L-Citrulline

evidence_span

{"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"}

experimental_model

Double-blind placebo-controlled crossover study

exposure

Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods

limitations

Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 20 healthy volunteers

plain_language

The substrate-to-inhibitor ratio changed; this does not mean ADMA itself was removed.

primary_references

[citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

tissue_or_cell_type

Plasma amino acids, urine NO markers and brachial FMD

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 879–890

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

### citrulline-adma-ratio At 3 g twice daily, the arginine/ADMA ratio rose from 186 to 278. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The substrate-to-inhibitor ratio changed; this does not mean ADMA itself was removed. organism: Human, 20 healthy volunteers tissue_or_cell_type: Plasma amino acids, urine NO markers and brachial FMD experimental_model: Double-blind placebo-controlled crossover study limitations: Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit. exposure: Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods evidence_span: {"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"} [citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

evidence_span

{"source_cache": "artifacts/citrulline-research/27648629.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7584e325856443da6067298d1c6ab31b95679839361f4a60adc5f7434944fb17", "start_char": 0, "end_char": 1848, "text_sha256": "7584e325856443da6067298d1c6ab31b95679839361f4a60adc5f7434944fb17"}

experimental_model

Randomized placebo crossover vascular trial

exposure

Fifteen-day L-citrulline and placebo periods

limitations

Small surrogate trial; abstract reports unusual FMD units, so only the dimensionless ratio is extracted.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 30 coronary-artery-disease patients

plain_language

A vascular-response ratio improved in this selected patient group.

primary_references

[citrulline-p27648629] The Assessment of short-term effect of L-Citrulline on endothelial function via FMD to NMD ratio in known CAD patients: A randomized, cross-over clinical trial (Clinical trial number: NCT02638727). (2017). https://pubmed.ncbi.nlm.nih.gov/27648629/ DOI: 10.1515/rjim-2016-0045

tissue_or_cell_type

Brachial FMD/NMD ratio

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1230–1241

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

### citrulline-cad-ratio The FMD/NMD ratio increased by 0.12 with citrulline versus 0.01 with placebo in the CAD trial. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vascular-response ratio improved in this selected patient group. organism: Human, 30 coronary-artery-disease patients tissue_or_cell_type: Brachial FMD/NMD ratio experimental_model: Randomized placebo crossover vascular trial limitations: Small surrogate trial; abstract reports unusual FMD units, so only the dimensionless ratio is extracted. exposure: Fifteen-day L-citrulline and placebo periods evidence_span: {"source_cache": "artifacts/citrulline-research/27648629.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7584e325856443da6067298d1c6ab31b95679839361f4a60adc5f7434944fb17", "start_char": 0, "end_char": 1848, "text_sha256": "7584e325856443da6067298d1c6ab31b95679839361f4a60adc5f7434944fb17"} [citrulline-p27648629] The Assessment of short-term effect of L-Citrulline on endothelial function via FMD to NMD ratio in known CAD patients: A randomized, cross-over clinical trial (Clinical trial number: NCT02638727). (2017). https://pubmed.ncbi.nlm.nih.gov/27648629/ DOI: 10.1515/rjim-2016-0045

evidence_span

{"source_cache": "artifacts/citrulline-research/17953788.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd", "start_char": 0, "end_char": 1603, "text_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd"}

experimental_model

Randomized-order oral dose-loading study

exposure

Separate 2, 5, 10 and 15 g citrulline loads

limitations

Small acute tolerance study; saturation was an interpretation, not directly localized or measured renal enzyme saturation.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, eight healthy fasting men

plain_language

More precursor did not yield a proportional arginine increase.

primary_references

[citrulline-p17953788] Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. (2008). https://pubmed.ncbi.nlm.nih.gov/17953788/ DOI: 10.1017/s0007114507841110

tissue_or_cell_type

Plasma amino acids and 24-hour urine

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 931–942

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized-order oral dose-loading study · source_derived_draft · unverified_draft

### citrulline-dose-disproportion At the largest doses, plasma citrulline accumulated while arginine rose less than expected. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: More precursor did not yield a proportional arginine increase. organism: Human, eight healthy fasting men tissue_or_cell_type: Plasma amino acids and 24-hour urine experimental_model: Randomized-order oral dose-loading study limitations: Small acute tolerance study; saturation was an interpretation, not directly localized or measured renal enzyme saturation. exposure: Separate 2, 5, 10 and 15 g citrulline loads evidence_span: {"source_cache": "artifacts/citrulline-research/17953788.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd", "start_char": 0, "end_char": 1603, "text_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd"} [citrulline-p17953788] Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. (2008). https://pubmed.ncbi.nlm.nih.gov/17953788/ DOI: 10.1017/s0007114507841110

evidence_span

{"source_cache": "artifacts/citrulline-research/21195829.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b85dfbc0993e9d8f01bdc021151650d6466c9204a7d7158e488ce66416e1df74", "start_char": 0, "end_char": 1897, "text_sha256": "b85dfbc0993e9d8f01bdc021151650d6466c9204a7d7158e488ce66416e1df74"}

experimental_model

Single-blind fixed-sequence placebo then active pilot

exposure

One month placebo followed by one month L-citrulline 1.5 g/day

limitations

Not a randomized-order crossover; expectation, time and sequence effects cannot be excluded; no direct PDE5-inhibitor comparison.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 24 men with mild erectile dysfunction

plain_language

An encouraging pilot finding needs stronger trial confirmation.

primary_references

[citrulline-p21195829] Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21195829/ DOI: 10.1016/j.urology.2010.08.028

tissue_or_cell_type

Erection hardness

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1243–1254

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind fixed-sequence placebo then active pilot · source_derived_draft · unverified_draft

### citrulline-erection-pilot Normal-range erection hardness was reported in 12/24 men during citrulline versus 2/24 during the preceding placebo month. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: An encouraging pilot finding needs stronger trial confirmation. organism: Human, 24 men with mild erectile dysfunction tissue_or_cell_type: Erection hardness experimental_model: Single-blind fixed-sequence placebo then active pilot limitations: Not a randomized-order crossover; expectation, time and sequence effects cannot be excluded; no direct PDE5-inhibitor comparison. exposure: One month placebo followed by one month L-citrulline 1.5 g/day evidence_span: {"source_cache": "artifacts/citrulline-research/21195829.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b85dfbc0993e9d8f01bdc021151650d6466c9204a7d7158e488ce66416e1df74", "start_char": 0, "end_char": 1897, "text_sha256": "b85dfbc0993e9d8f01bdc021151650d6466c9204a7d7158e488ce66416e1df74"} [citrulline-p21195829] Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21195829/ DOI: 10.1016/j.urology.2010.08.028

evidence_span

{"source_cache": "artifacts/citrulline-research/34882863.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3971162e4b915e3dadb6408a84cf3558526ee837e3446dd61c831f076f3fd901", "start_char": 0, "end_char": 1801, "text_sha256": "3971162e4b915e3dadb6408a84cf3558526ee837e3446dd61c831f076f3fd901"}

experimental_model

Six-hour human duodenal explant experiment

exposure

Control, hypoxia, inflammation and combined exposure

limitations

Short ex-vivo exposure cannot explain all low citrulline in prolonged critical illness; increased utilization remains a proposed explanation.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human biopsies from 25 selected patients

plain_language

Low circulating citrulline during illness cannot automatically be attributed to shut-down intestinal production.

primary_references

[citrulline-p34882863] Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation. (2022). https://pubmed.ncbi.nlm.nih.gov/34882863/ DOI: 10.1002/biof.1810

tissue_or_cell_type

Intestinal citrulline production

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1022–1033

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-hour human duodenal explant experiment · source_derived_draft · unverified_draft

### citrulline-explant-production-null Hypoxia and/or inflammation did not reduce citrulline production during the six-hour human explant experiment. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low circulating citrulline during illness cannot automatically be attributed to shut-down intestinal production. organism: Human biopsies from 25 selected patients tissue_or_cell_type: Intestinal citrulline production experimental_model: Six-hour human duodenal explant experiment limitations: Short ex-vivo exposure cannot explain all low citrulline in prolonged critical illness; increased utilization remains a proposed explanation. exposure: Control, hypoxia, inflammation and combined exposure evidence_span: {"source_cache": "artifacts/citrulline-research/34882863.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3971162e4b915e3dadb6408a84cf3558526ee837e3446dd61c831f076f3fd901", "start_char": 0, "end_char": 1801, "text_sha256": "3971162e4b915e3dadb6408a84cf3558526ee837e3446dd61c831f076f3fd901"} [citrulline-p34882863] Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation. (2022). https://pubmed.ncbi.nlm.nih.gov/34882863/ DOI: 10.1002/biof.1810

evidence_span

{"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"}

experimental_model

Double-blind placebo-controlled crossover study

exposure

Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods

limitations

Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 20 healthy volunteers

plain_language

Better precursor exposure did not produce a detectable improvement in this vascular endpoint.

primary_references

[citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

tissue_or_cell_type

Plasma amino acids, urine NO markers and brachial FMD

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 918–929

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

### citrulline-healthy-fmd-null No treatment improved FMD over baseline in the healthy-volunteer study. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Better precursor exposure did not produce a detectable improvement in this vascular endpoint. organism: Human, 20 healthy volunteers tissue_or_cell_type: Plasma amino acids, urine NO markers and brachial FMD experimental_model: Double-blind placebo-controlled crossover study limitations: Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit. exposure: Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods evidence_span: {"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"} [citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

evidence_span

{"source_cache": "artifacts/citrulline-research/17953788.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd", "start_char": 0, "end_char": 1603, "text_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd"}

experimental_model

Randomized-order oral dose-loading study

exposure

Separate 2, 5, 10 and 15 g citrulline loads

limitations

Small acute tolerance study; saturation was an interpretation, not directly localized or measured renal enzyme saturation.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, eight healthy fasting men

plain_language

The study did not show a growth-hormone or insulin boost.

primary_references

[citrulline-p17953788] Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. (2008). https://pubmed.ncbi.nlm.nih.gov/17953788/ DOI: 10.1017/s0007114507841110

tissue_or_cell_type

Plasma amino acids and 24-hour urine

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 957–968

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized-order oral dose-loading study · source_derived_draft · unverified_draft

### citrulline-hormone-null Plasma insulin and growth hormone were not affected by the oral citrulline loads. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study did not show a growth-hormone or insulin boost. organism: Human, eight healthy fasting men tissue_or_cell_type: Plasma amino acids and 24-hour urine experimental_model: Randomized-order oral dose-loading study limitations: Small acute tolerance study; saturation was an interpretation, not directly localized or measured renal enzyme saturation. exposure: Separate 2, 5, 10 and 15 g citrulline loads evidence_span: {"source_cache": "artifacts/citrulline-research/17953788.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd", "start_char": 0, "end_char": 1603, "text_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd"} [citrulline-p17953788] Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. (2008). https://pubmed.ncbi.nlm.nih.gov/17953788/ DOI: 10.1017/s0007114507841110

evidence_span

{"source_cache": "artifacts/citrulline-research/24972455.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "766ca1c6460f11fb78c1f94c02e42f53bf30269e7368cd62e0518e976e2b2995", "start_char": 0, "end_char": 1703, "text_sha256": "766ca1c6460f11fb78c1f94c02e42f53bf30269e7368cd62e0518e976e2b2995"}

experimental_model

Crossover isotope muscle-protein synthesis pilot

exposure

Oral citrulline versus a nonessential-amino-acid mixture over eight hours

limitations

Acute fractional synthesis is not long-term muscle growth; participants were not representative of all malnourished or older people.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, eight healthy adults after three days of low protein intake

plain_language

One muscle protein measure improved after a short low-protein diet.

primary_references

[citrulline-p24972455] Citrulline stimulates muscle protein synthesis in the post-absorptive state in healthy people fed a low-protein diet - A pilot study. (2015). https://pubmed.ncbi.nlm.nih.gov/24972455/ DOI: 10.1016/j.clnu.2014.04.019

tissue_or_cell_type

Mixed and mitochondrial muscle protein fractions

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1035–1046

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover isotope muscle-protein synthesis pilot · source_derived_draft · unverified_draft

### citrulline-low-protein-mps Mixed-muscle fractional synthesis was higher with citrulline than the comparator, 0.060 versus 0.049, P=0.03. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: One muscle protein measure improved after a short low-protein diet. organism: Human, eight healthy adults after three days of low protein intake tissue_or_cell_type: Mixed and mitochondrial muscle protein fractions experimental_model: Crossover isotope muscle-protein synthesis pilot limitations: Acute fractional synthesis is not long-term muscle growth; participants were not representative of all malnourished or older people. exposure: Oral citrulline versus a nonessential-amino-acid mixture over eight hours evidence_span: {"source_cache": "artifacts/citrulline-research/24972455.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "766ca1c6460f11fb78c1f94c02e42f53bf30269e7368cd62e0518e976e2b2995", "start_char": 0, "end_char": 1703, "text_sha256": "766ca1c6460f11fb78c1f94c02e42f53bf30269e7368cd62e0518e976e2b2995"} [citrulline-p24972455] Citrulline stimulates muscle protein synthesis in the post-absorptive state in healthy people fed a low-protein diet - A pilot study. (2015). https://pubmed.ncbi.nlm.nih.gov/24972455/ DOI: 10.1016/j.clnu.2014.04.019

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/citrulline-research/6776014.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6db6a42e66322b8ae26335a4f51284ede7691dcbb91e8cf7d7cd6671bd41b87d", "start_char": 0, "end_char": 1189, "text_sha256": "6db6a42e66322b8ae26335a4f51284ede7691dcbb91e8cf7d7cd6671bd41b87d"}

experimental_model

Oral amino-acid loading comparison

exposure

Separate diamino-acid and citrulline loads

limitations

Inherited transport disorder, not ordinary competition from mixed dietary protein; the study predates gene identification.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human LPI patients, heterozygotes and controls

plain_language

A different entry route can bypass this particular transport problem.

primary_references

[citrulline-p6776014] Intestinal absorption in lysinuric protein intolerance: impaired for diamino acids, normal for citrulline. (1980). https://pubmed.ncbi.nlm.nih.gov/6776014/ DOI: 10.1136/gut.21.6.519

tissue_or_cell_type

Intestinal amino-acid absorption inferred from plasma and urine

trigger_kind

machinery_impairment Imported condition classification; unverified.

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 840–851

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral amino-acid loading comparison · source_derived_draft · unverified_draft

### citrulline-lpi-citrulline-absorption Citrulline plasma increments after oral loads were similar in LPI homozygotes and controls, unlike diamino-acid increments. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different entry route can bypass this particular transport problem. organism: Human LPI patients, heterozygotes and controls tissue_or_cell_type: Intestinal amino-acid absorption inferred from plasma and urine experimental_model: Oral amino-acid loading comparison limitations: Inherited transport disorder, not ordinary competition from mixed dietary protein; the study predates gene identification. exposure: Separate diamino-acid and citrulline loads evidence_span: {"source_cache": "artifacts/citrulline-research/6776014.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6db6a42e66322b8ae26335a4f51284ede7691dcbb91e8cf7d7cd6671bd41b87d", "start_char": 0, "end_char": 1189, "text_sha256": "6db6a42e66322b8ae26335a4f51284ede7691dcbb91e8cf7d7cd6671bd41b87d"} [citrulline-p6776014] Intestinal absorption in lysinuric protein intolerance: impaired for diamino acids, normal for citrulline. (1980). https://pubmed.ncbi.nlm.nih.gov/6776014/ DOI: 10.1136/gut.21.6.519

evidence_span

{"source_cache": "artifacts/citrulline-research/6401349.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e98ad3132221fd0deae9dd89d6c14a4f6b010655656a6e0ea44a7c47f2ca1545", "start_char": 0, "end_char": 349, "text_sha256": "e98ad3132221fd0deae9dd89d6c14a4f6b010655656a6e0ea44a7c47f2ca1545"}

experimental_model

Clinical oral-intermediate comparison

exposure

Oral citrulline, arginine or ornithine

limitations

Brief indexed abstract; no trial size or dosing is inferred; not evidence that citrulline replaces lysine.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human lysinuric protein intolerance

plain_language

The alternative precursor improved downstream amino-acid availability in this disorder.

primary_references

[citrulline-p6401349] Oral administration of urea cycle intermediates in lysinuric protein intolerance: effect on plasma and urinary arginine and ornithine. (1983). https://pubmed.ncbi.nlm.nih.gov/6401349/ DOI: 10.1016/0026-0495(83)90154-3

tissue_or_cell_type

Plasma urea-cycle intermediates

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 853–864

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical oral-intermediate comparison · source_derived_draft · unverified_draft

### citrulline-lpi-precursor-response Oral citrulline raised plasma urea-cycle intermediates more than oral arginine or ornithine in the LPI report. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The alternative precursor improved downstream amino-acid availability in this disorder. organism: Human lysinuric protein intolerance tissue_or_cell_type: Plasma urea-cycle intermediates experimental_model: Clinical oral-intermediate comparison limitations: Brief indexed abstract; no trial size or dosing is inferred; not evidence that citrulline replaces lysine. exposure: Oral citrulline, arginine or ornithine evidence_span: {"source_cache": "artifacts/citrulline-research/6401349.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e98ad3132221fd0deae9dd89d6c14a4f6b010655656a6e0ea44a7c47f2ca1545", "start_char": 0, "end_char": 349, "text_sha256": "e98ad3132221fd0deae9dd89d6c14a4f6b010655656a6e0ea44a7c47f2ca1545"} [citrulline-p6401349] Oral administration of urea cycle intermediates in lysinuric protein intolerance: effect on plasma and urinary arginine and ornithine. (1983). https://pubmed.ncbi.nlm.nih.gov/6401349/ DOI: 10.1016/0026-0495(83)90154-3

evidence_span

{"source_cache": "artifacts/citrulline-research/39662304.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f26c60b31d2021fb82143a4780ab4437e58c18d1c482a0880fdc4321f224092", "start_char": 0, "end_char": 1816, "text_sha256": "3f26c60b31d2021fb82143a4780ab4437e58c18d1c482a0880fdc4321f224092"}

experimental_model

Randomized double-blind placebo-controlled crossover trial

exposure

5.3 g L-citrulline; or 5.3 g citrulline plus 2.7 g malate; or placebo 45 minutes pre-exercise

limitations

Acute low-to-moderate-volume protocol; not a universal finding for all doses, workouts or chronic use.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 43 trained adults including 21 women

plain_language

The pure amino acid did not produce a measurable advantage here.

primary_references

[citrulline-p39662304] Malate or Not? Acute Effects of L-Citrulline Versus Citrulline Malate on Neuromuscular Performance in Young, Trained Adults: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. (2025). https://pubmed.ncbi.nlm.nih.gov/39662304/ DOI: 10.1123/ijsnem.2024-0006

tissue_or_cell_type

Neuromuscular, ballistic and strength-endurance tests

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1178–1189

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

### citrulline-matched-pure-null Matched-dose L-citrulline did not improve maximal neuromuscular or ballistic performance versus placebo. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pure amino acid did not produce a measurable advantage here. organism: Human, 43 trained adults including 21 women tissue_or_cell_type: Neuromuscular, ballistic and strength-endurance tests experimental_model: Randomized double-blind placebo-controlled crossover trial limitations: Acute low-to-moderate-volume protocol; not a universal finding for all doses, workouts or chronic use. exposure: 5.3 g L-citrulline; or 5.3 g citrulline plus 2.7 g malate; or placebo 45 minutes pre-exercise evidence_span: {"source_cache": "artifacts/citrulline-research/39662304.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f26c60b31d2021fb82143a4780ab4437e58c18d1c482a0880fdc4321f224092", "start_char": 0, "end_char": 1816, "text_sha256": "3f26c60b31d2021fb82143a4780ab4437e58c18d1c482a0880fdc4321f224092"} [citrulline-p39662304] Malate or Not? Acute Effects of L-Citrulline Versus Citrulline Malate on Neuromuscular Performance in Young, Trained Adults: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. (2025). https://pubmed.ncbi.nlm.nih.gov/39662304/ DOI: 10.1123/ijsnem.2024-0006

evidence_span

{"source_cache": "artifacts/citrulline-research/24972455.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "766ca1c6460f11fb78c1f94c02e42f53bf30269e7368cd62e0518e976e2b2995", "start_char": 0, "end_char": 1703, "text_sha256": "766ca1c6460f11fb78c1f94c02e42f53bf30269e7368cd62e0518e976e2b2995"}

experimental_model

Crossover isotope muscle-protein synthesis pilot

exposure

Oral citrulline versus a nonessential-amino-acid mixture over eight hours

limitations

Acute fractional synthesis is not long-term muscle growth; participants were not representative of all malnourished or older people.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, eight healthy adults after three days of low protein intake

plain_language

The anabolic result did not apply to every protein compartment.

primary_references

[citrulline-p24972455] Citrulline stimulates muscle protein synthesis in the post-absorptive state in healthy people fed a low-protein diet - A pilot study. (2015). https://pubmed.ncbi.nlm.nih.gov/24972455/ DOI: 10.1016/j.clnu.2014.04.019

tissue_or_cell_type

Mixed and mitochondrial muscle protein fractions

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1048–1059

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover isotope muscle-protein synthesis pilot · source_derived_draft · unverified_draft

### citrulline-mitochondrial-mps-null Mitochondrial protein synthesis and whole-body protein turnover did not differ between treatments. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The anabolic result did not apply to every protein compartment. organism: Human, eight healthy adults after three days of low protein intake tissue_or_cell_type: Mixed and mitochondrial muscle protein fractions experimental_model: Crossover isotope muscle-protein synthesis pilot limitations: Acute fractional synthesis is not long-term muscle growth; participants were not representative of all malnourished or older people. exposure: Oral citrulline versus a nonessential-amino-acid mixture over eight hours evidence_span: {"source_cache": "artifacts/citrulline-research/24972455.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "766ca1c6460f11fb78c1f94c02e42f53bf30269e7368cd62e0518e976e2b2995", "start_char": 0, "end_char": 1703, "text_sha256": "766ca1c6460f11fb78c1f94c02e42f53bf30269e7368cd62e0518e976e2b2995"} [citrulline-p24972455] Citrulline stimulates muscle protein synthesis in the post-absorptive state in healthy people fed a low-protein diet - A pilot study. (2015). https://pubmed.ncbi.nlm.nih.gov/24972455/ DOI: 10.1016/j.clnu.2014.04.019

evidence_span

{"source_cache": "artifacts/citrulline-research/24824653.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c9cb88e6978c602b77415910ae94823f258788387d0623bfe89af339fed5ebb", "start_char": 0, "end_char": 1815, "text_sha256": "3c9cb88e6978c602b77415910ae94823f258788387d0623bfe89af339fed5ebb"}

experimental_model

Postexercise feeding and tracer study

exposure

15 g whey plus 10 g citrulline or nonessential amino acids; comparator 45 g whey

limitations

Different population, protein background and protein fraction from the low-protein pilot; no automatic claim of contradiction.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 21 men aged 65-80

plain_language

Citrulline did not substitute for a larger protein meal in this trial.

primary_references

[citrulline-p24824653] Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise. (2014). https://pubmed.ncbi.nlm.nih.gov/24824653/ DOI: 10.1152/ajpendo.00096.2014

tissue_or_cell_type

Rested and exercised skeletal muscle

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1061–1072

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Postexercise feeding and tracer study · source_derived_draft · unverified_draft

### citrulline-older-mps-null Adding citrulline to 15 g whey did not augment myofibrillar protein synthesis compared with the nonessential-amino-acid addition. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Citrulline did not substitute for a larger protein meal in this trial. organism: Human, 21 men aged 65-80 tissue_or_cell_type: Rested and exercised skeletal muscle experimental_model: Postexercise feeding and tracer study limitations: Different population, protein background and protein fraction from the low-protein pilot; no automatic claim of contradiction. exposure: 15 g whey plus 10 g citrulline or nonessential amino acids; comparator 45 g whey evidence_span: {"source_cache": "artifacts/citrulline-research/24824653.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c9cb88e6978c602b77415910ae94823f258788387d0623bfe89af339fed5ebb", "start_char": 0, "end_char": 1815, "text_sha256": "3c9cb88e6978c602b77415910ae94823f258788387d0623bfe89af339fed5ebb"} [citrulline-p24824653] Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise. (2014). https://pubmed.ncbi.nlm.nih.gov/24824653/ DOI: 10.1152/ajpendo.00096.2014

evidence_span

{"source_cache": "artifacts/citrulline-research/24824653.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c9cb88e6978c602b77415910ae94823f258788387d0623bfe89af339fed5ebb", "start_char": 0, "end_char": 1815, "text_sha256": "3c9cb88e6978c602b77415910ae94823f258788387d0623bfe89af339fed5ebb"}

experimental_model

Postexercise feeding and tracer study

exposure

15 g whey plus 10 g citrulline or nonessential amino acids; comparator 45 g whey

limitations

Different population, protein background and protein fraction from the low-protein pilot; no automatic claim of contradiction.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 21 men aged 65-80

plain_language

Higher blood arginine was not enough to improve measured muscle perfusion.

primary_references

[citrulline-p24824653] Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise. (2014). https://pubmed.ncbi.nlm.nih.gov/24824653/ DOI: 10.1152/ajpendo.00096.2014

tissue_or_cell_type

Rested and exercised skeletal muscle

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1074–1085

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Postexercise feeding and tracer study · source_derived_draft · unverified_draft

### citrulline-older-perfusion-null Despite higher arginine, blood flow and muscle microvascular perfusion did not differ between treatments. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher blood arginine was not enough to improve measured muscle perfusion. organism: Human, 21 men aged 65-80 tissue_or_cell_type: Rested and exercised skeletal muscle experimental_model: Postexercise feeding and tracer study limitations: Different population, protein background and protein fraction from the low-protein pilot; no automatic claim of contradiction. exposure: 15 g whey plus 10 g citrulline or nonessential amino acids; comparator 45 g whey evidence_span: {"source_cache": "artifacts/citrulline-research/24824653.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c9cb88e6978c602b77415910ae94823f258788387d0623bfe89af339fed5ebb", "start_char": 0, "end_char": 1815, "text_sha256": "3c9cb88e6978c602b77415910ae94823f258788387d0623bfe89af339fed5ebb"} [citrulline-p24824653] Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise. (2014). https://pubmed.ncbi.nlm.nih.gov/24824653/ DOI: 10.1152/ajpendo.00096.2014

evidence_span

{"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"}

experimental_model

Double-blind placebo-controlled crossover study

exposure

Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods

limitations

Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 20 healthy volunteers

plain_language

Taking the precursor can raise circulating arginine efficiently.

primary_references

[citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

tissue_or_cell_type

Plasma amino acids, urine NO markers and brachial FMD

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 866–877

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

### citrulline-oral-arginine Oral citrulline increased plasma arginine AUC and peak concentration dose-dependently, more effectively than the tested oral arginine regimens. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Taking the precursor can raise circulating arginine efficiently. organism: Human, 20 healthy volunteers tissue_or_cell_type: Plasma amino acids, urine NO markers and brachial FMD experimental_model: Double-blind placebo-controlled crossover study limitations: Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit. exposure: Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods evidence_span: {"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"} [citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

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

A patient-relevant walking endpoint improved in this preliminary PAD trial.

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 1204–1215

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-walking Walking-distance change was 20.11% with citrulline versus 5.73% with placebo, P=0.011. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A patient-relevant walking endpoint improved in this preliminary PAD trial. 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

evidence_span

{"source_cache": "artifacts/citrulline-research/38825026.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a41a36f1d4539b1bb87cbfbd145f54655183855c1a4ad0061589bee0c13df062", "start_char": 0, "end_char": 1404, "text_sha256": "a41a36f1d4539b1bb87cbfbd145f54655183855c1a4ad0061589bee0c13df062"}

experimental_model

Controlled infection experiment with oral or intravenous supplementation

exposure

Citrulline 1 g/kg followed by Staphylococcus epidermidis inoculation; 14-hour monitoring

limitations

Preclinical high-exposure neonatal infection model; does not establish harm from usual adult supplementation or benefit in human sepsis.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Preterm pigs; related cord-blood experiments

plain_language

Effects on immunity and timing can matter beyond the NO pathway.

primary_references

[citrulline-p38825026] Citrulline supplementation exacerbates sepsis severity in infected preterm piglets via early induced immunosuppression. (2024). https://pubmed.ncbi.nlm.nih.gov/38825026/ DOI: 10.1016/j.jnutbio.2024.109674

tissue_or_cell_type

Bacterial load, inflammation and survival

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1269–1280

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled infection experiment with oral or intravenous supplementation · source_derived_draft · unverified_draft

### citrulline-preterm-sepsis-burden Both oral and intravenous citrulline groups showed increased bacterial burden and inflammation. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Effects on immunity and timing can matter beyond the NO pathway. organism: Preterm pigs; related cord-blood experiments tissue_or_cell_type: Bacterial load, inflammation and survival experimental_model: Controlled infection experiment with oral or intravenous supplementation limitations: Preclinical high-exposure neonatal infection model; does not establish harm from usual adult supplementation or benefit in human sepsis. exposure: Citrulline 1 g/kg followed by Staphylococcus epidermidis inoculation; 14-hour monitoring evidence_span: {"source_cache": "artifacts/citrulline-research/38825026.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a41a36f1d4539b1bb87cbfbd145f54655183855c1a4ad0061589bee0c13df062", "start_char": 0, "end_char": 1404, "text_sha256": "a41a36f1d4539b1bb87cbfbd145f54655183855c1a4ad0061589bee0c13df062"} [citrulline-p38825026] Citrulline supplementation exacerbates sepsis severity in infected preterm piglets via early induced immunosuppression. (2024). https://pubmed.ncbi.nlm.nih.gov/38825026/ DOI: 10.1016/j.jnutbio.2024.109674

evidence_span

{"source_cache": "artifacts/citrulline-research/38825026.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a41a36f1d4539b1bb87cbfbd145f54655183855c1a4ad0061589bee0c13df062", "start_char": 0, "end_char": 1404, "text_sha256": "a41a36f1d4539b1bb87cbfbd145f54655183855c1a4ad0061589bee0c13df062"}

experimental_model

Controlled infection experiment with oral or intravenous supplementation

exposure

Citrulline 1 g/kg followed by Staphylococcus epidermidis inoculation; 14-hour monitoring

limitations

Preclinical high-exposure neonatal infection model; does not establish harm from usual adult supplementation or benefit in human sepsis.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Preterm pigs; related cord-blood experiments

plain_language

Correcting a presumed precursor shortage did not improve this infection model.

primary_references

[citrulline-p38825026] Citrulline supplementation exacerbates sepsis severity in infected preterm piglets via early induced immunosuppression. (2024). https://pubmed.ncbi.nlm.nih.gov/38825026/ DOI: 10.1016/j.jnutbio.2024.109674

tissue_or_cell_type

Bacterial load, inflammation and survival

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1256–1267

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled infection experiment with oral or intravenous supplementation · source_derived_draft · unverified_draft

### citrulline-preterm-sepsis-mortality Oral citrulline increased mortality in infected preterm pigs; intravenous exposure did not significantly change mortality. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting a presumed precursor shortage did not improve this infection model. organism: Preterm pigs; related cord-blood experiments tissue_or_cell_type: Bacterial load, inflammation and survival experimental_model: Controlled infection experiment with oral or intravenous supplementation limitations: Preclinical high-exposure neonatal infection model; does not establish harm from usual adult supplementation or benefit in human sepsis. exposure: Citrulline 1 g/kg followed by Staphylococcus epidermidis inoculation; 14-hour monitoring evidence_span: {"source_cache": "artifacts/citrulline-research/38825026.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a41a36f1d4539b1bb87cbfbd145f54655183855c1a4ad0061589bee0c13df062", "start_char": 0, "end_char": 1404, "text_sha256": "a41a36f1d4539b1bb87cbfbd145f54655183855c1a4ad0061589bee0c13df062"} [citrulline-p38825026] Citrulline supplementation exacerbates sepsis severity in infected preterm piglets via early induced immunosuppression. (2024). https://pubmed.ncbi.nlm.nih.gov/38825026/ DOI: 10.1016/j.jnutbio.2024.109674

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/citrulline-research/10791996.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80c58ac3892fcee1c04da2c05c0005b4b40e6c3479127a3da3528e46162c7f49", "start_char": 0, "end_char": 1285, "text_sha256": "80c58ac3892fcee1c04da2c05c0005b4b40e6c3479127a3da3528e46162c7f49"}

experimental_model

Stable-isotope kinetic study around hemodialysis

exposure

Two pre- and two postdialysis tracer studies

limitations

Whole-body flux does not locate the compensating tissues; elevated plasma concentration is not evidence of adequate function in every compartment.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, six end-stage renal disease patients

plain_language

Loss of kidney function did not abolish all arginine synthesis in this small study.

primary_references

[citrulline-p10791996] Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients. (2000). https://pubmed.ncbi.nlm.nih.gov/10791996/ DOI: 10.1172/jci7199

tissue_or_cell_type

Whole-body arginine and NO metabolism

trigger_kind

biomarker_context Imported condition classification; unverified.

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1009–1020

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope kinetic study around hemodialysis · source_derived_draft · unverified_draft

### citrulline-renal-arginine-preserved Despite reduced renal function, whole-body de novo arginine synthesis appeared preserved in the ESRD patients. Condition category: biomarker_context nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of kidney function did not abolish all arginine synthesis in this small study. organism: Human, six end-stage renal disease patients tissue_or_cell_type: Whole-body arginine and NO metabolism experimental_model: Stable-isotope kinetic study around hemodialysis limitations: Whole-body flux does not locate the compensating tissues; elevated plasma concentration is not evidence of adequate function in every compartment. exposure: Two pre- and two postdialysis tracer studies evidence_span: {"source_cache": "artifacts/citrulline-research/10791996.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80c58ac3892fcee1c04da2c05c0005b4b40e6c3479127a3da3528e46162c7f49", "start_char": 0, "end_char": 1285, "text_sha256": "80c58ac3892fcee1c04da2c05c0005b4b40e6c3479127a3da3528e46162c7f49"} [citrulline-p10791996] Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients. (2000). https://pubmed.ncbi.nlm.nih.gov/10791996/ DOI: 10.1172/jci7199

evidence_span

{"source_cache": "artifacts/citrulline-research/25332337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d517656dd9033a9df73e29b10d07fdccbc7c369155450ba662fe006d045cf4d0", "start_char": 0, "end_char": 1788, "text_sha256": "d517656dd9033a9df73e29b10d07fdccbc7c369155450ba662fe006d045cf4d0"}

experimental_model

Stable-isotope whole-body and renal balance study

exposure

Perioperative intravenous alanyl-glutamine 0.5 g/kg/day

limitations

Small perioperative study; the reported doubling versus previous studies was not a concurrent randomized control comparison.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, seven surgical patients

plain_language

The kidney is a major conversion site, but it is not the only possible site.

primary_references

[citrulline-p25332337] Intravenous glutamine supplementation enhances renal de novo arginine synthesis in humans: a stable isotope study. (2014). https://pubmed.ncbi.nlm.nih.gov/25332337/ DOI: 10.3945/ajcn.113.081547

tissue_or_cell_type

Intestinal-renal amino-acid axis

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 450–461

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope whole-body and renal balance study · source_derived_draft · unverified_draft

### citrulline-renal-conversion The kidneys accounted for 75% of whole-body arginine production from citrulline in the isotope study. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney is a major conversion site, but it is not the only possible site. organism: Human, seven surgical patients tissue_or_cell_type: Intestinal-renal amino-acid axis experimental_model: Stable-isotope whole-body and renal balance study limitations: Small perioperative study; the reported doubling versus previous studies was not a concurrent randomized control comparison. exposure: Perioperative intravenous alanyl-glutamine 0.5 g/kg/day evidence_span: {"source_cache": "artifacts/citrulline-research/25332337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d517656dd9033a9df73e29b10d07fdccbc7c369155450ba662fe006d045cf4d0", "start_char": 0, "end_char": 1788, "text_sha256": "d517656dd9033a9df73e29b10d07fdccbc7c369155450ba662fe006d045cf4d0"} [citrulline-p25332337] Intravenous glutamine supplementation enhances renal de novo arginine synthesis in humans: a stable isotope study. (2014). https://pubmed.ncbi.nlm.nih.gov/25332337/ DOI: 10.3945/ajcn.113.081547

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/citrulline-research/10791996.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80c58ac3892fcee1c04da2c05c0005b4b40e6c3479127a3da3528e46162c7f49", "start_char": 0, "end_char": 1285, "text_sha256": "80c58ac3892fcee1c04da2c05c0005b4b40e6c3479127a3da3528e46162c7f49"}

experimental_model

Stable-isotope kinetic study around hemodialysis

exposure

Two pre- and two postdialysis tracer studies

limitations

Whole-body flux does not locate the compensating tissues; elevated plasma concentration is not evidence of adequate function in every compartment.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, six end-stage renal disease patients

plain_language

A high value can coexist with severe kidney disease.

primary_references

[citrulline-p10791996] Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients. (2000). https://pubmed.ncbi.nlm.nih.gov/10791996/ DOI: 10.1172/jci7199

tissue_or_cell_type

Whole-body arginine and NO metabolism

trigger_kind

biomarker_context Imported condition classification; unverified.

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 996–1007

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope kinetic study around hemodialysis · source_derived_draft · unverified_draft

### citrulline-renal-high-citrulline ESRD patients had elevated plasma citrulline and citrulline flux compared with healthy adults. Condition category: biomarker_context nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A high value can coexist with severe kidney disease. organism: Human, six end-stage renal disease patients tissue_or_cell_type: Whole-body arginine and NO metabolism experimental_model: Stable-isotope kinetic study around hemodialysis limitations: Whole-body flux does not locate the compensating tissues; elevated plasma concentration is not evidence of adequate function in every compartment. exposure: Two pre- and two postdialysis tracer studies evidence_span: {"source_cache": "artifacts/citrulline-research/10791996.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "80c58ac3892fcee1c04da2c05c0005b4b40e6c3479127a3da3528e46162c7f49", "start_char": 0, "end_char": 1285, "text_sha256": "80c58ac3892fcee1c04da2c05c0005b4b40e6c3479127a3da3528e46162c7f49"} [citrulline-p10791996] Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients. (2000). https://pubmed.ncbi.nlm.nih.gov/10791996/ DOI: 10.1172/jci7199

evidence_span

{"source_cache": "artifacts/citrulline-research/30642738.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d8869660890cdf77bcc2056b8871bc7be2b4828791a4681c87657a8efe42737", "start_char": 0, "end_char": 2343, "text_sha256": "0d8869660890cdf77bcc2056b8871bc7be2b4828791a4681c87657a8efe42737"}

experimental_model

Double-blind crossover isotope study

exposure

0.18 g/kg/day citrulline for seven days versus isonitrogenous placebo

limitations

Near-normal nutritional status long after surgery; exploratory low-baseline subgroups were too small for a treatment rule.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, nine adults with stable nonmalignant short-bowel syndrome

plain_language

The oral precursor reached blood and increased downstream arginine.

primary_references

[citrulline-p30642738] Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study. (2019). https://pubmed.ncbi.nlm.nih.gov/30642738/ DOI: 10.1016/j.clnu.2018.12.030

tissue_or_cell_type

Whole-body protein metabolism

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1087–1098

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind crossover isotope study · source_derived_draft · unverified_draft

### citrulline-sbs-exposure Citrulline supplementation increased plasma citrulline seventeenfold and arginine threefold in the SBS trial. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The oral precursor reached blood and increased downstream arginine. organism: Human, nine adults with stable nonmalignant short-bowel syndrome tissue_or_cell_type: Whole-body protein metabolism experimental_model: Double-blind crossover isotope study limitations: Near-normal nutritional status long after surgery; exploratory low-baseline subgroups were too small for a treatment rule. exposure: 0.18 g/kg/day citrulline for seven days versus isonitrogenous placebo evidence_span: {"source_cache": "artifacts/citrulline-research/30642738.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d8869660890cdf77bcc2056b8871bc7be2b4828791a4681c87657a8efe42737", "start_char": 0, "end_char": 2343, "text_sha256": "0d8869660890cdf77bcc2056b8871bc7be2b4828791a4681c87657a8efe42737"} [citrulline-p30642738] Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study. (2019). https://pubmed.ncbi.nlm.nih.gov/30642738/ DOI: 10.1016/j.clnu.2018.12.030

evidence_span

{"source_cache": "artifacts/citrulline-research/30642738.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d8869660890cdf77bcc2056b8871bc7be2b4828791a4681c87657a8efe42737", "start_char": 0, "end_char": 2343, "text_sha256": "0d8869660890cdf77bcc2056b8871bc7be2b4828791a4681c87657a8efe42737"}

experimental_model

Double-blind crossover isotope study

exposure

0.18 g/kg/day citrulline for seven days versus isonitrogenous placebo

limitations

Near-normal nutritional status long after surgery; exploratory low-baseline subgroups were too small for a treatment rule.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, nine adults with stable nonmalignant short-bowel syndrome

plain_language

Higher exposure did not establish an overall anabolic benefit.

primary_references

[citrulline-p30642738] Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study. (2019). https://pubmed.ncbi.nlm.nih.gov/30642738/ DOI: 10.1016/j.clnu.2018.12.030

tissue_or_cell_type

Whole-body protein metabolism

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1100–1111

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind crossover isotope study · source_derived_draft · unverified_draft

### citrulline-sbs-protein-null Whole-body synthesis estimated by nonoxidative leucine disposal did not significantly change in the overall SBS group. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher exposure did not establish an overall anabolic benefit. organism: Human, nine adults with stable nonmalignant short-bowel syndrome tissue_or_cell_type: Whole-body protein metabolism experimental_model: Double-blind crossover isotope study limitations: Near-normal nutritional status long after surgery; exploratory low-baseline subgroups were too small for a treatment rule. exposure: 0.18 g/kg/day citrulline for seven days versus isonitrogenous placebo evidence_span: {"source_cache": "artifacts/citrulline-research/30642738.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d8869660890cdf77bcc2056b8871bc7be2b4828791a4681c87657a8efe42737", "start_char": 0, "end_char": 2343, "text_sha256": "0d8869660890cdf77bcc2056b8871bc7be2b4828791a4681c87657a8efe42737"} [citrulline-p30642738] Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study. (2019). https://pubmed.ncbi.nlm.nih.gov/30642738/ DOI: 10.1016/j.clnu.2018.12.030

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/citrulline-research/11113071.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2470fc206e5913038da9bb8d7a38677533224bd369ccd02563cefe760727246", "start_char": 0, "end_char": 2196, "text_sha256": "e2470fc206e5913038da9bb8d7a38677533224bd369ccd02563cefe760727246"}

experimental_model

Observational diagnostic study after intestinal adaptation

exposure

At least two years after final bowel reconstruction

limitations

The 20 micromolar classifier belongs to this cohort and indication, not a universal dietary deficiency cutoff.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 57 adults with short-bowel syndrome and 51 controls

plain_language

A low value can mark reduced intestinal production rather than low dietary intake.

primary_references

[citrulline-p11113071] Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. (2000). https://pubmed.ncbi.nlm.nih.gov/11113071/ DOI: 10.1053/gast.2000.20227

tissue_or_cell_type

Postabsorptive blood and intestinal absorptive function

trigger_kind

biomarker_context Imported condition classification; unverified.

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 970–981

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Observational diagnostic study after intestinal adaptation · source_derived_draft · unverified_draft

### citrulline-short-bowel-low Mean plasma citrulline was 20 ± 13 micromolar in short-bowel patients versus 40 ± 10 in controls. Condition category: biomarker_context nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low value can mark reduced intestinal production rather than low dietary intake. organism: Human, 57 adults with short-bowel syndrome and 51 controls tissue_or_cell_type: Postabsorptive blood and intestinal absorptive function experimental_model: Observational diagnostic study after intestinal adaptation limitations: The 20 micromolar classifier belongs to this cohort and indication, not a universal dietary deficiency cutoff. exposure: At least two years after final bowel reconstruction evidence_span: {"source_cache": "artifacts/citrulline-research/11113071.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2470fc206e5913038da9bb8d7a38677533224bd369ccd02563cefe760727246", "start_char": 0, "end_char": 2196, "text_sha256": "e2470fc206e5913038da9bb8d7a38677533224bd369ccd02563cefe760727246"} [citrulline-p11113071] Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. (2000). https://pubmed.ncbi.nlm.nih.gov/11113071/ DOI: 10.1053/gast.2000.20227

evidence_span

{"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"}

experimental_model

Double-blind placebo-controlled crossover study

exposure

Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods

limitations

Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 20 healthy volunteers

plain_language

A downstream signaling marker increased.

primary_references

[citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

tissue_or_cell_type

Plasma amino acids, urine NO markers and brachial FMD

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 892–903

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

### citrulline-urine-cgmp The highest citrulline regimen increased urinary cGMP from 38 to 50 nmol/mmol creatinine. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A downstream signaling marker increased. organism: Human, 20 healthy volunteers tissue_or_cell_type: Plasma amino acids, urine NO markers and brachial FMD experimental_model: Double-blind placebo-controlled crossover study limitations: Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit. exposure: Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods evidence_span: {"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"} [citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

evidence_span

{"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"}

experimental_model

Double-blind placebo-controlled crossover study

exposure

Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods

limitations

Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 20 healthy volunteers

plain_language

Another NO-related marker changed.

primary_references

[citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

tissue_or_cell_type

Plasma amino acids, urine NO markers and brachial FMD

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 905–916

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

### citrulline-urine-nitrate The highest regimen increased urinary nitrate from 92 to 125 micromol/mmol creatinine. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Another NO-related marker changed. organism: Human, 20 healthy volunteers tissue_or_cell_type: Plasma amino acids, urine NO markers and brachial FMD experimental_model: Double-blind placebo-controlled crossover study limitations: Small short trial; NO-related urine markers do not establish a clinically meaningful vascular benefit. exposure: Citrulline 0.75, 1.5 or 3 g twice daily versus arginine formulations; one-week periods evidence_span: {"source_cache": "artifacts/citrulline-research/17662090.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b", "start_char": 0, "end_char": 1980, "text_sha256": "32e6ddf6d263120576f0f73c7fe3dd104904f3c0ba0a1c3f69cdca5751c4fa3b"} [citrulline-p17662090] Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/17662090/ DOI: 10.1111/j.1365-2125.2007.02990.x

evidence_span

{"source_cache": "artifacts/citrulline-research/17953788.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd", "start_char": 0, "end_char": 1603, "text_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd"}

experimental_model

Randomized-order oral dose-loading study

exposure

Separate 2, 5, 10 and 15 g citrulline loads

limitations

Small acute tolerance study; saturation was an interpretation, not directly localized or measured renal enzyme saturation.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, eight healthy fasting men

plain_language

Most of the dose was not simply lost unchanged in urine.

primary_references

[citrulline-p17953788] Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. (2008). https://pubmed.ncbi.nlm.nih.gov/17953788/ DOI: 10.1017/s0007114507841110

tissue_or_cell_type

Plasma amino acids and 24-hour urine

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 944–955

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized-order oral dose-loading study · source_derived_draft · unverified_draft

### citrulline-urine-retention Less than 5% of administered citrulline was excreted in urine, even at the higher tested doses. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Most of the dose was not simply lost unchanged in urine. organism: Human, eight healthy fasting men tissue_or_cell_type: Plasma amino acids and 24-hour urine experimental_model: Randomized-order oral dose-loading study limitations: Small acute tolerance study; saturation was an interpretation, not directly localized or measured renal enzyme saturation. exposure: Separate 2, 5, 10 and 15 g citrulline loads evidence_span: {"source_cache": "artifacts/citrulline-research/17953788.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd", "start_char": 0, "end_char": 1603, "text_sha256": "b57ecb5b3484e857904f38ae7c5d5eea51177e2e0a9a9c15ba5f81c2200a11bd"} [citrulline-p17953788] Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. (2008). https://pubmed.ncbi.nlm.nih.gov/17953788/ DOI: 10.1017/s0007114507841110

evidence_span

{"source_cache": "artifacts/citrulline-research/25332337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d517656dd9033a9df73e29b10d07fdccbc7c369155450ba662fe006d045cf4d0", "start_char": 0, "end_char": 1788, "text_sha256": "d517656dd9033a9df73e29b10d07fdccbc7c369155450ba662fe006d045cf4d0"}

experimental_model

Stable-isotope whole-body and renal balance study

exposure

Perioperative intravenous alanyl-glutamine 0.5 g/kg/day

limitations

Small perioperative study; the reported doubling versus previous studies was not a concurrent randomized control comparison.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, seven surgical patients

plain_language

Glutamine supplied much of the precursor carbon in this experimental setting.

primary_references

[citrulline-p25332337] Intravenous glutamine supplementation enhances renal de novo arginine synthesis in humans: a stable isotope study. (2014). https://pubmed.ncbi.nlm.nih.gov/25332337/ DOI: 10.3945/ajcn.113.081547

tissue_or_cell_type

Intestinal-renal amino-acid axis

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 437–448

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope whole-body and renal balance study · source_derived_draft · unverified_draft

### citrulline-glutamine-source In glutamine-supplemented surgical patients, 91% of total citrulline turnover was attributed to glutamine. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutamine supplied much of the precursor carbon in this experimental setting. organism: Human, seven surgical patients tissue_or_cell_type: Intestinal-renal amino-acid axis experimental_model: Stable-isotope whole-body and renal balance study limitations: Small perioperative study; the reported doubling versus previous studies was not a concurrent randomized control comparison. exposure: Perioperative intravenous alanyl-glutamine 0.5 g/kg/day evidence_span: {"source_cache": "artifacts/citrulline-research/25332337.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d517656dd9033a9df73e29b10d07fdccbc7c369155450ba662fe006d045cf4d0", "start_char": 0, "end_char": 1788, "text_sha256": "d517656dd9033a9df73e29b10d07fdccbc7c369155450ba662fe006d045cf4d0"} [citrulline-p25332337] Intravenous glutamine supplementation enhances renal de novo arginine synthesis in humans: a stable isotope study. (2014). https://pubmed.ncbi.nlm.nih.gov/25332337/ DOI: 10.3945/ajcn.113.081547

evidence_span

{"source_cache": "artifacts/citrulline-research/10608822.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1600b193cc63f30b204285729710bb81f34bc2918a8ca7f97aa97bc4acd998fd", "start_char": 0, "end_char": 2100, "text_sha256": "1600b193cc63f30b204285729710bb81f34bc2918a8ca7f97aa97bc4acd998fd"}

experimental_model

Purified recombinant enzyme activity and cofactor analysis

exposure

Arginine substrate; BH4, FAD, FMN, heme, iron and zinc measurements

limitations

Biochemical cofactor findings do not show that extra dietary cofactors increase NO in healthy people.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human NOS3 expressed in yeast

plain_language

Citrulline is also produced when the nitric-oxide pathway uses arginine.

primary_references

[citrulline-p10608822] Characterization of recombinant human endothelial nitric-oxide synthase purified from the yeast Pichia pastoris. (1999). https://pubmed.ncbi.nlm.nih.gov/10608822/ DOI: 10.1074/jbc.274.53.37658

tissue_or_cell_type

Endothelial NOS enzyme preparation

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 502–513

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant enzyme activity and cofactor analysis · source_derived_draft · unverified_draft

### citrulline-nos-citrulline Purified human eNOS converted arginine in an assay measuring citrulline formation, with an arginine Km of 3.9 micromolar. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Citrulline is also produced when the nitric-oxide pathway uses arginine. organism: Human NOS3 expressed in yeast tissue_or_cell_type: Endothelial NOS enzyme preparation experimental_model: Purified recombinant enzyme activity and cofactor analysis limitations: Biochemical cofactor findings do not show that extra dietary cofactors increase NO in healthy people. exposure: Arginine substrate; BH4, FAD, FMN, heme, iron and zinc measurements evidence_span: {"source_cache": "artifacts/citrulline-research/10608822.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1600b193cc63f30b204285729710bb81f34bc2918a8ca7f97aa97bc4acd998fd", "start_char": 0, "end_char": 2100, "text_sha256": "1600b193cc63f30b204285729710bb81f34bc2918a8ca7f97aa97bc4acd998fd"} [citrulline-p10608822] Characterization of recombinant human endothelial nitric-oxide synthase purified from the yeast Pichia pastoris. (1999). https://pubmed.ncbi.nlm.nih.gov/10608822/ DOI: 10.1074/jbc.274.53.37658

evidence_span

{"source_cache": "artifacts/citrulline-research/38940639.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eca9d57812cf3d8efe7c0beb62b9b364cc25e1aeca647c95e4abf0fd9eb8365", "start_char": 194, "end_char": 364, "text_sha256": "c5ddbcd5c91cfcdc72d6e556c77228f8ecd6c25ebaa3c25fd9617f6baa145692"}

experimental_model

Recombinant enzyme site-directed mutagenesis and kinetic assays

exposure

Ornithine and carbamoyl phosphate; active-site and remote variants

limitations

Recombinant mutation experiments; do not equate altered enzyme function with a dietary shortage.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human OTC

plain_language

Citrulline is built from ornithine and a nitrogen-containing carbamoyl group.

primary_references

[citrulline-p38940639] Revisiting the Roles of Catalytic Residues in Human Ornithine Transcarbamylase. (2024). https://pubmed.ncbi.nlm.nih.gov/38940639/ DOI: 10.1021/acs.biochem.4c00206

tissue_or_cell_type

Mitochondrial urea-cycle enzyme

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 203–214

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme site-directed mutagenesis and kinetic assays · source_derived_draft · unverified_draft

### citrulline-otc-citrulline Human OTC converts ornithine and carbamoyl phosphate into citrulline, releasing inorganic phosphate. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Citrulline is built from ornithine and a nitrogen-containing carbamoyl group. organism: Human OTC tissue_or_cell_type: Mitochondrial urea-cycle enzyme experimental_model: Recombinant enzyme site-directed mutagenesis and kinetic assays limitations: Recombinant mutation experiments; do not equate altered enzyme function with a dietary shortage. exposure: Ornithine and carbamoyl phosphate; active-site and remote variants evidence_span: {"source_cache": "artifacts/citrulline-research/38940639.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eca9d57812cf3d8efe7c0beb62b9b364cc25e1aeca647c95e4abf0fd9eb8365", "start_char": 194, "end_char": 364, "text_sha256": "c5ddbcd5c91cfcdc72d6e556c77228f8ecd6c25ebaa3c25fd9617f6baa145692"} [citrulline-p38940639] Revisiting the Roles of Catalytic Residues in Human Ornithine Transcarbamylase. (2024). https://pubmed.ncbi.nlm.nih.gov/38940639/ DOI: 10.1021/acs.biochem.4c00206

evidence_access

Primary abstract

experimental_model

NOS activity measured by nitrite or citrulline production; species not specified in accessed abstract.

limitations

Isolated-preparation potency does not quantify inhibition after an oral sulfate dose.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

An arginine-related compound can inhibit the enzyme rather than supply its product.

primary_references

Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 220–226

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · NOS activity measured by nitrite or citrulline production; species not specified in accessed abstract. · source_derived_draft · unverified_draft

## agmatine-sulfate-nos1-inhibition An arginine-related compound can inhibit the enzyme rather than supply its product. Agmatine competitively inhibited the brain-derived NOS I preparation with approximate Ki 660 micromolar and was not an NO precursor. Model: NOS activity measured by nitrite or citrulline production; species not specified in accessed abstract. Limitations: Isolated-preparation potency does not quantify inhibition after an oral sulfate dose. Evidence access: Primary abstract Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

evidence_access

Primary abstract

experimental_model

Macrophage NOS preparation; enzymatic activity assay.

limitations

This is not a universal inflammatory-cell response or a human concentration target.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

NOS isoforms showed different assay sensitivities.

primary_references

Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Macrophage NOS preparation; enzymatic activity assay. · source_derived_draft · unverified_draft

## agmatine-sulfate-nos2-inhibition NOS isoforms showed different assay sensitivities. Agmatine competitively inhibited macrophage-derived NOS II with approximate Ki 220 micromolar. Model: Macrophage NOS preparation; enzymatic activity assay. Limitations: This is not a universal inflammatory-cell response or a human concentration target. Evidence access: Primary abstract Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

evidence_span

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experimental_model

Crystal structure and biochemical reaction characterization

exposure

Citrulline and aspartate bound to recombinant enzyme

limitations

Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human ASS1

plain_language

Aspartate supplies part of the molecule built at this step.

primary_references

[citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455

tissue_or_cell_type

Cytosolic arginine-regeneration reaction

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 138–149

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and biochemical reaction characterization · source_derived_draft · unverified_draft

### citrulline-ass1-aspartate Aspartate is a substrate of human ASS1 and was resolved with citrulline in the enzyme structure. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Aspartate supplies part of the molecule built at this step. organism: Human ASS1 tissue_or_cell_type: Cytosolic arginine-regeneration reaction experimental_model: Crystal structure and biochemical reaction characterization limitations: Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established. exposure: Citrulline and aspartate bound to recombinant enzyme evidence_span: {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"} [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455

evidence_span

{"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"}

experimental_model

Crystal structure and biochemical reaction characterization

exposure

Citrulline and aspartate bound to recombinant enzyme

limitations

Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human ASS1

plain_language

Arginine regeneration has an energy cost.

primary_references

[citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455

tissue_or_cell_type

Cytosolic arginine-regeneration reaction

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 151–162

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and biochemical reaction characterization · source_derived_draft · unverified_draft

### citrulline-ass1-energy The ASS1 reaction uses ATP cleavage to AMP and pyrophosphate. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Arginine regeneration has an energy cost. organism: Human ASS1 tissue_or_cell_type: Cytosolic arginine-regeneration reaction experimental_model: Crystal structure and biochemical reaction characterization limitations: Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established. exposure: Citrulline and aspartate bound to recombinant enzyme evidence_span: {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"} [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/citrulline-research/14970240.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d7acfd232edfd5d968d7afcbaf80ea27807a4313b5a385c90fd11b437403056", "start_char": 0, "end_char": 1589, "text_sha256": "7d7acfd232edfd5d968d7afcbaf80ea27807a4313b5a385c90fd11b437403056"}

experimental_model

RNA-interference and NO-donor rescue experiments

exposure

ASS1 knockdown despite saturating extracellular arginine

limitations

Bovine cell model; no claim that every human tissue exclusively uses regenerated arginine.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Bovine aortic endothelial cells

plain_language

Bulk substrate abundance did not compensate for impaired local recycling.

primary_references

[citrulline-p14970240] Argininosuccinate synthase expression is required to maintain nitric oxide production and cell viability in aortic endothelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/14970240/ DOI: 10.1074/jbc.m308160200

tissue_or_cell_type

Citrulline recycling, NO synthesis and viability

trigger_kind

machinery_impairment Imported condition classification; unverified.

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 658–669

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RNA-interference and NO-donor rescue experiments · source_derived_draft · unverified_draft

### citrulline-ass1-local-no ASS1 knockdown reduced basal and stimulated NO despite saturating arginine in the culture medium. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Bulk substrate abundance did not compensate for impaired local recycling. organism: Bovine aortic endothelial cells tissue_or_cell_type: Citrulline recycling, NO synthesis and viability experimental_model: RNA-interference and NO-donor rescue experiments limitations: Bovine cell model; no claim that every human tissue exclusively uses regenerated arginine. exposure: ASS1 knockdown despite saturating extracellular arginine evidence_span: {"source_cache": "artifacts/citrulline-research/14970240.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d7acfd232edfd5d968d7afcbaf80ea27807a4313b5a385c90fd11b437403056", "start_char": 0, "end_char": 1589, "text_sha256": "7d7acfd232edfd5d968d7afcbaf80ea27807a4313b5a385c90fd11b437403056"} [citrulline-p14970240] Argininosuccinate synthase expression is required to maintain nitric oxide production and cell viability in aortic endothelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/14970240/ DOI: 10.1074/jbc.m308160200

evidence_span

{"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"}

experimental_model

Crystal structure and biochemical reaction characterization

exposure

Citrulline and aspartate bound to recombinant enzyme

limitations

Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human ASS1

plain_language

Citrulline needs a second amino acid and an enzyme-controlled step before it becomes arginine.

primary_references

[citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455

tissue_or_cell_type

Cytosolic arginine-regeneration reaction

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 125–136

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and biochemical reaction characterization · source_derived_draft · unverified_draft

### citrulline-ass1-reaction Human ASS1 combines citrulline and aspartate to form argininosuccinate in an ATP-dependent reaction. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Citrulline needs a second amino acid and an enzyme-controlled step before it becomes arginine. organism: Human ASS1 tissue_or_cell_type: Cytosolic arginine-regeneration reaction experimental_model: Crystal structure and biochemical reaction characterization limitations: Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established. exposure: Citrulline and aspartate bound to recombinant enzyme evidence_span: {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"} [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455

evidence_span

{"source_cache": "artifacts/citrulline-research/30097067.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f08d4e244a48b116a8a2a734514e0cf13d3953bcae33722f996121bab8efbb2", "start_char": 0, "end_char": 1678, "text_sha256": "8f08d4e244a48b116a8a2a734514e0cf13d3953bcae33722f996121bab8efbb2"}

experimental_model

Randomized double-blind counterbalanced exercise study and product analysis

exposure

8 g CM with measured citrulline:malate ratio 1.11:1

limitations

Exercise, participant mix and product composition differed from the 2010 study; the cause of discrepant soreness is unproven.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human recreationally active men and women

plain_language

This protocol did not reproduce a performance gain.

primary_references

[citrulline-p30097067] Citrulline malate supplementation does not improve German Volume Training performance or reduce muscle soreness in moderately trained males and females. (2018). https://pubmed.ncbi.nlm.nih.gov/30097067/ DOI: 10.1186/s12970-018-0245-8

tissue_or_cell_type

Isokinetic German Volume Training and 72-hour soreness

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1152–1163

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind counterbalanced exercise study and product analysis · source_derived_draft · unverified_draft

### citrulline-exercise-null Repetitions did not improve with CM: 90.9 versus 94.0 on placebo, P=0.33. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This protocol did not reproduce a performance gain. organism: Human recreationally active men and women tissue_or_cell_type: Isokinetic German Volume Training and 72-hour soreness experimental_model: Randomized double-blind counterbalanced exercise study and product analysis limitations: Exercise, participant mix and product composition differed from the 2010 study; the cause of discrepant soreness is unproven. exposure: 8 g CM with measured citrulline:malate ratio 1.11:1 evidence_span: {"source_cache": "artifacts/citrulline-research/30097067.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f08d4e244a48b116a8a2a734514e0cf13d3953bcae33722f996121bab8efbb2", "start_char": 0, "end_char": 1678, "text_sha256": "8f08d4e244a48b116a8a2a734514e0cf13d3953bcae33722f996121bab8efbb2"} [citrulline-p30097067] Citrulline malate supplementation does not improve German Volume Training performance or reduce muscle soreness in moderately trained males and females. (2018). https://pubmed.ncbi.nlm.nih.gov/30097067/ DOI: 10.1186/s12970-018-0245-8

evidence_span

{"source_cache": "artifacts/citrulline-research/20386132.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847", "start_char": 0, "end_char": 1637, "text_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847"}

experimental_model

Randomized double-blind crossover exercise trial

exposure

8 g citrulline malate before a high-volume pectoral session

limitations

CM is not pure L-citrulline; last-set relative change is not a whole-workout gain; perceived soreness is subjective.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 41 men

plain_language

This result belongs to a demanding repeated-set protocol.

primary_references

[citrulline-p20386132] Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. (2010). https://pubmed.ncbi.nlm.nih.gov/20386132/ DOI: 10.1519/jsc.0b013e3181cb28e0

tissue_or_cell_type

Bench-press repetitions and self-reported soreness

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1113–1124

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

### citrulline-exercise-positive CM increased repetitions in later bench-press sets; the reported final-set relative gain was 52.92%. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This result belongs to a demanding repeated-set protocol. organism: Human, 41 men tissue_or_cell_type: Bench-press repetitions and self-reported soreness experimental_model: Randomized double-blind crossover exercise trial limitations: CM is not pure L-citrulline; last-set relative change is not a whole-workout gain; perceived soreness is subjective. exposure: 8 g citrulline malate before a high-volume pectoral session evidence_span: {"source_cache": "artifacts/citrulline-research/20386132.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847", "start_char": 0, "end_char": 1637, "text_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847"} [citrulline-p20386132] Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. (2010). https://pubmed.ncbi.nlm.nih.gov/20386132/ DOI: 10.1519/jsc.0b013e3181cb28e0

evidence_span

{"source_cache": "artifacts/citrulline-research/39662304.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f26c60b31d2021fb82143a4780ab4437e58c18d1c482a0880fdc4321f224092", "start_char": 0, "end_char": 1816, "text_sha256": "3f26c60b31d2021fb82143a4780ab4437e58c18d1c482a0880fdc4321f224092"}

experimental_model

Randomized double-blind placebo-controlled crossover trial

exposure

5.3 g L-citrulline; or 5.3 g citrulline plus 2.7 g malate; or placebo 45 minutes pre-exercise

limitations

Acute low-to-moderate-volume protocol; not a universal finding for all doses, workouts or chronic use.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 43 trained adults including 21 women

plain_language

Adding malate did not demonstrate an extra benefit in this trial.

primary_references

[citrulline-p39662304] Malate or Not? Acute Effects of L-Citrulline Versus Citrulline Malate on Neuromuscular Performance in Young, Trained Adults: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. (2025). https://pubmed.ncbi.nlm.nih.gov/39662304/ DOI: 10.1123/ijsnem.2024-0006

tissue_or_cell_type

Neuromuscular, ballistic and strength-endurance tests

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1191–1202

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

### citrulline-matched-malate-null Neither pure citrulline nor matched-citrulline-dose CM improved repetitions or other strength-endurance measures. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding malate did not demonstrate an extra benefit in this trial. organism: Human, 43 trained adults including 21 women tissue_or_cell_type: Neuromuscular, ballistic and strength-endurance tests experimental_model: Randomized double-blind placebo-controlled crossover trial limitations: Acute low-to-moderate-volume protocol; not a universal finding for all doses, workouts or chronic use. exposure: 5.3 g L-citrulline; or 5.3 g citrulline plus 2.7 g malate; or placebo 45 minutes pre-exercise evidence_span: {"source_cache": "artifacts/citrulline-research/39662304.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f26c60b31d2021fb82143a4780ab4437e58c18d1c482a0880fdc4321f224092", "start_char": 0, "end_char": 1816, "text_sha256": "3f26c60b31d2021fb82143a4780ab4437e58c18d1c482a0880fdc4321f224092"} [citrulline-p39662304] Malate or Not? Acute Effects of L-Citrulline Versus Citrulline Malate on Neuromuscular Performance in Young, Trained Adults: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. (2025). https://pubmed.ncbi.nlm.nih.gov/39662304/ DOI: 10.1123/ijsnem.2024-0006

evidence_span

{"source_cache": "artifacts/citrulline-research/1378832.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "265be186f6d8172b272e7b1e75b4fbae12a6df78c7396cad499bce2b195b1206", "start_char": 0, "end_char": 1652, "text_sha256": "265be186f6d8172b272e7b1e75b4fbae12a6df78c7396cad499bce2b195b1206"}

experimental_model

Functional expression and reporter-cell coculture

exposure

NOS3 transfection and calcium ionophore A23187

limitations

Heterologous expression; reporter activation supports bioactive NO production, not a clinical calcium supplementation effect.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human NOS3 expressed in NIH3T3 cells; rat reporter fibroblasts

plain_language

Arginine feeds an enzyme that makes the signal NO while also producing citrulline.

primary_references

[citrulline-p1378832] Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. (1992). https://pubmed.ncbi.nlm.nih.gov/1378832/ DOI: 10.1016/s0021-9258(18)42066-2

tissue_or_cell_type

Arginine conversion and NO-dependent reporter guanylate cyclase activity

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 463–474

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Functional expression and reporter-cell coculture · source_derived_draft · unverified_draft

### citrulline-nos-no Cells expressing human endothelial NOS produced bioactive NO that increased guanylate cyclase activity in cocultured reporter cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Arginine feeds an enzyme that makes the signal NO while also producing citrulline. organism: Human NOS3 expressed in NIH3T3 cells; rat reporter fibroblasts tissue_or_cell_type: Arginine conversion and NO-dependent reporter guanylate cyclase activity experimental_model: Functional expression and reporter-cell coculture limitations: Heterologous expression; reporter activation supports bioactive NO production, not a clinical calcium supplementation effect. exposure: NOS3 transfection and calcium ionophore A23187 evidence_span: {"source_cache": "artifacts/citrulline-research/1378832.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "265be186f6d8172b272e7b1e75b4fbae12a6df78c7396cad499bce2b195b1206", "start_char": 0, "end_char": 1652, "text_sha256": "265be186f6d8172b272e7b1e75b4fbae12a6df78c7396cad499bce2b195b1206"} [citrulline-p1378832] Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. (1992). https://pubmed.ncbi.nlm.nih.gov/1378832/ DOI: 10.1016/s0021-9258(18)42066-2

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"}

experimental_model

Patient genetics and recombinant variant expression

exposure

ALDH18A1 R84Q compared with wild-type isoforms

limitations

Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, two siblings and mammalian expression systems

plain_language

Low citrulline can arise from a defective upstream enzyme.

primary_references

[citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853

tissue_or_cell_type

Mitochondrial P5CS and circulating amino acids

trigger_kind

machinery_impairment Imported condition classification; unverified.

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 320–331

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient genetics and recombinant variant expression · source_derived_draft · unverified_draft

### citrulline-p5cs-low-citrulline The two R84Q siblings had hypocitrullinemia with low ornithine, arginine and proline; the variant strongly reduced expressed P5CS activity. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low citrulline can arise from a defective upstream enzyme. organism: Human, two siblings and mammalian expression systems tissue_or_cell_type: Mitochondrial P5CS and circulating amino acids experimental_model: Patient genetics and recombinant variant expression limitations: Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype. exposure: ALDH18A1 R84Q compared with wild-type isoforms evidence_span: {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"} [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853

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

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

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

evidence_span

{"source_cache": "artifacts/citrulline-research/19322909.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece", "start_char": 0, "end_char": 1531, "text_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece"}

experimental_model

Apical transport kinetics and transporter knockdown

exposure

Citrulline uptake on permeable supports; SLC6A19 or SLC7A9 silencing

limitations

Renal evidence must not be relabeled as a demonstrated human intestinal transport mechanism.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human HK-2 cells; rat cultures studied separately

plain_language

A neutral-amino-acid transporter contributes to kidney uptake.

primary_references

[citrulline-p19322909] Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19322909/ DOI: 10.1002/bdd.653

tissue_or_cell_type

Renal proximal tubular epithelium

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 398–409

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Apical transport kinetics and transporter knockdown · source_derived_draft · unverified_draft

### citrulline-renal-b0at1 Silencing SLC6A19 reduced citrulline uptake in human HK-2 renal cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A neutral-amino-acid transporter contributes to kidney uptake. organism: Human HK-2 cells; rat cultures studied separately tissue_or_cell_type: Renal proximal tubular epithelium experimental_model: Apical transport kinetics and transporter knockdown limitations: Renal evidence must not be relabeled as a demonstrated human intestinal transport mechanism. exposure: Citrulline uptake on permeable supports; SLC6A19 or SLC7A9 silencing evidence_span: {"source_cache": "artifacts/citrulline-research/19322909.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece", "start_char": 0, "end_char": 1531, "text_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece"} [citrulline-p19322909] Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19322909/ DOI: 10.1002/bdd.653

evidence_span

{"source_cache": "artifacts/citrulline-research/19322909.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece", "start_char": 0, "end_char": 1531, "text_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece"}

experimental_model

Apical transport kinetics and transporter knockdown

exposure

Citrulline uptake on permeable supports; SLC6A19 or SLC7A9 silencing

limitations

Renal evidence must not be relabeled as a demonstrated human intestinal transport mechanism.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human HK-2 cells; rat cultures studied separately

plain_language

A separate transporter contributes to the measured uptake.

primary_references

[citrulline-p19322909] Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19322909/ DOI: 10.1002/bdd.653

tissue_or_cell_type

Renal proximal tubular epithelium

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 411–422

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Apical transport kinetics and transporter knockdown · source_derived_draft · unverified_draft

### citrulline-renal-b0plus Silencing SLC7A9 also reduced citrulline uptake in HK-2 cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate transporter contributes to the measured uptake. organism: Human HK-2 cells; rat cultures studied separately tissue_or_cell_type: Renal proximal tubular epithelium experimental_model: Apical transport kinetics and transporter knockdown limitations: Renal evidence must not be relabeled as a demonstrated human intestinal transport mechanism. exposure: Citrulline uptake on permeable supports; SLC6A19 or SLC7A9 silencing evidence_span: {"source_cache": "artifacts/citrulline-research/19322909.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece", "start_char": 0, "end_char": 1531, "text_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece"} [citrulline-p19322909] Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19322909/ DOI: 10.1002/bdd.653

evidence_span

{"source_cache": "artifacts/citrulline-research/19322909.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece", "start_char": 0, "end_char": 1531, "text_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece"}

experimental_model

Apical transport kinetics and transporter knockdown

exposure

Citrulline uptake on permeable supports; SLC6A19 or SLC7A9 silencing

limitations

Renal evidence must not be relabeled as a demonstrated human intestinal transport mechanism.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human HK-2 cells; rat cultures studied separately

plain_language

Sodium dependence applies to part of the transport system, not every citrulline transporter.

primary_references

[citrulline-p19322909] Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19322909/ DOI: 10.1002/bdd.653

tissue_or_cell_type

Renal proximal tubular epithelium

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 424–435

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Apical transport kinetics and transporter knockdown · source_derived_draft · unverified_draft

### citrulline-renal-sodium HK-2 citrulline uptake included two sodium-dependent saturable components and one sodium-independent component. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium dependence applies to part of the transport system, not every citrulline transporter. organism: Human HK-2 cells; rat cultures studied separately tissue_or_cell_type: Renal proximal tubular epithelium experimental_model: Apical transport kinetics and transporter knockdown limitations: Renal evidence must not be relabeled as a demonstrated human intestinal transport mechanism. exposure: Citrulline uptake on permeable supports; SLC6A19 or SLC7A9 silencing evidence_span: {"source_cache": "artifacts/citrulline-research/19322909.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece", "start_char": 0, "end_char": 1531, "text_sha256": "f466fcced77ee9fe7a97f010112a035332d513382d13e6187d10bc02be152ece"} [citrulline-p19322909] Transport characteristics of L-citrulline in renal apical membrane of proximal tubular cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19322909/ DOI: 10.1002/bdd.653

evidence_span

{"source_cache": "artifacts/citrulline-research/20386132.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847", "start_char": 0, "end_char": 1637, "text_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847"}

experimental_model

Randomized double-blind crossover exercise trial

exposure

8 g citrulline malate before a high-volume pectoral session

limitations

CM is not pure L-citrulline; last-set relative change is not a whole-workout gain; perceived soreness is subjective.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 41 men

plain_language

Participants reported less soreness after this protocol.

primary_references

[citrulline-p20386132] Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. (2010). https://pubmed.ncbi.nlm.nih.gov/20386132/ DOI: 10.1519/jsc.0b013e3181cb28e0

tissue_or_cell_type

Bench-press repetitions and self-reported soreness

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1126–1137

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

### citrulline-soreness-decreased The trial reported approximately 40% lower soreness at 24 and 48 hours with CM. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Participants reported less soreness after this protocol. organism: Human, 41 men tissue_or_cell_type: Bench-press repetitions and self-reported soreness experimental_model: Randomized double-blind crossover exercise trial limitations: CM is not pure L-citrulline; last-set relative change is not a whole-workout gain; perceived soreness is subjective. exposure: 8 g citrulline malate before a high-volume pectoral session evidence_span: {"source_cache": "artifacts/citrulline-research/20386132.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847", "start_char": 0, "end_char": 1637, "text_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847"} [citrulline-p20386132] Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. (2010). https://pubmed.ncbi.nlm.nih.gov/20386132/ DOI: 10.1519/jsc.0b013e3181cb28e0

evidence_span

{"source_cache": "artifacts/citrulline-research/30097067.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f08d4e244a48b116a8a2a734514e0cf13d3953bcae33722f996121bab8efbb2", "start_char": 0, "end_char": 1678, "text_sha256": "8f08d4e244a48b116a8a2a734514e0cf13d3953bcae33722f996121bab8efbb2"}

experimental_model

Randomized double-blind counterbalanced exercise study and product analysis

exposure

8 g CM with measured citrulline:malate ratio 1.11:1

limitations

Exercise, participant mix and product composition differed from the 2010 study; the cause of discrepant soreness is unproven.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human recreationally active men and women

plain_language

This study reported more soreness, the opposite of the earlier soreness result.

primary_references

[citrulline-p30097067] Citrulline malate supplementation does not improve German Volume Training performance or reduce muscle soreness in moderately trained males and females. (2018). https://pubmed.ncbi.nlm.nih.gov/30097067/ DOI: 10.1186/s12970-018-0245-8

tissue_or_cell_type

Isokinetic German Volume Training and 72-hour soreness

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1165–1176

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind counterbalanced exercise study and product analysis · source_derived_draft · unverified_draft

### citrulline-soreness-increased Total soreness over 72 hours was higher after CM than placebo, P=0.01, without a greater workload. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This study reported more soreness, the opposite of the earlier soreness result. organism: Human recreationally active men and women tissue_or_cell_type: Isokinetic German Volume Training and 72-hour soreness experimental_model: Randomized double-blind counterbalanced exercise study and product analysis limitations: Exercise, participant mix and product composition differed from the 2010 study; the cause of discrepant soreness is unproven. exposure: 8 g CM with measured citrulline:malate ratio 1.11:1 evidence_span: {"source_cache": "artifacts/citrulline-research/30097067.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8f08d4e244a48b116a8a2a734514e0cf13d3953bcae33722f996121bab8efbb2", "start_char": 0, "end_char": 1678, "text_sha256": "8f08d4e244a48b116a8a2a734514e0cf13d3953bcae33722f996121bab8efbb2"} [citrulline-p30097067] Citrulline malate supplementation does not improve German Volume Training performance or reduce muscle soreness in moderately trained males and females. (2018). https://pubmed.ncbi.nlm.nih.gov/30097067/ DOI: 10.1186/s12970-018-0245-8

evidence_span

{"source_cache": "artifacts/citrulline-research/20386132.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847", "start_char": 0, "end_char": 1637, "text_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847"}

experimental_model

Randomized double-blind crossover exercise trial

exposure

8 g citrulline malate before a high-volume pectoral session

limitations

CM is not pure L-citrulline; last-set relative change is not a whole-workout gain; perceived soreness is subjective.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human, 41 men

plain_language

The study preparation was not symptom-free for everyone.

primary_references

[citrulline-p20386132] Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. (2010). https://pubmed.ncbi.nlm.nih.gov/20386132/ DOI: 10.1519/jsc.0b013e3181cb28e0

tissue_or_cell_type

Bench-press repetitions and self-reported soreness

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 1139–1150

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

### citrulline-stomach-discomfort Stomach discomfort was reported by 14.63% of participants with CM. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study preparation was not symptom-free for everyone. organism: Human, 41 men tissue_or_cell_type: Bench-press repetitions and self-reported soreness experimental_model: Randomized double-blind crossover exercise trial limitations: CM is not pure L-citrulline; last-set relative change is not a whole-workout gain; perceived soreness is subjective. exposure: 8 g citrulline malate before a high-volume pectoral session evidence_span: {"source_cache": "artifacts/citrulline-research/20386132.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847", "start_char": 0, "end_char": 1637, "text_sha256": "a095891368caeebaa857f5dcf2651e1498924f2006969255d252c1d8caa91847"} [citrulline-p20386132] Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. (2010). https://pubmed.ncbi.nlm.nih.gov/20386132/ DOI: 10.1519/jsc.0b013e3181cb28e0

evidence_span

{"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"}

experimental_model

Cell exposure and recombinant-enzyme assays

exposure

Ascorbate loading; BH4 or sepiapterin comparisons

limitations

Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Porcine aortic endothelial cells and bovine eNOS

plain_language

Vitamin C can affect cofactor availability in this cell model.

primary_references

[citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200

tissue_or_cell_type

BH4 availability and NO bioactivity

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 697–708

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell exposure and recombinant-enzyme assays · source_derived_draft · unverified_draft

### citrulline-vitaminc-bh4 Ascorbate increased intracellular BH4 in porcine aortic endothelial cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C can affect cofactor availability in this cell model. organism: Porcine aortic endothelial cells and bovine eNOS tissue_or_cell_type: BH4 availability and NO bioactivity experimental_model: Cell exposure and recombinant-enzyme assays limitations: Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline. exposure: Ascorbate loading; BH4 or sepiapterin comparisons evidence_span: {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"} [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200

evidence_span

{"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"}

experimental_model

Cell exposure and recombinant-enzyme assays

exposure

Ascorbate loading; BH4 or sepiapterin comparisons

limitations

Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Porcine aortic endothelial cells and bovine eNOS

plain_language

The benefit depended on the starting cofactor conditions.

primary_references

[citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200

tissue_or_cell_type

BH4 availability and NO bioactivity

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 723–734

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell exposure and recombinant-enzyme assays · source_derived_draft · unverified_draft

### citrulline-vitaminc-bh4-saturation Ascorbate had no additional effect at high BH4 or after sepiapterin raised cellular BH4. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The benefit depended on the starting cofactor conditions. organism: Porcine aortic endothelial cells and bovine eNOS tissue_or_cell_type: BH4 availability and NO bioactivity experimental_model: Cell exposure and recombinant-enzyme assays limitations: Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline. exposure: Ascorbate loading; BH4 or sepiapterin comparisons evidence_span: {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"} [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200

evidence_span

{"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"}

experimental_model

Cell exposure and recombinant-enzyme assays

exposure

Ascorbate loading; BH4 or sepiapterin comparisons

limitations

Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Porcine aortic endothelial cells and bovine eNOS

plain_language

Protecting the machinery can matter as well as supplying arginine.

primary_references

[citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200

tissue_or_cell_type

BH4 availability and NO bioactivity

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 710–721

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell exposure and recombinant-enzyme assays · source_derived_draft · unverified_draft

### citrulline-vitaminc-no Ascorbate increased arginine-to-citrulline conversion and NO-related output in porcine endothelial cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protecting the machinery can matter as well as supplying arginine. organism: Porcine aortic endothelial cells and bovine eNOS tissue_or_cell_type: BH4 availability and NO bioactivity experimental_model: Cell exposure and recombinant-enzyme assays limitations: Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline. exposure: Ascorbate loading; BH4 or sepiapterin comparisons evidence_span: {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"} [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human cancer-cell perturbations, metabolic analysis and disease-related comparisons.

limitations

The finding does not mean reducing nitrogen disposal is beneficial; it is a tumor-model mechanism.

nutrient_topic

L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate

plain_language

Using less aspartate for arginine synthesis can leave more for nucleotide synthesis.

primary_references

Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 170–176

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell perturbations, metabolic analysis and disease-related comparisons. · source_derived_draft · unverified_draft

## l-aspartate-ass1-diversion Using less aspartate for arginine synthesis can leave more for nucleotide synthesis. Reduced ASS1 activity increased cytosolic aspartate availability and CAD-dependent pyrimidine synthesis in the studied cancer models. Model: Human cancer-cell perturbations, metabolic analysis and disease-related comparisons. Limitations: The finding does not mean reducing nitrogen disposal is beneficial; it is a tumor-model mechanism. Evidence access: Primary abstract Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529

evidence_access

Primary abstract

experimental_model

Rat cerebellar NOS preparation; separated partial reactions.

limitations

Purified preparation; residual enzyme reductant supported a limited first reaction without added NADPH. This does not imply physiological NOS is NADPH independent.

nutrient_topic

L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine

plain_language

The next reaction produces the signal and recycles the carbon skeleton.

primary_references

Characteristics of the nitric oxide synthase-catalyzed conversion of arginine to N-hydroxyarginine, the first oxygenation step in the enzymic synthesis of nitric oxide. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7530247/ · DOI 10.1074/jbc.270.4.1721

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 78–84

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rat cerebellar NOS preparation; separated partial reactions. · source_derived_draft · unverified_draft

## arg-nos-second The next reaction produces the signal and recycles the carbon skeleton. The second oxygenation yielded NO and citrulline and required added NADPH and calcium/calmodulin. Model: Rat cerebellar NOS preparation; separated partial reactions. Limitations: Purified preparation; residual enzyme reductant supported a limited first reaction without added NADPH. This does not imply physiological NOS is NADPH independent. Evidence access: Primary abstract Characteristics of the nitric oxide synthase-catalyzed conversion of arginine to N-hydroxyarginine, the first oxygenation step in the enzymic synthesis of nitric oxide. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7530247/ · DOI 10.1074/jbc.270.4.1721

evidence_access

Primary abstract

experimental_model

Nine men in oral lysine tests; three men in intravenous amino-acid loading tests.

limitations

Small historical experiment; no molecular transporter identified and no ordinary-meal effect size established.

nutrient_topic

L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine

plain_language

Related amino acids interacted at a kidney transport step.

primary_references

A new transport interaction of dibasic amino acids and citrulline in human kidney. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6797099/ · DOI 10.1620/tjem.134.55

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 54–60

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Nine men in oral lysine tests; three men in intravenous amino-acid loading tests. · source_derived_draft · unverified_draft

## arg-renal-competition Related amino acids interacted at a kidney transport step. Amino-acid loading experiments indicated inhibition of renal citrulline transport by arginine, lysine and ornithine. Model: Nine men in oral lysine tests; three men in intravenous amino-acid loading tests. Limitations: Small historical experiment; no molecular transporter identified and no ordinary-meal effect size established. Evidence access: Primary abstract A new transport interaction of dibasic amino acids and citrulline in human kidney. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6797099/ · DOI 10.1620/tjem.134.55