Component

L-Citrulline plus tetrahydrobiopterin, study-specific combination

L-Citrulline plus tetrahydrobiopterin, study-specific combination. Species, exposure and limitations are retained in each linked claim.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Adding BH4 increased the reported walking-distance change to 28.15% only in the subgroup with baseline ADMA above 0.4 micromolar.

    L-Citrulline plus tetrahydrobiopterin, study-specific combination → Absolute claudication walking distance source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/39985883.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0007fe7b3fcc746e77c450f3aca50ca2834c78b84aa83977b3078ae05051ab9c", "start_char": 0, "end_char": 1888, "text_sha256": "0007fe7b3fcc746e77c450f3aca50ca2834c78b84aa83977b3078ae05051ab9c"}
    experimental_model
    Phase II double-blind placebo-controlled crossover trial
    exposure
    3 g citrulline twice daily for 12 weeks; additional BH4 0.45 g/day for two weeks in one arm
    limitations
    Preliminary trial; subgroup-dependent BH4 result and study-specific ADMA cutoff require confirmation; not a general supplement prescription.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human, 51 peripheral-artery-disease patients
    plain_language
    The cofactor combination result depended on the measured starting state.
    primary_references
    [citrulline-p39985883] Nutritional L-Citrulline and Tetrahydrobiopterin in Peripheral Artery Disease: A Phase II Randomized Trial (CIPER Study). (2025). https://pubmed.ncbi.nlm.nih.gov/39985883/ DOI: 10.1016/j.jacadv.2025.101590
    tissue_or_cell_type
    Absolute claudication distance and plasma biomarkers

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1217–1228

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phase II double-blind placebo-controlled crossover trial · source_derived_draft · unverified_draft

    ### citrulline-pad-bh4-subgroup Adding BH4 increased the reported walking-distance change to 28.15% only in the subgroup with baseline ADMA above 0.4 micromolar. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor combination result depended on the measured starting state. organism: Human, 51 peripheral-artery-disease patients tissue_or_cell_type: Absolute claudication distance and plasma biomarkers experimental_model: Phase II double-blind placebo-controlled crossover trial limitations: Preliminary trial; subgroup-dependent BH4 result and study-specific ADMA cutoff require confirmation; not a general supplement prescription. exposure: 3 g citrulline twice daily for 12 weeks; additional BH4 0.45 g/day for two weeks in one arm evidence_span: {"source_cache": "artifacts/citrulline-research/39985883.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0007fe7b3fcc746e77c450f3aca50ca2834c78b84aa83977b3078ae05051ab9c", "start_char": 0, "end_char": 1888, "text_sha256": "0007fe7b3fcc746e77c450f3aca50ca2834c78b84aa83977b3078ae05051ab9c"} [citrulline-p39985883] Nutritional L-Citrulline and Tetrahydrobiopterin in Peripheral Artery Disease: A Phase II Randomized Trial (CIPER Study). (2025). https://pubmed.ncbi.nlm.nih.gov/39985883/ DOI: 10.1016/j.jacadv.2025.101590
    Complete structured claim and evidence

  2. Combination treatment improved eNOS dimer ratios and NO production more than either single intervention.

    L-Citrulline plus tetrahydrobiopterin, study-specific combination → Pig pulmonary-artery eNOS dimer-to-monomer ratio source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/32073878.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f", "start_char": 0, "end_char": 1850, "text_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f"}
    experimental_model
    Controlled neonatal hypoxia and combination-treatment experiment
    exposure
    L-citrulline, sapropterin, or both during days 3-10 of hypoxia
    limitations
    Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Newborn pig
    plain_language
    The measured signaling machinery responded alongside the vascular outcome.
    primary_references
    [citrulline-p32073878] Combined l-citrulline and tetrahydrobiopterin therapy improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. (2020). https://pubmed.ncbi.nlm.nih.gov/32073878/ DOI: 10.1152/ajplung.00280.2019
    tissue_or_cell_type
    Pulmonary arteries and hemodynamics

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 827–838

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled neonatal hypoxia and combination-treatment experiment · source_derived_draft · unverified_draft

    ### citrulline-pig-combination-coupling Combination treatment improved eNOS dimer ratios and NO production more than either single intervention. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured signaling machinery responded alongside the vascular outcome. organism: Newborn pig tissue_or_cell_type: Pulmonary arteries and hemodynamics experimental_model: Controlled neonatal hypoxia and combination-treatment experiment limitations: Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans. exposure: L-citrulline, sapropterin, or both during days 3-10 of hypoxia evidence_span: {"source_cache": "artifacts/citrulline-research/32073878.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f", "start_char": 0, "end_char": 1850, "text_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f"} [citrulline-p32073878] Combined l-citrulline and tetrahydrobiopterin therapy improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. (2020). https://pubmed.ncbi.nlm.nih.gov/32073878/ DOI: 10.1152/ajplung.00280.2019
    Complete structured claim and evidence

  3. Combined citrulline and BH4 improved pulmonary vascular resistance more than either alone in hypoxic piglets.

    L-Citrulline plus tetrahydrobiopterin, study-specific combination → Pulmonary vascular resistance source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/32073878.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f", "start_char": 0, "end_char": 1850, "text_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f"}
    experimental_model
    Controlled neonatal hypoxia and combination-treatment experiment
    exposure
    L-citrulline, sapropterin, or both during days 3-10 of hypoxia
    limitations
    Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Newborn pig
    plain_language
    Both substrate supply and cofactor support mattered in this animal model.
    primary_references
    [citrulline-p32073878] Combined l-citrulline and tetrahydrobiopterin therapy improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. (2020). https://pubmed.ncbi.nlm.nih.gov/32073878/ DOI: 10.1152/ajplung.00280.2019
    tissue_or_cell_type
    Pulmonary arteries and hemodynamics

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 814–825

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled neonatal hypoxia and combination-treatment experiment · source_derived_draft · unverified_draft

    ### citrulline-pig-combination-pvr Combined citrulline and BH4 improved pulmonary vascular resistance more than either alone in hypoxic piglets. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both substrate supply and cofactor support mattered in this animal model. organism: Newborn pig tissue_or_cell_type: Pulmonary arteries and hemodynamics experimental_model: Controlled neonatal hypoxia and combination-treatment experiment limitations: Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans. exposure: L-citrulline, sapropterin, or both during days 3-10 of hypoxia evidence_span: {"source_cache": "artifacts/citrulline-research/32073878.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f", "start_char": 0, "end_char": 1850, "text_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f"} [citrulline-p32073878] Combined l-citrulline and tetrahydrobiopterin therapy improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. (2020). https://pubmed.ncbi.nlm.nih.gov/32073878/ DOI: 10.1152/ajplung.00280.2019
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards