Dietary Supplements

Effect of Dietary Nitrate Intake on Fatigue Resistance Following Ischemia-Induced Microvascular Dysfunction in Males and Females.

TL;DR

Acute dietary nitrate supplementation preserves fatigue resistance in males despite persistent microvascular dysfunction, whereas in females it attenuates ischemia-induced microvascular impairment without affecting fatigue resistance, supporting sex-specific protective effects of dietary nitrate against transient vascular stress.

Key Findings

Circulating nitrate and nitrite increased significantly after nitrate-rich beetroot juice consumption in both males and females.

  • Participants consumed either nitrate-rich beetroot juice (NR-BJ, ~10 mmol nitrate) or nitrate-depleted beetroot juice (ND-BJ, ~0.34 mmol nitrate)
  • Serum nitrate and nitrite were measured by high-performance liquid chromatography
  • The increase in circulating nitrate and nitrite occurred in both sexes following NR-BJ ingestion
  • Measurements were taken approximately 2 hours post-ingestion

Prolonged forearm arterial occlusion reduced the tissue oxygen saturation resaturation slope in both sexes under the nitrate-depleted condition.

  • 20 minutes of forearm arterial occlusion was used to induce microvascular dysfunction
  • Microvascular reactivity was assessed by near-infrared spectroscopy via the tissue oxygen saturation resaturation slope
  • The decline in resaturation slope occurred under ND-BJ conditions in both males and females
  • This finding confirms the model of ischemia-induced microvascular dysfunction

NR-BJ attenuated the ischemia-induced decline in microvascular reactivity in females but not in males.

  • The tissue oxygen saturation resaturation slope was preserved in females following NR-BJ supplementation
  • Males did not show attenuation of the ischemia-induced microvascular dysfunction under NR-BJ
  • This represents a sex-specific difference in microvascular response to dietary nitrate
  • The study included 8 males and 8 females aged 20-40 years in a randomized, double-blind, crossover design

Ischemia reduced total work and early-phase work during maximal isokinetic contractions in males under the nitrate-depleted condition, effects that were prevented by NR-BJ.

  • Fatigue resistance was determined during 50 maximal isokinetic wrist flexion-extension contractions
  • Early-phase work was defined as work performed during the first one-third of repetitions
  • Both total work and early-phase work were reduced by ischemia in males under ND-BJ
  • NR-BJ prevented these ischemia-induced reductions in males despite persistent microvascular dysfunction

Fatigue resistance was preserved in females across both NR-BJ and ND-BJ conditions regardless of nitrate supplementation.

  • Females did not show ischemia-induced impairments in fatigue resistance under the ND-BJ condition
  • NR-BJ did not further affect fatigue resistance in females
  • This contrasts with the male response where NR-BJ was required to preserve fatigue resistance
  • The finding suggests females may have baseline protection against ischemia-induced fatigue decrements

The study employed a randomized, double-blind, crossover design to test the effects of dietary nitrate on ischemia-induced microvascular dysfunction and fatigue resistance.

  • Sixteen healthy adults participated (8 males, 8 females; aged 20-40 years)
  • Participants completed both NR-BJ (~10 mmol nitrate) and ND-BJ (~0.34 mmol nitrate) conditions
  • A 20-minute forearm arterial occlusion protocol was used to induce transient microvascular dysfunction
  • Assessments included near-infrared spectroscopy for microvascular reactivity and isokinetic dynamometry for fatigue resistance

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Citation

Souza Filho C, Ramos O, Soares R, Alvares T. (2026). Effect of Dietary Nitrate Intake on Fatigue Resistance Following Ischemia-Induced Microvascular Dysfunction in Males and Females.. The Journal of nutrition. https://doi.org/10.1016/j.tjnut.2025.101263