Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Department of Kinesiology, Pennsylvania State University, University Park, PA 16802, USA.
Nutrients. 2018 Jul 19;10(7):921. doi: 10.3390/nu10070921.
Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations. In this review, we examine the impact of supplementing this important urea cycle intermediate on cardiovascular and metabolic health outcomes and identify future directions for investigating its therapeutic impact on cardiometabolic health.
一氧化氮（NO）生物利用度降低，这种参与调节众多重要生物功能的气态信号分子，导致多种与年龄和生活方式相关的疾病的发生和发展。虽然 l-精氨酸是内皮型一氧化氮合酶（eNOS）合成 NO 的前体，但由于多种原因，口服 l-精氨酸补充剂在增加 NO 合成和/或生物利用度方面效果不大。l-瓜氨酸是一种在西瓜中高浓度存在的中性α-氨基酸，由线粒体中的酶形成，也可作为 l-精氨酸再循环的底物。与 l-精氨酸不同，l-瓜氨酸不会从胃肠道（即肠细胞）或肝脏中定量提取，因此其补充剂更有效地增加 l-精氨酸水平和 NO 合成。补充 l-瓜氨酸已被证明是一种降低血压的干预措施（包括静息和应激诱导），可用于治疗高血压前期和高血压患者，并且在动脉粥样硬化性内皮保护方面有临床前（动物）证据。初步证据也表明，l-瓜氨酸可通过血管和非血管途径对肌肉和代谢健康（易患/老年人群）产生有益影响。在这篇综述中，我们研究了补充这种重要的尿素循环中间产物对心血管和代谢健康结果的影响，并确定了研究其对心脏代谢健康的治疗影响的未来方向。
