Dietary Supplements

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.

TL;DR

CIT supplementation is beneficial to improve vascular function and glucose levels during chronic and acute hyperglycemia in middle-aged and older adults with T2DM.

Key Findings

L-citrulline supplementation improved brachial artery flow-mediated dilation (FMD) in the fasted state compared to placebo in patients with T2DM.

  • 16 patients with T2DM were randomized to CIT (6 g/day) or placebo for 4 weeks
  • Mean age of participants was 62 ± 6 years
  • FMD improvement in fasted state reached statistical significance (p < 0.05)
  • FMD measures endothelial function via brachial artery response to increased blood flow

L-citrulline supplementation reduced femoral-ankle pulse wave velocity (PWV) in the fasted state compared to placebo.

  • Femoral-ankle PWV was used as a measure of leg arterial stiffness
  • Reduction in femoral-ankle PWV reached statistical significance (p < 0.05)
  • Both aortic and leg arterial stiffness (PWV) were assessed in the study
  • The study also assessed carotid-femoral PWV as a measure of aortic arterial stiffness

L-citrulline supplementation reduced aortic systolic blood pressure in the fasted state compared to placebo.

  • Aortic systolic blood pressure reduction was statistically significant (p < 0.05)
  • Both brachial and aortic blood pressure were assessed
  • Participants consumed either CIT (6 g/day) or placebo for 4 weeks
  • Assessments were performed in the fasted state

L-citrulline supplementation reduced fasting blood glucose concentration compared to placebo in patients with T2DM.

  • Blood glucose concentration was assessed in the fasted state
  • Reduction in fasting glucose reached statistical significance (p < 0.05)
  • This finding is consistent with prior literature showing CIT decreases fasting glucose in those with T2DM
  • 16 patients with T2DM participated in the randomized design

During acute hyperglycemia induced by glucose ingestion, L-citrulline supplementation increased FMD compared to placebo.

  • Acute hyperglycemia was induced 60 minutes following glucose ingestion
  • FMD increase during acute hyperglycemia was statistically significant (p < 0.05)
  • This finding addresses a previously unknown question of whether CIT improves vascular function during acute hyperglycemic states in T2DM
  • Assessments were performed at 60 min post-glucose ingestion

During acute hyperglycemia, L-citrulline supplementation reduced femoral-ankle PWV, aortic systolic blood pressure, and blood glucose levels compared to placebo.

  • All three outcomes during acute hyperglycemia reached statistical significance (p < 0.05)
  • Acute hyperglycemia was assessed 60 minutes following glucose ingestion
  • Reduction in blood glucose during acute hyperglycemia suggests a role for CIT in modulating postprandial glycemia
  • These findings collectively indicate CIT benefits both vascular function and metabolic control in the acute hyperglycemic state

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Citation

Kang Y, Dillon K, Levitt D, Figueroa A. (2025). 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.. Nutrients. https://doi.org/10.3390/nu17233739