TL;DR: LDL cholesterol has long been framed as the primary cause of heart disease. But when we examine evolutionary biology, epidemiology, imaging, and real-world outcomes, the story becomes far more complex. This episode explores why aggressively lowering LDL may not always protect and in some cases may even harm, especially when we ignore context, age, and underlying vascular health. Click to listen.
Hi everyone,
For decades, we’ve been taught a simple message:
High LDL causes heart disease. Lower is always better.
It’s a clean narrative, and it’s comforting, but biology is rarely that simple.
If LDL cholesterol were inherently toxic, then people with the highest levels should reliably have the worst outcomes. Yet when we look closely at traditional cultures, large population studies, imaging data, and even patients actively having heart attacks, the picture begins to fracture.
Humans evolved with a wide range of cholesterol levels. Many traditional populations live with LDL levels that would alarm modern clinicians, yet they experience little ischemic heart disease. Cholesterol, after all, is not a toxin. It is essential for cellular repair, hormone production, immune defense, and survival.
Modern epidemiology adds another layer of complexity. Multiple large studies show that very low LDL, particularly below 70 mg/dL, is associated with higher all-cause mortality, higher cardiovascular mortality, and in some cases dramatically higher stroke risk. This is especially pronounced in older adults.
Even more striking, patients admitted with heart attacks often have lower, not higher, LDL levels, and those with the lowest cholesterol frequently fare the worst.
So what’s going on?
A growing body of evidence supports a different framework: heart disease does not begin with cholesterol. It begins with injury. Damage to the endothelium from smoking, high blood pressure, metabolic disease, inflammation, and oxidative stress, creates the conditions for plaque formation. LDL arrives not as a villain, but as a repair molecule. In the wrong environment, it becomes trapped, oxidized, and inflammatory.
This is where modern tools like coronary artery calcium scans become invaluable. They allow us to look directly for disease rather than infer risk from a single lab value. High LDL with a calcium score of zero tells a very different story than high LDL with established plaque.
The lesson is not that LDL is irrelevant.
It’s that context matters.
In some cases, temporarily lowering LDL can be protective, especially when disease is already present. But long-term health does not come from chasing numbers. It comes from reducing injury, restoring metabolic balance, and addressing root causes.
This episode is not about rejecting medicine, i t’s about using it wisely.
Clarity begins when we stop asking, “What number should I fear?” And start asking, “What is actually happening in my body?”
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