A Betalain-rich Dietary Supplement, But Not PETN, Increases Vasodilation and Nitric Oxide: A Comparative, Single-dose, Randomized, Placebo-controlled, Blinded, Crossover Pilot Study

Abstract

Nutraceutical supplements have demonstrated promise as agents for improving athletic performance and for positively affecting cardiovascular health and vigor through modulation of endothelial function at the cellular level. High-nitrate products, such as red beet juices and powders, have been observed to improve athletic performance potentially through increased nitric oxide (NO) concentrations in the blood. Similarly, a patented low nitrate, low sugar betalain-rich supplement has also been reported to significantly improve athletic performance. To the best of our knowledge, no acute clinical studies have been conducted that have demonstrated the comparative efficacies of high-nitrate or betalain-rich, low nitrate materials on measures of endothelial function in real time. In this acute single-dose, double-blinded, randomized, placebo-controlled, crossover study, we examined the effects of the betalain-rich low nitrate dietary supplement, (BRS, 50mg), in comparison to pentaerythritol tetranitrate (PETN, 40mg), a pharmaceutical drug that is a potent source of organic nitrate, and a placebo, on various measures of endothelial function for up to 4-hours post-ingestion. More specifically, in order to gauge post-treatment changes in endothelial function we measured flow-mediated dilation (FMD), nitrite (NO2)/nitrate (NO3) content, circulating nitrosyl-hemoglobin (NOHb) concentration, and cellular metabolic activity (CMA) measured as generation of reactive oxygen species, a side reaction of oxidative-reductive cellular metabolism. Ten participants completed all arms of the study. Results suggest that within 2 hours, BRS, but not PETN or placebo, resulted in significantly elevated levels of NOHb (a measure of bioavailable NO●) (p = 0.017) and increased vasodilation as measured by FMD, (p = 0.025). As expected, due to its high nitrate content, NO2/NO3 levels were increased by PETN within 2-hours (p = 0.048), but not by BRS or placebo. Finally, under these experimental conditions, PETN and BRS produced no significant changes for mitochondrial, NADPH-oxidase dependent or cellular CMA. These data provide preliminary support for single-dose effectiveness of BRS, but not PETN, on levels of bioavailable NO● and FMD, both important measures of endothelial function. Additionally, these data suggest potentially different mechanisms of action related to low nitrate BRS and organic nitrate PETN.