Fructose

dose

Fructose concentration series, EC50 0.155 mM; blocker experiment 10 mM fructose plus 340 micromolar diazoxide

duration

2 h

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Mouse GLUTag enteroendocrine cell line

exposure_scope

Isolated fructose / drug-peptide assay

limitations

Pharmacological channel control in a cell line does not establish a human drug-food interaction or a reason to consume fructose therapeutically.

nutrient_topic

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

organism

Mouse GLUTag enteroendocrine cell line

plain_language

Fructose stimulated GLP-1 secretion in mouse GLUTag cells with a reported EC50 of 0.155 mM.

primary_references

Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24525020/ DOI: 10.1152/ajpgi.00372.2013

route

In vitro sugar and drug exposure

tissue

GLP-1 secretion assay

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 473–483

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 · Mouse GLUTag enteroendocrine cell line · source_derived_draft · unverified_draft

## hfcs-cell-glp1 Fructose stimulated GLP-1 secretion in mouse GLUTag cells with a reported EC50 of 0.155 mM. Model/species: Mouse GLUTag enteroendocrine cell line Tissue: GLP-1 secretion assay Exposure: Fructose concentration series, EC50 0.155 mM; blocker experiment 10 mM fructose plus 340 micromolar diazoxide Route: In vitro sugar and drug exposure Duration: 2 h Exposure scope: Isolated fructose / drug-peptide assay Limits: Pharmacological channel control in a cell line does not establish a human drug-food interaction or a reason to consume fructose therapeutically. Reference: Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24525020/ DOI: 10.1152/ajpgi.00372.2013 Access: Primary full-text methods/results and metadata inspected.

dose

Fructose, sucrose or glucose 80 g/day versus sweetened-beverage abstinence

duration

7 weeks

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

94 healthy men completing randomized beverage intervention

exposure_scope

Component sugars and sucrose

limitations

Total reported energy intake was similar across groups; this was not a metabolic-ward clamp. Fractional fatty-acid synthesis is distinct from total liver fat and VLDL-TG output. No HFCS arm.

nutrient_topic

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

organism

94 healthy men completing randomized beverage intervention

plain_language

Fructose beverages increased basal hepatic fractional fatty-acid synthesis/secretion versus control after seven weeks.

primary_references

Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33684506/ DOI: 10.1016/j.jhep.2021.02.027

route

Oral beverages in addition to usual diet

tissue

Stable-isotope hepatic lipid synthesis

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 389–399

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 · 94 healthy men completing randomized beverage intervention · source_derived_draft · unverified_draft

## hfcs-component-dnl Fructose beverages increased basal hepatic fractional fatty-acid synthesis/secretion versus control after seven weeks. Model/species: 94 healthy men completing randomized beverage intervention Tissue: Stable-isotope hepatic lipid synthesis Exposure: Fructose, sucrose or glucose 80 g/day versus sweetened-beverage abstinence Route: Oral beverages in addition to usual diet Duration: 7 weeks Exposure scope: Component sugars and sucrose Limits: Total reported energy intake was similar across groups; this was not a metabolic-ward clamp. Fractional fatty-acid synthesis is distinct from total liver fat and VLDL-TG output. No HFCS arm. Reference: Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33684506/ DOI: 10.1016/j.jhep.2021.02.027 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

availability_state

nutrient_deficiency Imported condition classification; unverified.

dose

Dietary copper 6 or 1.6 mg/kg diet; water with or without 30% w/v fructose

duration

4 weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Male weanling Sprague-Dawley rats

exposure_scope

Isolated fructose with copper restriction

limitations

High-fructose component experiment. Copper concentrations refer to diet, not body weight. Ctr1 expression is not direct copper flux, and human HFCS-induced copper deficiency is not established.

nutrient_topic

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

organism

Male weanling Sprague-Dawley rats

plain_language

The combination of marginal copper deficiency and fructose feeding increased hepatic triglyceride and liver injury in rats.

primary_references

High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver. (2012). https://pubmed.ncbi.nlm.nih.gov/21781943/ DOI: 10.1016/j.jhep.2011.05.030

route

Oral diet and drinking water

tissue

Copper status, duodenum and hepatic triglyceride

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 521–531

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 · Male weanling Sprague-Dawley rats · source_derived_draft · unverified_draft

## hfcs-copper-liver The combination of marginal copper deficiency and fructose feeding increased hepatic triglyceride and liver injury in rats. Model/species: Male weanling Sprague-Dawley rats Tissue: Copper status, duodenum and hepatic triglyceride Exposure: Dietary copper 6 or 1.6 mg/kg diet; water with or without 30% w/v fructose Route: Oral diet and drinking water Duration: 4 weeks Exposure scope: Isolated fructose with copper restriction Limits: High-fructose component experiment. Copper concentrations refer to diet, not body weight. Ctr1 expression is not direct copper flux, and human HFCS-induced copper deficiency is not established. Reference: High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver. (2012). https://pubmed.ncbi.nlm.nih.gov/21781943/ DOI: 10.1016/j.jhep.2011.05.030 Access: Primary full-text methods/results and metadata inspected.

dose

Dietary copper 6 or 1.6 mg/kg diet; water with or without 30% w/v fructose

duration

4 weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Male weanling Sprague-Dawley rats

exposure_scope

Isolated fructose with copper restriction

limitations

High-fructose component experiment. Copper concentrations refer to diet, not body weight. Ctr1 expression is not direct copper flux, and human HFCS-induced copper deficiency is not established.

nutrient_topic

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

organism

Male weanling Sprague-Dawley rats

plain_language

High-fructose feeding worsened copper status in the rat dietary experiment.

primary_references

High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver. (2012). https://pubmed.ncbi.nlm.nih.gov/21781943/ DOI: 10.1016/j.jhep.2011.05.030

route

Oral diet and drinking water

tissue

Copper status, duodenum and hepatic triglyceride

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 497–507

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 · Male weanling Sprague-Dawley rats · source_derived_draft · unverified_draft

## hfcs-copper-status High-fructose feeding worsened copper status in the rat dietary experiment. Model/species: Male weanling Sprague-Dawley rats Tissue: Copper status, duodenum and hepatic triglyceride Exposure: Dietary copper 6 or 1.6 mg/kg diet; water with or without 30% w/v fructose Route: Oral diet and drinking water Duration: 4 weeks Exposure scope: Isolated fructose with copper restriction Limits: High-fructose component experiment. Copper concentrations refer to diet, not body weight. Ctr1 expression is not direct copper flux, and human HFCS-induced copper deficiency is not established. Reference: High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver. (2012). https://pubmed.ncbi.nlm.nih.gov/21781943/ DOI: 10.1016/j.jhep.2011.05.030 Access: Primary full-text methods/results and metadata inspected.

availability_state

nutrient_deficiency Imported condition classification; unverified.

dose

Dietary copper 6 or 1.6 mg/kg diet; water with or without 30% w/v fructose

duration

4 weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Male weanling Sprague-Dawley rats

exposure_scope

Isolated fructose with copper restriction

limitations

High-fructose component experiment. Copper concentrations refer to diet, not body weight. Ctr1 expression is not direct copper flux, and human HFCS-induced copper deficiency is not established.

nutrient_topic

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

organism

Male weanling Sprague-Dawley rats

plain_language

Fructose feeding prevented the duodenal Ctr1 increase otherwise observed with marginal copper deficiency in rats.

primary_references

High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver. (2012). https://pubmed.ncbi.nlm.nih.gov/21781943/ DOI: 10.1016/j.jhep.2011.05.030

route

Oral diet and drinking water

tissue

Copper status, duodenum and hepatic triglyceride

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 509–519

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 · Male weanling Sprague-Dawley rats · source_derived_draft · unverified_draft

## hfcs-copper-transporter Fructose feeding prevented the duodenal Ctr1 increase otherwise observed with marginal copper deficiency in rats. Model/species: Male weanling Sprague-Dawley rats Tissue: Copper status, duodenum and hepatic triglyceride Exposure: Dietary copper 6 or 1.6 mg/kg diet; water with or without 30% w/v fructose Route: Oral diet and drinking water Duration: 4 weeks Exposure scope: Isolated fructose with copper restriction Limits: High-fructose component experiment. Copper concentrations refer to diet, not body weight. Ctr1 expression is not direct copper flux, and human HFCS-induced copper deficiency is not established. Reference: High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver. (2012). https://pubmed.ncbi.nlm.nih.gov/21781943/ DOI: 10.1016/j.jhep.2011.05.030 Access: Primary full-text methods/results and metadata inspected.

dose

2 g/kg fructose plus matched glucose once versus four 0.5 g/kg fructose doses 15 min apart

duration

Equal total dose delivered over 45 min versus one bolus

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Tracer experiments in mice

exposure_scope

Component mixture

limitations

Same sugar amount with different delivery rates; does not quantify a recommended human rate.

nutrient_topic

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

organism

Tracer experiments in mice

plain_language

Dividing the same fructose dose over 45 minutes reduced hepatic lipogenesis relative to a single mouse gavage bolus.

primary_references

The small intestine shields the liver from fructose-induced steatosis. (2020). https://pubmed.ncbi.nlm.nih.gov/32694791/ DOI: 10.1038/s42255-020-0222-9

route

Oral gavage

tissue

Intestinal processing and hepatic lipogenesis

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 197–207

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 · Tracer experiments in mice · source_derived_draft · unverified_draft

## hfcs-delivery-rate Dividing the same fructose dose over 45 minutes reduced hepatic lipogenesis relative to a single mouse gavage bolus. Model/species: Tracer experiments in mice Tissue: Intestinal processing and hepatic lipogenesis Exposure: 2 g/kg fructose plus matched glucose once versus four 0.5 g/kg fructose doses 15 min apart Route: Oral gavage Duration: Equal total dose delivered over 45 min versus one bolus Exposure scope: Component mixture Limits: Same sugar amount with different delivery rates; does not quantify a recommended human rate. Reference: The small intestine shields the liver from fructose-induced steatosis. (2020). https://pubmed.ncbi.nlm.nih.gov/32694791/ DOI: 10.1038/s42255-020-0222-9 Access: Primary full-text methods/results and metadata inspected.

dose

50 g fructose alone or with 12.5, 25 or 50 g glucose; 10% fructose solutions

duration

Breath sampling over 3-4 h

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Ten healthy adult volunteers

exposure_scope

Component sugar mixtures, not a commercial HFCS product

limitations

Small physiological study; breath hydrogen is an indirect absorption readout and symptoms were mild or absent. No specific transporter mechanism was proven by adding glucose.

nutrient_topic

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

organism

Ten healthy adult volunteers

plain_language

Fructose alone exceeded measured absorption capacity at different doses across the ten healthy volunteers.

primary_references

Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. (1986). https://pubmed.ncbi.nlm.nih.gov/3781328/ DOI: 10.1136/gut.27.10.1161

route

Oral sugar challenges

tissue

Hydrogen breath tests

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 89–99

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 · Ten healthy adult volunteers · source_derived_draft · unverified_draft

## hfcs-fructose-malabsorption Fructose alone exceeded measured absorption capacity at different doses across the ten healthy volunteers. Model/species: Ten healthy adult volunteers Tissue: Hydrogen breath tests Exposure: 50 g fructose alone or with 12.5, 25 or 50 g glucose; 10% fructose solutions Route: Oral sugar challenges Duration: Breath sampling over 3-4 h Exposure scope: Component sugar mixtures, not a commercial HFCS product Limits: Small physiological study; breath hydrogen is an indirect absorption readout and symptoms were mild or absent. No specific transporter mechanism was proven by adding glucose. Reference: Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. (1986). https://pubmed.ncbi.nlm.nih.gov/3781328/ DOI: 10.1136/gut.27.10.1161 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

75 g fructose or glucose in 300 mL water after overnight fast

duration

120 min

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Nine healthy adults, paired single-blinded challenges

exposure_scope

Isolated fructose / peptide response

limitations

Pure fructose stimulated some hormones less than glucose, but was not hormonally inert; not an HFCS meal or chronic satiety study.

nutrient_topic

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

organism

Nine healthy adults, paired single-blinded challenges

plain_language

Fructose did not stimulate GIP release, whereas glucose did in the paired human challenge.

primary_references

Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24525020/ DOI: 10.1152/ajpgi.00372.2013

route

Oral solution

tissue

Plasma gut-hormone response

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 461–471

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 · Nine healthy adults, paired single-blinded challenges · source_derived_draft · unverified_draft

## hfcs-human-gip-null Fructose did not stimulate GIP release, whereas glucose did in the paired human challenge. Model/species: Nine healthy adults, paired single-blinded challenges Tissue: Plasma gut-hormone response Exposure: 75 g fructose or glucose in 300 mL water after overnight fast Route: Oral solution Duration: 120 min Exposure scope: Isolated fructose / peptide response Limits: Pure fructose stimulated some hormones less than glucose, but was not hormonally inert; not an HFCS meal or chronic satiety study. Reference: Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24525020/ DOI: 10.1152/ajpgi.00372.2013 Access: Primary full-text methods/results and metadata inspected.

dose

75 g fructose or glucose in 300 mL water after overnight fast

duration

120 min

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Nine healthy adults, paired single-blinded challenges

exposure_scope

Isolated fructose / peptide response

limitations

Pure fructose stimulated some hormones less than glucose, but was not hormonally inert; not an HFCS meal or chronic satiety study.

nutrient_topic

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

organism

Nine healthy adults, paired single-blinded challenges

plain_language

Oral fructose stimulated GLP-1 release in healthy adults, less strongly than isocaloric glucose.

primary_references

Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24525020/ DOI: 10.1152/ajpgi.00372.2013

route

Oral solution

tissue

Plasma gut-hormone response

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 449–459

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 · Nine healthy adults, paired single-blinded challenges · source_derived_draft · unverified_draft

## hfcs-human-glp1 Oral fructose stimulated GLP-1 release in healthy adults, less strongly than isocaloric glucose. Model/species: Nine healthy adults, paired single-blinded challenges Tissue: Plasma gut-hormone response Exposure: 75 g fructose or glucose in 300 mL water after overnight fast Route: Oral solution Duration: 120 min Exposure scope: Isolated fructose / peptide response Limits: Pure fructose stimulated some hormones less than glucose, but was not hormonally inert; not an HFCS meal or chronic satiety study. Reference: Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24525020/ DOI: 10.1152/ajpgi.00372.2013 Access: Primary full-text methods/results and metadata inspected.

dose

1:1 fructose/glucose gavage, typically 0.5 g/kg each; dose series 0.25-2 g/kg each

duration

Acute tracing; knockout portal AUC 0-30 min

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Male C57BL/6 mice, with Khk knockout comparisons

exposure_scope

Component mixture

limitations

Approximately 90% low-dose clearance is a mouse result, not an established human percentage. Fasting, feeding and prior exposure change clearance.

nutrient_topic

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

organism

Male C57BL/6 mice, with Khk knockout comparisons

plain_language

Low-dose oral fructose was approximately 90% cleared by the small intestine in the mouse tracer experiment.

primary_references

The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. (2018). https://pubmed.ncbi.nlm.nih.gov/29414685/ DOI: 10.1016/j.cmet.2017.12.016

route

Oral gavage with isotope tracers

tissue

Small intestine, portal blood and liver

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 137–147

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 · Male C57BL/6 mice, with Khk knockout comparisons · source_derived_draft · unverified_draft

## hfcs-intestinal-clearance Low-dose oral fructose was approximately 90% cleared by the small intestine in the mouse tracer experiment. Model/species: Male C57BL/6 mice, with Khk knockout comparisons Tissue: Small intestine, portal blood and liver Exposure: 1:1 fructose/glucose gavage, typically 0.5 g/kg each; dose series 0.25-2 g/kg each Route: Oral gavage with isotope tracers Duration: Acute tracing; knockout portal AUC 0-30 min Exposure scope: Component mixture Limits: Approximately 90% low-dose clearance is a mouse result, not an established human percentage. Fasting, feeding and prior exposure change clearance. Reference: The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. (2018). https://pubmed.ncbi.nlm.nih.gov/29414685/ DOI: 10.1016/j.cmet.2017.12.016 Access: Primary full-text methods/results and metadata inspected.

dose

1:1 fructose/glucose gavage, typically 0.5 g/kg each; dose series 0.25-2 g/kg each

duration

Acute tracing; knockout portal AUC 0-30 min

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Male C57BL/6 mice, with Khk knockout comparisons

exposure_scope

Component mixture

limitations

Approximately 90% low-dose clearance is a mouse result, not an established human percentage. Fasting, feeding and prior exposure change clearance.

nutrient_topic

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

organism

Male C57BL/6 mice, with Khk knockout comparisons

plain_language

Mouse intestinal tracing detected fructose-derived glucose in portal blood.

primary_references

The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. (2018). https://pubmed.ncbi.nlm.nih.gov/29414685/ DOI: 10.1016/j.cmet.2017.12.016

route

Oral gavage with isotope tracers

tissue

Small intestine, portal blood and liver

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 149–159

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 · Male C57BL/6 mice, with Khk knockout comparisons · source_derived_draft · unverified_draft

## hfcs-intestinal-glucose Mouse intestinal tracing detected fructose-derived glucose in portal blood. Model/species: Male C57BL/6 mice, with Khk knockout comparisons Tissue: Small intestine, portal blood and liver Exposure: 1:1 fructose/glucose gavage, typically 0.5 g/kg each; dose series 0.25-2 g/kg each Route: Oral gavage with isotope tracers Duration: Acute tracing; knockout portal AUC 0-30 min Exposure scope: Component mixture Limits: Approximately 90% low-dose clearance is a mouse result, not an established human percentage. Fasting, feeding and prior exposure change clearance. Reference: The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. (2018). https://pubmed.ncbi.nlm.nih.gov/29414685/ DOI: 10.1016/j.cmet.2017.12.016 Access: Primary full-text methods/results and metadata inspected.

dose

1:1 fructose/glucose gavage, typically 0.5 g/kg each; dose series 0.25-2 g/kg each

duration

Acute tracing; knockout portal AUC 0-30 min

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Male C57BL/6 mice, with Khk knockout comparisons

exposure_scope

Component mixture

limitations

Approximately 90% low-dose clearance is a mouse result, not an established human percentage. Fasting, feeding and prior exposure change clearance.

nutrient_topic

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

organism

Male C57BL/6 mice, with Khk knockout comparisons

plain_language

Mouse intestinal tracing detected fructose-derived lactate in portal blood.

primary_references

The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. (2018). https://pubmed.ncbi.nlm.nih.gov/29414685/ DOI: 10.1016/j.cmet.2017.12.016

route

Oral gavage with isotope tracers

tissue

Small intestine, portal blood and liver

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 161–171

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 · Male C57BL/6 mice, with Khk knockout comparisons · source_derived_draft · unverified_draft

## hfcs-intestinal-lactate Mouse intestinal tracing detected fructose-derived lactate in portal blood. Model/species: Male C57BL/6 mice, with Khk knockout comparisons Tissue: Small intestine, portal blood and liver Exposure: 1:1 fructose/glucose gavage, typically 0.5 g/kg each; dose series 0.25-2 g/kg each Route: Oral gavage with isotope tracers Duration: Acute tracing; knockout portal AUC 0-30 min Exposure scope: Component mixture Limits: Approximately 90% low-dose clearance is a mouse result, not an established human percentage. Fasting, feeding and prior exposure change clearance. Reference: The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. (2018). https://pubmed.ncbi.nlm.nih.gov/29414685/ DOI: 10.1016/j.cmet.2017.12.016 Access: Primary full-text methods/results and metadata inspected.

dose

1:1 fructose/glucose gavage, typically 0.5 g/kg each; dose series 0.25-2 g/kg each

duration

Acute tracing; knockout portal AUC 0-30 min

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Male C57BL/6 mice, with Khk knockout comparisons

exposure_scope

Component mixture

limitations

Approximately 90% low-dose clearance is a mouse result, not an established human percentage. Fasting, feeding and prior exposure change clearance.

nutrient_topic

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

organism

Male C57BL/6 mice, with Khk knockout comparisons

plain_language

At higher gavage doses, intestinal processing saturated and more intact fructose reached mouse portal blood and the liver.

primary_references

The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. (2018). https://pubmed.ncbi.nlm.nih.gov/29414685/ DOI: 10.1016/j.cmet.2017.12.016

route

Oral gavage with isotope tracers

tissue

Small intestine, portal blood and liver

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 173–183

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 · Male C57BL/6 mice, with Khk knockout comparisons · source_derived_draft · unverified_draft

## hfcs-intestinal-overflow At higher gavage doses, intestinal processing saturated and more intact fructose reached mouse portal blood and the liver. Model/species: Male C57BL/6 mice, with Khk knockout comparisons Tissue: Small intestine, portal blood and liver Exposure: 1:1 fructose/glucose gavage, typically 0.5 g/kg each; dose series 0.25-2 g/kg each Route: Oral gavage with isotope tracers Duration: Acute tracing; knockout portal AUC 0-30 min Exposure scope: Component mixture Limits: Approximately 90% low-dose clearance is a mouse result, not an established human percentage. Fasting, feeding and prior exposure change clearance. Reference: The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. (2018). https://pubmed.ncbi.nlm.nih.gov/29414685/ DOI: 10.1016/j.cmet.2017.12.016 Access: Primary full-text methods/results and metadata inspected.

dose

Fructose 250 mg/kg bolus

duration

Early 5 min changes; sugar-phosphate recovery within about 20 min

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Seven healthy human volunteers

exposure_scope

Isolated fructose, intravenous

limitations

Injection bypasses the intestine. Magnitude cannot be assigned to a normal oral HFCS serving or to dietary phosphate deficiency.

nutrient_topic

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

organism

Seven healthy human volunteers

plain_language

Intravenous fructose acutely lowered hepatic ATP in seven healthy volunteers.

primary_references

Assessment of human liver metabolism by phosphorus-31 magnetic resonance spectroscopy. (1986). https://pubmed.ncbi.nlm.nih.gov/3730768/ DOI: 10.1259/0007-1285-59-703-695

route

Intravenous injection

tissue

Liver phosphorus-31 MRS

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 233–243

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 · Seven healthy human volunteers · source_derived_draft · unverified_draft

## hfcs-iv-atp Intravenous fructose acutely lowered hepatic ATP in seven healthy volunteers. Model/species: Seven healthy human volunteers Tissue: Liver phosphorus-31 MRS Exposure: Fructose 250 mg/kg bolus Route: Intravenous injection Duration: Early 5 min changes; sugar-phosphate recovery within about 20 min Exposure scope: Isolated fructose, intravenous Limits: Injection bypasses the intestine. Magnitude cannot be assigned to a normal oral HFCS serving or to dietary phosphate deficiency. Reference: Assessment of human liver metabolism by phosphorus-31 magnetic resonance spectroscopy. (1986). https://pubmed.ncbi.nlm.nih.gov/3730768/ DOI: 10.1259/0007-1285-59-703-695 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

Fructose 250 mg/kg bolus

duration

Early 5 min changes; sugar-phosphate recovery within about 20 min

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Seven healthy human volunteers

exposure_scope

Isolated fructose, intravenous

limitations

Injection bypasses the intestine. Magnitude cannot be assigned to a normal oral HFCS serving or to dietary phosphate deficiency.

nutrient_topic

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

organism

Seven healthy human volunteers

plain_language

The intravenous fructose bolus acutely lowered hepatic inorganic phosphate as sugar phosphates accumulated.

primary_references

Assessment of human liver metabolism by phosphorus-31 magnetic resonance spectroscopy. (1986). https://pubmed.ncbi.nlm.nih.gov/3730768/ DOI: 10.1259/0007-1285-59-703-695

route

Intravenous injection

tissue

Liver phosphorus-31 MRS

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 245–255

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 · Seven healthy human volunteers · source_derived_draft · unverified_draft

## hfcs-iv-phosphate The intravenous fructose bolus acutely lowered hepatic inorganic phosphate as sugar phosphates accumulated. Model/species: Seven healthy human volunteers Tissue: Liver phosphorus-31 MRS Exposure: Fructose 250 mg/kg bolus Route: Intravenous injection Duration: Early 5 min changes; sugar-phosphate recovery within about 20 min Exposure scope: Isolated fructose, intravenous Limits: Injection bypasses the intestine. Magnitude cannot be assigned to a normal oral HFCS serving or to dietary phosphate deficiency. Reference: Assessment of human liver metabolism by phosphorus-31 magnetic resonance spectroscopy. (1986). https://pubmed.ncbi.nlm.nih.gov/3730768/ DOI: 10.1259/0007-1285-59-703-695 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

Bolus 2 g/kg labeled fructose plus 2 g/kg glucose; interventions specified by claim

duration

Acute isotope sampling up to 6 h

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Wild-type mice, microbiota depletion and liver Acss2-silencing experiments

exposure_scope

Component mixture

limitations

Carbon tracing supports microbial acetate supply; antibiotic depletion is not a clinical recommendation and microbiota effects are not universal across diets.

nutrient_topic

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

organism

Wild-type mice, microbiota depletion and liver Acss2-silencing experiments

plain_language

Mouse tracer experiments identified gut-microbial acetate derived from ingested fructose.

primary_references

Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

route

Oral gavage and experimental microbiota/gene perturbation

tissue

Portal acetate and hepatic fatty-acid labeling

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 209–219

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 · Wild-type mice, microbiota depletion and liver Acss2-silencing experiments · source_derived_draft · unverified_draft

## hfcs-microbial-acetate Mouse tracer experiments identified gut-microbial acetate derived from ingested fructose. Model/species: Wild-type mice, microbiota depletion and liver Acss2-silencing experiments Tissue: Portal acetate and hepatic fatty-acid labeling Exposure: Bolus 2 g/kg labeled fructose plus 2 g/kg glucose; interventions specified by claim Route: Oral gavage and experimental microbiota/gene perturbation Duration: Acute isotope sampling up to 6 h Exposure scope: Component mixture Limits: Carbon tracing supports microbial acetate supply; antibiotic depletion is not a clinical recommendation and microbiota effects are not universal across diets. Reference: Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7 Access: Primary full-text methods/results and metadata inspected.

dose

75 g fructose challenge

duration

60 min

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

37 overweight/obese adults without diabetes, stratified by MASLD

exposure_scope

Isolated fructose, oral

limitations

Small acute component study; the ATP response was blunted in MASLD, not uniformly greater. Metabolite signals are not chronic clinical outcomes.

nutrient_topic

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

organism

37 overweight/obese adults without diabetes, stratified by MASLD

plain_language

After 75 g oral fructose, hepatic ATP decreased within 15 minutes and remained lower at 60 minutes in participants without MASLD.

primary_references

Patients with MASLD exhibit in vivo changes in hepatic response to oral fructose consumption. (2026). https://pubmed.ncbi.nlm.nih.gov/41866318/ DOI: 10.1210/clinem/dgag125

route

Oral solution

tissue

Liver phosphorus-31 MRS

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 257–267

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 · 37 overweight/obese adults without diabetes, stratified by MASLD · source_derived_draft · unverified_draft

## hfcs-oral-atp After 75 g oral fructose, hepatic ATP decreased within 15 minutes and remained lower at 60 minutes in participants without MASLD. Model/species: 37 overweight/obese adults without diabetes, stratified by MASLD Tissue: Liver phosphorus-31 MRS Exposure: 75 g fructose challenge Route: Oral solution Duration: 60 min Exposure scope: Isolated fructose, oral Limits: Small acute component study; the ATP response was blunted in MASLD, not uniformly greater. Metabolite signals are not chronic clinical outcomes. Reference: Patients with MASLD exhibit in vivo changes in hepatic response to oral fructose consumption. (2026). https://pubmed.ncbi.nlm.nih.gov/41866318/ DOI: 10.1210/clinem/dgag125 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

75 g fructose challenge

duration

60 min

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

37 overweight/obese adults without diabetes, stratified by MASLD

exposure_scope

Isolated fructose, oral

limitations

Small acute component study; the ATP response was blunted in MASLD, not uniformly greater. Metabolite signals are not chronic clinical outcomes.

nutrient_topic

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

organism

37 overweight/obese adults without diabetes, stratified by MASLD

plain_language

Participants with MASLD showed a blunted ATP response to oral fructose, with only a nonsignificant early drop and recovery by 30 minutes.

primary_references

Patients with MASLD exhibit in vivo changes in hepatic response to oral fructose consumption. (2026). https://pubmed.ncbi.nlm.nih.gov/41866318/ DOI: 10.1210/clinem/dgag125

route

Oral solution

tissue

Liver phosphorus-31 MRS

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 269–279

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 · 37 overweight/obese adults without diabetes, stratified by MASLD · source_derived_draft · unverified_draft

## hfcs-oral-atp-masld Participants with MASLD showed a blunted ATP response to oral fructose, with only a nonsignificant early drop and recovery by 30 minutes. Model/species: 37 overweight/obese adults without diabetes, stratified by MASLD Tissue: Liver phosphorus-31 MRS Exposure: 75 g fructose challenge Route: Oral solution Duration: 60 min Exposure scope: Isolated fructose, oral Limits: Small acute component study; the ATP response was blunted in MASLD, not uniformly greater. Metabolite signals are not chronic clinical outcomes. Reference: Patients with MASLD exhibit in vivo changes in hepatic response to oral fructose consumption. (2026). https://pubmed.ncbi.nlm.nih.gov/41866318/ DOI: 10.1210/clinem/dgag125 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

Fructose, sucrose or glucose 80 g/day versus sweetened-beverage abstinence

duration

7 weeks

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

94 healthy men completing randomized beverage intervention

exposure_scope

Component sugars and sucrose

limitations

Total reported energy intake was similar across groups; this was not a metabolic-ward clamp. Fractional fatty-acid synthesis is distinct from total liver fat and VLDL-TG output. No HFCS arm.

nutrient_topic

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

organism

94 healthy men completing randomized beverage intervention

plain_language

Fructose did not increase basal secretion of newly synthesized VLDL triglyceride in that trial.

primary_references

Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33684506/ DOI: 10.1016/j.jhep.2021.02.027

route

Oral beverages in addition to usual diet

tissue

Stable-isotope hepatic lipid synthesis

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 413–423

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 · 94 healthy men completing randomized beverage intervention · source_derived_draft · unverified_draft

## hfcs-vldl-null Fructose did not increase basal secretion of newly synthesized VLDL triglyceride in that trial. Model/species: 94 healthy men completing randomized beverage intervention Tissue: Stable-isotope hepatic lipid synthesis Exposure: Fructose, sucrose or glucose 80 g/day versus sweetened-beverage abstinence Route: Oral beverages in addition to usual diet Duration: 7 weeks Exposure scope: Component sugars and sucrose Limits: Total reported energy intake was similar across groups; this was not a metabolic-ward clamp. Fractional fatty-acid synthesis is distinct from total liver fat and VLDL-TG output. No HFCS arm. Reference: Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial. (2021). https://pubmed.ncbi.nlm.nih.gov/33684506/ DOI: 10.1016/j.jhep.2021.02.027 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

HFCS-42 and HFCS-55; no administered dose

duration

Composition reference accessed 2026-09-20

evidence_access

Official FDA composition page; not a primary experiment.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Official description of HFCS formulations

exposure_scope

HFCS identity

limitations

Percentages describe sweetener composition, not beverage volume. This source is not a primary metabolic experiment.

nutrient_topic

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

organism

Official description of HFCS formulations

plain_language

HFCS contains free fructose rather than fructose linked to glucose in sucrose.

primary_references

[fda-hfcs-composition] High Fructose Corn Syrup Questions and Answers (accessed 2026). https://www.fda.gov/food/food-additives-petitions/high-fructose-corn-syrup-questions-and-answers

route

Not an intervention

tissue

Ingredient chemistry

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 41–51

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 · Official description of HFCS formulations · source_derived_draft · unverified_draft

## hfcs-fructose-component HFCS contains free fructose rather than fructose linked to glucose in sucrose. Model/species: Official description of HFCS formulations Tissue: Ingredient chemistry Exposure: HFCS-42 and HFCS-55; no administered dose Route: Not an intervention Duration: Composition reference accessed 2026-09-20 Exposure scope: HFCS identity Limits: Percentages describe sweetener composition, not beverage volume. This source is not a primary metabolic experiment. Reference: [fda-hfcs-composition] High Fructose Corn Syrup Questions and Answers (accessed 2026). https://www.fda.gov/food/food-additives-petitions/high-fructose-corn-syrup-questions-and-answers Access: Official FDA composition page; not a primary experiment.

dose

Fructose kinetic series; reported Km about 6 mM

duration

Assay interval unavailable in abstract

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Human GLUT5 expressed in Xenopus oocytes

exposure_scope

Isolated fructose / human protein

limitations

Human protein in an amphibian expression system; not a measured human intake threshold.

nutrient_topic

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

organism

Human GLUT5 expressed in Xenopus oocytes

plain_language

Expressed human GLUT5 selectively transported fructose, with a reported Km near 6 mM.

primary_references

Fructose transporter in human spermatozoa and small intestine is GLUT5. (1992). https://pubmed.ncbi.nlm.nih.gov/1634504/

route

In vitro substrate addition

tissue

Recombinant transport assay

transport_effect

raises Fructose uptake measured in the expressing cell with a reported Km near 6 mM.

transport_pool

the expressing cell Fructose uptake measured in the expressing cell with a reported Km near 6 mM.

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 65–75

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 · Human GLUT5 expressed in Xenopus oocytes · source_derived_draft · unverified_draft

## hfcs-glut5 Expressed human GLUT5 selectively transported fructose, with a reported Km near 6 mM. Model/species: Human GLUT5 expressed in Xenopus oocytes Tissue: Recombinant transport assay Exposure: Fructose kinetic series; reported Km about 6 mM Route: In vitro substrate addition Duration: Assay interval unavailable in abstract Exposure scope: Isolated fructose / human protein Limits: Human protein in an amphibian expression system; not a measured human intake threshold. Reference: Fructose transporter in human spermatozoa and small intestine is GLUT5. (1992). https://pubmed.ncbi.nlm.nih.gov/1634504/ Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

75 mM sucrose for expressed-SI activity; 0.7 mM added glucose in brush-border kinetic experiments

duration

1 hour at 37 C for expressed-enzyme activity; kinetic series for product inhibition

evidence_access

Selected primary full-text sections inspected via indexed PMC page; local XML has abstract only.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Human SI expressed in COS-1 cells; isolated human intestinal brush border

exposure_scope

Human enzyme mechanism

limitations

Glucose feedback was measured in an enzyme preparation, not demonstrated as a whole-body blood-glucose control mechanism. Selected full-text methods/results inspected; archived PubMed/PMC XML contains abstract only.

nutrient_topic

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

organism

Human SI expressed in COS-1 cells; isolated human intestinal brush border

plain_language

Cleavage of sucrose by human sucrase-isomaltase also releases fructose.

primary_references

Structure-function analysis of human sucrase-isomaltase identifies key residues required for catalytic activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28522605/ DOI: 10.1074/jbc.M117.791939

route

In vitro enzyme/substrate incubation

tissue

Brush-border carbohydrate digestion

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 31–41

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 · Human SI expressed in COS-1 cells; isolated human intestinal brush border · source_derived_draft · unverified_draft

## sucrose-hydrolysis-fructose Cleavage of sucrose by human sucrase-isomaltase also releases fructose. Model/species: Human SI expressed in COS-1 cells; isolated human intestinal brush border Tissue: Brush-border carbohydrate digestion Exposure: 75 mM sucrose for expressed-SI activity; 0.7 mM added glucose in brush-border kinetic experiments Route: In vitro enzyme/substrate incubation Duration: 1 hour at 37 C for expressed-enzyme activity; kinetic series for product inhibition Exposure scope: Human enzyme mechanism Limits: Glucose feedback was measured in an enzyme preparation, not demonstrated as a whole-body blood-glucose control mechanism. Selected full-text methods/results inspected; archived PubMed/PMC XML contains abstract only. Reference: Structure-function analysis of human sucrase-isomaltase identifies key residues required for catalytic activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28522605/ DOI: 10.1074/jbc.M117.791939 Access: Selected primary full-text sections inspected via indexed PMC page; local XML has abstract only.

evidence_access

Primary full text PMC11120408

experimental_model

Cell-free bovine albumin and fructose experiment.

limitations

Not purified ankaflavin alone, and fluorescence inhibition is not a clinical diabetes endpoint.

nutrient_topic

Red yeast rice collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Red yeast rice

plain_language

A particular mixture changed a glycation readout.

primary_references

[38790873] Revealing the Hypoglycemic Effect of Red Yeast Rice: Perspectives from the Inhibition of α-Glucosidase and the Anti-Glycation Capability by Ankaflavin and Monascin. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38790873/ · DOI 10.3390/foods13101573

Red yeast rice: constituents, mevalonate, CoQ and product-specific interactions (2026-09-20) · lines 308–314

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free bovine albumin and fructose experiment. · source_derived_draft · unverified_draft

## red-yeast-rice-mixture-glycation A particular mixture changed a glycation readout. The pigment-rich fermentation product at 0.2 mg/mL reduced fluorescent AGE formation by 87.1% in the BSA–fructose assay. Model: Cell-free bovine albumin and fructose experiment. Limitations: Not purified ankaflavin alone, and fluorescence inhibition is not a clinical diabetes endpoint. Evidence access: Primary full text PMC11120408 [38790873] Revealing the Hypoglycemic Effect of Red Yeast Rice: Perspectives from the Inhibition of α-Glucosidase and the Anti-Glycation Capability by Ankaflavin and Monascin. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38790873/ · DOI 10.3390/foods13101573

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing

exposure

Bolus or gradual dietary fructose, with genetic, microbial and dose-rate manipulation

limitations

Three independent manipulations converge on the same route. Its dominance depends on how fast the fructose is eaten, and the human contribution is not established here.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Mouse

plain_language

Deleting the enzyme everyone assumed was responsible did not stop the fat being made.

primary_references

[acetate-p32214246] Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

tissue_or_cell_type

Liver and gut

trigger_kind

machinery_impairment Imported condition classification; unverified.

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 550–561

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing · source_derived_draft · unverified_draft

### acetate-acly-deletion-insufficient Using in vivo isotope tracing, liver-specific deletion of Acly in mice was unable to suppress fructose-induced lipogenesis. Condition category: machinery_impairment nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: Deleting the enzyme everyone assumed was responsible did not stop the fat being made. organism: Mouse tissue_or_cell_type: Liver and gut experimental_model: In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing limitations: Three independent manipulations converge on the same route. Its dominance depends on how fast the fructose is eaten, and the human contribution is not established here. exposure: Bolus or gradual dietary fructose, with genetic, microbial and dose-rate manipulation evidence_span: {"source_cache": "artifacts/acetate-research/32214246.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1", "start_char": 0, "end_char": 1782, "text_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1"} [acetate-p32214246] Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

evidence_span

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experimental_model

In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing

exposure

Bolus or gradual dietary fructose, with genetic, microbial and dose-rate manipulation

limitations

Three independent manipulations converge on the same route. Its dominance depends on how fast the fructose is eaten, and the human contribution is not established here.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Mouse

plain_language

How fast the sugar is eaten decides which of the two routes supplies the carbon; the signal that switches the genes on is separate from either.

primary_references

[acetate-p32214246] Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

tissue_or_cell_type

Liver and gut

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 576–587

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing · source_derived_draft · unverified_draft

### acetate-intake-rate-decides When fructose is consumed more gradually to facilitate its absorption in the small intestine, both citrate cleavage in hepatocytes and microorganism-derived acetate contribute to lipogenesis, whereas the lipogenic transcriptional program is activated in response to fructose independently of acetyl-CoA metabolism, revealing a two-pronged mechanism in which fructolysis within hepatocytes provides the signal to express lipogenic genes while microbial acetate feeds the lipogenic acetyl-CoA pools. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: How fast the sugar is eaten decides which of the two routes supplies the carbon; the signal that switches the genes on is separate from either. organism: Mouse tissue_or_cell_type: Liver and gut experimental_model: In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing limitations: Three independent manipulations converge on the same route. Its dominance depends on how fast the fructose is eaten, and the human contribution is not established here. exposure: Bolus or gradual dietary fructose, with genetic, microbial and dose-rate manipulation evidence_span: {"source_cache": "artifacts/acetate-research/32214246.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1", "start_char": 0, "end_char": 1782, "text_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1"} [acetate-p32214246] Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing

exposure

Bolus or gradual dietary fructose, with genetic, microbial and dose-rate manipulation

limitations

Three independent manipulations converge on the same route. Its dominance depends on how fast the fructose is eaten, and the human contribution is not established here.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Mouse

plain_language

The sugar becomes acetate in the gut, and the liver builds fat out of that.

primary_references

[acetate-p32214246] Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

tissue_or_cell_type

Liver and gut

trigger_kind

machinery_impairment Imported condition classification; unverified.

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 563–574

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing · source_derived_draft · unverified_draft

### acetate-microbial-acetate-route Dietary fructose is converted to acetate by the gut microbiota and this supplies lipogenic acetyl-CoA independently of ACLY, with depletion of the microbiota or silencing of hepatic ACSS2, which generates acetyl-CoA from acetate, potently suppressing the conversion of bolus fructose into hepatic acetyl-CoA and fatty acids. Condition category: machinery_impairment nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: The sugar becomes acetate in the gut, and the liver builds fat out of that. organism: Mouse tissue_or_cell_type: Liver and gut experimental_model: In vivo isotope tracing in mice with liver-specific Acly deletion, microbiota depletion and hepatic ACSS2 silencing limitations: Three independent manipulations converge on the same route. Its dominance depends on how fast the fructose is eaten, and the human contribution is not established here. exposure: Bolus or gradual dietary fructose, with genetic, microbial and dose-rate manipulation evidence_span: {"source_cache": "artifacts/acetate-research/32214246.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1", "start_char": 0, "end_char": 1782, "text_sha256": "302837a9fc88030dce2c74e65053f8baae65863245d2d811ccbb3231b95a99e1"} [acetate-p32214246] Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Bolus 2 g/kg labeled fructose plus 2 g/kg glucose; interventions specified by claim

duration

Acute isotope sampling up to 6 h

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Wild-type mice, microbiota depletion and liver Acss2-silencing experiments

exposure_scope

Component mixture

limitations

Carbon tracing supports microbial acetate supply; antibiotic depletion is not a clinical recommendation and microbiota effects are not universal across diets.

nutrient_topic

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

organism

Wild-type mice, microbiota depletion and liver Acss2-silencing experiments

plain_language

Silencing hepatic Acss2 suppressed conversion of bolus fructose carbon into hepatic acetyl-CoA and fatty acids in mice.

primary_references

Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7

route

Oral gavage and experimental microbiota/gene perturbation

tissue

Portal acetate and hepatic fatty-acid labeling

trigger_kind

machinery_impairment Imported condition classification; unverified.

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 221–231

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 · Wild-type mice, microbiota depletion and liver Acss2-silencing experiments · source_derived_draft · unverified_draft

## hfcs-acss2-silencing Silencing hepatic Acss2 suppressed conversion of bolus fructose carbon into hepatic acetyl-CoA and fatty acids in mice. Model/species: Wild-type mice, microbiota depletion and liver Acss2-silencing experiments Tissue: Portal acetate and hepatic fatty-acid labeling Exposure: Bolus 2 g/kg labeled fructose plus 2 g/kg glucose; interventions specified by claim Route: Oral gavage and experimental microbiota/gene perturbation Duration: Acute isotope sampling up to 6 h Exposure scope: Component mixture Limits: Carbon tracing supports microbial acetate supply; antibiotic depletion is not a clinical recommendation and microbiota effects are not universal across diets. Reference: Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. (2020). https://pubmed.ncbi.nlm.nih.gov/32214246/ DOI: 10.1038/s41586-020-2101-7 Access: Primary full-text methods/results and metadata inspected.

dose

HFCS or sucrose beverages with 3 isocaloric meals; exact sugar allocation not recovered from primary abstract

duration

24-hour profiles

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

34 adults in crossover meal study; 8 men also received pure monosaccharides

exposure_scope

Direct HFCS versus sucrose

limitations

Short feeding study; eight-man fructose/glucose comparison is a subset and does not establish long-term equivalence or appetite control.

nutrient_topic

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

organism

34 adults in crossover meal study; 8 men also received pure monosaccharides

plain_language

In the eight-man subset, HFCS and sucrose produced postprandial triglyceride responses comparable to pure fructose.

primary_references

Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. (2008). https://pubmed.ncbi.nlm.nih.gov/18469239/ DOI: 10.1093/ajcn/87.5.1194

route

Oral beverages with meals

tissue

24-hour endocrine and triglyceride profiles

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 377–387

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 · 34 adults in crossover meal study; 8 men also received pure monosaccharides · source_derived_draft · unverified_draft

## hfcs-acute-tg In the eight-man subset, HFCS and sucrose produced postprandial triglyceride responses comparable to pure fructose. Model/species: 34 adults in crossover meal study; 8 men also received pure monosaccharides Tissue: 24-hour endocrine and triglyceride profiles Exposure: HFCS or sucrose beverages with 3 isocaloric meals; exact sugar allocation not recovered from primary abstract Route: Oral beverages with meals Duration: 24-hour profiles Exposure scope: Direct HFCS versus sucrose Limits: Short feeding study; eight-man fructose/glucose comparison is a subset and does not establish long-term equivalence or appetite control. Reference: Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. (2008). https://pubmed.ncbi.nlm.nih.gov/18469239/ DOI: 10.1093/ajcn/87.5.1194 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

200 g fructose/day with or without allopurinol; drug dose not recovered in accessed abstract

duration

2 weeks

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

74 adult men in randomized fructose-loading intervention

exposure_scope

Isolated fructose / drug perturbation

limitations

Very high pure-fructose dose; allopurinol did not correct every outcome. Pharmacological rescue does not prove sole mediation by urate or justify treatment of ordinary HFCS intake.

nutrient_topic

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

organism

74 adult men in randomized fructose-loading intervention

plain_language

Allopurinol prevented the fructose-associated increase in 24-hour diastolic and daytime systolic/diastolic blood pressure.

primary_references

Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. (2010). https://pubmed.ncbi.nlm.nih.gov/20029377/ DOI: 10.1038/ijo.2009.259

route

Oral fructose and oral drug

tissue

Urate, ambulatory blood pressure and metabolic markers

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 545–555

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 · 74 adult men in randomized fructose-loading intervention · source_derived_draft · unverified_draft

## hfcs-allopurinol-bp Allopurinol prevented the fructose-associated increase in 24-hour diastolic and daytime systolic/diastolic blood pressure. Model/species: 74 adult men in randomized fructose-loading intervention Tissue: Urate, ambulatory blood pressure and metabolic markers Exposure: 200 g fructose/day with or without allopurinol; drug dose not recovered in accessed abstract Route: Oral fructose and oral drug Duration: 2 weeks Exposure scope: Isolated fructose / drug perturbation Limits: Very high pure-fructose dose; allopurinol did not correct every outcome. Pharmacological rescue does not prove sole mediation by urate or justify treatment of ordinary HFCS intake. Reference: Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. (2010). https://pubmed.ncbi.nlm.nih.gov/20029377/ DOI: 10.1038/ijo.2009.259 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

200 g fructose/day with or without allopurinol; drug dose not recovered in accessed abstract

duration

2 weeks

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

74 adult men in randomized fructose-loading intervention

exposure_scope

Isolated fructose / drug perturbation

limitations

Very high pure-fructose dose; allopurinol did not correct every outcome. Pharmacological rescue does not prove sole mediation by urate or justify treatment of ordinary HFCS intake.

nutrient_topic

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

organism

74 adult men in randomized fructose-loading intervention

plain_language

Allopurinol did not reduce the HOMA insulin-resistance index during the fructose-loading trial.

primary_references

Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. (2010). https://pubmed.ncbi.nlm.nih.gov/20029377/ DOI: 10.1038/ijo.2009.259

route

Oral fructose and oral drug

tissue

Urate, ambulatory blood pressure and metabolic markers

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 557–567

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 · 74 adult men in randomized fructose-loading intervention · source_derived_draft · unverified_draft

## hfcs-allopurinol-homa-null Allopurinol did not reduce the HOMA insulin-resistance index during the fructose-loading trial. Model/species: 74 adult men in randomized fructose-loading intervention Tissue: Urate, ambulatory blood pressure and metabolic markers Exposure: 200 g fructose/day with or without allopurinol; drug dose not recovered in accessed abstract Route: Oral fructose and oral drug Duration: 2 weeks Exposure scope: Isolated fructose / drug perturbation Limits: Very high pure-fructose dose; allopurinol did not correct every outcome. Pharmacological rescue does not prove sole mediation by urate or justify treatment of ordinary HFCS intake. Reference: Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. (2010). https://pubmed.ncbi.nlm.nih.gov/20029377/ DOI: 10.1038/ijo.2009.259 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

200 g fructose/day with or without allopurinol; drug dose not recovered in accessed abstract

duration

2 weeks

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

74 adult men in randomized fructose-loading intervention

exposure_scope

Isolated fructose / drug perturbation

limitations

Very high pure-fructose dose; allopurinol did not correct every outcome. Pharmacological rescue does not prove sole mediation by urate or justify treatment of ordinary HFCS intake.

nutrient_topic

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

organism

74 adult men in randomized fructose-loading intervention

plain_language

Allopurinol lowered serum urate during the high-dose fructose intervention.

primary_references

Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. (2010). https://pubmed.ncbi.nlm.nih.gov/20029377/ DOI: 10.1038/ijo.2009.259

route

Oral fructose and oral drug

tissue

Urate, ambulatory blood pressure and metabolic markers

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 533–543

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 · 74 adult men in randomized fructose-loading intervention · source_derived_draft · unverified_draft

## hfcs-allopurinol-urate Allopurinol lowered serum urate during the high-dose fructose intervention. Model/species: 74 adult men in randomized fructose-loading intervention Tissue: Urate, ambulatory blood pressure and metabolic markers Exposure: 200 g fructose/day with or without allopurinol; drug dose not recovered in accessed abstract Route: Oral fructose and oral drug Duration: 2 weeks Exposure scope: Isolated fructose / drug perturbation Limits: Very high pure-fructose dose; allopurinol did not correct every outcome. Pharmacological rescue does not prove sole mediation by urate or justify treatment of ordinary HFCS intake. Reference: Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. (2010). https://pubmed.ncbi.nlm.nih.gov/20029377/ DOI: 10.1038/ijo.2009.259 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Fructose concentration series, EC50 0.155 mM; blocker experiment 10 mM fructose plus 340 micromolar diazoxide

duration

2 h

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Mouse GLUTag enteroendocrine cell line

exposure_scope

Isolated fructose / drug-peptide assay

limitations

Pharmacological channel control in a cell line does not establish a human drug-food interaction or a reason to consume fructose therapeutically.

nutrient_topic

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

organism

Mouse GLUTag enteroendocrine cell line

plain_language

Diazoxide at 340 micromolar abolished fructose-stimulated GLP-1 secretion in GLUTag cells.

primary_references

Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24525020/ DOI: 10.1152/ajpgi.00372.2013

route

In vitro sugar and drug exposure

tissue

GLP-1 secretion assay

trigger_kind

machinery_impairment Imported condition classification; unverified.

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 485–495

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 · Mouse GLUTag enteroendocrine cell line · source_derived_draft · unverified_draft

## hfcs-diazoxide Diazoxide at 340 micromolar abolished fructose-stimulated GLP-1 secretion in GLUTag cells. Model/species: Mouse GLUTag enteroendocrine cell line Tissue: GLP-1 secretion assay Exposure: Fructose concentration series, EC50 0.155 mM; blocker experiment 10 mM fructose plus 340 micromolar diazoxide Route: In vitro sugar and drug exposure Duration: 2 h Exposure scope: Isolated fructose / drug-peptide assay Limits: Pharmacological channel control in a cell line does not establish a human drug-food interaction or a reason to consume fructose therapeutically. Reference: Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans. (2014). https://pubmed.ncbi.nlm.nih.gov/24525020/ DOI: 10.1152/ajpgi.00372.2013 Access: Primary full-text methods/results and metadata inspected.

dose

50 g fructose alone or with 12.5, 25 or 50 g glucose; 10% fructose solutions

duration

Breath sampling over 3-4 h

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Ten healthy adult volunteers

exposure_scope

Component sugar mixtures, not a commercial HFCS product

limitations

Small physiological study; breath hydrogen is an indirect absorption readout and symptoms were mild or absent. No specific transporter mechanism was proven by adding glucose.

nutrient_topic

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

organism

Ten healthy adult volunteers

plain_language

Adding 50 g glucose to 50 g fructose eliminated detectable breath-test malabsorption in all ten volunteers, compared with eight positive tests after fructose alone.

primary_references

Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. (1986). https://pubmed.ncbi.nlm.nih.gov/3781328/ DOI: 10.1136/gut.27.10.1161

route

Oral sugar challenges

tissue

Hydrogen breath tests

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 77–87

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 · Ten healthy adult volunteers · source_derived_draft · unverified_draft

## hfcs-glucose-absorption Adding 50 g glucose to 50 g fructose eliminated detectable breath-test malabsorption in all ten volunteers, compared with eight positive tests after fructose alone. Model/species: Ten healthy adult volunteers Tissue: Hydrogen breath tests Exposure: 50 g fructose alone or with 12.5, 25 or 50 g glucose; 10% fructose solutions Route: Oral sugar challenges Duration: Breath sampling over 3-4 h Exposure scope: Component sugar mixtures, not a commercial HFCS product Limits: Small physiological study; breath hydrogen is an indirect absorption readout and symptoms were mild or absent. No specific transporter mechanism was proven by adding glucose. Reference: Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. (1986). https://pubmed.ncbi.nlm.nih.gov/3781328/ DOI: 10.1136/gut.27.10.1161 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

10% sucrose in drinking water

duration

8 weeks

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Intestine-specific Khk-C knockout mice and littermate controls

exposure_scope

Sucrose / fructose-component mechanism

limitations

Tissue-specific deletion differs from systemic KHK inhibition. Source is sucrose exposure, not an HFCS trial; mouse intake patterns are not a human safety threshold.

nutrient_topic

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

organism

Intestine-specific Khk-C knockout mice and littermate controls

plain_language

Deleting intestinal Khk-C increased fructose spillover and hepatic lipogenesis during sucrose feeding in mice.

primary_references

The small intestine shields the liver from fructose-induced steatosis. (2020). https://pubmed.ncbi.nlm.nih.gov/32694791/ DOI: 10.1038/s42255-020-0222-9

route

Oral ad libitum sucrose with genetic deletion

tissue

Intestinal clearance and liver lipid metabolism

trigger_kind

machinery_impairment Imported condition classification; unverified.

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 185–195

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 · Intestine-specific Khk-C knockout mice and littermate controls · source_derived_draft · unverified_draft

## hfcs-intestinal-khk-deletion Deleting intestinal Khk-C increased fructose spillover and hepatic lipogenesis during sucrose feeding in mice. Model/species: Intestine-specific Khk-C knockout mice and littermate controls Tissue: Intestinal clearance and liver lipid metabolism Exposure: 10% sucrose in drinking water Route: Oral ad libitum sucrose with genetic deletion Duration: 8 weeks Exposure scope: Sucrose / fructose-component mechanism Limits: Tissue-specific deletion differs from systemic KHK inhibition. Source is sucrose exposure, not an HFCS trial; mouse intake patterns are not a human safety threshold. Reference: The small intestine shields the liver from fructose-induced steatosis. (2020). https://pubmed.ncbi.nlm.nih.gov/32694791/ DOI: 10.1038/s42255-020-0222-9 Access: Primary full-text methods/results and metadata inspected.

dose

Fructose substrate and ATP-dependent enzyme characterization; exact concentrations not in abstract

duration

Assay duration not recovered

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Ketohexokinase purified from human liver

exposure_scope

Human component biochemistry

limitations

Isoform unresolved; enzyme chemistry does not quantify whole-body flux after ordinary HFCS intake. Only abstract/metadata recovered for this scanned article.

nutrient_topic

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

organism

Ketohexokinase purified from human liver

plain_language

Purified human liver ketohexokinase catalyzed the ATP-dependent phosphorylation of fructose.

primary_references

The purification and properties of human liver ketohexokinase. A role for ketohexokinase and fructose-bisphosphate aldolase in the metabolic production of oxalate from xylitol. (1985). https://pubmed.ncbi.nlm.nih.gov/2996495/ DOI: 10.1042/bj2300053

route

In vitro enzyme/substrate incubation

tissue

Cell-free enzyme kinetics

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 101–111

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 · Ketohexokinase purified from human liver · source_derived_draft · unverified_draft

## hfcs-khk-phosphorylation Purified human liver ketohexokinase catalyzed the ATP-dependent phosphorylation of fructose. Model/species: Ketohexokinase purified from human liver Tissue: Cell-free enzyme kinetics Exposure: Fructose substrate and ATP-dependent enzyme characterization; exact concentrations not in abstract Route: In vitro enzyme/substrate incubation Duration: Assay duration not recovered Exposure scope: Human component biochemistry Limits: Isoform unresolved; enzyme chemistry does not quantify whole-body flux after ordinary HFCS intake. Only abstract/metadata recovered for this scanned article. Reference: The purification and properties of human liver ketohexokinase. A role for ketohexokinase and fructose-bisphosphate aldolase in the metabolic production of oxalate from xylitol. (1985). https://pubmed.ncbi.nlm.nih.gov/2996495/ DOI: 10.1042/bj2300053 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

10 mM fructose with or without 30 micromolar PF-06835919

duration

Overnight

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Primary rat hepatocytes

exposure_scope

Isolated fructose / investigational drug

limitations

Cell-model transcriptional effect; not established human lipid or disease prevention.

nutrient_topic

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

organism

Primary rat hepatocytes

plain_language

PF-06835919 reduced fructose-associated nuclear ChREBP localization in primary rat hepatocytes.

primary_references

Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction. (2021). https://pubmed.ncbi.nlm.nih.gov/33667726/ DOI: 10.1016/j.molmet.2021.101196

route

In vitro exposure

tissue

ChREBP nuclear localization

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 581–591

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 · Primary rat hepatocytes · source_derived_draft · unverified_draft

## hfcs-pf-chrebp PF-06835919 reduced fructose-associated nuclear ChREBP localization in primary rat hepatocytes. Model/species: Primary rat hepatocytes Tissue: ChREBP nuclear localization Exposure: 10 mM fructose with or without 30 micromolar PF-06835919 Route: In vitro exposure Duration: Overnight Exposure scope: Isolated fructose / investigational drug Limits: Cell-model transcriptional effect; not established human lipid or disease prevention. Reference: Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction. (2021). https://pubmed.ncbi.nlm.nih.gov/33667726/ DOI: 10.1016/j.molmet.2021.101196 Access: Primary full-text methods/results and metadata inspected.

dose

PF-06835919 concentration series; 10 mM labeled fructose

duration

30 min pretreatment; 20 min fructose reaction

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Primary human hepatocytes

exposure_scope

Isolated fructose / investigational drug

limitations

Functional KHK inhibition in cells; PF-06835919 is investigational. Study sponsored/conducted by industry; pharmacological target engagement is not dietary efficacy.

nutrient_topic

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

organism

Primary human hepatocytes

plain_language

PF-06835919 inhibited labeled fructose-1-phosphate formation in primary human hepatocytes.

primary_references

Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction. (2021). https://pubmed.ncbi.nlm.nih.gov/33667726/ DOI: 10.1016/j.molmet.2021.101196

route

In vitro inhibitor pretreatment and fructose addition

tissue

Labeled fructose-1-phosphate production

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 569–579

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 · Primary human hepatocytes · source_derived_draft · unverified_draft

## hfcs-pf-hepatocytes PF-06835919 inhibited labeled fructose-1-phosphate formation in primary human hepatocytes. Model/species: Primary human hepatocytes Tissue: Labeled fructose-1-phosphate production Exposure: PF-06835919 concentration series; 10 mM labeled fructose Route: In vitro inhibitor pretreatment and fructose addition Duration: 30 min pretreatment; 20 min fructose reaction Exposure scope: Isolated fructose / investigational drug Limits: Functional KHK inhibition in cells; PF-06835919 is investigational. Study sponsored/conducted by industry; pharmacological target engagement is not dietary efficacy. Reference: Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction. (2021). https://pubmed.ncbi.nlm.nih.gov/33667726/ DOI: 10.1016/j.molmet.2021.101196 Access: Primary full-text methods/results and metadata inspected.

dose

13% w/v HFCS-55, sucrose or fructose solution versus water

duration

8 weeks

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Female rats, seven per group

exposure_scope

Direct HFCS-55 animal evidence

limitations

Hypercaloric animal setting. Expression and fatty-acid composition suggest lipogenesis but are not isotope flux measurements; differences do not establish HFCS superiority/inferiority in humans.

nutrient_topic

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

organism

Female rats, seven per group

plain_language

Rats drinking HFCS-55 had the highest hepatic triglyceride and total lipid content among the tested solutions.

primary_references

High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation. (2017). https://pubmed.ncbi.nlm.nih.gov/27768909/ DOI: 10.1016/j.jnutbio.2016.09.010

route

Oral ad libitum solution

tissue

Hepatic lipid and expression endpoints

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 425–435

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 · Female rats, seven per group · source_derived_draft · unverified_draft

## hfcs-rat-hfcs-lipid Rats drinking HFCS-55 had the highest hepatic triglyceride and total lipid content among the tested solutions. Model/species: Female rats, seven per group Tissue: Hepatic lipid and expression endpoints Exposure: 13% w/v HFCS-55, sucrose or fructose solution versus water Route: Oral ad libitum solution Duration: 8 weeks Exposure scope: Direct HFCS-55 animal evidence Limits: Hypercaloric animal setting. Expression and fatty-acid composition suggest lipogenesis but are not isotope flux measurements; differences do not establish HFCS superiority/inferiority in humans. Reference: High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation. (2017). https://pubmed.ncbi.nlm.nih.gov/27768909/ DOI: 10.1016/j.jnutbio.2016.09.010 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

400 microliters of 25% HFCS solution daily, approximately 3% of mouse daily calories

duration

8 weeks; acute bolus for ATP analysis

evidence_access

Primary full-text methods/results and metadata inspected.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Genetically Apc-deficient mice predisposed to intestinal adenomas

exposure_scope

Direct HFCS in predisposed mice

limitations

Growth of predisposed mouse tumors, not initiation of cancer in healthy humans. Total tumor number was similar in the main comparison; human-equivalent risk is unresolved.

nutrient_topic

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

organism

Genetically Apc-deficient mice predisposed to intestinal adenomas

plain_language

Restricted daily HFCS gavage increased large and high-grade intestinal tumors in Apc-deficient mice without inducing obesity.

primary_references

High-fructose corn syrup enhances intestinal tumor growth in mice. (2019). https://pubmed.ncbi.nlm.nih.gov/30898933/ DOI: 10.1126/science.aat8515

route

Oral gavage; Khk or Fasn deletion where specified

tissue

Tumor size/grade and metabolic perturbations

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 617–627

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 · Genetically Apc-deficient mice predisposed to intestinal adenomas · source_derived_draft · unverified_draft

## hfcs-tumor-growth Restricted daily HFCS gavage increased large and high-grade intestinal tumors in Apc-deficient mice without inducing obesity. Model/species: Genetically Apc-deficient mice predisposed to intestinal adenomas Tissue: Tumor size/grade and metabolic perturbations Exposure: 400 microliters of 25% HFCS solution daily, approximately 3% of mouse daily calories Route: Oral gavage; Khk or Fasn deletion where specified Duration: 8 weeks; acute bolus for ATP analysis Exposure scope: Direct HFCS in predisposed mice Limits: Growth of predisposed mouse tumors, not initiation of cancer in healthy humans. Total tumor number was similar in the main comparison; human-equivalent risk is unresolved. Reference: High-fructose corn syrup enhances intestinal tumor growth in mice. (2019). https://pubmed.ncbi.nlm.nih.gov/30898933/ DOI: 10.1126/science.aat8515 Access: Primary full-text methods/results and metadata inspected.

dose

75 mM sucrose for expressed-SI activity; 0.7 mM added glucose in brush-border kinetic experiments

duration

1 hour at 37 C for expressed-enzyme activity; kinetic series for product inhibition

evidence_access

Selected primary full-text sections inspected via indexed PMC page; local XML has abstract only.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Human SI expressed in COS-1 cells; isolated human intestinal brush border

exposure_scope

Human enzyme mechanism

limitations

Glucose feedback was measured in an enzyme preparation, not demonstrated as a whole-body blood-glucose control mechanism. Selected full-text methods/results inspected; archived PubMed/PMC XML contains abstract only.

nutrient_topic

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

organism

Human SI expressed in COS-1 cells; isolated human intestinal brush border

plain_language

Human sucrase-isomaltase hydrolyzes sucrose, releasing its glucose moiety.

primary_references

Structure-function analysis of human sucrase-isomaltase identifies key residues required for catalytic activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28522605/ DOI: 10.1074/jbc.M117.791939

route

In vitro enzyme/substrate incubation

tissue

Brush-border carbohydrate digestion

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 19–29

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 · Human SI expressed in COS-1 cells; isolated human intestinal brush border · source_derived_draft · unverified_draft

## sucrose-hydrolysis-glucose Human sucrase-isomaltase hydrolyzes sucrose, releasing its glucose moiety. Model/species: Human SI expressed in COS-1 cells; isolated human intestinal brush border Tissue: Brush-border carbohydrate digestion Exposure: 75 mM sucrose for expressed-SI activity; 0.7 mM added glucose in brush-border kinetic experiments Route: In vitro enzyme/substrate incubation Duration: 1 hour at 37 C for expressed-enzyme activity; kinetic series for product inhibition Exposure scope: Human enzyme mechanism Limits: Glucose feedback was measured in an enzyme preparation, not demonstrated as a whole-body blood-glucose control mechanism. Selected full-text methods/results inspected; archived PubMed/PMC XML contains abstract only. Reference: Structure-function analysis of human sucrase-isomaltase identifies key residues required for catalytic activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28522605/ DOI: 10.1074/jbc.M117.791939 Access: Selected primary full-text sections inspected via indexed PMC page; local XML has abstract only.