Cholesterol, Genetics, and Arterial Health: Why High Levels Aren’t Always Harmful
Here is an easy-to-follow breakdown of what cholesterol is, how it really works physiologically, genetically, and its role in arterial health. We must understand what cholesterol is and how it works so that we can begin to question the old paradigm and know that statins are not about health, they are about profit. In fact, they cause more damage than good. We do not want to get into other topics here, but it is worth mentioning. For this article we are focusing on the basics.
You need cholesterol to live. Your body uses it to build cell membranes, make hormones, produce vitamin D, and form bile acids for fat digestion.
The liver makes most of your cholesterol and adjusts production minute by minute because your demand changes. If your body needs more steroid hormones, bile acids, or new cell membranes, the liver ramps up production. If demand is lower or dietary intake is higher, the liver slows down. This regulation keeps blood levels within a range set largely by your genes.
The cholesterol you consume in food is absorbed in the small intestine with the help of bile acids. Some gets incorporated into chylomicrons and delivered to tissues. But the body also blocks excess absorption. When intake goes up, the liver reduces its own production. When intake goes down, the liver makes more. This explains why dietary cholesterol usually has little effect on blood cholesterol levels.
This is why two people can eat the same way and show very different blood levels. Their genetics determine how sensitive their liver is to cholesterol feedback and how efficiently their LDL receptors recycle cholesterol from the blood.
Genetics set your baseline
Your genes influence LDL receptors on liver cells, how many ApoB particles you make, and how fast you recycle cholesterol.
Variants in LDLR, APOB, PCSK9, HMGCR, and SREBF2 help explain wide differences between people.
Familial hypercholesterolemia is the clearest example. LDL runs high from birth because the receptor pathway does not clear ApoB particles well.
Lp(a) is also mostly genetic. It rides on an ApoB particle and tracks with risk for some people independent of diet.
Why high cholesterol can be “ok”
Cholesterol is part of normal repair. Tissues call for it during growth, hormone production, and healing.
LDL carries triglyceride fuel and cholesterol to cells. HDL and the liver bring extra cholesterol back for reuse or removal. This loop is constant.
In a low-inflammation state with good insulin sensitivity, higher LDL alone often tracks poorly with events compared with stronger markers like ApoB count, triglyceride-to-HDL ratio, and high-sensitivity CRP.
When it becomes “not ok”
The problem is not cholesterol by itself. The problem is the context that turns lipid traffic into plaque.
Endothelial injury: High blood pressure, smoking, high glucose, and chronic stress chemistry injure the inner vessel lining.
Retention: ApoB particles (VLDL remnants, IDL, LDL, and Lp(a)) can get trapped in the vessel wall. Retention is the first step toward plaque.
Oxidation: Trapped particles oxidize. Oxidized lipids trigger an immune response.
Glycation: High glucose modifies LDL and makes it easier to oxidize and harder to clear.
Inflammation: Macrophages eat oxidized particles and become foam cells. Over time this forms fatty streaks and plaques.
Particle burden: More ApoB particles raise the odds that some will be retained. Small, dense LDL tends to penetrate and oxidize faster in a high-sugar, high-seed-oil environment.
Key physiology in plain language
Production: The liver packages triglycerides and cholesterol into VLDL with one ApoB100 per particle.
Delivery: Lipoprotein lipase offloads triglycerides to muscles and fat tissue. VLDL becomes IDL, then LDL.
Clearance: The LDL receptor pulls LDL back into the liver. PCSK9 controls how many receptors survive on the surface.
Reverse transport: HDL picks up free cholesterol from tissues via ABCA1, esterifies it with LCAT, and returns it to the liver. CETP swaps lipids between HDL and ApoB particles.
Disposal: The liver excretes cholesterol in bile. Some leaves the body in stool. Some is reabsorbed.
Cholesterol does not cause arteriosclerosis
Cholesterol does not “clog” pipes on its own.
Arteriosclerosis begins with endothelial injury. ApoB particles then enter and get retained. Oxidation, glycation, and inflammation drive plaque growth.
Cholesterol shows up at the scene because it is part of transport and repair. It is present in plaques, but it is not the initiator.
What to measure beyond total cholesterol
ApoB: a direct count of atherogenic particles.
Triglyceride-to-HDL ratio: lower is better, tracks with insulin sensitivity.
High-sensitivity CRP: a window into systemic inflammation.
Fasting insulin or HOMA-IR: insulin resistance raises risk even with normal glucose.
Lp(a): genetically set and useful to check once.
Blood pressure and smoking status: direct drivers of endothelial injury.
Why some people run high and stay healthy
Strong LDL receptor function and low inflammation mean high LDL can reflect a genetic set point, not disease.
Low triglycerides with high HDL signal good fat metabolism and fewer small dense LDL particles.
Normal blood pressure, no smoking, active life, and stable glucose protect the endothelium.
Why others with similar numbers do not
Insulin resistance raises VLDL production, raises triglycerides, lowers HDL, and shifts LDL smaller and denser.
Chronic hyperglycemia glycates lipoproteins and vessel proteins.
Seed-oil heavy diets rich in linoleic acid increase oxidized lipids in a high-sugar context.
Hypertension and smoking injure the endothelium and speed retention.
High ApoB plus high inflammation is the high-risk pairing.
How to improve the context
Control glucose: focus on protein, natural fats, and low-starch vegetables. Avoid sugar and refined grains.
Replace seed oils with butter, olive oil, avocado oil, beef tallow, or ghee.
Eat seafood for omega-3 intake.
Maintain a healthy waistline. Walk daily and include resistance exercise.
Support blood pressure control: sleep well, address apnea if present, limit alcohol, and do not smoke.
Get morning sunlight. Manage stress with breath work, prayer, or time in nature.
Track ApoB, triglycerides, HDL, hs-CRP, fasting insulin, and blood pressure. Recheck after lifestyle changes.
Dr. Bart Kay’s Insight
Dr. Bart Kay brings deep insight and expertise as a former senior lecturer in cardiovascular and respiratory physiology, exercise physiology, and human nutrition. He spent years teaching medical and health science students at universities in New Zealand and Australia, building a reputation for breaking down complex physiology into clear, evidence-based explanations. His background in metabolism and lipid transport gives weight to his position on cholesterol.
Mainstream medicine has long focused on lowering cholesterol, especially LDL, as the main way to reduce heart disease risk. Statins became the standard prescription, often given without addressing diet, lifestyle, or metabolic health. This view treats cholesterol itself as the cause of cardiovascular disease.
Kay challenges this paradigm. He emphasizes that the body regulates cholesterol tightly, and your genes set your personal baseline. High cholesterol alone is not a disease. Instead, he points to the real drivers: retention of ApoB particles in the arterial wall, oxidation of LDL, glycation from high blood sugar, and chronic inflammation. These processes, not cholesterol itself, are what damage arteries and promote plaque.
His focus is on fixing the context. Improving insulin sensitivity, lowering blood sugar, avoiding unstable seed oils, controlling blood pressure, and reducing inflammation all protect arterial health. In this framework, cholesterol functions as it should: a vital molecule needed for cell membranes, hormones, vitamin D, and bile acids.
Kay’s expertise highlights a critical shift. Cholesterol is not the villain, but a misunderstood player. It becomes problematic only when the metabolic environment is broken.
Simple takeaways
Cholesterol is essential. Your genes set much of your baseline.
High LDL can be fine in a low-inflammation, insulin-sensitive state.
Risk rises when ApoB is high in an injured, inflamed endothelium.
Test beyond total cholesterol. Improve the metabolic context. Protect the vessel wall.
Disclaimer: The content shared here is for informational and educational purposes only and should never be taken as medical advice.
In writing this blog post, my goal is to distill research findings into a clear, approachable format that encourages critical thinking and empowers you to make informed decisions about your health.
