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. 2023 Jan 28;15(3):660. doi: 10.3390/nu15030660

Table 4.

Summary of studies investigating the effect of synergistic effects of multiple nitric oxide precursors.

Study Subjects Design Intervention Performance Tests Main Findings
L-citrulline/L-arginine + nitrates
Burgos et al. (2022) [120] 32 male endurance athletes (32.2 ± 4.9 y; 22.6 ± 1.8 kg·m2) Randomized, double-blind, placebo-controlled trial 3 g L-citrulline vs. 300 mg nitrates vs. 3 g L-citrulline + 300 mg nitrates vs. placebo; 9 weeks Horizontal jump test

Handgrip dynamometer test

1 min abdominal test
↔ horizontal jump distance *
↔ handgrip strength
↔ abdominal crunch repetitions *
Le Roux-Mallouf et al. (2017) [116] 14 healthy, physically active men and women (27.8 ± 7.5 y; 64.3 ± 9.1 kg) Randomized, double-blind, placebo-controlled, crossover study BRJ containing 1200 mg nitrates + 6 g L-citrulline vs. placebo; 90 min prior Thigh ischemia-reperfusion test ↑ post-occlusive hemoglobin/oxyhemoglobin response suggesting enhanced vasodilation
Le Roux-Mallouf, Laurent, et al. (2019) [117] 15 healthy, physically active men (28 ± 6 y; 73 ± 6 kg) Randomized, double-blind, placebo-controlled, crossover study BRJ (520 mg nitrate) vs. BRJ (520 mg nitrate) + 6 g L-citrulline vs. BRJ (520 mg nitrate + 6 g L-arginine; 90 min prior Thigh ischemia-reperfusion test

Isometric knee extension repetitions-to-failure (5 s on-4 s off at 45% of MVC)
↑ post-occlusive hemoglobin/oxyhemoglobin response suggesting enhanced vasodilation (nitrate and nitrate/citrulline group)
↔ knee extension repetitions
Le Roux-Mallouf, Pelen, et al. (2019) [118] 24 healthy older adult men and women (64 ± 2 y; 73.5 ±6.1 kg) Randomized, double-blind, placebo-controlled trial 6 g L-citrulline + 520 mg nitrate vs. placebo; 4 weeks Thigh ischemia-reperfusion test

Incremental isometric knee extension test
↔ ischemia-reperfusion test
↔ knee extension performance
Le Roux-Mallouf et al. (2020) [119] 24 healthy men and women (26 ± 3 y; 76.4 ± 5.1 kg) Randomized, double-blind, placebo-controlled trial 6 g L-citrulline + 520 mg nitrate vs. placebo; 8 weeks Thigh ischemia-reperfusion test

Incremental isometric knee extension test
↔ ischemia-reperfusion test
↑ maximal knee extensor strength
↔ knee extension performance *
L-citrulline + L-arginine
Suzuki et al. (2019) [115] 20 male collegiate soccer players (19.0 ± 0.2 y; 65.4 ± 0.1 kg) Randomized, double-blind, placebo-controlled, crossover study 1.2 g L-citrulline + 1.2 g L-arginine vs. placebo; 7 days (60 min prior) 10 min full-power cycling test ↑ mean power output
↔ peak pedaling speed
↑ subjective “leg muscle soreness”
↑ subjective “ease of pedaling”

↑ = significantly greater (p < 0.05) than placebo; ↓ = significantly less (p < 0.05) than placebo; ↔ = no significant difference between supplement and placebo; * = trend towards significance (p < 0.10); BRJ = beetroot juice; MVC = maximal voluntary contraction; MIPS = multi-ingredient pre-workout supplement.