Component

Steviol

Context-specific entity; species, compartment and exposure are stated on each claim.

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

Read recorded mechanisms Open recursive mind map

How nutrients influence it

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

How nutrients reach it in more than one step

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

Tracing routes…

What it does

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

Recorded relationships

What it acts on

  1. Steviol acutely reduced forskolin-stimulated apical chloride current in canine MDCK epithelia.

    Steviol → Canine cystic fibrosis transmembrane conductance regulator / CFTR source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Canine kidney epithelial Ussing-chamber measurements; concentration-dependent bath exposure.
    limitations
    The source identifies CFTR-associated current; this is not a human dietary chloride-depletion mechanism.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Chloride movement can determine fluid accumulation in a tissue model.
    primary_references
    Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 298–304

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Canine kidney epithelial Ussing-chamber measurements; concentration-dependent bath exposure. · source_derived_draft · unverified_draft

    ## stevia-cftr-current Chloride movement can determine fluid accumulation in a tissue model. Steviol acutely reduced forskolin-stimulated apical chloride current in canine MDCK epithelia. Model: Canine kidney epithelial Ussing-chamber measurements; concentration-dependent bath exposure. Limitations: The source identifies CFTR-associated current; this is not a human dietary chloride-depletion mechanism. Evidence access: Primary abstract Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871
    Complete structured claim and evidence

  2. Steviol at 100 micromolar for 24 hours reduced CFTR protein expression in MDCK cells; MG-132 abolished the expression effect.

    Steviol → Canine cystic fibrosis transmembrane conductance regulator / CFTR source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Canine MDCK culture with proteasome-inhibitor intervention.
    limitations
    Proteasomal involvement is supported; a specific ubiquitination enzyme or human treatment effect is not established.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    A longer exposure changes protein abundance as well as acute channel activity.
    primary_references
    Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 306–312

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Canine MDCK culture with proteasome-inhibitor intervention. · source_derived_draft · unverified_draft

    ## stevia-cftr-degradation A longer exposure changes protein abundance as well as acute channel activity. Steviol at 100 micromolar for 24 hours reduced CFTR protein expression in MDCK cells; MG-132 abolished the expression effect. Model: Canine MDCK culture with proteasome-inhibitor intervention. Limitations: Proteasomal involvement is supported; a specific ubiquitination enzyme or human treatment effect is not established. Evidence access: Primary abstract Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871
    Complete structured claim and evidence

  3. Steviol at 100 micromolar reversibly inhibited MDCK cyst formation and growth; doses up to 200 micromolar did not alter measured cell viability, proliferation or apoptosis.

    Steviol → Canine MDCK cyst growth source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Three-dimensional canine kidney cyst culture.
    limitations
    This does not show clinical treatment of human polycystic kidney disease.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Reduced fluid-secretion-associated growth was separable from measured cell killing in this assay.
    primary_references
    Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 314–320

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Three-dimensional canine kidney cyst culture. · source_derived_draft · unverified_draft

    ## stevia-cyst-growth Reduced fluid-secretion-associated growth was separable from measured cell killing in this assay. Steviol at 100 micromolar reversibly inhibited MDCK cyst formation and growth; doses up to 200 micromolar did not alter measured cell viability, proliferation or apoptosis. Model: Three-dimensional canine kidney cyst culture. Limitations: This does not show clinical treatment of human polycystic kidney disease. Evidence access: Primary abstract Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23536832/ · DOI 10.1371/journal.pone.0058871
    Complete structured claim and evidence

  4. In everted hamster jejunum, 1 mM steviol reduced glucose absorption by 29%, accompanied by reduced mucosal ATP and altered absorptive morphology; stevioside at 1 or 5 mM did not inhibit absorption.

    Steviol → Hamster jejunal glucose absorption source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Hamster ex vivo intestine; mitochondrial enzyme activity and morphology assays.
    limitations
    This potentially disruptive millimolar exposure is not proof of safe, selective glucose blocking in humans.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    High local exposure impaired the tissue machinery supporting absorption.
    primary_references
    Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 346–352

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Hamster ex vivo intestine; mitochondrial enzyme activity and morphology assays. · source_derived_draft · unverified_draft

    ## stevia-hamster-energy High local exposure impaired the tissue machinery supporting absorption. In everted hamster jejunum, 1 mM steviol reduced glucose absorption by 29%, accompanied by reduced mucosal ATP and altered absorptive morphology; stevioside at 1 or 5 mM did not inhibit absorption. Model: Hamster ex vivo intestine; mitochondrial enzyme activity and morphology assays. Limitations: This potentially disruptive millimolar exposure is not proof of safe, selective glucose blocking in humans. Evidence access: Primary abstract Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w
    Complete structured claim and evidence

  5. Steviol did not inhibit intestinal sodium-potassium ATPase activity or brush-border-vesicle glucose uptake in the hamster experiment.

    Steviol → Hamster intestinal sodium-potassium ATPase activity source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Hamster enzyme and membrane-vesicle controls.
    limitations
    Negative controls narrow the interpretation; they do not rule out every ion-transport effect.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Reduced whole-tissue absorption did not identify a direct sodium-pump or brush-border transport block.
    primary_references
    Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 354–360

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Hamster enzyme and membrane-vesicle controls. · source_derived_draft · unverified_draft

    ## stevia-hamster-pump-control Reduced whole-tissue absorption did not identify a direct sodium-pump or brush-border transport block. Steviol did not inhibit intestinal sodium-potassium ATPase activity or brush-border-vesicle glucose uptake in the hamster experiment. Model: Hamster enzyme and membrane-vesicle controls. Limitations: Negative controls narrow the interpretation; they do not rule out every ion-transport effect. Evidence access: Primary abstract Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w
    Complete structured claim and evidence

  6. Steviol at 0.08 or 0.2 mg/mL showed no detected degradation over 24 hours in pooled anaerobic fecal homogenates from five volunteers.

    Steviol → Human fecal steviol incubation source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Pooled human fecal material; LC/MS/ESI.
    limitations
    No detected degradation under these conditions does not mean steviol is universally inert.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    The gut conversion endpoint is not necessarily the same as the liver endpoint.
    primary_references
    In vitro metabolism of the glycosidic sweeteners, stevia mixture and enzymatically modified stevia in human intestinal microflora. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12504168/ · DOI 10.1016/s0278-6915(02)00235-1

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 42–48

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pooled human fecal material; LC/MS/ESI. · source_derived_draft · unverified_draft

    ## stevia-metabolic-endpoint The gut conversion endpoint is not necessarily the same as the liver endpoint. Steviol at 0.08 or 0.2 mg/mL showed no detected degradation over 24 hours in pooled anaerobic fecal homogenates from five volunteers. Model: Pooled human fecal material; LC/MS/ESI. Limitations: No detected degradation under these conditions does not mean steviol is universally inert. Evidence access: Primary abstract In vitro metabolism of the glycosidic sweeteners, stevia mixture and enzymatically modified stevia in human intestinal microflora. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12504168/ · DOI 10.1016/s0278-6915(02)00235-1
    Complete structured claim and evidence

  7. Steviol at 100 micromolar did not reproduce the LPS-response suppression observed with 1 mM stevioside.

    Steviol → Human THP-1 LPS-induced cytokine release source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human THP-1 assay comparing distinct compounds at different concentrations.
    limitations
    Different doses prevent a simple potency ranking; no universal inactivity claim is made.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Metabolism changes which immune effects are observed.
    primary_references
    Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its Metabolite Steviol on THP-1 Cells. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16448183/ · DOI 10.1021/jf0523465

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 338–344

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human THP-1 assay comparing distinct compounds at different concentrations. · source_derived_draft · unverified_draft

    ## stevia-steviol-immune-null Metabolism changes which immune effects are observed. Steviol at 100 micromolar did not reproduce the LPS-response suppression observed with 1 mM stevioside. Model: Human THP-1 assay comparing distinct compounds at different concentrations. Limitations: Different doses prevent a simple potency ranking; no universal inactivity claim is made. Evidence access: Primary abstract Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its Metabolite Steviol on THP-1 Cells. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16448183/ · DOI 10.1021/jf0523465
    Complete structured claim and evidence

  8. Steviol also potentiated calcium-activated TRPM5 currents, showing that the aglycone retains activity in this assay.

    Steviol → TRPM5 channel in the 2017 expression assay, construct species not independently verified source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text; Figure 1 and supplementary-patch description
    experimental_model
    Whole-cell and excised-patch experiments.
    limitations
    Activity of steviol does not prove equivalent activity of its glucuronide at TRPM5.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Removing sugar groups does not eliminate this channel effect.
    primary_references
    Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 186–192

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Whole-cell and excised-patch experiments. · source_derived_draft · unverified_draft

    ## stevia-trpm5-steviol Removing sugar groups does not eliminate this channel effect. Steviol also potentiated calcium-activated TRPM5 currents, showing that the aglycone retains activity in this assay. Model: Whole-cell and excised-patch experiments. Limitations: Activity of steviol does not prove equivalent activity of its glucuronide at TRPM5. Evidence access: Primary full text; Figure 1 and supplementary-patch description Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733
    Complete structured claim and evidence

What acts on it

  1. Rebaudioside A was completely hydrolyzed to steviol in 24 hours in the same human fecal culture experiments.

    Rebaudioside A → Steviol source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Anaerobic fecal cultures; isolated bacterial groups.
    limitations
    Rate differences depend on culture conditions and microbial composition.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Closely related glycosides can reach a shared metabolite at different rates.
    primary_references
    Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14558786/ · DOI 10.1021/jf0303619

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 26–32

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Anaerobic fecal cultures; isolated bacterial groups. · source_derived_draft · unverified_draft

    ## stevia-microbial-reba Closely related glycosides can reach a shared metabolite at different rates. Rebaudioside A was completely hydrolyzed to steviol in 24 hours in the same human fecal culture experiments. Model: Anaerobic fecal cultures; isolated bacterial groups. Limitations: Rate differences depend on culture conditions and microbial composition. Evidence access: Primary abstract Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14558786/ · DOI 10.1021/jf0303619
    Complete structured claim and evidence

  2. Anaerobic human fecal cultures completely hydrolyzed stevioside to steviol in 10 hours.

    Stevioside → Steviol source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human fecal batch cultures; chromatographic product identification.
    limitations
    An incubation time is not a universal intestinal transit time. No human systemic efficacy was tested.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Gut microbes transform the sweetener before much of its systemic exposure.
    primary_references
    Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14558786/ · DOI 10.1021/jf0303619

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 18–24

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human fecal batch cultures; chromatographic product identification. · source_derived_draft · unverified_draft

    ## stevia-microbial-stevioside Gut microbes transform the sweetener before much of its systemic exposure. Anaerobic human fecal cultures completely hydrolyzed stevioside to steviol in 10 hours. Model: Human fecal batch cultures; chromatographic product identification. Limitations: An incubation time is not a universal intestinal transit time. No human systemic efficacy was tested. Evidence access: Primary abstract Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14558786/ · DOI 10.1021/jf0303619
    Complete structured claim and evidence

  3. Steviol trans-stimulated labeled para-aminohippurate efflux in human OAT1-expressing Xenopus oocytes, supporting transporter-mediated steviol movement.

    Human organic anion transporter 1 / SLC22A6 → Steviol source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human cloned transporter in frog oocytes; 1 micromolar steviol trans-stimulation.
    limitations
    A heterologous transport assay is not a clinical renal clearance measurement.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    A renal transporter recognizes the aglycone.
    primary_references
    Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). · 2005 · https://pubmed.ncbi.nlm.nih.gov/15644426/ · DOI 10.1124/jpet.104.080366
    transport_effect
    depends Inferred from trans-stimulation of a tracer's efflux, which shows movement without fixing its direction.
    transport_pool
    the cytosol across the basolateral membrane Inferred from trans-stimulation of a tracer's efflux, which shows movement without fixing its direction.

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 98–104

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cloned transporter in frog oocytes; 1 micromolar steviol trans-stimulation. · source_derived_draft · unverified_draft

    ## stevia-oat1 A renal transporter recognizes the aglycone. Steviol trans-stimulated labeled para-aminohippurate efflux in human OAT1-expressing Xenopus oocytes, supporting transporter-mediated steviol movement. Model: Human cloned transporter in frog oocytes; 1 micromolar steviol trans-stimulation. Limitations: A heterologous transport assay is not a clinical renal clearance measurement. Evidence access: Primary abstract Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). · 2005 · https://pubmed.ncbi.nlm.nih.gov/15644426/ · DOI 10.1124/jpet.104.080366
    Complete structured claim and evidence

  4. Steviol trans-stimulated tracer efflux through human OAT3 expressed in Xenopus oocytes.

    Human organic anion transporter 3 / SLC22A8 → Steviol source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human cloned transporter in frog oocytes.
    limitations
    OAT3 and OATP transporters are different families and are not merged here.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    A second renal organic-anion transporter handles the same metabolite.
    primary_references
    Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). · 2005 · https://pubmed.ncbi.nlm.nih.gov/15644426/ · DOI 10.1124/jpet.104.080366
    transport_effect
    depends Inferred from trans-stimulation of a tracer's efflux, which shows movement without fixing its direction.
    transport_pool
    the cytosol across the basolateral membrane Inferred from trans-stimulation of a tracer's efflux, which shows movement without fixing its direction.

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 106–112

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cloned transporter in frog oocytes. · source_derived_draft · unverified_draft

    ## stevia-oat3 A second renal organic-anion transporter handles the same metabolite. Steviol trans-stimulated tracer efflux through human OAT3 expressed in Xenopus oocytes. Model: Human cloned transporter in frog oocytes. Limitations: OAT3 and OATP transporters are different families and are not merged here. Evidence access: Primary abstract Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). · 2005 · https://pubmed.ncbi.nlm.nih.gov/15644426/ · DOI 10.1124/jpet.104.080366
    Complete structured claim and evidence

  5. UGT1A3 contributed alongside UGT2B7 to steviol glucuronidation at high substrate concentration.

    Human UDP-glucuronosyltransferase 1A3 / UGT1A3 → Steviol source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Recombinant human enzyme screening and microsomal kinetics.
    limitations
    High versus low assay concentration must not be converted into an unmeasured dietary threshold.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    The participating enzyme mix changes with substrate concentration.
    primary_references
    Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24296138/ · DOI 10.1016/j.fct.2013.11.028

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 58–64

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme screening and microsomal kinetics. · source_derived_draft · unverified_draft

    ## stevia-ugt1a3 The participating enzyme mix changes with substrate concentration. UGT1A3 contributed alongside UGT2B7 to steviol glucuronidation at high substrate concentration. Model: Recombinant human enzyme screening and microsomal kinetics. Limitations: High versus low assay concentration must not be converted into an unmeasured dietary threshold. Evidence access: Primary abstract Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24296138/ · DOI 10.1016/j.fct.2013.11.028
    Complete structured claim and evidence

  6. Recombinant enzyme and microsomal assays identified UGT2B7 as the main contributor to steviol glucuronidation at low substrate concentration.

    Human UDP-glucuronosyltransferase 2B7 / UGT2B7 → Steviol source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human and rat microsomes with recombinant human UGT assays.
    limitations
    Organ-specific clearance differed; in vitro enzyme contribution is not a measured whole-body clearance fraction.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    A liver clearance enzyme changes the circulating chemical form.
    primary_references
    Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24296138/ · DOI 10.1016/j.fct.2013.11.028

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 50–56

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human and rat microsomes with recombinant human UGT assays. · source_derived_draft · unverified_draft

    ## stevia-ugt2b7 A liver clearance enzyme changes the circulating chemical form. Recombinant enzyme and microsomal assays identified UGT2B7 as the main contributor to steviol glucuronidation at low substrate concentration. Model: Human and rat microsomes with recombinant human UGT assays. Limitations: Organ-specific clearance differed; in vitro enzyme contribution is not a measured whole-body clearance fraction. Evidence access: Primary abstract Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24296138/ · DOI 10.1016/j.fct.2013.11.028
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Among the tested intestinal bacterial groups, Bacteroides isolates most efficiently hydrolyzed stevioside and rebaudioside A to steviol.

    Bacteroides isolates in the human fecal stevia assay → Microbial production of steviol source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Selected bacterial isolates and mixed fecal cultures.
    limitations
    The experiment does not prove a single necessary species or a clinical probiotic strategy.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Which microbes are present can influence conversion capacity.
    primary_references
    Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14558786/ · DOI 10.1021/jf0303619

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 34–40

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Selected bacterial isolates and mixed fecal cultures. · source_derived_draft · unverified_draft

    ## stevia-bacteroides Which microbes are present can influence conversion capacity. Among the tested intestinal bacterial groups, Bacteroides isolates most efficiently hydrolyzed stevioside and rebaudioside A to steviol. Model: Selected bacterial isolates and mixed fecal cultures. Limitations: The experiment does not prove a single necessary species or a clinical probiotic strategy. Evidence access: Primary abstract Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14558786/ · DOI 10.1021/jf0303619
    Complete structured claim and evidence

  2. Diclofenac inhibited steviol glucuronidation in human liver microsomes, with reported Ki 4.2 micromolar.

    Diclofenac → Human microsomal steviol glucuronidation source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    In vitro human liver microsomes.
    limitations
    Clinical relevance at ordinary sweetener exposure was not established; steviol is the possible interaction victim.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    A drug can interfere with the clearance step for a plant-derived metabolite.
    primary_references
    Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24296138/ · DOI 10.1016/j.fct.2013.11.028

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 66–72

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro human liver microsomes. · source_derived_draft · unverified_draft

    ## stevia-diclofenac-conjugation A drug can interfere with the clearance step for a plant-derived metabolite. Diclofenac inhibited steviol glucuronidation in human liver microsomes, with reported Ki 4.2 micromolar. Model: In vitro human liver microsomes. Limitations: Clinical relevance at ordinary sweetener exposure was not established; steviol is the possible interaction victim. Evidence access: Primary abstract Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24296138/ · DOI 10.1016/j.fct.2013.11.028
    Complete structured claim and evidence

  3. Following a single 3 g oral dose, rebaudioside A was detected in plasma as early as one hour in nearly all participants; steviol and its glucuronide peaked at 19.5 hours.

    Rebaudioside A → Human plasma rebaudioside A source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Thirty adults with type 2 diabetes; open-label randomized placebo crossover; metformin or no therapy.
    limitations
    This does not establish the fraction absorbed intact or justify a blanket statement that glycosides are never absorbed.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Some intact parent compound can be detected after a large dose.
    primary_references
    Pharmacokinetics of Oral Rebaudioside A in Patients with Type 2 Diabetes Mellitus and Its Effects on Glucose Homeostasis: A Placebo-Controlled Crossover Trial. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36057030/ · DOI 10.1007/s13318-022-00792-7
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 90–96

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Thirty adults with type 2 diabetes; open-label randomized placebo crossover; metformin or no therapy. · source_derived_draft · unverified_draft

    ## stevia-intact-reba Some intact parent compound can be detected after a large dose. Following a single 3 g oral dose, rebaudioside A was detected in plasma as early as one hour in nearly all participants; steviol and its glucuronide peaked at 19.5 hours. Model: Thirty adults with type 2 diabetes; open-label randomized placebo crossover; metformin or no therapy. Limitations: This does not establish the fraction absorbed intact or justify a blanket statement that glycosides are never absorbed. Evidence access: Primary abstract Pharmacokinetics of Oral Rebaudioside A in Patients with Type 2 Diabetes Mellitus and Its Effects on Glucose Homeostasis: A Placebo-Controlled Crossover Trial. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36057030/ · DOI 10.1007/s13318-022-00792-7
    Complete structured claim and evidence

  4. Stevioside at 1–100 micromolar did not alter ATP-sensitive potassium-channel activity in the reported beta-cell experiments.

    Stevioside → Beta-cell KATP activity in the 2000 stevioside assay, channel-recording species unresolved source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse islets and rat INS-1 beta-cell experiments; channel findings summarized in the primary abstract.
    limitations
    The accessed abstract includes mouse islets and rat INS-1 cells but does not unambiguously assign the channel recording to one preparation; full protocol-level reconciliation with the later positive report is incomplete.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    One experiment found insulin stimulation without a detected potassium-channel effect.
    primary_references
    Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10690946/ · DOI 10.1016/s0026-0495(00)91325-8

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 226–232

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse islets and rat INS-1 beta-cell experiments; channel findings summarized in the primary abstract. · source_derived_draft · unverified_draft

    ## stevia-katp-null One experiment found insulin stimulation without a detected potassium-channel effect. Stevioside at 1–100 micromolar did not alter ATP-sensitive potassium-channel activity in the reported beta-cell experiments. Model: Mouse islets and rat INS-1 beta-cell experiments; channel findings summarized in the primary abstract. Limitations: The accessed abstract includes mouse islets and rat INS-1 cells but does not unambiguously assign the channel recording to one preparation; full protocol-level reconciliation with the later positive report is incomplete. Evidence access: Primary abstract Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10690946/ · DOI 10.1016/s0026-0495(00)91325-8
    Complete structured claim and evidence

  5. Stevioside did not inhibit human OAT3-mediated estrone-sulfate uptake or OAT1-mediated para-aminohippurate uptake, whereas steviol did.

    Stevioside → Human organic anion transporter 3 / SLC22A8 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human OAT expression in Xenopus oocytes.
    limitations
    A negative uptake-inhibition assay does not rule out all other transporters.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    The parent sweetener and its metabolite do not share every transport interaction.
    primary_references
    Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). · 2005 · https://pubmed.ncbi.nlm.nih.gov/15644426/ · DOI 10.1124/jpet.104.080366

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 114–120

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human OAT expression in Xenopus oocytes. · source_derived_draft · unverified_draft

    ## stevia-parent-oat-null The parent sweetener and its metabolite do not share every transport interaction. Stevioside did not inhibit human OAT3-mediated estrone-sulfate uptake or OAT1-mediated para-aminohippurate uptake, whereas steviol did. Model: Human OAT expression in Xenopus oocytes. Limitations: A negative uptake-inhibition assay does not rule out all other transporters. Evidence access: Primary abstract Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). · 2005 · https://pubmed.ncbi.nlm.nih.gov/15644426/ · DOI 10.1124/jpet.104.080366
    Complete structured claim and evidence

  6. In 30 adults with type 2 diabetes, 3 g oral rebaudioside A did not reduce two-hour OGTT glucose AUC versus placebo at the planned metabolite-peak time; insulin and C-peptide excursions were also comparable.

    Rebaudioside A → Human OGTT glucose AUC after rebaudioside A source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Randomized open-label crossover; OGTT 19 hours after dosing.
    limitations
    Different molecule and test timing from the stevioside meal trial; not an automatic contradiction.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    Measurable circulating metabolites did not guarantee a glucose-lowering response.
    primary_references
    Pharmacokinetics of Oral Rebaudioside A in Patients with Type 2 Diabetes Mellitus and Its Effects on Glucose Homeostasis: A Placebo-Controlled Crossover Trial. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36057030/ · DOI 10.1007/s13318-022-00792-7

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 370–376

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized open-label crossover; OGTT 19 hours after dosing. · source_derived_draft · unverified_draft

    ## stevia-reba-ogtt-null Measurable circulating metabolites did not guarantee a glucose-lowering response. In 30 adults with type 2 diabetes, 3 g oral rebaudioside A did not reduce two-hour OGTT glucose AUC versus placebo at the planned metabolite-peak time; insulin and C-peptide excursions were also comparable. Model: Randomized open-label crossover; OGTT 19 hours after dosing. Limitations: Different molecule and test timing from the stevioside meal trial; not an automatic contradiction. Evidence access: Primary abstract Pharmacokinetics of Oral Rebaudioside A in Patients with Type 2 Diabetes Mellitus and Its Effects on Glucose Homeostasis: A Placebo-Controlled Crossover Trial. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36057030/ · DOI 10.1007/s13318-022-00792-7
    Complete structured claim and evidence

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