Dose–Response Effect of Dietary Nitrate on Muscle Contractility and Blood Pressure in Older Subjects: A Pilot Study

Abstract

We have recently demonstrated that dietary nitrate, a source of nitric oxide (NO) via the nitrate → nitrite → NO enterosalivary pathway, can improve muscle contractility in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. A pilot randomized, double-blind, placebo-controlled crossover study was therefore performed to determine the effects of ingesting 3.3 mL/kg of concentrated beetroot juice containing 0, 200, or 400 µmol/kg of nitrate in 9 healthy older subjects (mean age 70 ± 1 years). Maximal knee extensor power (Pmax) and speed (Vmax) were measured ~2.5 hours after nitrate ingestion using isokinetic dynamometry. Blood pressure was monitored periodically throughout each study. Pmax (in W/kg) was higher (p < .05) after the lower dose (3.9 ± 0.4) compared to the placebo (3.7 ± 0.4) or higher dose (3.7 ± 0.4). Vmax (in rad/s) also tended to be higher (p = .08) after the lower dose (11.9 ± 0.7) compared to the placebo (10.8 ± 0.8) or higher dose (11.2 ± 0.8). Eight out of 9 subjects achieved a higher Pmax and Vmax after the lower versus the higher dose. These dose-related changes in muscle contractility generally paralleled changes in breath NO levels. No significant changes were found in systolic, diastolic, or mean arterial blood pressure. A lower dose of nitrate increases muscle speed and power in healthy older individuals, but these improvements are lost at a higher dose. Blood pressure, on the other hand, is not reduced even with a higher dose.

Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis

“…− ingested [59] and/or the plasma levels of NO 3 − and/or NO 2 − attained following NO 3 − ingestion [50]. We did not attempt to assess these factors in the present metaanalysis, however, because less than half of the included studies directly measured either of these parameters, and aside from our studies [43,44,50,56,59] only Wylie et al [48] and Jonvik et al [57] measured both.…”

“…− ingested [59] and/or the plasma levels of NO 3 − and/or NO 2 − attained following NO 3 − ingestion [50]. We did not attempt to assess these factors in the present metaanalysis, however, because less than half of the included studies directly measured either of these parameters, and aside from our studies [43,44,50,56,59] only Wylie et al [48] and Jonvik et al [57] measured both. This is a significant weakness of the current literature in this area, as we have found the NO 3 − content of various BRJ supplements commonly used in such studies can vary considerably [68], even when obtained from the same manufacturer.…”

“…Specifically, studies using a multi-day supplementation protocol exhibited a lower (but still significant) ES compared to studies employing an acute dose of NO 3 − . One possible explanation for this finding is that repeated dosing exceeds the optimal NO 3 − concentration for enhancing contractile function in skeletal muscle [59]. However, pharmacokinetic modeling of the combined NO 3 − /NO 2 − system indicates that there should be little further accumulation in tissue after the first couple of doses [67].…”

“…Data extraction was then independently performed by the same three authors. Specifically, study design, sample size, subject characteristics, form, dose, and duration of NO 3 − supplementation, placebo characteristics, experimental procedures, and testing conditions were obtained from the text of eligible papers [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60]. Effect sizes (ES), i.e., Hedge's g, for NO 3 − -induced changes in peak or maximal power were calculated from either 1) the means and SDs for the NO 3 − and placebo trials along with the exact P values for the within-subject comparison [49,53,55,58,60], or 2) anonymized individual subject data obtained from the authors [42-48, 50-52, 54, 56, 57, 59].…”

“…Plotting of peak power against inertial load demonstrated that this resistance was close to optimal for determination of maximal muscle power. Finally, since we have recently shown that there is no beneficial effect of dietary NO 3 − on muscle power at very high doses (i.e., 400 μmol/kg, or on average 27.4 mmol) [59], only the data from the low dose (i.e., 200 μmol/ kg, or 13.7 mmol) trial of this study were used. (Why the beneficial effect of dietary NO 3 − on muscle contractile function is diminished or even completely lost at very high doses is unclear.…”