While inorganic nitrate (NO₃⁻) supplementation has increased in popularity as an ergogenic aid to improve exercise performance, the role of sex in NO₃⁻ supplementation on exercise outcomes is lacking despite known physiological differences during exercise between sex. This study revealed that males, but not females, improved exercise economy during submaximal exercise and exercise capacity during exercise within the severe-intensity domain following NO₃⁻ supplementation.

Background: Inorganic nitrate (NO₃⁻) supplementation is purported to benefit short-term exercise performance, but it is unclear whether NO₃⁻ improves longer-term exercise training responses (such as improvements in VO_2peak or time to exhaustion (TTE)) versus exercise training alone. The purpose of this systematic review and meta-analysis was to determine the effects of NO₃⁻ supplementation combined with exercise training on VO_2peak and TTE, and to identify potential factors that may impact outcomes. Methods: Electronic databases (PubMed, Medscape, and Web of Science) were searched for articles published through June 2022 with article inclusion determined a priori as: (1) randomized placebo-controlled trials, (2) exercise training lasted at least three weeks, (3) treatment groups received identical exercise training, (4) treatment groups had matched VO_2peak at baseline. Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Standardized mean difference (SMD) with 95% confidence intervals (CI) were calculated using restricted maximum likelihood estimation between pre- and post-training differences in outcomes. Moderator subgroup and meta-regression analyses were completed to determine whether the overall effect was influenced by age, sex, NO₃⁻ dosage, baseline VO_2peak, health status, NO₃⁻ administration route, and training conditions. Results: Nine studies consisting of eleven trials were included: n = 228 (72 females); age = 37.7 ± 21 years; VO_2peak: 40 ± 18 ml/kg/min. NO₃⁻ supplementation did not enhance exercise training with respect to VO_2peak (SMD: 0.18; 95% CI: -0.09, 0.44; p = 0.19) or TTE (SMD: 0.08; 95% CI: − 0.21, 0.37; p = 0.58). No significant moderators were revealed on either outcome. Subset analysis on healthy participants who consumed beetroot juice (BRJ) revealed stronger trends for NO₃⁻ improving VO_2peak (p = 0.08) compared with TTE (p = 0.19), with no significant moderators. Sunset funnel plot revealed low statistical power in all trials. Conclusions: NO₃⁻ supplementation combined with exercise training may not enhance exercise outcomes such as VO_2peak or TTE. A trend for greater improvement in VO_2peak in healthy participants supplemented with BRJ may exist (p = 0.08). Overall, future studies in this area need increased sample sizes, more unified methodologies, longer training interventions, and examination of sex as a biological variable to strengthen conclusions.

This study compared exercise-induced changes in flow-mediated dilation after acute moderate- and high-intensity exercise in females postmenopause supplementing either inorganic nitrate (beetroot juice) or placebo. BRJ improved peak ΔFMD postexercise, and BRJ + HIE increased FMD measured as FMD over time. Neither PL + MIE nor PL + HIE improved FMD. These findings suggest that inorganic nitrate supplementation combined with high-intensity exercise may benefit vascular health in females PM.

Posttraumatic stress disorder (PTSD) has been associated with an increase in risk of cardiovascular disease (CVD). The goal of this study was to determine if peripheral vascular dysfunction, a precursor to CVD, was present in young adults with PTSD, and if an acute antioxidant (AO) supplementation could modify this potential PTSD-induced vascular dysfunction. Thirteen individuals with PTSD were recruited for this investigation and were compared with 35 age- and sex-matched controls (CTRL). The PTSD group participated in two visits, consuming either a placebo (PTSD-PL) or antioxidants (PTSD-AO; vitamins C and E; α-lipoic acid) before their visits, whereas the CTRL subjects only participated in one visit. Upper and lower limb vascular functions were assessed via flow-mediated dilation and passive leg movement technique. Heart rate variability was utilized to assess autonomic nervous system modulation. The PTSD-PL condition, when compared with the CTRL group, reported lower arm and leg microvascular function as well as sympathetic nervous system (SNS) predominance. After acute AO supplementation, arm, but not leg, microvascular function was improved and SNS predominance was lowered to which the prior difference between PTSD group and CTRL was no longer significant. Young individuals with PTSD demonstrated lower arm and leg microvascular function as well as greater SNS predominance when compared with age- and sex-matched controls. Furthermore, this lower vascular/autonomic function was augmented by an acute AO supplementation to the level of the healthy controls, potentially implicating oxidative stress as a contributor to this blunted vascular/autonomic function.

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.

Inorganic nitrate (NO₃^-) 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 NO₃^- 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 ~13mmol NO₃^- (BRJ), or an identical NO₃^--depleted beverage (PL), for ~3 days and 2 hours 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°/sec (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±158s and M: PL; 228±171 vs BRJ; 194±100s; p > 0.05). Cohen's d effect sizes for peak power showed moderate to large effect sizes at 270 (d=0.92) and 360 deg/sec (d=0.81), showing a possible differentiated effect of dietary nitrate in females and males. The present data indicate that NO₃^- 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.