A randomized controlled trial of nitrate supplementation in well-trained middle and older-aged adults

Abstract

Purpose: Nitrate (NO3-), through its conversion to nitrite (NO2-) and nitric oxide, has been shown to increase exercise tolerance in healthy younger adults and older diseased patients. Nitrate's effect in well-trained middle to older-aged adults has not been studied. Therefore, the purpose of this investigation was to examine the effects of a NO3- rich beverage on submaximal constant work rate exercise time in well-trained middle to older-aged adults.

Methods: This was a randomized controlled cross-over trial with 15 well-trained middle to older-aged adults, 41-64 year-old, who received one of two treatments (NO3- rich beverage then placebo or placebo then NO3- rich beverage), after which an exercise test at 75 percent of the subject's maximal work rate was completed.

Results: The NO3- rich beverage increased plasma NO3- and NO2- levels by 260 μM and 0.47 μM, respectively (p<0.001). Exercise time was not significantly different (p = 0.31) between the NO3- rich versus placebo conditions (1130±151 vs 1060±132 sec, respectively). Changes in exercise time between the two conditions ranged from a 55% improvement to a 40% decrease with the NO3- rich beverage. Oxygen consumption and rating of perceived exertion were not significantly different between the two conditions.

Conclusion: In middle to older-aged well-trained adults, NO3- supplementation has non-significant, albeit highly variable, effects on exercise tolerance. ClinicalTrials.gov Identifier: NCT03371966.

Conflict of interest statement

This work was supported by a grant from Isagenix International LLC, Gilbert, AZ awarded to MJB. MJB, GDM, DBK-S and SB received funding from Isagenix LLC to conduct the study. Contents of the manuscript are the sole responsibility of the authors. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funding source had no involvement with the study design, data collection, data analysis and interpretation or the decision to submit this work for publication. The results of the study are presented clearly, honestly, and without fabrication, falsification or inappropriate data manipulation. Dr. Kim-Shapiro is co-inventor on a patent related to the use of nitrite for cardiovascular conditions, and owns stock in and serves on the scientific advisory board for Beverage Operations LLC, which has licensed Wake Forest University intellectual properties and thus has a financial interest in Beverage Operations LLC. None of the other authors have any financial, non-financial, professional or personal competing interests to declare.

Figures

Fig 1. Subject flow through study.

Fig 2. Schematic of study design.

Fig 3. Plasma NO3- levels at visit 1 (V1) and the high and low NO3- beverage trials.

Post NO3- levels at V1 were obtained two hours post consumption of a high NO3- beverage. Plasma NO3- levels at the high and low NO3- beverage trials were obtained two hours post consumption of the respective beverage. Plasma NO3- levels were not significantly different when comparing the high NO3- beverage trial values to the post consumption values at V1 (p = 1.0) or when comparing the low NO3- beverage trial values to the pre-consumption values at V1 (p = 1.0). Values are represented as median values with box ends representing the 25th and 75th percentiles and error bars representing the 5th and 95th percentiles. Dotted lines represent the mean values, and individual dots represent subject values.

Fig 4. Plasma NO2- levels at visit 1 (V1) and the high and low NO3- beverage trials.

Post NO2- levels at V1 were obtained two hours post consumption of a high NO3- beverage. Plasma NO2- levels at the high and low NO3- beverage trials were obtained two hours post consumption of the respective beverage. Plasma NO2- levels were not significantly different when comparing the high NO3- beverage trial values to the post consumption values at V1 (p = 1.0) or when comparing the low NO3- beverage trial values to the pre-consumption values at V1 (p = 1.0). Values are represented as median values with box ends representing the 25th and 75th percentiles and error bars representing the 5th and 95th percentiles. Dotted lines represent the mean values, and individual dots represent subject values.

Fig 5. Individual subject responses.

Bars represent individual subject responses that ranged from a 55 percent improvement in exercise time during the high NO3- beverage trial as compared to the low NO3- beverage trial to as low as a 40 percent decrement in performance.