Jahangir Eiman, Vita Joseph A, Handy Diane, Holbrook Monica, Palmisano Joseph, Beal Ryan, Loscalzo Joseph, Eberhardt Robert T
Boston University School of Medicine, Boston, MA 02118, USA.
Vasc Med. 2009 Aug;14(3):239-48. doi: 10.1177/1358863X08100834.
Studies with L-arginine supplementation have shown inconsistent effects on endothelial function. The generation of guanidinoacetate (GAA) from L-arginine with subsequent formation of creatine and homocysteine and consumption of methionine may reduce the pool of L-arginine available for nitric oxide generation. Experimental studies suggest that creatine supplementation might block this pathway. We sought to determine the effects of L-arginine, creatine, or the combination on endothelium-dependent vasodilation and homocysteine metabolism in patients with coronary artery disease. Patients with coronary artery disease were randomized to L-arginine (9 g/day), creatine (21 g/day), L-arginine plus creatine, or placebo for 4 days (n = 26-29/group). Brachial artery flow-mediated dilation and plasma levels of L-arginine, creatine, homocysteine, methionine, and GAA were measured at baseline and follow-up. L-arginine and creatine supplementation had no effects on vascular function. L-arginine alone increased GAA (p < 0.01) and the ratio of homocysteine to methionine (p < 0.01), suggesting increased methylation demand. The combination of creatinine and L-arginine did not suppress GAA production or prevent the increase in homocysteine-to-methionine ratio. Unexpectedly, creatine supplementation (alone or in combination with L-arginine) was associated with an 11-20% increase in homocysteine concentration (p < 0.05), which was not attributable to worsened renal function, providing evidence against an effect of creatine on decreasing methylation demand. In conclusion, the present study provides no evidence that L-arginine supplementation improves endothelial function and suggests that l-arginine may increase methylation demand. Creatine supplementation failed to alter the actions of L-arginine on vascular function or suppress methylation demand. The unexpected increase in homocysteine levels following creatine supplementation could have adverse effects and merits further study, since creatine is a commonly used dietary supplement.
补充L-精氨酸的研究对内皮功能的影响并不一致。L-精氨酸生成胍基乙酸（GAA），随后形成肌酸和同型半胱氨酸，并消耗甲硫氨酸，这可能会减少可用于生成一氧化氮的L-精氨酸储备。实验研究表明，补充肌酸可能会阻断这一途径。我们试图确定L-精氨酸、肌酸或两者联合使用对冠心病患者内皮依赖性血管舒张和同型半胱氨酸代谢的影响。冠心病患者被随机分为L-精氨酸组（9克/天）、肌酸组（21克/天）、L-精氨酸加肌酸组或安慰剂组，为期4天（每组n = 26 - 29）。在基线和随访时测量肱动脉血流介导的舒张以及L-精氨酸、肌酸、同型半胱氨酸、甲硫氨酸和GAA的血浆水平。补充L-精氨酸和肌酸对血管功能没有影响。单独补充L-精氨酸会增加GAA（p < 0.01）以及同型半胱氨酸与甲硫氨酸的比值（p < 0.01），表明甲基化需求增加。肌酸和L-精氨酸联合使用并未抑制GAA的产生，也未阻止同型半胱氨酸与甲硫氨酸比值的升高。出乎意料的是，补充肌酸（单独或与L-精氨酸联合使用）与同型半胱氨酸浓度升高11% - 20%相关（p < 0.05），这并非由于肾功能恶化所致，这为肌酸对降低甲基化需求没有作用提供了证据。总之，本研究没有提供证据表明补充L-精氨酸可改善内皮功能，并表明L-精氨酸可能会增加甲基化需求。补充肌酸未能改变L-精氨酸对血管功能的作用，也未能抑制甲基化需求。补充肌酸后同型半胱氨酸水平意外升高可能会产生不利影响，值得进一步研究，因为肌酸是一种常用的膳食补充剂。
