reactivity in patients with peripheral artery disease.

This was a block-randomized, placebo-controlled study in adults with diagnosed peripheral artery disease recruited from the University of Iowa Vascular Clinic. Participants were older patients with mild-to-moderate PAD (Fontaine Stage 1-2a, Rutherford 0-1); 21 patients were enrolled overall, with calf outcome analyses reported for NaNO3 n=11 and placebo n=7.

Sodium nitrate (NaNO3) 1 g/day, 8.5 mM, was given daily for 8 weeks. The route of administration was not explicitly stated; the comparison arm received placebo.

Eight weeks of sodium nitrate supplementation improved lower-limb vascular function and functional capacity in patients with PAD. Calf peak blood flow increased from 11.6±4.9 to 14.1±5.1 mL/dL tissue/min (p<0.05, d=0.50) and calf peak vascular conductance increased from 11.1±4.3 to 14.2±4.9 mL/dL tissue/min/mmHg (p<0.05, d=2.21), while placebo showed no improvement. Six-minute walk distance increased by nearly 40 meters, and the paper reports increased plasma nitrate/nitrite with no change in forearm vascular function, inflammatory/adhesion biomarkers, or adverse effects. No group-by-time interactions were found for IL-6, sICAM-1, sVCAM-1, or MCP-1.

The trial was small, single-center, and short duration (8 weeks), with some outcome analyses based on even smaller subsets than the enrolled sample. Generalizability is limited by the older PAD population, mild-to-moderate disease severity, and incomplete reporting of some participant characteristics such as ethnicity and BMI. Route of administration and the exact randomized active-arm sample size were not explicitly stated.