Vascular effects of l-citrulline supplementation in healthy adults are largely influenced by the prehypertensive range of blood pressure: A double-blind, randomized, placebo-controlled, parallel-group study.
- 2026-06
- Nutrition research (New York, N.Y.) 150
- Dai Nogimura
- Kenjiro Nagaoka
- Keiki Ogino
- Noriyoshi Ogino
- Kazuki Moriyasu
- Masahiko Morita
- PubMed: 42142423
- DOI: 10.1016/j.nutres.2026.04.008
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 66
- Population
- 66 participants (33 L-citrulline, 33 placebo; 21% female; age 63 ± 5 years and 62 ± 5 years; systolic blood pressure ~130 mm Hg; diastolic blood pressure ~80 mm Hg)
- Methods
- randomized, 3000 mg of L-citrulline or placebo for 12 weeks
- Blinding
- Double-blind
- Duration
- 12 weeks
- Funding
- Unclear
Age-related deterioration in vascular function can lead to cardiovascular diseases and other health problems. The effects of L-citrulline on flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity have been reported; however, its effects on vascular function have only been investigated in high-dose studies of patients with angina pectoris and obesity. We hypothesized that low L-citrulline doses may be effective in healthy adults with declining vascular function and that blood pressure range could be a crucial determinant considering its strong influence on vascular function. This study evaluated the effects of relatively low L-citrulline doses on vascular function in healthy participants and compared its efficacy between participants with normal and high-normal blood pressure. We randomized 66 participants to receive 3000 mg of L-citrulline (n = 33; 21% female; age 63 ± 5 years; systolic blood pressure 130 ± 11 mm Hg; diastolic blood pressure 80 ± 8 mm Hg) or placebo (n = 33; 21% female; age 62 ± 5 years; systolic blood pressure 131 ± 9 mm Hg; diastolic blood pressure 79 ± 8 mm Hg) for 12 weeks. L-citrulline significantly improved FMD (L-citrulline 4.66 ± 0.45%; placebo 3.46 ± 0.37%, p = .045) at week 12 in participants with high-normal blood pressure at baseline. l-citrulline also significantly improved subjective feelings of low back pain and shoulder stiffness among participants with high-normal blood pressure. Moreover, it significantly reduced blood 3-nitrotyrosine concentrations in the overall study population and in the subgroup with high-normal blood pressure. In conclusion, an improvement in FMD after 12 weeks of low-dose l-citrulline supplementation was observed only among participants who had high-normal blood pressure at baseline, indicating that baseline blood pressure influences the vascular response to l-citrulline.
Research Insights
L-citrulline significantly improved FMD (L-citrulline 4.66 ± 0.45%; placebo 3.46 ± 0.37%, p = .045) at week 12 in participants with high-normal blood pressure at baseline.
- Effect
- Beneficial
- Effect size
- Moderate
- Dose
- 3000 mg/day
Moreover, it significantly reduced blood 3-nitrotyrosine concentrations in the overall study population and in the subgroup with high-normal blood pressure.
- Effect
- Beneficial
- Effect size
- Small
- Dose
- 3000 mg/day
l-citrulline also significantly improved subjective feelings of low back pain and shoulder stiffness among participants with high-normal blood pressure.
- Effect
- Beneficial
- Effect size
- Small
- Dose
- 3000 mg/day
l-citrulline also significantly improved subjective feelings of low back pain and shoulder stiffness among participants with high-normal blood pressure.
- Effect
- Beneficial
- Effect size
- Small
- Dose
- 3000 mg/day