Supplemental Watermelon Juice Attenuates Acute Hyperglycemia-Induced Macro-and Microvascular Dysfunction in Healthy Adults

Abstract

Background Acute hyperglycemia reduces NO bioavailability and causes macro- and microvascular dysfunction. Watermelon juice (WMJ) is a natural source of the amino acid citrulline, which is metabolized to form arginine for the NO cycle and may improve vascular function. Objectives We examined the effects of 2 weeks of WMJ compared to a calorie-matched placebo (PLA) to attenuate acute hyperglycemia-induced vascular dysfunction. Methods In a randomized, placebo-controlled, double-blind, crossover trial, 6 men and 11 women (aged 21–25; BMI, 23.5 ± 3.2 kg/m2) received 2 weeks of daily WMJ (500 mL) or a PLA drink followed by an oral-glucose-tolerance test. Postprandial flow-mediated dilation (FMD) was measured by ultrasound (primary outcome), while postprandial microvascular blood flow (MVBF) and ischemic reperfusion were measured by near-infrared spectroscopy (NIRS) vascular occlusion test (VOT). Results The postprandial FMD area AUC was higher after WMJ supplementation compared to PLA supplementation (838 ± 459% · 90 min compared with 539 ± 278% · 90 min; P = 0.03). The postprandial MVBF (AUC) was higher (P = 0.01) following WMJ supplementation (51.0 ± 29.1 mL blood · 100 mL tissue–1 · min–1 · 90 min) compared to the PLA (36.0 ± 20.5 mL blood · 100 mL tissue–1 · min–1 · 90 min; P = 0.01). There was a significant treatment effect (P = 0.048) for WMJ supplementation (71.2 ± 1.5%) to increase baseline tissue oxygen saturation (StO2%) when compared to PLA (65.9 ± 1.7%). The ischemic-reperfusion slope was not affected by WMJ treatment (P = 0.83). Conclusions Two weeks of daily WMJ supplementation improved FMD and some aspects of microvascular function (NIRS-VOT) during experimentally induced acute hyperglycemia in healthy adults. Preserved postprandial endothelial function and enhanced skeletal muscle StO2% are likely partially mediated by increased NO production (via citrulline conversion into arginine) and by the potential antioxidant effect of other bioactive compounds in WMJ.

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

“…Ellis et al [ 9 ] observed that plasma ADMA was unaffected by ingestion of 360 mL watermelon juice twice a day (1.63 g of L-citrulline) for four weeks in healthy postmenopausal women. Two recent studies [ 8 , 9 ] did not observe significant increases in circulating L-arginine following watermelon supplementation, indicating that insufficient substrate for NO production may have contributed to the lack of improvement in FMD. Moreover, Shanely et al [ 27 ] demonstrated that 710 mL of watermelon puree (2.28 g of L-citrulline/L-arginine) for six weeks reduced sVCAM-1, but not soluble platelet selectin (sP-Selectin), high-sensitivity C-reactive protein (hs-CRP), and soluble intercellular adhesion molecule-1 (sICAM-1) in overweight and obese postmenopausal women.…”

“…Several previous studies have evaluated the effect of watermelon products on macro- and microvascular responsiveness assessed by brachial FMD and near-infrared spectroscopy, respectively [ 5 , 8 , 9 ] ( Table 1 ). Vincellete et al [ 8 ] investigated the effect of a two-week watermelon juice ingestion (500 mL–795 mg of L-citrulline) on attenuating acute hyperglycemia-induced vascular dysfunction in young healthy adults. It was observed that watermelon juice increased the postprandial FMD and microvascular blood flow area under the curve (AUC) (slope of the linear increase in total hemoglobin) compared to placebo.…”

“…Although a great volume of watermelon juice or puree was provided, the supplementation did not improve vascular function [ 9 , 27 ]. Increased plasma arginine is important for improving endothelial function and watermelon supplementations failed to provide this effect [ 8 , 9 ]. Thus, it is likely necessary to provide a higher volume of watermelon juice or puree (>720 mL) and L-citrulline content to improve vascular function.…”

“…Impaired vascular function is associated with reduced L-arginine availability and increased reactive oxygen species (ROS) that can negatively impact NO synthesis or increase its degradation [ 6 , 7 ]. For this reason, previous studies have investigated the effect of NO precursors-rich food on flow-mediated dilation (FMD, a gold standard measure of endothelial function), pulse wave velocity (a measure of arterial stiffness), and blood pressure in individuals with cardiovascular risk factors [ 2 , 8 , 9 , 10 , 11 ].…”

“…However, there is evidence reporting the absence of a positive vascular effect after watermelon ingestion [ 8 , 9 , 12 ]. Interestingly, the studies that failed to improve vascular parameters provided a low dose of L-citrulline in watermelon products, suggesting that delivering an adequate amount of L-citrulline is crucial to ensure vascular benefits.…”