Nutrient chapter

Stevia

Botanical sweetener collection from Stevia rebaudiana. A grouping of preparations, not one chemically pure molecule and not an essential nutrient. Individual glycosides and metabolites are separately identified.

57 recorded mechanisms · 4 availability situations · 4 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

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
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
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
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
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
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
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
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.
Steviol glucuronide → Human urinary steviol-glucuronide elimination source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Median plasma steviol-glucuronide peak times were 12 hours after rebaudioside A and 8 hours after stevioside; elimination half-lives were approximately 14 hours.
Rebaudioside A → Human steviol-glucuronide time to peak source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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
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
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
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
OAT3 mediated predominant uptake of steviol glucuronide relative to the tested OATP1B1, OATP1B3 and OATP2B1 systems.
Human organic anion transporter 3 / SLC22A8 → Steviol glucuronide source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Quercetin inhibited OAT3-mediated steviol-glucuronide uptake, with IC50 1.8 micromolar.
Quercetin → Human OAT3-mediated steviol-glucuronide uptake source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Diclofenac inhibited OAT3-mediated steviol-glucuronide uptake, with IC50 8.0 micromolar.
Diclofenac → Human OAT3-mediated steviol-glucuronide uptake source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 138–144
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
Complete structured claim and evidence
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.
Stevioside → Human sweet taste receptor TAS1R2/TAS1R3 source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 146–152
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
Complete structured claim and evidence
Screening 25 human bitter taste receptors identified TAS2R4 among the receptors mediating steviol-glycoside bitter off-taste.
Stevioside → Human bitter taste receptor / TAS2R4 source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 154–160
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
Complete structured claim and evidence
TAS2R14 was the other human receptor identified in the functional screen as mediating steviol-glycoside bitter off-taste.
Stevioside → Human bitter taste receptor / TAS2R14 source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 162–168
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
Complete structured claim and evidence
Stevioside increased calcium-activated TRPM5 currents in transfected HEK293T cells; the effect reversed with washout.
Stevioside → 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 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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 170–176
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
Complete structured claim and evidence
Rebaudioside A increased calcium-activated TRPM5 currents in the expression system.
Rebaudioside A → 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
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 178–184
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
Complete structured claim and evidence
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
Buffering intracellular free calcium prevented stevioside from activating TRPM5 in the expression assay.
Calcium ion → TRPM5 channel in the 2017 expression assay, construct species not independently verified source_derived_draftungraded
Experimental context and source evidence
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.
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 194–200
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
Complete structured claim and evidence
Stevioside increased calcium-oscillation frequency in wild-type mouse islets at 10 mM glucose; the reported concentration-response EC50 was 690 nM.
Stevioside → Mouse islet calcium-oscillation frequency source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 202–208
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
Complete structured claim and evidence
Trpm5 knockout abolished the stevioside-associated increase in glucose-driven calcium-oscillation frequency and enhancement of insulin release in mouse islets.
Mouse calcium-activated monovalent cation channel / Trpm5 → Mouse stevioside-induced islet potentiation source_derived_draftungraded
Experimental context and source evidence
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.
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 210–216
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
Complete structured claim and evidence
Stevioside did not elicit islet calcium signals at 3 mM glucose in the tested mouse preparation.
Stevioside → Mouse low-glucose islet calcium response source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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
Stevioside at 1 micromolar reduced ATP-sensitive potassium conductance in a glucose-dependent manner in dispersed mouse beta cells.
Stevioside → Mouse pancreatic beta-cell ATP-sensitive potassium conductance source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Rebaudioside A at 1 nM increased the ATP/ADP ratio at 16.7 mM glucose while not changing measured cAMP.
Rebaudioside A → Mouse islet ATP-to-ADP ratio source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 242–248
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
Complete structured claim and evidence
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.
Steviol glucuronide → Mouse insulin secretion after steviol glucuronide source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 250–256
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
Complete structured claim and evidence
Rebaudioside A concentration-dependently stimulated GLP-1 release in human HuTu-80 enteroendocrine cells.
Rebaudioside A → Human HuTu-80 GLP-1 release source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 258–264
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
Complete structured claim and evidence
Inhibitor experiments in human HuTu-80 cells supported TAS2R4 involvement in rebaudioside-A-evoked GLP-1 release.
Human bitter taste receptor / TAS2R4 → Human HuTu-80 GLP-1 release source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 266–272
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
Complete structured claim and evidence
The human HuTu-80 experiments also supported TRPM5 involvement in rebaudioside-A-evoked GLP-1 release.
Human calcium-activated monovalent cation channel / TRPM5 → Human HuTu-80 GLP-1 release source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 274–280
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
Complete structured claim and evidence
The study reported that GABA and 6-methoxyflavanone can modulate rebaudioside-A-dependent GLP-1 release.
Gamma-aminobutyric acid → Rebaudioside-A GLP-1 modulation assay, cell-specific assignment unresolved source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 282–288
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
Complete structured claim and evidence
Stevioside relaxed vasopressin-contracted rat aortic rings and inhibited calcium influx in A7r5 smooth-muscle cells; the relaxation disappeared in calcium-free medium.
Stevioside → Rat vascular calcium influx during stevioside exposure source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 290–296
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
Complete structured claim and evidence
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
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
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
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.
Stevioside → Human THP-1 LPS-induced cytokine release source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
In unstimulated THP-1 cells, stevioside induced TNF, IL-1beta and nitric oxide release; anti-TLR4 antibody partially neutralized TNF release.
Stevioside → Human unstimulated THP-1 cytokine release source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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
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
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
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.
Stevioside → Human meal glucose incremental AUC with stevioside source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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
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.
Rebaudioside A → Human HbA1c after 16-week rebaudioside A source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 378–384
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
Complete structured claim and evidence
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.
Stevioside → Human blood pressure during long-term stevioside source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 386–392
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
Complete structured claim and evidence
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.
Crude stevioside preparation from the 2006 hypertension trial → Human blood pressure during crude-stevioside trial source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 394–400
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
Complete structured claim and evidence
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.
Stevia → Human 12-week stevia gut-community composition source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 402–408
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
Complete structured claim and evidence
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.
Stevia → Human two-week stevia microbiome and metabolome responses source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 410–416
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
Complete structured claim and evidence
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.
Rebaudioside D → Mouse rebaudioside-D hepatic lipid accumulation source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 418–424
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
Complete structured claim and evidence
Rebaudioside D treatment was associated with greater secondary bile-acid metabolism and enrichment of Faecalibaculum rodentium in the same mouse experiment.
Rebaudioside D → Mouse rebaudioside-D-associated secondary bile-acid metabolism source_derived_draftungraded
Experimental context and source evidence
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
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 426–432
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
Complete structured claim and evidence
CFTR pore-region mutations changed anion selectivity, demonstrating that CFTR forms an anion channel.
Human cystic fibrosis transmembrane conductance regulator / CFTR → Chloride ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
CFTR expression and pore-residue mutagenesis
exposure
K95 or K335 substitutions
limitations
Selectivity experiment; not a supplementation study.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human CFTR in expression systems
plain_language
CFTR provides a route through which chloride can cross a membrane.
primary_references
[chloride-p1712984] Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. (1991). https://pubmed.ncbi.nlm.nih.gov/1712984/ DOI: 10.1126/science.1712984
tissue_or_cell_type
Cell plasma membrane
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 224–235
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CFTR expression and pore-residue mutagenesis · source_derived_draft · unverified_draft
### chloride-cftr-channel CFTR pore-region mutations changed anion selectivity, demonstrating that CFTR forms an anion channel. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: CFTR provides a route through which chloride can cross a membrane. organism: Human CFTR in expression systems tissue_or_cell_type: Cell plasma membrane experimental_model: CFTR expression and pore-residue mutagenesis limitations: Selectivity experiment; not a supplementation study. exposure: K95 or K335 substitutions evidence_span: {"source_cache": "artifacts/chloride-research/1712984.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b", "start_char": 0, "end_char": 849, "text_sha256": "d35ab648c3b60da00912ec5a2921115c14aa33b138ed2aa408e66d5153aa9d3b"} [chloride-p1712984] Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. (1991). https://pubmed.ncbi.nlm.nih.gov/1712984/ DOI: 10.1126/science.1712984
Complete structured claim and evidence
PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal.
Protein kinase A → Human cystic fibrosis transmembrane conductance regulator / CFTR source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"}
experimental_model
PKA phosphorylation and CFTR mutagenesis
exposure
Serines 660, 737, 795 and 813
limitations
Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model.
nutrient_topic
Chloride research collection; topical membership is not evidence of a direct dietary effect. · Chloride
organism
Human CFTR in cells
plain_language
A kinase switches the channel into a state that can respond to stimulation.
primary_references
[chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6
tissue_or_cell_type
CFTR regulatory domain
Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 237–248
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PKA phosphorylation and CFTR mutagenesis · source_derived_draft · unverified_draft
### chloride-pka-cftr PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase switches the channel into a state that can respond to stimulation. organism: Human CFTR in cells tissue_or_cell_type: CFTR regulatory domain experimental_model: PKA phosphorylation and CFTR mutagenesis limitations: Early site mapping; do not imply these are the only regulatory sites or endorse the historical gating model. exposure: Serines 660, 737, 795 and 813 evidence_span: {"source_cache": "artifacts/chloride-research/1716180.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5", "start_char": 0, "end_char": 961, "text_sha256": "8b48fbd8f484e2ed58382af512ac2b1f08ca87b9ea2db5faf920ce71d1f631d5"} [chloride-p1716180] Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1716180/ DOI: 10.1016/0092-8674(91)90446-6
Complete structured claim and evidence
UGT2B7 supported curcumin glucuronidation in the experimental system.
Human UDP-glucuronosyltransferase 2B7 / UGT2B7 → Curcumin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/curcumin-research/38522299.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84f7b5a7112090e4cc09dfd8b0bfce03908e6dd800773861d42815d71caf261c", "start_char": 0, "end_char": 1005, "text_sha256": "84f7b5a7112090e4cc09dfd8b0bfce03908e6dd800773861d42815d71caf261c"}
experimental_model
Glucuronidation assays with human liver microsomes and UGT2B7
exposure
Curcumin compared with tetrahydrocurcumin; pH-dependent structural analysis
limitations
Kinetic and structural comparisons do not establish comparative clinical efficacy; docking hypotheses are not imported as proven steps.
nutrient_topic
Curcumin research collection; topical membership is not evidence of a direct dietary effect. · Curcumin
organism
Human tissue and enzyme systems
plain_language
A named enzyme contributes to curcumin conjugation.
primary_references
[curcumin-p38522299] Glucuronidation dynamics of curcumin and tetrahydrocurcumin for differential structures and chemical reactivities in human liver microsome and uridine diphosphate glucuronosyltransferase 2B7. (2024). https://pubmed.ncbi.nlm.nih.gov/38522299/ DOI: 10.1016/j.foodchem.2024.138929
tissue_or_cell_type
Microsomes and recombinant UGT2B7
Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 177–188
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Glucuronidation assays with human liver microsomes and UGT2B7 · source_derived_draft · unverified_draft
### curcumin-ugt2b7-cur UGT2B7 supported curcumin glucuronidation in the experimental system. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A named enzyme contributes to curcumin conjugation. organism: Human tissue and enzyme systems tissue_or_cell_type: Microsomes and recombinant UGT2B7 experimental_model: Glucuronidation assays with human liver microsomes and UGT2B7 limitations: Kinetic and structural comparisons do not establish comparative clinical efficacy; docking hypotheses are not imported as proven steps. exposure: Curcumin compared with tetrahydrocurcumin; pH-dependent structural analysis evidence_span: {"source_cache": "artifacts/curcumin-research/38522299.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84f7b5a7112090e4cc09dfd8b0bfce03908e6dd800773861d42815d71caf261c", "start_char": 0, "end_char": 1005, "text_sha256": "84f7b5a7112090e4cc09dfd8b0bfce03908e6dd800773861d42815d71caf261c"} [curcumin-p38522299] Glucuronidation dynamics of curcumin and tetrahydrocurcumin for differential structures and chemical reactivities in human liver microsome and uridine diphosphate glucuronosyltransferase 2B7. (2024). https://pubmed.ncbi.nlm.nih.gov/38522299/ DOI: 10.1016/j.foodchem.2024.138929
Complete structured claim and evidence
Norathyriol competitively inhibited UGT1A3; IC50 8.2 and Ki 1.6 micromolar.
Norathyriol → Human UDP-glucuronosyltransferase 1A3 / UGT1A3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/mangiferin-research/28621744.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2741f9036a84104809f4d9813afeb1603b3e93e1d247ea0e4b5ff31be0e1ae5", "start_char": 0, "end_char": 1562, "text_sha256": "e2741f9036a84104809f4d9813afeb1603b3e93e1d247ea0e4b5ff31be0e1ae5"}
experimental_model
Recombinant UGT inhibition kinetics
exposure
Micromolar norathyriol; initial comparison at 100 micromolar
limitations
Probe-dependent biochemical inhibition; no established human interaction threshold. Docking is not additional proof of binding in vivo.
nutrient_topic
Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin
organism
Recombinant enzyme assay
plain_language
The aglycone has its own conjugation-enzyme interaction profile.
primary_references
[mangiferin-p28621744] In Vitro Comparative Study of the Inhibitory Effects of Mangiferin and Its Aglycone Norathyriol towards UDP-Glucuronosyl Transferase (UGT) Isoforms. (2017). https://pubmed.ncbi.nlm.nih.gov/28621744/ DOI: 10.3390/molecules22061008
tissue_or_cell_type
4-methylumbelliferone glucuronidation
Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 874–885
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant UGT inhibition kinetics · source_derived_draft · unverified_draft
### mangiferin-norathyriol-ugt1a3 Norathyriol competitively inhibited UGT1A3; IC50 8.2 and Ki 1.6 micromolar. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The aglycone has its own conjugation-enzyme interaction profile. organism: Recombinant enzyme assay tissue_or_cell_type: 4-methylumbelliferone glucuronidation experimental_model: Recombinant UGT inhibition kinetics limitations: Probe-dependent biochemical inhibition; no established human interaction threshold. Docking is not additional proof of binding in vivo. exposure: Micromolar norathyriol; initial comparison at 100 micromolar evidence_span: {"source_cache": "artifacts/mangiferin-research/28621744.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2741f9036a84104809f4d9813afeb1603b3e93e1d247ea0e4b5ff31be0e1ae5", "start_char": 0, "end_char": 1562, "text_sha256": "e2741f9036a84104809f4d9813afeb1603b3e93e1d247ea0e4b5ff31be0e1ae5"} [mangiferin-p28621744] In Vitro Comparative Study of the Inhibitory Effects of Mangiferin and Its Aglycone Norathyriol towards UDP-Glucuronosyl Transferase (UGT) Isoforms. (2017). https://pubmed.ncbi.nlm.nih.gov/28621744/ DOI: 10.3390/molecules22061008
Complete structured claim and evidence
At 250 micrograms/mL, mangiferin reduced UGT2B7 activity by about 55 percent.
Mangiferin → Human UDP-glucuronosyltransferase 2B7 / UGT2B7 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/mangiferin-research/22815239.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0", "start_char": 0, "end_char": 1728, "text_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0"}
experimental_model
Primary human hepatocyte exposure
exposure
Mangiferin 50-250 micrograms/mL for 48 hours
limitations
High in vitro concentrations; decreased enzyme activity is not proof of human drug-level changes. Extract and isolated mangiferin are distinct.
nutrient_topic
Mangiferin research collection; topical membership is not evidence of a direct dietary effect. · Mangiferin
organism
Homo sapiens
plain_language
A conjugation pathway also responded in vitro.
primary_references
[mangiferin-p22815239] Mangifera indica L. extract and mangiferin modulate cytochrome P450 and UDP-glucuronosyltransferase enzymes in primary cultures of human hepatocytes. (2013). https://pubmed.ncbi.nlm.nih.gov/22815239/ DOI: 10.1002/ptr.4782
tissue_or_cell_type
Cultured hepatocytes
Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 848–859
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human hepatocyte exposure · source_derived_draft · unverified_draft
### mangiferin-ugt2b7-activity At 250 micrograms/mL, mangiferin reduced UGT2B7 activity by about 55 percent. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A conjugation pathway also responded in vitro. organism: Homo sapiens tissue_or_cell_type: Cultured hepatocytes experimental_model: Primary human hepatocyte exposure limitations: High in vitro concentrations; decreased enzyme activity is not proof of human drug-level changes. Extract and isolated mangiferin are distinct. exposure: Mangiferin 50-250 micrograms/mL for 48 hours evidence_span: {"source_cache": "artifacts/mangiferin-research/22815239.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0", "start_char": 0, "end_char": 1728, "text_sha256": "e85ebd0af89f030dbeda45ed922e93a8a616c51f5ce1b64badc44d90791716c0"} [mangiferin-p22815239] Mangifera indica L. extract and mangiferin modulate cytochrome P450 and UDP-glucuronosyltransferase enzymes in primary cultures of human hepatocytes. (2013). https://pubmed.ncbi.nlm.nih.gov/22815239/ DOI: 10.1002/ptr.4782
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Channel potentiation needs an activating calcium signal

Condition: machinery_impairment · Experimental buffering of free intracellular calcium.

Normal role: TRPM5 responds to intracellular calcium.

Recorded consequence: Stevioside did not activate TRPM5.

Scope: Heterologous patch-clamp system.

A missing target prevents the mouse islet response

Condition: machinery_impairment · Genetic Trpm5 deletion.

Normal role: Mouse Trpm5 contributes to glucose-driven electrical and calcium dynamics.

Recorded consequence: Stevioside-associated islet potentiation was lost.

Scope: Isolated mouse islets.

Sweet taste precedes the circulating metabolite peak

Condition: biomarker_context · Single oral doses of different glycosides.

Normal role: Gut conversion and host clearance shape systemic exposure.

Recorded consequence: Different median glucuronide peak times.

Scope: Healthy adult male pharmacokinetics.

Parent and metabolite measurements answer different questions

Condition: biomarker_context · Three-gram rebaudioside-A exposure.

Normal role: Different chemical forms can have different targets and transport routes.

Recorded consequence: Parent detected early; steviol and glucuronide peaked much later.

Scope: Adults with type 2 diabetes.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Curcumin: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Mangiferin: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Stevioside and beta-cell KATP activity: no effect versus reduced conductancePrimary reports disagree on the measured potassium-channel endpoint: the 2000 study reported no channel effect over 1–100 micromolar stevioside, while the 2008 study reported reduced conductance at 1 micromolar under high-glucose conditions. This is an apparent experimental discrepancy, not an editorial correction. Cell preparation, glucose and patch configuration may contribute, but the discrepancy has not been resolved by a matched reanalysis.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Stevia

The mechanisms

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

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

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

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

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

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

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

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.

Median plasma steviol-glucuronide peak times were 12 hours after rebaudioside A and 8 hours after stevioside; elimination half-lives were approximately 14 hours.

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.

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

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

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

OAT3 mediated predominant uptake of steviol glucuronide relative to the tested OATP1B1, OATP1B3 and OATP2B1 systems.

Quercetin inhibited OAT3-mediated steviol-glucuronide uptake, with IC50 1.8 micromolar.

Diclofenac inhibited OAT3-mediated steviol-glucuronide uptake, with IC50 8.0 micromolar.

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.

Screening 25 human bitter taste receptors identified TAS2R4 among the receptors mediating steviol-glycoside bitter off-taste.

TAS2R14 was the other human receptor identified in the functional screen as mediating steviol-glycoside bitter off-taste.

Stevioside increased calcium-activated TRPM5 currents in transfected HEK293T cells; the effect reversed with washout.

Rebaudioside A increased calcium-activated TRPM5 currents in the expression system.

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

Buffering intracellular free calcium prevented stevioside from activating TRPM5 in the expression assay.

Stevioside increased calcium-oscillation frequency in wild-type mouse islets at 10 mM glucose; the reported concentration-response EC50 was 690 nM.

Trpm5 knockout abolished the stevioside-associated increase in glucose-driven calcium-oscillation frequency and enhancement of insulin release in mouse islets.

Stevioside did not elicit islet calcium signals at 3 mM glucose in the tested mouse preparation.

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

Stevioside at 1 micromolar reduced ATP-sensitive potassium conductance in a glucose-dependent manner in dispersed mouse beta cells.

Rebaudioside A at 1 nM increased the ATP/ADP ratio at 16.7 mM glucose while not changing measured cAMP.

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.

Rebaudioside A concentration-dependently stimulated GLP-1 release in human HuTu-80 enteroendocrine cells.

Inhibitor experiments in human HuTu-80 cells supported TAS2R4 involvement in rebaudioside-A-evoked GLP-1 release.

The human HuTu-80 experiments also supported TRPM5 involvement in rebaudioside-A-evoked GLP-1 release.

The study reported that GABA and 6-methoxyflavanone can modulate rebaudioside-A-dependent GLP-1 release.

Stevioside relaxed vasopressin-contracted rat aortic rings and inhibited calcium influx in A7r5 smooth-muscle cells; the relaxation disappeared in calcium-free medium.

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

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

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.

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.

In unstimulated THP-1 cells, stevioside induced TNF, IL-1beta and nitric oxide release; anti-TLR4 antibody partially neutralized TNF release.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

Rebaudioside D treatment was associated with greater secondary bile-acid metabolism and enrichment of Faecalibaculum rodentium in the same mouse experiment.

CFTR pore-region mutations changed anion selectivity, demonstrating that CFTR forms an anion channel.

PKA phosphorylated CFTR regulatory-domain serines; combined mutation of the four tested sites abolished the cAMP-responsive chloride signal.

UGT2B7 supported curcumin glucuronidation in the experimental system.

Norathyriol competitively inhibited UGT1A3; IC50 8.2 and Ki 1.6 micromolar.

At 250 micrograms/mL, mangiferin reduced UGT2B7 activity by about 55 percent.

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