Stevia

evidence_access

Primary abstract

experimental_model

Two-week randomized human trial with glucose-vehicle and untreated controls.

limitations

The 120 participants were spread across arms; the findings do not make all sweeteners interchangeable or establish clinical disease causation.

nutrient_topic

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

plain_language

A microbiome change should not be relabeled as demonstrated stevia-induced glucose intolerance.

primary_references

Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35987213/ · DOI 10.1016/j.cell.2022.07.016

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two-week randomized human trial with glucose-vehicle and untreated controls. · source_derived_draft · unverified_draft

## stevia-microbiome-context A microbiome change should not be relabeled as demonstrated stevia-induced glucose intolerance. In a 120-person trial across four sweeteners and two controls, stevia was among the interventions associated with distinct microbiome and metabolome changes; significant group-level glycemic impairment was reported for saccharin and sucralose. Model: Two-week randomized human trial with glucose-vehicle and untreated controls. Limitations: The 120 participants were spread across arms; the findings do not make all sweeteners interchangeable or establish clinical disease causation. Evidence access: Primary abstract Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35987213/ · DOI 10.1016/j.cell.2022.07.016

evidence_access

Primary abstract

experimental_model

Healthy normal-BMI adults; fecal 16S profiling.

limitations

Small study; drop volume and formulation constrain generalization. Classification alone is not proof of a causal or harmful microbiome change.

nutrient_topic

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

plain_language

A negative broad-community comparison does not mean every microbial feature is unchanged.

primary_references

Consumption of the Non-Nutritive Sweetener Stevia for 12 Weeks Does Not Alter the Composition of the Human Gut Microbiota. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38257188/ · DOI 10.3390/nu16020296

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Healthy normal-BMI adults; fecal 16S profiling. · source_derived_draft · unverified_draft

## stevia-microbiome-null A negative broad-community comparison does not mean every microbial feature is unchanged. Five drops of stevia twice daily for 12 weeks produced no significant alpha- or beta-diversity change or clear taxon abundance differences in 14 users versus 13 controls; a classifier distinguished groups with about 75% accuracy. Model: Healthy normal-BMI adults; fecal 16S profiling. Limitations: Small study; drop volume and formulation constrain generalization. Classification alone is not proof of a causal or harmful microbiome change. Evidence access: Primary abstract Consumption of the Non-Nutritive Sweetener Stevia for 12 Weeks Does Not Alter the Composition of the Human Gut Microbiota. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38257188/ · DOI 10.3390/nu16020296

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

evidence_access

Primary abstract

experimental_model

Human cell-based receptor screening.

limitations

A tongue receptor response does not automatically reproduce in intestinal or immune tissue.

nutrient_topic

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

plain_language

Two separately stored receptors connect the taste profile to other research.

primary_references

Human psychometric and taste receptor responses to steviol glycosides. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22616809/ · DOI 10.1021/jf301297n

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell-based receptor screening. · source_derived_draft · unverified_draft

## stevia-bitter14 Two separately stored receptors connect the taste profile to other research. TAS2R14 was the other human receptor identified in the functional screen as mediating steviol-glycoside bitter off-taste. Model: Human cell-based receptor screening. Limitations: A tongue receptor response does not automatically reproduce in intestinal or immune tissue. Evidence access: Primary abstract Human psychometric and taste receptor responses to steviol glycosides. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22616809/ · DOI 10.1021/jf301297n

evidence_access

Primary abstract

experimental_model

Human receptor-expression assays and sensory studies.

limitations

Individual glycosides differ in receptor potency; this is not a claim that every glycoside is equally bitter.

nutrient_topic

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

plain_language

The sweetener can also engage a bitter receptor.

primary_references

Human psychometric and taste receptor responses to steviol glycosides. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22616809/ · DOI 10.1021/jf301297n

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human receptor-expression assays and sensory studies. · source_derived_draft · unverified_draft

## stevia-bitter4 The sweetener can also engage a bitter receptor. Screening 25 human bitter taste receptors identified TAS2R4 among the receptors mediating steviol-glycoside bitter off-taste. Model: Human receptor-expression assays and sensory studies. Limitations: Individual glycosides differ in receptor potency; this is not a claim that every glycoside is equally bitter. Evidence access: Primary abstract Human psychometric and taste receptor responses to steviol glycosides. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22616809/ · DOI 10.1021/jf301297n

evidence_access

Primary abstract

experimental_model

Multicenter randomized double-blind trial in Chinese adults with mild essential hypertension.

limitations

Gram-level daily exposure; this does not verify calcium-channel mediation in humans or make every stevia product an antihypertensive.

nutrient_topic

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

plain_language

A pharmacological-style oral regimen produced a clinical signal in one study.

primary_references

Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14693305/ · DOI 10.1016/s0149-2918(03)80334-x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Multicenter randomized double-blind trial in Chinese adults with mild essential hypertension. · source_derived_draft · unverified_draft

## stevia-blood-pressure-trial A pharmacological-style oral regimen produced a clinical signal in one study. A two-year placebo-controlled trial in mild hypertension reported lower blood pressure with 500 mg stevioside three times daily; 174 enrolled and 168 completed. Model: Multicenter randomized double-blind trial in Chinese adults with mild essential hypertension. Limitations: Gram-level daily exposure; this does not verify calcium-channel mediation in humans or make every stevia product an antihypertensive. Evidence access: Primary abstract Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14693305/ · DOI 10.1016/s0149-2918(03)80334-x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text; Figure 1d and methods

experimental_model

Intracellular calcium buffered with BAPTA; whole-cell recordings.

limitations

This is a local signaling requirement, not evidence of dietary calcium deficiency or benefit from a calcium supplement.

nutrient_topic

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

plain_language

Without the activating calcium signal, potentiation did not turn the channel on.

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

trigger_kind

machinery_impairment Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Intracellular calcium buffered with BAPTA; whole-cell recordings. · source_derived_draft · unverified_draft

## stevia-calcium-gate Without the activating calcium signal, potentiation did not turn the channel on. Buffering intracellular free calcium prevented stevioside from activating TRPM5 in the expression assay. Model: Intracellular calcium buffered with BAPTA; whole-cell recordings. Limitations: This is a local signaling requirement, not evidence of dietary calcium deficiency or benefit from a calcium supplement. Evidence access: Primary full text; Figure 1d and methods 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

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

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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

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

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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

evidence_access

Primary abstract

experimental_model

Controlled human intervention; ages 33–75.

limitations

This evaluates a particular purified glycoside and regimen, not every possible extract or sugar-replacement strategy.

nutrient_topic

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

plain_language

A longer human study did not confirm a general antidiabetic effect.

primary_references

Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18555575/ · DOI 10.1016/j.fct.2008.05.007

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Controlled human intervention; ages 33–75. · source_derived_draft · unverified_draft

## stevia-chronic-reba-null A longer human study did not confirm a general antidiabetic effect. A 16-week trial of 1000 mg/day rebaudioside A in 60 adults versus 62 placebo recipients with type 2 diabetes found no significant difference in HbA1c, fasting glucose, insulin or C-peptide changes. Model: Controlled human intervention; ages 33–75. Limitations: This evaluates a particular purified glycoside and regimen, not every possible extract or sugar-replacement strategy. Evidence access: Primary abstract Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18555575/ · DOI 10.1016/j.fct.2008.05.007

evidence_access

Primary abstract

experimental_model

Four-week placebo run-in followed by randomized dose-escalation treatment.

limitations

The formulation, doses, duration and population differ from the two-year trial; a direct same-condition contradiction is not established.

nutrient_topic

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

plain_language

Preparation and trial design matter when comparing apparent benefits.

primary_references

Investigation of the antihypertensive effect of oral crude stevioside in patients with mild essential hypertension. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16775813/ · DOI 10.1002/ptr.1944

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Four-week placebo run-in followed by randomized dose-escalation treatment. · source_derived_draft · unverified_draft

## stevia-crude-pressure-null Preparation and trial design matter when comparing apparent benefits. Crude stevioside increased from 3.75 to 15 mg/kg/day over 24 weeks did not lower blood pressure more than placebo in untreated mild hypertension. Model: Four-week placebo run-in followed by randomized dose-escalation treatment. Limitations: The formulation, doses, duration and population differ from the two-year trial; a direct same-condition contradiction is not established. Evidence access: Primary abstract Investigation of the antihypertensive effect of oral crude stevioside in patients with mild essential hypertension. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16775813/ · DOI 10.1002/ptr.1944

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

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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

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

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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

evidence_access

Primary abstract

experimental_model

In vitro uptake assay; distinct from the glucuronidation experiment.

limitations

Combining the two records does not quantify a net in vivo interaction.

nutrient_topic

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

plain_language

The same drug intersects two different clearance steps.

primary_references

Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26525112/ · DOI 10.1016/j.fct.2015.10.011

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro uptake assay; distinct from the glucuronidation experiment. · source_derived_draft · unverified_draft

## stevia-diclofenac-oat3 The same drug intersects two different clearance steps. Diclofenac inhibited OAT3-mediated steviol-glucuronide uptake, with IC50 8.0 micromolar. Model: In vitro uptake assay; distinct from the glucuronidation experiment. Limitations: Combining the two records does not quantify a net in vivo interaction. Evidence access: Primary abstract Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26525112/ · DOI 10.1016/j.fct.2015.10.011

evidence_access

Primary abstract

experimental_model

Mouse and human enteroendocrine signaling study; direction and cell-specific exposure unresolved in the accessed abstract.

limitations

This is recorded only as context-dependent modulation; no direction, effective dietary dose or supplement synergy is inferred.

nutrient_topic

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

plain_language

Other dietary compounds may change a response at a shared signaling system.

primary_references

Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse and human enteroendocrine signaling study; direction and cell-specific exposure unresolved in the accessed abstract. · source_derived_draft · unverified_draft

## stevia-gut-gaba Other dietary compounds may change a response at a shared signaling system. The study reported that GABA and 6-methoxyflavanone can modulate rebaudioside-A-dependent GLP-1 release. Model: Mouse and human enteroendocrine signaling study; direction and cell-specific exposure unresolved in the accessed abstract. Limitations: This is recorded only as context-dependent modulation; no direction, effective dietary dose or supplement synergy is inferred. Evidence access: Primary abstract Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

evidence_access

Primary abstract

experimental_model

Human HuTu-80 cells, with separate mouse STC-1 experiments.

limitations

The accessed abstract does not provide the tested concentration range; no oral human GLP-1 response is asserted.

nutrient_topic

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

plain_language

An intestinal cell sensor can connect exposure to hormone release.

primary_references

Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HuTu-80 cells, with separate mouse STC-1 experiments. · source_derived_draft · unverified_draft

## stevia-gut-glp1 An intestinal cell sensor can connect exposure to hormone release. Rebaudioside A concentration-dependently stimulated GLP-1 release in human HuTu-80 enteroendocrine cells. Model: Human HuTu-80 cells, with separate mouse STC-1 experiments. Limitations: The accessed abstract does not provide the tested concentration range; no oral human GLP-1 response is asserted. Evidence access: Primary abstract Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

evidence_access

Primary abstract

experimental_model

Human cell-line pharmacology; sweet-signaling inhibition did not explain the response.

limitations

Pharmacological inhibition does not establish exclusive receptor involvement or in vivo necessity.

nutrient_topic

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

plain_language

A bitter receptor participates in a gut-hormone response.

primary_references

Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell-line pharmacology; sweet-signaling inhibition did not explain the response. · source_derived_draft · unverified_draft

## stevia-gut-tas2r4 A bitter receptor participates in a gut-hormone response. Inhibitor experiments in human HuTu-80 cells supported TAS2R4 involvement in rebaudioside-A-evoked GLP-1 release. Model: Human cell-line pharmacology; sweet-signaling inhibition did not explain the response. Limitations: Pharmacological inhibition does not establish exclusive receptor involvement or in vivo necessity. Evidence access: Primary abstract Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

evidence_access

Primary abstract

experimental_model

Human enteroendocrine cell-line signaling experiments.

limitations

The species-specific human protein node is distinct from mouse Trpm5 and the incompletely resolved expression construct.

nutrient_topic

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

plain_language

Taste-associated ion-channel machinery is shared with intestinal signaling.

primary_references

Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enteroendocrine cell-line signaling experiments. · source_derived_draft · unverified_draft

## stevia-gut-trpm5 Taste-associated ion-channel machinery is shared with intestinal signaling. The human HuTu-80 experiments also supported TRPM5 involvement in rebaudioside-A-evoked GLP-1 release. Model: Human enteroendocrine cell-line signaling experiments. Limitations: The species-specific human protein node is distinct from mouse Trpm5 and the incompletely resolved expression construct. Evidence access: Primary abstract Rebaudioside A from Stevia rebaudiana stimulates GLP-1 release by enteroendocrine cells via bitter taste signalling pathways. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37431625/ · DOI 10.1039/d3fo00818e

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

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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

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

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Same crossover study in healthy men.

limitations

Group medians do not predict one person or another formulation.

nutrient_topic

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

plain_language

An oral sweet taste and a circulating metabolite peak occur on different timelines.

primary_references

Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18555578/ · DOI 10.1016/j.fct.2008.04.041

trigger_kind

biomarker_context Imported condition classification; unverified.

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 82–88

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same crossover study in healthy men. · source_derived_draft · unverified_draft

## stevia-human-timing An oral sweet taste and a circulating metabolite peak occur on different timelines. Median plasma steviol-glucuronide peak times were 12 hours after rebaudioside A and 8 hours after stevioside; elimination half-lives were approximately 14 hours. Model: Same crossover study in healthy men. Limitations: Group medians do not predict one person or another formulation. Evidence access: Primary abstract Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18555578/ · DOI 10.1016/j.fct.2008.04.041

evidence_access

Primary abstract

experimental_model

Randomized double-blind crossover pharmacokinetic study; dose values not specified in the accessed abstract.

limitations

Incomplete recovery is not evidence of permanent retention. These are healthy adult male pharmacokinetics.

nutrient_topic

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

plain_language

The conjugated metabolite is a major measured urinary exit route.

primary_references

Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18555578/ · DOI 10.1016/j.fct.2008.04.041

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 74–80

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized double-blind crossover pharmacokinetic study; dose values not specified in the accessed abstract. · source_derived_draft · unverified_draft

## stevia-human-urine The conjugated metabolite is a major measured urinary exit route. After single oral rebaudioside A or stevioside doses in healthy men, urinary steviol glucuronide accounted for 59% and 62% of the respective doses during 72-hour collection. Model: Randomized double-blind crossover pharmacokinetic study; dose values not specified in the accessed abstract. Limitations: Incomplete recovery is not evidence of permanent retention. These are healthy adult male pharmacokinetics. Evidence access: Primary abstract Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18555578/ · DOI 10.1016/j.fct.2008.04.041

evidence_access

Primary abstract

experimental_model

Human THP-1 cells; antibody perturbation.

limitations

This is an explained stimulus difference, not a contradiction or proof of a clinical immune benefit.

nutrient_topic

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

plain_language

The same compound can stimulate resting cells while suppressing an already stimulated response.

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 330–336

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human THP-1 cells; antibody perturbation. · source_derived_draft · unverified_draft

## stevia-immune-resting The same compound can stimulate resting cells while suppressing an already stimulated response. In unstimulated THP-1 cells, stevioside induced TNF, IL-1beta and nitric oxide release; anti-TLR4 antibody partially neutralized TNF release. Model: Human THP-1 cells; antibody perturbation. Limitations: This is an explained stimulus difference, not a contradiction or proof of a clinical immune benefit. 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

evidence_access

Primary abstract

experimental_model

Human monocyte-derived cell line with LPS stimulation.

limitations

High direct exposure is not demonstrated after dietary sweetener use; pathway inhibition does not establish direct protein binding.

nutrient_topic

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

plain_language

The inflammatory state changes what the compound does.

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 322–328

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human monocyte-derived cell line with LPS stimulation. · source_derived_draft · unverified_draft

## stevia-immune-stimulated The inflammatory state changes what the compound does. Stevioside at 1 mM suppressed LPS-induced TNF and IL-1beta release in human THP-1 cells, with suppression of IKKbeta and NF-kappaB activation. Model: Human monocyte-derived cell line with LPS stimulation. Limitations: High direct exposure is not demonstrated after dietary sweetener use; pathway inhibition does not establish direct protein binding. 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

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

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

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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

evidence_access

Primary abstract

experimental_model

Conventional and permeabilized whole-cell patch clamp of mouse islet beta cells.

limitations

This does not by itself establish direct pore binding; glucose dependence and recording conditions may explain the discrepancy.

nutrient_topic

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

plain_language

Another experiment detected a potassium-channel change at a concentration within the earlier tested range.

primary_references

Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18435771/ · DOI 10.1111/j.1463-1326.2008.00864.x

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 234–240

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Conventional and permeabilized whole-cell patch clamp of mouse islet beta cells. · source_derived_draft · unverified_draft

## stevia-katp-positive Another experiment detected a potassium-channel change at a concentration within the earlier tested range. Stevioside at 1 micromolar reduced ATP-sensitive potassium conductance in a glucose-dependent manner in dispersed mouse beta cells. Model: Conventional and permeabilized whole-cell patch clamp of mouse islet beta cells. Limitations: This does not by itself establish direct pore binding; glucose dependence and recording conditions may explain the discrepancy. Evidence access: Primary abstract Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18435771/ · DOI 10.1111/j.1463-1326.2008.00864.x

evidence_access

Primary full text; supplementary Figure 3 description

experimental_model

Mouse islet calcium imaging at low versus stimulatory glucose.

limitations

This does not establish zero human hypoglycemia risk under all combinations.

nutrient_topic

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

plain_language

The metabolic trigger still matters when a potentiator is present.

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 218–224

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse islet calcium imaging at low versus stimulatory glucose. · source_derived_draft · unverified_draft

## stevia-low-glucose The metabolic trigger still matters when a potentiator is present. Stevioside did not elicit islet calcium signals at 3 mM glucose in the tested mouse preparation. Model: Mouse islet calcium imaging at low versus stimulatory glucose. Limitations: This does not establish zero human hypoglycemia risk under all combinations. Evidence access: Primary full text; supplementary Figure 3 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

evidence_access

Primary abstract

experimental_model

Acute paired crossover; four-hour blood sampling.

limitations

Small study and gram-level dose; not evidence of long-term disease treatment or of equivalence to rebaudioside A.

nutrient_topic

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

plain_language

A small human meal trial found a glycemic effect but did not confirm every proposed hormonal route.

primary_references

Antihyperglycemic effects of stevioside in type 2 diabetic subjects. · 2004 · https://pubmed.ncbi.nlm.nih.gov/14681845/ · DOI 10.1016/j.metabol.2003.07.013

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 362–368

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Acute paired crossover; four-hour blood sampling. · source_derived_draft · unverified_draft

## stevia-meal-trial A small human meal trial found a glycemic effect but did not confirm every proposed hormonal route. In a 12-person type-2-diabetes crossover trial, adding 1 g stevioside to a meal reduced glucose incremental AUC by 18% versus maize starch, without a significant change in insulin or GLP-1 AUC. Model: Acute paired crossover; four-hour blood sampling. Limitations: Small study and gram-level dose; not evidence of long-term disease treatment or of equivalence to rebaudioside A. Evidence access: Primary abstract Antihyperglycemic effects of stevioside in type 2 diabetic subjects. · 2004 · https://pubmed.ncbi.nlm.nih.gov/14681845/ · DOI 10.1016/j.metabol.2003.07.013

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

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

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text; Figures 3 and 4

experimental_model

Wild-type versus Trpm5-null isolated mouse islets.

limitations

This is genetic machinery loss, not stevia deficiency; human efficacy is not inferred.

nutrient_topic

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

plain_language

An available compound cannot reproduce this effect when the target channel is missing.

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

trigger_kind

machinery_impairment Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Wild-type versus Trpm5-null isolated mouse islets. · source_derived_draft · unverified_draft

## stevia-mouse-knockout An available compound cannot reproduce this effect when the target channel is missing. Trpm5 knockout abolished the stevioside-associated increase in glucose-driven calcium-oscillation frequency and enhancement of insulin release in mouse islets. Model: Wild-type versus Trpm5-null isolated mouse islets. Limitations: This is genetic machinery loss, not stevia deficiency; human efficacy is not inferred. Evidence access: Primary full text; Figures 3 and 4 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

evidence_access

Primary full text; Figure 3

experimental_model

Mouse islets with calcium imaging; dose range 1 nM to 100 micromolar.

limitations

EC50 is an experimental response value, not a human blood target.

nutrient_topic

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

plain_language

The timing of calcium signals changes as well as their presence.

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

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse islets with calcium imaging; dose range 1 nM to 100 micromolar. · source_derived_draft · unverified_draft

## stevia-mouse-oscillations The timing of calcium signals changes as well as their presence. Stevioside increased calcium-oscillation frequency in wild-type mouse islets at 10 mM glucose; the reported concentration-response EC50 was 690 nM. Model: Mouse islets with calcium imaging; dose range 1 nM to 100 micromolar. Limitations: EC50 is an experimental response value, not a human blood target. Evidence access: Primary full text; Figure 3 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

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.

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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

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.

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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

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

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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

evidence_access

Primary abstract

experimental_model

In vitro transport inhibition assay.

limitations

Free tissue exposure and a human pharmacokinetic interaction were not established.

nutrient_topic

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

plain_language

A food-derived flavonoid intersects the metabolite clearance route.

primary_references

Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26525112/ · DOI 10.1016/j.fct.2015.10.011

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 130–136

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

## stevia-quercetin-oat3 A food-derived flavonoid intersects the metabolite clearance route. Quercetin inhibited OAT3-mediated steviol-glucuronide uptake, with IC50 1.8 micromolar. Model: In vitro transport inhibition assay. Limitations: Free tissue exposure and a human pharmacokinetic interaction were not established. Evidence access: Primary abstract Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26525112/ · DOI 10.1016/j.fct.2015.10.011

evidence_access

Primary abstract

experimental_model

Rat aorta with and without endothelium; cultured rat A7r5 cells; intraperitoneal 25 mg/kg also examined in hypertensive rats.

limitations

The specific calcium-channel molecular target was not established in the accessed abstract; parenteral dosing is not oral sweetener use.

nutrient_topic

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

plain_language

A vascular calcium-entry effect differs from pancreatic calcium-signal potentiation.

primary_references

Inhibitory effect of stevioside on calcium influx to produce antihypertension. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11745013/ · DOI 10.1055/s-2001-18841

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat aorta with and without endothelium; cultured rat A7r5 cells; intraperitoneal 25 mg/kg also examined in hypertensive rats. · source_derived_draft · unverified_draft

## stevia-rat-calcium A vascular calcium-entry effect differs from pancreatic calcium-signal potentiation. Stevioside relaxed vasopressin-contracted rat aortic rings and inhibited calcium influx in A7r5 smooth-muscle cells; the relaxation disappeared in calcium-free medium. Model: Rat aorta with and without endothelium; cultured rat A7r5 cells; intraperitoneal 25 mg/kg also examined in hypertensive rats. Limitations: The specific calcium-channel molecular target was not established in the accessed abstract; parenteral dosing is not oral sweetener use. Evidence access: Primary abstract Inhibitory effect of stevioside on calcium influx to produce antihypertension. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11745013/ · DOI 10.1055/s-2001-18841

evidence_access

Primary abstract

experimental_model

Mouse islet nucleotide assays; the same paper reports reduced KATP conductance.

limitations

The causal chain from nucleotide change to conductance was proposed rather than isolated by every possible intervention.

nutrient_topic

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

plain_language

Energy state may connect a glycoside response to potassium-channel closure.

primary_references

Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18435771/ · DOI 10.1111/j.1463-1326.2008.00864.x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse islet nucleotide assays; the same paper reports reduced KATP conductance. · source_derived_draft · unverified_draft

## stevia-reba-atp Energy state may connect a glycoside response to potassium-channel closure. Rebaudioside A at 1 nM increased the ATP/ADP ratio at 16.7 mM glucose while not changing measured cAMP. Model: Mouse islet nucleotide assays; the same paper reports reduced KATP conductance. Limitations: The causal chain from nucleotide change to conductance was proposed rather than isolated by every possible intervention. Evidence access: Primary abstract Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18435771/ · DOI 10.1111/j.1463-1326.2008.00864.x

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

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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

evidence_access

Primary abstract

experimental_model

Fecal metagenomics and bile-acid measurements in feces, plasma and liver.

limitations

Association does not prove the microbe or bile acids caused the hepatic effect; neither glycoside improved glucose homeostasis in this study.

nutrient_topic

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

plain_language

Microbial chemistry is a candidate link to the liver response.

primary_references

Rebaudioside D decreases adiposity and hepatic lipid accumulation in a mouse model of obesity. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38321177/ · DOI 10.1038/s41598-024-53587-y

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Fecal metagenomics and bile-acid measurements in feces, plasma and liver. · source_derived_draft · unverified_draft

## stevia-rebd-bile Microbial chemistry is a candidate link to the liver response. Rebaudioside D treatment was associated with greater secondary bile-acid metabolism and enrichment of Faecalibaculum rodentium in the same mouse experiment. Model: Fecal metagenomics and bile-acid measurements in feces, plasma and liver. Limitations: Association does not prove the microbe or bile acids caused the hepatic effect; neither glycoside improved glucose homeostasis in this study. Evidence access: Primary abstract Rebaudioside D decreases adiposity and hepatic lipid accumulation in a mouse model of obesity. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38321177/ · DOI 10.1038/s41598-024-53587-y

evidence_access

Primary abstract

experimental_model

Male C57BL/6J diet-induced obesity; rebaudioside A and vehicle comparators.

limitations

Mouse dosing is not ordinary human food exposure; lower lipid content does not identify a unique molecular target.

nutrient_topic

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

plain_language

A less common glycoside had a liver phenotype in an obesity model.

primary_references

Rebaudioside D decreases adiposity and hepatic lipid accumulation in a mouse model of obesity. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38321177/ · DOI 10.1038/s41598-024-53587-y

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Male C57BL/6J diet-induced obesity; rebaudioside A and vehicle comparators. · source_derived_draft · unverified_draft

## stevia-rebd-liver A less common glycoside had a liver phenotype in an obesity model. Rebaudioside D at 50 mg/kg orally for 12 weeks reduced hepatic triglycerides, cholesterol and lipid peroxidation in male high-fat/high-sucrose-fed mice. Model: Male C57BL/6J diet-induced obesity; rebaudioside A and vehicle comparators. Limitations: Mouse dosing is not ordinary human food exposure; lower lipid content does not identify a unique molecular target. Evidence access: Primary abstract Rebaudioside D decreases adiposity and hepatic lipid accumulation in a mouse model of obesity. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38321177/ · DOI 10.1038/s41598-024-53587-y

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

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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

evidence_access

Primary abstract

experimental_model

Sixty-minute static incubation and islet perifusion.

limitations

TRPM5 mediation was not established in this experiment; human glucose-lowering efficacy is separate.

nutrient_topic

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

plain_language

The conjugated metabolite is not necessarily biologically inactive.

primary_references

Steviol glucuronide, a metabolite of steviol glycosides, potently stimulates insulin secretion from isolated mouse islets: Studies in vitro. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31592450/ · DOI 10.1002/edm2.93

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Sixty-minute static incubation and islet perifusion. · source_derived_draft · unverified_draft

## stevia-svg-insulin The conjugated metabolite is not necessarily biologically inactive. Steviol glucuronide increased insulin release from isolated mouse islets, maximally at 100 nM with 16.7 mM glucose; enhancement required glucose of at least 11.1 mM in the tested range. Model: Sixty-minute static incubation and islet perifusion. Limitations: TRPM5 mediation was not established in this experiment; human glucose-lowering efficacy is separate. Evidence access: Primary abstract Steviol glucuronide, a metabolite of steviol glycosides, potently stimulates insulin secretion from isolated mouse islets: Studies in vitro. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31592450/ · DOI 10.1002/edm2.93

evidence_access

Primary abstract

experimental_model

In vitro transporter-expression comparison.

limitations

This compares tested systems, not every renal transporter or complete epithelial excretion.

nutrient_topic

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

plain_language

Conjugation changes the molecule without ending transporter dependence.

primary_references

Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26525112/ · DOI 10.1016/j.fct.2015.10.011

transport_effect

raises Recorded as predominant uptake of steviol glucuronide relative to the other tested systems.

transport_pool

the expressing cell Recorded as predominant uptake of steviol glucuronide relative to the other tested systems.

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

## stevia-svg-oat3 Conjugation changes the molecule without ending transporter dependence. OAT3 mediated predominant uptake of steviol glucuronide relative to the tested OATP1B1, OATP1B3 and OATP2B1 systems. Model: In vitro transporter-expression comparison. Limitations: This compares tested systems, not every renal transporter or complete epithelial excretion. Evidence access: Primary abstract Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26525112/ · DOI 10.1016/j.fct.2015.10.011

evidence_access

Primary abstract

experimental_model

Human sensory testing and cell-based functional receptor assays.

limitations

The sensory outcome does not establish pancreatic insulin release or systemic glucose lowering.

nutrient_topic

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

plain_language

Sweetness perception can change without direct inhibition of the sweet receptor.

primary_references

Human psychometric and taste receptor responses to steviol glycosides. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22616809/ · DOI 10.1021/jf301297n

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human sensory testing and cell-based functional receptor assays. · source_derived_draft · unverified_draft

## stevia-sweet-receptor Sweetness perception can change without direct inhibition of the sweet receptor. Human sensory and receptor-expression experiments examined stevioside sweet responses through TAS1R2/TAS1R3; falling sweetness at high concentration was not attributed to allosteric suppression of that receptor. Model: Human sensory testing and cell-based functional receptor assays. Limitations: The sensory outcome does not establish pancreatic insulin release or systemic glucose lowering. Evidence access: Primary abstract Human psychometric and taste receptor responses to steviol glycosides. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22616809/ · DOI 10.1021/jf301297n

evidence_access

Primary full text; Figure 1

experimental_model

HEK293T channel-expression patch clamp.

limitations

This direct bath exposure is not an oral human exposure study.

nutrient_topic

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

plain_language

A second glycoside reaches the same channel endpoint.

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

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HEK293T channel-expression patch clamp. · source_derived_draft · unverified_draft

## stevia-trpm5-reba A second glycoside reaches the same channel endpoint. Rebaudioside A increased calcium-activated TRPM5 currents in the expression system. Model: HEK293T channel-expression patch clamp. Limitations: This direct bath exposure is not an oral human exposure study. Evidence access: Primary full text; Figure 1 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

evidence_access

Primary full text; Figure 1 and patch-clamp methods

experimental_model

Whole-cell patch clamp with 1 micromolar free intracellular calcium.

limitations

Human host-cell origin does not establish construct species; that uncertainty is explicit in the channel node.

nutrient_topic

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

plain_language

It strengthens an existing ion-channel response rather than supplying the calcium signal.

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

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Whole-cell patch clamp with 1 micromolar free intracellular calcium. · source_derived_draft · unverified_draft

## stevia-trpm5-stev It strengthens an existing ion-channel response rather than supplying the calcium signal. Stevioside increased calcium-activated TRPM5 currents in transfected HEK293T cells; the effect reversed with washout. Model: Whole-cell patch clamp with 1 micromolar free intracellular calcium. Limitations: Human host-cell origin does not establish construct species; that uncertainty is explicit in the channel node. Evidence access: Primary full text; Figure 1 and patch-clamp methods 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

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

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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

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

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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

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

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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