Aspartame

evidence_access

Primary full text and author-list correction

experimental_model

Blinded randomized crossover; sessions at least seven days apart.

limitations

Not a test of all doses, repeated exposure or every vulnerable subgroup. Correction record: Publisher correction concerns author order, affiliations and citation; no experimental-result correction is stated. Correction PMID 25951455 inspected in full text. https://doi.org/10.1371/journal.pone.0126039

nutrient_topic

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

plain_language

A low-dose acute controlled challenge did not reproduce reported sensitivity.

primary_references

Aspartame sensitivity? A double blind randomised crossover study. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25786106/ · DOI 10.1371/journal.pone.0116212

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Blinded randomized crossover; sessions at least seven days apart. · source_derived_draft · unverified_draft

## aspartame-acute-sensitivity-null A low-dose acute controlled challenge did not reproduce reported sensitivity. In 48 self-described sensitive and 48 matched nonsensitive participants, rated symptoms did not differ between 100 mg aspartame and control bars. Model: Blinded randomized crossover; sessions at least seven days apart. Limitations: Not a test of all doses, repeated exposure or every vulnerable subgroup. Correction record: Publisher correction concerns author order, affiliations and citation; no experimental-result correction is stated. Correction PMID 25951455 inspected in full text. https://doi.org/10.1371/journal.pone.0126039 Evidence access: Primary full text and author-list correction Aspartame sensitivity? A double blind randomised crossover study. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25786106/ · DOI 10.1371/journal.pone.0116212

evidence_access

Primary abstract

experimental_model

Animal feeding experiments.

limitations

Exact duration and systemic dose not supplied by accessed abstract; do not infer ordinary human intake.

nutrient_topic

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

plain_language

A neural or hormonal route can differ from metabolite toxicity.

primary_references

Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

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

## aspartame-animal-insulin A neural or hormonal route can differ from metabolite toxicity. The study reported increased insulin secretion with 0.15% aspartame in mice and monkeys. Model: Animal feeding experiments. Limitations: Exact duration and systemic dose not supplied by accessed abstract; do not infer ordinary human intake. Evidence access: Primary abstract Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

evidence_access

Primary full text; methods and results

experimental_model

Human colon-cancer-derived cell line; dextran flux and electrical resistance assays.

limitations

Not a living human gut exposure or clinical disease endpoint.

nutrient_topic

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

plain_language

Intact sweetener altered a cultured epithelial barrier.

primary_references

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human colon-cancer-derived cell line; dextran flux and electrical resistance assays. · source_derived_draft · unverified_draft

## aspartame-barrier-permeability Intact sweetener altered a cultured epithelial barrier. Aspartame at 0.1 mM for 24 hours increased Caco-2 monolayer permeability. Model: Human colon-cancer-derived cell line; dextran flux and electrical resistance assays. Limitations: Not a living human gut exposure or clinical disease endpoint. Evidence access: Primary full text; methods and results Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

evidence_access

Primary abstract

experimental_model

Docking refined with functional mutagenesis.

limitations

Proposed molecular model, not a directly resolved bound-water structure.

nutrient_topic

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

plain_language

Water-mediated contacts are a testable structural explanation.

primary_references

Characterization of the Binding Site of Aspartame in the Human Sweet Taste Receptor. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26377607/ · DOI 10.1093/chemse/bjv045

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Docking refined with functional mutagenesis. · source_derived_draft · unverified_draft

## aspartame-binding-water-model Water-mediated contacts are a testable structural explanation. The model proposed two pocket waters bridging aspartame carbonyls to D142 and L279. Model: Docking refined with functional mutagenesis. Limitations: Proposed molecular model, not a directly resolved bound-water structure. Evidence access: Primary abstract Characterization of the Binding Site of Aspartame in the Human Sweet Taste Receptor. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26377607/ · DOI 10.1093/chemse/bjv045

evidence_access

Primary abstract

experimental_model

Prospective dietary-record cohort.

limitations

Residual confounding, selection and reverse causality remain possible; no molecular mediator was established.

nutrient_topic

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

plain_language

An observational association is a discovery lead rather than a proven causal chain.

primary_references

Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35324894/ · DOI 10.1371/journal.pmed.1003950

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Prospective dietary-record cohort. · source_derived_draft · unverified_draft

## aspartame-cancer-cohort An observational association is a discovery lead rather than a proven causal chain. In 102,865 adults followed a median 7.8 years, higher aspartame consumers had an adjusted overall-cancer hazard ratio of 1.15 versus nonconsumers, 95% CI 1.03–1.28. Model: Prospective dietary-record cohort. Limitations: Residual confounding, selection and reverse causality remain possible; no molecular mediator was established. Evidence access: Primary abstract Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35324894/ · DOI 10.1371/journal.pmed.1003950

evidence_access

Primary full text; Figure 4

experimental_model

24-hour exposure and surface ELISA.

limitations

Does not establish direct aspartame–claudin binding.

nutrient_topic

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

plain_language

Junction location matters as well as protein presence.

primary_references

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 24-hour exposure and surface ELISA. · source_derived_draft · unverified_draft

## aspartame-claudin-surface Junction location matters as well as protein presence. The Caco-2 study found reduced cell-surface claudin 3 after 0.1 mM aspartame exposure. Model: 24-hour exposure and surface ELISA. Limitations: Does not establish direct aspartame–claudin binding. Evidence access: Primary full text; Figure 4 Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

evidence_access

Primary abstract

experimental_model

Reaction background and human intestinal mucosal enzyme experiments.

limitations

This record does not assign the initial esterase to an unverified gene.

nutrient_topic

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

plain_language

Removing the methyl ester is separate from splitting the peptide.

primary_references

Intestinal hydrolysis of aspartylphenylalanine--the metabolic product of aspartame. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3743970/ · DOI 10.1016/0016-5085(86)90697-9

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Reaction background and human intestinal mucosal enzyme experiments. · source_derived_draft · unverified_draft

## aspartame-ester-cleavage Removing the methyl ester is separate from splitting the peptide. The intestinal study describes ester-bond hydrolysis of aspartame to Asp-Phe before further dipeptide digestion. Model: Reaction background and human intestinal mucosal enzyme experiments. Limitations: This record does not assign the initial esterase to an unverified gene. Evidence access: Primary abstract Intestinal hydrolysis of aspartylphenylalanine--the metabolic product of aspartame. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3743970/ · DOI 10.1016/0016-5085(86)90697-9

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Highest-dose subset of the loading study.

limitations

Limited sample, duration and assay; no inference about all metabolic disorders.

nutrient_topic

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

plain_language

Methanol appearance did not imply measured formate accumulation.

primary_references

Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame. · 1981 · https://pubmed.ncbi.nlm.nih.gov/7230276/ · DOI 10.1080/15287398109529979

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Highest-dose subset of the loading study. · source_derived_draft · unverified_draft

## aspartame-formate-loading Methanol appearance did not imply measured formate accumulation. Six adults receiving 200 mg/kg showed no significant increase in blood formate over baseline. Model: Highest-dose subset of the loading study. Limitations: Limited sample, duration and assay; no inference about all metabolic disorders. Evidence access: Primary abstract Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame. · 1981 · https://pubmed.ncbi.nlm.nih.gov/7230276/ · DOI 10.1080/15287398109529979

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Same human comparison.

limitations

Plasma is not synaptic aspartate.

nutrient_topic

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

plain_language

The other amino-acid product also shows formulation effects.

primary_references

Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3574137/ · DOI 10.1016/0026-0495(87)90052-7

trigger_kind

biomarker_context Imported condition classification; unverified.

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

## aspartame-formulation-aspartate The other amino-acid product also shows formulation effects. Peak plasma aspartate was higher and earlier with 3 g solution than capsules: 26.2 versus 10.4 micromol/L. Model: Same human comparison. Limitations: Plasma is not synaptic aspartate. Evidence access: Primary abstract Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3574137/ · DOI 10.1016/0026-0495(87)90052-7

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Balanced Latin-square comparison.

limitations

Acute high-dose kinetics, not brain or safety equivalence.

nutrient_topic

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

plain_language

The same dose need not give the same exposure.

primary_references

Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3574137/ · DOI 10.1016/0026-0495(87)90052-7

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Balanced Latin-square comparison. · source_derived_draft · unverified_draft

## aspartame-formulation-phe The same dose need not give the same exposure. In ten adults given 3 g, solution produced an earlier, higher phenylalanine peak than capsules: 191 versus 117 micromol/L at 32 versus 123 minutes. Model: Balanced Latin-square comparison. Limitations: Acute high-dose kinetics, not brain or safety equivalence. Evidence access: Primary abstract Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3574137/ · DOI 10.1016/0026-0495(87)90052-7

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Same ten-person 3 g comparison.

limitations

The ratio is not a measured change in brain serotonin or dopamine.

nutrient_topic

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

plain_language

Transport competition depends partly on the mixture reaching blood.

primary_references

Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3574137/ · DOI 10.1016/0026-0495(87)90052-7

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same ten-person 3 g comparison. · source_derived_draft · unverified_draft

## aspartame-formulation-ratio Transport competition depends partly on the mixture reaching blood. Solution versus capsules produced a higher plasma phenylalanine-to-other-LNAA ratio, 0.36 versus 0.23. Model: Same ten-person 3 g comparison. Limitations: The ratio is not a measured change in brain serotonin or dopamine. Evidence access: Primary abstract Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3574137/ · DOI 10.1016/0026-0495(87)90052-7

evidence_access

Primary abstract

experimental_model

Same randomized human trial.

limitations

Short duration and person-specific variation limit inference; not proof of no possible long-term effect.

nutrient_topic

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

plain_language

The result for one sweetener cannot be assigned to all of them.

primary_references

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

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same randomized human trial. · source_derived_draft · unverified_draft

## aspartame-glycemia-trial-limit The result for one sweetener cannot be assigned to all of them. Significant group-level glycemic impairment was reported for saccharin and sucralose, not aspartame, in the two-week trial. Model: Same randomized human trial. Limitations: Short duration and person-specific variation limit inference; not proof of no possible long-term effect. Evidence access: Primary abstract Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35987213/ · DOI 10.1016/j.cell.2022.07.016

evidence_access

Primary abstract

experimental_model

Acute human challenge.

limitations

Different exposure duration from the repeated trial; no molecular mechanism identified.

nutrient_topic

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

plain_language

Another blinded study did not reproduce increased headache frequency.

primary_references

Aspartame and susceptibility to headache. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3657889/ · DOI 10.1056/NEJM198711053171903

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

## aspartame-headache-null Another blinded study did not reproduce increased headache frequency. An acute crossover challenge in 40 self-reported headache-sensitive adults found headaches in 35% after 30 mg/kg aspartame versus 45% after placebo. Model: Acute human challenge. Limitations: Different exposure duration from the repeated trial; no molecular mechanism identified. Evidence access: Primary abstract Aspartame and susceptibility to headache. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3657889/ · DOI 10.1056/NEJM198711053171903

evidence_access

Primary abstract

experimental_model

About 30 mg/kg/day, seven-day periods; self-identified headache-sensitive volunteers.

limitations

No significant difference in headache duration or intensity; attrition and multiple analyses limit certainty.

nutrient_topic

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

plain_language

A positive symptom finding comes with substantial missing follow-up.

primary_references

Aspartame ingestion and headaches: a randomized crossover trial. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7936222/ · DOI 10.1212/wnl.44.10.1787

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · About 30 mg/kg/day, seven-day periods; self-identified headache-sensitive volunteers. · source_derived_draft · unverified_draft

## aspartame-headache-positive A positive symptom finding comes with substantial missing follow-up. A repeated crossover trial reported headaches on 33% of aspartame days versus 24% of placebo days, P=0.04; 18 of 32 randomized participants completed all periods. Model: About 30 mg/kg/day, seven-day periods; self-identified headache-sensitive volunteers. Limitations: No significant difference in headache duration or intensity; attrition and multiple analyses limit certainty. Evidence access: Primary abstract Aspartame ingestion and headaches: a randomized crossover trial. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7936222/ · DOI 10.1212/wnl.44.10.1787

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Six people per dose; aspartame in orange juice.

limitations

Healthy subjects, not PKU; no direct neurotransmitter assay.

nutrient_topic

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

plain_language

Large loads produce larger amino-acid excursions.

primary_references

Plasma and erythrocyte concentrations of free amino acids in adult humans administered abuse doses of aspartame. · 1981 · https://pubmed.ncbi.nlm.nih.gov/7230277/ · DOI 10.1080/15287398109529980

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Six people per dose; aspartame in orange juice. · source_derived_draft · unverified_draft

## aspartame-high-dose-phe Large loads produce larger amino-acid excursions. In 18 fasted adults across 100, 150 and 200 mg/kg cohorts, mean plasma phenylalanine peaks were 20.3, 35.1 and 48.7 micromol/dL. Model: Six people per dose; aspartame in orange juice. Limitations: Healthy subjects, not PKU; no direct neurotransmitter assay. Evidence access: Primary abstract Plasma and erythrocyte concentrations of free amino acids in adult humans administered abuse doses of aspartame. · 1981 · https://pubmed.ncbi.nlm.nih.gov/7230277/ · DOI 10.1080/15287398109529980

evidence_access

Primary article response panel and abstract

experimental_model

Human receptor coexpression, aspartame response panel.

limitations

Receptor activation is not a quantified human insulin response.

nutrient_topic

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

plain_language

The intact sweetener has a receptor action before its metabolites are considered.

primary_references

Human receptors for sweet and umami taste. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11917125/ · DOI 10.1073/pnas.072090199

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human receptor coexpression, aspartame response panel. · source_derived_draft · unverified_draft

## aspartame-human-sweet-receptor The intact sweetener has a receptor action before its metabolites are considered. Human T1R2/T1R3 responded to aspartame in heterologous receptor assays. Model: Human receptor coexpression, aspartame response panel. Limitations: Receptor activation is not a quantified human insulin response. Evidence access: Primary article response panel and abstract Human receptors for sweet and umami taste. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11917125/ · DOI 10.1073/pnas.072090199

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Thirty adults across dose cohorts.

limitations

These bolus doses and old detection limits do not define a universal toxicity threshold.

nutrient_topic

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

plain_language

A non-detect depends on the assay; large doses gave measurable exposure.

primary_references

Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame. · 1981 · https://pubmed.ncbi.nlm.nih.gov/7230276/ · DOI 10.1080/15287398109529979

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Thirty adults across dose cohorts. · source_derived_draft · unverified_draft

## aspartame-methanol-dose A non-detect depends on the assay; large doses gave measurable exposure. Blood methanol was below the 0.4 mg/dL detection limit at 34 mg/kg; 100–200 mg/kg doses produced dose-related peaks of 1.27–2.58 mg/dL. Model: Thirty adults across dose cohorts. Limitations: These bolus doses and old detection limits do not define a universal toxicity threshold. Evidence access: Primary abstract Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame. · 1981 · https://pubmed.ncbi.nlm.nih.gov/7230276/ · DOI 10.1080/15287398109529979

evidence_access

Primary abstract

experimental_model

Randomized human trial; aspartame arm compared with glucose-vehicle and no-supplement controls.

limitations

Total sample is not the aspartame-arm sample; no specific causal aspartame microbial metabolite is identified here.

nutrient_topic

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

plain_language

A biological change need not equal a harmful clinical outcome.

primary_references

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

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized human trial; aspartame arm compared with glucose-vehicle and no-supplement controls. · source_derived_draft · unverified_draft

## aspartame-microbiome-trial A biological change need not equal a harmful clinical outcome. The 120-person six-arm sweetener trial reported distinct microbiome and metabolome changes across the sweetener groups, including aspartame, over two weeks. Model: Randomized human trial; aspartame arm compared with glucose-vehicle and no-supplement controls. Limitations: Total sample is not the aspartame-arm sample; no specific causal aspartame microbial metabolite is identified here. Evidence access: Primary abstract Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35987213/ · DOI 10.1016/j.cell.2022.07.016

evidence_access

Primary abstract

experimental_model

Small human psychiatric-history comparison.

limitations

Early stopping, small sample and subgroup analysis; no measured neurotransmitter mechanism.

nutrient_topic

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

plain_language

An early-stopped study signals a question but cannot define a reliable population effect.

primary_references

Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8373935/ · DOI 10.1016/0006-3223(93)90251-8

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small human psychiatric-history comparison. · source_derived_draft · unverified_draft

## aspartame-mood-disorder-trial An early-stopped study signals a question but cannot define a reliable population effect. A seven-day 30 mg/kg/day crossover reported more severe symptoms in participants with depression; the study stopped after 13 people completed because of reactions. Model: Small human psychiatric-history comparison. Limitations: Early stopping, small sample and subgroup analysis; no measured neurotransmitter mechanism. Evidence access: Primary abstract Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8373935/ · DOI 10.1016/0006-3223(93)90251-8

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human carrier comparison, also including twelve noncarrier men.

limitations

Heterozygotes do not represent patients with biallelic PAH deficiency; the damaged male-baseline sentence in indexed abstract is not reconstructed.

nutrient_topic

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

plain_language

Reduced metabolic reserve can change the response to a precursor source.

primary_references

Plasma phenylalanine levels in phenylketonuric heterozygous and normal adults administered aspartame at 34 mg/kg body weight. · 1981 · https://pubmed.ncbi.nlm.nih.gov/7268794/ · DOI 10.1016/0300-483x(81)90108-6

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human carrier comparison, also including twelve noncarrier men. · source_derived_draft · unverified_draft

## aspartame-pku-carrier-kinetics Reduced metabolic reserve can change the response to a precursor source. After 34 mg/kg, twelve female PKU heterozygotes had higher peak phenylalanine than ten noncarrier females, 15.1 versus 8.95 micromol/dL. Model: Human carrier comparison, also including twelve noncarrier men. Limitations: Heterozygotes do not represent patients with biallelic PAH deficiency; the damaged male-baseline sentence in indexed abstract is not reconstructed. Evidence access: Primary abstract Plasma phenylalanine levels in phenylketonuric heterozygous and normal adults administered aspartame at 34 mg/kg body weight. · 1981 · https://pubmed.ncbi.nlm.nih.gov/7268794/ · DOI 10.1016/0300-483x(81)90108-6

evidence_access

Primary abstract

experimental_model

ApoE-deficient mouse feeding study.

limitations

Not a human cardiovascular risk estimate.

nutrient_topic

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

plain_language

A susceptible vascular model produced a disease endpoint.

primary_references

Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · ApoE-deficient mouse feeding study. · source_derived_draft · unverified_draft

## aspartame-plaque-feeding A susceptible vascular model produced a disease endpoint. Sustained aspartame feeding aggravated plaque formation in ApoE-null mice. Model: ApoE-deficient mouse feeding study. Limitations: Not a human cardiovascular risk estimate. Evidence access: Primary abstract Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

evidence_access

Primary abstract

experimental_model

Six healthy young adults.

limitations

Normal range is protocol- and assay-dependent, not proof that no metabolism occurred.

nutrient_topic

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

plain_language

Products can be generated without a sustained high blood pool.

primary_references

Effect of repeated ingestion of aspartame-sweetened beverage on plasma amino acid, blood methanol, and blood formate concentrations in normal adults. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2566887/ · DOI 10.1016/0026-0495(89)90125-x

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 114–120

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Six healthy young adults. · source_derived_draft · unverified_draft

## aspartame-repeated-metabolites Products can be generated without a sustained high blood pool. Methanol and formate remained within reported normal limits; plasma aspartate did not significantly rise in the eight-serving experiment. Model: Six healthy young adults. Limitations: Normal range is protocol- and assay-dependent, not proof that no metabolism occurred. Evidence access: Primary abstract Effect of repeated ingestion of aspartame-sweetened beverage on plasma amino acid, blood methanol, and blood formate concentrations in normal adults. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2566887/ · DOI 10.1016/0026-0495(89)90125-x

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human beverage crossover; 4.8 g total over eight servings.

limitations

Small healthy-adult study; not a PKU population or a long-term trial.

nutrient_topic

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

plain_language

Repeated exposure did not produce unlimited accumulation in this protocol.

primary_references

Effect of repeated ingestion of aspartame-sweetened beverage on plasma amino acid, blood methanol, and blood formate concentrations in normal adults. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2566887/ · DOI 10.1016/0026-0495(89)90125-x

trigger_kind

biomarker_context Imported condition classification; unverified.

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 106–112

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human beverage crossover; 4.8 g total over eight servings. · source_derived_draft · unverified_draft

## aspartame-repeated-phenylalanine Repeated exposure did not produce unlimited accumulation in this protocol. Six adults consumed eight hourly 600 mg servings; phenylalanine rose modestly and plateaued after four to five servings within the reported normal postprandial range. Model: Human beverage crossover; 4.8 g total over eight servings. Limitations: Small healthy-adult study; not a PKU population or a long-term trial. Evidence access: Primary abstract Effect of repeated ingestion of aspartame-sweetened beverage on plasma amino acid, blood methanol, and blood formate concentrations in normal adults. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2566887/ · DOI 10.1016/0026-0495(89)90125-x

evidence_access

Primary full text; Figure 5

experimental_model

0.1 mM, 24 hours; DCFDA assay.

limitations

Probe fluorescence does not identify a single radical species.

nutrient_topic

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

plain_language

Oxidative signaling is an experimentally measured intermediate.

primary_references

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 0.1 mM, 24 hours; DCFDA assay. · source_derived_draft · unverified_draft

## aspartame-ros-induction Oxidative signaling is an experimentally measured intermediate. Aspartame increased the ROS-sensitive fluorescence signal in exposed Caco-2 cells. Model: 0.1 mM, 24 hours; DCFDA assay. Limitations: Probe fluorescence does not identify a single radical species. Evidence access: Primary full text; Figure 5 Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

evidence_access

Primary full text and author-list correction

experimental_model

Same human crossover.

limitations

Not comparable to isolated cells or susceptible-mouse feeding by dose or endpoint. Correction record: Publisher correction concerns author order, affiliations and citation; no experimental-result correction is stated. Correction PMID 25951455 inspected in full text. https://doi.org/10.1371/journal.pone.0126039

nutrient_topic

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

plain_language

Receptor activity did not translate into a distinct measured response in this meal.

primary_references

Aspartame sensitivity? A double blind randomised crossover study. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25786106/ · DOI 10.1371/journal.pone.0116212

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

## aspartame-snackbar-hormones Receptor activity did not translate into a distinct measured response in this meal. GLP-1, GIP, tyrosine and phenylalanine responses were similar with aspartame and control snack bars. Model: Same human crossover. Limitations: Not comparable to isolated cells or susceptible-mouse feeding by dose or endpoint. Correction record: Publisher correction concerns author order, affiliations and citation; no experimental-result correction is stated. Correction PMID 25951455 inspected in full text. https://doi.org/10.1371/journal.pone.0126039 Evidence access: Primary full text and author-list correction Aspartame sensitivity? A double blind randomised crossover study. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25786106/ · DOI 10.1371/journal.pone.0116212

evidence_access

Primary abstract

experimental_model

Purified preparation versus membrane assays.

limitations

Species of purified preparation unresolved in accessed abstract.

nutrient_topic

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

plain_language

An inhibitor result alone can misidentify the enzyme.

primary_references

Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 66–72

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified preparation versus membrane assays. · source_derived_draft · unverified_draft

## aspartame-anpep-specificity An inhibitor result alone can misidentify the enzyme. Purified aminopeptidase N did not hydrolyze aspartame despite partial inhibition of membrane metabolism by actinonin. Model: Purified preparation versus membrane assays. Limitations: Species of purified preparation unresolved in accessed abstract. Evidence access: Primary abstract Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

evidence_access

Primary abstract

experimental_model

Human receptor mutants and homology models.

limitations

Loss of response can affect binding, folding or activation; not every residue is necessarily a direct contact.

nutrient_topic

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

plain_language

Small changes in the sensor can alter recognition.

primary_references

Characterization of the Binding Site of Aspartame in the Human Sweet Taste Receptor. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26377607/ · DOI 10.1093/chemse/bjv045

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

## aspartame-binding-residues Small changes in the sensor can alter recognition. Mutagenesis identified eleven T1R2 residues important for aspartame responses: S40, Y103, D142, S144, S165, S168, Y215, D278, E302, D307 and R383. Model: Human receptor mutants and homology models. Limitations: Loss of response can affect binding, folding or activation; not every residue is necessarily a direct contact. Evidence access: Primary abstract Characterization of the Binding Site of Aspartame in the Human Sweet Taste Receptor. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26377607/ · DOI 10.1093/chemse/bjv045

evidence_access

Primary abstract

experimental_model

Site-directed mutagenesis and docking.

limitations

A shared receptor is not proof that all sweeteners have interchangeable systemic effects.

nutrient_topic

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

plain_language

Aspartame and other sweeteners need not perturb every receptor contact equally.

primary_references

Characterization of the modes of binding between human sweet taste receptor and low-molecular-weight sweet compounds. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22536376/ · DOI 10.1371/journal.pone.0035380

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 186–192

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Site-directed mutagenesis and docking. · source_derived_draft · unverified_draft

## aspartame-ligand-specific-sites Aspartame and other sweeteners need not perturb every receptor contact equally. Human T1R2 amino-terminal-domain mutants showed ligand-specific and shared requirements across chemically different sweeteners. Model: Site-directed mutagenesis and docking. Limitations: A shared receptor is not proof that all sweeteners have interchangeable systemic effects. Evidence access: Primary abstract Characterization of the modes of binding between human sweet taste receptor and low-molecular-weight sweet compounds. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22536376/ · DOI 10.1371/journal.pone.0035380

evidence_access

Primary abstract

experimental_model

Human membranes; parallel pig preparations.

limitations

Does not quantify whole-body absorption or intact circulating parent.

nutrient_topic

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

plain_language

Digestion is supported across sampled intestinal regions.

primary_references

Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 42–48

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human membranes; parallel pig preparations. · source_derived_draft · unverified_draft

## aspartame-microvillar-cleavage Digestion is supported across sampled intestinal regions. Human duodenal, jejunal and ileal microvillar preparations hydrolyzed aspartame. Model: Human membranes; parallel pig preparations. Limitations: Does not quantify whole-body absorption or intact circulating parent. Evidence access: Primary abstract Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

evidence_access

Primary abstract

experimental_model

Ex vivo microvillar assays.

limitations

Not evidence that calcium supplements improve tolerance.

nutrient_topic

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

plain_language

Calcium availability affected measured enzyme activity.

primary_references

Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ex vivo microvillar assays. · source_derived_draft · unverified_draft

## aspartame-calcium-activation Calcium availability affected measured enzyme activity. CaCl2 increased aspartame hydrolysis 2.9–4.5-fold in the tested human and pig membrane preparations. Model: Ex vivo microvillar assays. Limitations: Not evidence that calcium supplements improve tolerance. Evidence access: Primary abstract Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

evidence_access

Primary full text

experimental_model

Human cell-line expression rescue.

limitations

Does not establish that the same rescue is clinically achievable.

nutrient_topic

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

plain_language

Restoring a barrier component altered downstream readouts.

primary_references

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

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

## aspartame-claudin-rescue Restoring a barrier component altered downstream readouts. Claudin-3 overexpression attenuated aspartame-associated permeability and ROS changes in Caco-2 cells. Model: Human cell-line expression rescue. Limitations: Does not establish that the same rescue is clinically achievable. Evidence access: Primary full text Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Conditional mouse genetic perturbation.

limitations

One preclinical study, not independently replicated clinical causality.

nutrient_topic

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

plain_language

A separate immune receptor was required for the added plaque effect.

primary_references

Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

trigger_kind

machinery_impairment Imported condition classification; unverified.

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 282–288

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Conditional mouse genetic perturbation. · source_derived_draft · unverified_draft

## aspartame-cx3cr1-loss A separate immune receptor was required for the added plaque effect. Monocyte/macrophage Cx3cr1 deletion abolished aspartame-exacerbated atherosclerosis in the model. Model: Conditional mouse genetic perturbation. Limitations: One preclinical study, not independently replicated clinical causality. Evidence access: Primary abstract Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

evidence_access

Primary abstract

experimental_model

Human/pig membranes and purified peptidases.

limitations

Enzyme resistance does not establish toxicity or systemic persistence.

nutrient_topic

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

plain_language

Changed molecular geometry changes processing.

primary_references

Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human/pig membranes and purified peptidases. · source_derived_draft · unverified_draft

## aspartame-degradation-product-resistance Changed molecular geometry changes processing. Cyclo-Asp-Phe and beta-Asp-Phe methyl ester resisted the tested microvillar and purified A/W peptidase preparations. Model: Human/pig membranes and purified peptidases. Limitations: Enzyme resistance does not establish toxicity or systemic persistence. Evidence access: Primary abstract Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

evidence_access

Primary abstract

experimental_model

Human intestinal mucosa and red-cell lysate fractionation.

limitations

Intact dipeptide transport was proposed; the cytosolic enzyme was not molecularly identified.

nutrient_topic

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

plain_language

The amino-acid pair can be processed after reaching a different cell compartment.

primary_references

Intestinal hydrolysis of aspartylphenylalanine--the metabolic product of aspartame. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3743970/ · DOI 10.1016/0016-5085(86)90697-9

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 26–32

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human intestinal mucosa and red-cell lysate fractionation. · source_derived_draft · unverified_draft

## aspartame-dipeptide-cleavage The amino-acid pair can be processed after reaching a different cell compartment. Brush-border and cytosolic preparations hydrolyzed Asp-Phe; cytosolic fractionation identified one activity peak distinct from seven previously described peptidases. Model: Human intestinal mucosa and red-cell lysate fractionation. Limitations: Intact dipeptide transport was proposed; the cytosolic enzyme was not molecularly identified. Evidence access: Primary abstract Intestinal hydrolysis of aspartylphenylalanine--the metabolic product of aspartame. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3743970/ · DOI 10.1016/0016-5085(86)90697-9

evidence_access

Primary abstract

experimental_model

Arterial endothelial-cell expression profiling.

limitations

Cell species unresolved in accessed abstract; direct aspartame exposure is not asserted.

nutrient_topic

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

plain_language

A hormone can change an immune-cell recruitment signal.

primary_references

Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 274–280

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Arterial endothelial-cell expression profiling. · source_derived_draft · unverified_draft

## aspartame-endothelial-chemokine A hormone can change an immune-cell recruitment signal. Insulin-stimulated arterial endothelial cells upregulated CX3CL1. Model: Arterial endothelial-cell expression profiling. Limitations: Cell species unresolved in accessed abstract; direct aspartame exposure is not asserted. Evidence access: Primary abstract Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Two-hour lung-only labeled-methanol exposure; repeated after diet-induced folate deficiency.

limitations

This was not aspartame feeding, and does not show aspartame causes folate depletion.

nutrient_topic

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

plain_language

Downstream handling depends on nutrient state and exposure route.

primary_references

Pharmacokinetics of inhaled [14C]methanol and methanol-derived [14C]formate in normal and folate-deficient cynomolgus monkeys. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7940538/ · DOI 10.1006/taap.1994.1202

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 154–160

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two-hour lung-only labeled-methanol exposure; repeated after diet-induced folate deficiency. · source_derived_draft · unverified_draft

## aspartame-folate-methanol-context Downstream handling depends on nutrient state and exposure route. Four cynomolgus monkeys had higher labeled blood formate after 900 ppm methanol inhalation when folate-deficient than before depletion, while tracer-derived concentrations remained below endogenous formate. Model: Two-hour lung-only labeled-methanol exposure; repeated after diet-induced folate deficiency. Limitations: This was not aspartame feeding, and does not show aspartame causes folate depletion. Evidence access: Primary abstract Pharmacokinetics of inhaled [14C]methanol and methanol-derived [14C]formate in normal and folate-deficient cynomolgus monkeys. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7940538/ · DOI 10.1006/taap.1994.1202

evidence_access

Primary abstract

experimental_model

Mouse insulin-pump experiment.

limitations

Does not prove every aspartame effect is insulin-mediated.

nutrient_topic

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

plain_language

A mediator intervention supported the proposed chain.

primary_references

Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 266–272

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse insulin-pump experiment. · source_derived_draft · unverified_draft

## aspartame-insulin-pump A mediator intervention supported the proposed chain. Slow-release insulin pumps worsened atherosclerosis in ApoE-null mice. Model: Mouse insulin-pump experiment. Limitations: Does not prove every aspartame effect is insulin-mediated. Evidence access: Primary abstract Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human and pig membrane inhibitor assays.

limitations

Inhibitor patterns support aminopeptidase A involvement, not an exclusive gene assignment.

nutrient_topic

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

plain_language

Metal-sensitive peptidase activity is a digestive gate.

primary_references

Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

trigger_kind

machinery_impairment Imported condition classification; unverified.

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 58–64

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human and pig membrane inhibitor assays. · source_derived_draft · unverified_draft

## aspartame-metal-sensitive-hydrolysis Metal-sensitive peptidase activity is a digestive gate. 1,10-Phenanthroline or amastatin inhibited membrane aspartame metabolism by more than 78%. Model: Human and pig membrane inhibitor assays. Limitations: Inhibitor patterns support aminopeptidase A involvement, not an exclusive gene assignment. Evidence access: Primary abstract Metabolism of aspartame by human and pig intestinal microvillar peptidases. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8141778/ · DOI 10.1042/bj2980635

evidence_access

Primary abstract

experimental_model

Four female monkeys; lung-only exposure for two hours at 10–900 ppm.

limitations

Not an aspartame feeding study; the route and systemic dose differ from digestion of a food sweetener.

nutrient_topic

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

plain_language

A traced precursor-product link connects two separate metabolite nodes.

primary_references

Pharmacokinetics of inhaled [14C]methanol and methanol-derived [14C]formate in normal and folate-deficient cynomolgus monkeys. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7940538/ · DOI 10.1006/taap.1994.1202

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 354–360

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Four female monkeys; lung-only exposure for two hours at 10–900 ppm. · source_derived_draft · unverified_draft

## aspartame-methanol-formate-tracer A traced precursor-product link connects two separate metabolite nodes. Labeled methanol inhalation produced labeled blood formate in cynomolgus monkeys. Model: Four female monkeys; lung-only exposure for two hours at 10–900 ppm. Limitations: Not an aspartame feeding study; the route and systemic dose differ from digestion of a food sweetener. Evidence access: Primary abstract Pharmacokinetics of inhaled [14C]methanol and methanol-derived [14C]formate in normal and folate-deficient cynomolgus monkeys. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7940538/ · DOI 10.1006/taap.1994.1202

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human mucosal enzyme comparison.

limitations

No demonstrated aspartame-sensitivity syndrome or successful enzyme repletion was established.

nutrient_topic

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

plain_language

General mucosal disease can change digestive capacity.

primary_references

Intestinal hydrolysis of aspartylphenylalanine--the metabolic product of aspartame. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3743970/ · DOI 10.1016/0016-5085(86)90697-9

trigger_kind

machinery_impairment Imported condition classification; unverified.

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 34–40

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human mucosal enzyme comparison. · source_derived_draft · unverified_draft

## aspartame-mucosal-loss General mucosal disease can change digestive capacity. Diseased intestinal mucosa showed reduced brush-border and cytosolic Asp-Phe hydrolase activity alongside reductions in other enzymes. Model: Human mucosal enzyme comparison. Limitations: No demonstrated aspartame-sensitivity syndrome or successful enzyme repletion was established. Evidence access: Primary abstract Intestinal hydrolysis of aspartylphenylalanine--the metabolic product of aspartame. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3743970/ · DOI 10.1016/0016-5085(86)90697-9

evidence_access

Primary full text; Figure 5

experimental_model

Caco-2 co-exposure experiments.

limitations

Not evidence that NAC supplements prevent effects of dietary aspartame.

nutrient_topic

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

plain_language

An antioxidant-related perturbation changed the pathway response.

primary_references

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Caco-2 co-exposure experiments. · source_derived_draft · unverified_draft

## aspartame-nac-rescue An antioxidant-related perturbation changed the pathway response. N-acetylcysteine at 1 mM attenuated aspartame-associated oxidative and barrier changes. Model: Caco-2 co-exposure experiments. Limitations: Not evidence that NAC supplements prevent effects of dietary aspartame. Evidence access: Primary full text; Figure 5 Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cell-line siRNA perturbation.

limitations

Supports functional involvement, not proof of direct binding to T1R3 alone.

nutrient_topic

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

plain_language

Removing a signaling component reduced the response.

primary_references

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

trigger_kind

machinery_impairment Imported condition classification; unverified.

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 210–216

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

## aspartame-t1r3-knockdown Removing a signaling component reduced the response. T1R3 siRNA attenuated aspartame-associated barrier and claudin-3 changes in Caco-2 cells. Model: Human cell-line siRNA perturbation. Limitations: Supports functional involvement, not proof of direct binding to T1R3 alone. Evidence access: Primary full text Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Animal surgical perturbation in the feeding study.

limitations

Does not uniquely identify the initial sweet receptor.

nutrient_topic

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

plain_language

Interrupting the nerve route interrupted the hormone response.

primary_references

Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

trigger_kind

machinery_impairment Imported condition classification; unverified.

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 250–256

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Animal surgical perturbation in the feeding study. · source_derived_draft · unverified_draft

## aspartame-vagotomy-gate Interrupting the nerve route interrupted the hormone response. Subdiaphragmatic vagotomy abolished the aspartame-associated insulin rise in the reported experiment. Model: Animal surgical perturbation in the feeding study. Limitations: Does not uniquely identify the initial sweet receptor. Evidence access: Primary abstract Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39978336/ · DOI 10.1016/j.cmet.2025.01.006

dose

HFCS-55 beverages at 0%, 10%, 17.5% or 25% energy requirement; 0% aspartame control

duration

Approximately 2 weeks

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

85 adults aged 18-40; nonrandomized double-blinded matched groups

exposure_scope

Direct HFCS-55 evidence

limitations

Short biomarker study; outpatient calories were not fixed and clinical cardiovascular events were not measured. NCT01103921 overlaps HFCS/control participants with the 2021 report.

nutrient_topic

HFCS chapter: actual formulation studies, component biochemistry and interventions are explicitly distinguished. · High-Fructose Corn Syrup / HFCS

organism

85 adults aged 18-40; nonrandomized double-blinded matched groups

plain_language

HFCS beverage dose was associated with increasing postprandial triglycerides; all three sugar doses exceeded the aspartame control.

primary_references

A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults. (2015). https://pubmed.ncbi.nlm.nih.gov/25904601/ DOI: 10.3945/ajcn.114.100461

route

Oral beverages, with outpatient ad libitum diet and controlled inpatient meals

tissue

Circulating lipids and urate

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 281–291

Original AI-assisted curation of twenty primary studies and official FDA composition information, with one reused canonical glucose-transport claim. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · 85 adults aged 18-40; nonrandomized double-blinded matched groups · source_derived_draft · unverified_draft

## hfcs-dose-triglycerides HFCS beverage dose was associated with increasing postprandial triglycerides; all three sugar doses exceeded the aspartame control. Model/species: 85 adults aged 18-40; nonrandomized double-blinded matched groups Tissue: Circulating lipids and urate Exposure: HFCS-55 beverages at 0%, 10%, 17.5% or 25% energy requirement; 0% aspartame control Route: Oral beverages, with outpatient ad libitum diet and controlled inpatient meals Duration: Approximately 2 weeks Exposure scope: Direct HFCS-55 evidence Limits: Short biomarker study; outpatient calories were not fixed and clinical cardiovascular events were not measured. NCT01103921 overlaps HFCS/control participants with the 2021 report. Reference: A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults. (2015). https://pubmed.ncbi.nlm.nih.gov/25904601/ DOI: 10.3945/ajcn.114.100461 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

HFCS-55 or sucrose at 25% energy requirement versus aspartame; HFCS n=28, sucrose n=24, control n=23

duration

16 days of beverages, approximately 2 weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

75 adults in nonrandomized double-blinded matched beverage groups

exposure_scope

Direct HFCS-55 comparison

limitations

No random assignment; 66 paired MRI scans, including 23 HFCS. Liver-fat HFCS significance was versus baseline, not established versus aspartame. No detected HFCS-sucrose difference is not universal equivalence. HFCS/control lipid data overlap PMID 25904601.

nutrient_topic

HFCS chapter: actual formulation studies, component biochemistry and interventions are explicitly distinguished. · High-Fructose Corn Syrup / HFCS

organism

75 adults in nonrandomized double-blinded matched beverage groups

plain_language

HFCS beverages reduced Matsuda insulin sensitivity compared with aspartame in the matched-group intervention.

primary_references

Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508

route

Oral 3 servings/day; usual diet outpatient, isocaloric substitutions during inpatient testing

tissue

MRI liver fat, oral-glucose-derived sensitivity, plasma markers

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 329–339

Original AI-assisted curation of twenty primary studies and official FDA composition information, with one reused canonical glucose-transport claim. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · 75 adults in nonrandomized double-blinded matched beverage groups · source_derived_draft · unverified_draft

## hfcs-insulin-sensitivity HFCS beverages reduced Matsuda insulin sensitivity compared with aspartame in the matched-group intervention. Model/species: 75 adults in nonrandomized double-blinded matched beverage groups Tissue: MRI liver fat, oral-glucose-derived sensitivity, plasma markers Exposure: HFCS-55 or sucrose at 25% energy requirement versus aspartame; HFCS n=28, sucrose n=24, control n=23 Route: Oral 3 servings/day; usual diet outpatient, isocaloric substitutions during inpatient testing Duration: 16 days of beverages, approximately 2 weeks Exposure scope: Direct HFCS-55 comparison Limits: No random assignment; 66 paired MRI scans, including 23 HFCS. Liver-fat HFCS significance was versus baseline, not established versus aspartame. No detected HFCS-sucrose difference is not universal equivalence. HFCS/control lipid data overlap PMID 25904601. Reference: Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508 Access: Primary full-text methods/results and metadata inspected.

dose

Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day

duration

16 days, approximately two weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

exposure_scope

Direct sucrose beverage comparison

limitations

Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

plain_language

Sucrose beverages increased fasting LDL cholesterol compared with aspartame.

primary_references

Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508

route

Oral beverages; outpatient usual diet, controlled inpatient meal substitutions

tissue

MRI liver fat, OGTT-derived insulin sensitivity and plasma markers

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 367–377

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 · source_derived_draft · unverified_draft

## sucrose-ldl Sucrose beverages increased fasting LDL cholesterol compared with aspartame. Model/species: 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 Tissue: MRI liver fat, OGTT-derived insulin sensitivity and plasma markers Exposure: Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day Route: Oral beverages; outpatient usual diet, controlled inpatient meal substitutions Duration: 16 days, approximately two weeks Exposure scope: Direct sucrose beverage comparison Limits: Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence. Reference: Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508 Access: Primary full-text methods/results and metadata inspected.

dose

Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day

duration

16 days, approximately two weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

exposure_scope

Direct sucrose beverage comparison

limitations

Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

plain_language

Sucrose beverages increased hepatic lipid by 0.6 +/- 0.2 percentage points from baseline, with a significant contrast against aspartame.

primary_references

Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508

route

Oral beverages; outpatient usual diet, controlled inpatient meal substitutions

tissue

MRI liver fat, OGTT-derived insulin sensitivity and plasma markers

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 331–341

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 · source_derived_draft · unverified_draft

## sucrose-liver-fat Sucrose beverages increased hepatic lipid by 0.6 +/- 0.2 percentage points from baseline, with a significant contrast against aspartame. Model/species: 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 Tissue: MRI liver fat, OGTT-derived insulin sensitivity and plasma markers Exposure: Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day Route: Oral beverages; outpatient usual diet, controlled inpatient meal substitutions Duration: 16 days, approximately two weeks Exposure scope: Direct sucrose beverage comparison Limits: Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence. Reference: Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508 Access: Primary full-text methods/results and metadata inspected.

dose

Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day

duration

16 days, approximately two weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

exposure_scope

Direct sucrose beverage comparison

limitations

Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

plain_language

Sucrose beverages reduced Matsuda insulin sensitivity compared with aspartame in the matched-group intervention.

primary_references

Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508

route

Oral beverages; outpatient usual diet, controlled inpatient meal substitutions

tissue

MRI liver fat, OGTT-derived insulin sensitivity and plasma markers

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 343–353

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 · source_derived_draft · unverified_draft

## sucrose-matsuda Sucrose beverages reduced Matsuda insulin sensitivity compared with aspartame in the matched-group intervention. Model/species: 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 Tissue: MRI liver fat, OGTT-derived insulin sensitivity and plasma markers Exposure: Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day Route: Oral beverages; outpatient usual diet, controlled inpatient meal substitutions Duration: 16 days, approximately two weeks Exposure scope: Direct sucrose beverage comparison Limits: Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence. Reference: Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508 Access: Primary full-text methods/results and metadata inspected.

dose

50 versus 5 g sucrose; 5 g plus mixed sucralose/acesulfame/aspartame/erythritol to match sweetness

duration

15-minute comparison; sampling to 60 minutes

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Healthy Japanese men in low-sucrose meal substudy

exposure_scope

Sucrose dose versus matched perceived sweetness

limitations

Methods say n=6 for sweetener substudy, results report n=7; discrepancy preserved. Lower sucrose also lowers calories; this is not a calorie-matched isolated receptor experiment.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

Healthy Japanese men in low-sucrose meal substudy

plain_language

Matching sweetness with nonnutritive sweeteners did not restore the GLP-1 response lost when meal sucrose was reduced.

primary_references

Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar vs non-nutritive sweetener. (2012). https://pubmed.ncbi.nlm.nih.gov/24843559/ DOI: 10.1111/j.2040-1124.2011.00163.x

route

Oral mixed meal

tissue

Plasma active GLP-1 after mixed meal

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 259–269

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · Healthy Japanese men in low-sucrose meal substudy · source_derived_draft · unverified_draft

## sucrose-sweetness-glp1-null Matching sweetness with nonnutritive sweeteners did not restore the GLP-1 response lost when meal sucrose was reduced. Model/species: Healthy Japanese men in low-sucrose meal substudy Tissue: Plasma active GLP-1 after mixed meal Exposure: 50 versus 5 g sucrose; 5 g plus mixed sucralose/acesulfame/aspartame/erythritol to match sweetness Route: Oral mixed meal Duration: 15-minute comparison; sampling to 60 minutes Exposure scope: Sucrose dose versus matched perceived sweetness Limits: Methods say n=6 for sweetener substudy, results report n=7; discrepancy preserved. Lower sucrose also lowers calories; this is not a calorie-matched isolated receptor experiment. Reference: Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar vs non-nutritive sweetener. (2012). https://pubmed.ncbi.nlm.nih.gov/24843559/ DOI: 10.1111/j.2040-1124.2011.00163.x Access: Primary full-text methods/results and metadata inspected.

dose

Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day

duration

16 days, approximately two weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

exposure_scope

Direct sucrose beverage comparison

limitations

Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

plain_language

Sucrose beverages increased postprandial triglycerides compared with aspartame after the intervention.

primary_references

Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508

route

Oral beverages; outpatient usual diet, controlled inpatient meal substitutions

tissue

MRI liver fat, OGTT-derived insulin sensitivity and plasma markers

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 355–365

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 · source_derived_draft · unverified_draft

## sucrose-triglycerides Sucrose beverages increased postprandial triglycerides compared with aspartame after the intervention. Model/species: 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 Tissue: MRI liver fat, OGTT-derived insulin sensitivity and plasma markers Exposure: Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day Route: Oral beverages; outpatient usual diet, controlled inpatient meal substitutions Duration: 16 days, approximately two weeks Exposure scope: Direct sucrose beverage comparison Limits: Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence. Reference: Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508 Access: Primary full-text methods/results and metadata inspected.

dose

Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day

duration

16 days, approximately two weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

exposure_scope

Direct sucrose beverage comparison

limitations

Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence.

nutrient_topic

Sucrose chapter; direct sucrose observations are distinguished from shared component metabolism. · Sucrose

organism

75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23

plain_language

Sucrose beverages increased 24-hour plasma urate exposure compared with aspartame.

primary_references

Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508

route

Oral beverages; outpatient usual diet, controlled inpatient meal substitutions

tissue

MRI liver fat, OGTT-derived insulin sensitivity and plasma markers

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 379–389

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 · source_derived_draft · unverified_draft

## sucrose-urate Sucrose beverages increased 24-hour plasma urate exposure compared with aspartame. Model/species: 75 adults in nonrandomized double-blind matched groups; sucrose n=24, HFCS n=28, aspartame n=23 Tissue: MRI liver fat, OGTT-derived insulin sensitivity and plasma markers Exposure: Sucrose or HFCS beverages at 25% of energy requirement versus aspartame, 3 servings/day Route: Oral beverages; outpatient usual diet, controlled inpatient meal substitutions Duration: 16 days, approximately two weeks Exposure scope: Direct sucrose beverage comparison Limits: Nonrandomized; paired MRI n=23 sucrose, 23 HFCS, 20 control. Outpatient calories not clamped; weight adjustment does not establish calorie independence. HFCS/control participants and some plasma outcomes overlap PMID 25904601. Short biomarkers are not clinical disease incidence. Reference: Consuming Sucrose- or HFCS-sweetened Beverages Increases Hepatic Lipid and Decreases Insulin Sensitivity in Adults. (2021). https://pubmed.ncbi.nlm.nih.gov/34265055/ DOI: 10.1210/clinem/dgab508 Access: Primary full-text methods/results and metadata inspected.