In this episode of the Dr. Kumar Discovery Podcast, we dive deep into one of the most controversial questions in cardiology: Does high LDL cholesterol actually cause heart disease? We explore the historical origins of the cholesterol hypothesis, unpack evidence from traditional societies and modern studies, and challenge the “lower is better” narrative. You’ll learn how cholesterol functions in the body, why LDL may not be the villain it’s made out to be, and when lowering it actually makes sense. We cover: The story of President Roosevelt and how his death led to the Framingham Heart StudyWhat traditional cultures like the Tsimane, Maasai, and Inuit reveal about “normal” cholesterolWhy very low LDL is associated with higher all-cause mortalityWhat CAC scans tell us about real cardiovascular riskThe Injury Response Hypothesis — a new way to view atherosclerosisWhether statins make sense in every case — and how to personalize your approachWhether you’re taking a statin, being told to start one, or just want a deeper understanding of cholesterol and cardiovascular risk, this episode offers a balanced, evidence-based perspective that cuts through the noise. References & Key Studies 1. The Origins of Cholesterol GuidelinesThe Framingham Heart StudyNIH Open AccessA landmark cohort study launched in 1948 to uncover causes of cardiovascular disease. It helped establish cholesterol, smoking, and blood pressure as key risk factors. 2. Traditional Populations with High LDL but Low Heart DiseaseTokelauan IslandersScienceDirectDespite diets high in saturated fat, Tokelauans showed high LDL and low heart disease.Hadza Hunter-GatherersPubMedThis Tanzanian tribe showed favorable cardiometabolic profiles with variable LDL levels.Greenland InuitResearchGateSpringerLinkScienceDirectAHA JournalsInuit with high cholesterol levels showed little ischemic heart disease, suggesting a different pathophysiology in traditional diets.Tsimane of BoliviaPubMedA pre-industrial society with extremely low rates of coronary artery disease.Kitavan IslandersResearchGateTandfonlineLow CVD despite higher saturated fat intake and varied lipid profiles.!Kung and Other African Hunter-GatherersPerfect Health Diet SummaryDocumentation of cholesterol values in pre-modern hunter-gatherer groups with virtually no atherosclerosis.Maasai of TanzaniaPLOS ONEDespite a high-saturated-fat diet, the Maasai show low coronary artery disease incidence3. Risks of Very Low LDLLDL and Mortality in the Elderly (Meta-analysis)BMJ OpenAmong 68,000+ people aged 60+, higher LDL was associated with lower mortality risk.NHANES III: U-shaped Risk CurvePubMed CentralBoth very low and very high LDL were linked to increased cardiovascular and all-cause mortality.Framingham 30-Year Follow-UpJAMAAfter age 50, each 1 mg/dL drop in total cholesterol was linked to an 11% increase in mortality and 14% increase in cardiovascular death.4. Familial Hypercholesterolemia in Modern PopulationsLDL and Cardiovascular Risk in FHAHA JournalsFH patients had increased cardiovascular mortality before age 70, but no increased risk after 70—challenging the assumption that LDL is always harmful.5. CAC Scans: Real-World Evidence of RiskHigh LDL with CAC Score of ZeroCirculationEuropean Heart JournalHigh LDL was not associated with plaque burden or events if CAC score was zero — highlighting the importance of measuring arterial damage directly. 6. Cholesterol and Atherosclerosis in Autopsy Studies1961 Indian Autopsy StudyAHA JournalsNo correlation between cholesterol levels and severity of atherosclerosis at autopsy, even in high-cholesterol individuals.7. LDL in Heart Attack PatientsLow LDL and Poor Outcomes in MI PatientsScienceDirectIn over 115,000 patients hospitalized with acute MI, those with the lowest LDL had the highest in-hospital mortality and worse cardiac outcomes.NSTEMI Patients and 3-Year RiskCardiology JournalAmong NSTEMI patients, those with LDL below 105 mg/dL had over twice the risk of death over 3 years compared to those with higher LDL.
