Dose–Response Effect of Watermelon Consumption on Ambulatory Blood Pressure in Adults with Elevated Blood Pressure: A Randomized Controlled Pilot Trial

<b>Background/Objectives</b>: Watermelon (<i>Citrullus lanatus</i>) is a natural dietary source of L-citrulline and L-arginine, the two amino acids involved in nitric oxide (NO) production and vasodilation. Pre-clinical and clinical studies using isolated amino acids or watermelon extracts suggest blood pressure (BP)-lowering potential; however, limited research has been conducted on the impact of watermelon flesh (WM) on BP in adults at risk for hypertension. Therefore, the primary objective of this study was to assess the effect of daily WM intake for four weeks on 24 h ambulatory BP in adults with elevated blood pressure. The secondary outcomes of this study include changes in glucose and insulin markers, lipid profile, NO, L-citrulline, L-arginine, asymmetric dimethylarginine (ADMA) concentrations, and the L-arginine/ADMA ratio. <b>Methods</b>: In this randomized, placebo controlled parallel study design, 39 adults (age: 41 ± 14 years, BMI: 31 ± 6 kg/m², mean ± SD) with elevated BP were randomly assigned to one of three groups for a 4-week intervention: control (0 g WM), WM-1 cup (152 g/day), or WM-2 cups (304 g/day). Ambulatory BP was measured over 24 h at baseline and the end of the intervention period. Fasting plasma samples were analyzed for metabolic biomarkers on a clinical analyzer and NO using a colorimetric assay. L-citrulline, L-arginine, and ADMA were analyzed using an ultra-high-performance liquid chromatography triple quadrupole mass spectrometer (UHPLC-QQQ-MS/MS). Statistical analyses were conducted using SPSS software (IBM SPSS Statistics, Version 29.0.0). <b>Results</b>: After 4 weeks, mean 24 h ambulatory BP was 130.2 ± 3.9 mm Hg (control), 130 ± 3.2 mm Hg (WM-1 cup), and 124.9 ± 3.9 mm Hg (WM-2 cups), with no statistically significant differences between study interventions (<i>p</i> > 0.05). Similarly, no significant changes were observed in fasting plasma glucose, insulin, lipid profile, or NO concentrations. However, plasma L-arginine concentrations and L-arginine/ADMA ratios significantly increased in the WM groups compared to the control (<i>p</i> = 0.009) after adjusting for age, BMI, race, and gender in the statistical model. <b>Conclusion</b>: Overall, BP was not significantly different after two different doses of watermelon compared to control; however, improvements in NO synthesis pathway precursors (L-arginine, ADMA) suggest potential for dietary modulation to support endothelial function and BP regulation.