D-glucose

evidence_access

Primary abstract

experimental_model

Anaerobic batch cultures.

limitations

A substrate-preference experiment does not mean dietary glucose universally suppresses human butyrate production.

nutrient_topic

Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate

plain_language

The available carbohydrate changed which substrate microbes used first.

primary_references

Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15466518/ · DOI 10.1128/AEM.70.10.5810-5817.2004

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 70–76

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Anaerobic batch cultures. · source_derived_draft · unverified_draft

## butyrate-glucose-switch The available carbohydrate changed which substrate microbes used first. Adding glucose prevented lactate utilization by the tested lactate-to-butyrate isolates until glucose was exhausted. Model: Anaerobic batch cultures. Limitations: A substrate-preference experiment does not mean dietary glucose universally suppresses human butyrate production. Evidence access: Primary abstract Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15466518/ · DOI 10.1128/AEM.70.10.5810-5817.2004

curation_topic

thiamine · Thiamine (vitamin B1)

experimental_condition

5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Transporter abundance", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human primary proximal-tubule epithelial cells; 5-day culture

limitations

Cell culture; does not by itself establish patient-level thiamine loss.

primary_references

Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

Diabetes cascade: targeted primary-source supplement · lines 18–18

See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human primary proximal-tubule epithelial cells; 5-day culture · source_derived_draft · unverified_draft

SLC19A2 mRNA fell 76% and THTR-1 protein 77% under high glucose. Model: Human primary proximal-tubule epithelial cells; 5-day culture. Limits: Cell culture; does not by itself establish patient-level thiamine loss. Primary reference: Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

curation_topic

thiamine · Thiamine (vitamin B1)

experimental_condition

5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Transporter abundance", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human primary proximal-tubule epithelial cells; 5-day culture

limitations

Cell culture; does not by itself establish patient-level thiamine loss.

primary_references

Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

Diabetes cascade: targeted primary-source supplement · lines 21–21

See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human primary proximal-tubule epithelial cells; 5-day culture · source_derived_draft · unverified_draft

SLC19A3 mRNA fell 53% and THTR-2 protein 83% under high glucose. Model: Human primary proximal-tubule epithelial cells; 5-day culture. Limits: Cell culture; does not by itself establish patient-level thiamine loss. Primary reference: Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

curation_topic

thiamine · Thiamine (vitamin B1)

experimental_condition

5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Directional thiamine transport", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human primary proximal-tubule epithelial cells; 5-day culture

limitations

Transport assay; transporter-expression changes accompany the effect without proving exclusive mediation.

primary_references

Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

Diabetes cascade: targeted primary-source supplement · lines 24–24

See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human primary proximal-tubule epithelial cells; 5-day culture · source_derived_draft · unverified_draft

High glucose reduced apical-to-basolateral thiamine transport across proximal-tubule monolayers by 37%. Model: Human primary proximal-tubule epithelial cells; 5-day culture. Limits: Transport assay; transporter-expression changes accompany the effect without proving exclusive mediation. Primary reference: Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175

cross_nutrient

Carbohydrate metabolism regulates a potassium conductance rather than proving potassium supplementation benefit.

experimental_model

Cell-attached patch recordings in isolated rat pancreatic beta cells; glucose and metabolism perturbation.

limitations

The experiment does not establish dietary potassium control of insulin secretion.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Rat

plain_language

The glucose fuel signal reduced potassium conductance.

primary_references

[ashcroft-1984-glucose] Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells (1984). https://www.nature.com/articles/312446a0 DOI: 10.1038/312446a0

tissue_or_cell_type

Pancreatic beta cells

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 774–784

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-attached patch recordings in isolated rat pancreatic beta cells; glucose and metabolism perturbation. · source_derived_draft · unverified_draft

### k-glucose-closes-beta-channel Glucose metabolism closed resting potassium channels in cell-attached rat beta-cell recordings. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The glucose fuel signal reduced potassium conductance. organism: Rat tissue_or_cell_type: Pancreatic beta cells experimental_model: Cell-attached patch recordings in isolated rat pancreatic beta cells; glucose and metabolism perturbation. limitations: The experiment does not establish dietary potassium control of insulin secretion. cross_nutrient: Carbohydrate metabolism regulates a potassium conductance rather than proving potassium supplementation benefit. [ashcroft-1984-glucose] Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells (1984). https://www.nature.com/articles/312446a0 DOI: 10.1038/312446a0

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.

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

Adding 0.7 mM glucose partially inhibited sucrose hydrolysis in the human intestinal brush-border enzyme preparation.

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 43–53

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-glucose-feedback Adding 0.7 mM glucose partially inhibited sucrose hydrolysis in the human intestinal brush-border enzyme preparation. 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.

cross_nutrient

true

experimental_model

Mammalian GLUT cDNAs expressed in Xenopus laevis oocytes; CHO overexpression

exposure

D-glucose during heterologous-transporter DHA uptake

limitations

Not evidence that eating carbohydrate causes vitamin C deficiency; do not generalize across transporters, redox forms or tissue kinetics.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Xenopus laevis host; mammalian clones

plain_language

Glucose competed with oxidized vitamin C uptake in this laboratory transport model.

primary_references

[rumsey1997] Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. (1997). https://pubmed.ncbi.nlm.nih.gov/9228080/ DOI: 10.1074/jbc.272.30.18982

tissue_or_cell_type

Oocyte membrane

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 273–284

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mammalian GLUT cDNAs expressed in Xenopus laevis oocytes; CHO overexpression · source_derived_draft · unverified_draft

### vc-transport-glut-glucose-inhibition D-glucose inhibited GLUT1- and GLUT3-mediated DHA uptake in the oocyte expression system. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glucose competed with oxidized vitamin C uptake in this laboratory transport model. organism: Xenopus laevis host; mammalian clones tissue_or_cell_type: Oocyte membrane experimental_model: Mammalian GLUT cDNAs expressed in Xenopus laevis oocytes; CHO overexpression limitations: Not evidence that eating carbohydrate causes vitamin C deficiency; do not generalize across transporters, redox forms or tissue kinetics. exposure: D-glucose during heterologous-transporter DHA uptake cross_nutrient: true [rumsey1997] Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. (1997). https://pubmed.ncbi.nlm.nih.gov/9228080/ DOI: 10.1074/jbc.272.30.18982

cross_nutrient

true

experimental_model

Human erythroid progenitors, mature RBCs and A431 stomatin transfection

exposure

5 mM glucose with radiolabeled DHA; room-temperature uptake time courses

limitations

Published interpretation challenged by kinetic analyses that distinguish transport, intracellular reduction and sugar loading.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

One study reported that glucose did not compete with oxidized vitamin C uptake in mature red cells.

primary_references

[montelhagen2008] Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C. (2008). https://pubmed.ncbi.nlm.nih.gov/18358815/ DOI: 10.1016/j.cell.2008.01.042

tissue_or_cell_type

Mature erythrocytes

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 520–531

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythroid progenitors, mature RBCs and A431 stomatin transfection · source_derived_draft · unverified_draft

### vc-transport-rbc-glucose-noncompetition Montel-Hagen et al. reported that 5 mM glucose did not inhibit DHA accumulation in mature human erythrocytes and interpreted this as preferential DHA transport. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: One study reported that glucose did not compete with oxidized vitamin C uptake in mature red cells. organism: Homo sapiens tissue_or_cell_type: Mature erythrocytes experimental_model: Human erythroid progenitors, mature RBCs and A431 stomatin transfection limitations: Published interpretation challenged by kinetic analyses that distinguish transport, intracellular reduction and sugar loading. exposure: 5 mM glucose with radiolabeled DHA; room-temperature uptake time courses cross_nutrient: true [montelhagen2008] Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C. (2008). https://pubmed.ncbi.nlm.nih.gov/18358815/ DOI: 10.1016/j.cell.2008.01.042

cross_nutrient

true

experimental_model

Human volunteer erythrocytes ex vivo

exposure

DHA challenge with or without 5 mM glucose

limitations

Metabolic support and transporter competition are different processes; this does not imply dietary sugar supplementation is needed.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Homo sapiens

plain_language

Glucose metabolism helped sustain the reducing resources used to recycle vitamin C.

primary_references

[may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

tissue_or_cell_type

Erythrocytes

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 325–336

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteer erythrocytes ex vivo · source_derived_draft · unverified_draft

### vc-transport-rbc-glucose-support During DHA reduction by human erythrocytes, 5 mM D-glucose maintained GSH and NADH concentrations whereas NADPH still declined; without glucose all three fell. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glucose metabolism helped sustain the reducing resources used to recycle vitamin C. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human volunteer erythrocytes ex vivo limitations: Metabolic support and transporter competition are different processes; this does not imply dietary sugar supplementation is needed. exposure: DHA challenge with or without 5 mM glucose cross_nutrient: true [may2001] Mechanisms of ascorbic acid recycling in human erythrocytes. (2001). https://pubmed.ncbi.nlm.nih.gov/11687303/ DOI: 10.1016/s0304-4165(01)00188-x

evidence_span

{"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"}

experimental_model

Human SMIT2 overexpression and radiotracer uptake

exposure

Overexpression, glucose competition and insulin exposure

limitations

Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Human transporter in rat L6 myoblasts

plain_language

Glucose competed for entry without itself becoming demonstrated cargo of this transporter.

primary_references

[ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008

tissue_or_cell_type

Skeletal-muscle cell model

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 314–325

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMIT2 overexpression and radiotracer uptake · source_derived_draft · unverified_draft

### ino-smit2-glucose Glucose competed for D-chiro-inositol uptake with a reported Ki of 6.1 mM in the SMIT2 expression system, without evidence that SMIT2 transported glucose in those assays. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glucose competed for entry without itself becoming demonstrated cargo of this transporter. organism: Human transporter in rat L6 myoblasts tissue_or_cell_type: Skeletal-muscle cell model experimental_model: Human SMIT2 overexpression and radiotracer uptake limitations: Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here. exposure: Overexpression, glucose competition and insulin exposure evidence_span: {"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"} [ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008

cross_nutrient

true

evidence_location

BioC text line 21; Fig. 3B–C

experimental_model

Serum stimulation with/without glucose and Acly siRNA

exposure

Experimental serum stimulation and glucose withdrawal; no selective pantothenate deprivation.

limitations

Glucose was the experimentally varied fuel. This is not evidence of B5 deficiency; cellular acetyl-CoA sources differ by context. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Mus musculus

plain_language

Glucose supply affected histone acetylation through an acetyl-CoA-producing enzyme in this cell model.

primary_references

[b5-met-chromatin2009] ATP-citrate lyase links cellular metabolism to histone acetylation. (2009). https://pubmed.ncbi.nlm.nih.gov/19461003/ DOI: 10.1126/science.1164097

tissue_or_cell_type

Immortalized mouse embryonic fibroblasts

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1019–1031

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Serum stimulation with/without glucose and Acly siRNA · source_derived_draft · unverified_draft

### b5-met-glucose-acly-histones Serum-induced histone acetylation in immortalized mouse embryonic fibroblasts depended on glucose availability and was prevented by Acly silencing. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glucose supply affected histone acetylation through an acetyl-CoA-producing enzyme in this cell model. organism: Mus musculus tissue_or_cell_type: Immortalized mouse embryonic fibroblasts experimental_model: Serum stimulation with/without glucose and Acly siRNA limitations: Glucose was the experimentally varied fuel. This is not evidence of B5 deficiency; cellular acetyl-CoA sources differ by context. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Experimental serum stimulation and glucose withdrawal; no selective pantothenate deprivation. cross_nutrient: true evidence_location: BioC text line 21; Fig. 3B–C [b5-met-chromatin2009] ATP-citrate lyase links cellular metabolism to histone acetylation. (2009). https://pubmed.ncbi.nlm.nih.gov/19461003/ DOI: 10.1126/science.1164097

evidence_span

{"source_cache": "artifacts/sodium-research/2008213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74", "start_char": 0, "end_char": 1357, "text_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74"}

experimental_model

Family segregation and Xenopus oocyte transport assay

exposure

Disease-associated SGLT1 missense variant versus normal transporter

limitations

A genetic transporter defect is not sodium dietary deficiency; the sugar-malabsorption phenotype must not be presented as a reason to add salt.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Human SGLT1 expressed in frog oocytes

plain_language

A sodium gradient helps intestinal cells take up glucose.

primary_references

[sodium-p2008213] Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. (1991). https://pubmed.ncbi.nlm.nih.gov/2008213/ DOI: 10.1038/350354a0

tissue_or_cell_type

Intestinal brush border

transport_effect

raises Couples glucose entry to the inward sodium electrochemical gradient.

transport_pool

the enterocyte interior Couples glucose entry to the inward sodium electrochemical gradient.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 291–302

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Family segregation and Xenopus oocyte transport assay · source_derived_draft · unverified_draft

### sodium-sglt1-gradient Normal intestinal SGLT1 couples glucose entry to the inward sodium electrochemical gradient. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium gradient helps intestinal cells take up glucose. organism: Human SGLT1 expressed in frog oocytes tissue_or_cell_type: Intestinal brush border experimental_model: Family segregation and Xenopus oocyte transport assay limitations: A genetic transporter defect is not sodium dietary deficiency; the sugar-malabsorption phenotype must not be presented as a reason to add salt. exposure: Disease-associated SGLT1 missense variant versus normal transporter evidence_span: {"source_cache": "artifacts/sodium-research/2008213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74", "start_char": 0, "end_char": 1357, "text_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74"} [sodium-p2008213] Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. (1991). https://pubmed.ncbi.nlm.nih.gov/2008213/ DOI: 10.1038/350354a0

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 glucose alongside fructose.

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 53–63

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-glucose-component HFCS contains free glucose alongside fructose. 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

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

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.

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Magnesium/insulin/glucose; impaired sensitivity is distinct from absence of transport.

experimental_model

Perfused rat hindquarter.

limitations

Muscle GLUT4 abundance was similar; the experiment does not establish a single causal intermediate.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Rattus norvegicus

plain_language

The response became less sensitive rather than completely stopping.

primary_references

[mg-suarez1995] Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats (1995). https://pubmed.ncbi.nlm.nih.gov/8582534/ DOI: 10.1007/bf00401757

tissue_or_cell_type

Rat gastrocnemius receptor preparations and perfused hindquarter

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1515–1525

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused rat hindquarter. · source_derived_draft · unverified_draft

### mg-deficiency-muscle-insulin-response Mg-deficient rat muscle had lower glucose uptake at submaximal insulin; basal and maximal-insulin uptake were preserved. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response became less sensitive rather than completely stopping. organism: Rattus norvegicus tissue_or_cell_type: Rat gastrocnemius receptor preparations and perfused hindquarter experimental_model: Perfused rat hindquarter. limitations: Muscle GLUT4 abundance was similar; the experiment does not establish a single causal intermediate. cross_nutrient: Magnesium/insulin/glucose; impaired sensitivity is distinct from absence of transport. [mg-suarez1995] Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats (1995). https://pubmed.ncbi.nlm.nih.gov/8582534/ DOI: 10.1007/bf00401757

cross_nutrient

Magnesium/insulin/glucose: biochemical repletion and clinical response are separate.

experimental_model

14-person, six-week randomized crossover trial.

exposure

15 mmol/day trial exposure, not advice. Clamp M 4.6 versus 4.4 mg/kg/min; p=0.108.

limitations

Small trial and modest biochemical change; not proof of zero effect. Differs from the 2003 trial in treatment, duration and endpoint, not a fabricated scientific contradiction.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

Raising the blood magnesium value did not establish improved insulin sensitivity in this trial.

primary_references

[mg-drenthen2024] Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial (2024). https://pubmed.ncbi.nlm.nih.gov/37922013/ DOI: 10.1007/s00125-023-06029-9

tissue_or_cell_type

Human whole-body glucose clamp and blood measurements

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1564–1575

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 14-person, six-week randomized crossover trial. · source_derived_draft · unverified_draft

### mg-diabetes-clamp-trial2024 Magnesium increased serum Mg but did not significantly change the primary clamp outcome in insulin-treated adults with low serum Mg. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Raising the blood magnesium value did not establish improved insulin sensitivity in this trial. organism: Homo sapiens tissue_or_cell_type: Human whole-body glucose clamp and blood measurements experimental_model: 14-person, six-week randomized crossover trial. limitations: Small trial and modest biochemical change; not proof of zero effect. Differs from the 2003 trial in treatment, duration and endpoint, not a fabricated scientific contradiction. cross_nutrient: Magnesium/insulin/glucose: biochemical repletion and clinical response are separate. exposure: 15 mmol/day trial exposure, not advice. Clamp M 4.6 versus 4.4 mg/kg/min; p=0.108. [mg-drenthen2024] Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial (2024). https://pubmed.ncbi.nlm.nih.gov/37922013/ DOI: 10.1007/s00125-023-06029-9

cross_nutrient

Magnesium -> insulin/glucose endpoints; treatment context matters.

experimental_model

63-person, 16-week randomized trial.

exposure

Eligibility serum Mg at most 0.74 mmol/L. End-study HOMA-IR means 3.8 versus 5.0.

limitations

HOMA is a surrogate, not a clamp; renal impairment was excluded. Not proof that all diabetes responds to Mg.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

One trial found improved insulin-resistance estimates in a specific low-magnesium group.

primary_references

[mg-rodriguezmoran2003] Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial (2003). https://pubmed.ncbi.nlm.nih.gov/12663588/ DOI: 10.2337/diacare.26.4.1147

tissue_or_cell_type

Human blood-based metabolic endpoints

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1551–1562

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 63-person, 16-week randomized trial. · source_derived_draft · unverified_draft

### mg-diabetes-homa-trial2003 Magnesium treatment lowered HOMA-IR compared with placebo in hypomagnesemic adults with type 2 diabetes receiving glibenclamide. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: One trial found improved insulin-resistance estimates in a specific low-magnesium group. organism: Homo sapiens tissue_or_cell_type: Human blood-based metabolic endpoints experimental_model: 63-person, 16-week randomized trial. limitations: HOMA is a surrogate, not a clamp; renal impairment was excluded. Not proof that all diabetes responds to Mg. cross_nutrient: Magnesium -> insulin/glucose endpoints; treatment context matters. exposure: Eligibility serum Mg at most 0.74 mmol/L. End-study HOMA-IR means 3.8 versus 5.0. [mg-rodriguezmoran2003] Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial (2003). https://pubmed.ncbi.nlm.nih.gov/12663588/ DOI: 10.2337/diacare.26.4.1147

evidence_access

Primary full text

experimental_model

Mouse acute gavage and glucose-tolerance experiments.

limitations

High animal exposure; hepatic AMPK was not established as the sole cause, and human oral efficacy was not tested.

nutrient_topic

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

plain_language

Whole-body glucose responses can differ from the simple prediction that a glucose precursor must raise glucose.

primary_references

l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 288–294

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse acute gavage and glucose-tolerance experiments. · source_derived_draft · unverified_draft

## alanine-ampk-mouse-glucose Whole-body glucose responses can differ from the simple prediction that a glucose precursor must raise glucose. Acute oral alanine at roughly 1–1.5 g/kg improved glucose tolerance in the studied chow- and high-fat-fed mice; reduced AMPK activity attenuated efficacy in the tested model. Model: Mouse acute gavage and glucose-tolerance experiments. Limitations: High animal exposure; hepatic AMPK was not established as the sole cause, and human oral efficacy was not tested. Evidence access: Primary full text l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002

evidence_access

Primary abstract

experimental_model

Rat BRIN-BD11 culture, washout and rechallenge experiments.

limitations

Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred.

nutrient_topic

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

plain_language

A strong acute response need not persist after prolonged exposure.

primary_references

Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 400–406

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat BRIN-BD11 culture, washout and rechallenge experiments. · source_derived_draft · unverified_draft

## alanine-beta-chronic-desensitization A strong acute response need not persist after prolonged exposure. Prolonged alanine culture reduced subsequent acute alanine-stimulated insulin secretion by 74%, without reducing responses to glucose, KCl or ketoisocaproate; 18 hours without alanine partly restored responsiveness. Model: Rat BRIN-BD11 culture, washout and rechallenge experiments. Limitations: Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred. Evidence access: Primary abstract Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138

evidence_access

Primary abstract

experimental_model

Rat clonal beta-cell NMR experiments.

limitations

Millimolar culture exposures; normal rat islets show different responses under other conditions.

nutrient_topic

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

plain_language

Alanine changed how the cultured cell processed glucose.

primary_references

A nuclear magnetic resonance-based demonstration of substantial oxidative L-alanine metabolism and L-alanine-enhanced glucose metabolism in a clonal pancreatic beta-cell line: metabolism of L-alanine is important to the regulation of insulin secretion. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12031957/ · DOI 10.2337/diabetes.51.6.1714

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 368–374

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat clonal beta-cell NMR experiments. · source_derived_draft · unverified_draft

## alanine-beta-glucose-flux Alanine changed how the cultured cell processed glucose. Adding 10 mM alanine to 16.7 mM glucose increased glucose utilization about 2.4-fold in BRIN-BD11 cells and increased measured oxidative and nonoxidative metabolism. Model: Rat clonal beta-cell NMR experiments. Limitations: Millimolar culture exposures; normal rat islets show different responses under other conditions. Evidence access: Primary abstract A nuclear magnetic resonance-based demonstration of substantial oxidative L-alanine metabolism and L-alanine-enhanced glucose metabolism in a clonal pancreatic beta-cell line: metabolism of L-alanine is important to the regulation of insulin secretion. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12031957/ · DOI 10.2337/diabetes.51.6.1714

evidence_access

Primary abstract

experimental_model

Human arteriovenous balance study; postabsorptive state and 4–6 weeks of fasting.

limitations

Exchange measurements do not identify every intracellular reaction or prove that all released alanine becomes glucose.

nutrient_topic

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

plain_language

Muscle can send both carbon and amino nitrogen to the liver as alanine.

primary_references

Alanine: key role in gluconeogenesis. · 1970 · https://pubmed.ncbi.nlm.nih.gov/5411169/ · DOI 10.1126/science.167.3920.1003

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 16–22

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human arteriovenous balance study; postabsorptive state and 4–6 weeks of fasting. · source_derived_draft · unverified_draft

## alanine-human-forearm-liver Muscle can send both carbon and amino nitrogen to the liver as alanine. Arteriovenous measurements identified alanine as the principal amino acid released by forearm muscle and extracted by the liver in postabsorptive and prolonged-fasting subjects. Model: Human arteriovenous balance study; postabsorptive state and 4–6 weeks of fasting. Limitations: Exchange measurements do not identify every intracellular reaction or prove that all released alanine becomes glucose. Evidence access: Primary abstract Alanine: key role in gluconeogenesis. · 1970 · https://pubmed.ncbi.nlm.nih.gov/5411169/ · DOI 10.1126/science.167.3920.1003

evidence_access

Primary abstract

experimental_model

Isolated normal adult rat islets.

limitations

This setting differs from clonal cells; model and substrate conditions are retained rather than treated as an unexplained contradiction.

nutrient_topic

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

plain_language

The accompanying nutrient changed whether alanine increased insulin.

primary_references

The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 376–382

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated normal adult rat islets. · source_derived_draft · unverified_draft

## alanine-islet-leucine-combination The accompanying nutrient changed whether alanine increased insulin. Alanine augmented insulin release evoked by leucine or 2-ketoisocaproate in normal adult rat islets, while not significantly changing glucose-induced secretion. Model: Isolated normal adult rat islets. Limitations: This setting differs from clonal cells; model and substrate conditions are retained rather than treated as an unexplained contradiction. Evidence access: Primary abstract The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9

evidence_access

Primary abstract

experimental_model

Human and mouse islet perifusion; low-glucose amino-acid challenges.

limitations

Mixed-species functional observation, not a human supplementation trial; nutrient concentrations and glucose state determine interpretation.

nutrient_topic

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

plain_language

One amino acid can reduce the hormone response to another.

primary_references

Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38870025/ · DOI 10.2337/db23-1013

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 344–350

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human and mouse islet perifusion; low-glucose amino-acid challenges. · source_derived_draft · unverified_draft

## alanine-leucine-glucagon One amino acid can reduce the hormone response to another. Leucine suppressed alanine- and arginine-stimulated glucagon secretion in isolated human and mouse islets under the tested low-glucose conditions. Model: Human and mouse islet perifusion; low-glucose amino-acid challenges. Limitations: Mixed-species functional observation, not a human supplementation trial; nutrient concentrations and glucose state determine interpretation. Evidence access: Primary abstract Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38870025/ · DOI 10.2337/db23-1013

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Diabetic and lean mouse genetic experiments.

limitations

Not a demonstrated human diabetes treatment; compensatory pathways remain. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/

nutrient_topic

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

plain_language

The consequence of blocking one pathway depended on metabolic state.

primary_references

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 232–238

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

## alanine-liver-diabetes-context The consequence of blocking one pathway depended on metabolic state. Hepatic Gpt2 suppression improved hyperglycemia in db/db mice, whereas liver-specific loss in lean mice did not similarly alter ordinary blood glucose. Model: Diabetic and lean mouse genetic experiments. Limitations: Not a demonstrated human diabetes treatment; compensatory pathways remain. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/ Evidence access: Primary full text Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse liver Gpt2 genetic deletion; isotope tracing.

limitations

Does not mean GPT2 is the only route; lean knockout animals did not develop a general failure of glucose control. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/

nutrient_topic

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

plain_language

Mitochondrial transamination can feed alanine carbon into glucose.

primary_references

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 216–222

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse liver Gpt2 genetic deletion; isotope tracing. · source_derived_draft · unverified_draft

## alanine-liver-gpt2-flux Mitochondrial transamination can feed alanine carbon into glucose. Hepatocyte-specific Gpt2 deletion reduced labeled alanine contribution to glucose production in mouse hepatocyte experiments. Model: Mouse liver Gpt2 genetic deletion; isotope tracing. Limitations: Does not mean GPT2 is the only route; lean knockout animals did not develop a general failure of glucose control. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/ Evidence access: Primary full text Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

8988T, Tu8902 and MiaPaCa2 cell experiments.

limitations

Culture rescue does not establish safe dietary restriction or supplementation strategies. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf

nutrient_topic

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

plain_language

Different carbon sources were not interchangeable in the nutrient-limited culture.

primary_references

Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 168–174

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 8988T, Tu8902 and MiaPaCa2 cell experiments. · source_derived_draft · unverified_draft

## alanine-pdac-glucose-rescue Different carbon sources were not interchangeable in the nutrient-limited culture. Adding 1 mM alanine or pyruvate rescued proliferation under 0.5 mM glucose in the tested human PDAC cultures, while 1 mM lactate did not reproduce that rescue. Model: 8988T, Tu8902 and MiaPaCa2 cell experiments. Limitations: Culture rescue does not establish safe dietary restriction or supplementation strategies. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf Evidence access: Primary full text Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084

dose

Single 0, 1, 2 and 4 g leaf-powder doses

duration

Six hours

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Ten healthy adults

limitations

A null acute glucose response in healthy adults does not exclude effects during chronic use or in dysglycemia.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Ten healthy adults

plain_language

The same escalating-dose study found no difference in six-hour plasma glucose exposure after 0, 1, 2 or 4 g Moringa leaf powder.

primary_references

Moringa Oleifera Leaf Increases Insulin Secretion after Single Dose Administration: A Preliminary Study in Healthy Subjects. (2016). https://pubmed.ncbi.nlm.nih.gov/27276742/

route

Oral

tissue

Plasma glucose concentration and AUC

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 123–132

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Ten healthy adults · source_derived_draft · unverified_draft

## moringa-human-acute-glucose-null The same escalating-dose study found no difference in six-hour plasma glucose exposure after 0, 1, 2 or 4 g Moringa leaf powder. Model/species: Ten healthy adults Tissue/system: Plasma glucose concentration and AUC Exposure: Single 0, 1, 2 and 4 g leaf-powder doses Route: Oral Duration: Six hours Limits: A null acute glucose response in healthy adults does not exclude effects during chronic use or in dysglycemia. Primary reference: Moringa Oleifera Leaf Increases Insulin Secretion after Single Dose Administration: A Preliminary Study in Healthy Subjects. (2016). https://pubmed.ncbi.nlm.nih.gov/27276742/ Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Study-specific aqueous leaf extract

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Rat intestinal perfusion and glucose-fiber assay

limitations

Rat perfusion and fiber binding do not quantify post-meal glucose absorption in humans.

nutrient_topic

Moringa oleifera chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Moringa oleifera

organism

Rat intestinal perfusion and glucose-fiber assay

plain_language

The same aqueous leaf extract retarded intestinal glucose absorption in rat perfusion experiments and bound glucose in a fiber assay.

primary_references

Anti-hyperglycaemic activity of Moringa oleifera is partly mediated by carbohydrase inhibition and glucose-fibre binding. (2017). https://pubmed.ncbi.nlm.nih.gov/28336764/ DOI: 10.1042/BSR20170059

route

In situ and in vitro

tissue

Glucose absorption and binding

Moringa oleifera: mechanism of action and interactions (2026-09-20) · lines 277–286

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Rat intestinal perfusion and glucose-fiber assay · source_derived_draft · unverified_draft

## moringa-intestinal-glucose-binding The same aqueous leaf extract retarded intestinal glucose absorption in rat perfusion experiments and bound glucose in a fiber assay. Model/species: Rat intestinal perfusion and glucose-fiber assay Tissue/system: Glucose absorption and binding Exposure: Study-specific aqueous leaf extract Route: In situ and in vitro Duration: Acute Limits: Rat perfusion and fiber binding do not quantify post-meal glucose absorption in humans. Primary reference: Anti-hyperglycaemic activity of Moringa oleifera is partly mediated by carbohydrase inhibition and glucose-fibre binding. (2017). https://pubmed.ncbi.nlm.nih.gov/28336764/ DOI: 10.1042/BSR20170059 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/10440307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969", "start_char": 0, "end_char": 2141, "text_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969"}

experimental_model

Randomized double-blind comparison in 300 adults with severe cholera

exposure

Reduced-osmolarity versus then-standard WHO oral rehydration solution

limitations

Historical formulation comparison; not a current formulation recommendation. Both sodium and other solution properties changed; no isolated sodium effect.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Human

plain_language

Replacing fluid is not just replacing water: solution composition affected blood sodium.

primary_references

[sodium-p10440307] Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group. (1999). https://pubmed.ncbi.nlm.nih.gov/10440307/ DOI: 10.1016/s0140-6736(98)09332-5

tissue_or_cell_type

Intestinal fluid loss and serum sodium

trigger_kind

biomarker_context Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 1045–1056

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind comparison in 300 adults with severe cholera · source_derived_draft · unverified_draft

### sodium-ors-sodium Hyponatremia below 130 mmol/L occurred in 29/142 versus 16/150 participants receiving reduced-osmolarity versus standard ORS; affected participants were symptom-free. Condition category: biomarker_context nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing fluid is not just replacing water: solution composition affected blood sodium. organism: Human tissue_or_cell_type: Intestinal fluid loss and serum sodium experimental_model: Randomized double-blind comparison in 300 adults with severe cholera limitations: Historical formulation comparison; not a current formulation recommendation. Both sodium and other solution properties changed; no isolated sodium effect. exposure: Reduced-osmolarity versus then-standard WHO oral rehydration solution evidence_span: {"source_cache": "artifacts/sodium-research/10440307.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969", "start_char": 0, "end_char": 2141, "text_sha256": "cd7239d3f0a151f53930364ba35b974cd938a67bc4282e4b67a02e24f68e9969"} [sodium-p10440307] Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group. (1999). https://pubmed.ncbi.nlm.nih.gov/10440307/ DOI: 10.1016/s0140-6736(98)09332-5

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/2008213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74", "start_char": 0, "end_char": 1357, "text_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74"}

experimental_model

Family segregation and Xenopus oocyte transport assay

exposure

Disease-associated SGLT1 missense variant versus normal transporter

limitations

A genetic transporter defect is not sodium dietary deficiency; the sugar-malabsorption phenotype must not be presented as a reason to add salt.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Human SGLT1 expressed in frog oocytes

plain_language

The transport protein itself can be the limiting step.

primary_references

[sodium-p2008213] Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. (1991). https://pubmed.ncbi.nlm.nih.gov/2008213/ DOI: 10.1038/350354a0

tissue_or_cell_type

Intestinal brush border

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 304–315

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Family segregation and Xenopus oocyte transport assay · source_derived_draft · unverified_draft

### sodium-sglt1-loss The familial SGLT1 missense variant abolished sodium-dependent glucose transport in injected oocytes. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transport protein itself can be the limiting step. organism: Human SGLT1 expressed in frog oocytes tissue_or_cell_type: Intestinal brush border experimental_model: Family segregation and Xenopus oocyte transport assay limitations: A genetic transporter defect is not sodium dietary deficiency; the sugar-malabsorption phenotype must not be presented as a reason to add salt. exposure: Disease-associated SGLT1 missense variant versus normal transporter evidence_span: {"source_cache": "artifacts/sodium-research/2008213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74", "start_char": 0, "end_char": 1357, "text_sha256": "ba4e32dc5111895acfe9e109cf57a7e07bc3c4e07e82ad3b4f7715cfaf10af74"} [sodium-p2008213] Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. (1991). https://pubmed.ncbi.nlm.nih.gov/2008213/ DOI: 10.1038/350354a0

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/20616166.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0596ceea07c063931780bf6128a238c81622461ed65dd5b0d382f0202e1626f9", "start_char": 0, "end_char": 1704, "text_sha256": "0596ceea07c063931780bf6128a238c81622461ed65dd5b0d382f0202e1626f9"}

experimental_model

Sglt2-null mice, localization, clearance and micropuncture

exposure

Genetic Slc5a2 deletion

limitations

Renal glucose reabsorption and water output changed, but the knockout did not show the measured signs of volume depletion. Genetic deletion is not a dietary experiment.

nutrient_topic

Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium

organism

Mouse

plain_language

The early kidney tubule uses a specific sodium/glucose transporter to reclaim filtered glucose.

primary_references

[sodium-p20616166] SGLT2 mediates glucose reabsorption in the early proximal tubule. (2011). https://pubmed.ncbi.nlm.nih.gov/20616166/ DOI: 10.1681/asn.2010030246

tissue_or_cell_type

Renal early proximal tubule

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 317–328

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sglt2-null mice, localization, clearance and micropuncture · source_derived_draft · unverified_draft

### sodium-sglt2-early Early proximal glucose reabsorption was 78 ± 6% in wild-type mice and absent in Sglt2-null mice. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The early kidney tubule uses a specific sodium/glucose transporter to reclaim filtered glucose. organism: Mouse tissue_or_cell_type: Renal early proximal tubule experimental_model: Sglt2-null mice, localization, clearance and micropuncture limitations: Renal glucose reabsorption and water output changed, but the knockout did not show the measured signs of volume depletion. Genetic deletion is not a dietary experiment. exposure: Genetic Slc5a2 deletion evidence_span: {"source_cache": "artifacts/sodium-research/20616166.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0596ceea07c063931780bf6128a238c81622461ed65dd5b0d382f0202e1626f9", "start_char": 0, "end_char": 1704, "text_sha256": "0596ceea07c063931780bf6128a238c81622461ed65dd5b0d382f0202e1626f9"} [sodium-p20616166] SGLT2 mediates glucose reabsorption in the early proximal tubule. (2011). https://pubmed.ncbi.nlm.nih.gov/20616166/ DOI: 10.1681/asn.2010030246

evidence_access

Primary abstract

experimental_model

Human prostate-cancer cell experiments; xenografts also studied.

limitations

Not evidence of effective or safe diabetes treatment.

nutrient_topic

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

plain_language

Fuel handling changed in these cancer cells.

primary_references

Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30875788/ · DOI 10.3390/cancers11030364

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 308–314

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human prostate-cancer cell experiments; xenografts also studied. · source_derived_draft · unverified_draft

## cucurbitacin-d-glucose Fuel handling changed in these cancer cells. Cucurbitacin D at 0.1–1 micromolar reduced glucose uptake and lactate output in human PC3 and DU145 experiments. Model: Human prostate-cancer cell experiments; xenografts also studied. Limitations: Not evidence of effective or safe diabetes treatment. Evidence access: Primary abstract Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30875788/ · DOI 10.3390/cancers11030364

availability_state

nutrient_deficiency Imported condition classification; unverified.

curation_topic

thiamine · Thiamine (vitamin B1)

experimental_condition

5 mg/kg control diet 0 mg/kg added thiamine diet · Thiamine (vitamin B1) Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "0 mg/kg added thiamine diet", "comparator": "5 mg/kg control diet", "endpoint": "Plasma glucose", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "thiamine", "state": "0 mg/kg added thiamine diet"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Mouse dietary experiment, figure 5; 16-hour fast before sampling; n=4 per genotype/treatment

limitations

A separate dietary arm of the OCT1 paper; not a berberine exposure experiment or direct proof of human diabetes causation.

primary_references

OCT1 cardiometabolic study 2018; DOI:10.1371/journal.pbio.2002907; PMID:29659562; https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2002907

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Diabetes cascade: targeted primary-source supplement · lines 36–36

See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Mouse dietary experiment, figure 5; 16-hour fast before sampling; n=4 per genotype/treatment · source_derived_draft · unverified_draft

Wild-type mice fed thiamine-deficient diet for 10 days had higher plasma glucose, hepatic glucose and hepatic glycogen. Model: Mouse dietary experiment, figure 5; 16-hour fast before sampling; n=4 per genotype/treatment. Limits: A separate dietary arm of the OCT1 paper; not a berberine exposure experiment or direct proof of human diabetes causation. Primary reference: OCT1 cardiometabolic study 2018; DOI:10.1371/journal.pbio.2002907; PMID:29659562; https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2002907

evidence_span

{"source_cache": "artifacts/creatine-research/8944667.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb8718a42f8bcb978e6cb3ec9bed92cb32b819ec2874ed111b82ff7b1bddd270", "start_char": 0, "end_char": 1014, "text_sha256": "bb8718a42f8bcb978e6cb3ec9bed92cb32b819ec2874ed111b82ff7b1bddd270"}

experimental_model

Controlled supplementation and muscle biopsy

exposure

5 g creatine alone or followed by 93 g simple carbohydrate, four times daily for five days

limitations

Large carbohydrate exposure; increased insulin was measured, but mediation was an interpretation. Not a suggested intake regimen.

nutrient_topic

Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine

organism

24 male participants

plain_language

Carbohydrate changed creatine retention under this loading protocol.

primary_references

[creatine-p8944667] Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8944667/ DOI: 10.1152/ajpendo.1996.271.5.e821

tissue_or_cell_type

Skeletal muscle, urine and serum

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 425–436

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation and muscle biopsy · source_derived_draft · unverified_draft

### creatine-carbohydrate-retention The increase in muscle total creatine was 60% greater with carbohydrate plus creatine than with creatine alone; urinary creatine loss was lower. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Carbohydrate changed creatine retention under this loading protocol. organism: 24 male participants tissue_or_cell_type: Skeletal muscle, urine and serum experimental_model: Controlled supplementation and muscle biopsy limitations: Large carbohydrate exposure; increased insulin was measured, but mediation was an interpretation. Not a suggested intake regimen. exposure: 5 g creatine alone or followed by 93 g simple carbohydrate, four times daily for five days evidence_span: {"source_cache": "artifacts/creatine-research/8944667.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb8718a42f8bcb978e6cb3ec9bed92cb32b819ec2874ed111b82ff7b1bddd270", "start_char": 0, "end_char": 1014, "text_sha256": "bb8718a42f8bcb978e6cb3ec9bed92cb32b819ec2874ed111b82ff7b1bddd270"} [creatine-p8944667] Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8944667/ DOI: 10.1152/ajpendo.1996.271.5.e821

evidence_span

{"source_cache": "artifacts/creatine-research/20881878.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52", "start_char": 0, "end_char": 1736, "text_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52"}

experimental_model

Twelve-week randomized double-blind trial with exercise in both arms

exposure

Creatine 5 g/day plus exercise versus placebo plus exercise

limitations

Small adjunct-to-exercise trial; no replacement for diabetes treatment or isolated creatine effect without exercise is established.

nutrient_topic

Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine

organism

25 adults with type 2 diabetes

plain_language

More of the glucose transporter was located at the muscle-cell surface in this trial.

primary_references

[creatine-p20881878] Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/20881878/ DOI: 10.1249/mss.0b013e3181fcee7d

tissue_or_cell_type

Blood glucose regulation and muscle GLUT4 localization

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 997–1008

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized double-blind trial with exercise in both arms · source_derived_draft · unverified_draft

### creatine-diabetes-glut4 Creatine plus exercise increased muscle GLUT4 translocation to the sarcolemma relative to placebo plus exercise. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: More of the glucose transporter was located at the muscle-cell surface in this trial. organism: 25 adults with type 2 diabetes tissue_or_cell_type: Blood glucose regulation and muscle GLUT4 localization experimental_model: Twelve-week randomized double-blind trial with exercise in both arms limitations: Small adjunct-to-exercise trial; no replacement for diabetes treatment or isolated creatine effect without exercise is established. exposure: Creatine 5 g/day plus exercise versus placebo plus exercise evidence_span: {"source_cache": "artifacts/creatine-research/20881878.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52", "start_char": 0, "end_char": 1736, "text_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52"} [creatine-p20881878] Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/20881878/ DOI: 10.1249/mss.0b013e3181fcee7d

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B1 repletion and K/P/Mg management address different requirements.

experimental_model

Prospective cohort and individual case histories.

exposure

Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.

limitations

No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Providing vitamins did not by itself prevent every electrolyte and fluid complication.

primary_references

[b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173

tissue_or_cell_type

Whole-body clinical nutrition

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1733–1744

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective cohort and individual case histories. · source_derived_draft · unverified_draft

### b1-refeeding-vitamins-not-complete-rescue Refeeding syndrome occurred in three cohort participants; two had received vitamin B/C preparations before nutrition support. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing vitamins did not by itself prevent every electrolyte and fluid complication. organism: Homo sapiens tissue_or_cell_type: Whole-body clinical nutrition experimental_model: Prospective cohort and individual case histories. limitations: No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency. cross_nutrient: B1 repletion and K/P/Mg management address different requirements. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Six postoperative cases with severely limited oral intake.

exposure

Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.

limitations

Clinical observations; no isolated test of PDH activity or tissue-specific thiamine threshold.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Calories alone did not supply the cofactors needed to use them normally.

primary_references

[b1-nakasaki1997] Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition (1997). https://pubmed.ncbi.nlm.nih.gov/9106788/ DOI: 10.1016/s0899-9007(96)00384-x

tissue_or_cell_type

Blood/systemic metabolism

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1783–1793

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six postoperative cases with severely limited oral intake. · source_derived_draft · unverified_draft

### b1-tpn-lactate-pyruvate Six patients developed severe lactic acidosis within four weeks of vitamin-unsupplemented parenteral nutrition; lactate and pyruvate were elevated. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calories alone did not supply the cofactors needed to use them normally. organism: Homo sapiens tissue_or_cell_type: Blood/systemic metabolism experimental_model: Six postoperative cases with severely limited oral intake. limitations: Clinical observations; no isolated test of PDH activity or tissue-specific thiamine threshold. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-nakasaki1997] Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition (1997). https://pubmed.ncbi.nlm.nih.gov/9106788/ DOI: 10.1016/s0899-9007(96)00384-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested.

evidence_location

Abstract

evidence_span

declined by 50 and 75%, respectively

experimental_model

Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm.

exposure

Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices

limitations

This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon.

primary_references

[gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

tissue_or_cell_type

Brain slices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1112–1125

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. · source_derived_draft · unverified_draft

### thiamine-def-stimulated-acetylcholine-synthesis The potassium-induced increment in glucose-derived carbon-14 acetylcholine was 75% lower in deficient rat brain slices. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Thiamine disruption limited stimulated production of the choline-containing transmitter from glucose-derived carbon. organism: Rattus norvegicus tissue_or_cell_type: Brain slices experimental_model: Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. limitations: This tracer experiment did not test choline deficiency or choline supplementation; synthesis labeling is not transmitter release. evidence_location: Abstract evidence_span: declined by 50 and 75%, respectively cross_nutrient: Links thiamine-dependent carbon metabolism with synthesis of a choline-containing transmitter; no choline repletion outcome was tested. exposure: Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices [gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract

evidence_span

under resting conditions

experimental_model

Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm.

exposure

Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices

limitations

Carbon dioxide labeling measures glucose oxidation under this stimulation protocol, not whole-brain ATP directly. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

The slices could maintain resting oxidation but had less capacity to increase it when stimulated.

primary_references

[gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

tissue_or_cell_type

Brain slices

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1098–1110

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. · source_derived_draft · unverified_draft

### thiamine-def-stimulated-glucose-oxidation The potassium-induced increment in carbon-14 carbon dioxide production from labeled glucose was 50% lower in deficient rat brain slices; resting production was similar to controls. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The slices could maintain resting oxidation but had less capacity to increase it when stimulated. organism: Rattus norvegicus tissue_or_cell_type: Brain slices experimental_model: Symptomatic pyrithiamine-induced thiamine-deficient rats; brain slices assayed with uniformly carbon-14-labeled glucose at rest and during potassium stimulation; seven-day thiamine reversal arm. limitations: Carbon dioxide labeling measures glucose oxidation under this stimulation protocol, not whole-brain ATP directly. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold. evidence_location: Abstract evidence_span: under resting conditions exposure: Pyrithiamine-induced deficiency followed by potassium stimulation of rat brain slices [gibson-1984-brain-flux] Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal (1984). https://pubmed.ncbi.nlm.nih.gov/6149477/ DOI: 10.1007/BF00965667

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium depletion altered carbohydrate handling; the precise cellular link remains unmeasured.

experimental_contrast

{"combination": "single", "comparator": "Before depletion in the reported clamp study", "conditions": [{"entity_slug": "potassium", "state": "Experimentally depleted"}], "effect_direction": "decrease", "endpoint": "Clamp insulin response", "intervention": "Experimental potassium depletion"} Comparison extracted from the existing source-pinned Rowe 1980 claim (PMID 6991855); no new primary full-text access in this pass. The raw supports/positive relationship is retained independently.

experimental_model

Seven healthy young men; 7-8 days, 40 mEq K/day diet plus 60 g/day sodium polystyrene sulfonate; 2-hour hyperglycemic clamp 125 mg/dL above baseline.

limitations

Seven men; diet-plus-resin exposure. No direct beta-cell channel measurement.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Human

plain_language

Depletion impaired glucose handling alongside a smaller insulin response.

primary_references

[rowe-1980-depletion] Effect of experimental potassium deficiency on glucose and insulin metabolism (1980). https://www.sciencedirect.com/science/article/pii/0026049580900748 DOI: 10.1016/0026-0495(80)90074-8

tissue_or_cell_type

Systemic glucose/insulin response

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 834–844

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven healthy young men; 7-8 days, 40 mEq K/day diet plus 60 g/day sodium polystyrene sulfonate; 2-hour hyperglycemic clamp 125 mg/dL above baseline. · source_derived_draft · unverified_draft

### k-human-depletion-insulin Experimental depletion lowered clamp insulin response by 26% and glucose disposal by 27.4%; estimated tissue insulin sensitivity was unchanged. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Depletion impaired glucose handling alongside a smaller insulin response. organism: Human tissue_or_cell_type: Systemic glucose/insulin response experimental_model: Seven healthy young men; 7-8 days, 40 mEq K/day diet plus 60 g/day sodium polystyrene sulfonate; 2-hour hyperglycemic clamp 125 mg/dL above baseline. limitations: Seven men; diet-plus-resin exposure. No direct beta-cell channel measurement. cross_nutrient: Potassium depletion altered carbohydrate handling; the precise cellular link remains unmeasured. [rowe-1980-depletion] Effect of experimental potassium deficiency on glucose and insulin metabolism (1980). https://www.sciencedirect.com/science/article/pii/0026049580900748 DOI: 10.1016/0026-0495(80)90074-8

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Seven experimentally depleted subjects, mean deficit 326 mEq; five oral and two intravenous glucose tests, followed by repletion.

limitations

Different small subject groups, not randomized route comparison. No contradiction with a scoped clamp result.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Human

plain_language

The measured glucose effect depended on the test and was mild.

primary_references

[gorden-1973-depletion] Glucose Intolerance with Hypokalemia: Failure of Short-term Potassium Depletion in Normal Subjects to Reproduce the Glucose and Insulin Abnormalities of Clinical Hypokalemia (1973). https://diabetesjournals.org/diabetes/article-pdf/22/7/544/347377/22-7-544.pdf DOI: 10.2337/diab.22.7.544

tissue_or_cell_type

Systemic glucose regulation

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 846–855

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven experimentally depleted subjects, mean deficit 326 mEq; five oral and two intravenous glucose tests, followed by repletion. · source_derived_draft · unverified_draft

### k-human-depletion-route-boundary Five depleted subjects had impaired oral glucose tolerance; two tested intravenously did not, and insulin-resistance tests were negative. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured glucose effect depended on the test and was mild. organism: Human tissue_or_cell_type: Systemic glucose regulation experimental_model: Seven experimentally depleted subjects, mean deficit 326 mEq; five oral and two intravenous glucose tests, followed by repletion. limitations: Different small subject groups, not randomized route comparison. No contradiction with a scoped clamp result. [gorden-1973-depletion] Glucose Intolerance with Hypokalemia: Failure of Short-term Potassium Depletion in Normal Subjects to Reproduce the Glucose and Insulin Abnormalities of Clinical Hypokalemia (1973). https://diabetesjournals.org/diabetes/article-pdf/22/7/544/347377/22-7-544.pdf DOI: 10.2337/diab.22.7.544

availability_state

biomarker_context Imported condition classification; unverified.

experimental_model

Same 12-week prediabetes pilot.

limitations

Small sample and multiple endpoints; no diabetes-prevention endpoint.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Human

plain_language

Fasting glucose worsened less in the supplemented group.

primary_references

[chatterjee-2017-pilot] Effects of potassium supplements on glucose metabolism in African Americans with prediabetes: a pilot trial (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5698842/ DOI: 10.3945/ajcn.117.161570

tissue_or_cell_type

Blood

trigger_kind

biomarker_context Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 935–944

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same 12-week prediabetes pilot. · source_derived_draft · unverified_draft

### k-pilot-fasting-glucose Fasting glucose changed -1.1 versus +6.1 mg/dL with KCl versus placebo, a secondary endpoint difference (P=0.03). Condition category: biomarker_context nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Fasting glucose worsened less in the supplemented group. organism: Human tissue_or_cell_type: Blood experimental_model: Same 12-week prediabetes pilot. limitations: Small sample and multiple endpoints; no diabetes-prevention endpoint. [chatterjee-2017-pilot] Effects of potassium supplements on glucose metabolism in African Americans with prediabetes: a pilot trial (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5698842/ DOI: 10.3945/ajcn.117.161570

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

Potassium and accompanying alkali cannot be treated as an identical intervention.

experimental_model

Eleven non-acidotic normokalemic adults, 7 men/4 women, ages 47-63; double-blind placebo-controlled KCl/K-citrate 90 mEq/day, two weeks each.

limitations

Eleven subjects, short duration and surrogate estimates; no established molecular pathway or prevention effect.

nutrient_topic

Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium

organism

Human

plain_language

The accompanying anion changed the observed metabolic response.

primary_references

[conen-2016-pilot] Effects of potassium citrate or potassium chloride in patients with combined glucose intolerance: A placebo-controlled pilot study (2016). https://www.sciencedirect.com/science/article/abs/pii/S105687271630054X DOI: 10.1016/j.jdiacomp.2016.03.017

tissue_or_cell_type

Systemic glucose regulation

trigger_kind

biomarker_context Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 946–956

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eleven non-acidotic normokalemic adults, 7 men/4 women, ages 47-63; double-blind placebo-controlled KCl/K-citrate 90 mEq/day, two weeks each. · source_derived_draft · unverified_draft

### k-salt-glycemic-anion-boundary Both potassium salts improved beta-cell-function estimates; only citrate improved insulin-sensitivity estimates in this small normokalemic pilot. Condition category: biomarker_context nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The accompanying anion changed the observed metabolic response. organism: Human tissue_or_cell_type: Systemic glucose regulation experimental_model: Eleven non-acidotic normokalemic adults, 7 men/4 women, ages 47-63; double-blind placebo-controlled KCl/K-citrate 90 mEq/day, two weeks each. limitations: Eleven subjects, short duration and surrogate estimates; no established molecular pathway or prevention effect. cross_nutrient: Potassium and accompanying alkali cannot be treated as an identical intervention. [conen-2016-pilot] Effects of potassium citrate or potassium chloride in patients with combined glucose intolerance: A placebo-controlled pilot study (2016). https://www.sciencedirect.com/science/article/abs/pii/S105687271630054X DOI: 10.1016/j.jdiacomp.2016.03.017

evidence_access

Primary abstract

experimental_model

Same nine-person acute study.

limitations

No diabetes-treatment efficacy or durable metabolic benefit was tested.

nutrient_topic

Monosodium Glutamate (MSG) collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Monosodium L-glutamate

plain_language

A measured glucose effect does not by itself reveal the enzyme responsible.

primary_references

Glutamate supplementation is associated with improved glucose metabolism following carbohydrate ingestion in healthy males. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23750536/ · DOI 10.1017/S0007114513001633

Monosodium Glutamate (MSG): taste, gut sensing, exposure and cross-nutrient mechanisms (2026-09-20) · lines 58–64

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

## monosodium-glutamate-glucose-response A measured glucose effect does not by itself reveal the enzyme responsible. The MSG-plus-carbohydrate condition had lower peak serum glucose than carbohydrate alone, 5.50 versus 7.69 mmol/L. Model: Same nine-person acute study. Limitations: No diabetes-treatment efficacy or durable metabolic benefit was tested. Evidence access: Primary abstract Glutamate supplementation is associated with improved glucose metabolism following carbohydrate ingestion in healthy males. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23750536/ · DOI 10.1017/S0007114513001633

evidence_access

Primary abstract

experimental_model

Controlled human intervention; ages 33–75.

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 378–384

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

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

evidence_access

Primary abstract

experimental_model

Hamster ex vivo intestine; mitochondrial enzyme activity and morphology assays.

limitations

This potentially disruptive millimolar exposure is not proof of safe, selective glucose blocking in humans.

nutrient_topic

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

plain_language

High local exposure impaired the tissue machinery supporting absorption.

primary_references

Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w

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

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

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

evidence_access

Primary abstract

experimental_model

Hamster enzyme and membrane-vesicle controls.

limitations

Negative controls narrow the interpretation; they do not rule out every ion-transport effect.

nutrient_topic

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

plain_language

Reduced whole-tissue absorption did not identify a direct sodium-pump or brush-border transport block.

primary_references

Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7482583/ · DOI 10.1016/0378-4274(95)03391-w

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

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

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

evidence_access

Primary abstract

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

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

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

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

evidence_access

Primary full text; supplementary Figure 3 description

experimental_model

Mouse islet calcium imaging at low versus stimulatory glucose.

limitations

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

nutrient_topic

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

plain_language

The metabolic trigger still matters when a potentiator is present.

primary_references

Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 218–224

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

## stevia-low-glucose The metabolic trigger still matters when a potentiator is present. Stevioside did not elicit islet calcium signals at 3 mM glucose in the tested mouse preparation. Model: Mouse islet calcium imaging at low versus stimulatory glucose. Limitations: This does not establish zero human hypoglycemia risk under all combinations. Evidence access: Primary full text; supplementary Figure 3 description Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733

evidence_access

Primary abstract

experimental_model

Acute paired crossover; four-hour blood sampling.

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

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

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

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

evidence_access

Primary full text; Figure 3

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

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

primary_references

Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 202–208

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

## stevia-mouse-oscillations The timing of calcium signals changes as well as their presence. Stevioside increased calcium-oscillation frequency in wild-type mouse islets at 10 mM glucose; the reported concentration-response EC50 was 690 nM. Model: Mouse islets with calcium imaging; dose range 1 nM to 100 micromolar. Limitations: EC50 is an experimental response value, not a human blood target. Evidence access: Primary full text; Figure 3 Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28361903/ · DOI 10.1038/ncomms14733

evidence_access

Primary abstract

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 242–248

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

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

evidence_access

Primary abstract

experimental_model

Randomized open-label crossover; OGTT 19 hours after dosing.

limitations

Different molecule and test timing from the stevioside meal trial; not an automatic contradiction.

nutrient_topic

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

plain_language

Measurable circulating metabolites did not guarantee a glucose-lowering response.

primary_references

Pharmacokinetics of Oral Rebaudioside A in Patients with Type 2 Diabetes Mellitus and Its Effects on Glucose Homeostasis: A Placebo-Controlled Crossover Trial. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36057030/ · DOI 10.1007/s13318-022-00792-7

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

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

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

evidence_access

Primary abstract

experimental_model

Sixty-minute static incubation and islet perifusion.

limitations

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

nutrient_topic

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

plain_language

The conjugated metabolite is not necessarily biologically inactive.

primary_references

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

Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 250–256

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

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

evidence_span

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experimental_model

Acute glucose-uptake kinetics and kinase inhibitors

exposure

Minutes of berberine exposure; maximum stimulation above 40 micromolar

limitations

Single-cell model and high concentrations; kinase inhibitors are not fully selective. No inference of a matching human glucose-lowering magnitude.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Mouse L929 fibroblasts expressing GLUT1

plain_language

A transporter can move glucose differently without the cell making more transporters.

primary_references

[berberine-p21545824] Berberine acutely activates the glucose transport activity of GLUT1. (2011). https://pubmed.ncbi.nlm.nih.gov/21545824/ DOI: 10.1016/j.biochi.2011.04.013

tissue_or_cell_type

GLUT1-mediated glucose uptake

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 519–530

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute glucose-uptake kinetics and kinase inhibitors · source_derived_draft · unverified_draft

### berberine-glut1-activation Berberine acutely increased GLUT1-mediated uptake in L929 cells and decreased apparent glucose-uptake Km without changing Vmax. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter can move glucose differently without the cell making more transporters. organism: Mouse L929 fibroblasts expressing GLUT1 tissue_or_cell_type: GLUT1-mediated glucose uptake experimental_model: Acute glucose-uptake kinetics and kinase inhibitors limitations: Single-cell model and high concentrations; kinase inhibitors are not fully selective. No inference of a matching human glucose-lowering magnitude. exposure: Minutes of berberine exposure; maximum stimulation above 40 micromolar evidence_span: {"source_cache": "artifacts/berberine-research/21545824.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "18e315a501ae688fc71a7761667e58ae71fdd4b3fae19b7ef0f83889dbae2825", "start_char": 0, "end_char": 1865, "text_sha256": "18e315a501ae688fc71a7761667e58ae71fdd4b3fae19b7ef0f83889dbae2825"} [berberine-p21545824] Berberine acutely activates the glucose transport activity of GLUT1. (2011). https://pubmed.ncbi.nlm.nih.gov/21545824/ DOI: 10.1016/j.biochi.2011.04.013

evidence_span

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experimental_model

Pharmacological inhibition, siRNA and dominant-negative AMPK experiments

exposure

Berberine concentration-response; 20 micromolar in phosphorylation experiments

limitations

AMPK is not necessary for every glucose response. This does not show that all other berberine actions are AMPK-independent; cell concentrations may exceed circulating parent drug.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human HepG2 hepatocytes and mouse C2C12 myotubes

plain_language

More glycolytic use of glucose can increase lactate production; this is not a clinical lactic-acidosis incidence estimate.

primary_references

[berberine-p25072399] Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. (2014). https://pubmed.ncbi.nlm.nih.gov/25072399/ DOI: 10.1371/journal.pone.0103702

tissue_or_cell_type

Glucose consumption, lactate release and mitochondrial respiration

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 363–374

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacological inhibition, siRNA and dominant-negative AMPK experiments · source_derived_draft · unverified_draft

### berberine-glycolytic-lactate Berberine increased lactate release in HepG2 and C2C12 cells, including during AMPK-pathway blockade. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: More glycolytic use of glucose can increase lactate production; this is not a clinical lactic-acidosis incidence estimate. organism: Human HepG2 hepatocytes and mouse C2C12 myotubes tissue_or_cell_type: Glucose consumption, lactate release and mitochondrial respiration experimental_model: Pharmacological inhibition, siRNA and dominant-negative AMPK experiments limitations: AMPK is not necessary for every glucose response. This does not show that all other berberine actions are AMPK-independent; cell concentrations may exceed circulating parent drug. exposure: Berberine concentration-response; 20 micromolar in phosphorylation experiments evidence_span: {"source_cache": "artifacts/berberine-research/25072399.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a", "start_char": 0, "end_char": 1385, "text_sha256": "aa8c67580ab0a69c335873a80e94bbe418ac93b88bcad42c72e1eeb564ff828a"} [berberine-p25072399] Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. (2014). https://pubmed.ncbi.nlm.nih.gov/25072399/ DOI: 10.1371/journal.pone.0103702

evidence_access

Primary abstract

experimental_model

Fed and fasted rat liver perfusions.

limitations

High ex vivo exposure, not a demonstrated human glucose-lowering dose.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

Liver glucose output changed through more than one route.

primary_references

The actions of fisetin on glucose metabolism in the rat liver. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20084677/ · DOI 10.1002/cbf.1635

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 312–318

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Fed and fasted rat liver perfusions. · source_derived_draft · unverified_draft

## fisetin-rat-glucose-release Liver glucose output changed through more than one route. Fisetin inhibited glycogen-derived glucose release and gluconeogenesis in isolated rat liver at 200-300 micromolar. Model: Fed and fasted rat liver perfusions. Limitations: High ex vivo exposure, not a demonstrated human glucose-lowering dose. Evidence access: Primary abstract The actions of fisetin on glucose metabolism in the rat liver. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20084677/ · DOI 10.1002/cbf.1635

evidence_access

Primary abstract

experimental_model

Isolated rat adipocytes; lipogenesis EC50 about 65 micromolar.

limitations

Not a universal insulin mimic; membrane transporter activity and tissue context matter.

nutrient_topic

Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin

plain_language

Increased uptake need not mean more GLUT4 moved to the membrane.

primary_references

Insulinomimetic effects of myricetin on lipogenesis and glucose transport in rat adipocytes but not glucose transport translocation. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8619886/ · DOI 10.1016/0006-2952(95)02195-7

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 492–498

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated rat adipocytes; lipogenesis EC50 about 65 micromolar. · source_derived_draft · unverified_draft

## myricetin-adipocyte-uptake Increased uptake need not mean more GLUT4 moved to the membrane. Myricetin increased glucose uptake and lipogenesis in isolated rat adipocytes without detected insulin-receptor autophosphorylation or GLUT4 translocation. Model: Isolated rat adipocytes; lipogenesis EC50 about 65 micromolar. Limitations: Not a universal insulin mimic; membrane transporter activity and tissue context matter. Evidence access: Primary abstract Insulinomimetic effects of myricetin on lipogenesis and glucose transport in rat adipocytes but not glucose transport translocation. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8619886/ · DOI 10.1016/0006-2952(95)02195-7

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cancer-cell transporter manipulation, glucose withdrawal and metabolic assays.

limitations

Complete glucose withdrawal in culture is not ordinary fasting or dietary carbohydrate restriction.

nutrient_topic

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

plain_language

Importing more oxidized nutrient also creates more work for the reducing system.

primary_references

Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 236–242

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell transporter manipulation, glucose withdrawal and metabolic assays. · source_derived_draft · unverified_draft

## l-cysteine-cystine-nadph-demand Importing more oxidized nutrient also creates more work for the reducing system. High SLC7A11-mediated cystine uptake increased reliance on glucose and the pentose phosphate pathway; glucose deprivation depleted NADPH and promoted intracellular disulfide accumulation. Model: Human cancer-cell transporter manipulation, glucose withdrawal and metabolic assays. Limitations: Complete glucose withdrawal in culture is not ordinary fasting or dietary carbohydrate restriction. Evidence access: Primary full text Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract and primary publisher figure descriptions

experimental_model

Human cancer cultures, chemical proteomics and cell-biological assays.

limitations

Experimental deprivation; do not infer this occurs whenever blood glucose falls modestly.

nutrient_topic

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

plain_language

The damage involved cross-linked structural proteins rather than the same lipid-peroxide pathway.

primary_references

Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 252–258

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer cultures, chemical proteomics and cell-biological assays. · source_derived_draft · unverified_draft

## l-cysteine-disulfidptosis-actin The damage involved cross-linked structural proteins rather than the same lipid-peroxide pathway. Glucose starvation of SLC7A11-high human cancer cells induced abnormal disulfide bonding in actin-cytoskeleton proteins, F-actin collapse and disulfidptosis, distinct from apoptosis and ferroptosis. Model: Human cancer cultures, chemical proteomics and cell-biological assays. Limitations: Experimental deprivation; do not infer this occurs whenever blood glucose falls modestly. Evidence access: Primary abstract and primary publisher figure descriptions Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2

evidence_access

Primary abstract

experimental_model

Rat hepatocytes; 20 mM glucose; concentration/time dependence.

limitations

Isolated cells, not a diabetes treatment trial.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A carbohydrate-storage response depends on the available carbon source.

primary_references

Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 304–310

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hepatocytes; 20 mM glucose; concentration/time dependence. · source_derived_draft · unverified_draft

## lithium-glycogen-glucose A carbohydrate-storage response depends on the available carbon source. LiCl stimulated glycogen synthesis from glucose in normal and diabetic-rat hepatocytes, with increased glycogen-synthase activity ratio. Model: Rat hepatocytes; 20 mM glucose; concentration/time dependence. Limitations: Isolated cells, not a diabetes treatment trial. Evidence access: Primary abstract Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164

dose

Phlorizin sufficient to normalize blood glucose

duration

Chronic normalization interval

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Ninety-percent-pancreatectomized diabetic rats and isolated adipocytes

limitations

Restored function without restored expression points to ambient-glucose effects; it does not identify a direct phlorizin target in adipocytes.

nutrient_topic

Phlorizin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Phlorizin

organism

Ninety-percent-pancreatectomized diabetic rats and isolated adipocytes

plain_language

Phlorizin normalization of glycemia restored adipocyte insulin-stimulated glucose transport and whole-body disposal despite persistently reduced transporter protein and mRNA.

primary_references

Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression. (1991). https://pubmed.ncbi.nlm.nih.gov/1991839/ DOI: 10.1172/JCI115031

route

In vivo treatment followed by ex-vivo cells

tissue

Glucose clamps, 3-O-methylglucose transport and transporter expression

Phlorizin: mechanism of action and interactions (2026-09-20) · lines 110–119

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Ninety-percent-pancreatectomized diabetic rats and isolated adipocytes · source_derived_draft · unverified_draft

## phlorizin-adipocyte-transport-restoration Phlorizin normalization of glycemia restored adipocyte insulin-stimulated glucose transport and whole-body disposal despite persistently reduced transporter protein and mRNA. Model/species: Ninety-percent-pancreatectomized diabetic rats and isolated adipocytes Tissue/system: Glucose clamps, 3-O-methylglucose transport and transporter expression Exposure: Phlorizin sufficient to normalize blood glucose Route: In vivo treatment followed by ex-vivo cells Duration: Chronic normalization interval Limits: Restored function without restored expression points to ambient-glucose effects; it does not identify a direct phlorizin target in adipocytes. Primary reference: Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression. (1991). https://pubmed.ncbi.nlm.nih.gov/1991839/ DOI: 10.1172/JCI115031 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Chronic phlorizin by osmotic minipump

duration

4 weeks

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Adult rats with neonatal-streptozotocin-induced diabetes

limitations

The study supports reversal of glucose toxicity in this rat model, not direct insulin-receptor agonism or human use.

nutrient_topic

Phlorizin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Phlorizin

organism

Adult rats with neonatal-streptozotocin-induced diabetes

plain_language

Four weeks of phlorizin lowered hyperglycemia and normalized clamp-measured hepatic and peripheral insulin action in neonatal-streptozotocin diabetic rats without changing insulin secretion or pancreatic insulin content.

primary_references

Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: evidence for reversal following phlorizin treatment. (1990). https://pubmed.ncbi.nlm.nih.gov/2198430/ DOI: 10.1016/0026-0495(90)90120-2

route

Parenteral infusion

tissue

Euglycemic-hyperinsulinemic clamp and insulin secretion

Phlorizin: mechanism of action and interactions (2026-09-20) · lines 99–108

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Adult rats with neonatal-streptozotocin-induced diabetes · source_derived_draft · unverified_draft

## phlorizin-diabetic-rat-insulin-sensitivity Four weeks of phlorizin lowered hyperglycemia and normalized clamp-measured hepatic and peripheral insulin action in neonatal-streptozotocin diabetic rats without changing insulin secretion or pancreatic insulin content. Model/species: Adult rats with neonatal-streptozotocin-induced diabetes Tissue/system: Euglycemic-hyperinsulinemic clamp and insulin secretion Exposure: Chronic phlorizin by osmotic minipump Route: Parenteral infusion Duration: 4 weeks Limits: The study supports reversal of glucose toxicity in this rat model, not direct insulin-receptor agonism or human use. Primary reference: Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: evidence for reversal following phlorizin treatment. (1990). https://pubmed.ncbi.nlm.nih.gov/2198430/ DOI: 10.1016/0026-0495(90)90120-2 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Glucose or alpha-methylglucose with sodium and phlorizin

duration

Acute transport assay

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human SGLT2 expressed in Xenopus oocytes

limitations

Oocyte transport identifies function but does not define human oral phlorizin exposure or renal selectivity in vivo.

nutrient_topic

Phlorizin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Phlorizin

organism

Human SGLT2 expressed in Xenopus oocytes

plain_language

Human SGLT2 expressed in Xenopus oocytes transported glucose with a 1:1 sodium-to-glucose ratio and was phlorizin-sensitive.

primary_references

The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. (1994). https://pubmed.ncbi.nlm.nih.gov/8282810/ DOI: 10.1172/JCI116972

route

In vitro

tissue

Radiotracer uptake and voltage-clamp current

Phlorizin: mechanism of action and interactions (2026-09-20) · lines 11–20

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Human SGLT2 expressed in Xenopus oocytes · source_derived_draft · unverified_draft

## phlorizin-human-sglt2-identification Human SGLT2 expressed in Xenopus oocytes transported glucose with a 1:1 sodium-to-glucose ratio and was phlorizin-sensitive. Model/species: Human SGLT2 expressed in Xenopus oocytes Tissue/system: Radiotracer uptake and voltage-clamp current Exposure: Glucose or alpha-methylglucose with sodium and phlorizin Route: In vitro Duration: Acute transport assay Limits: Oocyte transport identifies function but does not define human oral phlorizin exposure or renal selectivity in vivo. Primary reference: The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. (1994). https://pubmed.ncbi.nlm.nih.gov/8282810/ DOI: 10.1172/JCI116972 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

dose

Millimolar phlorizin with or without insulin

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Isolated surviving rat diaphragm

limitations

This high-concentration extra-renal effect does not represent selective SGLT2 inhibition or typical human exposure.

nutrient_topic

Phlorizin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Phlorizin

organism

Isolated surviving rat diaphragm

plain_language

Millimolar phlorizin inhibited glucose transport in isolated rat diaphragm with and without insulin and added a smaller inhibition of glycogen synthesis.

primary_references

The combined action of insulin and phlorizin on transport and metabolism of sugars and nucleotide turnover in the isolated rat diaphragm. (1977). https://pubmed.ncbi.nlm.nih.gov/889936/ DOI: 10.1016/s0300-9084(77)80058-8

route

Ex vivo

tissue

Sugar transport, glycogen synthesis and nucleotide turnover

Phlorizin: mechanism of action and interactions (2026-09-20) · lines 121–130

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Isolated surviving rat diaphragm · source_derived_draft · unverified_draft

## phlorizin-insulin-diaphragm Millimolar phlorizin inhibited glucose transport in isolated rat diaphragm with and without insulin and added a smaller inhibition of glycogen synthesis. Model/species: Isolated surviving rat diaphragm Tissue/system: Sugar transport, glycogen synthesis and nucleotide turnover Exposure: Millimolar phlorizin with or without insulin Route: Ex vivo Duration: Acute Limits: This high-concentration extra-renal effect does not represent selective SGLT2 inhibition or typical human exposure. Primary reference: The combined action of insulin and phlorizin on transport and metabolism of sugars and nucleotide turnover in the isolated rat diaphragm. (1977). https://pubmed.ncbi.nlm.nih.gov/889936/ DOI: 10.1016/s0300-9084(77)80058-8 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Phlorizin concentration-response

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

HEK293T cells expressing human SGLT2 or SGLT1

limitations

The indexed article has an erratum notice; the exact correction was not recovered in this curation and the numerical values require rechecking before quantitative reuse.

nutrient_topic

Phlorizin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Phlorizin

organism

HEK293T cells expressing human SGLT2 or SGLT1

plain_language

Phlorizin inhibited human SGLT2 more strongly than SGLT1 in HEK293T electrophysiology, with reported Ki values of 11 and 140 nM, respectively.

primary_references

Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. (2011). https://pubmed.ncbi.nlm.nih.gov/20980548/ DOI: 10.1152/ajpcell.00388.2010

route

In vitro

tissue

Whole-cell sodium/glucose cotransport current

trigger_kind

machinery_impairment Imported condition classification; unverified.

Phlorizin: mechanism of action and interactions (2026-09-20) · lines 22–31

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · HEK293T cells expressing human SGLT2 or SGLT1 · source_derived_draft · unverified_draft

## phlorizin-sglt1-sglt2-affinity Phlorizin inhibited human SGLT2 more strongly than SGLT1 in HEK293T electrophysiology, with reported Ki values of 11 and 140 nM, respectively. Model/species: HEK293T cells expressing human SGLT2 or SGLT1 Tissue/system: Whole-cell sodium/glucose cotransport current Exposure: Phlorizin concentration-response Route: In vitro Duration: Acute Limits: The indexed article has an erratum notice; the exact correction was not recovered in this curation and the numerical values require rechecking before quantitative reuse. Primary reference: Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. (2011). https://pubmed.ncbi.nlm.nih.gov/20980548/ DOI: 10.1152/ajpcell.00388.2010 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

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

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

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, 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

Sucrose beverages also increased basal hepatic fractional fatty-acid synthesis/secretion; glucose did not in the same 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 401–411

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-sucrose-dnl Sucrose beverages also increased basal hepatic fractional fatty-acid synthesis/secretion; glucose did not in the same 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

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

50 g carbohydrate load; 200 or 50 mg acarbose

duration

Acute tolerance tests; exact sampling duration unrecovered

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Healthy human volunteers; sample size unavailable in accessed abstract

exposure_scope

Drug and nutrient interaction

limitations

Acarbose inhibits carbohydrate hydrolysis. The glucose-only comparison does not support direct blockade of glucose transport. Experimental doses are not a dosing recommendation.

nutrient_topic

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

organism

Healthy human volunteers; sample size unavailable in accessed abstract

plain_language

Acarbose 200 mg had no detected effect on the blood-glucose response to a glucose-only load.

primary_references

Scope and specificity of acarbose in slowing carbohydrate absorption in man. (1981). https://pubmed.ncbi.nlm.nih.gov/7028548/ DOI: 10.2337/diab.30.11.951

route

Oral carbohydrate and drug

tissue

Carbohydrate tolerance and breath hydrogen

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 223–233

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · Healthy human volunteers; sample size unavailable in accessed abstract · source_derived_draft · unverified_draft

## sucrose-acarbose-glucose-null Acarbose 200 mg had no detected effect on the blood-glucose response to a glucose-only load. Model/species: Healthy human volunteers; sample size unavailable in accessed abstract Tissue: Carbohydrate tolerance and breath hydrogen Exposure: 50 g carbohydrate load; 200 or 50 mg acarbose Route: Oral carbohydrate and drug Duration: Acute tolerance tests; exact sampling duration unrecovered Exposure scope: Drug and nutrient interaction Limits: Acarbose inhibits carbohydrate hydrolysis. The glucose-only comparison does not support direct blockade of glucose transport. Experimental doses are not a dosing recommendation. Reference: Scope and specificity of acarbose in slowing carbohydrate absorption in man. (1981). https://pubmed.ncbi.nlm.nih.gov/7028548/ DOI: 10.2337/diab.30.11.951 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

50 g carbohydrate load; 200 or 50 mg acarbose

duration

Acute tolerance tests; exact sampling duration unrecovered

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Healthy human volunteers; sample size unavailable in accessed abstract

exposure_scope

Drug and nutrient interaction

limitations

Acarbose inhibits carbohydrate hydrolysis. The glucose-only comparison does not support direct blockade of glucose transport. Experimental doses are not a dosing recommendation.

nutrient_topic

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

organism

Healthy human volunteers; sample size unavailable in accessed abstract

plain_language

Acarbose 200 mg reduced blood-glucose response area by 89% after a 50 g sucrose load in healthy volunteers.

primary_references

Scope and specificity of acarbose in slowing carbohydrate absorption in man. (1981). https://pubmed.ncbi.nlm.nih.gov/7028548/ DOI: 10.2337/diab.30.11.951

route

Oral carbohydrate and drug

tissue

Carbohydrate tolerance and breath hydrogen

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 199–209

Original AI-assisted source-specific sucrose curation with shared canonical claims retained by identity. Primary-study citations, negative findings, exposure details and limitations preserved. Not publisher full text. · supports · Healthy human volunteers; sample size unavailable in accessed abstract · source_derived_draft · unverified_draft

## sucrose-acarbose-glycemia Acarbose 200 mg reduced blood-glucose response area by 89% after a 50 g sucrose load in healthy volunteers. Model/species: Healthy human volunteers; sample size unavailable in accessed abstract Tissue: Carbohydrate tolerance and breath hydrogen Exposure: 50 g carbohydrate load; 200 or 50 mg acarbose Route: Oral carbohydrate and drug Duration: Acute tolerance tests; exact sampling duration unrecovered Exposure scope: Drug and nutrient interaction Limits: Acarbose inhibits carbohydrate hydrolysis. The glucose-only comparison does not support direct blockade of glucose transport. Experimental doses are not a dosing recommendation. Reference: Scope and specificity of acarbose in slowing carbohydrate absorption in man. (1981). https://pubmed.ncbi.nlm.nih.gov/7028548/ DOI: 10.2337/diab.30.11.951 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

Sucrose versus glucose growth conditions; gtfB or gtfB/gtfC deletion

duration

Biofilm maturation series; exact dose and duration not recovered from accessed abstract

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Streptococcus mutans with Streptococcus oralis and Actinomyces naeslundii; gtf mutants

exposure_scope

Sucrose-dependent oral bacterial machinery

limitations

Bacterial matrix formation and mutant phenotypes; not a clinical caries incidence trial. GtfB and GtfC have different contributions. Only primary abstract and metadata used.

nutrient_topic

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

organism

Streptococcus mutans with Streptococcus oralis and Actinomyces naeslundii; gtf mutants

plain_language

Sucrose-supported multispecies cultures formed a glucan matrix and structured microcolonies; glucose cultures did not form that matrix under the tested conditions.

primary_references

Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms. (2010). https://pubmed.ncbi.nlm.nih.gov/20233920/ DOI: 10.1128/JB.01649-09

route

In vitro bacterial culture

tissue

Biofilm on saliva-coated hydroxyapatite

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 403–413

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 · Streptococcus mutans with Streptococcus oralis and Actinomyces naeslundii; gtf mutants · source_derived_draft · unverified_draft

## sucrose-biofilm-matrix Sucrose-supported multispecies cultures formed a glucan matrix and structured microcolonies; glucose cultures did not form that matrix under the tested conditions. Model/species: Streptococcus mutans with Streptococcus oralis and Actinomyces naeslundii; gtf mutants Tissue: Biofilm on saliva-coated hydroxyapatite Exposure: Sucrose versus glucose growth conditions; gtfB or gtfB/gtfC deletion Route: In vitro bacterial culture Duration: Biofilm maturation series; exact dose and duration not recovered from accessed abstract Exposure scope: Sucrose-dependent oral bacterial machinery Limits: Bacterial matrix formation and mutant phenotypes; not a clinical caries incidence trial. GtfB and GtfC have different contributions. Only primary abstract and metadata used. Reference: Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms. (2010). https://pubmed.ncbi.nlm.nih.gov/20233920/ DOI: 10.1128/JB.01649-09 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

Sucrose or glucose 1.7 g/min, 102 g/hour, during cycling at 50% peak power

duration

3 hours

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

14 trained cyclists in crossover; four completed additional water reference trial

exposure_scope

Exercise fuel, not sedentary beverage exposure

limitations

Water reference had four participants, not all 14. Whole-body utilization is not isolated exogenous sucrose oxidation. No demonstrated sucrose advantage for liver glycogen preservation. NCT02110836; Sugar Nutrition UK sponsor listed in trial record.

nutrient_topic

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

organism

14 trained cyclists in crossover; four completed additional water reference trial

plain_language

Liver glycogen did not significantly decline during three hours of cycling with sucrose ingestion; preservation did not differ from glucose.

primary_references

Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists. (2015). https://pubmed.ncbi.nlm.nih.gov/26487008/ DOI: 10.1152/ajpendo.00376.2015

route

Oral carbohydrate during exercise

tissue

Liver and muscle glycogen by carbon-13 MRS; expired-gas substrate use

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 295–305

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 · 14 trained cyclists in crossover; four completed additional water reference trial · source_derived_draft · unverified_draft

## sucrose-exercise-liver Liver glycogen did not significantly decline during three hours of cycling with sucrose ingestion; preservation did not differ from glucose. Model/species: 14 trained cyclists in crossover; four completed additional water reference trial Tissue: Liver and muscle glycogen by carbon-13 MRS; expired-gas substrate use Exposure: Sucrose or glucose 1.7 g/min, 102 g/hour, during cycling at 50% peak power Route: Oral carbohydrate during exercise Duration: 3 hours Exposure scope: Exercise fuel, not sedentary beverage exposure Limits: Water reference had four participants, not all 14. Whole-body utilization is not isolated exogenous sucrose oxidation. No demonstrated sucrose advantage for liver glycogen preservation. NCT02110836; Sugar Nutrition UK sponsor listed in trial record. Reference: Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists. (2015). https://pubmed.ncbi.nlm.nih.gov/26487008/ DOI: 10.1152/ajpendo.00376.2015 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

Sucrose or glucose 1.7 g/min, 102 g/hour, during cycling at 50% peak power

duration

3 hours

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

14 trained cyclists in crossover; four completed additional water reference trial

exposure_scope

Exercise fuel, not sedentary beverage exposure

limitations

Water reference had four participants, not all 14. Whole-body utilization is not isolated exogenous sucrose oxidation. No demonstrated sucrose advantage for liver glycogen preservation. NCT02110836; Sugar Nutrition UK sponsor listed in trial record.

nutrient_topic

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

organism

14 trained cyclists in crossover; four completed additional water reference trial

plain_language

Muscle glycogen declined during prolonged cycling despite sucrose ingestion, as it did with glucose ingestion.

primary_references

Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists. (2015). https://pubmed.ncbi.nlm.nih.gov/26487008/ DOI: 10.1152/ajpendo.00376.2015

route

Oral carbohydrate during exercise

tissue

Liver and muscle glycogen by carbon-13 MRS; expired-gas substrate use

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 307–317

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 · 14 trained cyclists in crossover; four completed additional water reference trial · source_derived_draft · unverified_draft

## sucrose-exercise-muscle Muscle glycogen declined during prolonged cycling despite sucrose ingestion, as it did with glucose ingestion. Model/species: 14 trained cyclists in crossover; four completed additional water reference trial Tissue: Liver and muscle glycogen by carbon-13 MRS; expired-gas substrate use Exposure: Sucrose or glucose 1.7 g/min, 102 g/hour, during cycling at 50% peak power Route: Oral carbohydrate during exercise Duration: 3 hours Exposure scope: Exercise fuel, not sedentary beverage exposure Limits: Water reference had four participants, not all 14. Whole-body utilization is not isolated exogenous sucrose oxidation. No demonstrated sucrose advantage for liver glycogen preservation. NCT02110836; Sugar Nutrition UK sponsor listed in trial record. Reference: Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists. (2015). https://pubmed.ncbi.nlm.nih.gov/26487008/ DOI: 10.1152/ajpendo.00376.2015 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

dose

Sucrose or glucose 1.7 g/min, 102 g/hour, during cycling at 50% peak power

duration

3 hours

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

14 trained cyclists in crossover; four completed additional water reference trial

exposure_scope

Exercise fuel, not sedentary beverage exposure

limitations

Water reference had four participants, not all 14. Whole-body utilization is not isolated exogenous sucrose oxidation. No demonstrated sucrose advantage for liver glycogen preservation. NCT02110836; Sugar Nutrition UK sponsor listed in trial record.

nutrient_topic

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

organism

14 trained cyclists in crossover; four completed additional water reference trial

plain_language

Whole-body carbohydrate utilization during cycling was greater with sucrose than glucose, 2.03 versus 1.66 g/min.

primary_references

Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists. (2015). https://pubmed.ncbi.nlm.nih.gov/26487008/ DOI: 10.1152/ajpendo.00376.2015

route

Oral carbohydrate during exercise

tissue

Liver and muscle glycogen by carbon-13 MRS; expired-gas substrate use

Sucrose: mechanism of action and metabolic impact (2026-09-20) · lines 319–329

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 · 14 trained cyclists in crossover; four completed additional water reference trial · source_derived_draft · unverified_draft

## sucrose-exercise-utilization Whole-body carbohydrate utilization during cycling was greater with sucrose than glucose, 2.03 versus 1.66 g/min. Model/species: 14 trained cyclists in crossover; four completed additional water reference trial Tissue: Liver and muscle glycogen by carbon-13 MRS; expired-gas substrate use Exposure: Sucrose or glucose 1.7 g/min, 102 g/hour, during cycling at 50% peak power Route: Oral carbohydrate during exercise Duration: 3 hours Exposure scope: Exercise fuel, not sedentary beverage exposure Limits: Water reference had four participants, not all 14. Whole-body utilization is not isolated exogenous sucrose oxidation. No demonstrated sucrose advantage for liver glycogen preservation. NCT02110836; Sugar Nutrition UK sponsor listed in trial record. Reference: Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists. (2015). https://pubmed.ncbi.nlm.nih.gov/26487008/ DOI: 10.1152/ajpendo.00376.2015 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 abstract and primary figure descriptions

experimental_model

Proliferating-cell perturbation and tracer study, including human NSCLC models.

limitations

Substrate availability in cell models is not evidence for benefits of oral L-aspartate.

nutrient_topic

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

plain_language

Aspartate demand for building material can compete with its participation in redox transfer.

primary_references

Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Proliferating-cell perturbation and tracer study, including human NSCLC models. · source_derived_draft · unverified_draft

## l-aspartate-shuttle-aspartate-availability Aspartate demand for building material can compete with its participation in redox transfer. Increasing aspartate availability enhanced malate–aspartate shuttle use and mitochondrial metabolism of glucose-derived pyruvate in proliferating cell experiments. Model: Proliferating-cell perturbation and tracer study, including human NSCLC models. Limitations: Substrate availability in cell models is not evidence for benefits of oral L-aspartate. Evidence access: Primary abstract and primary figure descriptions Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Full text lines 107, 123–125; Fig. 4F–G; Extended Data Fig. 5G–H

experimental_model

Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts with carbon-13 glucose tracing

exposure

Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice. Carbon-13 glucose tracing followed by LC-MS.

limitations

The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Human HCI002 grafts in Mus musculus hosts

plain_language

B5 restriction also reduced the measured labeled acetyl-CoA formed from glucose in these tumors.

primary_references

[b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

tissue_or_cell_type

Orthotopic HCI002 tumor tissue

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 1117–1129

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts with carbon-13 glucose tracing · source_derived_draft · unverified_draft

### b5-met-diet-hci002-acetylcoa Pantothenate deprivation reduced the amount of glucose-derived carbon-13-labeled acetyl-CoA in HCI002 xenografts. Condition category: nutrient_deficiency nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: B5 restriction also reduced the measured labeled acetyl-CoA formed from glucose in these tumors. organism: Human HCI002 grafts in Mus musculus hosts tissue_or_cell_type: Orthotopic HCI002 tumor tissue experimental_model: Matched PA-free/control diets in NOD/Scid mice bearing orthotopic human HCI002 breast-cancer xenografts with carbon-13 glucose tracing limitations: The same paper found no significant fall in the corresponding CoA/acetyl-CoA pools in WMmix tumors. Tumor concentration and tracer labeling do not establish universal CoA depletion or a human anticancer diet; cellular composition and pool size can affect the measured label. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Diets introduced at 6 weeks of age, progressively over 4 days; typically 5 weeks on the assigned diet before implantation and continued until collection. PA absence verified by LC-MS; control was composition-matched with PA added. Control n=7, PA-free n=8 tumors from independent mice. Carbon-13 glucose tracing followed by LC-MS. cross_nutrient: true evidence_location: Full text lines 107, 123–125; Fig. 4F–G; Extended Data Fig. 5G–H [b5-met-myc2024] Vitamin B<sub>5</sub> supports MYC oncogenic metabolism and tumor progression in breast cancer. (2023). https://pubmed.ncbi.nlm.nih.gov/37946084/ DOI: 10.1038/s42255-023-00915-7

dose

(S)-6-Gingerol; dose-response, exact range not in accessed abstract

duration

Time-dependent response; exact times not in accessed abstract

evidence_access

Primary PubMed abstract.

evidence_scope

literature_reviewed; model-specific source-derived curation, not universally established human effects

experimental_model

Rat L6 skeletal muscle myotubes

limitations

Calcium/CaMKK-associated signaling does not demonstrate dietary calcium depletion or calcium-supplement synergy; no human glycemic outcome was tested.

nutrient_topic

Gingerols collection; each molecular form and experimental preparation remains explicit. · Gingerols

organism

Rat L6 skeletal muscle myotubes

plain_language

Adding (S)-6-gingerol increased glucose uptake in rat L6 myotubes.

primary_references

(S)-[6]-Gingerol enhances glucose uptake in L6 myotubes by activation of AMPK in response to [Ca2+]i. (2013). https://pubmed.ncbi.nlm.nih.gov/23958199/ DOI: 10.18433/j34g7p

route

In vitro addition

tissue

Skeletal muscle cell model

Gingerols: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 173–182

Original AI-assisted curation of thirteen primary research papers; study-specific PubMed/DOI links and limitations retained. Not publisher full text. · supports · Rat L6 skeletal muscle myotubes · source_derived_draft · unverified_draft

## gingerols-6-l6-glucose Adding (S)-6-gingerol increased glucose uptake in rat L6 myotubes. Model/species: Rat L6 skeletal muscle myotubes Tissue: Skeletal muscle cell model Exposure: (S)-6-Gingerol; dose-response, exact range not in accessed abstract Route: In vitro addition Duration: Time-dependent response; exact times not in accessed abstract Limits: Calcium/CaMKK-associated signaling does not demonstrate dietary calcium depletion or calcium-supplement synergy; no human glycemic outcome was tested. Primary reference: (S)-[6]-Gingerol enhances glucose uptake in L6 myotubes by activation of AMPK in response to [Ca2+]i. (2013). https://pubmed.ncbi.nlm.nih.gov/23958199/ DOI: 10.18433/j34g7p Access: Primary PubMed abstract.