Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study

Randomized, double-blind, placebo-controlled trial in nonsmoking, nondiabetic, otherwise healthy adults with untreated hypercholesterolemia. The nitrate arm included 33 participants aged 18-80 years, with BMI 18.5 to 40, recruited in London, United Kingdom.

The active regimen was 250 mL/day of nitrate-rich beetroot juice taken orally for 6 weeks, providing about 6.0 mmol nitrate per daily dose. The comparator was nitrate-depleted beetroot juice.

Six weeks of daily dietary nitrate improved vascular function and reduced platelet activation, with no detected adverse effects. Flow-mediated dilatation increased by 1.1% in the nitrate group versus -0.3% with placebo (P < 0.001). Arterial stiffness decreased in the nitrate group by 0.22 m/s, with a trend versus placebo (P = 0.06), and platelet-monocyte aggregates fell by 7.6% versus a 10.1% increase in placebo (P = 0.004). Stimulated P-selectin expression also decreased versus placebo (P < 0.05), and oral microbiome changes included increased Neisseria flavescens. The authors conclude that dietary nitrate is safe and potentially useful for prevention of atherogenesis.

The intervention period was short, and the active-arm sample size was small. Outcomes were surrogate vascular, platelet, and microbiome measures rather than clinical cardiovascular events, and several findings were modest or borderline, including arterial stiffness. Generalizability is limited to relatively healthy, nonsmoking, nondiabetic adults with hypercholesterolemia.