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Diet exposures and the pathograph: disposition of 42 candidates, 2026-09-01

The diet representation audit — diet-representation-audit-2026-09-01.md, added by PR #10358 — found 42 environmental[] diet entries that carry a supporting, snippet-backed citation but no influences_mechanisms link, so they never appear in the mechanism graph. This records what was decided for each.

27 got an edge. 2 remain unsupported. 13 were left alone.

Two of those were reached independently by main while this work was in review, and main's version won on the merits in both cases — see Superseded by main below. The change here is 25 new links across 14 entries, plus evidence blocks on two edges main created.

An earlier revision of this file recorded 20 added, 8 proposed-not-added and 14 left alone. Six of the eight proposed were then resolved by finding a citation that measures the target node, and one entry from the left-alone list the same way — see Resolved by finding node-level evidence below. Nothing was moved by relaxing the rule.

The rule applied

An influences_mechanisms edge asserts that the exposure acts on a named mechanism node. So the test is not "is this a real risk factor" — it is:

Does the cited snippet name something that maps to a node or phenotype in this file, or does it only say the exposure raises the risk of the disease?

A snippet that says only "X is associated with an increased risk of [the disease]" identifies no node. Those were left alone. This is the distinction the audit flagged and could not make itself: an association is not a mechanism.

Two schema slots were needed, and they are easy to conflate:

  • causal_link_type is graph topology — does the edge jump over mechanism steps that are themselves nodes in this file? DIRECT, or INDIRECT_KNOWN_INTERMEDIATES when it does.
  • directness on the evidence item is about the quote — does it assert the claim, or does the claim follow from it by an inference step?

They vary independently. Wilson Disease's dietary copper edge is topologically DIRECT (intake feeds the hepatic copper pool with nothing in between) but its evidence is INDIRECT, because the source says lowering intake prevents re-accumulation and the forward claim is inferred from that removal design.

Entry Exposure Target node Effect Why
Celiac Disease Gluten Exposure Gluten-Triggered Immune Response TRIGGERS Snippet names gluten as required to trigger the enteropathy
Celiac Disease Wheat / Barley / Rye Gluten-Triggered Immune Response TRIGGERS One snippet names all three grains as triggering and maintaining it (3 links)
Gastroesophageal Reflux Alcohol Consumption Lower Esophageal Sphincter Dysfunction EXACERBATES Snippet states the sphincter-pressure reduction
Gastroesophageal Reflux Dietary Factors Lower Esophageal Sphincter Dysfunction EXACERBATES Physiologic evidence for chocolate and high-fat meals on the same node
Heart Failure Alcohol Abuse Myocardial Contractile Dysfunction TRIGGERS Snippet names chronic cardiac dysfunction and alcoholic dilated cardiomyopathy. Edge created by main; this adds its evidence block
Hyperlipidemia High Saturated Fat Diet Increased LDL Cholesterol EXACERBATES Snippet attributes the LDL-C rise to saturated fat substitution
Obesity High-Calorie Diet Energy Imbalance TRIGGERS Inpatient randomised crossover trial; excess intake attributable to processing itself
Obesity Obesogenic Environment Increased Body Mass Index PREDISPOSES Causal-inference systematic review linking outlet density to BMI
Osteoporosis Vitamin D Deficiency Bone Remodeling Imbalance PREDISPOSES Snippet gives the deficiency → hyperparathyroidism → bone loss route
Phenylketonuria Dairy Intake Hyperphenylalaninemia EXACERBATES Randomised crossover trial measuring phenylalanine tolerance from milk protein
Phenylketonuria Mammalian Meat / Nut Intake Hyperphenylalaninemia EXACERBATES Named among high-protein foods the diet avoids (2 links)
Wilson Disease Dietary Copper Hepatic Copper Accumulation EXACERBATES Snippet ties intake to copper re-accumulation
Irritable Bowel Syndrome Dietary Triggers Abdominal Pain, Bloating EXACERBATES Low-FODMAP meta-analysis reports both (2 links)
Migraine Dietary Triggers Headache TRIGGERS Provocation studies for caffeine withdrawal and MSG
Carotid Stenosis Smoking and diet Atherosclerotic carotid plaque formation PREDISPOSES Snippet names plaque development specifically
Lathyrism Grass pea overconsumption Beta-ODAP Receptor Agonism TRIGGERS Study attributes the disease to prolonged overconsumption
Gout Red Meat and Organ Meat Intake Hyperuricemia EXACERBATES NHANES III measures serum uric acid rising with meat intake
Gout Shellfish Intake Hyperuricemia EXACERBATES Same source, seafood arm
Gout Beer Intake Hyperuricemia EXACERBATES 78,153 participants; beer raises serum urate where sake at matched ethanol does not
Gout Fructose-Sweetened Soft Drink Intake Hyperuricemia EXACERBATES Meta-analysis measuring serum uric acid, not incident gout
Liver Cirrhosis Alcohol Consumption Hepatocyte Injury and Death TRIGGERS Hepatocyte apoptosis markers ~5x normal in 114 heavy drinkers
Polycystic Kidney Disease Caffeine Consumption Vasopressin/cAMP-Driven Cyst Expansion EXACERBATES Caffeine potentiates desmopressin-driven cAMP in ADPKD cyst cells
Coronary Artery Disease High-Fat Diet Coronary Endothelial Injury and Subendothelial LDL Retention PREDISPOSES Controlled-feeding meta-analysis quantifies the LDL step. Edge created by main; this adds its evidence block

Every edge carries its own evidence, copied byte-exact from the entry it sits on so the snippet stays verified and evidence_source cannot drift.

Several edges are deliberately narrower than the entry they hang on. The GERD dietary edge is scoped to the sphincter effect, because the same review found no evidence that dietary avoidance improves outcomes. The IBS edge is scoped to FODMAPs, because the gluten half of that annotation is uncited. The migraine edge is scoped to caffeine withdrawal and MSG, because the entry's own REFUTE item withdraws chocolate and aged cheese.

Superseded by main

Two of the 20 were curated independently on main while this sat in review. In both cases main's version is kept, on the merits rather than by merge order.

Marchiafava-Bignami — dropped entirely. Main linked the same exposure to the same node using a better sentence from the same paper: "The main pathophysiological mechanisms involve alcohol consumption, which leads to thiamine depletion and disrupts various metabolic pathways." That names thiamine depletion, so main's TRIGGERS / directness: DIRECT is justified where this pass had PREDISPOSES / INDIRECT — graded down precisely because the quote it used ("predominantly afflicts individuals with chronic alcohol abuse and malnutrition") did not name the node. Better evidence beats an earlier claim.

Heart Failure — edge kept, evidence added. Main created the same edge with a fuller description and no evidence; this attaches the citation to it.

The history record written for the Marchiafava-Bignami session is left untouched, since history is append-only and it accurately describes what that session did. A later record notes the supersession.

Originally withheld (8), and why

Kept for the record: this is the state each of these was in before the citation search below. Each had good evidence for a risk claim and a plausible target node, but the snippet did not reach the node — so adding the edge would have meant accepting a disease-level association as node-level support. Six were subsequently resolved by finding a citation that does reach the node; two were not.

Entry Exposure Proposed target The problem
Gout Red Meat and Organ Meat Hyperuricemia Cohort measures incident gout, not urate. Purine → urate is textbook, but this snippet does not say it
Gout Shellfish Intake Hyperuricemia Same; the entry's own explanation already notes it measures incident gout rather than flares
Gout Beer Intake Hyperuricemia UK Biobank per-drink association with incident gout
Gout Fructose-Sweetened Soft Drink Hyperuricemia Meta-analysis of incident gout; note claims urate production
Liver Cirrhosis Alcohol Consumption Hepatocyte Injury and Death Steep dose-response over 3M participants, but for cirrhosis risk, not hepatocyte injury
Coronary Artery Disease High-Fat Diet Coronary Endothelial Injury and Subendothelial LDL Retention Cochrane RCT meta-analysis measures CVD events; the entry's own note says the LDL effect is small
Generalized Anxiety Disorder Caffeine (a phenotype) Controlled trial shows GAD patients are abnormally caffeine-sensitive, but names no node or specific symptom
Tyrosinemia Type I Catabolic and dietary stress Toxic FAA/MAA accumulation GeneReviews avoid-list; naming circumstances to avoid is not a mechanism measurement

The four Gout entries are the cleanest illustration of the whole problem, and the best fix is probably not a judgement call at all — it is a citation that measures serum urate after a purine load, which would turn all four into ordinary EXACERBATES edges on Hyperuricemia.

That is what happened. Six of these eight, and one entry from the left-alone list, were resolved by citation rather than by ruling. See the next section; the two that remain are the two where no such citation exists.

Resolved by finding node-level evidence (7)

The rule was never "these exposures are not real". It was that the cited quote stopped at disease risk. That is a citation problem, so the fix is a citation — and for seven of these it exists. Each one below is now an ordinary edge with evidence that measures the target node itself. No edge here was added by relaxing the rule.

Entry Exposure Node New citation What it measures
Gout Red Meat and Organ Meat Hyperuricemia PMID:15641075 Serum uric acid across meat intake quintiles, NHANES III, n=14,809
Gout Shellfish Hyperuricemia PMID:15641075 Same study's seafood arm
Gout Beer Hyperuricemia PMID:36930152 Serum urate by beverage at 20 g ethanol per standard drink, n=78,153
Gout Fructose-Sweetened Soft Drink Hyperuricemia PMID:32683776 Serum uric acid, +0.18 mg/dL highest vs lowest intake
Liver Cirrhosis Alcohol Consumption Hepatocyte Injury and Death PMID:34305638 Caspase-cleaved CK-18 (M30) and M65 in 114 heavy drinkers
Polycystic Kidney Disease Caffeine Consumption Vasopressin/cAMP-Driven Cyst Expansion PMID:12397042 Proliferation and transepithelial fluid secretion in ADPKD cyst epithelium under caffeine
Coronary Artery Disease High-Fat Diet Coronary Endothelial Injury and Subendothelial LDL Retention PMID:40885400 LDL cholesterol in 24 randomised complete-feeding trials

Three of these are worth reading closely, because they change what the entry says rather than just adding to it:

  • The four Gout edges turn on the difference between incident gout and serum urate. Every citation the entries already carried measured who develops gout, which is a disease-risk claim. Choi's NHANES analysis measures serum uric acid itself, so it reaches the Hyperuricemia node directly, and the beer study is stronger still: sake at the same standardised ethanol content shows no urate association, so the effect is attributable to beer rather than to ethanol.
  • The Liver Cirrhosis edge is graded DIRECT, not INDIRECT, because M30 is caspase-cleaved cytokeratin-18 released by dying hepatocytes. The quote measures the node, not a proxy for it.
  • The Coronary Artery Disease evidence contradicts the edge's own description. That description said the trial effect on LDL is small, which came from free-living trials. Controlled feeding gives 15.72 mg/dL when the diets differ in saturated fat, so the qualifier was removed from the edge and the entry-level notes rewritten to name both designs rather than leave a reader hitting the older claim first. The link is still graded directness: INDIRECT, because the trials lower saturated fat and the forward claim is inferred from that removal. The snippet runs through the study's own null arm — no significant LDL difference when the diets are saturated-fat-matched — so the quote carries its own control instead of the caveat living only in prose.

The PKD edge is evidence_source: IN_VITRO — cultured patient-derived cyst epithelium, not patients. That is a weaker footing than the other six and is recorded as such rather than smoothed over. Its snippet is the abstract's concluding sentence, which names proliferation and transepithelial fluid secretion; the same abstract identifies those two as the mechanisms underlying cyst expansion, so the quote reaches the node instead of stopping at cAMP and inferring the rest.

Still unsupported (2)

Searched and not found. These are not withheld on judgement any more; there is no quote to add.

Entry Exposure Why no edge
Generalized Anxiety Disorder Caffeine The one human imaging study (PMID:21972425, double-blind crossover fMRI) is 14 healthy males, not GAD patients, and its amygdala result is a tolerance finding — the caffeine effect correlated negatively with habitual intake. It does not support Amygdala Hyperactivity, and no other node in the entry matches caffeine's adenosine-antagonist action
Tyrosinemia Type I Catabolic and dietary stress The node is Toxic fumarylacetoacetate and maleylacetoacetate accumulation. FAA and MAA are not measured in patients — succinylacetone is the clinical surrogate — and no study links catabolic stress to either. The GeneReviews avoid-list remains the only source

The GAD case is the more interesting of the two: the gap is not missing literature but a missing node. Caffeine acts on adenosine signalling, and the entry models GABA, serotonin, noradrenergic, HPA and amygdala mechanisms with no adenosine node to attach to. Adding one is a curation decision beyond this PR's scope.

Left alone (13)

All have solid evidence for a disease-level risk association and no node the snippet reaches. This is the correct resting state, not a backlog.

Breast Carcinoma (alcohol), Colon Adenocarcinoma (alcohol), Essential Hypertension (alcohol), Familial Hypercholesterolemia (alcohol), HPV-Negative Head and Neck Cancer (ethanol), Laryngeal SCC (alcohol), Oral Cavity SCC (ethanol), Postcricoid Region Cancer (tobacco and alcohol), Obstructive Sleep Apnea (alcohol), Scurvy (vitamin C deficiency), Thyroid Follicular Carcinoma (iodine deficiency), Type 2 Diabetes Mellitus (high-calorie diet), Congestive Splenomegaly (alcohol).

Four are worth singling out:

  • Laryngeal SCC and Obstructive Sleep Apnea already say so themselves. The laryngeal entry's notes record that it "makes a risk-association claim and describes no ethanol or acetaldehyde mechanism"; the OSA explanation says the meta-analysis "measures the association, not the airway-relaxation mechanism". Those entries were curated correctly and need nothing.
  • Congestive Splenomegaly has a different problem: its description argues alcohol → cirrhosis → portal hypertension → splenomegaly, but the cited snippet is about anemia from direct bone-marrow toxicity. The evidence does not support the claim the entry makes. That is an evidence defect, not a missing edge, and it is not fixed here.
  • Polycystic Kidney Disease has moved. It was in this list because its only citation was a GeneReviews avoid-list; it now carries an edge on the strength of PMID:12397042. See the resolved section above.
  • Scurvy stays. Vitamin C → collagen prolyl hydroxylation is textbook, but searches for a human or fibroblast study stating it returned guinea-pig and mouse work and general biochemistry reviews, nothing quotable that names the Collagen Synthesis Impairment node in humans. The entry's case report is still the only source.

One thing fixed in passing

Wilson Disease graded PMID:36010023 as OTHER on a treatment and left evidence_source absent on the environmental entry, which counts as HUMAN_CLINICAL. Copying the quote onto the new edge made check-snippet-grading fail. The paper is a narrative review of dietary recommendations with no primary data, so OTHER is right; the environmental item was corrected to match rather than the new edge being graded to fit.