Dihydrocapsaicin

evidence_span

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experimental_model

In vivo and in situ gastrointestinal absorption studies in rats with tritiated dihydrocapsaicin

exposure

Capsaicin and dihydrocapsaicin administered into stomach, jejunum and ileum, with 2,4-dinitrophenol and sodium cyanide as metabolic inhibitors

limitations

Establishes both the route and the first metabolite by direct measurement in portal blood. A 1984 rat study using tritium label rather than mass spectrometry.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

It crosses the gut wall quickly and without being pumped, mostly in the small intestine.

primary_references

[dhc-p6710495] Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin in rats. (1984). https://pubmed.ncbi.nlm.nih.gov/6710495/ DOI: 10.1016/0041-008x(84)90121-2

tissue_or_cell_type

Stomach, jejunum, ileum and portal blood

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 478–489

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo and in situ gastrointestinal absorption studies in rats with tritiated dihydrocapsaicin · source_derived_draft · unverified_draft

### dhc-absorbed-passively About 85% of the dose of capsaicin or dihydrocapsaicin was absorbed in the gastrointestinal tract within 3 hours in vivo, and in situ about 50, 80 and 70% of the dose disappeared from the lumen of stomach, jejunum and ileum within 60 minutes, while addition of 2,4-dinitrophenol or sodium cyanide produced no significant reduction in uptake of tritiated dihydrocapsaicin in the jejunum, suggesting absorption by a nonactive process. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It crosses the gut wall quickly and without being pumped, mostly in the small intestine. organism: Rat tissue_or_cell_type: Stomach, jejunum, ileum and portal blood experimental_model: In vivo and in situ gastrointestinal absorption studies in rats with tritiated dihydrocapsaicin limitations: Establishes both the route and the first metabolite by direct measurement in portal blood. A 1984 rat study using tritium label rather than mass spectrometry. exposure: Capsaicin and dihydrocapsaicin administered into stomach, jejunum and ileum, with 2,4-dinitrophenol and sodium cyanide as metabolic inhibitors evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/6710495.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0a9a5cb2178f2b266fffe5efbd9580a0a1b5c03dd86b4bfe92b105194eb1f9b", "start_char": 0, "end_char": 1416, "text_sha256": "a0a9a5cb2178f2b266fffe5efbd9580a0a1b5c03dd86b4bfe92b105194eb1f9b"} [dhc-p6710495] Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin in rats. (1984). https://pubmed.ncbi.nlm.nih.gov/6710495/ DOI: 10.1016/0041-008x(84)90121-2

evidence_span

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experimental_model

Human prostate cancer cell lines with in vivo tumour growth and in silico binding analysis

exposure

Dihydrocapsaicin applied to human prostate cancer cells and to xenografts

limitations

Combines cell, animal and computational arms. The binding to the ligand-binding domain is in silico and is recorded as such.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human cells and mouse

plain_language

It stops the hormone receptor that drives prostate cancer from reaching the nucleus, and marks it for disposal.

primary_references

[dhc-p41045970] Androgen receptor inhibitory activity of dihydrocapsaicin: Insights from in vitro, in vivo and in silico studies. (2026). https://pubmed.ncbi.nlm.nih.gov/41045970/ DOI: 10.1016/j.jsbmb.2025.106872

tissue_or_cell_type

Prostate cancer

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 751–762

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human prostate cancer cell lines with in vivo tumour growth and in silico binding analysis · source_derived_draft · unverified_draft

### dhc-androgen-receptor-inhibition Dihydrocapsaicin induced proliferation suppression in human prostate cancer cells by hindering the cell cycle at the G0/G1 phase, probably inhibited androgen receptor activity by blocking its movement from the cytoplasm to the nucleus through binding to the receptor ligand-binding domain, and mechanistically facilitated androgen receptor release from a stabilizing chaperone complex and enhanced its ubiquitination by E3 ligases resulting in partial degradation via the ubiquitin-proteasome pathway, while also reducing tumour growth in vivo. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It stops the hormone receptor that drives prostate cancer from reaching the nucleus, and marks it for disposal. organism: Human cells and mouse tissue_or_cell_type: Prostate cancer experimental_model: Human prostate cancer cell lines with in vivo tumour growth and in silico binding analysis limitations: Combines cell, animal and computational arms. The binding to the ligand-binding domain is in silico and is recorded as such. exposure: Dihydrocapsaicin applied to human prostate cancer cells and to xenografts evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/41045970.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "232b30793c88e9e8fca6110ff6390d2d343ed78114d2daf849984cf2d2b80981", "start_char": 0, "end_char": 1566, "text_sha256": "232b30793c88e9e8fca6110ff6390d2d343ed78114d2daf849984cf2d2b80981"} [dhc-p41045970] Androgen receptor inhibitory activity of dihydrocapsaicin: Insights from in vitro, in vivo and in silico studies. (2026). https://pubmed.ncbi.nlm.nih.gov/41045970/ DOI: 10.1016/j.jsbmb.2025.106872

evidence_span

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experimental_model

Fourteen-day outcome study after middle cerebral artery occlusion in rats with BrdU labelling

exposure

Dihydrocapsaicin at 10 mg/kg body weight after 2 hours of occlusion

limitations

The dose here is roughly an order of magnitude above the hypothermia studies and no temperature is reported, so this may not be a hypothermic effect at all. Recorded with that stated.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

At a much larger dose it made new blood vessels grow into the damaged area over two weeks.

primary_references

[dhc-p32107104] Dihydrocapsaicin-induced angiogenesis and improved functional recovery after cerebral ischemia and reperfusion in a rat model. (2020). https://pubmed.ncbi.nlm.nih.gov/32107104/ DOI: 10.1016/j.jphs.2020.02.001

tissue_or_cell_type

Brain vasculature

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 465–476

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fourteen-day outcome study after middle cerebral artery occlusion in rats with BrdU labelling · source_derived_draft · unverified_draft

### dhc-angiogenesis-at-high-dose Dihydrocapsaicin at 10 mg/kg increased the expression of hypoxia inducible factor 1 alpha, vascular endothelial growth factor and matrix metalloprotease 9 at 3 and 14 days after ischaemia-reperfusion and of angiopoietin 1 and its receptor Tie-2 at 14 days, with angiogenesis confirmed by BrdU labelling co-localised with von Willebrand factor, alongside decreased neurological deficit scores and infarct volume and improved rotarod and pole test performance. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: At a much larger dose it made new blood vessels grow into the damaged area over two weeks. organism: Rat tissue_or_cell_type: Brain vasculature experimental_model: Fourteen-day outcome study after middle cerebral artery occlusion in rats with BrdU labelling limitations: The dose here is roughly an order of magnitude above the hypothermia studies and no temperature is reported, so this may not be a hypothermic effect at all. Recorded with that stated. exposure: Dihydrocapsaicin at 10 mg/kg body weight after 2 hours of occlusion evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/32107104.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a00c09c7443e15a674b7e9c6451ddd60a161f69ff98e33c32bcce0039662f8b1", "start_char": 0, "end_char": 1350, "text_sha256": "a00c09c7443e15a674b7e9c6451ddd60a161f69ff98e33c32bcce0039662f8b1"} [dhc-p32107104] Dihydrocapsaicin-induced angiogenesis and improved functional recovery after cerebral ischemia and reperfusion in a rat model. (2020). https://pubmed.ncbi.nlm.nih.gov/32107104/ DOI: 10.1016/j.jphs.2020.02.001

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

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experimental_model

Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment

exposure

Dihydrocapsaicin by continuous intravenous infusion at doses up to and beyond 2.0 mg/kg/h

limitations

The most important safety record in this collection, and the one whose population is the same population the therapy is aimed at. It is a rat study and the episodes are described rather than counted per animal.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

After a cardiac arrest the same drug triggers dangerous slowing of the heart at a third of the dose, and atropine stops it.

primary_references

[dhc-p20807439] Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin. (2010). https://pubmed.ncbi.nlm.nih.gov/20807439/ DOI: 10.1186/1471-2261-10-39

tissue_or_cell_type

Cardiovascular system

trigger_kind

biomarker_context Imported condition classification; unverified.

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 374–385

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment · source_derived_draft · unverified_draft

### dhc-bezold-jarisch-susceptibility At high levels of dihydrocapsaicin infusion above 2.0 mg/kg/h two single episodes of transient bradycardia and hypotension were observed in 33% of healthy rats, consistent with a TRPV1-agonist-induced Bezold-Jarisch reflex, whereas in resuscitated rats multiple episodes were observed in 100% of the rats at a dose of 0.65 mg/kg/h, and this effect could be completely blocked in the resuscitated rats by pre-treatment with the muscarinic acetylcholine antagonist atropine. Condition category: biomarker_context nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: After a cardiac arrest the same drug triggers dangerous slowing of the heart at a third of the dose, and atropine stops it. organism: Rat tissue_or_cell_type: Cardiovascular system experimental_model: Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment limitations: The most important safety record in this collection, and the one whose population is the same population the therapy is aimed at. It is a rat study and the episodes are described rather than counted per animal. exposure: Dihydrocapsaicin by continuous intravenous infusion at doses up to and beyond 2.0 mg/kg/h evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/20807439.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c", "start_char": 0, "end_char": 1709, "text_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c"} [dhc-p20807439] Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin. (2010). https://pubmed.ncbi.nlm.nih.gov/20807439/ DOI: 10.1186/1471-2261-10-39

evidence_span

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experimental_model

Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method

exposure

Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine

limitations

An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Frog

plain_language

This block is not the famous receptor at work: blocking the receptor does not stop it, and a stronger agonist does not cause it.

primary_references

[dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011

tissue_or_cell_type

Sciatic nerve

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 127–138

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method · source_derived_draft · unverified_draft

### dhc-conduction-block-not-trpv1 Capsaicin reversibly and concentration-dependently reduced the peak amplitude of the compound action potential, the TRPV1 antagonist capsazepine did not affect this activity, and the powerful TRPV1 agonist resiniferatoxin had no effect on compound action potentials, indicating no involvement of TRPV1 channels; capsaicin analogs and other vanilloids inhibited them in the same concentration-dependent way. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: This block is not the famous receptor at work: blocking the receptor does not stop it, and a stronger agonist does not cause it. organism: Frog tissue_or_cell_type: Sciatic nerve experimental_model: Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method limitations: An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds. exposure: Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/23352977.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb", "start_char": 0, "end_char": 1707, "text_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb"} [dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011

evidence_span

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experimental_model

Liquid chromatography-mass spectrometry of fresh peppers, oleoresin capsicum and commercial pepper sprays

exposure

Quantification of capsaicinoid analogues across pepper types, geographical origins and product lots

limitations

An analytical survey, not a biological study. It is recorded because it fixes what a capsaicinoid exposure actually contains, and because the product variability it found is a safety finding in its own right.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Plant and product extracts

plain_language

Two molecules carry almost all the heat of a chilli, and dihydrocapsaicin is the second of them.

primary_references

[dhc-p11372985] Quantitative analysis of capsaicinoids in fresh peppers, oleoresin capsicum and pepper spray products. (2001). https://pubmed.ncbi.nlm.nih.gov/11372985/ DOI: 10.1520/jfs14999j

tissue_or_cell_type

Pepper fruit and commercial products

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 75–86

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Liquid chromatography-mass spectrometry of fresh peppers, oleoresin capsicum and commercial pepper sprays · source_derived_draft · unverified_draft

### dhc-dhc-is-a-principal-capsaicinoid The principal analogues detected in oleoresin capsicum were capsaicin and dihydrocapsaicin, and these appeared to be the analogues primarily responsible for the pungency of the sample, with pungency proportional to total capsaicinoid concentration at roughly 15,000 Scoville Heat Units per microgram of total capsaicinoids. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Two molecules carry almost all the heat of a chilli, and dihydrocapsaicin is the second of them. organism: Plant and product extracts tissue_or_cell_type: Pepper fruit and commercial products experimental_model: Liquid chromatography-mass spectrometry of fresh peppers, oleoresin capsicum and commercial pepper sprays limitations: An analytical survey, not a biological study. It is recorded because it fixes what a capsaicinoid exposure actually contains, and because the product variability it found is a safety finding in its own right. exposure: Quantification of capsaicinoid analogues across pepper types, geographical origins and product lots evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/11372985.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "461cec319d02d96558b372027ffdcc391d17a12ebfbda0f441a0cd45d5c85eb7", "start_char": 0, "end_char": 1517, "text_sha256": "461cec319d02d96558b372027ffdcc391d17a12ebfbda0f441a0cd45d5c85eb7"} [dhc-p11372985] Quantitative analysis of capsaicinoids in fresh peppers, oleoresin capsicum and pepper spray products. (2001). https://pubmed.ncbi.nlm.nih.gov/11372985/ DOI: 10.1520/jfs14999j

evidence_span

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experimental_model

Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays

exposure

Dihydrocapsaicin from below 50 up to 500 micromolar, against capsaicin and vitamin C

limitations

The only head-to-head cytotoxicity comparison in this collection. Concentrations of 100 micromolar and above are far higher than any plasma level reported here.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human

plain_language

On blood vessel lining cells dihydrocapsaicin turns toxic at a fifth of the concentration capsaicin needs.

primary_references

[dhc-p36007275] Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity. (2022). https://pubmed.ncbi.nlm.nih.gov/36007275/ DOI: 10.1016/j.biopha.2022.113521

tissue_or_cell_type

Vascular endothelium

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 660–671

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays · source_derived_draft · unverified_draft

### dhc-dhc-more-cytotoxic Dihydrocapsaicin at concentrations up to 50 micromolar did not affect cell viability while 100 and 500 micromolar led to endothelial cytotoxicity, whereas capsaicin decreased cell viability only at a concentration of 500 micromolar. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: On blood vessel lining cells dihydrocapsaicin turns toxic at a fifth of the concentration capsaicin needs. organism: Human tissue_or_cell_type: Vascular endothelium experimental_model: Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays limitations: The only head-to-head cytotoxicity comparison in this collection. Concentrations of 100 micromolar and above are far higher than any plasma level reported here. exposure: Dihydrocapsaicin from below 50 up to 500 micromolar, against capsaicin and vitamin C evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/36007275.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b04a74a345c83df1454aa34ad591c7cefd04325de39cde8d5118bbea005aba3b", "start_char": 0, "end_char": 1605, "text_sha256": "b04a74a345c83df1454aa34ad591c7cefd04325de39cde8d5118bbea005aba3b"} [dhc-p36007275] Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity. (2022). https://pubmed.ncbi.nlm.nih.gov/36007275/ DOI: 10.1016/j.biopha.2022.113521

evidence_span

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experimental_model

Dose-ranging subcutaneous administration in rats with repeated dosing, antinociception testing and regional substance P measurement

exposure

Dihydrocapsaicin 0.5 to 10 mg/kg subcutaneously, single and repeated, against capsaicin

limitations

The founding comparison. It is a 1982 study and the antinociception endpoints are behavioural, but it is the only record here that puts a number on how the two compounds differ on temperature.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

For lowering body temperature, dihydrocapsaicin is roughly two thirds more powerful than capsaicin.

primary_references

[dhc-p6184240] Dihydrocapsaicin-induced hypothermia and substance P depletion. (1982). https://pubmed.ncbi.nlm.nih.gov/6184240/ DOI: 10.1016/0014-2999(82)90263-1

tissue_or_cell_type

Whole body, dorsal root ganglia and spinal cord

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 179–190

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dose-ranging subcutaneous administration in rats with repeated dosing, antinociception testing and regional substance P measurement · source_derived_draft · unverified_draft

### dhc-dhc-more-hypothermic Administration of dihydrocapsaicin to rats resulted in a dose-dependent hypothermia over 0.5 to 10 mg/kg subcutaneously, and dihydrocapsaicin was approximately 65% more effective in producing hypothermia than capsaicin. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: For lowering body temperature, dihydrocapsaicin is roughly two thirds more powerful than capsaicin. organism: Rat tissue_or_cell_type: Whole body, dorsal root ganglia and spinal cord experimental_model: Dose-ranging subcutaneous administration in rats with repeated dosing, antinociception testing and regional substance P measurement limitations: The founding comparison. It is a 1982 study and the antinociception endpoints are behavioural, but it is the only record here that puts a number on how the two compounds differ on temperature. exposure: Dihydrocapsaicin 0.5 to 10 mg/kg subcutaneously, single and repeated, against capsaicin evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/6184240.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dbeb69d90d490215b73d7a6f70fab0043e16cfdc8659c0daa4fda2cc0a7f6eaa", "start_char": 0, "end_char": 897, "text_sha256": "dbeb69d90d490215b73d7a6f70fab0043e16cfdc8659c0daa4fda2cc0a7f6eaa"} [dhc-p6184240] Dihydrocapsaicin-induced hypothermia and substance P depletion. (1982). https://pubmed.ncbi.nlm.nih.gov/6184240/ DOI: 10.1016/0014-2999(82)90263-1

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/6184240.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dbeb69d90d490215b73d7a6f70fab0043e16cfdc8659c0daa4fda2cc0a7f6eaa", "start_char": 0, "end_char": 897, "text_sha256": "dbeb69d90d490215b73d7a6f70fab0043e16cfdc8659c0daa4fda2cc0a7f6eaa"}

experimental_model

Dose-ranging subcutaneous administration in rats with repeated dosing, antinociception testing and regional substance P measurement

exposure

Dihydrocapsaicin 0.5 to 10 mg/kg subcutaneously, single and repeated, against capsaicin

limitations

The founding comparison. It is a 1982 study and the antinociception endpoints are behavioural, but it is the only record here that puts a number on how the two compounds differ on temperature.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Give it repeatedly and the cooling effect fades, and the fading carries across to capsaicin.

primary_references

[dhc-p6184240] Dihydrocapsaicin-induced hypothermia and substance P depletion. (1982). https://pubmed.ncbi.nlm.nih.gov/6184240/ DOI: 10.1016/0014-2999(82)90263-1

tissue_or_cell_type

Whole body, dorsal root ganglia and spinal cord

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 192–203

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dose-ranging subcutaneous administration in rats with repeated dosing, antinociception testing and regional substance P measurement · source_derived_draft · unverified_draft

### dhc-early-desensitisation Desensitization and cross-tolerance occurred to the hypothermic effects of both capsaicin and dihydrocapsaicin in rats, and repeated administration of either compound resulted in chemogenic antinociception but not marked thermal antinociception. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Give it repeatedly and the cooling effect fades, and the fading carries across to capsaicin. organism: Rat tissue_or_cell_type: Whole body, dorsal root ganglia and spinal cord experimental_model: Dose-ranging subcutaneous administration in rats with repeated dosing, antinociception testing and regional substance P measurement limitations: The founding comparison. It is a 1982 study and the antinociception endpoints are behavioural, but it is the only record here that puts a number on how the two compounds differ on temperature. exposure: Dihydrocapsaicin 0.5 to 10 mg/kg subcutaneously, single and repeated, against capsaicin evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/6184240.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dbeb69d90d490215b73d7a6f70fab0043e16cfdc8659c0daa4fda2cc0a7f6eaa", "start_char": 0, "end_char": 897, "text_sha256": "dbeb69d90d490215b73d7a6f70fab0043e16cfdc8659c0daa4fda2cc0a7f6eaa"} [dhc-p6184240] Dihydrocapsaicin-induced hypothermia and substance P depletion. (1982). https://pubmed.ncbi.nlm.nih.gov/6184240/ DOI: 10.1016/0014-2999(82)90263-1

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/41286578.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9063b8f1265e2ca00078e7452f81fc480eea4995c88a595cfbd42d245e74f68e", "start_char": 0, "end_char": 1538, "text_sha256": "9063b8f1265e2ca00078e7452f81fc480eea4995c88a595cfbd42d245e74f68e"}

experimental_model

Twelve Sprague-Dawley rats pretreated for two weeks, with rat liver microsome experiments

exposure

Dihydrocapsaicin 10 mg/kg/day for two weeks before a single oral 56 mg/kg dose of efavirenz

limitations

A named drug interaction with both in vivo and in vitro arms. Twelve rats in two groups, and a rat liver microsome system rather than a human one.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Two weeks of the compound left two and a half times as much of an HIV drug in the blood.

primary_references

[dhc-p41286578] Impact of Dihydrocapsaicin on the Metabolism of Efavirenz In Vitro and In Vivo. (2025). https://pubmed.ncbi.nlm.nih.gov/41286578/ DOI: 10.1002/prp2.70189

tissue_or_cell_type

Liver and plasma

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 595–606

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve Sprague-Dawley rats pretreated for two weeks, with rat liver microsome experiments · source_derived_draft · unverified_draft

### dhc-efavirenz-interaction After two weeks of dihydrocapsaicin at 10 mg/kg/day the area under the plasma concentration-time curve for efavirenz increased from 8821 to 22347 micrograms per millilitre per hour, time to maximum plasma concentration increased from 2.50 to 3.50 hours and elimination half-life from 3.13 to 3.51 hours, while plasma clearance fell from 6.71 to 2.65 litres per hour per kilogram, and dihydrocapsaicin significantly inhibited the metabolism of efavirenz in rat liver microsomes; the authors conclude the dose should be monitored in patients on efavirenz maintenance therapy. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Two weeks of the compound left two and a half times as much of an HIV drug in the blood. organism: Rat tissue_or_cell_type: Liver and plasma experimental_model: Twelve Sprague-Dawley rats pretreated for two weeks, with rat liver microsome experiments limitations: A named drug interaction with both in vivo and in vitro arms. Twelve rats in two groups, and a rat liver microsome system rather than a human one. exposure: Dihydrocapsaicin 10 mg/kg/day for two weeks before a single oral 56 mg/kg dose of efavirenz evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/41286578.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9063b8f1265e2ca00078e7452f81fc480eea4995c88a595cfbd42d245e74f68e", "start_char": 0, "end_char": 1538, "text_sha256": "9063b8f1265e2ca00078e7452f81fc480eea4995c88a595cfbd42d245e74f68e"} [dhc-p41286578] Impact of Dihydrocapsaicin on the Metabolism of Efavirenz In Vitro and In Vivo. (2025). https://pubmed.ncbi.nlm.nih.gov/41286578/ DOI: 10.1002/prp2.70189

evidence_span

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experimental_model

Ethidium bromide accumulation assay in Mycobacterium smegmatis with natural and synthetic capsaicinoids and capsinoids

exposure

Natural and synthetic capsaicinoids and synthetic capsinoids, against verapamil as the standard efflux pump inhibitor

limitations

A bacterial assay with a recognised positive control. Efflux inhibition in M. smegmatis is a model for, not a demonstration of, activity against pathogenic mycobacteria.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mycobacterium smegmatis

plain_language

Both compounds jam the pumps bacteria use to spit out antibiotics, better than the drug normally used for this.

primary_references

[dhc-p30428416] Resistance modulatory and efflux-inhibitory activities of capsaicinoids and capsinoids. (2019). https://pubmed.ncbi.nlm.nih.gov/30428416/ DOI: 10.1016/j.bioorg.2018.10.062

tissue_or_cell_type

Bacterial cell

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 764–775

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ethidium bromide accumulation assay in Mycobacterium smegmatis with natural and synthetic capsaicinoids and capsinoids · source_derived_draft · unverified_draft

### dhc-efflux-pump-inhibition Capsaicin and dihydrocapsaicin, the two most abundant capsaicinoids in Capsicum species, proved to be superior efflux pump inhibitors compared with the standard verapamil in an ethidium bromide accumulation assay in mycobacteria, and a dilution series showed dose dependency of both compounds. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Both compounds jam the pumps bacteria use to spit out antibiotics, better than the drug normally used for this. organism: Mycobacterium smegmatis tissue_or_cell_type: Bacterial cell experimental_model: Ethidium bromide accumulation assay in Mycobacterium smegmatis with natural and synthetic capsaicinoids and capsinoids limitations: A bacterial assay with a recognised positive control. Efflux inhibition in M. smegmatis is a model for, not a demonstration of, activity against pathogenic mycobacteria. exposure: Natural and synthetic capsaicinoids and synthetic capsinoids, against verapamil as the standard efflux pump inhibitor evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/30428416.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f94c6eead19764b3486e3cf015e5083de38b48d72f88cf31826a75fadb8a6fa3", "start_char": 0, "end_char": 1034, "text_sha256": "f94c6eead19764b3486e3cf015e5083de38b48d72f88cf31826a75fadb8a6fa3"} [dhc-p30428416] Resistance modulatory and efflux-inhibitory activities of capsaicinoids and capsinoids. (2019). https://pubmed.ncbi.nlm.nih.gov/30428416/ DOI: 10.1016/j.bioorg.2018.10.062

evidence_span

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experimental_model

Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays

exposure

Dihydrocapsaicin from below 50 up to 500 micromolar, against capsaicin and vitamin C

limitations

The only head-to-head cytotoxicity comparison in this collection. Concentrations of 100 micromolar and above are far higher than any plasma level reported here.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human

plain_language

Below the toxic range it calms the inflamed vessel lining and stops immune cells sticking to it.

primary_references

[dhc-p36007275] Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity. (2022). https://pubmed.ncbi.nlm.nih.gov/36007275/ DOI: 10.1016/j.biopha.2022.113521

tissue_or_cell_type

Vascular endothelium

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 673–684

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays · source_derived_draft · unverified_draft

### dhc-endothelial-anti-inflammatory Tumour necrosis factor alpha induced Ser536 phosphorylation of p65 NF-kappa-B, expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1, and interleukin 6 production in primary human endothelial cells, and these effects were robustly abrogated by dihydrocapsaicin, which also led to a marked reduction in tumour-necrosis-factor-mediated monocyte adhesion to endothelial cells. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Below the toxic range it calms the inflamed vessel lining and stops immune cells sticking to it. organism: Human tissue_or_cell_type: Vascular endothelium experimental_model: Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays limitations: The only head-to-head cytotoxicity comparison in this collection. Concentrations of 100 micromolar and above are far higher than any plasma level reported here. exposure: Dihydrocapsaicin from below 50 up to 500 micromolar, against capsaicin and vitamin C evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/36007275.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b04a74a345c83df1454aa34ad591c7cefd04325de39cde8d5118bbea005aba3b", "start_char": 0, "end_char": 1605, "text_sha256": "b04a74a345c83df1454aa34ad591c7cefd04325de39cde8d5118bbea005aba3b"} [dhc-p36007275] Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity. (2022). https://pubmed.ncbi.nlm.nih.gov/36007275/ DOI: 10.1016/j.biopha.2022.113521

evidence_span

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experimental_model

Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method

exposure

Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine

limitations

An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Frog

plain_language

For blocking nerve conduction the two compounds are equally strong, and stronger than a local anaesthetic.

primary_references

[dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011

tissue_or_cell_type

Sciatic nerve

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 114–125

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method · source_derived_draft · unverified_draft

### dhc-equal-conduction-block In the efficacy sequence for inhibition of compound action potentials the order was capsaicin equal to dihydrocapsaicin, then capsiate, eugenol, guaiacol, zingerone, vanillin and vanillylamine, with capsaicin ten-fold more effective than procaine; the extent of inhibition is determined by the property of the side chain bound to the vanillyl group. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: For blocking nerve conduction the two compounds are equally strong, and stronger than a local anaesthetic. organism: Frog tissue_or_cell_type: Sciatic nerve experimental_model: Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method limitations: An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds. exposure: Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/23352977.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb", "start_char": 0, "end_char": 1707, "text_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb"} [dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011

evidence_span

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experimental_model

Four-group asphyxia arrest study in 24 male Sprague Dawley rats with immunohistochemistry and tissue assays

exposure

Dihydrocapsaicin against cardiopulmonary resuscitation alone and against body surface cooling

limitations

Proposes the central mechanism and measures each step, but with six animals per group and immunohistochemical rather than functional readouts.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Fewer brain cells died, by about as much as physical cooling achieved.

primary_references

[dhc-p29035676] The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced Mild Hypothermia After Cardiopulmonary Resuscitation in Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29035676/ DOI: 10.1089/ther.2017.0032

tissue_or_cell_type

Hypothalamus, ventral septum and cerebral cortex

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 439–450

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-group asphyxia arrest study in 24 male Sprague Dawley rats with immunohistochemistry and tissue assays · source_derived_draft · unverified_draft

### dhc-fewer-apoptotic-cells Neurological deficit scores in the dihydrocapsaicin group were significantly higher than in the cardiopulmonary resuscitation and body surface cooling groups, and there were significantly fewer apoptotic cells in the dihydrocapsaicin and body surface cooling groups than in the resuscitation group. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Fewer brain cells died, by about as much as physical cooling achieved. organism: Rat tissue_or_cell_type: Hypothalamus, ventral septum and cerebral cortex experimental_model: Four-group asphyxia arrest study in 24 male Sprague Dawley rats with immunohistochemistry and tissue assays limitations: Proposes the central mechanism and measures each step, but with six animals per group and immunohistochemical rather than functional readouts. exposure: Dihydrocapsaicin against cardiopulmonary resuscitation alone and against body surface cooling evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/29035676.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb8f6fadb6a90a5afbd08a767fde07137140f2bf8cc536207ca8619e4168bf98", "start_char": 0, "end_char": 2035, "text_sha256": "bb8f6fadb6a90a5afbd08a767fde07137140f2bf8cc536207ca8619e4168bf98"} [dhc-p29035676] The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced Mild Hypothermia After Cardiopulmonary Resuscitation in Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29035676/ DOI: 10.1089/ther.2017.0032

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/36578383.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a36fc63af6f17ba1a551c87f5c73e288e9f468affcd39bcba5baad1ee1acf338", "start_char": 0, "end_char": 1090, "text_sha256": "a36fc63af6f17ba1a551c87f5c73e288e9f468affcd39bcba5baad1ee1acf338"}

experimental_model

Biotransformation of dihydrocapsaicin by four cultivated human intestinal fungal strains with NMR and HRESIMS structure determination

exposure

Dihydrocapsaicin incubated with cultivated human intestinal fungal strains

limitations

An in vitro biotransformation study with cultivated strains, not a gut community. The enzyme-inhibition result is a property of an isolated metabolite, not a demonstrated effect in an animal.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human intestinal fungi

plain_language

One of those fungal products blocks an enzyme that edits chromatin, at a low concentration.

primary_references

[dhc-p36578383] Biotransformation of dihydrocapsaicin by human intestinal fungi and the inhibitory effects of metabolites against LSD1. (2022). https://pubmed.ncbi.nlm.nih.gov/36578383/ DOI: 10.1016/j.heliyon.2022.e12325

tissue_or_cell_type

In vitro culture

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 582–593

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biotransformation of dihydrocapsaicin by four cultivated human intestinal fungal strains with NMR and HRESIMS structure determination · source_derived_draft · unverified_draft

### dhc-fungal-metabolite-inhibits-lsd1 One of the dihydrocapsaicin metabolites obtained from intestinal fungal biotransformation showed significant inhibitory effect on lysine-specific demethylase 1 with a half-maximal inhibitory concentration of 1.99 micromolar. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: One of those fungal products blocks an enzyme that edits chromatin, at a low concentration. organism: Human intestinal fungi tissue_or_cell_type: In vitro culture experimental_model: Biotransformation of dihydrocapsaicin by four cultivated human intestinal fungal strains with NMR and HRESIMS structure determination limitations: An in vitro biotransformation study with cultivated strains, not a gut community. The enzyme-inhibition result is a property of an isolated metabolite, not a demonstrated effect in an animal. exposure: Dihydrocapsaicin incubated with cultivated human intestinal fungal strains evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/36578383.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a36fc63af6f17ba1a551c87f5c73e288e9f468affcd39bcba5baad1ee1acf338", "start_char": 0, "end_char": 1090, "text_sha256": "a36fc63af6f17ba1a551c87f5c73e288e9f468affcd39bcba5baad1ee1acf338"} [dhc-p36578383] Biotransformation of dihydrocapsaicin by human intestinal fungi and the inhibitory effects of metabolites against LSD1. (2022). https://pubmed.ncbi.nlm.nih.gov/36578383/ DOI: 10.1016/j.heliyon.2022.e12325

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Human gastric cancer cell lines NCI-N87 and HGC-27 with western blotting and TRPV1 knockdown rescue experiments

exposure

Dihydrocapsaicin at a range of concentrations, with TRPV1 expression interfered as the test of mediation

limitations

The knockdown rescue is the strength here. Note the unusual direction: the compound raised expression of its own receptor rather than merely activating it.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human cells

plain_language

It holds gastric cancer cells in place by pushing them back towards a settled, non-migrating state.

primary_references

[dhc-p42509404] Dihydrocapsaicin suppresses the migration and invasion of gastric cancer cells by upregulating TRPV1 expression. (2026). https://pubmed.ncbi.nlm.nih.gov/42509404/ DOI: 10.1007/s11626-026-01226-3

tissue_or_cell_type

Gastric cancer cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 725–736

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human gastric cancer cell lines NCI-N87 and HGC-27 with western blotting and TRPV1 knockdown rescue experiments · source_derived_draft · unverified_draft

### dhc-gastric-cancer-migration Dihydrocapsaicin significantly and dose-dependently inhibited the migration and invasion of gastric cancer cells NCI-N87 and HGC-27, significantly increased the expression of TRPV1 and E-cadherin proteins and inhibited the expression of N-cadherin, vimentin and Snail proteins, and functional rescue experiments confirmed that when TRPV1 expression was inhibited the inhibitory effect on migration and invasion was significantly weakened. Condition category: machinery_impairment nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It holds gastric cancer cells in place by pushing them back towards a settled, non-migrating state. organism: Human cells tissue_or_cell_type: Gastric cancer cells experimental_model: Human gastric cancer cell lines NCI-N87 and HGC-27 with western blotting and TRPV1 knockdown rescue experiments limitations: The knockdown rescue is the strength here. Note the unusual direction: the compound raised expression of its own receptor rather than merely activating it. exposure: Dihydrocapsaicin at a range of concentrations, with TRPV1 expression interfered as the test of mediation evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/42509404.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55ec938b5e2c0b1421c473c60c3468ad24770198ee9d1f6549c62af579bf4c4c", "start_char": 0, "end_char": 1925, "text_sha256": "55ec938b5e2c0b1421c473c60c3468ad24770198ee9d1f6549c62af579bf4c4c"} [dhc-p42509404] Dihydrocapsaicin suppresses the migration and invasion of gastric cancer cells by upregulating TRPV1 expression. (2026). https://pubmed.ncbi.nlm.nih.gov/42509404/ DOI: 10.1007/s11626-026-01226-3

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/27748914.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ffc172fb64714099772462ba33304b69637efac75f1f218f2032e26bbc32dc90", "start_char": 0, "end_char": 1610, "text_sha256": "ffc172fb64714099772462ba33304b69637efac75f1f218f2032e26bbc32dc90"}

experimental_model

U251 human glioma cells with flow cytometry, transmission electron microscopy and a murine xenograft model

exposure

Capsaicin and dihydrocapsaicin applied across doses and times, with L929 normal fibroblasts as a selectivity control

limitations

Includes a normal-cell control and an in vivo arm. Cell-line concentrations are not stated in the abstract and are not assumed here.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human cells and mouse

plain_language

It kills glioma cells through the mitochondria while largely sparing normal cells.

primary_references

[dhc-p27748914] Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+‑mediated mitochondrial pathway. (2016). https://pubmed.ncbi.nlm.nih.gov/27748914/ DOI: 10.3892/mmr.2016.5784

tissue_or_cell_type

Glioma cells

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 712–723

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · U251 human glioma cells with flow cytometry, transmission electron microscopy and a murine xenograft model · source_derived_draft · unverified_draft

### dhc-glioma-apoptosis Treatment of U251 glioma cells with capsaicin and dihydrocapsaicin resulted in a dose- and time-dependent inhibition of cell viability and induction of apoptosis, whereas few effects were observed on the viability of L929 normal murine fibroblast cells, and the apoptosis was associated with generation of reactive oxygen species, increased calcium concentrations, mitochondrial depolarization, release of cytochrome c into the cytosol and activation of caspase-9 and caspase-3, with anti-tumour effects confirmed in a murine tumour xenograft model. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It kills glioma cells through the mitochondria while largely sparing normal cells. organism: Human cells and mouse tissue_or_cell_type: Glioma cells experimental_model: U251 human glioma cells with flow cytometry, transmission electron microscopy and a murine xenograft model limitations: Includes a normal-cell control and an in vivo arm. Cell-line concentrations are not stated in the abstract and are not assumed here. exposure: Capsaicin and dihydrocapsaicin applied across doses and times, with L929 normal fibroblasts as a selectivity control evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/27748914.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ffc172fb64714099772462ba33304b69637efac75f1f218f2032e26bbc32dc90", "start_char": 0, "end_char": 1610, "text_sha256": "ffc172fb64714099772462ba33304b69637efac75f1f218f2032e26bbc32dc90"} [dhc-p27748914] Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+‑mediated mitochondrial pathway. (2016). https://pubmed.ncbi.nlm.nih.gov/27748914/ DOI: 10.3892/mmr.2016.5784

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/25462121.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "667a4d33ee4b6423efe4532d0138ba6eb68a08fcc41b33ff5d04f442ad6f6177", "start_char": 0, "end_char": 1576, "text_sha256": "667a4d33ee4b6423efe4532d0138ba6eb68a08fcc41b33ff5d04f442ad6f6177"}

experimental_model

Validated reverse-phase HPLC with fluorescence detection applied to rat small intestine luminal perfusion

exposure

Standardised Capsicum extract at 30 micrograms per millilitre perfused luminally for 90 minutes

limitations

Primarily a method development paper. The substantive finding recorded here is the identification of glucuronide conjugates of both compounds in the perfusate by mass spectrometry.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

The gut also attaches a sugar group to both compounds while they are being absorbed.

primary_references

[dhc-p25462121] A validated HPLC-FLD method for analysis of intestinal absorption and metabolism of capsaicin and dihydrocapsaicin in the rat. (2015). https://pubmed.ncbi.nlm.nih.gov/25462121/ DOI: 10.1016/j.jpba.2014.10.007

tissue_or_cell_type

Small intestine lumen

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 556–567

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Validated reverse-phase HPLC with fluorescence detection applied to rat small intestine luminal perfusion · source_derived_draft · unverified_draft

### dhc-glucuronidation-in-gut The structure of the glucuronide metabolites of capsaicin and dihydrocapsaicin that appeared in the perfusate during 90 minutes of luminal perfusion of a standardised Capsicum extract was identified by mass spectrometry. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The gut also attaches a sugar group to both compounds while they are being absorbed. organism: Rat tissue_or_cell_type: Small intestine lumen experimental_model: Validated reverse-phase HPLC with fluorescence detection applied to rat small intestine luminal perfusion limitations: Primarily a method development paper. The substantive finding recorded here is the identification of glucuronide conjugates of both compounds in the perfusate by mass spectrometry. exposure: Standardised Capsicum extract at 30 micrograms per millilitre perfused luminally for 90 minutes evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/25462121.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "667a4d33ee4b6423efe4532d0138ba6eb68a08fcc41b33ff5d04f442ad6f6177", "start_char": 0, "end_char": 1576, "text_sha256": "667a4d33ee4b6423efe4532d0138ba6eb68a08fcc41b33ff5d04f442ad6f6177"} [dhc-p25462121] A validated HPLC-FLD method for analysis of intestinal absorption and metabolism of capsaicin and dihydrocapsaicin in the rat. (2015). https://pubmed.ncbi.nlm.nih.gov/25462121/ DOI: 10.1016/j.jpba.2014.10.007

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/30090648.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c", "start_char": 0, "end_char": 2110, "text_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c"}

experimental_model

Randomised seven-group study in 144 male Sprague Dawley rats after middle cerebral artery occlusion

exposure

Low-dose dihydrocapsaicin at 0.5 mg/kg or high-dose at 1.5 mg/kg, an ice pad at 31 degrees, and the combination, with an external-temperature-control arm

limitations

A large randomised design with a dose-response surprise: the high dose alone did nothing while the low dose worked. That non-monotonicity is recorded because it contradicts the simple dose-response in the other records.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Tripling the dose did not help and in this design the higher dose alone did nothing at all.

primary_references

[dhc-p30090648] Synergistically Induced Hypothermia and Enhanced Neuroprotection by Pharmacological and Physical Approaches in Stroke. (2018). https://pubmed.ncbi.nlm.nih.gov/30090648/ DOI: 10.14336/ad.2017.0817

tissue_or_cell_type

Brain

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 348–359

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised seven-group study in 144 male Sprague Dawley rats after middle cerebral artery occlusion · source_derived_draft · unverified_draft

### dhc-high-dose-alone-failed No effect was observed when using the ice pad alone or high-dose dihydrocapsaicin at 1.5 mg/kg alone, while low-dose dihydrocapsaicin at 0.5 mg/kg reduced neurological deficits by 26%. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Tripling the dose did not help and in this design the higher dose alone did nothing at all. organism: Rat tissue_or_cell_type: Brain experimental_model: Randomised seven-group study in 144 male Sprague Dawley rats after middle cerebral artery occlusion limitations: A large randomised design with a dose-response surprise: the high dose alone did nothing while the low dose worked. That non-monotonicity is recorded because it contradicts the simple dose-response in the other records. exposure: Low-dose dihydrocapsaicin at 0.5 mg/kg or high-dose at 1.5 mg/kg, an ice pad at 31 degrees, and the combination, with an external-temperature-control arm evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/30090648.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c", "start_char": 0, "end_char": 2110, "text_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c"} [dhc-p30090648] Synergistically Induced Hypothermia and Enhanced Neuroprotection by Pharmacological and Physical Approaches in Stroke. (2018). https://pubmed.ncbi.nlm.nih.gov/30090648/ DOI: 10.14336/ad.2017.0817

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/29035676.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb8f6fadb6a90a5afbd08a767fde07137140f2bf8cc536207ca8619e4168bf98", "start_char": 0, "end_char": 2035, "text_sha256": "bb8f6fadb6a90a5afbd08a767fde07137140f2bf8cc536207ca8619e4168bf98"}

experimental_model

Four-group asphyxia arrest study in 24 male Sprague Dawley rats with immunohistochemistry and tissue assays

exposure

Dihydrocapsaicin against cardiopulmonary resuscitation alone and against body surface cooling

limitations

Proposes the central mechanism and measures each step, but with six animals per group and immunohistochemical rather than functional readouts.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

The proposed route runs through the brain’s thermostat: calcium floods in and a hormone is released.

primary_references

[dhc-p29035676] The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced Mild Hypothermia After Cardiopulmonary Resuscitation in Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29035676/ DOI: 10.1089/ther.2017.0032

tissue_or_cell_type

Hypothalamus, ventral septum and cerebral cortex

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 426–437

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-group asphyxia arrest study in 24 male Sprague Dawley rats with immunohistochemistry and tissue assays · source_derived_draft · unverified_draft

### dhc-hypothalamic-calcium-avp Hypothalamic TRPV1 expression, hypothalamic intracellular calcium concentration and arginine vasopressin concentration in the ventral septum were significantly higher in the dihydrocapsaicin group than in the control, resuscitation and body surface cooling groups, and the authors concluded that dihydrocapsaicin activates TRPV1 on hypothalamic cells to cause a large calcium influx which causes the release of vasopressin to induce hypothermia. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The proposed route runs through the brain’s thermostat: calcium floods in and a hormone is released. organism: Rat tissue_or_cell_type: Hypothalamus, ventral septum and cerebral cortex experimental_model: Four-group asphyxia arrest study in 24 male Sprague Dawley rats with immunohistochemistry and tissue assays limitations: Proposes the central mechanism and measures each step, but with six animals per group and immunohistochemical rather than functional readouts. exposure: Dihydrocapsaicin against cardiopulmonary resuscitation alone and against body surface cooling evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/29035676.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb8f6fadb6a90a5afbd08a767fde07137140f2bf8cc536207ca8619e4168bf98", "start_char": 0, "end_char": 2035, "text_sha256": "bb8f6fadb6a90a5afbd08a767fde07137140f2bf8cc536207ca8619e4168bf98"} [dhc-p29035676] The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced Mild Hypothermia After Cardiopulmonary Resuscitation in Rats. (2018). https://pubmed.ncbi.nlm.nih.gov/29035676/ DOI: 10.1089/ther.2017.0032

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/24305062.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f48560ff0df2e92e757c483dad96056155b0b629ddf0b5d5b41416201adfe17", "start_char": 0, "end_char": 1711, "text_sha256": "6f48560ff0df2e92e757c483dad96056155b0b629ddf0b5d5b41416201adfe17"}

experimental_model

Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion

exposure

Dihydrocapsaicin 1.25 mg/kg subcutaneously, begun 90 minutes after the start of reperfusion, with normothermia by external heat support as a control arm

limitations

The two control arms are what make this the strongest record here: the knockout shows the receptor is required, and the heat-support arm shows the temperature drop rather than receptor activation is what protects.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mouse

plain_language

The cooling happens through the receptor, and in these mice it barely touched the circulation.

primary_references

[dhc-p24305062] Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion. (2014). https://pubmed.ncbi.nlm.nih.gov/24305062/ DOI: 10.1152/ajpregu.00329.2013

tissue_or_cell_type

Brain and cardiovascular system

trigger_kind

machinery_impairment Imported condition classification; unverified.

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 296–307

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion · source_derived_draft · unverified_draft

### dhc-hypothermia-requires-trpv1 Dihydrocapsaicin at 1.25 mg/kg produced a stable drop in core temperature to 33 degrees in naive and ischaemia-reperfusion mice but not in TRPV1 knockout mice, and had no measurable effect on heart rate or cerebral perfusion while producing a slight transient drop in mean arterial pressure of less than 6 millimetres of mercury. Condition category: machinery_impairment nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The cooling happens through the receptor, and in these mice it barely touched the circulation. organism: Mouse tissue_or_cell_type: Brain and cardiovascular system experimental_model: Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion limitations: The two control arms are what make this the strongest record here: the knockout shows the receptor is required, and the heat-support arm shows the temperature drop rather than receptor activation is what protects. exposure: Dihydrocapsaicin 1.25 mg/kg subcutaneously, begun 90 minutes after the start of reperfusion, with normothermia by external heat support as a control arm evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24305062.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f48560ff0df2e92e757c483dad96056155b0b629ddf0b5d5b41416201adfe17", "start_char": 0, "end_char": 1711, "text_sha256": "6f48560ff0df2e92e757c483dad96056155b0b629ddf0b5d5b41416201adfe17"} [dhc-p24305062] Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion. (2014). https://pubmed.ncbi.nlm.nih.gov/24305062/ DOI: 10.1152/ajpregu.00329.2013

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/20807439.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c", "start_char": 0, "end_char": 1709, "text_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c"}

experimental_model

Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment

exposure

Dihydrocapsaicin by continuous intravenous infusion at doses up to and beyond 2.0 mg/kg/h

limitations

The most important safety record in this collection, and the one whose population is the same population the therapy is aimed at. It is a rat study and the episodes are described rather than counted per animal.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

The first thing it does is push blood pressure and heart rate up, before anything else happens.

primary_references

[dhc-p20807439] Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin. (2010). https://pubmed.ncbi.nlm.nih.gov/20807439/ DOI: 10.1186/1471-2261-10-39

tissue_or_cell_type

Cardiovascular system

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 387–398

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment · source_derived_draft · unverified_draft

### dhc-initial-pressor-response Compared to baseline, infusion of dihydrocapsaicin caused an initial increase in mean arterial blood pressure of 25% in healthy rats and 10% in resuscitated rats, and an initial tachycardic response of 30% and 20% respectively. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The first thing it does is push blood pressure and heart rate up, before anything else happens. organism: Rat tissue_or_cell_type: Cardiovascular system experimental_model: Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment limitations: The most important safety record in this collection, and the one whose population is the same population the therapy is aimed at. It is a rat study and the episodes are described rather than counted per animal. exposure: Dihydrocapsaicin by continuous intravenous infusion at doses up to and beyond 2.0 mg/kg/h evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/20807439.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c", "start_char": 0, "end_char": 1709, "text_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c"} [dhc-p20807439] Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin. (2010). https://pubmed.ncbi.nlm.nih.gov/20807439/ DOI: 10.1186/1471-2261-10-39

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/2280802.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1", "start_char": 0, "end_char": 1280, "text_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1"}

experimental_model

Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction

exposure

Tritiated dihydrocapsaicin and unlabelled capsaicin given intragastrically, intravenously or subcutaneously

limitations

The comparison across routes is the point, and it is the reason every hypothermia study in this collection injects the drug rather than feeding it. Anaesthetised rats, and identification is chromatographic.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

The liver breaks it down and the brain does not, and what the liver makes is inert.

primary_references

[dhc-p2280802] Absorption and metabolism of capsaicinoids following intragastric administration in rats. (1990). https://pubmed.ncbi.nlm.nih.gov/2280802/ DOI: 10.1007/bf00169449

tissue_or_cell_type

Portal blood, trunk blood, brain and liver

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 517–528

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction · source_derived_draft · unverified_draft

### dhc-liver-not-brain Dihydrocapsaicin was metabolized when incubated in vitro with liver tissue but not with brain tissue, a certain degree of biotransformation already took place in the intestinal lumen, there appears to be a saturable absorption and degradation process in the gastrointestinal tract and very effective metabolism in the liver, and the metabolic products did not show capsaicin-like biological activity. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The liver breaks it down and the brain does not, and what the liver makes is inert. organism: Rat tissue_or_cell_type: Portal blood, trunk blood, brain and liver experimental_model: Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction limitations: The comparison across routes is the point, and it is the reason every hypothermia study in this collection injects the drug rather than feeding it. Anaesthetised rats, and identification is chromatographic. exposure: Tritiated dihydrocapsaicin and unlabelled capsaicin given intragastrically, intravenously or subcutaneously evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/2280802.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1", "start_char": 0, "end_char": 1280, "text_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1"} [dhc-p2280802] Absorption and metabolism of capsaicinoids following intragastric administration in rats. (1990). https://pubmed.ncbi.nlm.nih.gov/2280802/ DOI: 10.1007/bf00169449

evidence_span

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experimental_model

Blinded rat cervical spinal cord injury study with telemetry and histopathology at 48 hours and 6 weeks

exposure

Intravenous dihydrocapsaicin totalling about 0.60 mg/kg begun after a 4 hour delay, against physical cooling, both to 33 degrees for 4 hours

limitations

A head-to-head against physical cooling with blinded assessment at two timepoints. It shows equivalence, not superiority, which is what the authors claim.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

The drug worked about as well as packing the animal in cold fluid, and is easier to give.

primary_references

[dhc-p35675523] A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury. (2022). https://pubmed.ncbi.nlm.nih.gov/35675523/ DOI: 10.1089/ther.2021.0013

tissue_or_cell_type

Cervical spinal cord

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 452–463

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Blinded rat cervical spinal cord injury study with telemetry and histopathology at 48 hours and 6 weeks · source_derived_draft · unverified_draft

### dhc-matches-physical-cooling In a rat model of cervical spinal cord injury, dihydrocapsaicin reliably induced systemic cooling to 32 to 33 degrees, and at both 48 hours and 6 weeks the two modes of hypothermia yielded similar improvements in neurological function and lesion size compared with normothermic controls, indicating that dihydrocapsaicin-induced hypothermia may be comparable with physical hypothermia in efficacy but more clinically feasible to administer. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The drug worked about as well as packing the animal in cold fluid, and is easier to give. organism: Rat tissue_or_cell_type: Cervical spinal cord experimental_model: Blinded rat cervical spinal cord injury study with telemetry and histopathology at 48 hours and 6 weeks limitations: A head-to-head against physical cooling with blinded assessment at two timepoints. It shows equivalence, not superiority, which is what the authors claim. exposure: Intravenous dihydrocapsaicin totalling about 0.60 mg/kg begun after a 4 hour delay, against physical cooling, both to 33 degrees for 4 hours evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/35675523.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "be32dc3c18b06ec73979a729e98459c00fb147186da0b9601fb1a8e96586fccf", "start_char": 0, "end_char": 1650, "text_sha256": "be32dc3c18b06ec73979a729e98459c00fb147186da0b9601fb1a8e96586fccf"} [dhc-p35675523] A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury. (2022). https://pubmed.ncbi.nlm.nih.gov/35675523/ DOI: 10.1089/ther.2021.0013

evidence_span

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experimental_model

Melanoma A375 and MV3 cell lines with a NOD/SCID mouse xenograft and beta-catenin overexpression rescue

exposure

Dihydrocapsaicin at 100 micromolar, with exogenous beta-catenin overexpression as the rescue

limitations

A corrigendum was published against this article in 2022 stating that four transwell and soft agar images in Figures 5 and 6 were presented with incorrect pictures. Those are the beta-catenin rescue figures, which carry the mechanistic conclusion. The descriptive anti-proliferative result does not rest on them; the mechanism does.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human cells and mouse

plain_language

It slowed melanoma growth and spread, apparently by marking a growth signal for destruction.

primary_references

[dhc-p33833997] Dihydrocapsaicin Inhibits Cell Proliferation and Metastasis in Melanoma via Down-regulating β-Catenin Pathway. (2021). https://pubmed.ncbi.nlm.nih.gov/33833997/ DOI: 10.3389/fonc.2021.648052

tissue_or_cell_type

Melanoma

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 738–749

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Melanoma A375 and MV3 cell lines with a NOD/SCID mouse xenograft and beta-catenin overexpression rescue · source_derived_draft · unverified_draft

### dhc-melanoma-beta-catenin Melanoma A375 and MV3 cell lines treated with dihydrocapsaicin showed significantly suppressed proliferation, migration and invasion, dihydrocapsaicin inhibited xenograft tumour growth and pulmonary metastasis in a NOD/SCID mouse model, beta-catenin was downregulated after treatment along with cyclin D1, c-Myc, MMP2 and MMP7, and mechanistically dihydrocapsaicin accelerated ubiquitination of beta-catenin and upregulated the E3 ubiquitin protein ligase BTRC. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It slowed melanoma growth and spread, apparently by marking a growth signal for destruction. organism: Human cells and mouse tissue_or_cell_type: Melanoma experimental_model: Melanoma A375 and MV3 cell lines with a NOD/SCID mouse xenograft and beta-catenin overexpression rescue limitations: A corrigendum was published against this article in 2022 stating that four transwell and soft agar images in Figures 5 and 6 were presented with incorrect pictures. Those are the beta-catenin rescue figures, which carry the mechanistic conclusion. The descriptive anti-proliferative result does not rest on them; the mechanism does. exposure: Dihydrocapsaicin at 100 micromolar, with exogenous beta-catenin overexpression as the rescue evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/33833997.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5da9019700891a189af0778272381e19a8f276d17d20c59c5f74fbc67b15454e", "start_char": 0, "end_char": 1370, "text_sha256": "5da9019700891a189af0778272381e19a8f276d17d20c59c5f74fbc67b15454e"} [dhc-p33833997] Dihydrocapsaicin Inhibits Cell Proliferation and Metastasis in Melanoma via Down-regulating β-Catenin Pathway. (2021). https://pubmed.ncbi.nlm.nih.gov/33833997/ DOI: 10.3389/fonc.2021.648052

evidence_span

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experimental_model

Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays

exposure

Dihydrocapsaicin from below 50 up to 500 micromolar, against capsaicin and vitamin C

limitations

The only head-to-head cytotoxicity comparison in this collection. Concentrations of 100 micromolar and above are far higher than any plasma level reported here.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human

plain_language

It raises the signal that relaxes blood vessels, and mops up free radicals in a test tube.

primary_references

[dhc-p36007275] Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity. (2022). https://pubmed.ncbi.nlm.nih.gov/36007275/ DOI: 10.1016/j.biopha.2022.113521

tissue_or_cell_type

Vascular endothelium

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 686–697

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays · source_derived_draft · unverified_draft

### dhc-nitric-oxide-and-radicals Nitric oxide production was significantly induced by dihydrocapsaicin and by capsaicin compared with vehicle control, and similar to capsaicin and vitamin C, dihydrocapsaicin scavenged DPPH free radicals in vitro. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It raises the signal that relaxes blood vessels, and mops up free radicals in a test tube. organism: Human tissue_or_cell_type: Vascular endothelium experimental_model: Primary human endothelial cells stimulated with tumour necrosis factor alpha, with viability, adhesion and radical scavenging assays limitations: The only head-to-head cytotoxicity comparison in this collection. Concentrations of 100 micromolar and above are far higher than any plasma level reported here. exposure: Dihydrocapsaicin from below 50 up to 500 micromolar, against capsaicin and vitamin C evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/36007275.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b04a74a345c83df1454aa34ad591c7cefd04325de39cde8d5118bbea005aba3b", "start_char": 0, "end_char": 1605, "text_sha256": "b04a74a345c83df1454aa34ad591c7cefd04325de39cde8d5118bbea005aba3b"} [dhc-p36007275] Beneficial effects of capsaicin and dihydrocapsaicin on endothelial inflammation, nitric oxide production and antioxidant activity. (2022). https://pubmed.ncbi.nlm.nih.gov/36007275/ DOI: 10.1016/j.biopha.2022.113521

evidence_span

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experimental_model

Controlled prospective study in conscious unrestrained young and aged male mice with implanted thermocouples and wireless transponders

exposure

Dihydrocapsaicin 2 to 4 mg/kg subcutaneously, alone and combined with the TRPM8 inhibitor compound 5 at 20 to 30 mg/kg

limitations

Includes aged animals, which most of this collection does not. Its finding that the effect does not desensitise is the direct opposite of the 1982 rat result and the two are recorded as conflicting.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mouse

plain_language

Given this way the cooling did not wear off with repetition, and it worked harder in old mice than young ones.

primary_references

[dhc-p24595220] Transient receptor potential melastatin 8 channel inhibition potentiates the hypothermic response to transient receptor potential vanilloid 1 activation in the conscious mouse. (2014). https://pubmed.ncbi.nlm.nih.gov/24595220/ DOI: 10.1097/ccm.0000000000000229

tissue_or_cell_type

Core temperature

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 270–281

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled prospective study in conscious unrestrained young and aged male mice with implanted thermocouples and wireless transponders · source_derived_draft · unverified_draft

### dhc-no-desensitisation Dihydrocapsaicin produced a dose-dependent drop in core temperature over 2 to 4 mg/kg subcutaneously, a loading dose followed by continuous infusion produced a rapid and prolonged drop of more than six hours within the therapeutic range of 32 to 34 degrees, and the hypothermic effect was augmented in aged mice and was not desensitised with repeated administration. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Given this way the cooling did not wear off with repetition, and it worked harder in old mice than young ones. organism: Mouse tissue_or_cell_type: Core temperature experimental_model: Controlled prospective study in conscious unrestrained young and aged male mice with implanted thermocouples and wireless transponders limitations: Includes aged animals, which most of this collection does not. Its finding that the effect does not desensitise is the direct opposite of the 1982 rat result and the two are recorded as conflicting. exposure: Dihydrocapsaicin 2 to 4 mg/kg subcutaneously, alone and combined with the TRPM8 inhibitor compound 5 at 20 to 30 mg/kg evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24595220.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87", "start_char": 0, "end_char": 1882, "text_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87"} [dhc-p24595220] Transient receptor potential melastatin 8 channel inhibition potentiates the hypothermic response to transient receptor potential vanilloid 1 activation in the conscious mouse. (2014). https://pubmed.ncbi.nlm.nih.gov/24595220/ DOI: 10.1097/ccm.0000000000000229

evidence_span

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experimental_model

In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control

exposure

Capsaicin and dihydrocapsaicin against the endogenous vanilloids N-oleoyldopamine and N-arachidonoyl-dopamine, with ADP, collagen and arachidonic acid as agonists

limitations

The agonist-by-agonist design is what makes this useful: it separates the two plant compounds where a single-agonist study would have merged them. A TRPV1 antagonist control was included.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human

plain_language

Capsaicin blocks clumping triggered two ways; dihydrocapsaicin blocks only one of them.

primary_references

[dhc-p24953906] Vanilloid-like agents inhibit aggregation of human platelets. (2014). https://pubmed.ncbi.nlm.nih.gov/24953906/ DOI: 10.1016/j.thromres.2014.05.038

tissue_or_cell_type

Platelets

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 153–164

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control · source_derived_draft · unverified_draft

### dhc-platelet-divergence Capsaicin, N-oleoyldopamine and N-arachidonoyl-dopamine inhibited ADP-induced platelet aggregation in a concentration-dependent manner, while arachidonic-acid-induced aggregation was inhibited by capsaicin, dihydrocapsaicin and N-arachidonoyl-dopamine but not by N-oleoyldopamine, and collagen-induced aggregation was inhibited only by the endogenous vanilloids and not by capsaicin or dihydrocapsaicin. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Capsaicin blocks clumping triggered two ways; dihydrocapsaicin blocks only one of them. organism: Human tissue_or_cell_type: Platelets experimental_model: In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control limitations: The agonist-by-agonist design is what makes this useful: it separates the two plant compounds where a single-agonist study would have merged them. A TRPV1 antagonist control was included. exposure: Capsaicin and dihydrocapsaicin against the endogenous vanilloids N-oleoyldopamine and N-arachidonoyl-dopamine, with ADP, collagen and arachidonic acid as agonists evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24953906.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717", "start_char": 0, "end_char": 1870, "text_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717"} [dhc-p24953906] Vanilloid-like agents inhibit aggregation of human platelets. (2014). https://pubmed.ncbi.nlm.nih.gov/24953906/ DOI: 10.1016/j.thromres.2014.05.038

evidence_span

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experimental_model

In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control

exposure

Capsaicin and dihydrocapsaicin against the endogenous vanilloids N-oleoyldopamine and N-arachidonoyl-dopamine, with ADP, collagen and arachidonic acid as agonists

limitations

The agonist-by-agonist design is what makes this useful: it separates the two plant compounds where a single-agonist study would have merged them. A TRPV1 antagonist control was included.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human

plain_language

The platelets were not simply being killed, and again the receptor is not the route.

primary_references

[dhc-p24953906] Vanilloid-like agents inhibit aggregation of human platelets. (2014). https://pubmed.ncbi.nlm.nih.gov/24953906/ DOI: 10.1016/j.thromres.2014.05.038

tissue_or_cell_type

Platelets

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 166–177

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control · source_derived_draft · unverified_draft

### dhc-platelet-effect-not-trpv1 Inhibition of aggregation was not due to direct toxicity of these agents towards platelets as judged by LDH release, and the TRPV1 antagonist SB-452533 did not affect inhibition of ADP-induced platelet aggregation by capsaicin and N-oleoyldopamine. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The platelets were not simply being killed, and again the receptor is not the route. organism: Human tissue_or_cell_type: Platelets experimental_model: In-vitro human platelet aggregation with agonist-specified stimulation and an LDH viability control limitations: The agonist-by-agonist design is what makes this useful: it separates the two plant compounds where a single-agonist study would have merged them. A TRPV1 antagonist control was included. exposure: Capsaicin and dihydrocapsaicin against the endogenous vanilloids N-oleoyldopamine and N-arachidonoyl-dopamine, with ADP, collagen and arachidonic acid as agonists evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24953906.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717", "start_char": 0, "end_char": 1870, "text_sha256": "8d11f6733abf59c36bf8e2b6ed6f44f759cab3fdd209ff3c84c21b20e178a717"} [dhc-p24953906] Vanilloid-like agents inhibit aggregation of human platelets. (2014). https://pubmed.ncbi.nlm.nih.gov/24953906/ DOI: 10.1016/j.thromres.2014.05.038

evidence_span

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experimental_model

In vivo and in situ gastrointestinal absorption studies in rats with tritiated dihydrocapsaicin

exposure

Capsaicin and dihydrocapsaicin administered into stomach, jejunum and ileum, with 2,4-dinitrophenol and sodium cyanide as metabolic inhibitors

limitations

Establishes both the route and the first metabolite by direct measurement in portal blood. A 1984 rat study using tritium label rather than mass spectrometry.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

The gut wall snips the molecule in two, and one of the pieces is a small fatty acid that travels on in the blood.

primary_references

[dhc-p6710495] Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin in rats. (1984). https://pubmed.ncbi.nlm.nih.gov/6710495/ DOI: 10.1016/0041-008x(84)90121-2

tissue_or_cell_type

Stomach, jejunum, ileum and portal blood

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 491–502

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo and in situ gastrointestinal absorption studies in rats with tritiated dihydrocapsaicin · source_derived_draft · unverified_draft

### dhc-releases-8-mna Tritiated dihydrocapsaicin was mainly absorbed via the portal system and not by a mesenteric lymphangial one, and the radioactivity in portal blood was composed of 85% dihydrocapsaicin and 15% of its metabolite 8-methyl nonanoic acid bound to the albumin fraction, with dihydrocapsaicin-hydrolysing enzyme activity found in jejunal tissue, indicating a partial first-pass effect during absorption. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The gut wall snips the molecule in two, and one of the pieces is a small fatty acid that travels on in the blood. organism: Rat tissue_or_cell_type: Stomach, jejunum, ileum and portal blood experimental_model: In vivo and in situ gastrointestinal absorption studies in rats with tritiated dihydrocapsaicin limitations: Establishes both the route and the first metabolite by direct measurement in portal blood. A 1984 rat study using tritium label rather than mass spectrometry. exposure: Capsaicin and dihydrocapsaicin administered into stomach, jejunum and ileum, with 2,4-dinitrophenol and sodium cyanide as metabolic inhibitors evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/6710495.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0a9a5cb2178f2b266fffe5efbd9580a0a1b5c03dd86b4bfe92b105194eb1f9b", "start_char": 0, "end_char": 1416, "text_sha256": "a0a9a5cb2178f2b266fffe5efbd9580a0a1b5c03dd86b4bfe92b105194eb1f9b"} [dhc-p6710495] Gastrointestinal absorption and metabolism of capsaicin and dihydrocapsaicin in rats. (1984). https://pubmed.ncbi.nlm.nih.gov/6710495/ DOI: 10.1016/0041-008x(84)90121-2

evidence_span

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experimental_model

Asphyxial cardiac arrest in rats comparing bolus injection with femoral vein infusion

exposure

Dihydrocapsaicin by bolus injection or by infusion at 0.75 mg/kg/h for four hours after cardiac arrest

limitations

Directly compares two routes of the same drug and finds the route decides whether the cardiovascular effects appear. Neurological recovery was followed for only three days.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Injected all at once it disturbs the heart; infused slowly it does not, and the animals did better.

primary_references

[dhc-p28268688] Dihydrocapsaicin-induced hypothermia after asphyxiai cardiac arrest in rats. (2016). https://pubmed.ncbi.nlm.nih.gov/28268688/ DOI: 10.1109/embc.2016.7591082

tissue_or_cell_type

Brain and cardiovascular system

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 361–372

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Asphyxial cardiac arrest in rats comparing bolus injection with femoral vein infusion · source_derived_draft · unverified_draft

### dhc-route-decides-safety Comparing bolus injection with femoral vein infusion, cardiovascular effects were seen only with a large-dose dihydrocapsaicin bolus injection, and four-hour infusion at 0.75 mg/kg/h after cardiac arrest maintained a body temperature of about 34 degrees for at least eight hours with treated rats remaining viable, showing higher electrical activity during the first four hours and better neurological recovery over three days than normothermia rats. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Injected all at once it disturbs the heart; infused slowly it does not, and the animals did better. organism: Rat tissue_or_cell_type: Brain and cardiovascular system experimental_model: Asphyxial cardiac arrest in rats comparing bolus injection with femoral vein infusion limitations: Directly compares two routes of the same drug and finds the route decides whether the cardiovascular effects appear. Neurological recovery was followed for only three days. exposure: Dihydrocapsaicin by bolus injection or by infusion at 0.75 mg/kg/h for four hours after cardiac arrest evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/28268688.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90c0491fa4681d112ecfc224671b763a608eeb03af4bf563955dc49ef628b851", "start_char": 0, "end_char": 1500, "text_sha256": "90c0491fa4681d112ecfc224671b763a608eeb03af4bf563955dc49ef628b851"} [dhc-p28268688] Dihydrocapsaicin-induced hypothermia after asphyxiai cardiac arrest in rats. (2016). https://pubmed.ncbi.nlm.nih.gov/28268688/ DOI: 10.1109/embc.2016.7591082

evidence_span

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experimental_model

Screening of a heterogeneous group of TRPV1 agonists followed by dose-response studies in three species

exposure

Continuous intravenous infusion of dihydrocapsaicin at 0.125 to 0.75 mg/kg/h in conscious animals

limitations

The reason dihydrocapsaicin rather than capsaicin is the agent used for this purpose: it was selected out of a screen. The calf arm matters because it is the only body mass here comparable to an adult human.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat, cynomolgus monkey and calf

plain_language

In an animal the size of a person it held the temperature down for half a day.

primary_references

[dhc-p20932337] Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. (2010). https://pubmed.ncbi.nlm.nih.gov/20932337/ DOI: 10.1186/1471-2261-10-51

tissue_or_cell_type

Whole body

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 231–242

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Screening of a heterogeneous group of TRPV1 agonists followed by dose-response studies in three species · source_derived_draft · unverified_draft

### dhc-scales-to-human-mass In conscious young cattle, with a body weight comparable to that of an adult human, intravenous infusion of dihydrocapsaicin maintained mild hypothermia of more than 3 degrees below baseline for more than 12 hours. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: In an animal the size of a person it held the temperature down for half a day. organism: Rat, cynomolgus monkey and calf tissue_or_cell_type: Whole body experimental_model: Screening of a heterogeneous group of TRPV1 agonists followed by dose-response studies in three species limitations: The reason dihydrocapsaicin rather than capsaicin is the agent used for this purpose: it was selected out of a screen. The calf arm matters because it is the only body mass here comparable to an adult human. exposure: Continuous intravenous infusion of dihydrocapsaicin at 0.125 to 0.75 mg/kg/h in conscious animals evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/20932337.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "add9a23357b3b1d89126189d178c377e3b4934e1c047d4022cf4aa15fdfa6602", "start_char": 0, "end_char": 1847, "text_sha256": "add9a23357b3b1d89126189d178c377e3b4934e1c047d4022cf4aa15fdfa6602"} [dhc-p20932337] Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. (2010). https://pubmed.ncbi.nlm.nih.gov/20932337/ DOI: 10.1186/1471-2261-10-51

evidence_span

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experimental_model

Screening of a heterogeneous group of TRPV1 agonists followed by dose-response studies in three species

exposure

Continuous intravenous infusion of dihydrocapsaicin at 0.125 to 0.75 mg/kg/h in conscious animals

limitations

The reason dihydrocapsaicin rather than capsaicin is the agent used for this purpose: it was selected out of a screen. The calf arm matters because it is the only body mass here comparable to an adult human.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat, cynomolgus monkey and calf

plain_language

Out of a set of receptor agonists, this one gave the most controllable cooling, and the deeper the dose the deeper the drop.

primary_references

[dhc-p20932337] Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. (2010). https://pubmed.ncbi.nlm.nih.gov/20932337/ DOI: 10.1186/1471-2261-10-51

tissue_or_cell_type

Whole body

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 218–229

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Screening of a heterogeneous group of TRPV1 agonists followed by dose-response studies in three species · source_derived_draft · unverified_draft

### dhc-selected-from-a-screen On screening a heterogeneous group of TRPV1 agonists in conscious rats, dihydrocapsaicin displayed a desirable hypothermic profile with regard to duration, depth and control, and in rats infusion at 0.125, 0.25, 0.50 and 0.75 mg/kg/h caused maximal temperature changes against vehicle of -0.9, -1.5, -2.0 and -4.2 degrees within about one hour until the six hour infusion was stopped, with dose-dependent immediate decreases also in cynomolgus monkeys. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Out of a set of receptor agonists, this one gave the most controllable cooling, and the deeper the dose the deeper the drop. organism: Rat, cynomolgus monkey and calf tissue_or_cell_type: Whole body experimental_model: Screening of a heterogeneous group of TRPV1 agonists followed by dose-response studies in three species limitations: The reason dihydrocapsaicin rather than capsaicin is the agent used for this purpose: it was selected out of a screen. The calf arm matters because it is the only body mass here comparable to an adult human. exposure: Continuous intravenous infusion of dihydrocapsaicin at 0.125 to 0.75 mg/kg/h in conscious animals evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/20932337.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "add9a23357b3b1d89126189d178c377e3b4934e1c047d4022cf4aa15fdfa6602", "start_char": 0, "end_char": 1847, "text_sha256": "add9a23357b3b1d89126189d178c377e3b4934e1c047d4022cf4aa15fdfa6602"} [dhc-p20932337] Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist. (2010). https://pubmed.ncbi.nlm.nih.gov/20932337/ DOI: 10.1186/1471-2261-10-51

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/29590555.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a", "start_char": 0, "end_char": 1882, "text_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a"}

experimental_model

Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy

exposure

Intravenous dihydrocapsaicin, against resiniferatoxin nanoinjected into the nucleus tractus solitarius, with capsazepine and bilateral cervical or subdiaphragmatic vagotomy

limitations

The vagotomy control separates a central vagal route from whatever systemic dihydrocapsaicin uses. Anaesthetised animals, so the cardiovascular numbers are not directly comparable with the conscious studies here.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

It turns down the body’s own heater, which is part of why the temperature falls.

primary_references

[dhc-p29590555] Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue thermogenesis, arterial pressure, and heart rate. (2018). https://pubmed.ncbi.nlm.nih.gov/29590555/ DOI: 10.1152/ajpregu.00049.2018

tissue_or_cell_type

Nucleus tractus solitarius and brown adipose tissue

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 400–411

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy · source_derived_draft · unverified_draft

### dhc-shuts-down-brown-fat Intravenous injection of the TRPV1 agonist dihydrocapsaicin decreased brown adipose tissue sympathetic nerve activity, brown adipose tissue temperature, expired carbon dioxide and heart rate, though not mean arterial pressure, during skin cooling in anaesthetised rats. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It turns down the body’s own heater, which is part of why the temperature falls. organism: Rat tissue_or_cell_type: Nucleus tractus solitarius and brown adipose tissue experimental_model: Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy limitations: The vagotomy control separates a central vagal route from whatever systemic dihydrocapsaicin uses. Anaesthetised animals, so the cardiovascular numbers are not directly comparable with the conscious studies here. exposure: Intravenous dihydrocapsaicin, against resiniferatoxin nanoinjected into the nucleus tractus solitarius, with capsazepine and bilateral cervical or subdiaphragmatic vagotomy evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/29590555.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a", "start_char": 0, "end_char": 1882, "text_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a"} [dhc-p29590555] Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue thermogenesis, arterial pressure, and heart rate. (2018). https://pubmed.ncbi.nlm.nih.gov/29590555/ DOI: 10.1152/ajpregu.00049.2018

evidence_span

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experimental_model

Incubation with phenobarbital-induced rat liver postmitochondrial supernatant, with rabbit urine confirmation and in vivo activity testing

exposure

Capsaicin, dihydrocapsaicin and nonivamide incubated with an NADPH-generating system, with pentobarbital sleeping time as a readout of enzyme inhibition

limitations

Identifies side-chain hydroxylation as a shared detoxification route and shows the products are inactive. The enzyme-inhibition arm tested capsaicin, not dihydrocapsaicin, which is recorded on that claim.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat and rabbit

plain_language

Putting a hydroxyl on the tail switches the molecule off, for both heat and pain relief.

primary_references

[dhc-p8614248] Metabolism of capsaicinoids: evidence for aliphatic hydroxylation and its pharmacological implications. (1995). https://pubmed.ncbi.nlm.nih.gov/8614248/ DOI: 10.1016/0024-3205(95)00091-7

tissue_or_cell_type

Liver

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 530–541

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Incubation with phenobarbital-induced rat liver postmitochondrial supernatant, with rabbit urine confirmation and in vivo activity testing · source_derived_draft · unverified_draft

### dhc-side-chain-hydroxylation Incubation of capsaicin with phenobarbital-induced rat liver postmitochondrial supernatant produced omega-hydroxycapsaicin, also detected in the urine of rabbits given capsaicin, and other analogs of capsaicin such as dihydrocapsaicin and nonivamide also formed similar metabolites via aliphatic hydroxylation; the polar metabolites were inactive when tested for antinociceptive activity and pungency while their parent compounds exhibited strong sensory effects, suggesting that hydroxylation of the side chain plays an important role in detoxification. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Putting a hydroxyl on the tail switches the molecule off, for both heat and pain relief. organism: Rat and rabbit tissue_or_cell_type: Liver experimental_model: Incubation with phenobarbital-induced rat liver postmitochondrial supernatant, with rabbit urine confirmation and in vivo activity testing limitations: Identifies side-chain hydroxylation as a shared detoxification route and shows the products are inactive. The enzyme-inhibition arm tested capsaicin, not dihydrocapsaicin, which is recorded on that claim. exposure: Capsaicin, dihydrocapsaicin and nonivamide incubated with an NADPH-generating system, with pentobarbital sleeping time as a readout of enzyme inhibition evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/8614248.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c4eee5bf34dac159665170e5eca63fcbf3a5146133b9d7dc0b6ec01bda4493a", "start_char": 0, "end_char": 1399, "text_sha256": "7c4eee5bf34dac159665170e5eca63fcbf3a5146133b9d7dc0b6ec01bda4493a"} [dhc-p8614248] Metabolism of capsaicinoids: evidence for aliphatic hydroxylation and its pharmacological implications. (1995). https://pubmed.ncbi.nlm.nih.gov/8614248/ DOI: 10.1016/0024-3205(95)00091-7

evidence_span

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experimental_model

Dose-ranging subcutaneous administration in rats with repeated dosing, antinociception testing and regional substance P measurement

exposure

Dihydrocapsaicin 0.5 to 10 mg/kg subcutaneously, single and repeated, against capsaicin

limitations

The founding comparison. It is a 1982 study and the antinociception endpoints are behavioural, but it is the only record here that puts a number on how the two compounds differ on temperature.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

It empties a pain-signalling peptide from the sensory nerves specifically, leaving the brain stores alone.

primary_references

[dhc-p6184240] Dihydrocapsaicin-induced hypothermia and substance P depletion. (1982). https://pubmed.ncbi.nlm.nih.gov/6184240/ DOI: 10.1016/0014-2999(82)90263-1

tissue_or_cell_type

Whole body, dorsal root ganglia and spinal cord

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 205–216

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dose-ranging subcutaneous administration in rats with repeated dosing, antinociception testing and regional substance P measurement · source_derived_draft · unverified_draft

### dhc-substance-p-depletion Repeated administration of dihydrocapsaicin, like capsaicin, resulted in depletion of substance P from dorsal root ganglia and dorsal spinal cord but not from the hypothalamus, corpus striatum or ventral spinal cord. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It empties a pain-signalling peptide from the sensory nerves specifically, leaving the brain stores alone. organism: Rat tissue_or_cell_type: Whole body, dorsal root ganglia and spinal cord experimental_model: Dose-ranging subcutaneous administration in rats with repeated dosing, antinociception testing and regional substance P measurement limitations: The founding comparison. It is a 1982 study and the antinociception endpoints are behavioural, but it is the only record here that puts a number on how the two compounds differ on temperature. exposure: Dihydrocapsaicin 0.5 to 10 mg/kg subcutaneously, single and repeated, against capsaicin evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/6184240.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dbeb69d90d490215b73d7a6f70fab0043e16cfdc8659c0daa4fda2cc0a7f6eaa", "start_char": 0, "end_char": 897, "text_sha256": "dbeb69d90d490215b73d7a6f70fab0043e16cfdc8659c0daa4fda2cc0a7f6eaa"} [dhc-p6184240] Dihydrocapsaicin-induced hypothermia and substance P depletion. (1982). https://pubmed.ncbi.nlm.nih.gov/6184240/ DOI: 10.1016/0014-2999(82)90263-1

evidence_span

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experimental_model

Conscious mice exposed to 10 degree cooling with implanted electromyography electrodes, electrocardiography and abdominal temperature transmitters

exposure

TRPV1 agonist dihydrocapsaicin or TRPM8 inhibitor compound 5, with TRPM8 knockout mice as a control

limitations

This is the record that explains why the drug is clinically interesting rather than merely cooling: it removes the defence that makes physical cooling intolerable in a conscious patient.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mouse

plain_language

It switches off the shivering and racing heart that normally fight off cooling, so the temperature falls much further.

primary_references

[dhc-p24005250] Shivering and tachycardic responses to external cooling in mice are substantially suppressed by TRPV1 activation but not by TRPM8 inhibition. (2013). https://pubmed.ncbi.nlm.nih.gov/24005250/ DOI: 10.1152/ajpregu.00296.2013

tissue_or_cell_type

Back muscle, heart and core

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 244–255

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conscious mice exposed to 10 degree cooling with implanted electromyography electrodes, electrocardiography and abdominal temperature transmitters · source_derived_draft · unverified_draft

### dhc-suppresses-cold-defence In conscious mice exposed to cooling at 10 degrees, TRPV1 activation by dihydrocapsaicin substantially suppressed total electromyographic muscle activity from 25.6 to 5.1 volt-seconds per minute, abolished the tachycardic response with heart rate change falling from 204 to 3 beats per minute, and produced a profound drop in core temperature from -2.2 to -8.9 degrees. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It switches off the shivering and racing heart that normally fight off cooling, so the temperature falls much further. organism: Mouse tissue_or_cell_type: Back muscle, heart and core experimental_model: Conscious mice exposed to 10 degree cooling with implanted electromyography electrodes, electrocardiography and abdominal temperature transmitters limitations: This is the record that explains why the drug is clinically interesting rather than merely cooling: it removes the defence that makes physical cooling intolerable in a conscious patient. exposure: TRPV1 agonist dihydrocapsaicin or TRPM8 inhibitor compound 5, with TRPM8 knockout mice as a control evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24005250.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e9d99ac4cc7a031474975ac4d7f3bcff0df922dc01047fe94bd51817ef5b3fea", "start_char": 0, "end_char": 1963, "text_sha256": "e9d99ac4cc7a031474975ac4d7f3bcff0df922dc01047fe94bd51817ef5b3fea"} [dhc-p24005250] Shivering and tachycardic responses to external cooling in mice are substantially suppressed by TRPV1 activation but not by TRPM8 inhibition. (2013). https://pubmed.ncbi.nlm.nih.gov/24005250/ DOI: 10.1152/ajpregu.00296.2013

evidence_span

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experimental_model

Rat multizone perforator flap ischaemia-reperfusion model with network pharmacology prediction and pathway manipulation

exposure

Dihydrocapsaicin with cGAS-STING pathway activation as a test of mediation

limitations

The pathway-activation arm is the useful control: switching the pathway back on removed the benefit. Network pharmacology prediction is hypothesis generation, not evidence.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

It protects starved tissue by switching off an inflammatory alarm; turn the alarm back on and the protection goes.

primary_references

[dhc-p38459660] Dihydrocapsaicin suppresses the STING-mediated accumulation of ROS and NLRP3 inflammasome and alleviates apoptosis after ischemia-reperfusion injury of perforator skin flap. (2024). https://pubmed.ncbi.nlm.nih.gov/38459660/ DOI: 10.1002/ptr.8167

tissue_or_cell_type

Skin flap vasculature

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 699–710

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat multizone perforator flap ischaemia-reperfusion model with network pharmacology prediction and pathway manipulation · source_derived_draft · unverified_draft

### dhc-suppresses-sting Dihydrocapsaicin enhanced the survival of multizone perforator flaps by suppressing the cGAS-STING pathway, oxidative stress and formation of the NLRP3 inflammasome, inducing oxidative stress resistance and preventing apoptosis in vascular endothelial cells, whereas activation of the cGAS-STING pathway led to accumulation of reactive oxygen species and NLRP3 inflammasome and diminished the protective role of dihydrocapsaicin. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It protects starved tissue by switching off an inflammatory alarm; turn the alarm back on and the protection goes. organism: Rat tissue_or_cell_type: Skin flap vasculature experimental_model: Rat multizone perforator flap ischaemia-reperfusion model with network pharmacology prediction and pathway manipulation limitations: The pathway-activation arm is the useful control: switching the pathway back on removed the benefit. Network pharmacology prediction is hypothesis generation, not evidence. exposure: Dihydrocapsaicin with cGAS-STING pathway activation as a test of mediation evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/38459660.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f1a586e910230094fc4d9c5c54d57fb7ccab56a5c6565737d15a38c16f0567cf", "start_char": 0, "end_char": 1793, "text_sha256": "f1a586e910230094fc4d9c5c54d57fb7ccab56a5c6565737d15a38c16f0567cf"} [dhc-p38459660] Dihydrocapsaicin suppresses the STING-mediated accumulation of ROS and NLRP3 inflammasome and alleviates apoptosis after ischemia-reperfusion injury of perforator skin flap. (2024). https://pubmed.ncbi.nlm.nih.gov/38459660/ DOI: 10.1002/ptr.8167

evidence_span

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experimental_model

Enzymatically synthesised capsaicin analogues applied to voltage-dependent calcium channels

exposure

Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9, N-VAMC10, olvanil, capsiate and vanillylamine on T-type channels

limitations

A second TRPV1-independent target, with a clear structural boundary: the ester analogue and the free amine do not do it. The channel work is in isolated preparations.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Sensory neuron preparations

plain_language

Both compounds shut down a second kind of calcium channel in pain neurons, again without the receptor.

primary_references

[dhc-p17362879] Enzymatic synthesis of capsaicin analogs and their effect on the T-type Ca2+ channels. (2007). https://pubmed.ncbi.nlm.nih.gov/17362879/ DOI: 10.1016/j.bbrc.2007.02.144

tissue_or_cell_type

Primary sensory neurons

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 140–151

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzymatically synthesised capsaicin analogues applied to voltage-dependent calcium channels · source_derived_draft · unverified_draft

### dhc-t-type-inhibition Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9 and N-VAMC10 directly and partially reversibly inhibited low-voltage-activated T-type calcium channels, whereas olvanil, capsiate and vanillylamine could not, and the capsaicin inhibition of T-type channels was independent of TRPV1 activation. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Both compounds shut down a second kind of calcium channel in pain neurons, again without the receptor. organism: Sensory neuron preparations tissue_or_cell_type: Primary sensory neurons experimental_model: Enzymatically synthesised capsaicin analogues applied to voltage-dependent calcium channels limitations: A second TRPV1-independent target, with a clear structural boundary: the ester analogue and the free amine do not do it. The channel work is in isolated preparations. exposure: Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9, N-VAMC10, olvanil, capsiate and vanillylamine on T-type channels evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/17362879.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e28fe88d1e616cf4d60ccadcf38ae9b0890891513dcda0d9623e5d3579d7201", "start_char": 0, "end_char": 1243, "text_sha256": "7e28fe88d1e616cf4d60ccadcf38ae9b0890891513dcda0d9623e5d3579d7201"} [dhc-p17362879] Enzymatic synthesis of capsaicin analogs and their effect on the T-type Ca2+ channels. (2007). https://pubmed.ncbi.nlm.nih.gov/17362879/ DOI: 10.1016/j.bbrc.2007.02.144

evidence_span

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experimental_model

Biotransformation of dihydrocapsaicin by four cultivated human intestinal fungal strains with NMR and HRESIMS structure determination

exposure

Dihydrocapsaicin incubated with cultivated human intestinal fungal strains

limitations

An in vitro biotransformation study with cultivated strains, not a gut community. The enzyme-inhibition result is a property of an isolated metabolite, not a demonstrated effect in an animal.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human intestinal fungi

plain_language

Fungi living in the human gut rework the molecule into eight different products, most of them new to science.

primary_references

[dhc-p36578383] Biotransformation of dihydrocapsaicin by human intestinal fungi and the inhibitory effects of metabolites against LSD1. (2022). https://pubmed.ncbi.nlm.nih.gov/36578383/ DOI: 10.1016/j.heliyon.2022.e12325

tissue_or_cell_type

In vitro culture

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 569–580

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biotransformation of dihydrocapsaicin by four cultivated human intestinal fungal strains with NMR and HRESIMS structure determination · source_derived_draft · unverified_draft

### dhc-fungal-biotransformation Biotransformation of dihydrocapsaicin by four cultivated human intestinal fungal strains yielded eight metabolites including seven previously undescribed ones, with the main reactions revealed to be hydroxylation, alcohol oxidation and lactylation, the lactylation of hydroxyl groups being mediated mainly by Rhizopus oryzae. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Fungi living in the human gut rework the molecule into eight different products, most of them new to science. organism: Human intestinal fungi tissue_or_cell_type: In vitro culture experimental_model: Biotransformation of dihydrocapsaicin by four cultivated human intestinal fungal strains with NMR and HRESIMS structure determination limitations: An in vitro biotransformation study with cultivated strains, not a gut community. The enzyme-inhibition result is a property of an isolated metabolite, not a demonstrated effect in an animal. exposure: Dihydrocapsaicin incubated with cultivated human intestinal fungal strains evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/36578383.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a36fc63af6f17ba1a551c87f5c73e288e9f468affcd39bcba5baad1ee1acf338", "start_char": 0, "end_char": 1090, "text_sha256": "a36fc63af6f17ba1a551c87f5c73e288e9f468affcd39bcba5baad1ee1acf338"} [dhc-p36578383] Biotransformation of dihydrocapsaicin by human intestinal fungi and the inhibitory effects of metabolites against LSD1. (2022). https://pubmed.ncbi.nlm.nih.gov/36578383/ DOI: 10.1016/j.heliyon.2022.e12325

evidence_span

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experimental_model

In vitro metabolism of pure capsaicin in human, rat and dog microsomes and S9 fractions and in human skin

exposure

Pure capsaicin rather than pepper extract

limitations

Recorded here for the attribution warning it states rather than for its capsaicin metabolites: it is explicit that much published capsaicin literature used mixtures containing dihydrocapsaicin.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Human, rat and dog

plain_language

A warning worth keeping: a great deal of what is filed under capsaicin was measured on a mixture that contained this compound too.

primary_references

[dhc-p18180272] In vitro hepatic and skin metabolism of capsaicin. (2008). https://pubmed.ncbi.nlm.nih.gov/18180272/ DOI: 10.1124/dmd.107.019240

tissue_or_cell_type

Liver microsomes and skin

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 647–658

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vitro metabolism of pure capsaicin in human, rat and dog microsomes and S9 fractions and in human skin · source_derived_draft · unverified_draft

### dhc-published-work-used-mixtures Much of the published literature on capsaicin is based on pepper extracts, which are typically a mixture of capsaicin and other capsaicinoids including norhydrocapsaicin, dihydrocapsaicin, homocapsaicin and homodihydrocapsaicin, which is why this study examined the in vitro metabolism of pure capsaicin; that metabolism was similar in human, rat and dog microsomes, yielding 16-hydroxycapsaicin, 17-hydroxycapsaicin and 16,17-dehydrocapsaicin, with biotransformation slow in human skin so that cytochrome P450 metabolism in skin is minimal relative to hepatic metabolism. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: A warning worth keeping: a great deal of what is filed under capsaicin was measured on a mixture that contained this compound too. organism: Human, rat and dog tissue_or_cell_type: Liver microsomes and skin experimental_model: In vitro metabolism of pure capsaicin in human, rat and dog microsomes and S9 fractions and in human skin limitations: Recorded here for the attribution warning it states rather than for its capsaicin metabolites: it is explicit that much published capsaicin literature used mixtures containing dihydrocapsaicin. exposure: Pure capsaicin rather than pepper extract evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/18180272.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cea281309b45a5605f8f845cee01a296e7b62c24db52bc517c968c3750394baf", "start_char": 0, "end_char": 1289, "text_sha256": "cea281309b45a5605f8f845cee01a296e7b62c24db52bc517c968c3750394baf"} [dhc-p18180272] In vitro hepatic and skin metabolism of capsaicin. (2008). https://pubmed.ncbi.nlm.nih.gov/18180272/ DOI: 10.1124/dmd.107.019240

evidence_span

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experimental_model

3T3-L1 adipocytes assayed for viability, lipid accumulation, AMPK activity, lipolysis and glucose uptake

exposure

8-methyl nonanoic acid applied during 48-hour nutrient starvation or 5-day maturation

limitations

A cell-line study of the metabolite. The two exposure windows give different effects, which is recorded rather than averaged.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mouse cells

plain_language

In fat cells under starvation the fragment switches on the energy sensor and less fat accumulates.

primary_references

[dhc-p36681810] Cellular responses to 8-methyl nonanoic acid, a degradation by-product of dihydrocapsaicin, in 3T3-L1 adipocytes. (2023). https://pubmed.ncbi.nlm.nih.gov/36681810/ DOI: 10.1186/s12906-023-03844-w

tissue_or_cell_type

Adipocytes

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 621–632

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 3T3-L1 adipocytes assayed for viability, lipid accumulation, AMPK activity, lipolysis and glucose uptake · source_derived_draft · unverified_draft

### dhc-8-mna-activates-ampk In 3T3-L1 adipocytes 8-methyl nonanoic acid caused no impact on cell viability, and during nutrient starvation it decreased lipid amounts in association with AMP-activated protein kinase activation, a molecular event that suppresses lipogenic processes. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: In fat cells under starvation the fragment switches on the energy sensor and less fat accumulates. organism: Mouse cells tissue_or_cell_type: Adipocytes experimental_model: 3T3-L1 adipocytes assayed for viability, lipid accumulation, AMPK activity, lipolysis and glucose uptake limitations: A cell-line study of the metabolite. The two exposure windows give different effects, which is recorded rather than averaged. exposure: 8-methyl nonanoic acid applied during 48-hour nutrient starvation or 5-day maturation evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/36681810.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14c4f7752262c5a27fb7b848664015595f598cb51edcc2d5df96f1140be143cb", "start_char": 0, "end_char": 1600, "text_sha256": "14c4f7752262c5a27fb7b848664015595f598cb51edcc2d5df96f1140be143cb"} [dhc-p36681810] Cellular responses to 8-methyl nonanoic acid, a degradation by-product of dihydrocapsaicin, in 3T3-L1 adipocytes. (2023). https://pubmed.ncbi.nlm.nih.gov/36681810/ DOI: 10.1186/s12906-023-03844-w

evidence_span

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experimental_model

C57BL/6NJcl mice fed for 18 weeks with glucose and insulin tolerance testing

exposure

High-fat diet supplemented with triacylglycerols consisting of 8-methyl nonanoic acid or isocaloric soybean oil

limitations

Tests the metabolite rather than the parent compound, over a long feeding period, and reports a clear negative alongside the positives. 8-methyl nonanoic acid is non-pungent.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mouse

plain_language

The fragment left when the molecule is cut apart slows weight gain and delays insulin resistance, without improving the glucose tests.

primary_references

[dhc-p40827132] Effect of 8-Methyl Nonanoic Acid, a Degradation By-Product of Dihydrocapsaicin, on Energy and Glucose Homeostasis in Diet-Induced Obese Mice. (2025). https://pubmed.ncbi.nlm.nih.gov/40827132/ DOI: 10.2147/jep.s536185

tissue_or_cell_type

Whole body, hypothalamus and adipose tissue

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 608–619

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · C57BL/6NJcl mice fed for 18 weeks with glucose and insulin tolerance testing · source_derived_draft · unverified_draft

### dhc-8-mna-slows-metabolic-syndrome Compared with high-fat-diet mice given isocaloric soybean oil, 8-methyl nonanoic acid feeding reduced caloric intake and body weight gain in diet-induced obese mice in association with weight loss in several tissues and organs and transcriptional downregulation of the orexigenic agouti-related protein in the hypothalamus, and despite no improvement in glucose or insulin tolerance tests it delayed the onset of high-fat-diet-induced insulin resistance during the early experimental period. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The fragment left when the molecule is cut apart slows weight gain and delays insulin resistance, without improving the glucose tests. organism: Mouse tissue_or_cell_type: Whole body, hypothalamus and adipose tissue experimental_model: C57BL/6NJcl mice fed for 18 weeks with glucose and insulin tolerance testing limitations: Tests the metabolite rather than the parent compound, over a long feeding period, and reports a clear negative alongside the positives. 8-methyl nonanoic acid is non-pungent. exposure: High-fat diet supplemented with triacylglycerols consisting of 8-methyl nonanoic acid or isocaloric soybean oil evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/40827132.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ec9a287d601f180f392c2944bd9bf509dbc0f27924ec10143aa9a2a5bc77b817", "start_char": 0, "end_char": 1954, "text_sha256": "ec9a287d601f180f392c2944bd9bf509dbc0f27924ec10143aa9a2a5bc77b817"} [dhc-p40827132] Effect of 8-Methyl Nonanoic Acid, a Degradation By-Product of Dihydrocapsaicin, on Energy and Glucose Homeostasis in Diet-Induced Obese Mice. (2025). https://pubmed.ncbi.nlm.nih.gov/40827132/ DOI: 10.2147/jep.s536185

evidence_span

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experimental_model

Randomised seven-group study in 144 male Sprague Dawley rats after middle cerebral artery occlusion

exposure

Low-dose dihydrocapsaicin at 0.5 mg/kg or high-dose at 1.5 mg/kg, an ice pad at 31 degrees, and the combination, with an external-temperature-control arm

limitations

A large randomised design with a dose-response surprise: the high dose alone did nothing while the low dose worked. That non-monotonicity is recorded because it contradicts the simple dose-response in the other records.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Drug plus ice pack cooled faster and protected better than either on its own.

primary_references

[dhc-p30090648] Synergistically Induced Hypothermia and Enhanced Neuroprotection by Pharmacological and Physical Approaches in Stroke. (2018). https://pubmed.ncbi.nlm.nih.gov/30090648/ DOI: 10.14336/ad.2017.0817

tissue_or_cell_type

Brain

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 335–346

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised seven-group study in 144 male Sprague Dawley rats after middle cerebral artery occlusion · source_derived_draft · unverified_draft

### dhc-combination-beats-either Combination therapy of low-dose dihydrocapsaicin and an ice pad significantly improved every measured outcome compared with monotherapies, achieving hypothermia faster by 28.6% than the ice pad, 350% than low-dose dihydrocapsaicin and 200% than high-dose dihydrocapsaicin alone, reducing neurological deficits by 63% against 26% with low-dose alone, reducing reactive oxygen species at 6 and 24 hours, increasing ATP by 42.9% against 25%, and decreasing apoptotic cell death by 48.5% against 24.9%. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Drug plus ice pack cooled faster and protected better than either on its own. organism: Rat tissue_or_cell_type: Brain experimental_model: Randomised seven-group study in 144 male Sprague Dawley rats after middle cerebral artery occlusion limitations: A large randomised design with a dose-response surprise: the high dose alone did nothing while the low dose worked. That non-monotonicity is recorded because it contradicts the simple dose-response in the other records. exposure: Low-dose dihydrocapsaicin at 0.5 mg/kg or high-dose at 1.5 mg/kg, an ice pad at 31 degrees, and the combination, with an external-temperature-control arm evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/30090648.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c", "start_char": 0, "end_char": 2110, "text_sha256": "e688b4cd16fdd3847d8fe10113d243edf17839f32bef46fe85790a18ad6b920c"} [dhc-p30090648] Synergistically Induced Hypothermia and Enhanced Neuroprotection by Pharmacological and Physical Approaches in Stroke. (2018). https://pubmed.ncbi.nlm.nih.gov/30090648/ DOI: 10.14336/ad.2017.0817

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

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experimental_model

Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction

exposure

Tritiated dihydrocapsaicin and unlabelled capsaicin given intragastrically, intravenously or subcutaneously

limitations

The comparison across routes is the point, and it is the reason every hypothermia study in this collection injects the drug rather than feeding it. Anaesthetised rats, and identification is chromatographic.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Swallowed, almost none of it reaches the brain intact; injected, about half does.

primary_references

[dhc-p2280802] Absorption and metabolism of capsaicinoids following intragastric administration in rats. (1990). https://pubmed.ncbi.nlm.nih.gov/2280802/ DOI: 10.1007/bf00169449

tissue_or_cell_type

Portal blood, trunk blood, brain and liver

trigger_kind

biomarker_context Imported condition classification; unverified.

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 504–515

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction · source_derived_draft · unverified_draft

### dhc-first-pass-destroys-it Tritiated dihydrocapsaicin and unlabelled capsaicin were readily absorbed from the gastrointestinal tract but were almost completely metabolized before reaching the general circulation, with less than 5% of total extracted radioactivity consisting of unchanged dihydrocapsaicin in trunk blood and brain 15 minutes after gastrointestinal application, against approximately 50% unchanged 3 minutes after intravenous or 90 minutes after subcutaneous application. Condition category: biomarker_context nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Swallowed, almost none of it reaches the brain intact; injected, about half does. organism: Rat tissue_or_cell_type: Portal blood, trunk blood, brain and liver experimental_model: Intragastric, intravenous and subcutaneous administration of tritiated dihydrocapsaicin in anaesthetised rats with tissue extraction limitations: The comparison across routes is the point, and it is the reason every hypothermia study in this collection injects the drug rather than feeding it. Anaesthetised rats, and identification is chromatographic. exposure: Tritiated dihydrocapsaicin and unlabelled capsaicin given intragastrically, intravenously or subcutaneously evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/2280802.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1", "start_char": 0, "end_char": 1280, "text_sha256": "92a4527b69cd4c342da3d0aed850597ef4491122baf20b6a681e43ab0a8e2dd1"} [dhc-p2280802] Absorption and metabolism of capsaicinoids following intragastric administration in rats. (1990). https://pubmed.ncbi.nlm.nih.gov/2280802/ DOI: 10.1007/bf00169449

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/29590555.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a", "start_char": 0, "end_char": 1882, "text_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a"}

experimental_model

Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy

exposure

Intravenous dihydrocapsaicin, against resiniferatoxin nanoinjected into the nucleus tractus solitarius, with capsazepine and bilateral cervical or subdiaphragmatic vagotomy

limitations

The vagotomy control separates a central vagal route from whatever systemic dihydrocapsaicin uses. Anaesthetised animals, so the cardiovascular numbers are not directly comparable with the conscious studies here.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Cutting the vagus nerve stopped the brain-injected agonist working but not the injected one, so they reach the heater by different roads.

primary_references

[dhc-p29590555] Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue thermogenesis, arterial pressure, and heart rate. (2018). https://pubmed.ncbi.nlm.nih.gov/29590555/ DOI: 10.1152/ajpregu.00049.2018

tissue_or_cell_type

Nucleus tractus solitarius and brown adipose tissue

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 413–424

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy · source_derived_draft · unverified_draft

### dhc-not-a-vagal-route Bilateral cervical or subdiaphragmatic vagotomy attenuated the decreases in brown adipose tissue sympathetic nerve activity and thermogenesis evoked by nanoinjection of resiniferatoxin into the nucleus tractus solitarius but did not prevent the decreases evoked by intravenous dihydrocapsaicin, consistent with a non-vagal pathway through which systemic TRPV1 agonists can inhibit brown adipose tissue thermogenesis. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Cutting the vagus nerve stopped the brain-injected agonist working but not the injected one, so they reach the heater by different roads. organism: Rat tissue_or_cell_type: Nucleus tractus solitarius and brown adipose tissue experimental_model: Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy limitations: The vagotomy control separates a central vagal route from whatever systemic dihydrocapsaicin uses. Anaesthetised animals, so the cardiovascular numbers are not directly comparable with the conscious studies here. exposure: Intravenous dihydrocapsaicin, against resiniferatoxin nanoinjected into the nucleus tractus solitarius, with capsazepine and bilateral cervical or subdiaphragmatic vagotomy evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/29590555.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a", "start_char": 0, "end_char": 1882, "text_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a"} [dhc-p29590555] Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue thermogenesis, arterial pressure, and heart rate. (2018). https://pubmed.ncbi.nlm.nih.gov/29590555/ DOI: 10.1152/ajpregu.00049.2018

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/31613626.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5677dc745ff36e42e2ced1c852984f119d1116b5ef5c60e1449645ad1827cf58", "start_char": 0, "end_char": 1077, "text_sha256": "5677dc745ff36e42e2ced1c852984f119d1116b5ef5c60e1449645ad1827cf58"}

experimental_model

Quantification of capsinoids and capsaicinoids across fruit development in three Capsicum genotypes

exposure

Chiltepin, Tampiqueno 74 and Bhut Jolokia sampled from 10 to 60 days post-anthesis

limitations

A plant developmental study. It bears on the chapter only because it measures how stable the capsaicin to dihydrocapsaicin ratio is, which decides whether a chilli exposure can be treated as a fixed mixture.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Plant

plain_language

The proportions of the two hot compounds hold fairly steady across varieties and ripeness, unlike their non-pungent cousins.

primary_references

[dhc-p31613626] Assessment of Capsaicinoid and Capsinoid Accumulation Patterns during Fruit Development in Three Chili Pepper Genotypes (Capsicum spp.) Carrying Pun1 and pAMT Alleles Related to Pungency. (2019). https://pubmed.ncbi.nlm.nih.gov/31613626/ DOI: 10.1021/acs.jafc.9b05332

tissue_or_cell_type

Pepper fruit

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 101–112

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantification of capsinoids and capsaicinoids across fruit development in three Capsicum genotypes · source_derived_draft · unverified_draft

### dhc-ratio-is-relatively-stable The capsiate to dihydrocapsiate ratio presented a higher variation between genotypes and developmental stages than the capsaicin to dihydrocapsaicin ratio, and capsaicinoids could already be determined at 10 days post-anthesis in Bhut Jolokia with an accumulation pattern different from that of the capsinoids. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The proportions of the two hot compounds hold fairly steady across varieties and ripeness, unlike their non-pungent cousins. organism: Plant tissue_or_cell_type: Pepper fruit experimental_model: Quantification of capsinoids and capsaicinoids across fruit development in three Capsicum genotypes limitations: A plant developmental study. It bears on the chapter only because it measures how stable the capsaicin to dihydrocapsaicin ratio is, which decides whether a chilli exposure can be treated as a fixed mixture. exposure: Chiltepin, Tampiqueno 74 and Bhut Jolokia sampled from 10 to 60 days post-anthesis evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/31613626.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5677dc745ff36e42e2ced1c852984f119d1116b5ef5c60e1449645ad1827cf58", "start_char": 0, "end_char": 1077, "text_sha256": "5677dc745ff36e42e2ced1c852984f119d1116b5ef5c60e1449645ad1827cf58"} [dhc-p31613626] Assessment of Capsaicinoid and Capsinoid Accumulation Patterns during Fruit Development in Three Chili Pepper Genotypes (Capsicum spp.) Carrying Pun1 and pAMT Alleles Related to Pungency. (2019). https://pubmed.ncbi.nlm.nih.gov/31613626/ DOI: 10.1021/acs.jafc.9b05332

evidence_span

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experimental_model

Long-term outcome study in mice with diffusion tensor imaging and one-month behavioural follow-up

exposure

A single 8 hour treatment of dihydrocapsaicin-induced hypothermia begun 3.5 hours after stroke

limitations

The long follow-up and the remote-injury endpoint are unusual and valuable. Still one model and one species.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mouse

plain_language

Cooling for eight hours protected not only the injured area but a distant region that degenerates later, and the benefit was still there a month on.

primary_references

[dhc-p29247238] TRPV1-mediated Pharmacological Hypothermia Promotes Improved Functional Recovery Following Ischemic Stroke. (2017). https://pubmed.ncbi.nlm.nih.gov/29247238/ DOI: 10.1038/s41598-017-17548-y

tissue_or_cell_type

Cortex and thalamus

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 322–333

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Long-term outcome study in mice with diffusion tensor imaging and one-month behavioural follow-up · source_derived_draft · unverified_draft

### dhc-secondary-injury-reduced Hypothermia by dihydrocapsaicin initiated 3.5 hours after stroke significantly reduced primary cortical injury and also reduced secondary thalamic injury, with treated mice showing 53% smaller thalamic lesion size, decreased neuronal loss and astrogliosis in the thalamus and less thalamic fibre loss by diffusion tensor imaging, and a single 8 hour treatment produced improved behavioural recovery at one month after stroke. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Cooling for eight hours protected not only the injured area but a distant region that degenerates later, and the benefit was still there a month on. organism: Mouse tissue_or_cell_type: Cortex and thalamus experimental_model: Long-term outcome study in mice with diffusion tensor imaging and one-month behavioural follow-up limitations: The long follow-up and the remote-injury endpoint are unusual and valuable. Still one model and one species. exposure: A single 8 hour treatment of dihydrocapsaicin-induced hypothermia begun 3.5 hours after stroke evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/29247238.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02b1d92f9972bd978e0b35a0a4f8130145f3dcd6832ff8a95f9d022fc7a4ce08", "start_char": 0, "end_char": 1517, "text_sha256": "02b1d92f9972bd978e0b35a0a4f8130145f3dcd6832ff8a95f9d022fc7a4ce08"} [dhc-p29247238] TRPV1-mediated Pharmacological Hypothermia Promotes Improved Functional Recovery Following Ischemic Stroke. (2017). https://pubmed.ncbi.nlm.nih.gov/29247238/ DOI: 10.1038/s41598-017-17548-y

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/24595220.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87", "start_char": 0, "end_char": 1882, "text_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87"}

experimental_model

Controlled prospective study in conscious unrestrained young and aged male mice with implanted thermocouples and wireless transponders

exposure

Dihydrocapsaicin 2 to 4 mg/kg subcutaneously, alone and combined with the TRPM8 inhibitor compound 5 at 20 to 30 mg/kg

limitations

Includes aged animals, which most of this collection does not. Its finding that the effect does not desensitise is the direct opposite of the 1982 rat result and the two are recorded as conflicting.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mouse

plain_language

Blocking the cold sensor at the same time makes the cooling go deeper and last longer.

primary_references

[dhc-p24595220] Transient receptor potential melastatin 8 channel inhibition potentiates the hypothermic response to transient receptor potential vanilloid 1 activation in the conscious mouse. (2014). https://pubmed.ncbi.nlm.nih.gov/24595220/ DOI: 10.1097/ccm.0000000000000229

tissue_or_cell_type

Core temperature

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 283–294

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled prospective study in conscious unrestrained young and aged male mice with implanted thermocouples and wireless transponders · source_derived_draft · unverified_draft

### dhc-trpm8-inhibition-potentiates The TRPM8 inhibitor compound 5 at 20 mg/kg subcutaneously augmented the drop in core temperature during cold exposure at 8 degrees, and when combined with dihydrocapsaicin at 1.25 to 2.5 mg/kg the drop in core temperature was amplified and prolonged, so that activating warm receptors and simultaneously inhibiting cold receptors potentiated the effect. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Blocking the cold sensor at the same time makes the cooling go deeper and last longer. organism: Mouse tissue_or_cell_type: Core temperature experimental_model: Controlled prospective study in conscious unrestrained young and aged male mice with implanted thermocouples and wireless transponders limitations: Includes aged animals, which most of this collection does not. Its finding that the effect does not desensitise is the direct opposite of the 1982 rat result and the two are recorded as conflicting. exposure: Dihydrocapsaicin 2 to 4 mg/kg subcutaneously, alone and combined with the TRPM8 inhibitor compound 5 at 20 to 30 mg/kg evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24595220.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87", "start_char": 0, "end_char": 1882, "text_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87"} [dhc-p24595220] Transient receptor potential melastatin 8 channel inhibition potentiates the hypothermic response to transient receptor potential vanilloid 1 activation in the conscious mouse. (2014). https://pubmed.ncbi.nlm.nih.gov/24595220/ DOI: 10.1097/ccm.0000000000000229