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Nick Norwitz MD PhD

@nicknorwitz

Jan 17

A Nuance Hidden in a Historic Statin Trial (link in 12/12)

1/12) Medicine is supposed to treat individuals, not populations averages. And yet, the imprecision remains, like an intellectual cancer.

So, let’s look back at one of the most pivotal studies in cardiovascular history: the 4S trial, an see what is reveals when we stratify but just two biomarkers: TG and HDL

(And if you think you know where this goes, you're in for at least one plot Twist... 🚭)

2/12) According to cardiologists, the 4S trial is widely regarded as the study that launched the statin era.

4S was a randomized, double-blind, placebo-controlled study that enrolled 4,444 participants established coronary heart disease.

Patients were assigned to receive either simvastatin (20–40 mg daily) or a placebo and followed for 5.4 years.

The headline findings were that the statin (simvastatin) significantly reduced overall and cardiovascular mortality.

But there’s another part of the story—

3/12) A follow-up published in Circulation in 2001 reanalyzed 4S participants by their HDL-C and triglyceride (TG) levels as well.

“Lipid Triad” = those with highest quartile of TG + lowest quartile HDL-C

(This pattern is characteristic of insulin resistance and metabolic syndrome.)

“Isolated High LDL” = Those with lowest quartile of TG + highest quartile HDL-C

So how did these groups differ in terms of outcomes?

Read 12 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 15

Dr @PeterAttiaMD recently published an article entitled, "Pitting facts against sensationalism regarding the role of LDL cholesterol in ASCVD"

1/9) Peter opens with a quote: “We must admit that our opponents in this argument have a marked advantage over us. They need only a few words to set forth a half-truth; whereas, in order to show that it is a half-truth, we have to resort to long and arid dissertations.” ― Frédéric Bastiat

I could not agree more.

That's the purpose of today's letter... to discuss Where's the Nuance, Really?!

Specifically, where is the nuance on Longevity, Cholesterol and ApoB?

What follows is a teaser for a 25 page, 4000 word "long and arid dissertations" -- linked in 7/9 🔗

Punchline: When talking about deceptive simple messaging and biased narratives, medicine should look in the mirror as well.

Let's begin...

2/9) Here's where I want to start: The three dumbest words in medicine are: “Lower is better.”

This refers to lowering LDL cholesterol or ApoB.

It’s medical clickbait—seductive, oversimplified, and deeply devoid of nuance.

3/9) But better for what? How much better? And how are we lowering it?

“Better” typically means cardiovascular outcomes only—not brain health, not metabolic health, not overall healthspan or lifespan.

“How much better” matters too. Saving 1 life per 10,000 patients treated vs 1 life per 10 treated are radically different facts in a risk‑benefit calculation—yet both get flattened into “better.”

It’s like comparing getting a double-yolk egg to the birth of your child. Stupid.

Read 9 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 13

“You are going to die young.”

1/8) The first time I heard those six words, they were jarring. I was 23.

The insult that provoked that perceived threat was a single number on a lab report: my LDL cholesterol (LDL-C).

After I started a ketogenic diet (June 1, 2019), my LDL-C more than tripled from 95 mg/dl to 321 mg/dl.

Link at the end...

2/8) The logic was straightforward:

If I allowed my LDL-C levels to remain in the stratosphere, I would inevitably develop cardiovascular disease and die of a heart attack—young.

The question is this: Does LDL—or more accurately, ApoB—kill?

It sounds like an easy question. But it isn’t.

3/8) Now, there is controversy about the relationship of ApoB to All-Cause Mortality (ACM), or death by any cause.

Some people note that there’s a J-shaped relationship between ApoB and ACM and read into this that lower ApoB might not necessarily be better.

Read 8 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 11

🚨The New Dietary Guidelines Are Internally Inconsistent

1/7) Publicly, RFK Jr. says “we’re ending the war on saturated fat.” The iconic food pyramid has been flipped, with butter and beef now at the top.

But read the actual guidelines, and you’ll find the exact same restriction: saturated fat still capped at 10% of daily calories. No change.

(People may not like this thread or the linked long-form letter. But I'm not here to pander or choose political sides. I'm here to seek the clarifications I know Americans want and to 'tough love' this step in the right direction into a proper leap...)

cc @RobertKennedyJr @HHSGov

2/7) How can one recommend:
👉Cooking with butter and tallow
👉Eating full-fat dairy three times a day
👉Prioritizing red meat…

🚨Yet still limit saturated fat to 10% of calories? That’s not an opinion. The math doesn’t math?!

Full Breakdown: staycuriousmetabolism.substack.com/p/the-new-diet…

3/7) Other surprises you might have missed:

The sodium cap? Still 2,300 mg/day.

There's still a minimum serving of whole grains

Yes, there are changes. But this isn’t the radical inversion it’s being made out to be. My two cents.

I’m not saying that’s bad. It just is.

Read 7 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 10

1/10) No word yet from 'Dr' Johnson. So, I've decided to use this as a springboard to deeper learning.

Quick review: in a recent Twitter exchange between @chamath and @bryan_johnson, Bryan proclaimed: “Definitely do not stop statins.”

Today, we deconstruct common logical missteps that could lead to this misguided medical mandate.

A 🔗 to the full letter is at the end.

This won't be shallow reaction content, but an opportunity to dive deep...

2/10) Main Point #1: Causality is Overrated

Just because a molecule or biomarker plays a causal role in a disease process does not mean it is sufficient to cause disease.

More importantly, it does not mean intervention is the prudent path.

The presence of a “causal” variable does not ensure disease nor is the treatment benign.

3/10) Let me emphasize the point with an intentionally absurd analogy.

A penis is part of the causal pathway by which a biological male contracts a sexually transmitted disease. Amputation of the causal variable will reduce STD risk.

But in this case, as with the case of LDL cholesterol, presence of the causal variable does not ensure disease nor is the treatment benign.

Read 10 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 8

Can TUDCA Really Slow Atherosclerosis? 🫀

1/6) The bile acid and supplement, TUDCA, has the potential to reduce atherosclerosis.

And it appears to do so not by lowering cholesterol, but by reducing inflammation inside arteries. (Red = fatty deposits in arteries)...🔗 in 6/6

2/6) In atherosclerosis, macrophages in the artery wall take up too much oxidized LDL.

This can trigger *ER stress* and activate inflammation, pushing the macrophages into *foam cells* that are a cause and hallmark of atherosclerosis.

3/6) In TUDCA supplementation experiments, TUDCA did not alter total cholesterol or LDL cholesterol levels but led to a significant reduction in arterial fatty deposits in arteries (red staining).

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More from @nicknorwitz

Nick Norwitz MD PhD

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Nick Norwitz MD PhD

Nick Norwitz MD PhD

Nick Norwitz MD PhD

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