# Comparison of Bioavailability of Nitrates and Nitrites in 3 Species of Amaranthus: A Randomized, Double-Blind, Placebo-Controlled, 4-Way Crossover Study in Healthy Subjects Under Fasting Conditions

## TL;DR

This study compares the absorption of nitrates and nitrites from three types of Amaranthus in healthy people, finding they are equally absorbed and better than a placebo.

## Contribution

The study provides the first pharmacokinetic and bioequivalence data for nitrates and nitrites from three Amaranthus species in a controlled clinical trial.

## Key findings

- All three Amaranthus species showed significantly higher nitrate and nitrite levels in plasma and saliva compared to placebo.
- Pharmacokinetic profiles of nitrate and nitrite were similar across the three species but distinct from placebo.
- Bioequivalence was confirmed among the three Amaranthus extracts for both nitrate and nitrite.

## Abstract

Amaranthus is a significant source of dietary nitrates, which have been known to improve aerobic capacity and exercise performance in physically active individuals. There is a significant data gap on nonpartitive pharmacokinetics and bioequivalence studies of nitrate and nitrite from 3 species of Amaranth (A. hybridus, A. hypochondriacus, and A. tricolor).

This study aimed to assess the bioavailability of nitrates and nitrites from 3 Amaranthus species in a randomized, placebo-controlled design, thereby filling this gap.

A double-blinded, 4-way crossover study was conducted in 16 healthy participants. Each participant enrolled in the study received a single dose of 2000 mg of Amaranthus extract or a placebo. The plasma and saliva samples were collected at specific intervals over 24 hours. Nitrate and nitrite concentrations were analyzed using a validated LCMS/MS method.

After the administration of amaranth extracts, both plasma and saliva samples were observed significantly higher levels of nitrate and nitrite compared with the placebo group. Pharmacokinetic variables (Cmax, AUC0-t24, and AUC0-∞) found a similar pattern for nitrite and nitrate in the 3 amaranth products but were significantly different from placebo (P < 0.05), in both plasma and saliva samples. Bioequivalence analysis confirmed significant bioequivalence among the 3 amaranth extracts for nitrite and nitrate.

This study concludes that the 3 species of Amaranthus—A. hybridus, A. hypochondriacus, and A. tricolor are bioequivalent in terms of plasma and saliva nitrate and nitrite levels from a single dose of 2000 mg amaranth extract and have higher bioavailability than placebo. These findings report that Amaranthus extracts could potentially act as a daily diet supplement for improving the cardiovascular and neurogenerative health of the body, particularly aging people.