Effects Of Inorganic Nitrate Supplementation Research Articles

The effects of inorganic nitrate supplementation on muscular power and endurance across the menstrual cycle.

Oral inorganic nitrate ([Formula: see text]) supplementation increases nitric oxide (NO) bioavailability and may improve muscular power in males and females, although data in females are limited. Estrogen increases NO bioavailability and fluctuates throughout the menstrual cycle, with low levels in the early follicular (EF) phase and peaking during the late follicular (LF) phase. The purpose of the present study was to examine the effects of [Formula: see text] supplementation on isokinetic peak power, maximal voluntary isometric contraction (MVIC) force, muscular endurance, and recovery from fatigue in healthy young females during the EF and LF phases of the menstrual cycle. Ten eumenorrheic females were tested in a double-blinded, randomized, placebo-controlled design. Participants consumed ∼13 mmol [Formula: see text], in the form of 140 mL beetroot juice (BRJ), or an identical [Formula: see text]-depleted placebo (PL), for ∼5 days prior to visits and 2 h prior to testing. Plasma estradiol was elevated in the LF phase, and plasma nitrite and nitrate were elevated in the BRJ condition (P < 0.05). Although isokinetic peak power was unchanged, calculated maximal power (Pmax) and maximal velocity (Vmax) were significantly worsened in the BRJ treatment independent of the menstrual cycle phase (P = 0.02 and 0.03, respectively). Muscular endurance, MVIC, and fatigue recovery were unaltered by BRJ or the menstrual cycle. These data indicate that [Formula: see text] supplementation decreased maximal power and velocity in females and suggest that the benefits of [Formula: see text] supplementation previously found in males may not extend to young females.NEW & NOTEWORTHY Recent data have suggested that inorganic nitrate ([Formula: see text]) supplementation may benefit males, however, females may experience worsened endurance capacity independent of menstrual cycle phase. This study revealed neither [Formula: see text] supplementation nor the follicular phase of the menstrual cycle influenced maximal isometric voluntary contraction or endurance capacity in healthy, young, naturally menstruating females, whereas [Formula: see text] supplementation significantly worsened estimated peak power (Pmax) and velocity (Vmax) independent of the menstrual cycle phase.

The influence of sex on the effects of inorganic nitrate supplementation on muscular power and endurance.

Inorganic nitrate ([Formula: see text]) supplementation increases nitric oxide (NO) bioavailability and may improve muscular power and endurance, although most studies are in males. Therefore, the present double-blind, randomized, placebo-controlled study examined the effects of [Formula: see text] supplementation on isokinetic peak power, maximal voluntary isometric contraction (MVIC) force, muscular endurance (time-to-task failure; TTF), and recovery from fatigue in young females (n = 12) and males (n = 14). Participants consumed ∼13 mmol [Formula: see text] [beetroot juice (BRJ)], or an identical [Formula: see text]-depleted beverage placebo (PL), for ∼3 days and 2 h before testing visits. Plasma nitrate and nitrite were elevated in the BRJ condition (P ≤ 0.05). Peak power (W·kg-1) showed a sex effect (P ≤ 0.05) at all angular velocities and a sex-by-treatment effect at 270 and 360°/s (P ≤ 0.05). Post hoc analysis revealed no significant differences between treatments (P > 0.05). Estimated maximal knee extension power (Pmax) and maximal knee extension velocity (Vmax) demonstrated no sex, treatment, or sex-by-treatment effect (P > 0.05). There were no significant effects for TTF (F: PL; 269 ± 161 vs. BRJ; 277 ± 158 s and M: PL; 228 ± 171 vs. BRJ; 194 ± 100 s; P > 0.05). Cohen's d effect sizes for peak power showed moderate to large effect sizes at 270 (d = 0.92) and 360°/s (d = 0.81), showing a possible differentiated effect of dietary nitrate in females and males. The present data indicate that [Formula: see text] supplementation does not significantly affect knee extensor maximal power, maximal contraction velocity, and muscular endurance in either sex. The sex-dependent response to dietary nitrate supplementation requires further investigation as data on females is scarce.NEW & NOTEWORTHY Recent data have suggested that inorganic nitrate ([Formula: see text]) supplementation may benefit males; however, females may experience worsened endurance capacity. This study revealed a potential differentiated effect of [Formula: see text] supplementation on outcomes of muscle contractile function between healthy, young males and females. The specific responses of [Formula: see text] supplementation in females and across sexes remain understudied and require further investigation.

The effects of inorganic nitrate supplementation on exercise economy and endurance capacity across the menstrual cycle.

Oral inorganic nitrate (NO3-) supplementation has been shown to increase bioavailable NO and provide potential ergogenic benefits in males; however, data in females is scarce. Estrogen is known to increase endogenous NO bioavailability and to fluctuate throughout the menstrual cycle (MC), being lowest in the early follicular (EF) phase and highest during the late follicular (LF) phase. This study examined the effects of oral NO3- supplementation on exercise economy, endurance capacity, and vascular health in young females across the MC. Ten normally menstruating females' MCs were tested in a double-blinded, randomized design during both the EF and LF phases of the MC. Participants consumed ∼13 mmol NO3-, in the form of 140 mL beetroot juice (BRJ) or an identical NO3--depleted placebo (PL) for ∼3 days before lab visits and 2 h before testing on lab visits. Plasma nitrate, nitrite, and estradiol were assessed, as was blood pressure and pulse wave velocity. Moderate-intensity exercise economy and severe intensity time to exhaustion (TTE) were tested on a cycle ergometer. As expected, plasma estradiol was elevated in the LF phase, and plasma nitrite and nitrate were elevated in the BRJ condition. Exercise economy was unaltered by BRJ or the MC, however TTE was significantly worsened by 48 s (∼10%) after BRJ supplementation (P = 0.04), but was not different across the MC with no interaction effects. In conclusion, NO3- supplementation did not affect exercise economy or vascular health and worsened aerobic endurance capacity (TTE), suggesting healthy females should proceed with caution when considering supplementation with BRJ.NEW & NOTEWORTHY Although inorganic nitrate (NO3-) supplementation has increased in popularity as a means of improving exercise performance, data in females at different phases of the menstrual cycle are lacking despite known interactions of estrogen with NO. This study revealed neither NO3- supplementation nor the menstrual cycle influenced exercise economy or vascular health in healthy young naturally menstruating females, while NO3- supplementation significantly worsened endurance capacity (10%) independent of the menstrual cycle phase.

The Effects Of Inorganic Nitrate Supplementation And Exercise Intensity On Vascular Health In Post-Menopausal Females

The Effects Of Inorganic Nitrate Supplementation And Exercise Intensity On Vascular Health In Post-Menopausal Females

Effects of inorganic nitrate supplementation on cardiovascular function and exercise tolerance in heart failure.

Heart failure (HF) results in a myriad of central and peripheral abnormalities that impair the ability to sustain skeletal muscle contractions and, therefore, limit tolerance to exercise. Chief among these abnormalities is the lowered maximal oxygen uptake, which is brought about by reduced cardiac output and exacerbated by O2 delivery-utilization mismatch within the active skeletal muscle. Impaired nitric oxide (NO) bioavailability is considered to play a vital role in the vascular dysfunction of both reduced and preserved ejection fraction HF (HFrEF and HFpEF, respectively), leading to the pursuit of therapies aimed at restoring NO levels in these patient populations. Considering the complementary role of the nitrate-nitrite-NO pathway in the regulation of enzymatic NO signaling, this review explores the potential utility of inorganic nitrate interventions to increase NO bioavailability in the HFrEF and HFpEF patient population. Although many preclinical investigations have suggested that enhanced reduction of nitrite to NO in low Po2 and pH environments may make a nitrate-based therapy especially efficacious in patients with HF, inconsistent results have been found thus far in clinical settings. This brief review provides a summary of the effectiveness (or lack thereof) of inorganic nitrate interventions on exercise tolerance in patients with HFrEF and HFpEF. Focus is also given to practical considerations and current gaps in the literature to facilitate the development of effective nitrate-based interventions to improve exercise tolerance in patients with HF.

Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) have increased cardiovascular disease risk largely attributable to hypertension. Heightened peripheral chemoreflex sensitivity (i.e., exaggerated responsiveness to hypoxia) facilitates hypertension in these patients. Nitric oxide blunts the peripheral chemoreflex, and patients with OSA have reduced nitric oxide bioavailability. We therefore investigated the dose-dependent effects of acute inorganic nitrate supplementation (beetroot juice), an exogenous nitric oxide source, on blood pressure and cardiopulmonary responses to hypoxia in patients with OSA using a randomized, double-blind, placebo-controlled crossover design. Fourteen patients with OSA (53 ± 10 yr, 29.2 ± 5.8 kg/m2, apnea-hypopnea index = 17.8 ± 8.1, 43%F) completed three visits. Resting brachial blood pressure and cardiopulmonary responses to inspiratory hypoxia were measured before, and 2 h after, acute inorganic nitrate supplementation [∼0.10 mmol (placebo), 4.03 mmol (low dose), and 8.06 mmol (high dose)]. Placebo increased neither plasma [nitrate] (30 ± 52 to 52 ± 23 μM, P = 0.26) nor [nitrite] (266 ± 153 to 277 ± 164 nM, P = 0.21); however, both increased following low (29 ± 17 to 175 ± 42 μM, 220 ± 137 to 514 ± 352 nM) and high doses (26 ± 11 to 292 ± 90 μM, 248 ± 155 to 738 ± 427 nM, respectively, P < 0.01 for all). Following placebo, systolic blood pressure increased (120 ± 9 to 128 ± 10 mmHg, P < 0.05), whereas no changes were observed following low (121 ± 11 to 123 ± 8 mmHg, P = 0.19) or high doses (124 ± 13 to 124 ± 9 mmHg, P = 0.96). The peak ventilatory response to hypoxia increased following placebo (3.1 ± 1.2 to 4.4 ± 2.6 L/min, P < 0.01) but not low (4.4 ± 2.4 to 5.4 ± 3.4 L/min, P = 0.11) or high doses (4.3 ± 2.3 to 4.8 ± 2.7 L/min, P = 0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time P = 0.64). Acute inorganic nitrate supplementation appears to blunt an early-morning rise in systolic blood pressure potentially through suppression of peripheral chemoreflex sensitivity in patients with OSA.NEW & NOTEWORTHY The present study is the first to examine the acute effects of inorganic nitrate supplementation on resting blood pressure and cardiopulmonary responses to hypoxia (e.g., peripheral chemoreflex sensitivity) in patients with obstructive sleep apnea (OSA). Our data indicate inorganic nitrate supplementation attenuates an early-morning rise in systolic blood pressure potentially attributable to blunted peripheral chemoreflex sensitivity. These data show proof-of-concept that inorganic nitrate supplementation could reduce the risk of cardiovascular disease in patients with OSA.

Effects of Red Beetroot Juice and Inorganic Nitrate Supplementation on Oral Bacteria and Nitric Oxide Metabolites in Middle-Aged/Older Adults with Overweight and Obesity

Abstract Objectives Dietary inorganic nitrate from foods such as red beetroot juice (RBJ) can contribute to nitric oxide (NO) bioavailability through the enterosalivary nitrate-nitrite-NO pathway. A critical step in this pathway is the reduction of nitrate to nitrite by oral bacteria. We investigated the effects of inorganic nitrate supplementation, as RBJ or placebo + potassium nitrate (PBO+NIT), on the oral microbiota, and its relationship with saliva and plasma NO metabolites and vascular endothelial function. Methods In a randomized, double-blind, placebo-controlled trial, we measured the abundance of oral nitrate-reducing bacteria in saliva samples from 15 middle-aged/older adults with overweight and obesity using 16 rRNA sequencing. We also assessed the relationship of oral nitrate-reducing bacteria with the physiological responses to acute (4 hours) and chronic (4 weeks) RBJ, PBO+NIT, nitrate-free RBJ, and placebo supplementation via measurement of saliva and plasma nitrate/nitrite (NOx), plasma nitrite levels, and reactive hyperemia index (RHI). Results A significant decrease in the alpha diversity metric, Pileou's Evenness, was detected after chronic consumption of PBO+NIT (0.69 ± 0.05 at week 0 vs. 0.65 ± 0.05 at week 4; P &amp;lt; 0.05), while there was a trend for a decline following RBJ consumption (0.69 ± 0.05 at week 0 vs. 0.65 ± 0.05 at week 4; P = 0.08). No significant differences in abundance of nitrate-reducing bacteria were observed after chronic supplementation, although abundance of the species Neisseria subflava was trending toward an increase in the RBJ group (10.8% at week 0 vs. 12.2% at week 4; P = 0.07). Plasma and saliva NOx increased from baseline and remained elevated for the 4-hour testing period after acute and chronic RBJ and PBO+NIT supplementation (all P &amp;lt; 0.05), while plasma nitrite only peaked at 2 hours in the RBJ group after acute supplementation and was significantly higher than PBO+NIT group (P &amp;lt; 0.01). RHI change from baseline to 4 hours was positively correlated with total abundance of nitrate-reducing species after chronic RBJ supplementation (r = 0.5; P = 0.05). Conclusions Acute and chronic RBJ and PBO+NIT supplementation increases NO metabolites and may alter the oral microbiota to favorably affect vascular endothelial function in middle-aged/older adults with overweight and obesity. Funding Sources NIFA, USDA.

Effect of inorganic nitrate on exercise capacity, mitochondria respiration, and vascular function in heart failure with reduced ejection fraction.

Chronic underperfusion of the skeletal muscle tissues is a contributor to a decrease in exercise capacity in patients with heart failure with reduced ejection fraction (HFrEF). This underperfusion is due, at least in part, to impaired nitric oxide (NO) bioavailability. Oral inorganic nitrate supplementation increases NO bioavailability and may be used to improve exercise capacity, vascular function, and mitochondrial respiration. Sixteen patients with HFrEF (fifteen men, 63 ± 4 yr, body mass index: 31.8 ± 2.1 kg/m2) participated in a randomized, double-blind, crossover design study. Following consumption of either nitrate-rich beetroot juice (16 mmol nitrate/day) or a nitrate-depleted placebo for 5 days, participants completed separate visits for assessment of exercise capacity, endothelial function, and muscle mitochondrial respiration. Participants then had a 2-wk washout before completion of the same protocol with the other intervention. Statistical significance was set a priori at P < 0.05, and between-treatment differences were analyzed via paired t test analysis. Following nitrate supplementation, both plasma nitrate and nitrite increased (933%, P < 0.001 and 94%, P < 0.05, respectively). No differences were observed for peak oxygen consumption (nitrate: 18.5 ± 1.4 mL·kg-1·min-1, placebo: 19.3 ± 1.4 mL·kg-1·min-1; P = 0.13) or time to exhaustion (nitrate: 1,165 ± 92 s, placebo: 1,207 ± 96 s; P = 0.16) following supplementation. There were no differences between interventions for measures of vascular function, mitochondrial respiratory function, or protein expression (all P > 0.05). Inorganic nitrate supplementation did not improve exercise capacity and skeletal muscle mitochondrial respiratory function in HFrEF. Future studies should explore alternative interventions to improve peripheral muscle tissue function in HFrEF.NEW & NOTEWORTHY This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure with reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration. Although daily supplementation increased plasma nitrite, our data indicate that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.

Modulation of the orthostatic blood pressure response by acute nitrate consumption is dependent upon ethnic origin.

Orthostatic stress triggers a response to maintain cerebral perfusion and prevent syncope. Given the hypotensive effects of inorganic nitrate this response to orthostasis may be altered by acute supplementation with inorganic nitrate and modified by ethnic origin. Caucasian and SE Asian (n=30 for both), were recruited and subjected to an 'active stand test' and brachial artery blood pressure (BP), digit blood flow and ECG were recorded. Following inorganic nitrate supplementation, (10mg/kg body mass) the tests were repeated. For both Caucasian and SE Asians transition to standing increased diastolic pressure (DP) and heart rate (HR) (P<0.001 for both) and by calculation increased rate-pressure product (P<0.001) and decreased pulse pressure (P<0.01 for both) indicative of decreased ventricular filling. Nitrate supplementation decreased both DP (P<0.001) and HR (P<0.001). Assessment of HR variability suggested sympathetic nerve activity, was higher throughout in Caucasians (P<0.05) coupled with higher parasympathetic tone (P<0.01). Nitrate had no effect on cardiac autonomic nerve activity, as estimated using HR variability, for supine or standing subjects. The tachycardia and hypertension associated with orthostatic stress were preserved in both Caucasian and SE Asian subjects, however, we highlight possible differences in autonomic nervous system activity between Caucasians and SE Asians. SE Asians are resistant to the hypotensive effects of inorganic nitrate supplementation suggesting the absence of a crucial mechanism for activation of the nitrate-nitrite-nitric oxide system.

Heart Failure, Left Ventricular Remodeling, and Circulating Nitric Oxide Metabolites

BackgroundStable plasma nitric oxide (NO) metabolites (NOM), composed predominantly of nitrate and nitrite, are attractive biomarkers of NO bioavailability. NOM levels integrate the influence of NO‐synthase‐derived NO production/metabolism, dietary intake of inorganic nitrate/nitrite, and clearance of NOM. Furthermore, nitrate and nitrite, the most abundant NOM, can be reduced to NO via the nitrate‐nitrite‐NO pathway.Methods and ResultsWe compared serum NOM among subjects without heart failure (n=126), subjects with heart failure and preserved ejection fraction (HFpEF; n=43), and subjects with heart failure and reduced ejection fraction (HFrEF; n=32). LV mass and extracellular volume fraction were measured with cardiac MRI. Plasma NOM levels were measured after reduction to NO via reaction with vanadium (III)/hydrochloric acid. Subjects with HFpEF demonstrated significantly lower unadjusted levels of NOM (8.0 μmol/L; 95% CI 6.2–10.4 μmol/L; ANOVA P=0.013) than subjects without HF (12.0 μmol/L; 95% CI 10.4–13.9 μmol/L) or those with HFrEF (13.5 μmol/L; 95% CI 9.7–18.9 μmol/L). There were no significant differences in NOM between subjects with HFrEF and subjects without HF. In a multivariable model that adjusted for age, sex, race, diabetes mellitus, body mass index, current smoking, systolic blood pressure, and glomerular filtration rate, HFpEF remained a predictor of lower NOM (β=−0.43; P=0.013). NOM did not correlate with LV mass, or LV diffuse fibrosis.Conclusions HFpEF, but not HFrEF, is associated with reduced plasma NOM, suggesting greater endothelial dysfunction, enhanced clearance, or deficient dietary ingestion of inorganic nitrate. Our findings may underlie the salutary effects of inorganic nitrate supplementation demonstrated in recent clinical trials in HFpEF.