{
  "cutoff": "2026-10-13",
  "note": "Selected publication milestones, not an exhaustive history or discovery priority claim.",
  "milestones": [
    {
      "pmid": "5900208",
      "year": "1966",
      "title": "Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat.",
      "doi": "",
      "url": "https://pubmed.ncbi.nlm.nih.gov/5900208/",
      "interpretation": "1966 prolonged randomized Veterans feeding documents lipid lowering and tissue-linoleic enrichment; this examined report does not supply coronary-event outcomes."
    },
    {
      "pmid": "393644",
      "year": "1979",
      "title": "Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study.",
      "doi": "10.1093/ije/8.2.99",
      "url": "https://pubmed.ncbi.nlm.nih.gov/393644/",
      "interpretation": "1979 Finnish hospital-period male coronary findings are favourable under controlled dietary reversal, with allocation and period confounding retained."
    },
    {
      "pmid": "6840954",
      "year": "1983",
      "title": "Dietary prevention of coronary heart disease in women: the Finnish mental hospital study.",
      "doi": "10.1093/ije/12.1.17",
      "url": "https://pubmed.ncbi.nlm.nih.gov/6840954/",
      "interpretation": "1983 the Finnish women's companion reports a nonsignificant coronary difference despite lipid lowering, illustrating endpoint and context limits."
    },
    {
      "pmid": "2643423",
      "year": "1989",
      "title": "Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey.",
      "doi": "10.1161/01.atv.9.1.129",
      "url": "https://pubmed.ncbi.nlm.nih.gov/2643423/",
      "interpretation": "1989 the Minnesotaoriginal clinical report finds no overall cardiovascular-event or mortality benefit despite cholesterol lowering."
    },
    {
      "pmid": "7911176",
      "year": "1994",
      "title": "Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.",
      "doi": "10.1016/s0140-6736(94)92580-1",
      "url": "https://pubmed.ncbi.nlm.nih.gov/7911176/",
      "interpretation": "1994 Lyon demonstrates clinical benefit from a mixed Mediterranean dietary pattern, without isolating an LA-rich oil component."
    },
    {
      "pmid": "22492369",
      "year": "2012",
      "title": "Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial.",
      "doi": "10.3945/ajcn.111.030114",
      "url": "https://pubmed.ncbi.nlm.nih.gov/22492369/",
      "interpretation": "2012 an isocaloric vegetableomega6-versus-butter experiment finds no proinflammatory signal and lower liver fat, with biomarkers kept separate from coronary events."
    },
    {
      "pmid": "23386268",
      "year": "2013",
      "title": "Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis.",
      "doi": "10.1136/bmj.e8707",
      "url": "https://pubmed.ncbi.nlm.nih.gov/23386268/",
      "interpretation": "2013 Sydneyrecovered participant data reveal an adverse coronary-mortality contrast under a highLAhistorical intervention; the meta-analysis is counted separately from original-data credit."
    },
    {
      "pmid": "26016869",
      "year": "2015",
      "title": "Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study.",
      "doi": "10.3945/ajcn.114.097089",
      "url": "https://pubmed.ncbi.nlm.nih.gov/26016869/",
      "interpretation": "2015 DIVASimproves lipid markers but not its primary vascular outcome; estimated mortality benefit remains an extrapolation."
    },
    {
      "pmid": "26429077",
      "year": "2015",
      "title": "Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease: A Prospective Cohort Study.",
      "doi": "10.1016/j.jacc.2015.07.055",
      "url": "https://pubmed.ncbi.nlm.nih.gov/26429077/",
      "interpretation": "2015 long-term dietary substitution models favour PUFAand whole-grain replacement over refined carbohydrates, while allocation remains observational."
    },
    {
      "pmid": "27071971",
      "year": "2016",
      "title": "Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73).",
      "doi": "10.1136/bmj.i1246",
      "url": "https://pubmed.ncbi.nlm.nih.gov/27071971/",
      "interpretation": "2016 the recovered Minnesotaanalysis adds original longitudinal and partial-autopsy information to the same parent trial; the clinical null is not a new independent trial."
    },
    {
      "pmid": "30624587",
      "year": "2019",
      "title": "Inflammatory response to dietary linoleic acid depends on FADS1 genotype.",
      "doi": "10.1093/ajcn/nqy287",
      "url": "https://pubmed.ncbi.nlm.nih.gov/30624587/",
      "interpretation": "2019 FADSDIETreports genotype-dependent short marker responses, requiring prospective controlled clinical validation."
    },
    {
      "pmid": "34934897",
      "year": "2021",
      "title": "Behavioral Characteristics and Self-Reported Health Status among 2029 Adults Consuming a \"Carnivore Diet\".",
      "doi": "10.1093/cdn/nzab133",
      "url": "https://pubmed.ncbi.nlm.nih.gov/34934897/",
      "interpretation": "2021 a large carnivore-maintainer survey records perceived benefits and lipid uncertainty without a long-term cardiovascular comparison."
    },
    {
      "pmid": "33924952",
      "year": "2021",
      "title": "Causal Effects of Serum Levels of n-3 or n-6 Polyunsaturated Fatty Acids on Coronary Artery Disease: Mendelian Randomization Study.",
      "doi": "10.3390/nu13051490",
      "url": "https://pubmed.ncbi.nlm.nih.gov/33924952/",
      "interpretation": "2021 fatty-acid genetic analysis supports selected linoleic-CAD estimates, with endogenous-metabolism scope retained."
    },
    {
      "pmid": "35692035",
      "year": "2022",
      "title": "Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.",
      "doi": "10.1186/s12916-022-02399-w",
      "url": "https://pubmed.ncbi.nlm.nih.gov/35692035/",
      "interpretation": "2022 a largerPUFAGWAS/MRanalysis finds inconsistent cardiovascular estimates and lipoprotein/FADSlocus sensitivity."
    },
    {
      "pmid": "40385902",
      "year": "2025",
      "title": "Subjective Experiences and Blood Parameter Changes in Individuals From Germany Following a Self-Conceived \"Carnivore Diet\": An Explorative Study.",
      "doi": "10.7759/cureus.82521",
      "url": "https://pubmed.ncbi.nlm.nih.gov/40385902/",
      "interpretation": "2025 a small German carnivorepre/post study reports perceived benefits and increased LDLrather than adjudicated clinical superiority."
    },
    {
      "pmid": "40199060",
      "year": "2025",
      "title": "Circulating polyunsaturated fatty acids percentages and coronary artery disease incidence and mortality: Observational and Mendelian randomization analyses.",
      "doi": "10.1016/j.clnu.2025.03.020",
      "url": "https://pubmed.ncbi.nlm.nih.gov/40199060/",
      "interpretation": "2025 observational and genetic analyses report sex-specificomega6-CADsupport, without equating plasma percentages to an allocated oil substitution."
    }
  ],
  "gaps": [
    "Accessible primary-result verification of the old VA, Oslo Diet-Heart, MRCsoybean and Rose clinical studies, with actual composition and endpoint hierarchy",
    "Modern long-term allocated oil-swap coronary-event trials with contemporary prevention care",
    "Distinct causal identification of dietary LA-rich oil exposure versus circulating fatty-acid metabolism and shared FADSor lipoprotein instrument pathways",
    "Usual-intake inflammatory coronary harm versus high-dose historical margarine, repeated heating and short biomarker changes",
    "Food-matrix and comparator effects, including saturated-fat sources, refined carbohydrate replacement and mixedomega3/omega6oils",
    "Defined carnivore patterns assessed against an active balanced comparator on actual cardiovascular events rather than maintainer surveys"
  ],
  "decisive_experiment": "Randomize adults with prospectively defined coronary risk to isocaloric replacement of a specified saturated-fat food source with a chemically characterized LA-rich oil, versus retained saturated-fat food and an independently specified unsaturated-oil comparator. Prespecify adjudicated fatal and nonfatal coronary events over multiple years, achieved dietary intake, trans-fat exposure, background omega3, medication stability and analysis. Use LDL/apoBand inflammatory measurements as candidate mediators, not as substituted clinical outcomes."
}