L-Citrulline and Improved Flow-Mediated Dilation

Research synthesisModerate evidenceModerate effect5 studies · 5 beneficial · 0 neutral · 0 harmful

Across all 5 studies, L-citrulline supplementation consistently improved flow-mediated dilation (FMD), with 5 of 5 studies reporting beneficial effects and all reaching statistical significance. Effect sizes were predominantly moderate, with one large effect observed. The most-studied doses were 6 g/day and 3 g/day, and effects were typically observed over 4–12 weeks in clinical populations such as individuals with high-normal blood pressure, hypertensive postmenopausal women, and patients with type 2 diabetes.

Effective dose range: 3000–6000 mg/day
Studied populations: Individuals with high-normal blood pressure, hypertensive postmenopausal women, patients with type 2 diabetes, patients with heart failure with preserved ejection fraction

Caveats: Available evidence is overwhelmingly positive — clinical literature in this area is subject to publication bias (null-result studies are less likely to be published or indexed). Most studies had small sample sizes (14–66 participants), and two of five studies lacked a randomized controlled design. The evidence base includes only 5 studies, so conclusions should be considered preliminary.

Generated Jul 11, 2026

Doses used in studies

g/day: 6–10 (median 6, IQR 6–8) — 3 studies
mg/day: 3,000 (median 3,000, IQR 3,000–3,000) — 1 study

Time to effect

Median: 4 weeks · IQR 3.3 weeks–6 weeks · Range 7 days–2.8 months — Reported in 4 of 5 studies

Safety in these studies

Overall tolerabilityReported
Across all studies, no adverse effects related to citrulline supplementation were reported.
from: Citrulline supplementation in postmenopausal women: a systematic review of vascular, muscu

5 of 5 papersPopulation:

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
- RCT · n = 66
- 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
4 Insights on
- Improved Flow-Mediated Dilation
- High evidence
- Clinical
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
Significant
Yes
Dose
3000 mg/day
L-Citrulline Supplementation Improves Arterial Blood Flow and Muscle Oxygenation during Handgrip Exercise in Hypertensive Postmenopausal Women.
- 2024-06-19
- RCT
- Nutrients 16(12)
- - Yejin Kang
  - Katherine N Dillon
  - Mauricio A Martinez
  - Arun Maharaj
  - Stephen M Fischer
  - Arturo Figueroa
- PubMed: 38931289
- DOI: 10.3390/nu16121935
6 Insights on
- Improved Flow-Mediated Dilation
- High evidence
- Rigorous Journal
- Clinical
Compared to the placebo, CIT significantly (p < 0.05) increased FMD (Δ-0.7 ± 0.6% vs. Δ1.6 ± 0.7%)
Effect
Beneficial
Effect size
Large
Significant
Yes
Dose
10 g/day
Citrulline supplementation in postmenopausal women: a systematic review of vascular, muscular, and metabolic effects.
- 2026-01-26
- Systematic Review
- BMC women's health 26(1)
- - Hossein Bahari
  - Elmira Ramezani
  - Mahsa Malekahmadi
- PubMed: 41588439
- DOI: 10.1186/s12905-026-04277-6
9 Insights on
- Improved Flow-Mediated Dilation
- High evidence
- Elderly
Four studies assessed endothelial function, two of which demonstrated significant improvements in flow-mediated dilation
Effect
Beneficial
Effect size
Small
Significant
Yes
Dose
not specified in abstract
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
- RCT · n = 16
- Nutrients 17(23)
- - Yejin Kang
  - Katherine N Dillon
  - Danielle E Levitt
  - Arturo Figueroa
- PubMed: 41374029
- DOI: 10.3390/nu17233739
4 Insights on
- Improved Flow-Mediated Dilation
- High evidence
- Rigorous Journal
- Clinical
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
Significant
Yes
Dose
6 g/day
Improved vascular function and functional capacity following l-citrulline administration in patients with heart failure with preserved ejection fraction: a single-arm, open-label, prospective pilot study.
- 2023-02-01
- Clinical Trial · n = 14
- Journal of applied physiology (Bethesda, Md. : 1985) 134(2)
- - Stephen M Ratchford
  - Kanokwan Bunsawat
  - Jeremy K Alpenglow
  - Jia Zhao
  - Josephine B Wright
  - John J Ryan
  - D Walter Wray
- PubMed: 36476159
- DOI: 10.1152/japplphysiol.00445.2022
4 Insights on
- Improved Flow-Mediated Dilation
- Moderate evidence
- Clinical
7 days of l-Cit administration improved FMD (0d: 2.5 ± 1.6%, 7d: 4.5 ± 2.9%)
Effect
Beneficial
Effect size
Moderate
Significant
Yes
Dose
6 g/day

L-Citrulline and Improved Flow-Mediated Dilation

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.

L-Citrulline Supplementation Improves Arterial Blood Flow and Muscle Oxygenation during Handgrip Exercise in Hypertensive Postmenopausal Women.

Citrulline supplementation in postmenopausal women: a systematic review of vascular, muscular, and metabolic effects.

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.

Improved vascular function and functional capacity following l-citrulline administration in patients with heart failure with preserved ejection fraction: a single-arm, open-label, prospective pilot study.