Chasing the wrong rabbit – why cholesterol levels are just a distraction

The statin industry runs to roughly 30 billion dollars a year in the United States. A meaningful portion of cardiology research budget is spent on what amount to repeated justifications of that spend. The JUPITER trial, the IMPROVE-IT trial, the various other primary and secondary prevention studies, all of them with a similar structure. Lower LDL cholesterol, claim a reduction in cardiovascular events, conclude that statins should be prescribed more aggressively.

I am not anti-statin. I have prescribed them in the right patients. I am anti-distraction. And the cholesterol-as-master-risk-factor framing has become a distraction from the variables that actually drive risk in most patients.

The populations that break the cholesterol model

Look at traditional Inuit populations on their ancestral diet. Many have elevated total cholesterol. Many have meaningful body weight and elevated blood pressure. They have, historically, very low rates of clinical coronary heart disease.

Look at traditional Japanese populations on the ancestral diet. Similar picture. LDL cholesterol levels that would prompt any U.S. primary care doctor to start prescribing statins. Much lower clinical heart disease rates than equivalent Americans.

And this is not driven by some hidden HDL benefit. Yes, these populations tend to run higher HDL than Western controls. The LDL numbers are still the kind that, by current treatment guidelines, would prompt aggressive intervention.

So is it genetics? An Inuit-specific allele that protects against atherosclerosis despite cholesterol? Not really. When traditional populations move to a Western diet, their cardiovascular disease rates converge with American rates within a generation or two. The protection is dietary, not genetic.

What the diet has in common

The protective traditional diets share a few features.

• A much more favorable omega-6 to omega-3 ratio. The Inuit pattern runs close to 1:1 or even omega-3 dominant. The Western pattern runs around 15:1 to 25:1.
• Lower glycemic load. Less refined carbohydrate. Smaller insulin excursions.
• More nutrient density per calorie. More minerals, more fat-soluble vitamins, more polyphenols.
• Smaller individual meal sizes. Less of a free-fatty-acid release burden on the liver.

The mechanism most clinicians do not talk about

LDL particles do not cause atherosclerosis by being present at a certain blood concentration. They contribute to atherosclerosis when they are oxidized and when they pass into a vascular wall that is already inflamed. The inflammation is the precondition. Without it, LDL is largely a transport vehicle.

What drives the inflammation? Several things, but among them, prominently, is the imbalance between omega-6 and omega-3 fatty acids in cell membranes and the eicosanoid pathways they feed. High omega-6, low omega-3 means the body’s resolution-of-inflammation pathways are starved of substrate while the pro-inflammatory pathways are flooded with it.

The other driver is metabolic. Large boluses of calories, particularly in the form of refined carbohydrate plus fat, force the liver into free fatty acid release. The released free fatty acids contribute to small-particle LDL formation, which is the more atherogenic LDL pattern. Smaller meals, with adequate protein and fiber, reduce that flux.

What to actually do

If you want to lower your cardiovascular risk in ways that respect the actual biology, three changes do most of the work.

1. Reduce omega-6 intake. Cut seed oils, switch to olive oil, butter, ghee, and animal fats from well-raised sources. Read labels.
2. Increase omega-3 intake. Eat fatty fish two to three times a week, supplement with a clinically dosed fish oil to a measured omega-3 index above 8 percent.
3. Eat smaller, more frequent meals with adequate protein and fiber. Avoid the large evening meal that loads the liver after the day’s metabolic flexibility is exhausted.

You can do most of this with food. You will not be able to do all of it. Few of us live a perfectly clean dietary life. That is what supplementation is for.

A note on fish oil purity

Mercury is a real concern in fish, particularly larger predator species. The FDA’s current advisories acknowledge limits for pregnant women and young children. For long-term high-frequency consumption in adults, the cumulative load matters even if the individual meals are below the official action level. The long latency of mercury toxicity, particularly the neurological forms, means that finding the source decades later is hard. A purified fish oil, distilled to remove mercury and PCBs, sidesteps the concern.

I have my own product purified to parts-per-trillion levels for that reason. Whatever brand you choose, ask for the certificate of analysis. Any reputable manufacturer will provide one.

The cholesterol story has a place. It is not the whole story. Probably not even the most important part of the story for most people. Chase the right rabbit.

— Doc