L-citrulline, Arginase Activity, and Nitrate As Potential Nitric Oxide-Related Markers of Subclinical Atherosclerosis in Healthy Middle-Aged Non-smokers: A Cross-Sectional Study

Alterations in circulating nitric oxide (NO)-related factors, which play a key role in maintaining endothelial function, are thought to precede the development of atherosclerosis. These factors are also relatively modifiable through diet and supplements. Therefore, this cross-sectional exploratory study aimed to identify blood NO-related factors associated with the risk of subclinical atherosclerosis in 124 healthy, treatment-naïve, non-smoking individuals aged 45-70 years. As a result, significant associations were observed between brachial-ankle pulse wave velocity (PWV), an indicator of arterial stiffness, and circulating levels of L-citrulline, arginase activity, and nitrate (NO3-). Specifically, circulating L-citrulline showed a negative association with PWV in non-drinkers (p = 0.007, β = -0.222). Arginase activity was positively associated with PWV among participants with a body mass index (BMI) ≤ 23 (p = 0.011, β = 0.196). Furthermore, plasma NO3- levels exhibited a negative association with PWV in drinkers (p = 0.001, β = -0.274) and a positive association in non-drinkers (p = 0.005, β = 0.241). In conclusion, L-citrulline, arginase activity, and plasma NO3- are potential markers of early vascular changes within subgroups of healthy middle-aged adults and may serve as targets for preventive medical approaches using diet or supplementation.