Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women

Maharaj, Arun; Fischer, Sophia; Dillon, Katherine N.; Kang, Yejin; Martinez, Mauricio A.; Figueroa, Arturo

doi:10.3390/nu14204396

Cited by 14 publications

(33 citation statements)

References 79 publications

(106 reference statements)

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“…52,53 Oral consumption of watermelon juice has been reported to reduce circulating levels of soluble vascular cell adhesion molecule-1 (sVCAM-1, a biomarker of inflammatory endothelial activation) in obese postmenopausal women, 53 peripheral arterial stiffness in healthy young women, 54 and blood pressure in hypertensive postmenopausal women. 55 Cit and watermelon juice hold promise for improving reproductive health 30 as well as vascular and metabolic health 56,57 in humans.…”

Section: Discussionmentioning

confidence: 99%

Dietary supplementation with L-citrulline improves placental angiogenesis and embryonic survival in gilts

Bazer

Johnson

et al. 2023

Exp Biol Med (Maywood)

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This study was conducted with gilts as an animal model to test the hypothesis that dietary supplementation with L-citrulline (Cit) improves placental angiogenesis and embryonic survival. Between Days 14 and 25 of gestation, each gilt was fed a corn- and soybean-meal-based diet (2 kg/day) supplemented with 0.4% Cit or an isonitrogenous amount of L-alanine (Control). On Day 25 of gestation, gilts were hysterectomized to obtain conceptuses. Amniotic and allantoic fluids and placentae were analyzed for NOx [stable oxidation products of nitric oxide (NO)], polyamines, and amino acids (AAs). Placentae were also analyzed for syntheses of NO and polyamines; concentrations of AAs and related metabolites; and the expression of angiogenic factors and aquaporins (AQPs). Compared to the control group, Cit supplementation increased ( P < 0.01) the number of viable fetuses by 2.0 per litter, the number and diameter of placental blood vessels (21% and 24%, respectively), placental weight (15%), and total allantoic and amniotic fluid volumes (20% and 47%, respectively). Cit supplementation also increased ( P < 0.01) enzymatic activities of GTP-cyclohydrolase-1 (32%) and ornithine decarboxylase (27%) in placentae; syntheses of NO (29%) and polyamines (26%); concentrations of NOx (19%), tetrahydrobiopterin (28%), polyamines (22%), cAMP (26%), and cGMP (24%) in placentae; total amounts of NOx (22–40%), polyamines (23–40%), AAs (16–255%), glucose (22–44%), and fructose (22–43%) in allantoic and amniotic fluids. Furthermore, Cit supplementation increased ( P < 0.05) placental mRNA levels for angiogenic factors ( eNOS [84%], GTP-CH1 [55%], PGF [61%], VEGFA120 [26%], and VEGFR2 [137%], as well as AQPs – AQP1 [105%], AQP3 [53%], AQP5 [77%], AQP8 [57%], and AQP9 [31%]). Collectively, dietary Cit supplementation enhanced placental NO and polyamine syntheses as well as angiogenesis to improve conceptus development and survival.

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Section: Discussionmentioning

confidence: 99%

Dietary supplementation with L-citrulline improves placental angiogenesis and embryonic survival in gilts

Bazer

Johnson

et al. 2023

Exp Biol Med (Maywood)

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“…The AA metabolism is impaired in CKD and elevated ADMA levels are associated with higher vascular stiffness and reduced NO contribution. Several studies have suggested the exogenous supplementation of AAs, e.g., arginine [ 41 ], citrulline [ 42 ] and L- phenylalanine [ 43 ], as a potential therapeutic option to target vascular disease; however current evidence is contradictory and may depend on differences in dose and administration route. In conclusion, we suggest that uremia is associated with alterations in AA metabolism that may affect vascular function in CKD towards an increased risk for CVD.…”

Section: Discussionmentioning

confidence: 99%

Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease

Arefin

Löfgren

Stenvinkel

et al. 2023

IJMS

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We hypothesized that patients with chronic kidney disease (CKD) display an altered plasma amino acid (AA) metabolomic profile that could contribute to abnormal vascular maintenance of peripheral circulation in uremia. The relationships between plasma AAs and endothelial and vascular smooth muscle function in the microcirculation of CKD patients are not well understood. The objective of this study is to investigate to what extent the levels of AAs and its metabolites are changed in CKD patients and to test their relationship with endothelial and vascular smooth muscle function. Patients with CKD stages 3 and 5 and non-CKD controls are included in this study. We report that there was a significant reduction of the biopterin (BH4/BH2) ratio, which was accompanied by increased plasma levels of BH2, asymmetric dimethylarginine (ADMA) and citrulline in patients with CKD-5 vs. CKD-3 vs. controls. In vivo augmentation index measurement showed a positive association with ADMA in all participants. The contribution of nitric oxide, assessed by ex vivo assay, showed a negative association with creatinine, ADMA and citrulline in all participants. In CKD-5, BH4 negatively correlated with ADMA and ornithine levels, and the ex vivo endothelium-mediated dilatation positively correlated with phenylalanine levels. In conclusion, uremia is associated with alterations in AA metabolism that may affect endothelium-dependent dilatation and vascular stiffness in microcirculation. Interventional strategies aiming to normalize the AA metabolism could be of interest as treatment options.

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“…In contrast, evidence indicates that ARG supplementation improves endothelial function in individuals with a baseline brachial FMD lower than 7% [ 39 ], suggesting benefits of ARG and CIT are more prominent in individuals with endothelial dysfunction. Previous literature has elucidated 4 weeks of CIT significantly increased brachial FMD compared to PL in hypertensive postmenopausal women [ 40 ]. Our study demonstrated for the first time that sfemFMD increased after CIT supplementation alone compared to PL.…”

Section: Discussionmentioning

confidence: 99%

“…Oral CIT was an efficient ARG precursor that results in an important increase in systemic ARG availability [ 57 ]. We recently reported that this CIT dose for 4 weeks improved brachial FMD by increasing ARG availability in postmenopausal women with hypertension [ 40 ]. Our findings suggest that 10 g daily of CIT supplementation may help to increase leg LM when combined with SVLIRT, by increasing leg endothelial function via an ARG/NO pathway-induced vasodilation [ 33 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Combined L-Citrulline Supplementation and Slow Velocity Low-Intensity Resistance Training Improves Leg Endothelial Function, Lean Mass, and Strength in Hypertensive Postmenopausal Women

et al. 2022

Self Cite

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Hypertension is highly prevalent in postmenopausal women. Endothelial dysfunction is associated with hypertension and the age-related decreases in muscle mass and strength. L-citrulline supplementation (CIT) and slow velocity low-intensity resistance training (SVLIRT) have improved vascular function, but their effect on muscle mass is unclear. We investigated whether combined CIT and SVLIRT (CIT + SVLIRT) would have additional benefits on leg endothelial function (superficial femoral artery flow-mediated dilation (sfemFMD)), lean mass (LM), and strength in hypertensive postmenopausal women. Participants were randomized to CIT (10 g/day, n = 13) or placebo (PL, n = 11) alone for 4 weeks and CIT + SVLIRT or PL + SVLIRT for another 4 weeks. sfemFMD, leg LM and muscle strength were measured at 0, 4, and 8 weeks. CIT increased sfemFMD after 4 weeks (CIT: Δ1.8 ± 0.3% vs. PL: Δ−0.2 ± 0.5%, p < 0.05) and 8 weeks (CIT + SVLIRT: Δ2.7 ± 0.5% vs. PL + SVLIRT: Δ−0.02 ± 0.5, p = 0.003). Leg LM improved after CIT + SVLIRT compared to PL + SVLIRT (Δ0.49 ± 0.15 kg vs. Δ0.07 ± 0.12 kg, p < 0.05). Leg curl strength increased greater with CIT + SVLIRT compared to PL + SVLIRT (Δ6.9 ± 0.9 kg vs. Δ4.0 ± 1.0 kg, p < 0.05). CIT supplementation alone improved leg endothelial function and when combined with SVLIRT has additive benefits on leg LM and curl strength in hypertensive postmenopausal women.

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Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women

Cited by 14 publications

References 79 publications

Dietary supplementation with L-citrulline improves placental angiogenesis and embryonic survival in gilts

Dietary supplementation with L-citrulline improves placental angiogenesis and embryonic survival in gilts

Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease

Combined L-Citrulline Supplementation and Slow Velocity Low-Intensity Resistance Training Improves Leg Endothelial Function, Lean Mass, and Strength in Hypertensive Postmenopausal Women

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