Proposed centralized bibliography for The Fructose Model whitepaper series — 23 August 2026

This bibliography was rebuilt from the program's canonical evidence library. The frozen public bibliography was used only to identify legacy links; it was not treated as evidence that a citation was correct.

A whitepaper can properly use primary studies, systematic reviews, consensus guidance, and clearly identified hypothesis papers. The source class below tells readers what kind of support each item provides. A source can support a component of the map without proving the whole Fructose Model.

Evidence language. “Primary research” means the source reports an experiment, trial, cohort, or other original analysis. “Review and hypothesis synthesis” means it helps assemble the map but does not substitute for direct proof of a pivotal empirical claim. Product information establishes only what LIV3 currently says the product contains.

Commercial disclosure. LIV3 develops and sells SugarShield and therefore has a commercial interest in the formulation discussed in Paper 7. SugarShield itself was not used in the cited ingredient studies.

Core model

[CORE-J2023] The fructose survival hypothesis for obesity

Richard J. Johnson, Miguel A. Lanaspa, L. Gabriela Sanchez-Lozada, Dean Tolan, Takahiko Nakagawa, Takuji Ishimoto, et al. (2023). The fructose survival hypothesis for obesity. Philosophical Transactions of the Royal Society B, 378(1885).

Source class: Review or synthesis

Used in this series for: Integrative survival-pathway synthesis used to frame the unifying hypothesis

Boundary: Orientation and citation discovery

Canonical record: S017

Source link: Open source record

Mechanism and cellular energy

[MECH-P1978] Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat

R Curtis Morris Jr, Kathleen Nigon, Elizabeth B Reed (1978). Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat. Journal of Clinical Investigation, 61(1), 209-220.

Source class: Primary research

Used in this series for: Direct phosphate-depletion and adenine-nucleotide experiment

Boundary: Severe intraperitoneal fructose loading reduced phosphate ATP and total adenine nucleotides in rat liver and renal cortex; prior phosphate or adenosine loading produced tissue-specific rescue, but the design did not include washout or a later standardized challenge

Canonical record: S074

Source link: Open source record

[MECH-U2012] Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress

Miguel A Lanaspa, Laura G Sanchez-Lozada, Yea-Jin Choi, Christina Cicerchi, Mehmet Kanbay, Carlos A Roncal-Jimenez, et al. (2012). Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress. Journal of Biological Chemistry, 287(48), 40732-40744.

Source class: Primary research

Used in this series for: Urate-linked mitochondrial oxidative stress and hepatic fat mechanism

Boundary: HepG2 and mouse evidence linking fructose-derived urate with mitochondrial NOX4 redox effects and triglyceride accumulation; inhibitor off-target and conflict boundaries recorded

Canonical record: S043

Source link: Open source record

[MECH-H2012] Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes

MF Abdelmalek, M Lazo, A Horska, S Bonekamp, EW Lipkin, A Balasubramanyam, et al. (2012). Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes. Hepatology, 56(3), 952-960.

Source class: Primary research

Used in this series for: Human association between higher fructose exposure and impaired hepatic ATP recovery

Boundary: Exploratory human 31P-MRS subset for C018; full text reviewed in PMC

Canonical record: S022

Source link: Open source record

[MECH-H2016] Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: A 31P MRS study

S J Bawden, M C Stephenson, E Ciampi, K Hunter, L Marciani, I A Macdonald, et al. (2016). Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: A 31P MRS study. Clinical Nutrition, 35(3), 645-649.

Source class: Primary research

Used in this series for: Controlled human fructose-challenge study of hepatic ATP reserves

Boundary: Ten healthy men; registered study NCT02217605; publisher and registry records reviewed

Canonical record: S023

Source link: Open source record

Endogenous fructose

[ENDO-L2013] Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome

Miguel A Lanaspa, Takuji Ishimoto, Nanxing Li, Christina Cicerchi, David J Orlicky, Philip Ruzycki, et al. (2013). Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome. Nature Communications, 4, 2434.

Source class: Primary research

Used in this series for: High-glucose polyol-pathway fructose and metabolic phenotype in mice

Boundary: Wild-type KHK-A/C-null and aldose-reductase-null mice under fourteen weeks of ten-percent glucose support a hepatic endogenous-fructose contribution to selected metabolic phenotypes; an author-name correction changes Ruzicky to Ruzycki; no recovery or reserve endpoint was measured

Canonical record: S076

Source link: Open source record

[ENDO-S2018] High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism

Miguel A Lanaspa, Masanari Kuwabara, Ana Andres-Hernando, Nanxing Li, Christina Cicerchi, Thomas Jensen, et al. (2018). High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism. Proceedings of the National Academy of Sciences of the United States of America, 115(12), 3138-3143.

Source class: Primary research

Used in this series for: High-salt endogenous-fructose pathway in mice

Boundary: Mouse and adipocyte hyperosmolality evidence; salt insulin resistance retained a KHK-independent component; PMID 30224469 corrects only Nanxing Li's author name

Canonical record: S045

Source link: Open source record

[ENDO-A2025] Identification of a common ketohexokinase-dependent link driving alcohol intake and alcohol-associated liver disease in mice

Ana Andres-Hernando, David J Orlicky, Gabriela E Garcia, Esteban C Loetz, Richard Montoya, Vijay Kumar, et al. (2025). Identification of a common ketohexokinase-dependent link driving alcohol intake and alcohol-associated liver disease in mice. Nature Metabolism, 7(11), 2250-2267.

Source class: Primary research

Used in this series for: Alcohol-associated polyol-KHK activation in mouse liver and intestine

Boundary: Ethanol increased portal osmolality and liver or intestinal sorbitol fructose and pathway activity in mice; AR and global tissue-specific or pharmacologic KHK perturbations supported causal roles in alcohol preference and ALD; concentration dependence and mouse-to-human translation remain material boundaries; relevant patent and inhibitor-development conflicts disclosed

Canonical record: S-P005-021

Source link: Open source record

[ENDO-B2026] Endogenous fructose production in patients and mice with aldolase B deficiency

Amée M Buziau, Nynke Simons, Dean R Tolan, Florian Caiment, Jean L J M Scheijen, Marjo P van de Waarenburg, et al. (2026). Endogenous fructose production in patients and mice with aldolase B deficiency. Molecular Genetics and Metabolism, 149(1-2), 110219.

Source class: Primary research

Used in this series for: Human post-glucose serum-fructose response plus mouse glucose-to-F1P tracing and steatosis-null boundary

Boundary: In fourteen patients with hereditary fructose intolerance and fourteen matched controls serum fructose rose after a seventy-five-gram oral glucose challenge; mouse isotope tracing linked glucose carbon to hepatic F1P and aldose-reductase inhibition lowered hepatic fructose but did not lower intrahepatic lipid over nine days. Human glucose carbon was not isotope traced; tissue source flux magnitude KHK consequences and ordinary-diet clinical importance remain unresolved, and the mouse liver-fat null argues against endogenous fructose as the sole driver of established steatosis in this model

Canonical record: S-P005-045

Source link: Open source record

Nature and adaptation

[NAT-P2017] Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat

Thomas J Park, Jane Reznick, Bethany L Peterson, Gregory Blass, Damir Omerbasic, Nigel C Bennett, et al. (2017). Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat. Science, 356(6335), 307-311.

Source class: Primary research

Used in this series for: Fructose-supported anoxia tolerance in naked mole rats

Boundary: Supports anoxia-associated fructose-driven glycolysis in naked mole rats; does not test cancer resistance or human premalignant terrain

Canonical record: S-P005-012

Source link: Open source record

Fruit and food matrix

[FRUIT-G2024] Are all sugars equal? Role of the food source in physiological responses to sugars with an emphasis on fruit and fruit juice

Javier T Gonzalez (2024). Are all sugars equal? Role of the food source in physiological responses to sugars with an emphasis on fruit and fruit juice. European Journal of Nutrition, 63(5), 1435-1451.

Source class: Review or synthesis

Used in this series for: Human evidence synthesis on food source matrix and sugar physiology

Boundary: Review concludes that food source and matrix alter physiological responses to sugars and distinguishes evidence for whole fruit fruit juice and sugar-sweetened beverages; it synthesizes heterogeneous evidence and does not prove a fixed rank order for every person dose or endpoint

Canonical record: S-P005-033

Source link: Open source record

[FRUIT-N2024] Consumption of 100% Fruit Juice and Body Weight in Children and Adults: A Systematic Review and Meta-Analysis

Michelle Nguyen, Sarah E Jarvis, Laura Chiavaroli, Sonia Blanco Mejia, Andreea Zurbau, Tauseef A Khan, et al. (2024). Consumption of 100% Fruit Juice and Body Weight in Children and Adults: A Systematic Review and Meta-Analysis. JAMA Pediatrics, 178(3), 237-246.

Source class: Systematic review or meta-analysis

Used in this series for: Systematic review and meta-analysis of 100-percent fruit juice and body weight

Boundary: Meta-analysis found small prospective BMI gain per additional daily serving of 100-percent juice in children; adult cohorts differed by energy adjustment and adult randomized trials were null with wide uncertainty; does not establish a simple whole-fruit-to-juice causal gradient for every outcome

Canonical record: S-P005-032

Source link: Open source record

Historical context

[HIST-M1986] Sweetness and Power: The Place of Sugar in Modern History

Sidney W Mintz (1986). Sweetness and Power: The Place of Sugar in Modern History. Penguin Books, 320.

Source class: Scholarly historical synthesis

Used in this series for: Scholarly history of sugar commodification colonial production and forced labor

Boundary: Scholarly historical synthesis connecting sugar production colonial systems forced labor industrialization and the transition from luxury to everyday commodity; does not quantify modern individual exposure or establish biomedical causation

Canonical record: S-P005-037

Source link: Open source record

[HIST-USDA2025] Food Availability Per Capita Data System - Food Availability Documentation

Andrzej Blazejczyk, Linda Kantor, United States Department of Agriculture Economic Research Service (2025). Food Availability Per Capita Data System - Food Availability Documentation. USDA Economic Research Service.

Source class: Official government data documentation

Used in this series for: Official long-run caloric-sweetener availability documentation and measurement limits

Boundary: Documents annual United States caloric-sweetener availability estimates since 1941 and explicitly warns that availability can overstate ingestion and includes losses or exported ingredients; supports exposure history but not disease causation

Canonical record: S-P005-038

Source link: Open source record

Metabolic dysfunction

[MET-K2020] Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction

Ana Andres-Hernando, David J Orlicky, Masanari Kuwabara, Takuji Ishimoto, Takahiko Nakagawa, Richard J Johnson, et al. (2020). Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction. Cell Metabolism, 32(1), 117-127.e3.

Source class: Primary research

Used in this series for: Liver-versus-intestine KHK deletion and sugar-induced metabolic effects in mice

Boundary: Thirty-week male-mouse experiments separated intestinal from hepatic KHK. Intestinal deletion reduced sugar intake but lost metabolic protection when exposure was matched; liver deletion preserved intake yet protected against weight gain fatty liver adipose inflammation hyperinsulinemia hyperleptinemia and insulin resistance. Developmental deletion small groups extreme liquid sugar male-only design and investigator KHK-inhibitor patents limit transition and translation claims; no reproductive endpoints

Canonical record: S239

Source link: Open source record

[MET-K2021] Inhibition of ketohexokinase in adults with NAFLD reduces liver fat and inflammatory markers: A randomized phase 2 trial

David J Kazierad, Kristin Chidsey, Veena R Somayaji, Arthur J Bergman, Morris J Birnbaum, Roberto A Calle (2021). Inhibition of ketohexokinase in adults with NAFLD reduces liver fat and inflammatory markers: A randomized phase 2 trial. Med, 2(7), 800-813.e3.

Source class: Primary research

Used in this series for: Six-week randomized human KHK-inhibitor trial in NAFLD

Boundary: Six-week NCT03256526 KHK-inhibitor trial in 53 adults with NAFLD; high dose reduced MRI-PDFF but low dose did not; liver fat is not direct DNL or reserve evidence; Pfizer sponsored and authored

Canonical record: S050

Source link: Open source record

[MET-HFI2025] Safety and efficacy of pharmacological inhibition of ketohexokinase in hereditary fructose intolerance

Evi JC Koene, Amee M Buziau, David Cassiman, Timothy M Cox, Judith Bons, Jean LJM Scheijen, et al. (2025). Safety and efficacy of pharmacological inhibition of ketohexokinase in hereditary fructose intolerance. Journal of Clinical Investigation, 135(6), e187376.

Source class: Primary research

Used in this series for: Human KHK target engagement and acute F1P-phosphate response in hereditary fructose intolerance

Boundary: Human crossover KHK-inhibitor evidence for hepatic fructose-1-phosphate and Pi response; open PMC full text reviewed

Canonical record: S039

Source link: Open source record

[MET-F2025] LY3522348, A New Ketohexokinase Inhibitor: A First-in-Human Study in Healthy Adults

Tsuyoshi Fukuda, Brian R Thompson, Bram Brouwers, Hui-Rong Qian, Wei Wang, Bridget L Morse, et al. (2025). LY3522348, A New Ketohexokinase Inhibitor: A First-in-Human Study in Healthy Adults. Diabetes Therapy, 16(7), 1399-1415.

Source class: Primary research

Used in this series for: First-in-human study of a second KHK inhibitor

Boundary: Sixty-five healthy adults received single LY3522348 doses or up to fourteen to fifteen daily doses with fructose-challenge target engagement. No serious adverse event death or treatment-related discontinuation was reported. Women were not of childbearing potential and reproductive hormones cycles gonadal function fertility and thyroid-specific endpoints were not reported. Eli Lilly funded the study and all authors were current or former employees; most disclosed equity

Canonical record: S245

Source link: Open source record

[MET-EFG1994] Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase)

David T Bonthron, Nicola Brady, Iain A Donaldson, Beat Steinmann (1994). Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase). Human Molecular Genetics, 3(9), 1627-1631.

Source class: Primary research

Used in this series for: Family genetic evidence linking biallelic KHK variants to essential fructosuria

Boundary: All three affected siblings in one well-characterized family with essential fructosuria were compound heterozygous for KHK Gly40Arg and Ala43Thr variants absent from fifty-two unrelated controls; the paper establishes genotype-phenotype cosegregation but does not provide cardiometabolic outcomes or participant-linked modern functional assays

Canonical record: S-P001-200

Source link: Open source record

[MET-EF1994] Changes of liver metabolite concentrations in adults with disorders of fructose metabolism after intravenous fructose by 31P magnetic resonance spectroscopy

Peter Boesiger, Reto Buchli, Dieter Meier, Beat Steinmann, Rolf Gitzelmann (1994). Changes of liver metabolite concentrations in adults with disorders of fructose metabolism after intravenous fructose by 31P magnetic resonance spectroscopy. Pediatric Research, 36(4), 436-440.

Source class: Primary research

Used in this series for: Single-participant essential-fructosuria hepatic F1P ATP and phosphate challenge boundary

Boundary: After intravenous fructose one adult with essential fructosuria showed no hepatic fructose-1-phosphate ATP or inorganic-phosphate change whereas three controls showed rapid fructose-1-phosphate accumulation and ATP and phosphate drawdown; single-patient design and no genotype stated in the report prevent participant-level genotype-function linkage

Canonical record: S-P001-201

Source link: Open source record

Cardiovascular disease

[CVD-Z2008] Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells

Sergey Zharikov, Karina Krotova, Hanbo Hu, Chris Baylis, Richard J Johnson, Edward R Block, et al. (2008). Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells. American Journal of Physiology-Cell Physiology, 295(5), C1183-C1190.

Source class: Primary research

Used in this series for: Urate arginase and nitric-oxide mechanism in nonhuman vascular systems

Boundary: Urate reduced stimulated nitric-oxide and cGMP production and increased arginase activity in cultured pulmonary-artery endothelial cells and impaired vasodilation in isolated porcine arteries; nonhuman ex-vivo and cell conditions do not establish ordinary circulating urate as a cardiovascular cause in people

Canonical record: S-P005-031

Source link: Open source record

[CVD-K2012] Regulation of uric acid excretion by the kidney

Michael S Lipkowitz (2012). Regulation of uric acid excretion by the kidney. Current Rheumatology Reports, 14(2), 179-188.

Source class: Review or synthesis

Used in this series for: Review of human renal urate handling

Boundary: Reviews renal proximal-tubule urate transport and reports that renal excretion accounts for most urate elimination; does not establish fructose as the cause of impaired urate clearance or cardiovascular disease

Canonical record: S-P005-034

Source link: Open source record

[CVD-B2020] Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological genetic and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel

Jan Borén, M John Chapman, Ronald M Krauss, Chris J Packard, Jacob F Bentzon, Christoph J Binder, et al. (2020). Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological genetic and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal, 41(24), 2313-2330.

Source class: Consensus statement

Used in this series for: Consensus background for LDL-containing apoB particle causality in atherosclerosis

Boundary: European Atherosclerosis Society consensus integrates pathophysiologic genetic epidemiologic and therapeutic evidence that LDL-containing apoB particles are causal in atherosclerotic cardiovascular disease; consensus synthesis supports the established particle mechanism but does not implicate fructose or KHK as its exclusive upstream cause

Canonical record: S-P005-043

Source link: Open source record

[CVD-A2013] Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses

Nancy J Aburto, Sara Hanson, Hialy Gutierrez, Lee Hooper, Paul Elliott, Francesco P Cappuccio (2013). Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ, 346, f1378.

Source class: Systematic review or meta-analysis

Used in this series for: Systematic-review boundary for potassium intake and blood-pressure support

Boundary: Meta-analysis of twenty-two randomized trials found increased potassium intake lowered blood pressure in adults with hypertension but not normotensive adults; cohort synthesis associated higher intake with lower stroke risk while cardiovascular and coronary-disease associations were nonsignificant; conclusions do not apply without caution to impaired renal potassium handling and do not establish KHK mediation

Canonical record: S-P005-044

Source link: Open source record

[CVD-R2010] Mitochondrial reserve capacity in endothelial cells: The impact of nitric oxide and reactive oxygen species

Brian P Dranka, Bradford G Hill, Victor M Darley-Usmar (2010). Mitochondrial reserve capacity in endothelial cells: The impact of nitric oxide and reactive oxygen species. Free Radical Biology and Medicine, 48(7), 905-914.

Source class: Primary research

Used in this series for: Endothelial mitochondrial reserve and redox-nitric-oxide interaction

Boundary: Bovine endothelial-cell extracellular-flux study; nonlethal NO or oxidant exposure reduced FCCP-defined reserve with little basal-OCR change; combined stress linked irreversible reserve loss to cell death

Canonical record: S051

Source link: Open source record

Neurodegeneration

[NEURO-H2017] The human brain produces fructose from glucose

Janice J Hwang, Lihong Jiang, Muhammad Hamza, Feng Dai, Renata Belfort-DeAguiar, Gary Cline, et al. (2017). The human brain produces fructose from glucose. JCI Insight, 2(4), e90508.

Source class: Primary research

Used in this series for: Controlled human evidence that brain fructose can rise from glucose

Boundary: Eight healthy adults underwent a four-hour hyperglycemic clamp with proton MRS; intracerebral fructose signal rose with brain glucose rather than plasma fructose, but spectral overlap cannot exclude some sorbitol contribution and no KHK flux energetic outcome or recovery was measured

Canonical record: S073

Source link: Open source record

[NEURO-LI2023] Ketohexokinase-dependent metabolism of cerebral endogenous fructose in microglia drives diabetes-associated cognitive dysfunction

Yansong Li, Tao Jiang, Mengyu Du, Shuxuan He, Ning Huang, Bo Cheng, et al. (2023). Ketohexokinase-dependent metabolism of cerebral endogenous fructose in microglia drives diabetes-associated cognitive dysfunction. Experimental & Molecular Medicine, 55(11), 2417-2432.

Source class: Primary research

Used in this series for: Hippocampal KHK perturbation in a diabetic mouse cognition model

Boundary: db/db mouse hippocampus and microglia evidence for endogenous fructose KHK NOX4 redox and mitochondrial effects; diabetes model does not isolate hyperglycemia from obesity or leptin-receptor loss

Canonical record: S048

Source link: Open source record

[NEURO-J2020] Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer's Disease

Richard J Johnson, Fernando Gomez-Pinilla, Maria Nagel, Takahiko Nakagawa, Bernardo Rodriguez-Iturbe, Laura G Sanchez-Lozada, et al. (2020). Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer's Disease. Frontiers in Aging Neuroscience, 12, 560865.

Source class: Review and hypothesis synthesis

Used in this series for: Johnson cerebral-fructose Alzheimer hypothesis architecture

Boundary: Proposes cerebral fructose or KHK as an initiating energy-lowering pathway linking foraging food intake mitochondrial dysfunction insulin resistance neuroinflammation and Alzheimer pathology; integrative hypothesis rather than direct human KHK perturbation; multiple authors disclosed equity in fructose-metabolism inhibitor development

Canonical record: S-P005-022

Source link: Open source record

[NEURO-J2023] Could Alzheimer's disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?

Richard J Johnson, Dean R Tolan, Dale Bredesen, Maria Nagel, Laura G Sánchez-Lozada, Mehdi Fini, et al. (2023). Could Alzheimer's disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?. The American Journal of Clinical Nutrition, 117(3), 455-466.

Source class: Review and hypothesis synthesis

Used in this series for: Updated cerebral energy-triage and Alzheimer synthesis

Boundary: Extends the proposed fructose-triggered survival-state model to cerebral glucose hypometabolism mitochondrial dysfunction and neuroinflammation; valuable whitepaper synthesis but does not directly establish human brain KHK-mediated energy triage or treatment benefit

Canonical record: S-P005-023

Source link: Open source record

[NEURO-P2013] Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways

Kathleen A Page, Owen Chan, Jagriti Arora, Renata Belfort-Deaguiar, James Dzuira, Brian Roehmholdt, et al. (2013). Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. JAMA, 309(1), 63-70.

Source class: Primary research

Used in this series for: Acute human fructose-versus-glucose appetite and brain-response crossover

Boundary: Twenty-person acute crossover found greater hypothalamic CBF suppression and satiety after glucose than fructose; corrected whole-brain direct comparisons were null and the design did not manipulate or measure cerebral KHK

Canonical record: S-P005-024

Source link: Open source record

[NEURO-L2015] Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards

Shan Luo, John R Monterosso, Kayan Sarpelleh, Kathleen A Page (2015). Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards. Proceedings of the National Academy of Sciences of the United States of America, 112(20), 6509-6514.

Source class: Primary research

Used in this series for: Acute human food-cue and immediate-reward crossover

Boundary: Twenty-four-person acute crossover found greater food-cue reactivity hunger desire and willingness to choose immediate food after fructose than glucose; acute beverage contrast cannot establish chronic cognition Alzheimer risk or KHK mediation

Canonical record: S-P005-025

Source link: Open source record

[NEURO-O2017] Specific regions of the brain are capable of fructose metabolism

Sarah A Oppelt, Wanming Zhang, Dean R Tolan (2017). Specific regions of the brain are capable of fructose metabolism. Brain Research, 1657, 312-322.

Source class: Primary research

Used in this series for: Regional mapping of brain fructose-handling capacity

Boundary: Adult-mouse in-situ hybridization localized Khk Aldoc Slc2a5 and Slc2a9 mainly to cerebellum hippocampus cortex and olfactory bulb and dissected regions metabolized labeled fructose; hypothalamus and Kiss1 cells were not resolved and regional enzyme or oxidation assays cannot establish neuron-autonomous KHK flux

Canonical record: S150

Source link: Open source record

[NEURO-X2016] Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: metabolic basis for dementia

Jingshu Xu, Paul Begley, Stephanie J Church, Stefano Patassini, Selina McHarg, Nina Kureishy, et al. (2016). Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: metabolic basis for dementia. Scientific Reports, 6, 27524.

Source class: Primary research

Used in this series for: Postmortem Alzheimer brain glucose sorbitol and fructose pattern

Boundary: Nine Alzheimer cases and nine controls showed higher glucose sorbitol and fructose across sampled postmortem brain regions; small cross-sectional tissue study cannot establish temporal order KHK mediation disease initiation or treatment effect

Canonical record: S-P005-042

Source link: Open source record

[NEURO-B2026] A Unifying Theory of Alzheimer's and Other Neurodegenerative Diseases

Dale E Bredesen (2026). A Unifying Theory of Alzheimer's and Other Neurodegenerative Diseases. Journal of Advanced Therapeutic Science, 1(1), 20-51.

Source class: Review or synthesis

Used in this series for: Network support-to-demand theory of neurodegenerative insufficiency; hypothesis architecture only

Boundary: Proposes the Pr2 network-insufficiency theory in which energetic trophic and neurotransmitter supply can fall below demand from inflammation toxicity and stress; useful hypothesis architecture but no new empirical dataset no fructose or KHK analysis and no direct validation of the Fructose Model; Bredesen coauthored the 2023 cerebral-fructose hypothesis already registered as S-P005-023; abstract and body are inconsistent about whether a randomized trial is completed or ongoing

Canonical record: S-P005-046

Source link: Open source record

Cancer

[CANC-N2020] Fructose contributes to the Warburg effect for cancer growth

Takahiko Nakagawa, Miguel A Lanaspa, Inigo San Millan, Mehdi Fini, Christopher J Rivard, Laura G Sanchez-Lozada, et al. (2020). Fructose contributes to the Warburg effect for cancer growth. Cancer and Metabolism, 8(1), 16.

Source class: Review and hypothesis synthesis

Used in this series for: Review and hypothesis linking fructose metabolism to Warburg-like cancer energetics

Boundary: Relevant whitepaper synthesis and discovery source; may support hypothesis framing but not substitute for primary proof of universal mitochondrial suppression mutagenesis hypoxic survival or clinical KHK targeting

Canonical record: S-P005-013

Source link: Open source record

[CANC-F2024] Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer

Ronald Fowle-Grider, Joe L Rowles III, Isabel Shen, Yahui Wang, Michaela Schwaiger-Haber, Alden J Dunham, et al. (2024). Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer. Nature, 636(8043), 737-744.

Source class: Primary research

Used in this series for: Liver-KHK-dependent lipid transfer supporting selected mouse tumors

Boundary: Dietary fructose enhanced melanoma breast and cervical tumor growth in mouse models through liver KHK-dependent circulating LPC production; tumor cells did not readily catabolize fructose; pharmacologic KHK inhibition prevented the fructose-mediated growth effect in vivo but no human intervention was tested; archived BioC fetch error retained

Canonical record: S-P005-016

Source link: Open source record

[CANC-G2023] Genetic ablation of ketohexokinase C isoform impairs pancreatic cancer development

Ilaria Guccini, Guanghui Tang, Trang Thuy To, Laura Di Rito, Solange Le Blanc, Oliver Strobel, et al. (2023). Genetic ablation of ketohexokinase C isoform impairs pancreatic cancer development. iScience, 26(8), 107368.

Source class: Primary research

Used in this series for: KHK-C ablation in pancreatic-cancer models

Boundary: Pancreatic KhkC ablation delayed KPC-driven PDAC and extended survival even without a high-fructose diet while altering KRAS-MAPK and mTOR-linked signaling; preclinical genetic program with no human therapeutic intervention

Canonical record: S-P005-017

Source link: Open source record

[CANC-S2022] GLUT5-KHK axis-mediated fructose metabolism drives proliferation and chemotherapy resistance of colorectal cancer

Zhiyong Shen, Zhenkang Li, Yuechen Liu, Yongsheng Li, Xiaochuang Feng, Yizhi Zhan, et al. (2022). GLUT5-KHK axis-mediated fructose metabolism drives proliferation and chemotherapy resistance of colorectal cancer. Cancer Letters, 534, 215617.

Source class: Primary research

Used in this series for: GLUT5-KHK growth and chemotherapy-resistance phenotype in colorectal-cancer models

Boundary: GLUT5-KHK perturbation reduced colorectal-cancer growth and fructose-related chemotherapy resistance in reported preclinical systems; abstract-level audit and no human intervention limit therapeutic translation

Canonical record: S-P005-018

Source link: Open source record

[CANC-T2022] Ketohexokinase-mediated fructose metabolism is lost in hepatocellular carcinoma and can be leveraged for metabolic imaging

Sui Seng Tee, Nathaniel Kim, Quinlan Cullen, Roozbeh Eskandari, Arsen Mamakhanyan, Rami M Srouji, et al. (2022). Ketohexokinase-mediated fructose metabolism is lost in hepatocellular carcinoma and can be leveraged for metabolic imaging. Science Advances, 8(14), eabm7985.

Source class: Primary research

Used in this series for: Loss and forced restoration of KHK-C fructolysis in hepatocellular-carcinoma models

Boundary: HCC tissues and models showed reduced fructose-handling proteins and F1P production; forced KHK-C with fructose reduced ATP and selected against cells in reported systems; no clinical therapy or pan-cancer metabolic trap

Canonical record: S-P005-003

Source link: Open source record

[CANC-H2026] Fructose 1-phosphate inhibits mannose phosphate isomerase to suppress hepatocellular carcinogenesis

Yongqiang Wang, Xiangyang Zhang, Ningning Wang, Huimin Jiang, Ningning Liang, Chenxi Du, et al. (2026). Fructose 1-phosphate inhibits mannose phosphate isomerase to suppress hepatocellular carcinogenesis. Signal Transduction and Targeted Therapy, 11(1), 195.

Source class: Primary research

Used in this series for: F1P-MPI vulnerability in defined ALDOB-deficient hepatocellular-carcinoma models

Boundary: Human HCC profiling plus cell biochemical and genetically defined mouse studies support an ALDOB-deficient retained-KHK F1P-MPI liability; 10-percent fructose mouse exposure and no human intervention preclude treatment advice or broad protective claims

Canonical record: S-P005-001

Source link: Open source record

[CANC-O2026] The chemotherapy-induced senescence-associated secretome promotes cell detachment and metastatic dissemination through metabolic reprogramming

Aidan R Cole, Raquel Buj, Apoorva Uboveja, Evan Levasseur, Alexander Tom, Hui Wang, et al. (2026). The chemotherapy-induced senescence-associated secretome promotes cell detachment and metastatic dissemination through metabolic reprogramming. Nature Aging, 6, 1647-1666.

Source class: Primary research

Used in this series for: KHK-dependent dissemination after chemotherapy-induced senescence in ovarian-cancer models

Boundary: Final Nature Aging version published 2026-07-30; PMID 40832218 and PMCID PMC12363692 identify the bioRxiv preprint and are not attached here; supports defined HGSOC detachment and dissemination requiring KHK and complex I but not clinical dietary advice or polyol-pathway origin of secreted fructose

Canonical record: S-P005-002

Source link: Open source record

[CANC-A2016] Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential

Wen-Lian Chen, Yue-Ying Wang, Aihua Zhao, Li Xia, Guoxiang Xie, Mingming Su, et al. (2016). Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential. Cancer Cell, 30(5), 779-791.

Source class: Primary research

Used in this series for: SLC2A5-mediated fructose use in acute-myeloid-leukemia models

Boundary: Supports GLUT5-mediated fructose utilization in defined AML models and outcome associations; does not establish expression or dependence across many tumors

Canonical record: S-P005-007

Source link: Open source record

[CANC-L2018] Fructose fuels lung adenocarcinoma through GLUT5

Yuanyuan Weng, Jin Zhu, Zhenhong Chen, Jingqi Fu, Feng Zhang (2018). Fructose fuels lung adenocarcinoma through GLUT5. Cell Death and Disease, 9(5), 557.

Source class: Primary research

Used in this series for: GLUT5-dependent fructose phenotype in lung-adenocarcinoma models

Boundary: Supports GLUT5-dependent fructose-associated proliferation migration invasion and xenograft outcomes in reported lung-adenocarcinoma models; small preclinical program and no human intervention

Canonical record: S-P005-008

Source link: Open source record

[CANC-M2018] Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis

Pengcheng Bu, Kai-Yuan Chen, Kun Xiang, Christelle Johnson, Scott B Crown, Nikolai Rakhilin, et al. (2018). Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis. Cell Metabolism, 27(6), 1249-1262.e4.

Source class: Primary research

Used in this series for: ALDOB-dependent fructose use in colorectal-cancer liver metastasis

Boundary: Supports ALDOB upregulation and fructose use in colorectal-cancer liver metastasis with genetic and dietary perturbation; established metastatic context does not demonstrate premalignant genomic fragility

Canonical record: S-P005-006

Source link: Open source record

[CANC-I2019] High-fructose corn syrup enhances intestinal tumor growth in mice

Marcus D Goncalves, Changyuan Lu, Jordan Tutnauer, Travis E Hartman, Seo-Kyoung Hwang, Charles J Murphy, et al. (2019). High-fructose corn syrup enhances intestinal tumor growth in mice. Science, 363(6433), 1345-1349.

Source class: Primary research

Used in this series for: HFCS-associated intestinal-tumor growth in APC-deficient mice

Boundary: HFCS increased tumor size and grade in APC-deficient mice without obesity and supported glycolysis and fatty-acid synthesis; did not test metastasis or establish a general human-cancer effect

Canonical record: S-P005-010

Source link: Open source record

[CANC-WCRF2025] Limit sugar-sweetened drinks: recommendation evidence

World Cancer Research Fund (2025). Limit sugar-sweetened drinks: recommendation evidence. World Cancer Research Fund.

Source class: Consensus or public-health guidance

Used in this series for: Consensus prevention guidance for limiting sugar-sweetened beverages

Boundary: WCRF recommends limiting sugar-sweetened drinks chiefly through their contribution to excess energy intake overweight and obesity; it does not state that sugar uniquely feeds tumors or that restriction treats established cancer

Canonical record: S-P005-039

Source link: Open source record

[CANC-NCI2026] Common Cancer Myths and Misconceptions

National Cancer Institute (2026). Common Cancer Myths and Misconceptions. National Cancer Institute.

Source class: Consensus or public-health guidance

Used in this series for: Clinical boundary against presenting sugar restriction as tumor starvation or treatment

Boundary: NCI states that no studies show eating sugar makes cancer worse or stopping sugar makes it shrink while recognizing indirect obesity-related pathways; guidance bounds dietary and clinical implications

Canonical record: S-P005-040

Source link: Open source record

[CANC-VAX2024] Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised phase 2b study

Jeffrey S Weber, Matteo S Carlino, Adnan Khattak, Tarek Meniawy, George Ansstas, Matthew H Taylor, et al. (2024). Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised phase 2b study. Lancet, 403(10427), 632-644.

Source class: Primary research

Used in this series for: Randomized phase 2b individualized neoantigen therapy plus pembrolizumab in resected melanoma

Boundary: In 157 patients with completely resected high-risk melanoma individualized mRNA neoantigen therapy plus pembrolizumab produced a favorable recurrence-free-survival signal versus pembrolizumab alone; the primary analysis was a moderately sized open-label phase 2b study with a 95-percent confidence interval crossing 1 and two-sided P=0.053 and was funded by Moderna and Merck

Canonical record: S-P005-047

Source link: Open source record

[CANC-PDAC2023] Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer

Luis A Rojas, Zachary Sethna, Kevin C Soares, Cristina Olcese, Nan Pang, Erin Patterson, et al. (2023). Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature, 618(7963), 144-150.

Source class: Primary research

Used in this series for: Phase I personalized RNA neoantigen vaccination in resected pancreatic cancer

Boundary: Phase I adjuvant combination study in resected pancreatic cancer induced high-magnitude neoantigen-specific T cells in 8 of 16 vaccinated patients and response correlated with delayed recurrence; small nonrandomized multimodal treatment prevents attributing clinical outcome to vaccine alone

Canonical record: S-P005-048

Source link: Open source record

[CANC-METIMM2015] Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression

Chih-Hao Chang, Jing Qiu, David O'Sullivan, Michael D Buck, Takuro Noguchi, Jonathan D Curtis, et al. (2015). Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell, 162(6), 1229-1241.

Source class: Primary research

Used in this series for: Preclinical tumor glucose competition restricting T-cell function

Boundary: Mouse sarcoma experiments showed tumor glucose consumption restricted T-cell glycolysis and interferon-gamma output and that checkpoint blockade restored intratumoral glucose and T-cell function; does not test human patients fructose KHK cancer vaccines or clinical efficacy

Canonical record: S-P005-050

Source link: Open source record

Hormonal dysfunction

[HORM-C2008] Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake

Seung Hun Cha, Michael Wolfgang, Yuka Tokutake, Shigeru Chohnan, M Daniel Lane (2008). Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake. Proceedings of the National Academy of Sciences of the United States of America, 105(44), 16871-16875.

Source class: Primary research

Used in this series for: Central fructose-versus-glucose feeding signal in mice

Boundary: Acute intracerebroventricular fructose in fasted mice lowered whole-hypothalamus ATP and malonyl-CoA increased AMPK signaling and food intake relative to glucose; high-dose central delivery whole-hypothalamus assays and no KHK perturbation or Kiss1 measurement prevent endogenous or cell-specific inference

Canonical record: S142

Source link: Open source record

[HORM-P2025] Fructose-induced synaptic and neuronal adaptations at neuropeptide Y/agouti-related peptide neurons

Mikayla A Payant, Aditi S Sankhe, Persephone A Miller, Sarah S Vieira, Yasmina Dumiaty, Jenny Phy-Lim, et al. (2025). Fructose-induced synaptic and neuronal adaptations at neuropeptide Y/agouti-related peptide neurons. Molecular Metabolism, 99, 102209.

Source class: Primary research

Used in this series for: Sex-dependent NPY-AgRP circuit remodeling after high-fructose feeding in mice

Boundary: Male and female mice received chow or sixty-percent-calorie fructose or dextrose diets for up to eight weeks with one- or four-week withdrawal arms; fructose uniquely remodeled NPY-AgRP synaptic input with sex-dependent persistence while ninety-minute slice fructose was null; no KHK perturbation ATP measure Kiss1 endpoint or reproductive outcome

Canonical record: S160

Source link: Open source record

[HORM-S2008] Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding

Alexandra Shapiro, Wei Mu, Carlos Roncal, Kit-Yan Cheng, Richard J Johnson, Philip J Scarpace (2008). Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 295(5), R1370-R1375.

Source class: Primary research

Used in this series for: Leptin resistance preceding weight gain in a high-fructose male-rat model

Boundary: Male rats fed a sixty-percent-fructose versus fructose-free diet for six months lost the anorexic response to peripheral leptin and had lower basal whole-hypothalamus pSTAT3 despite similar weight adiposity leptin insulin and glucose; triglycerides rose and could impair leptin transport, and no identified AgRP cell KHK ATP Kiss1 or reproductive endpoint was measured

Canonical record: S180

Source link: Open source record

[HORM-T2004] Dietary fructose reduces circulating insulin and leptin attenuates postprandial suppression of ghrelin and increases triglycerides in women

Karen L Teff, Sharon S Elliott, Matthias Tschöp, Timothy J Kieffer, Daniel Rader, Mark Heiman, et al. (2004). Dietary fructose reduces circulating insulin and leptin attenuates postprandial suppression of ghrelin and increases triglycerides in women. The Journal of Clinical Endocrinology and Metabolism, 89(6), 2963-2972.

Source class: Primary research

Used in this series for: One-day human fructose-versus-glucose leptin ghrelin and insulin response

Boundary: Twelve normal-weight women completed two one-day isocaloric high-fructose-versus-high-glucose feeding conditions; fructose lowered insulin and leptin responses attenuated meal-related ghrelin suppression and raised triglycerides; extreme thirty-percent-energy monosaccharide exposure one-day duration female-only sample and lack of KHK measurement limit translation

Canonical record: S-P005-026

Source link: Open source record

[HORM-P2017] AgRP to Kiss1 neuron signaling links nutritional state and fertility

Stephanie L Padilla, Jian Qiu, Casey C Nestor, Chunguang Zhang, Arik W Smith, Benjamin B Whiddon, et al. (2017). AgRP to Kiss1 neuron signaling links nutritional state and fertility. Proceedings of the National Academy of Sciences of the United States of America, 114(9), 2413-2418.

Source class: Primary research

Used in this series for: AgRP-to-Kiss1 nutritional-state and fertility circuit in female mice

Boundary: AgRP neurons formed direct inhibitory synapses onto arcuate and AVPV Kiss1 neurons and sustained AgRP activation delayed estrous cycles and fertility in female mice; a pair-fed activated group was included because activation increased body weight but the accessible report does not provide a clean adult weight-independent mediation estimate; no fructose endogenous fructose KHK or male reproductive test

Canonical record: S141

Source link: Open source record

[HORM-B2022] Rescue of obesity-induced infertility in female mice by silencing AgRP neurons

Xueyan Bai, Lei Fu, Naiqian Jin, Xiaoyan Liu, Lili Chen, Yinghua Shan, et al. (2022). Rescue of obesity-induced infertility in female mice by silencing AgRP neurons. Biochemical and Biophysical Research Communications, 623, 32-38.

Source class: Primary research

Used in this series for: AgRP-neuron intervention in obesity-associated female infertility in mice

Boundary: Female mice received a sixty-percent-kilocalorie high-fat diet for ten weeks and chemogenetic AgRP-neuron inhibition restored reported sex-hormone ovulation and fecundity outcomes; a separate thirty-woman comparison found higher serum AgRP with overweight or obesity; no fructose KHK ATP Kiss1 or neuronal AgRP measurement in women and feeding or body-weight mediation of the rescue remains incompletely audited

Canonical record: S171

Source link: Open source record

[HORM-A2024] The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin

María S Avendaño, Cecilia Perdices-Lopez, Yolanda Guerrero-Ruiz, Francisco Ruiz-Pino, Ana B Rodriguez-Sanchez, María J Sanchez-Tapia, et al. (2024). The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin. Metabolism, 157, 155932.

Source class: Primary research

Used in this series for: Obesity-associated hypothalamic kisspeptin repression and rescue in male rodents

Boundary: Male rodent and cell evidence identifies miR-137/325 repression of Kiss1 and target-site-blocker rescue during continued obesogenic feeding; the model combines early overfeeding with 45-percent-fat feeding and does not test fructose KHK endogenous brain fructose females or human clinical efficacy

Canonical record: S131

Source link: Open source record

[HORM-S2013] Melatonin and diet-induced metabolic syndrome in rats: impact on the hypophysial-testicular axis

Pablo A Scacchi Bernasconi, Nancy P Cardoso, Roxana Reynoso, Pablo Scacchi, Daniel P Cardinali (2013). Melatonin and diet-induced metabolic syndrome in rats: impact on the hypophysial-testicular axis. Hormone Molecular Biology and Clinical Investigation, 16(2), 101-112.

Source class: Primary research

Used in this series for: Fructose-associated low testosterone with higher LH in male rats

Boundary: Rats drinking ten-percent fructose solution for ten weeks had higher LH and lower testosterone without FSH or most reproductive-organ-weight changes; the authors interpreted the pattern as compatible with primary testicular inhibition rather than central LH suppression; melatonin did not restore testosterone

Canonical record: S167

Source link: Open source record

[HORM-PMOS2026] Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: a multistep global consensus process

Helena J Teede, Mahnaz Bahri Khomami, Rachel Morman, Joop S E Laven, Anju E Joham, Michael F Costello, et al. (2026). Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: a multistep global consensus process. Lancet, 407(10545), 2329-2339.

Source class: Consensus statement

Used in this series for: Global consensus process adopting the PMOS name

Boundary: A global process involving 56 organisations iterative surveys with 14360 responses modified Delphi methods nominal group workshops and implementation analyses selected Polyendocrine Metabolic Ovarian Syndrome PMOS as the consensus new name for PCOS. The paper explicitly frames PMOS as capturing endocrine metabolic and ovarian dysfunction and describes a managed global transition. It establishes terminology and consensus rationale; it does not establish any specific fructose KHK mechanism.

Canonical record: S267

Source link: Open source record

[HORM-S2007] Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene

David M Selva, Kevin N Hogeveen, Sheila M Innis, Geoffrey L Hammond (2007). Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene. Journal of Clinical Investigation, 117(12), 3979-3987.

Source class: Primary research

Used in this series for: Monosaccharide-driven hepatic lipogenesis and SHBG expression

Boundary: Human-SHBG transgenic mice and HepG2 cells support reversible carbohydrate-associated SHBG suppression through lipogenesis HNF-4alpha and promoter regulation; tiny animal groups human transgene and tumor-derived cells limit translation and the study does not isolate KHK or test humans

Canonical record: S130

Source link: Open source record

[HORM-T2012] Hyperinsulinemia amplifies GnRH agonist stimulated ovarian steroid secretion in women with polycystic ovary syndrome

Flavia Tosi, Carlo Negri, Fabrizia Perrone, Romolo Dorizzi, Roberto Castello, Enzo Bonora, et al. (2012). Hyperinsulinemia amplifies GnRH agonist stimulated ovarian steroid secretion in women with polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism, 97(5), 1712-1719.

Source class: Primary research

Used in this series for: Hyperinsulinemia and stimulated ovarian steroid output in women with PCOS

Boundary: Hyperinsulinemia amplified GnRH-agonist-stimulated ovarian steroid secretion in women with PCOS; this supports a peripheral insulin-LH ovarian route but does not establish dietary fructose endogenous fructose KHK or kisspeptin causality

Canonical record: S134

Source link: Open source record

[HORM-C2024] Fructose intake from sugar-sweetened beverages is associated with a greater risk of hyperandrogenism in women: UK Biobank cohort study

Huadong Chen, Amée M Buziau, Miguel E Rentería, Pomme I H G Simons, Martijn C G J Brouwers (2024). Fructose intake from sugar-sweetened beverages is associated with a greater risk of hyperandrogenism in women: UK Biobank cohort study. European Journal of Endocrinology, 190(1), 104-112.

Source class: Primary research

Used in this series for: Sex-divergent androgen associations with estimated SSB fructose exposure

Boundary: UK Biobank dietary and KHK-variant analyses associate SSB fructose with lower SHBG in both sexes lower total testosterone in men and higher free testosterone plus slightly higher biochemical-hyperandrogenism risk in women; BMI may mediate most dietary association and neither component proves neuronal or endogenous-fructose causality

Canonical record: S129

Source link: Open source record

[HORM-N2025] Effects of glucose and fructose supplementation on serum sex hormone-binding globulin and testosterone levels: Post-hoc analysis of a double-blind randomized controlled trial

Huadong Chen, Pomme I H G Simons, Nynke Simons, Marjo P H van de Waarenburg, J A P Bons, E M C van der Ploeg, et al. (2025). Effects of glucose and fructose supplementation on serum sex hormone-binding globulin and testosterone levels: Post-hoc analysis of a double-blind randomized controlled trial. Clinical Nutrition ESPEN, 69, 384-388.

Source class: Primary research

Used in this series for: Six-week randomized fructose-versus-glucose sex-hormone null

Boundary: In 36 adults with BMI at least 28 and high fatty-liver index a six-week fructose-restricted diet supplemented with fructose versus glucose produced no significant differential SHBG total-testosterone or free-testosterone effect; small post-hoc mixed-sex analysis and replacement-level exposure do not address PCOS central signaling or high-dose SSB exposure

Canonical record: S159

Source link: Open source record

Interventions

[INT-PERL2020] Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes

Alessandro Doria, Andrzej T Galecki, Cathie Spino, Rodica Pop-Busui, David Z Cherney, Ildiko Lingvay, et al. (2020). Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes. New England Journal of Medicine, 382(26), 2493-2503.

Source class: Primary research

Used in this series for: Allopurinol kidney-outcome null despite serum-urate reduction

Boundary: In adults with type-1 diabetes and early-to-moderate diabetic kidney disease allopurinol substantially lowered serum urate but did not produce the prespecified clinically meaningful kidney-function benefit; disease-specific trial and xanthine-oxidase inhibition do not test intracellular urate signaling or KHK inhibition

Canonical record: S-P005-035

Source link: Open source record

[INT-FAST2020] Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre prospective randomised open-label non-inferiority trial

Isla S Mackenzie, Ian Ford, George Nuki, Jesper Hallas, Christopher J Hawkey, John Webster, et al. (2020). Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre prospective randomised open-label non-inferiority trial. Lancet, 396(10264), 1745-1757.

Source class: Primary research

Used in this series for: Febuxostat-versus-allopurinol cardiovascular safety trial

Boundary: Among older patients with gout and cardiovascular risk febuxostat was noninferior to optimized allopurinol for the primary cardiovascular endpoint; the comparator design does not show that urate lowering prevents cardiovascular disease or tests the fructose-KHK pathway

Canonical record: S-P005-036

Source link: Open source record

[INT-L2017] Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice

Ana Andres-Hernando, Nanxing Li, Christina Cicerchi, Shinichiro Inaba, Wei Chen, Carlos Roncal-Jimenez, et al. (2017). Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice. Nature Communications, 8, 14181.

Source class: Primary research

Used in this series for: Luteolin KHK inhibition in vitro kidney-cell ATP preservation and intravenous mouse AKI results

Boundary: Luteolin inhibited fructokinase in vitro with IC50 11.2 micromolar in human proximal-tubule cells and intravenous dosing improved ischemic AKI outcomes in mice alongside global KHK-knockout protection; kidney ischemia context dosing route off-target actions inventor conflicts and no human endocrine metabolic PCOS testosterone oral or product study prevent therapeutic extrapolation

Canonical record: S146

Source link: Open source record

[INT-M2019] Consumption of 100% Tart Cherry Juice Reduces Serum Urate in Overweight and Obese Adults

Keith R Martin, Katie M Coles (2019). Consumption of 100% Tart Cherry Juice Reduces Serum Urate in Overweight and Obese Adults. Current Developments in Nutrition, 3(5), nzz011.

Source class: Primary research

Used in this series for: Small controlled tart-cherry-juice urate signal

Boundary: Twenty-six overweight or obese adults completed four weeks each of 240 milliliters daily tart-cherry juice and calorie or carbohydrate-matched placebo; serum urate fell in the cherry arm while inflammatory outcomes were mostly nonsignificant trends; small industry-supported juice study does not establish extract efficacy KHK modulation gout treatment or product efficacy

Canonical record: S-P005-027

Source link: Open source record

[INT-S2020] Lack of effect of tart cherry concentrate dose on serum urate in people with gout

Lisa K Stamp, Peter Chapman, Christopher Frampton, Stephen B Duffull, Jill Drake, Yuqing Zhang, et al. (2020). Lack of effect of tart cherry concentrate dose on serum urate in people with gout. Rheumatology, 59(9), 2374-2380.

Source class: Primary research

Used in this series for: Randomized tart-cherry-concentrate urate null in gout

Boundary: Fifty people with gout were randomized across placebo and four twice-daily concentrate doses for twenty-eight days; no dose effect appeared for serum-urate exposure urinary urate or short-term flares; directly limits dependable urate-lowering claims while not testing standardized dry extract redox endpoints KHK or SugarShield

Canonical record: S-P005-028

Source link: Open source record

[INT-J2026] Effects of Tart Cherry Extract Supplementation on Plasma Urate and C-Reactive Protein Levels in Healthy Adults: a Randomized Controlled Trial

Ralf Jäger, Martin Purpura, Sebastian T Balcombe, Ashok Godavarthi, Suda A Reddy, Ecaterina Vasenina, et al. (2026). Effects of Tart Cherry Extract Supplementation on Plasma Urate and C-Reactive Protein Levels in Healthy Adults: a Randomized Controlled Trial. Journal of Dietary Supplements, 23(1), 42-57.

Source class: Primary research

Used in this series for: Very small standardized tart-cherry-extract urate and CRP signal

Boundary: Ten healthy adults completed two four-week phases of five-hundred-milligram standardized tart-cherry extract or placebo; acute measures were null while day-twenty-eight plasma urate and CRP were lower; extremely small study abstract audit and formulation specificity require replication and do not establish KHK or SugarShield efficacy

Canonical record: S-P005-029

Source link: Open source record

[INT-SS2026] SugarShield product page

LIV3 Health (2026). SugarShield product page. LIV3 Health.

Source class: Product information — not scientific evidence

Used in this series for: Official product composition and commercial disclosure only

Boundary: Official page states a 450-milligram proprietary liposomal blend containing 98-percent luteolin from Sophora japonica and 30-to-1 Prunus cerasus tart-cherry extract; it states SugarShield was not used in the cited studies and is not intended to diagnose treat or prevent disease; composition may change and snapshot is not efficacy evidence

Canonical record: S-P005-030

Source link: Open source record