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Effects of L-Citrulline Supplementation on Endothelial Function, Arterial Stiffness, and Blood Glucose Level in the Fasted and Acute Hyperglycemic States in Middle-Aged and Older Adults with Type 2 Diabetes.

  • 2025-11-28
  • Nutrients 17(23)
    • Yejin Kang
    • Katherine N Dillon
    • Danielle E Levitt
    • Arturo Figueroa

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 16
Population
16 patients with T2DM (age 62 ± 6 years)
Methods
Randomized to consume either CIT (6 g/day) or placebo for 4 weeks
Duration
4 weeks
  • Rigorous Journal
Background: Acute and chronic hyperglycemia in patients with type 2 diabetes mellitus (T2DM) causes endothelial dysfunction and arterial stiffness, contributing to early mortality from cardiovascular disease (CVD). Although L-citrulline (CIT) supplementation improves endothelial function in older women and decreases fasting glucose in those with T2DM, whether it improves vascular function and blood glucose during acute hyperglycemic states in T2DM is unknown. Methods: We randomized 16 patients with T2DM (age 62 ± 6 years) to consume either CIT (6 g/day) or placebo for 4 weeks. Brachial artery flow-mediated dilation (FMD), brachial and aortic blood pressure, aortic and leg arterial stiffness (pulse wave velocity, PWV), and blood glucose concentration were assessed in the fasted state and 60 min following glucose ingestion (during acute hyperglycemia). Results: Four weeks of L-citrulline supplementation improved FMD, femoral-ankle PWV, aortic systolic blood pressure, and blood glucose concentration in the fasted state compared to placebo (all p < 0.05). During acute hyperglycemia, CIT supplementation increased FMD and reduced femoral-ankle PWV, aortic systolic BP, and glucose levels compared to placebo (all p < 0.05). Conclusions: CIT supplementation is beneficial to improve vascular function and glucose levels during chronic and acute hyperglycemia in middle-aged and older adults with T2DM.

Research Insights

  • L-Citrulline→Improved Flow-Mediated Dilation

    Four weeks of L-citrulline supplementation improved FMD... in the fasted state compared to placebo (all p < 0.05). During acute hyperglycemia, CIT supplementation increased FMD... compared to placebo (all p < 0.05).

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    6 g/day
  • L-Citrulline→Reduced Aortic Systolic Blood Pressure

    Four weeks of L-citrulline supplementation improved... aortic systolic blood pressure... in the fasted state compared to placebo (all p < 0.05). During acute hyperglycemia, CIT supplementation... reduced aortic systolic BP... compared to placebo (all p < 0.05).

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    6 g/day
  • L-Citrulline→Reduced Arterial Stiffness

    Four weeks of L-citrulline supplementation improved... femoral-ankle PWV... in the fasted state compared to placebo (all p < 0.05). During acute hyperglycemia, CIT supplementation... reduced femoral-ankle PWV... compared to placebo (all p < 0.05).

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    6 g/day
  • L-Citrulline→Reduced Blood Glucose Level

    Four weeks of L-citrulline supplementation improved... blood glucose concentration in the fasted state compared to placebo (all p < 0.05). During acute hyperglycemia, CIT supplementation... reduced glucose levels compared to placebo (all p < 0.05).

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    6 g/day
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