Capsaicin

dose

Capsaicin-bound channel

duration

Acute

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

TRPV1 structural model with site-specific functional tests

limitations

The study resolves a binding mechanism but does not specify human dietary pharmacokinetics.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

TRPV1 structural model with site-specific functional tests

plain_language

Capsaicin binds TRPV1 in a tail-up, head-down configuration and stabilizes the open state through vanillyl-group contact with the S4-S5 linker.

primary_references

Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel. (2015). https://pubmed.ncbi.nlm.nih.gov/26053297/ DOI: 10.1038/nchembio.1835

route

Structural and in-vitro mutational analysis

tissue

Ligand binding and channel opening

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 22–31

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · TRPV1 structural model with site-specific functional tests · source_derived_draft · unverified_draft

## capsaicin-binding-pose Capsaicin binds TRPV1 in a tail-up, head-down configuration and stabilizes the open state through vanillyl-group contact with the S4-S5 linker. Model/species: TRPV1 structural model with site-specific functional tests Tissue/system: Ligand binding and channel opening Exposure: Capsaicin-bound channel Route: Structural and in-vitro mutational analysis Duration: Acute Limits: The study resolves a binding mechanism but does not specify human dietary pharmacokinetics. Primary reference: Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel. (2015). https://pubmed.ncbi.nlm.nih.gov/26053297/ DOI: 10.1038/nchembio.1835 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Repeated capsaicin; calcineurin inhibitor, forskolin and point mutants

duration

Acute repeated activation

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

TRPV1-transfected HEK293T or HeLa cells

limitations

Kinase and phosphatase manipulations identify regulatory machinery in engineered cells, not a dietary calcium threshold.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

TRPV1-transfected HEK293T or HeLa cells

plain_language

Repeated capsaicin activation caused calcium-dependent TRPV1 desensitization regulated in part by calcineurin and PKA at Thr370.

primary_references

Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase. (2005). https://pubmed.ncbi.nlm.nih.gov/15691846/ DOI: 10.1074/jbc.M410917200

route

In vitro

tissue

Whole-cell capsaicin currents

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 33–42

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · TRPV1-transfected HEK293T or HeLa cells · source_derived_draft · unverified_draft

## capsaicin-calcineurin-desensitization Repeated capsaicin activation caused calcium-dependent TRPV1 desensitization regulated in part by calcineurin and PKA at Thr370. Model/species: TRPV1-transfected HEK293T or HeLa cells Tissue/system: Whole-cell capsaicin currents Exposure: Repeated capsaicin; calcineurin inhibitor, forskolin and point mutants Route: In vitro Duration: Acute repeated activation Limits: Kinase and phosphatase manipulations identify regulatory machinery in engineered cells, not a dietary calcium threshold. Primary reference: Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase. (2005). https://pubmed.ncbi.nlm.nih.gov/15691846/ DOI: 10.1074/jbc.M410917200 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Capsaicin with capsazepine or cyclosporine controls

duration

Acute

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Primary cardiomyocytes; rat reperfusion model for downstream peptide work

limitations

The later infarct-size benefit was produced by the V1-cal peptide, not by capsaicin; capsaicin itself must not inherit that therapeutic result.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Primary cardiomyocytes; rat reperfusion model for downstream peptide work

plain_language

Capsaicin dose-dependently reduced mitochondrial membrane potential in primary cardiomyocytes, and capsazepine or cyclosporine blocked the effect.

primary_references

Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury. (2016). https://pubmed.ncbi.nlm.nih.gov/27671317/ DOI: 10.1161/JAHA.116.003774

route

In vitro

tissue

Mitochondrial TRPV1 and membrane potential

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 121–130

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Primary cardiomyocytes; rat reperfusion model for downstream peptide work · source_derived_draft · unverified_draft

## capsaicin-cardiomyocyte-mitochondria Capsaicin dose-dependently reduced mitochondrial membrane potential in primary cardiomyocytes, and capsazepine or cyclosporine blocked the effect. Model/species: Primary cardiomyocytes; rat reperfusion model for downstream peptide work Tissue/system: Mitochondrial TRPV1 and membrane potential Exposure: Capsaicin with capsazepine or cyclosporine controls Route: In vitro Duration: Acute Limits: The later infarct-size benefit was produced by the V1-cal peptide, not by capsaicin; capsaicin itself must not inherit that therapeutic result. Primary reference: Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury. (2016). https://pubmed.ncbi.nlm.nih.gov/27671317/ DOI: 10.1161/JAHA.116.003774 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Oral capsaicin arm versus placebo and other flavor agonists

duration

90 minutes

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Healthy human participants

limitations

Energy expenditure increased after cinnamaldehyde, not specifically after capsaicin in the reported abstract; the capsaicin dose was judged sensorially intense.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Healthy human participants

plain_language

In a randomized crossover trial, capsaicin maintained postprandial fat oxidation above placebo during the 90-minute observation period.

primary_references

Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects. (2016). https://pubmed.ncbi.nlm.nih.gov/26883089/ DOI: 10.1038/srep20795

route

Oral

tissue

Indirect calorimetry and autonomic measures

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 99–108

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Healthy human participants · source_derived_draft · unverified_draft

## capsaicin-fat-oxidation In a randomized crossover trial, capsaicin maintained postprandial fat oxidation above placebo during the 90-minute observation period. Model/species: Healthy human participants Tissue/system: Indirect calorimetry and autonomic measures Exposure: Oral capsaicin arm versus placebo and other flavor agonists Route: Oral Duration: 90 minutes Limits: Energy expenditure increased after cinnamaldehyde, not specifically after capsaicin in the reported abstract; the capsaicin dose was judged sensorially intense. Primary reference: Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects. (2016). https://pubmed.ncbi.nlm.nih.gov/26883089/ DOI: 10.1038/srep20795 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

6 ppm capsaicin rinse twice daily

duration

17 days

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Healthy human volunteers

limitations

The result shows selective sensory adaptation, not shared binding to one receptor for every stimulus.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Healthy human volunteers

plain_language

Repeated capsaicin rinsing reduced burn from vanillyl butyl ether, cinnamaldehyde and ethanol, while menthol cooling and sucrose sweetness did not change.

primary_references

Inducible desensitization to capsaicin with repeated low-dose exposure in human volunteers. (2024). https://pubmed.ncbi.nlm.nih.gov/38135109/ DOI: 10.1016/j.physbeh.2023.114447

route

Oral rinse

tissue

Cross-stimulus oral sensory ratings

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 77–86

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Healthy human volunteers · source_derived_draft · unverified_draft

## capsaicin-human-cross-desensitization Repeated capsaicin rinsing reduced burn from vanillyl butyl ether, cinnamaldehyde and ethanol, while menthol cooling and sucrose sweetness did not change. Model/species: Healthy human volunteers Tissue/system: Cross-stimulus oral sensory ratings Exposure: 6 ppm capsaicin rinse twice daily Route: Oral rinse Duration: 17 days Limits: The result shows selective sensory adaptation, not shared binding to one receptor for every stimulus. Primary reference: Inducible desensitization to capsaicin with repeated low-dose exposure in human volunteers. (2024). https://pubmed.ncbi.nlm.nih.gov/38135109/ DOI: 10.1016/j.physbeh.2023.114447 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

6 ppm capsaicin rinse twice daily

duration

Days 3-17

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Healthy human volunteers

limitations

Reduced sensation was not explained by TRPV1 transcript abundance; protein trafficking and neural adaptation were not resolved.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Healthy human volunteers

plain_language

Twice-daily 6 ppm capsaicin rinses reduced oral capsaicin burn over 17 days without a detected decrease in fungiform-papilla TRPV1 mRNA.

primary_references

Inducible desensitization to capsaicin with repeated low-dose exposure in human volunteers. (2024). https://pubmed.ncbi.nlm.nih.gov/38135109/ DOI: 10.1016/j.physbeh.2023.114447

route

Oral rinse

tissue

Oral sensory ratings and fungiform-papilla TRPV1 expression

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 66–75

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Healthy human volunteers · source_derived_draft · unverified_draft

## capsaicin-human-oral-desensitization Twice-daily 6 ppm capsaicin rinses reduced oral capsaicin burn over 17 days without a detected decrease in fungiform-papilla TRPV1 mRNA. Model/species: Healthy human volunteers Tissue/system: Oral sensory ratings and fungiform-papilla TRPV1 expression Exposure: 6 ppm capsaicin rinse twice daily Route: Oral rinse Duration: Days 3-17 Limits: Reduced sensation was not explained by TRPV1 transcript abundance; protein trafficking and neural adaptation were not resolved. Primary reference: Inducible desensitization to capsaicin with repeated low-dose exposure in human volunteers. (2024). https://pubmed.ncbi.nlm.nih.gov/38135109/ DOI: 10.1016/j.physbeh.2023.114447 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

8% capsaicin patch for 1 or 24 hours

duration

1, 7 and 21 days after removal

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Fourteen healthy human volunteers

limitations

This experimental 24-hour exposure exceeds ordinary patch use and does not establish efficacy in patients with neuropathic pain.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Fourteen healthy human volunteers

plain_language

A 24-hour 8% capsaicin patch reduced warmth detection, heat pain, histamine itch and neurogenic flare, with little effect on touch or cold and near-complete sensory recovery by day 21.

primary_references

The time course of brief and prolonged topical 8% capsaicin-induced desensitization in healthy volunteers evaluated by quantitative sensory testing and vasomotor imaging. (2018). https://pubmed.ncbi.nlm.nih.gov/29845449/ DOI: 10.1007/s00221-018-5299-y

route

Topical

tissue

Quantitative sensory testing and vasomotor imaging

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 88–97

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Fourteen healthy human volunteers · source_derived_draft · unverified_draft

## capsaicin-skin-selectivity A 24-hour 8% capsaicin patch reduced warmth detection, heat pain, histamine itch and neurogenic flare, with little effect on touch or cold and near-complete sensory recovery by day 21. Model/species: Fourteen healthy human volunteers Tissue/system: Quantitative sensory testing and vasomotor imaging Exposure: 8% capsaicin patch for 1 or 24 hours Route: Topical Duration: 1, 7 and 21 days after removal Limits: This experimental 24-hour exposure exceeds ordinary patch use and does not establish efficacy in patients with neuropathic pain. Primary reference: The time course of brief and prolonged topical 8% capsaicin-induced desensitization in healthy volunteers evaluated by quantitative sensory testing and vasomotor imaging. (2018). https://pubmed.ncbi.nlm.nih.gov/29845449/ DOI: 10.1007/s00221-018-5299-y Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Capsaicin followed by mustard oil/TRPA1 stimulation

duration

Acute sequential exposure

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Sensory neurons and heterologous channel expression

limitations

The mechanism differed from mustard-oil homologous desensitization and was not regulated by calcineurin in this study.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Sensory neurons and heterologous channel expression

plain_language

Capsaicin cross-desensitized TRPA1 through a calcium-dependent route associated with PLC activation and PIP2 depletion.

primary_references

Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. (2007). https://pubmed.ncbi.nlm.nih.gov/17584831/ DOI: 10.1113/jphysiol.2007.133231

route

In vitro

tissue

TRPA1 responses after TRPV1 agonism

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 55–64

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Sensory neurons and heterologous channel expression · source_derived_draft · unverified_draft

## capsaicin-trpa1-cross-desensitization Capsaicin cross-desensitized TRPA1 through a calcium-dependent route associated with PLC activation and PIP2 depletion. Model/species: Sensory neurons and heterologous channel expression Tissue/system: TRPA1 responses after TRPV1 agonism Exposure: Capsaicin followed by mustard oil/TRPA1 stimulation Route: In vitro Duration: Acute sequential exposure Limits: The mechanism differed from mustard-oil homologous desensitization and was not regulated by calcineurin in this study. Primary reference: Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. (2007). https://pubmed.ncbi.nlm.nih.gov/17584831/ DOI: 10.1113/jphysiol.2007.133231 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Capsaicin concentration-response and noxious-range temperature

duration

Acute

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Cloned capsaicin receptor expressed from sensory-neuron cDNA

limitations

The cloned receptor experiment establishes channel gating, not the whole organism response to chili foods.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Cloned capsaicin receptor expressed from sensory-neuron cDNA

plain_language

Capsaicin activates TRPV1, a nonselective cation channel that is also activated by noxious heat.

primary_references

The capsaicin receptor: a heat-activated ion channel in the pain pathway. (1997). https://pubmed.ncbi.nlm.nih.gov/9349813/ DOI: 10.1038/39807

route

In vitro

tissue

Calcium influx and heat activation

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 11–20

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Cloned capsaicin receptor expressed from sensory-neuron cDNA · source_derived_draft · unverified_draft

## capsaicin-trpv1-gating Capsaicin activates TRPV1, a nonselective cation channel that is also activated by noxious heat. Model/species: Cloned capsaicin receptor expressed from sensory-neuron cDNA Tissue/system: Calcium influx and heat activation Exposure: Capsaicin concentration-response and noxious-range temperature Route: In vitro Duration: Acute Limits: The cloned receptor experiment establishes channel gating, not the whole organism response to chili foods. Primary reference: The capsaicin receptor: a heat-activated ion channel in the pain pathway. (1997). https://pubmed.ncbi.nlm.nih.gov/9349813/ DOI: 10.1038/39807 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

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

plain_language

The parent compound jams the liver’s drug-clearing machinery; its hydroxylated product does not.

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 543–554

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-capsaicin-inhibits-enzymes Capsaicin interacted irreversibly with hepatic drug metabolizing enzymes, thereby inhibiting their activity as indicated by prolongation of pentobarbital sleeping time in rats, and such inhibition of drug metabolism was not observed with omega-hydroxycapsaicin; this arm of the study tested capsaicin rather than 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: The parent compound jams the liver’s drug-clearing machinery; its hydroxylated product does not. organism: Rat 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

{"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"}

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

dose

Capsaicin or piperine concentration-response; second exposure; SB366791 control

duration

Acute sequential exposure

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human PC-3 cells expressing TRPV1

limitations

Comparable assay behavior does not establish equivalent potency, oral exposure, or benefit in humans.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Human PC-3 cells expressing TRPV1

plain_language

Piperine and capsaicin both stimulated TRPV1-dependent calcium responses in human PC-3 cells and both showed reduced responses on second exposure.

primary_references

Pharmacodynamics of TRPV1 agonists in a bioassay using human PC-3 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24688365/ DOI: 10.1155/2014/184526

route

In vitro

tissue

Fluo-4 calcium-response bioassay

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 110–119

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human PC-3 cells expressing TRPV1 · source_derived_draft · unverified_draft

## capsaicin-piperine-shared-trpv1 Piperine and capsaicin both stimulated TRPV1-dependent calcium responses in human PC-3 cells and both showed reduced responses on second exposure. Model/species: Human PC-3 cells expressing TRPV1 Tissue/system: Fluo-4 calcium-response bioassay Exposure: Capsaicin or piperine concentration-response; second exposure; SB366791 control Route: In vitro Duration: Acute sequential exposure Limits: Comparable assay behavior does not establish equivalent potency, oral exposure, or benefit in humans. Primary reference: Pharmacodynamics of TRPV1 agonists in a bioassay using human PC-3 cells. (2014). https://pubmed.ncbi.nlm.nih.gov/24688365/ DOI: 10.1155/2014/184526 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

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

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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

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

dose

Seven days of simple, enteric-coated or placebo preparation

duration

7 days

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Nineteen overweight or obese men in a randomized three-way crossover trial

limitations

This is a mixture and formulation result, not an isolated-capsaicin estimate; the simple-versus-enteric comparison was P=0.09.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Nineteen overweight or obese men in a randomized three-way crossover trial

plain_language

A non-enteric capsaicin/green-tea/caffeine/tyrosine/calcium mixture increased 24-hour energy expenditure by 160 kJ/day versus placebo; the enteric version did not.

primary_references

Bioactive food stimulants of sympathetic activity: effect on 24-h energy expenditure and fat oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15870822/ DOI: 10.1038/sj.ejcn.1602121

route

Oral multi-ingredient supplement

tissue

Respiration-chamber energy expenditure

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 132–141

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Nineteen overweight or obese men in a randomized three-way crossover trial · source_derived_draft · unverified_draft

## capsaicin-multi-ingredient-energy A non-enteric capsaicin/green-tea/caffeine/tyrosine/calcium mixture increased 24-hour energy expenditure by 160 kJ/day versus placebo; the enteric version did not. Model/species: Nineteen overweight or obese men in a randomized three-way crossover trial Tissue/system: Respiration-chamber energy expenditure Exposure: Seven days of simple, enteric-coated or placebo preparation Route: Oral multi-ingredient supplement Duration: 7 days Limits: This is a mixture and formulation result, not an isolated-capsaicin estimate; the simple-versus-enteric comparison was P=0.09. Primary reference: Bioactive food stimulants of sympathetic activity: effect on 24-h energy expenditure and fat oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15870822/ DOI: 10.1038/sj.ejcn.1602121 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Prolonged capsaicin followed by lipid-kinase blockade

duration

Recovery interval

evidence_access

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

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

TRPV1-expressing cells with Kir2.1 PIP2 biosensor

limitations

High intracellular ATP and PIP2 resynthesis were required; this is an experimental machinery perturbation, not evidence that dietary ATP supplementation changes analgesia.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

TRPV1-expressing cells with Kir2.1 PIP2 biosensor

plain_language

Blocking phosphatidylinositol-4-kinase prevented recovery of TRPV1 after prolonged capsaicin desensitization, linking recovery to PIP2 resynthesis.

primary_references

Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate. (2005). https://pubmed.ncbi.nlm.nih.gov/15888659/ DOI: 10.1523/JNEUROSCI.1296-05.2005

route

In vitro

tissue

Channel recovery after desensitization

trigger_kind

machinery_impairment Imported condition classification; unverified.

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 44–53

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · TRPV1-expressing cells with Kir2.1 PIP2 biosensor · source_derived_draft · unverified_draft

## capsaicin-pip2-recovery Blocking phosphatidylinositol-4-kinase prevented recovery of TRPV1 after prolonged capsaicin desensitization, linking recovery to PIP2 resynthesis. Model/species: TRPV1-expressing cells with Kir2.1 PIP2 biosensor Tissue/system: Channel recovery after desensitization Exposure: Prolonged capsaicin followed by lipid-kinase blockade Route: In vitro Duration: Recovery interval Limits: High intracellular ATP and PIP2 resynthesis were required; this is an experimental machinery perturbation, not evidence that dietary ATP supplementation changes analgesia. Primary reference: Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate. (2005). https://pubmed.ncbi.nlm.nih.gov/15888659/ DOI: 10.1523/JNEUROSCI.1296-05.2005 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Gamma-nonalactone 2.56 mM with a capsaicin concentration series

duration

Acute calcium response

evidence_access

Primary full-text methods/results inspected; PubMed metadata where indexed.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human TRPV1-expressing HEK293 cells

limitations

Concentration-dependent mixed modulation; not a potent selective antagonist or established dietary interaction.

nutrient_topic

Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone

organism

Human TRPV1-expressing HEK293 cells

plain_language

At 2.56 mM, gamma-nonalactone reduced capsaicin sensitivity and maximum response.

primary_references

Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023

route

In vitro co-application

tissue

Capsaicin concentration-response assay

Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 48–57

Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1-expressing HEK293 cells · source_derived_draft · unverified_draft

## gamma-nonalactone-capsaicin-high At 2.56 mM, gamma-nonalactone reduced capsaicin sensitivity and maximum response. Model/species: Human TRPV1-expressing HEK293 cells Tissue: Capsaicin concentration-response assay Exposure: Gamma-nonalactone 2.56 mM with a capsaicin concentration series Route: In vitro co-application Duration: Acute calcium response Limits: Concentration-dependent mixed modulation; not a potent selective antagonist or established dietary interaction. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.

dose

Gamma-nonalactone 0.64 or 1.28 mM with a capsaicin concentration series

duration

Acute calcium response

evidence_access

Primary full-text methods/results inspected; PubMed metadata where indexed.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human TRPV1-expressing HEK293 cells

limitations

Functional curve shifts do not directly locate a binding site. No human pungency or pain outcome was tested.

nutrient_topic

Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone

organism

Human TRPV1-expressing HEK293 cells

plain_language

Lower gamma-nonalactone concentrations shifted the capsaicin response toward greater sensitivity with little change in maximum response.

primary_references

Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023

route

In vitro co-application

tissue

Capsaicin concentration-response assay

Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 37–46

Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1-expressing HEK293 cells · source_derived_draft · unverified_draft

## gamma-nonalactone-capsaicin-low Lower gamma-nonalactone concentrations shifted the capsaicin response toward greater sensitivity with little change in maximum response. Model/species: Human TRPV1-expressing HEK293 cells Tissue: Capsaicin concentration-response assay Exposure: Gamma-nonalactone 0.64 or 1.28 mM with a capsaicin concentration series Route: In vitro co-application Duration: Acute calcium response Limits: Functional curve shifts do not directly locate a binding site. No human pungency or pain outcome was tested. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.

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

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

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

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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

{"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

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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/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"}

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

{"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

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

{"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"}

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