Arterial blood pressure

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/22900702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f3cf1535535a14d11902c63d1f0be28faf07b80835cf5f1b296a62cc2e78e1b1", "start_char": 0, "end_char": 1044, "text_sha256": "f3cf1535535a14d11902c63d1f0be28faf07b80835cf5f1b296a62cc2e78e1b1"}

experimental_model

Randomized double-blind placebo-controlled acute crossover in 23 adults

exposure

400 mg chlorogenic acid; study product naming retained

limitations

A small acute surrogate-endpoint study, not cardiovascular event prevention. Later literature describes the product with a 3-CQA label; historical numbering must be checked before treating it as modern neochlorogenic acid.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Human

plain_language

The study found a small short-term blood-pressure difference.

primary_references

[chlorogenic_acid-p22900702] Acute effects of chlorogenic acid on nitric oxide status, endothelial function, and blood pressure in healthy volunteers: a randomized trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22900702/ DOI: 10.1021/jf303440j

tissue_or_cell_type

Blood pressure, endothelial function and NO-related markers

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 919–930

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 acute crossover in 23 adults · source_derived_draft · unverified_draft

### chlorogenic_acid-acute-bp Mean systolic/diastolic changes versus control were -2.41/-1.53 mmHg (P=0.05/0.04). Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study found a small short-term blood-pressure difference. organism: Human tissue_or_cell_type: Blood pressure, endothelial function and NO-related markers experimental_model: Randomized double-blind placebo-controlled acute crossover in 23 adults limitations: A small acute surrogate-endpoint study, not cardiovascular event prevention. Later literature describes the product with a 3-CQA label; historical numbering must be checked before treating it as modern neochlorogenic acid. exposure: 400 mg chlorogenic acid; study product naming retained evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/22900702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f3cf1535535a14d11902c63d1f0be28faf07b80835cf5f1b296a62cc2e78e1b1", "start_char": 0, "end_char": 1044, "text_sha256": "f3cf1535535a14d11902c63d1f0be28faf07b80835cf5f1b296a62cc2e78e1b1"} [chlorogenic_acid-p22900702] Acute effects of chlorogenic acid on nitric oxide status, endothelial function, and blood pressure in healthy volunteers: a randomized trial. (2012). https://pubmed.ncbi.nlm.nih.gov/22900702/ DOI: 10.1021/jf303440j

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/16820341.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "47326bb2b286adb85689ebeb57d99f79bde7d2a62cf8dcedc1a6e349aac986f9", "start_char": 0, "end_char": 906, "text_sha256": "47326bb2b286adb85689ebeb57d99f79bde7d2a62cf8dcedc1a6e349aac986f9"}

experimental_model

Placebo-controlled randomized trial in 28 participants with mild hypertension

exposure

Green coffee extract delivering 140 mg/day chlorogenic acids

limitations

The abstract reports within-group BP significance, not an explicit between-group effect estimate. Small-sample absence of apparent side effects does not establish universal safety or isolate a single isomer.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Human

plain_language

This result concerns a measured extract, with limited comparative statistics available.

primary_references

[chlorogenic_acid-p16820341] The blood pressure-lowering effect and safety of chlorogenic acid from green coffee bean extract in essential hypertension. (2006). https://pubmed.ncbi.nlm.nih.gov/16820341/ DOI: 10.1080/10641960600798655

tissue_or_cell_type

Blood pressure, pulse, BMI and safety observations

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 1023–1034

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo-controlled randomized trial in 28 participants with mild hypertension · source_derived_draft · unverified_draft

### chlorogenic_acid-extract-bp Blood pressure declined significantly within the extract group but not within placebo in the abstract report. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: This result concerns a measured extract, with limited comparative statistics available. organism: Human tissue_or_cell_type: Blood pressure, pulse, BMI and safety observations experimental_model: Placebo-controlled randomized trial in 28 participants with mild hypertension limitations: The abstract reports within-group BP significance, not an explicit between-group effect estimate. Small-sample absence of apparent side effects does not establish universal safety or isolate a single isomer. exposure: Green coffee extract delivering 140 mg/day chlorogenic acids evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/16820341.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "47326bb2b286adb85689ebeb57d99f79bde7d2a62cf8dcedc1a6e349aac986f9", "start_char": 0, "end_char": 906, "text_sha256": "47326bb2b286adb85689ebeb57d99f79bde7d2a62cf8dcedc1a6e349aac986f9"} [chlorogenic_acid-p16820341] The blood pressure-lowering effect and safety of chlorogenic acid from green coffee bean extract in essential hypertension. (2006). https://pubmed.ncbi.nlm.nih.gov/16820341/ DOI: 10.1080/10641960600798655

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/27109860.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8a19a33418ce3a635bd5d8d0d2189175a8e555131a1059441eac4d03dfc91c8", "start_char": 0, "end_char": 1585, "text_sha256": "e8a19a33418ce3a635bd5d8d0d2189175a8e555131a1059441eac4d03dfc91c8"}

experimental_model

Randomized-order acute crossover in 16 adults

exposure

0, 450 or 900 mg purified 5-CGA; 200 mg epicatechin comparator; one-week spacing

limitations

Peak and continuous-mean FMD are different endpoints. Secondary positive findings must not replace the null peak response; no long-term vascular outcome was tested.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Human

plain_language

This trial does not support an inevitable blood-pressure reduction.

primary_references

[chlorogenic_acid-p27109860] Acute effects of chlorogenic acids on endothelial function and blood pressure in healthy men and women. (2016). https://pubmed.ncbi.nlm.nih.gov/27109860/ DOI: 10.1039/c6fo00248j

tissue_or_cell_type

Brachial flow-mediated dilation and blood pressure

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 984–995

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized-order acute crossover in 16 adults · source_derived_draft · unverified_draft

### chlorogenic_acid-pure-bp-null Neither purified 5-CGA dose significantly altered blood pressure. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: This trial does not support an inevitable blood-pressure reduction. organism: Human tissue_or_cell_type: Brachial flow-mediated dilation and blood pressure experimental_model: Randomized-order acute crossover in 16 adults limitations: Peak and continuous-mean FMD are different endpoints. Secondary positive findings must not replace the null peak response; no long-term vascular outcome was tested. exposure: 0, 450 or 900 mg purified 5-CGA; 200 mg epicatechin comparator; one-week spacing evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/27109860.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8a19a33418ce3a635bd5d8d0d2189175a8e555131a1059441eac4d03dfc91c8", "start_char": 0, "end_char": 1585, "text_sha256": "e8a19a33418ce3a635bd5d8d0d2189175a8e555131a1059441eac4d03dfc91c8"} [chlorogenic_acid-p27109860] Acute effects of chlorogenic acids on endothelial function and blood pressure in healthy men and women. (2016). https://pubmed.ncbi.nlm.nih.gov/27109860/ DOI: 10.1039/c6fo00248j

evidence_span

{"source_cache": "artifacts/sodium-research/11136953.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7664fc223f123220dd64755a1e9bc4ee3e9942e09b5de444bd789f210f449133", "start_char": 0, "end_char": 1987, "text_sha256": "7664fc223f123220dd64755a1e9bc4ee3e9942e09b5de444bd789f210f449133"}

experimental_model

Randomized controlled feeding trial in 412 participants

exposure

Three sodium levels for 30 days each within assigned DASH or control diet

limitations

Blood-pressure trial, not a hard-outcome trial; DASH changes multiple nutrients and foods. Its combined effect cannot be assigned to one mineral.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Human adults with and without hypertension

plain_language

Diet composition and sodium reduction had a combined effect.

primary_references

[sodium-p11136953] Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. (2001). https://pubmed.ncbi.nlm.nih.gov/11136953/ DOI: 10.1056/nejm200101043440101

tissue_or_cell_type

Systemic blood pressure

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 1084–1095

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled feeding trial in 412 participants · source_derived_draft · unverified_draft

### sodium-dash-combination Low-sodium DASH versus high-sodium control produced mean systolic differences of 7.1 mmHg without hypertension and 11.5 mmHg with hypertension. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Diet composition and sodium reduction had a combined effect. organism: Human adults with and without hypertension tissue_or_cell_type: Systemic blood pressure experimental_model: Randomized controlled feeding trial in 412 participants limitations: Blood-pressure trial, not a hard-outcome trial; DASH changes multiple nutrients and foods. Its combined effect cannot be assigned to one mineral. exposure: Three sodium levels for 30 days each within assigned DASH or control diet evidence_span: {"source_cache": "artifacts/sodium-research/11136953.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7664fc223f123220dd64755a1e9bc4ee3e9942e09b5de444bd789f210f449133", "start_char": 0, "end_char": 1987, "text_sha256": "7664fc223f123220dd64755a1e9bc4ee3e9942e09b5de444bd789f210f449133"} [sodium-p11136953] Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. (2001). https://pubmed.ncbi.nlm.nih.gov/11136953/ DOI: 10.1056/nejm200101043440101

evidence_span

{"source_cache": "artifacts/sodium-research/11136953.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7664fc223f123220dd64755a1e9bc4ee3e9942e09b5de444bd789f210f449133", "start_char": 0, "end_char": 1987, "text_sha256": "7664fc223f123220dd64755a1e9bc4ee3e9942e09b5de444bd789f210f449133"}

experimental_model

Randomized controlled feeding trial in 412 participants

exposure

Three sodium levels for 30 days each within assigned DASH or control diet

limitations

Blood-pressure trial, not a hard-outcome trial; DASH changes multiple nutrients and foods. Its combined effect cannot be assigned to one mineral.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Human adults with and without hypertension

plain_language

Reducing sodium lowered blood pressure under both tested dietary patterns.

primary_references

[sodium-p11136953] Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. (2001). https://pubmed.ncbi.nlm.nih.gov/11136953/ DOI: 10.1056/nejm200101043440101

tissue_or_cell_type

Systemic blood pressure

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 1071–1082

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled feeding trial in 412 participants · source_derived_draft · unverified_draft

### sodium-dash-sodium High-to-intermediate sodium reduction lowered systolic pressure by 2.1 mmHg on the control diet and 1.3 mmHg on DASH; intermediate-to-low reduction lowered it by another 4.6 and 1.7 mmHg respectively. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing sodium lowered blood pressure under both tested dietary patterns. organism: Human adults with and without hypertension tissue_or_cell_type: Systemic blood pressure experimental_model: Randomized controlled feeding trial in 412 participants limitations: Blood-pressure trial, not a hard-outcome trial; DASH changes multiple nutrients and foods. Its combined effect cannot be assigned to one mineral. exposure: Three sodium levels for 30 days each within assigned DASH or control diet evidence_span: {"source_cache": "artifacts/sodium-research/11136953.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7664fc223f123220dd64755a1e9bc4ee3e9942e09b5de444bd789f210f449133", "start_char": 0, "end_char": 1987, "text_sha256": "7664fc223f123220dd64755a1e9bc4ee3e9942e09b5de444bd789f210f449133"} [sodium-p11136953] Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. (2001). https://pubmed.ncbi.nlm.nih.gov/11136953/ DOI: 10.1056/nejm200101043440101

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/30571224.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14f3ce82ae25bafc1d5d935be05b3a8d68420b6d8a36fdbbc5d7e89aba77bc33", "start_char": 0, "end_char": 1779, "text_sha256": "14f3ce82ae25bafc1d5d935be05b3a8d68420b6d8a36fdbbc5d7e89aba77bc33"}

experimental_model

Proximal-tubule-specific Slc9a3 knockout and controlled renal perfusion changes

exposure

Genetic deletion; increased perfusion pressure; saline and dietary salt challenges

limitations

Unlike intestinal deletion, the kidney-specific model retained measured baseline plasma sodium, pH and bicarbonate. Tissue context, not a contradiction.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Mouse

plain_language

A kidney sodium-transport change can affect blood pressure.

primary_references

[sodium-p30571224] Proximal Tubule-Specific Deletion of the NHE3 (Na+/H+ Exchanger 3) Promotes the Pressure-Natriuresis Response and Lowers Blood Pressure in Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/30571224/ DOI: 10.1161/hypertensionaha.118.10884

tissue_or_cell_type

Kidney proximal tubule

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 902–913

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Proximal-tubule-specific Slc9a3 knockout and controlled renal perfusion changes · source_derived_draft · unverified_draft

### sodium-renal-nhe3-pressure Proximal-tubule NHE3-null mice had lower basal systolic, diastolic and mean arterial pressure. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kidney sodium-transport change can affect blood pressure. organism: Mouse tissue_or_cell_type: Kidney proximal tubule experimental_model: Proximal-tubule-specific Slc9a3 knockout and controlled renal perfusion changes limitations: Unlike intestinal deletion, the kidney-specific model retained measured baseline plasma sodium, pH and bicarbonate. Tissue context, not a contradiction. exposure: Genetic deletion; increased perfusion pressure; saline and dietary salt challenges evidence_span: {"source_cache": "artifacts/sodium-research/30571224.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14f3ce82ae25bafc1d5d935be05b3a8d68420b6d8a36fdbbc5d7e89aba77bc33", "start_char": 0, "end_char": 1779, "text_sha256": "14f3ce82ae25bafc1d5d935be05b3a8d68420b6d8a36fdbbc5d7e89aba77bc33"} [sodium-p30571224] Proximal Tubule-Specific Deletion of the NHE3 (Na+/H+ Exchanger 3) Promotes the Pressure-Natriuresis Response and Lowers Blood Pressure in Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/30571224/ DOI: 10.1161/hypertensionaha.118.10884

evidence_span

{"source_cache": "artifacts/melatonin-research/10792199.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b", "start_char": 0, "end_char": 1482, "text_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b"}

experimental_model

Double-blind crossover drug-context trial

exposure

5 mg melatonin nightly for four weeks; nifedipine GITS 30 or 60 mg daily

limitations

Observed drug-context effect. The authors proposed competition, but a specific transporter, CYP interaction or calcium-channel mechanism was not proven.

nutrient_topic

Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

organism

47 hypertensive patients stable on nifedipine

plain_language

A favorable reputation for one pathway does not guarantee the same response with a particular medicine.

primary_references

[melatonin-p10792199] Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. (2000). https://pubmed.ncbi.nlm.nih.gov/10792199/ DOI: 10.1046/j.1365-2125.2000.00195.x

tissue_or_cell_type

Ambulatory blood pressure and heart rate

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1033–1044

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

### melatonin-nifedipine-pressure With nifedipine therapy, melatonin increased 24-hour systolic/diastolic pressure by about 6.5/4.9 mmHg. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A favorable reputation for one pathway does not guarantee the same response with a particular medicine. organism: 47 hypertensive patients stable on nifedipine tissue_or_cell_type: Ambulatory blood pressure and heart rate experimental_model: Double-blind crossover drug-context trial limitations: Observed drug-context effect. The authors proposed competition, but a specific transporter, CYP interaction or calcium-channel mechanism was not proven. exposure: 5 mg melatonin nightly for four weeks; nifedipine GITS 30 or 60 mg daily evidence_span: {"source_cache": "artifacts/melatonin-research/10792199.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b", "start_char": 0, "end_char": 1482, "text_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b"} [melatonin-p10792199] Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. (2000). https://pubmed.ncbi.nlm.nih.gov/10792199/ DOI: 10.1046/j.1365-2125.2000.00195.x

duration

8 weeks

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human (79 enrolled, 74 completed, systolic 130 or above or diastolic 90 or above)

exposure

NSK-SD, 100 mg per day

limitations

Randomized, double-blind, placebo-controlled and multicentre, with industry sponsorship and several exploratory subgroup analyses. The dose is stated in milligrams, not FU, so it is not directly comparable with the 2,000 FU trials without the product specification.

organism

Human (79 enrolled, 74 completed, systolic 130 or above or diastolic 90 or above)

plain_language

Average diastolic blood pressure fell from 87 to 84 mmHg with nattokinase against no change on placebo over eight weeks, reaching 86 to 81 mmHg in males.

primary_references

Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial. (2016) https://pubmed.ncbi.nlm.nih.gov/27785095/ DOI: 10.2147/IBPC.S99553

route

In vivo, oral

tissue

Arterial blood pressure

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1016–1016

Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (79 enrolled, 74 completed, systolic 130 or above or diastolic 90 or above) · source_derived_draft · unverified_draft

Average diastolic blood pressure fell from 87 to 84 mmHg with nattokinase against no change on placebo over eight weeks, reaching 86 to 81 mmHg in males.

duration

8 weeks

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human (86 randomized, 73 completed, untreated systolic 130-159 mmHg, ages 20-80)

exposure

Nattokinase, 2,000 FU per capsule

limitations

Randomized, double-blind and placebo-controlled, but small and short, with industry affiliations. The confidence intervals reach close to zero (-10.5 to -0.57 and -5.33 to -0.33). No mechanistic mediator beyond plasma renin activity was measured.

organism

Human (86 randomized, 73 completed, untreated systolic 130-159 mmHg, ages 20-80)

plain_language

Net changes of -5.55 mmHg systolic and -2.84 mmHg diastolic against placebo were reported after eight weeks at 2,000 FU per day.

primary_references

Effects of nattokinase on blood pressure: a randomized, controlled trial. (2008) https://pubmed.ncbi.nlm.nih.gov/18971533/ DOI: 10.1291/hypres.31.1583

route

In vivo, oral

tissue

Arterial blood pressure

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 994–994

Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (86 randomized, 73 completed, untreated systolic 130-159 mmHg, ages 20-80) · source_derived_draft · unverified_draft

Net changes of -5.55 mmHg systolic and -2.84 mmHg diastolic against placebo were reported after eight weeks at 2,000 FU per day.

duration

Trial durations differ

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human, systematic review and meta-analysis of randomized controlled trials

exposure

Nattokinase supplementation, doses and products differing between trials

limitations

Few small trials with different populations, doses and products, and predominantly surrogate outcomes. The pooled estimate inherits the industry affiliation of several component trials and does not include the three-year randomized trial that found no blood-pressure effect.

organism

Human, systematic review and meta-analysis of randomized controlled trials

plain_language

Across six randomized trials with 546 participants, pooled systolic blood pressure fell by 3.45 mmHg and diastolic by 2.32 mmHg against placebo.

primary_references

Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (2023) https://pubmed.ncbi.nlm.nih.gov/39076715/ DOI: 10.31083/j.rcm2408234

route

In vivo, oral

tissue

Arterial blood pressure

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1049–1049

Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human, systematic review and meta-analysis of randomized controlled trials · source_derived_draft · unverified_draft

Across six randomized trials with 546 participants, pooled systolic blood pressure fell by 3.45 mmHg and diastolic by 2.32 mmHg against placebo.

duration

Median 3 years

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human (265 randomized, low cardiovascular risk)

exposure

Nattokinase, 2,000 FU per day

limitations

This is the direct contradiction of the eight-week blood-pressure trials and of the pooled estimate. The populations differ: these participants were low-risk and not selected for elevated blood pressure.

organism

Human (265 randomized, low cardiovascular risk)

plain_language

There was no significant effect on blood pressure over the same three years.

primary_references

Nattokinase atherothrombotic prevention study: A randomized controlled trial. (2021) https://pubmed.ncbi.nlm.nih.gov/33843667/ DOI: 10.3233/CH-211147

route

In vivo, oral

tissue

Arterial blood pressure

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1126–1126

Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (265 randomized, low cardiovascular risk) · source_derived_draft · unverified_draft

There was no significant effect on blood pressure over the same three years.

evidence_span

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experimental_model

Uncontrolled phase I escalating-dose study

exposure

30 enrolled, 28 completed; water extract 85, 250 and 500 mg at successive monthly intervals

limitations

No placebo group; three months and a small healthy sample cannot establish long-term safety or efficacy in disease.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Human

plain_language

Blood pressure fell, but the study cannot separate extract effects from other changes over time.

primary_references

[ceylon-p29282046] Evaluation of pharmacodynamic properties and safety of Cinnamomum zeylanicum (Ceylon cinnamon) in healthy adults: a phase I clinical trial. (2017). https://pubmed.ncbi.nlm.nih.gov/29282046/ DOI: 10.1186/s12906-017-2067-7

tissue_or_cell_type

Healthy adults, clinical and laboratory measures

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 1130–1141

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Uncontrolled phase I escalating-dose study · source_derived_draft · unverified_draft

### ceylon-phase1-bp Blood pressure decreased during the uncontrolled phase I study, beginning in the first month. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood pressure fell, but the study cannot separate extract effects from other changes over time. organism: Human tissue_or_cell_type: Healthy adults, clinical and laboratory measures experimental_model: Uncontrolled phase I escalating-dose study limitations: No placebo group; three months and a small healthy sample cannot establish long-term safety or efficacy in disease. exposure: 30 enrolled, 28 completed; water extract 85, 250 and 500 mg at successive monthly intervals evidence_span: {"source_cache": "artifacts/ceylon-research/29282046.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9f042ba36cfd9e3e8a8e76e155c71d6b742c431c1ba4cf90c3a94115f3b06c61", "start_char": 0, "end_char": 2508, "text_sha256": "9f042ba36cfd9e3e8a8e76e155c71d6b742c431c1ba4cf90c3a94115f3b06c61"} [ceylon-p29282046] Evaluation of pharmacodynamic properties and safety of Cinnamomum zeylanicum (Ceylon cinnamon) in healthy adults: a phase I clinical trial. (2017). https://pubmed.ncbi.nlm.nih.gov/29282046/ DOI: 10.1186/s12906-017-2067-7

cross_nutrient

Chloride salt/kidney context -> pressure.

experimental_model

Same five-day periods.

limitations

Context difference, not proof of a universal adverse potassium effect; molecular mediator unproven.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

The pressure response differed from trials in people with better kidney function.

primary_references

[k-ckd-salts2026] Randomized Cross-Over Trial of Electrolyte, Acid-Base and Blood Pressure Effects of Salt Supplements in CKD (2026). https://pubmed.ncbi.nlm.nih.gov/42381762/ DOI: 10.1016/j.ekir.2026.106619

tissue_or_cell_type

Systemic circulation

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1685–1695

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same five-day periods. · source_derived_draft · unverified_draft

### k-ckd-chloride-salt-pressure Potassium chloride and sodium chloride increased home systolic pressure versus placebo in the CKD crossover. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pressure response differed from trials in people with better kidney function. organism: Homo sapiens tissue_or_cell_type: Systemic circulation experimental_model: Same five-day periods. limitations: Context difference, not proof of a universal adverse potassium effect; molecular mediator unproven. cross_nutrient: Chloride salt/kidney context -> pressure. [k-ckd-salts2026] Randomized Cross-Over Trial of Electrolyte, Acid-Base and Blood Pressure Effects of Salt Supplements in CKD (2026). https://pubmed.ncbi.nlm.nih.gov/42381762/ DOI: 10.1016/j.ekir.2026.106619

experimental_model

Four-week crossover; 36 completers.

limitations

Untreated elevated-pressure adults with relatively low baseline sodium/potassium intake; no detected pulse-wave-velocity benefit.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

The blood-pressure effect was measured directly in this trial.

primary_references

[k-gijsbers2015-bp] Effects of sodium and potassium supplementation on blood pressure and arterial stiffness: a fully controlled dietary intervention study (2015). https://pubmed.ncbi.nlm.nih.gov/25673113/ DOI: 10.1038/jhh.2015.3

tissue_or_cell_type

Systemic circulation

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1546–1555

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-week crossover; 36 completers. · source_derived_draft · unverified_draft

### k-controlled-feeding-pressure Potassium supplementation reduced 24-hour pressure by approximately 3.9/1.6 mmHg under controlled feeding. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood-pressure effect was measured directly in this trial. organism: Homo sapiens tissue_or_cell_type: Systemic circulation experimental_model: Four-week crossover; 36 completers. limitations: Untreated elevated-pressure adults with relatively low baseline sodium/potassium intake; no detected pulse-wave-velocity benefit. [k-gijsbers2015-bp] Effects of sodium and potassium supplementation on blood pressure and arterial stiffness: a fully controlled dietary intervention study (2015). https://pubmed.ncbi.nlm.nih.gov/25673113/ DOI: 10.1038/jhh.2015.3

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium/sodium balance -> pressure.

experimental_model

Same cohort and intervention.

limitations

Not an independent replication or proof of one molecular mediator.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Homo sapiens

plain_language

In this setting, lowering potassium raised blood pressure.

primary_references

[k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

tissue_or_cell_type

Systemic circulation

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1522–1532

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

### k-depletion-human-pressure Low potassium increased systolic/diastolic pressure by about 7/6 mmHg in the same crossover. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this setting, lowering potassium raised blood pressure. organism: Homo sapiens tissue_or_cell_type: Systemic circulation experimental_model: Same cohort and intervention. limitations: Not an independent replication or proof of one molecular mediator. cross_nutrient: Potassium/sodium balance -> pressure. [k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Four-year follow-up of 83 prior participants; 31 TT participants underwent repeat intervention with former treatment assignments reversed.

exposure

1.6 mg/day for 16 weeks in 2004 and again in 2008 with reversed allocations; not four years of continuous supplementation.

limitations

Follow-up selection, small TT sample and changing antihypertensive treatment limit inference; overlaps earlier cohort.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The earlier participants were studied again; this supports repeat responsiveness but is not an independent population or continuous four-year treatment.

primary_references

[b2-wilson2012] Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up (2012). https://pubmed.ncbi.nlm.nih.gov/22277556/ DOI: 10.3945/ajcn.111.026245

tissue_or_cell_type

Human clinical setting

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1540–1550

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-year follow-up of 83 prior participants; 31 TT participants underwent repeat intervention with former treatment assignments reversed. · source_derived_draft · unverified_draft

### b2-tt-bp-rechallenge A four-year follow-up with reversed intervention assignments in 31 TT participants again reported BP lowering during riboflavin administration. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The earlier participants were studied again; this supports repeat responsiveness but is not an independent population or continuous four-year treatment. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Four-year follow-up of 83 prior participants; 31 TT participants underwent repeat intervention with former treatment assignments reversed. limitations: Follow-up selection, small TT sample and changing antihypertensive treatment limit inference; overlaps earlier cohort. exposure: 1.6 mg/day for 16 weeks in 2004 and again in 2008 with reversed allocations; not four years of continuous supplementation. [b2-wilson2012] Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up (2012). https://pubmed.ncbi.nlm.nih.gov/22277556/ DOI: 10.3945/ajcn.111.026245

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Gene-cofactor clinical interaction; mechanism mediation was not demonstrated.

experimental_model

91 hypertensive adults with MTHFR 677TT and no overt cardiovascular disease; randomized trial on usual antihypertensive treatment.

exposure

1.6 mg/day riboflavin versus placebo for 16 weeks; experimental regimen.

limitations

Selected TT population; no proof of universal BP benefit, event reduction or a specific NO/methylation mechanism. Null diastolic endpoint retained.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

A genotype-targeted trial found a systolic blood-pressure benefit while participants continued their usual medicines.

primary_references

[b2-wilson2013] Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial (2013). https://pubmed.ncbi.nlm.nih.gov/23608654/ DOI: 10.1161/hypertensionaha.111.01047

tissue_or_cell_type

Human clinical setting

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1527–1538

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 91 hypertensive adults with MTHFR 677TT and no overt cardiovascular disease; randomized trial on usual antihypertensive treatment. · source_derived_draft · unverified_draft

### b2-tt-bp-trial In hypertensive adults with MTHFR 677TT, the systolic treatment effect was 5.6±2.6 mmHg favoring riboflavin; the diastolic effect was not significant. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A genotype-targeted trial found a systolic blood-pressure benefit while participants continued their usual medicines. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 91 hypertensive adults with MTHFR 677TT and no overt cardiovascular disease; randomized trial on usual antihypertensive treatment. limitations: Selected TT population; no proof of universal BP benefit, event reduction or a specific NO/methylation mechanism. Null diastolic endpoint retained. exposure: 1.6 mg/day riboflavin versus placebo for 16 weeks; experimental regimen. cross_nutrient: Gene-cofactor clinical interaction; mechanism mediation was not demonstrated. [b2-wilson2013] Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial (2013). https://pubmed.ncbi.nlm.nih.gov/23608654/ DOI: 10.1161/hypertensionaha.111.01047

evidence_span

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experimental_model

Randomized double-blind caffeine interaction experiment

exposure

250 mg caffeine with or without 200 mg theanine

limitations

Acute caffeine exposure; no basis for treating chronic hypertension or assuming caffeine adverse effects are all prevented.

nutrient_topic

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

organism

48 healthy humans

plain_language

One caffeine response was reduced; that does not make caffeine physiologically inactive.

primary_references

[theanine-p17891480] Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. (2008). https://pubmed.ncbi.nlm.nih.gov/17891480/ DOI: 10.1007/s00213-007-0938-1

tissue_or_cell_type

Blood pressure, mood and visual attention

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 1004–1015

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

### theanine-caffeine-pressure Theanine attenuated the caffeine-associated blood-pressure response in the experiment. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: One caffeine response was reduced; that does not make caffeine physiologically inactive. organism: 48 healthy humans tissue_or_cell_type: Blood pressure, mood and visual attention experimental_model: Randomized double-blind caffeine interaction experiment limitations: Acute caffeine exposure; no basis for treating chronic hypertension or assuming caffeine adverse effects are all prevented. exposure: 250 mg caffeine with or without 200 mg theanine evidence_span: {"source_cache": "artifacts/theanine-research/17891480.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dcd12cbd6fb30feee591192380733184f9928be3c146e39a4debc121a05b8815", "start_char": 0, "end_char": 1581, "text_sha256": "dcd12cbd6fb30feee591192380733184f9928be3c146e39a4debc121a05b8815"} [theanine-p17891480] Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. (2008). https://pubmed.ncbi.nlm.nih.gov/17891480/ DOI: 10.1007/s00213-007-0938-1

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium restriction changes sodium handling through NCC.

evidence_location

Figure 2A-C.

experimental_model

Wild-type versus Slc12a3-null dietary study

limitations

Knockout tests pathway contribution, not exclusive control of pressure.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Mus musculus

plain_language

Potassium scarcity can make sodium retention easier through NCC.

primary_references

[terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006

tissue_or_cell_type

Kidney

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 112–123

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type versus Slc12a3-null dietary study · source_derived_draft · unverified_draft

### renal-low-k-ncc-salt-retention Low-potassium feeding on high salt reduced sodium excretion; NCC deletion blunted the blood-pressure response. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium scarcity can make sodium retention easier through NCC. organism: Mus musculus tissue_or_cell_type: Kidney experimental_model: Wild-type versus Slc12a3-null dietary study limitations: Knockout tests pathway contribution, not exclusive control of pressure. cross_nutrient: Potassium restriction changes sodium handling through NCC. evidence_location: Figure 2A-C. [terker-2015-k-voltage-chloride] Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4332769/ DOI: 10.1016/j.cmet.2014.12.006

evidence_span

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experimental_model

Twenty subjects immersing finger, hand, or forearm and hand in 5 degrees C water

exposure

30 minutes of immersion at 5 degrees C followed by 15 minutes of recovery

limitations

The comparison of immersed areas is the point: the cardiovascular response depends on how much skin is cooled, not on the temperature alone.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

How much of you goes in the water decides what your heart and vessels do.

primary_references

[cold-p9202941] Cold induced vasodilatation and cardiovascular responses in humans during cold water immersion of various upper limb areas. (1997). https://pubmed.ncbi.nlm.nih.gov/9202941/ DOI: 10.1007/s004210050191

tissue_or_cell_type

Upper limb skin and cardiovascular system

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 221–232

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twenty subjects immersing finger, hand, or forearm and hand in 5 degrees C water · source_derived_draft · unverified_draft

### cold-civd-area-dependence Index-finger cooling produced cold-induced vasodilatation earlier than hand or forearm immersion (5.90 versus 7.95 and 9.26 minutes) and without significant cardiovascular change, whereas hand or forearm immersion produced a delayed and slower vasodilatation with bradycardia at the end of the test and a larger blood pressure rise. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: How much of you goes in the water decides what your heart and vessels do. organism: Human tissue_or_cell_type: Upper limb skin and cardiovascular system experimental_model: Twenty subjects immersing finger, hand, or forearm and hand in 5 degrees C water limitations: The comparison of immersed areas is the point: the cardiovascular response depends on how much skin is cooled, not on the temperature alone. exposure: 30 minutes of immersion at 5 degrees C followed by 15 minutes of recovery evidence_span: {"source_cache": "artifacts/cold-research/9202941.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c66741aac658e383d3e372a1c257db8dbcbce5e57d4dc053583181192f0c2e1", "start_char": 0, "end_char": 1846, "text_sha256": "0c66741aac658e383d3e372a1c257db8dbcbce5e57d4dc053583181192f0c2e1"} [cold-p9202941] Cold induced vasodilatation and cardiovascular responses in humans during cold water immersion of various upper limb areas. (1997). https://pubmed.ncbi.nlm.nih.gov/9202941/ DOI: 10.1007/s004210050191

evidence_span

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experimental_model

Young men during 1-hour head-out immersions at 32, 20 and 14 degrees C

exposure

One hour head-out immersion at three water temperatures

limitations

The thermoneutral arm separates hydrostatic pressure from cold. Cortisol did not rise at any temperature, which bears directly on calling immersion a stress response.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

Simply being in water, at any temperature, drops blood pressure and makes you urinate.

primary_references

[cold-p10751106] Human physiological responses to immersion into water of different temperatures. (2000). https://pubmed.ncbi.nlm.nih.gov/10751106/ DOI: 10.1007/s004210050065

tissue_or_cell_type

Whole body

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 169–180

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Young men during 1-hour head-out immersions at 32, 20 and 14 degrees C · source_derived_draft · unverified_draft

### cold-pressure-versus-cold Immersion at thermoneutral 32 degrees C did not change rectal temperature or metabolic rate but lowered heart rate by 15% and blood pressure by 11 to 12%, lowered plasma renin activity by 46%, cortisol by 34% and aldosterone by 17%, and increased diuresis by 107%. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Simply being in water, at any temperature, drops blood pressure and makes you urinate. organism: Human tissue_or_cell_type: Whole body experimental_model: Young men during 1-hour head-out immersions at 32, 20 and 14 degrees C limitations: The thermoneutral arm separates hydrostatic pressure from cold. Cortisol did not rise at any temperature, which bears directly on calling immersion a stress response. exposure: One hour head-out immersion at three water temperatures evidence_span: {"source_cache": "artifacts/cold-research/10751106.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d018fda7c67dc61bb0d4a38ddfd7850e7252897587c5a4477607271b10d42291", "start_char": 0, "end_char": 2332, "text_sha256": "d018fda7c67dc61bb0d4a38ddfd7850e7252897587c5a4477607271b10d42291"} [cold-p10751106] Human physiological responses to immersion into water of different temperatures. (2000). https://pubmed.ncbi.nlm.nih.gov/10751106/ DOI: 10.1007/s004210050065

evidence_span

{"source_cache": "artifacts/cold-research/12546194.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08c39cf0438d2f97c989e86721085415de696a3c7df99f5c2dc6529c40f7aeb2", "start_char": 0, "end_char": 1785, "text_sha256": "08c39cf0438d2f97c989e86721085415de696a3c7df99f5c2dc6529c40f7aeb2"}

experimental_model

Follow-up of winter swimmers and non-swimmer controls sampled in autumn, winter and spring

exposure

One winter swimming season

limitations

A seasonal follow-up with a control group. Its negative conclusion is explicit: the changes seen in swimmers also occurred in controls.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

Across a whole season the swimmers changed no more than the people who stayed dry.

primary_references

[cold-p12546194] Plasma catecholamines, serotonin and their metabolites and beta-endorphin of winter swimmers during one winter. Possible correlations to psychological traits. (2002). https://pubmed.ncbi.nlm.nih.gov/12546194/ DOI: 10.3402/ijch.v61i4.17494

tissue_or_cell_type

Plasma hormones and blood pressure

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 663–674

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Follow-up of winter swimmers and non-swimmer controls sampled in autumn, winter and spring · source_derived_draft · unverified_draft

### cold-seasonal-catecholamine-fall Mean plasma noradrenaline fell significantly from autumn to spring and more so in winter swimmers, but with no statistically significant difference between swimmers and controls; systolic blood pressure fell in swimmers, and plasma homovanillic acid and beta-endorphin were unchanged across all seasonal samples in both groups. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Across a whole season the swimmers changed no more than the people who stayed dry. organism: Human tissue_or_cell_type: Plasma hormones and blood pressure experimental_model: Follow-up of winter swimmers and non-swimmer controls sampled in autumn, winter and spring limitations: A seasonal follow-up with a control group. Its negative conclusion is explicit: the changes seen in swimmers also occurred in controls. exposure: One winter swimming season evidence_span: {"source_cache": "artifacts/cold-research/12546194.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08c39cf0438d2f97c989e86721085415de696a3c7df99f5c2dc6529c40f7aeb2", "start_char": 0, "end_char": 1785, "text_sha256": "08c39cf0438d2f97c989e86721085415de696a3c7df99f5c2dc6529c40f7aeb2"} [cold-p12546194] Plasma catecholamines, serotonin and their metabolites and beta-endorphin of winter swimmers during one winter. Possible correlations to psychological traits. (2002). https://pubmed.ncbi.nlm.nih.gov/12546194/ DOI: 10.3402/ijch.v61i4.17494