Sex differences in the effects of inorganic nitrate supplementation on exercise economy and endurance capacity in healthy young adults.

Dietary nitrate (NO) is a widely used supplement purported to provide beneficial effects during exercise. Most studies to date include predominantly males. Therefore, the present study aimed to investigate if there is a sex-dependent effect of NO supplementation on exercise outcomes. We hypothesized that both sexes would exhibit improvements in exercise economy and exercise capacity following NO supplementation, but males would benefit to a greater extent. In a double-blind, randomized, crossover study, twelve females (24 ± 4 yr) and fourteen males (23 ± 4 yr) completed two 4-min moderate-intensity (MOD) exercise bouts followed by a time-to-exhaustion (TTE) task after following 3 days of NO supplementation (beetroot juice or BRJ) or NO-depleted placebo (PL). Females were tested during the early follicular phase of the menstrual cycle. During MOD exercise, BRJ reduced the steady-state V̇o by ∼5% in males (M: Δ -87 ± 115 mL·min; < 0.05) but not in females (F: Δ 6 ± 195 mL·min). Similarly, BRJ extended TTE by ∼15% in males ( < 0.05) but not in females. Dietary NO supplementation improved exercise economy during moderate-intensity exercise and exercise capacity during severe-intensity TTE in males but not in females. These differences could be related to estrogen levels, antioxidant capacity, nitrate-reducing bacteria, or a variety of known physiologic differences such as skeletal muscle calcium handling, and/or fiber type. Overall, our data suggests the ergogenic benefits of oral NO supplementation found in studies predominantly on male subjects may not be applicable to females. While inorganic nitrate (NO) supplementation has increased in popularity as an ergogenic aid to improve exercise performance, the role of sex in NO 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 NO supplementation.