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

Abstract

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.

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

“…Thus, it would be necessary to ingest 1·6–8·6 kg and 2·7–14·3 kg of watermelon flesh or rind per day to get 6 g and 10 g of CIT, respectively. We have reported increases in ARG levels after 6 g (43) and 10 g (20) of CIT for 4 weeks in postmenopausal women. However, serum ARG levels did not increase significantly with 2 g of CIT (43) .…”

“…We have reported increases in ARG levels after 6 g (43) and 10 g (20) of CIT for 4 weeks in postmenopausal women. However, serum ARG levels did not increase significantly with 2 g of CIT (43) . Thus, CIT in the diet may have not affected the results of the present study.…”

Short-Term L-Citrulline Supplementation Does Not Affect Blood Pressure, Pulse Wave Reflection, or Arterial Stiffness at Rest and during Isometric Exercise in Older Males

“…Yet, the short-term supplementation period followed in our investigation may not suffice to induce these beneficial changes in blood pressure, pulse wave reflection, and arterial stiffness, as demonstrated in other L-citrulline studies with longer supplementation at rest or during disturbed hemodynamics [ 25 , 44 , 46 , 49 , 52 ]. Furthermore, a recent study by Figueroa et al [ 60 ] observed improvements in endothelial function in healthy postmenopausal women following four weeks of combined 2 g of citrulline with glutathione supplementation. In contrast, no changes were reported following 6 g of L-citrulline solely.…”

Endothelial Dysfunction in Diabetes Mellitus: New Insights

“…Several nutritional components have been studied, and their impact on endothelial function was demonstrated to be either positive (citrulline and glutathione [ 49 ]) or negative (α-ketoglutarate [ 50 ]).…”