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

  • 2026-01-26
  • BMC women's health 26(1)
    • Hossein Bahari
    • Elmira Ramezani
    • Mahsa Malekahmadi

Study Design

Type
Systematic Review
Population
360 postmenopausal women
Methods
comprehensive literature search using PubMed, Web of Science, and Scopus to identify RCTs; results synthesized narratively

Background

Postmenopausal women are at increased risk of developing cardiovascular, muscular, and metabolic dysfunction due to hormonal changes associated with aging. Citrulline, a non-essential amino acid and precursor to nitric oxide, has gained interest as a potential dietary supplement for improving vascular health, muscle function, and metabolic parameters in this population.

Objective

This systematic review aims to evaluate the effects of citrulline supplementation, administered directly or via watermelon products, on cardiovascular, muscular, and metabolic outcomes in postmenopausal women.

Methods

A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus databases to identify randomized controlled trials (RCTs) investigating citrulline supplementation in postmenopausal women. Studies were included if they reported outcomes related to blood pressure, arterial stiffness, endothelial function, muscle strength or mass, metabolic parameters, and safety. Study quality was assessed using the Cochrane Risk of Bias Tool 2. Due to heterogeneity in study designs and reported outcomes, results were synthesized narratively.

Results

Twelve RCTs involving 360 postmenopausal women were included. all conducted in the United States, with study durations ranging from 4 to 8 weeks and participant ages between 50 and 75 years. Seven studies reported blood pressure outcomes, with most showing reductions in systolic blood pressure and mean arterial pressure. Five studies examined arterial stiffness, with mixed findings on pulse wave velocity and augmentation index. Four studies assessed endothelial function, two of which demonstrated significant improvements in flow-mediated dilation. Muscle function outcomes were investigated in two studies, suggesting improvements only when citrulline was combined with resistance training. Six studies assessed metabolic parameters, with no consistent effects observed on body weight, glucose, insulin, or lipid profiles. Across all studies, no adverse effects related to citrulline supplementation were reported.

Conclusion

Citrulline supplementation may offer benefits for blood pressure regulation (up to 9 mmHg SBP reduction in some studies) in hypertensive postmenopausal women, but evidence for arterial stiffness, endothelial function, and metabolic outcomes remains inconsistent. Further large-scale studies are needed before clinical recommendations can be made.

Research Insights

  • L-Citrulline→Improved Blood Lipid Profile

    no consistent effects observed on body weight, glucose, insulin, or lipid profiles

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified in abstract
  • L-Citrulline→Improved Flow-Mediated Dilation

    Four studies assessed endothelial function, two of which demonstrated significant improvements in flow-mediated dilation

    Effect
    Beneficial
    Effect size
    Small
    Dose
    not specified in abstract
  • L-Citrulline→Improved Insulin Levels

    no consistent effects observed on body weight, glucose, insulin, or lipid profiles

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified in abstract
  • L-Citrulline→Improved Muscle Strength

    Muscle function outcomes were investigated in two studies, suggesting improvements only when citrulline was combined with resistance training

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified in abstract
  • L-Citrulline→Reduced Arterial Stiffness

    Five studies examined arterial stiffness, with mixed findings on pulse wave velocity and augmentation index

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified in abstract
  • L-Citrulline→Reduced Body Weight

    no consistent effects observed on body weight, glucose, insulin, or lipid profiles

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified in abstract
  • L-Citrulline→Reduced Fasting Glucose

    no consistent effects observed on body weight, glucose, insulin, or lipid profiles

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified in abstract
  • L-Citrulline→Reduced Mean Arterial Pressure

    most showing reductions in systolic blood pressure and mean arterial pressure

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified in abstract
  • L-Citrulline→Reduced Systolic Blood Pressure

    Citrulline supplementation may offer benefits for blood pressure regulation (up to 9 mmHg SBP reduction in some studies) in hypertensive postmenopausal women

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified in abstract

Adverse Events Reported

  • L-Citrulline→Overall tolerability

    Across all studies, no adverse effects related to citrulline supplementation were reported.

    Finding
    Reported
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