Episode 3: Is High LDL Really the Culprit? (Cardiovascular Disease Part 3)

The Dr Kumar Discovery

In this episode of the Dr. Kumar Discovery Podcast, we dive deep into one of the most controversial questions in human health: 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 Study
• What traditional cultures like the Tsimane, Maasai, and Inuit reveal about “normal” cholesterol
• Why very low LDL is associated with higher all-cause mortality
• What CAC scans tell us about real cardiovascular risk
• The Injury Response Hypothesis — a new way to view atherosclerosis
• Whether statins make sense in every case — and how to personalize your approach

Whether 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 Guidelines

• The Framingham Heart Study
• NIH Open Access
• A 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 Disease

• Tokelauan Islanders
  • ScienceDirect
  • Despite diets high in saturated fat, Tokelauans showed high LDL and low heart disease.
• Hadza Hunter-Gatherers
  • PubMed
  • This Tanzanian tribe showed favorable cardiometabolic profiles with variable LDL levels.
• Greenland Inuit
  • ResearchGate
  • SpringerLink
  • ScienceDirect
  • AHA Journals
  • Inuit with high cholesterol levels showed little ischemic heart disease, suggesting a different pathophysiology in traditional diets.
• Tsimane of Bolivia
  • PubMed
  • A pre-industrial society with extremely low rates of coronary artery disease.
• Kitavan Islanders
  • ResearchGate
  • Tandfonline
  • Low CVD despite higher saturated fat intake and varied lipid profiles.
• !Kung and Other African Hunter-Gatherers
  • Perfect Health Diet Summary
  • Documentation of cholesterol values in pre-modern hunter-gatherer groups with virtually no atherosclerosis.
• Maasai of Tanzania
  • PLOS ONE
  • Despite a high-saturated-fat diet, the Maasai show low coronary artery disease incidence

3. Risks of Very Low LDL

• LDL and Mortality in the Elderly (Meta-analysis)
  • BMJ Open
  • Among 68,000+ people aged 60+, higher LDL was associated with lower mortality risk.
• NHANES III: U-shaped Risk Curve
  • PubMed Central
  • Both very low and very high LDL were linked to increased cardiovascular and all-cause mortality.
• Framingham 30-Year Follow-Up
  • JAMA
  • After 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 Populations

• LDL and Cardiovascular Risk in FH
  • AHA Journals
  • FH 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 Risk

• High LDL with CAC Score of Zero
  • Circulation
  • European Heart Journal
  • High 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 Studies

• 1961 Indian Autopsy Study
  • AHA Journals
  • No correlation between cholesterol levels and severity of atherosclerosis at autopsy, even in high-cholesterol individuals.

7. LDL in Heart Attack Patients

• Low LDL and Poor Outcomes in MI Patients
  • ScienceDirect
  • In 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 Risk
  • Cardiology Journal
  • Among 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.