Two Major Papers Just Dropped: People With LDL of 300+ Can Be ‘Immune’ to Heart Disease (Top Journal Used That Exact Word)

In a recent livestream with Dr. Ken Berry, Dr. Nick Norwitz tackled a dilemma haunting plenty of carnivore dieters.

Energy soars, weight drops, then a doctor spots an LDL of 250 or 300 and reaches for the statin prescription pad.

Two brand-new papers fuel the debate.

One hints that some people with sky-high apoB may defy textbook predictions, while the other spotlights a gene that clogs arteries even when cholesterol looks perfectly normal.

Do they change what happens next?

Norwitz’s answer is more nuanced than either camp in the cholesterol wars might like.

The Big Takeaway: Context Rewrites the Meaning of LDL

Neither paper says “ignore your cholesterol.” Both say a single number means little without the surrounding metabolic picture.

Norwitz urges patients to question the default, not swear off medicine. Imaging, metabolic markers, and better questions all belong in the conversation.

Paper One: When HDL Is High, apoB Seems to Lose Its Grip

Lipidologist Alan Sniderman led the analysis, published in the European Journal of Preventive Cardiology. Roughly 293,000 people were included.

Norwitz highlighted one punchline from the paper:

When HDL cholesterol is high… the effect of changing apoB vanishes.

The authors even floated that this “might explain the apparent immunity” of some individuals to the clinical consequences of very high LDL and apoB.

How to Read the Graph

• Hazard ratio: 1.0 means neutral risk, above means higher risk, below means lower.
• Normalized apoB: Standard deviations from average, with +2 landing near the 98th percentile.
• Separate lines: Each tracks a different HDL level, from very low (poor metabolic health) to high.

As HDL climbs, risk falls. Meanwhile, the slope flattens from steep to almost flat.

Norwitz placed the lower line, at two standard deviations above the mean, around 84 mg/dL in this cohort. That sits right near the lean mass hyper-responder threshold.

What the Paper Does Not Prove

Norwitz stressed these participants were not carnivore dieters. They were simply people with one marker in a certain range.

It doesn’t mean if your HDL’s just above 84 that now you’re actually immune to apoB. I am not saying that.

Data like these are observational, so they reveal patterns rather than prove cause. For most people, the apoB-risk relationship still slopes upward.

Causality Is Not Importance

Norwitz argues LDL and apoB hog the spotlight because they are “causal” and easy to lower. Causal does not automatically mean most important.

Oxygen is causal to fire. But you don’t want to deplete all the oxygen in your environment. You won’t get a fire, but you’ll suffocate to death.

HDL, by contrast, works more like a litmus test for metabolic health than a lever to pull. Even then, he cautions that very high HDL can stem from different causes, from lean metabolic health to binge drinking.

Paper Two: The “Guardian of the Artery”

The second study, published in Cell, centers on an immunoregulatory gene called GIMAP6. Norwitz nicknamed its protein the “guardian of the artery.”

Knock it out in animals, and aortas fill with inflammatory immune cells and become leaky. Cholesterol stayed normal.

Humans carrying these mutations also have normal cholesterol, yet develop cardiovascular disease and die early. Norwitz pointed to UK Biobank data showing an odds ratio near eight for atherosclerosis, on a logarithmic scale.

His read: leakiness and inflammation appear to precede plaque. That challenges the classic “response-to-retention” model, where LDL drifts into the artery wall and seeds trouble.

Imagine, if rather than discovering those kids first, we discovered this other group who are at least at equal risk, maybe even greater risk, have normal cholesterol… How do you think history would have unfolded?

Keep perspective: this is a rare mutation, so it illustrates inflammation’s power rather than disproving LDL’s role. Norwitz’s practical lesson stayed simple: get inflammation down in your body and arteries.

Should Anyone Still Consider a Statin?

Norwitz steel-manned the conventional view. For people with low HDL and poor metabolic health, the apoB-risk slope is steep.

Statins also do more than lower LDL, since they can reduce arterial inflammation and support nitric oxide. If arteries are inflamed, those effects matter.

At an individual level, be thoughtful. Don’t necessarily extrapolate off population data.

He also flagged a 2024 Cell Metabolism study of 40 people in which a statin lowered GLP-1 levels by about 50% over 16 weeks. Small and not proof of clinical harm, but he argues molecular effects deserve far more attention.

Look Outside: Imaging Beats the Forecast

Both hosts landed on the same analogy. Lipid numbers are a weather forecast, while cardiac imaging is stepping outside to see whether it is actually raining.

You can actually go look in your arteries and see is there plaque there, which is always going to beat some biomarker.

Six Questions to Ask Your Cardiologist

Norwitz suggests walking in curious instead of combative:

1. How does my metabolic health influence your assessment of my heart health risk?
2. What evidence supports treatment in someone with my metabolic profile?
3. What is my expected absolute risk reduction from the treatment you recommend?
4. What testing would change your decision?
5. What are the potential harms of treatment?
6. What are the alternatives?

How somebody responds to a question is a really good litmus test. You don’t need a medical degree to figure out like is this person bullshitting me or patronizing to me? Or are they trying to work with me?

Markers Worth Tracking Beyond LDL

• Blood pressure: Described as “very important.”
• HDL and triglycerides: Read together with LDL, not in isolation.
• Waist-to-hip ratio: Under 0.8 for women, under 0.95 for men, as a poor man’s proxy for visceral fat.
• A1C and fasting insulin: Berry suggested under 10 is worth celebrating, with closer to 5 ideal.
• hs-CRP: Below 1 is a good inflammation sign.
• Cardiac imaging: Direct look at plaque, where accessible.

When Your Doctor Gets Defensive

Berry asked what it means when a cardiologist stiffens, sits taller, and looks down at a patient asking these questions. Norwitz’s verdict was blunt.

Find a new doctor.

He offered grace, too. Many physicians sincerely believe they are protecting patients, and handing over control is a legitimate choice for those who trust their doctor’s judgment.

For anyone wanting a partnership, though, Norwitz says to find someone who treats you “like a partner” instead of “an object to be manipulated.”