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

Arun Maharaj, Stephen M Fischer, Katherine N Dillon, Yejin Kang, Mauricio A Martinez, Arturo Figueroa, Arun Maharaj, Stephen M Fischer, Katherine N Dillon, Yejin Kang, Mauricio A Martinez, Arturo Figueroa

Abstract

Aging and menopause are associated with decreased nitric oxide bioavailability due to reduced L-arginine (L-ARG) levels contributing to endothelial dysfunction (ED). ED precedes arterial stiffness and hypertension development, a major risk factor for cardiovascular disease. This study investigated the effects of L-citrulline (L-CIT) on endothelial function, aortic stiffness, and resting brachial and aortic blood pressures (BP) in hypertensive postmenopausal women. Twenty-five postmenopausal women were randomized to 4 weeks of L-CIT (10 g) or placebo (PL). Serum L-ARG, brachial artery flow-mediated dilation (FMD), aortic stiffness (carotid-femoral pulse wave velocity, cfPWV), and resting brachial and aortic BP were assessed at 0 and 4 weeks. L-CIT supplementation increased L-ARG levels (Δ13 ± 2 vs. Δ−2 ± 2 µmol/L, p < 0.01) and FMD (Δ1.4 ± 2.0% vs. Δ−0.5 ± 1.7%, p = 0.03) compared to PL. Resting aortic diastolic BP (Δ−2 ± 4 vs. Δ2 ± 5 mmHg, p = 0.01) and mean arterial pressure (Δ−2 ± 4 vs. Δ2 ± 6 mmHg, p = 0.04) were significantly decreased after 4 weeks of L-CIT compared to PL. Although not statistically significant (p = 0.07), cfPWV decreased after L-CIT supplementation by ~0.66 m/s. These findings suggest that L-CIT supplementation improves endothelial function and aortic BP via increased L-ARG availability.

Keywords: aortic blood pressure; arterial stiffness; citrulline; endothelial function; hypertension; postmenopausal women.

Conflict of interest statement

The authors declare no conflict of interest with respect to this manuscript.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
Individual data and group mean changes (Δ) in serum L−Arginine concentrations from 0 to 4 weeks of L-citrulline (L−CIT) and placebo (PL) supplementation in hypertensive postmenopausal women. *p < 0.01 vs. PL. For both groups, n = 9.
Figure 3
Figure 3
Individual data and group mean changes (Δ) in brachial artery flow−mediated dilation (FMD) from 0 weeks to 4 weeks of L-citrulline (L−CIT) and placebo (PL) in hypertensive postmenopausal women. * p < 0.05 vs. PL.
Figure 4
Figure 4
Individual data and group mean changes (Δ) in resting aortic systolic blood pressure (SBP, (A)), diastolic BP (DBP, (B)) and mean arterial pressure (MAP, (C)) from 0 weeks to 4 weeks of L−citrulline (L−CIT) and placebo (PL) in hypertensive postmenopausal women. * p ≤ 0.05 vs. PL.

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