madman
Super Moderator
No longer beeting around the bush: a review of potential sex differences with dietary nitrate supplementation
Abstract: Over the last decade there has been substantial interest in the health and athletic performance benefits associated with acute and chronic dietary nitrate (NO3 –) supplementation. Dietary NO3 –, commonly found in leafy greens and root vegetables undergo sequential reduction to nitrite and nitric oxide (NO) via the enterosalivary circulation. Importantly, NO has been shown to elicit a number of biological effects ranging from blood pressure reduction to improved exercise economy and athletic performance. However, a common absence within biological research is the lack of female participants, which is often attributed to the added complexity of hormonal fluctuations throughout the menstrual cycle. Despite mounting evidence supporting significant anthropometric, metabolic, and physiological differences between the sexes, this problem extends to the field of dietary NO3 – supplementation where women are underrepresented as research participants. This review examines the existing dietary NO3 – supplementation research with regards to dietary NO3 – pharmacokinetics, resting blood pressure, exercise economy and performance, and mechanisms of action. It also provides evidence and rationale for potential sex differences in response to dietary NO3 – supplementation and future directions for this field of research.
Novelty
• Dietary NO3 – supplementation has been shown to have positive impacts on health and athletic performance in generally male populations. However, women are underrepresented in dietary NO3 – supplementation research.
• The present evidence suggests that sex differences exist in response to dietary NO3 – supplementation and this review highlights avenues for future research.
Supplemental NO3 – dose-response and pharmacokinetics
Key points
• Plasma [NO3 –] and [NO2 –] increase in a dose-dependent manner following dietary NO3 – supplementation in men and women.
• Following an acute dose of dietary NO3 –, plasma [NO3 –] and [NO2 –] remained significantly elevated above baseline for up to 24 h.
• Women appear to have elevated baseline plasma [NO2 –] and experience greater relative increases in plasma [NO3 –] and [NO2 –] following dietary NO3 – supplementation than men. However, this may reflect larger doses of dietary NO3 –/kg BM.
Blood pressure (BP)
Key points
• Healthy, young adults demonstrate BP reductions of 6 mm Hg in SBP and 3 mm Hg in DBP following acute and chronic dietary NO3 – supplementation.
• Women appear to have lower resting SBP and DBP compared with men and demonstrate less pronounced reductions in SBP and DBP following dietary NO3 – supplementation.
• Dietary NO3 – supplementation does not appear to reduce resting BP in trained populations, but females are severely underrepresented in this research.
Exercise economy and performance
Key points
• BRJ supplementation (>5 mmol NO3 –) decreased the O2 cost of submaximal exercise (3%–5%) and often improved exercise performance, both acutely and chronically in recreationally trained males.
• The effect of BRJ supplementation on O2 economy and performance has been studied much less in females and the existing results are equivocal.
• BRJ supplementation in well-trained males and females does not appear to improve O2 economy during submaximal exercise and TTE and TT performance. More work with trained female athletes is needed.
Mechanisms of action
Reduction in the oxygen cost of exercise
(i) Mitochondrial efficiency
(ii) Contractile efficiency
Key points
• NO is a potent signaling molecule that elicits many biological effects and therefore likely has a number of mechanisms of action that may work simultaneously.
• There is little evidence to suggest that NO3 – supplementation improves mitochondrial efficiency to reduce the O2 cost of submaximal exercise.
• The current leading hypothesis suggests dietary NO3 – supplementation improves excitation-contraction coupling to reduce the O2 cost of submaximal exercise.
• Women are heavily underrepresented in this mechanistic work and there are many potential areas where men and women may respond differently to NO3 – supplementation (Fig. 1).
Conclusion
Dietary NO3 – supplementation has the potential to elicit profound biological effects within the body, including lowering resting BP, reducing the O2 cost of submaximal exercise, and improving athletic performance. Due to the widespread effects of NO, the benefits of dietary NO3 – supplementation are likely a product of several mechanisms of action working together. However, despite significant anthropometric, metabolic, and physiological differences between the sexes, it is abundantly clear that women are underrepresented in dietary NO3 – supplementation research. There are many areas of research that may influence the sex-specific responses to dietary NO3 – supplementation (Fig. 2). Ultimately, addressing this gap will help target nutrition-based health initiatives aimed at lowering blood pressure and enhancing athletic performance.
Abstract: Over the last decade there has been substantial interest in the health and athletic performance benefits associated with acute and chronic dietary nitrate (NO3 –) supplementation. Dietary NO3 –, commonly found in leafy greens and root vegetables undergo sequential reduction to nitrite and nitric oxide (NO) via the enterosalivary circulation. Importantly, NO has been shown to elicit a number of biological effects ranging from blood pressure reduction to improved exercise economy and athletic performance. However, a common absence within biological research is the lack of female participants, which is often attributed to the added complexity of hormonal fluctuations throughout the menstrual cycle. Despite mounting evidence supporting significant anthropometric, metabolic, and physiological differences between the sexes, this problem extends to the field of dietary NO3 – supplementation where women are underrepresented as research participants. This review examines the existing dietary NO3 – supplementation research with regards to dietary NO3 – pharmacokinetics, resting blood pressure, exercise economy and performance, and mechanisms of action. It also provides evidence and rationale for potential sex differences in response to dietary NO3 – supplementation and future directions for this field of research.
Novelty
• Dietary NO3 – supplementation has been shown to have positive impacts on health and athletic performance in generally male populations. However, women are underrepresented in dietary NO3 – supplementation research.
• The present evidence suggests that sex differences exist in response to dietary NO3 – supplementation and this review highlights avenues for future research.
Supplemental NO3 – dose-response and pharmacokinetics
Key points
• Plasma [NO3 –] and [NO2 –] increase in a dose-dependent manner following dietary NO3 – supplementation in men and women.
• Following an acute dose of dietary NO3 –, plasma [NO3 –] and [NO2 –] remained significantly elevated above baseline for up to 24 h.
• Women appear to have elevated baseline plasma [NO2 –] and experience greater relative increases in plasma [NO3 –] and [NO2 –] following dietary NO3 – supplementation than men. However, this may reflect larger doses of dietary NO3 –/kg BM.
Blood pressure (BP)
Key points
• Healthy, young adults demonstrate BP reductions of 6 mm Hg in SBP and 3 mm Hg in DBP following acute and chronic dietary NO3 – supplementation.
• Women appear to have lower resting SBP and DBP compared with men and demonstrate less pronounced reductions in SBP and DBP following dietary NO3 – supplementation.
• Dietary NO3 – supplementation does not appear to reduce resting BP in trained populations, but females are severely underrepresented in this research.
Exercise economy and performance
Key points
• BRJ supplementation (>5 mmol NO3 –) decreased the O2 cost of submaximal exercise (3%–5%) and often improved exercise performance, both acutely and chronically in recreationally trained males.
• The effect of BRJ supplementation on O2 economy and performance has been studied much less in females and the existing results are equivocal.
• BRJ supplementation in well-trained males and females does not appear to improve O2 economy during submaximal exercise and TTE and TT performance. More work with trained female athletes is needed.
Mechanisms of action
Reduction in the oxygen cost of exercise
(i) Mitochondrial efficiency
(ii) Contractile efficiency
Key points
• NO is a potent signaling molecule that elicits many biological effects and therefore likely has a number of mechanisms of action that may work simultaneously.
• There is little evidence to suggest that NO3 – supplementation improves mitochondrial efficiency to reduce the O2 cost of submaximal exercise.
• The current leading hypothesis suggests dietary NO3 – supplementation improves excitation-contraction coupling to reduce the O2 cost of submaximal exercise.
• Women are heavily underrepresented in this mechanistic work and there are many potential areas where men and women may respond differently to NO3 – supplementation (Fig. 1).
Conclusion
Dietary NO3 – supplementation has the potential to elicit profound biological effects within the body, including lowering resting BP, reducing the O2 cost of submaximal exercise, and improving athletic performance. Due to the widespread effects of NO, the benefits of dietary NO3 – supplementation are likely a product of several mechanisms of action working together. However, despite significant anthropometric, metabolic, and physiological differences between the sexes, it is abundantly clear that women are underrepresented in dietary NO3 – supplementation research. There are many areas of research that may influence the sex-specific responses to dietary NO3 – supplementation (Fig. 2). Ultimately, addressing this gap will help target nutrition-based health initiatives aimed at lowering blood pressure and enhancing athletic performance.
