Strongest evidence
The most robust finding is for improved flow-mediated dilation (FMD), an indicator of endothelial function. All 5 studies (moderate evidence strength) reported beneficial effects, with moderate effect sizes at doses of 3000–6000 mg/day over 4–12 weeks. Reduced aortic systolic blood pressure also shows moderate evidence: 4 of 5 studies found benefit, typically with 6 g/day over 28 days in populations like hypertensive postmenopausal women and older adults with type 2 diabetes.
Mixed or weaker evidence
Evidence for reduced diastolic blood pressure is low and mixed: 3 of 6 studies showed benefit, while 3 found no effect; a 2018 meta-analysis reported no effect, but a 2025 analysis found a reduction only when L-citrulline was combined with L-arginine. Reduced blood pressure (general) has low evidence from 4 studies, with the strongest study (a meta-analysis of 2,028 women) showing no effect. Reduced systolic blood pressure alone has very low evidence: all 3 studies reported large effects (e.g., –10.44 mmHg in a 2025 meta-analysis), but the sample is tiny and no consistent dose data were reported.
Effective dose patterns
When effective doses were reported, they converged on 3000–6000 mg/day for FMD and 6–10 g/day for blood pressure outcomes. The higher end (6–10 g) was used in studies of aortic and diastolic blood pressure, while moderate doses sufficed for FMD. No consistent dose could be extracted for systolic blood pressure due to reporting gaps.
Population insights
Most studies focused on older adults, postmenopausal women, and individuals with hypertension, type 2 diabetes, or heart failure with preserved ejection fraction. Benefit was consistent across these groups for FMD and aortic systolic blood pressure, but no evidence suggests general population benefits. Study durations were short (median 28 days for blood pressure outcomes; 4–12 weeks for FMD), limiting long-term conclusions.
Notable caveats
- Publication bias is a concern across multiple outcomes: null results are less likely to be published or indexed.
- Small sample sizes (often 14–66 participants) reduce generalizability.
- Inconsistent meta-analyses for diastolic blood pressure highlight conflicting results; combining L-citrulline with L-arginine may confound findings.
- Evidence bases are small (3–6 studies per outcome), so all conclusions should be considered preliminary.