L-Citrulline supplementation attenuates aortic pulse pressure and wave reflection responses to cold stress in older adults

Jaime, Salvador J.; Nagel, Jessica; Maharaj, Arun; Fischer, Sophia; Schwab, Elizabeth; Martinson, Christopher; Radtke, Kim; Mikat, Richard P.; Figueroa, Arturo

doi:10.1016/j.exger.2021.111685

Cited by 8 publications

(19 citation statements)

References 43 publications

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“…Our participants had a normal or elevated SBP at rest. Our observation that the resting BP was unaffected by CIT and CIT+GSH supplementations is consistent with previous studies in normotensive adults [ 30 , 32 ] and middle-aged adults with elevated SBP and FBG [ 27 ]. Thus, we used the CPT as a systemic sympathetic vasoconstrictor stimulus to evaluate the efficacy of dietary supplements for attenuating BP reactivity to CPT [ 18 , 19 ].…”

Section: Discussionsupporting

confidence: 93%

“…We observed reductions of brachial and aortic SBP and MAP responses to CPT after CIT+GSH but not CIT supplementation. Previous evidence of blunted BP responsiveness to CPT after 2 weeks of CIT (6 g/day) was observed in healthy young [ 31 ] and older adults [ 32 ]. However, we did not measure FMD in those previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…Short-term CIT supplementation has been shown to improve plasma ARG, ARG/ADMA, arterial stiffness, and resting BP in middle-aged and older adults [ 23 , 25 , 26 , 27 , 28 , 29 ]. Evidence supports the benefit of CIT supplementation on the attenuation of BP reactivity to CPT in healthy adults [ 30 , 31 , 32 ]. A placebo-controlled study examined the effect of CIT supplementation on FMD but failed to detect improvements in healthy adults [ 24 ].…”

Section: Introductionmentioning

confidence: 92%

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Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women

et al. 2023

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Postmenopausal women (PMW) may experience endothelial dysfunction associated with arginine (ARG) deficiency relative to asymmetric dimethylarginine (ADMA) caused by oxidative stress. Endothelial dysfunction contributes to increased blood pressure (BP) responsiveness to sympathoexcitation induced by the cold pressor test (CPT). We investigated the effects of citrulline alone (CIT) and combined with the antioxidant glutathione (CIT+GSH) on vascular function. Forty-four healthy PMW were randomized to CIT (6 g), CIT+GSH (2 g + 200 mg: Setria®) or placebo (PL) for 4 weeks. Brachial artery flow-mediated dilation (FMD), aortic stiffness (pulse wave velocity, PWV), brachial and aortic BP reactivity to CPT, and serum fasting blood glucose (FBG), ARG, and ARG/ADMA ratio were measured. Baseline FBG was higher in CIT+GSH vs. PL. FMD increased after CIT+GSH vs. PL (p < 0.05). CIT and CIT+GSH increased ARG/ADMA (p < 0.05), but did not affect aortic PWV. CIT+GSH attenuated the brachial and aortic systolic BP and mean arterial pressure (MAP) responses to CPT vs. PL and CIT (p < 0.05). The improvements in FMD were related to baseline FMD (r = −0.39, p < 0.05) and aortic MAP response to CPT (r = −0.33, p < 0.05). This study showed that CIT+GSH improved FMD and attenuated systolic BP and MAP reactivity in PMW. Although CIT increased ARG/ADMA, it did not improve FMD in healthy PMW.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

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Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women

et al. 2023

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“…Watermelon powder reduced AIx and AIx normalized for a heart rate of 75 beats/min (AIx75), suggesting a reduced left ventricle afterload and risk for cardiovascular events in individuals with prehypertension [ 1 ]. Evidence has demonstrated that vascular benefits of L-CIT supplementation, if not apparent at rest, can be evident during sympathetic stimulation induced during the cold pressor test (CPT) in older adults [ 67 ]. Figueroa et al [ 10 ] investigated the effect of watermelon extract (4 g of L-citrulline) for 6 weeks on aortic hemodynamic responses to CPT in middle-aged adults with hypertension.…”

Section: Evidence Of Watermelon Ingestion On Vascular Healthmentioning

confidence: 99%

Current Evidence of Watermelon (Citrullus lanatus) Ingestion on Vascular Health: A Food Science and Technology Perspective

et al. 2022

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The amino acid L-arginine is crucial for nitric oxide (NO) synthesis, an important molecule regulating vascular tone. Considering that vascular dysfunction precedes cardiovascular disease, supplementation with precursors of NO synthesis (e.g., L-arginine) is warranted. However, supplementation of L-citrulline is recommended instead of L-arginine since most L-arginine is catabolized during its course to the endothelium. Given that L-citrulline, found mainly in watermelon, can be converted to L-arginine, watermelon supplementation seems to be effective in increasing plasma L-arginine and improving vascular function. Nonetheless, there are divergent findings when investigating the effect of watermelon supplementation on vascular function, which may be explained by the L-citrulline dose in watermelon products. In some instances, offering a sufficient amount of L-citrulline can be impaired by the greater volume (>700 mL) of watermelon needed to reach a proper dose of L-citrulline. Thus, food technology can be applied to reduce the watermelon volume and make supplementation more convenient. Therefore, this narrative review aims to discuss the current evidence showing the effects of watermelon ingestion on vascular health parameters, exploring the critical relevance of food technology for acceptable L-citrulline content in these products. Watermelon-derived L-citrulline appears as a supplementation that can improve vascular function, including arterial stiffness, endothelial function, and blood pressure. Applying food technologies to concentrate bioactive compounds in a reduced volume is warranted so that its ingestion can be more convenient, improving the adherence of those who want to ingest watermelon products daily.

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“…Previous data demonstrated that CIT increases plasma levels of ARG (20) and NO and reduces aortic SBP and PP at rest in postmenopausal women (21) . Moreover, evidence indicates that CIT can reduce aortic SBP, PP, and pressure wave amplitude responses to sympathetic overactivation induced via cold exposure in older adults (22) . Similarly, acute L-citrulline (6 g) and chronic CIT (6 g/d) attenuated aortic SBP responses to exercise and to PEMI combined with cold exposure in hypertensive postmenopausal women (17) and healthy young men (23) , demonstrating the ability of CIT to effectively control BP responses to conditions with excessive sympathetic activity.…”

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confidence: 99%

L-Citrulline supplementation attenuates aortic pressure and pressure waves during metaboreflex activation in postmenopausal women

Dillon,

Kang,

Maharaj

et al. 2023

Br J Nutr

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Postmenopausal women have augmented pressure wave responses to low-intensity isometric handgrip exercise (IHG) due to an overactive metaboreflex (postexercise muscle ischaemia, PEMI), contributing to increased aortic systolic blood pressure (SBP). Menopause-associated endothelial dysfunction via arginine (ARG) and nitric oxide deficiency may contribute to exaggerated exercise SBP responses. L-Citrulline supplementation (CIT) is an ARG precursor that decreases SBP, pulse pressure (PP) and pressure wave responses to cold exposure in older adults. We investigated the effects of CIT on aortic SBP, PP, and pressure of forward (Pf) and backward (Pb) waves during IHG and PEMI in twenty-two postmenopausal women. Participants were randomised to CIT (10 g/d) or placebo (PL) for 4 weeks. Aortic haemodynamics were assessed via applanation tonometry at rest, 2 min of IHG at 30 % of maximal strength, and 3 min of PEMI. Responses were analysed as change (Δ) from rest to IHG and PEMI at 0 and 4 weeks. CIT attenuated ΔSBP (−9 ± 2 v. −1 ± 1 mmHg, P = 0·006), ΔPP (−5 ± 2 v. 0 ± 1 mmHg, P = 0·03), ΔPf (−6 ± 2 v. −1 ± 1 mmHg, P = 0·01) and ΔPb (−3 ± 1 v. 0 ± 1 mmHg, P = 0·02) responses to PEMI v. PL. The ΔPP during PEMI was correlated with ΔPf (r = 0·743, P < 0·001) and ΔPb (r = 0·724, P < 0·001). Citrulline supplementation attenuates the increase in aortic pulsatile load induced by muscle metaboreflex activation via reductions in forward and backward pressure wave amplitudes in postmenopausal women.

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L-Citrulline supplementation attenuates aortic pulse pressure and wave reflection responses to cold stress in older adults

Cited by 8 publications

References 43 publications

Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women

Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women

Current Evidence of Watermelon (Citrullus lanatus) Ingestion on Vascular Health: A Food Science and Technology Perspective

L-Citrulline supplementation attenuates aortic pressure and pressure waves during metaboreflex activation in postmenopausal women

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