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Nick Norwitz MD PhD

@nicknorwitz

Feb 1

Cholesterol Debates in the Era of Medical Mistrust

1/4) This graph shows the hazard ratio for coronary heart disease associated with insulin resistance score (LP-IR) versus LDL cholesterol.

It’s not even close. Insulin resistance dwarfs LDL—with a >14-fold difference in relative risk.

2/4) So why does LDL get all the attention?

Simple: It’s easy to manipulate—and highly profitable.
The statin industry alone generates over $20 billion annually. It would be naive to pretend financial interests don’t shape medical priorities.

That’s not a conspiracy theory. It’s acknowledgement of incentive structures that ultimately dictate the spotlight of research, guidelines and medicine.

3/4) And—despite better drugs and relentless focus on LDL as the biomarker cardiology loves to hate—CVD remains a top killer.

That shouldn't be acceptable. Big problems demand hard conversations—and honest autopsies on where we’ve gone wrong in medicine.

If we’re serious about orphaning cardiovascular disease, we must target the metabolic dysfunctions beneath the surface—the ones that often get overlooked and left in the shadows.

Read 4 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 24

Protein-Maxing and the Illusion of Nutritional Progress

1/8) David Bar is the world’s most hyped protein bar—boasting ~75% of Calories From Protein (CFP) and the tagline “only what’s necessary.”

But how does it stack up? Let's have a dispassionate discussion...🧵👇 (link in 8/8)

2/8) Formulation: I’d give it a 3/10.

Despite the “only what’s necessary” claim, it contains two artificial sweeteners (Ace-K and sucralose) and the controversial artificial fat EPG.

Seems like inconsistent messaging at the very least. But what about these ingredients?

3/8) Take, sucralose, for example.... It has been shown in human-controlled studies in certain contexts (co-ingested with carbohydrates) to promote insulin resistance.

TL;DR: Don’t chase David Bar with a banana.
More in letter:

Read 8 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 20

🚨👉What if a diet that lowered your cholesterol… increased your risk of death? (link at the end)

1/12) That’s what a forgotten a double-blind, randomized controlled trial from the 1970s seemed to show.

It tested whether swapping saturated fats for unsaturated fats would improve heart health.

Results?

The group that lowered their cholesterol... died more often. And the lower their cholesterol went, the higher their risk of death.

And if you think you’ve heard this story before (including a proper assessment of the counterarguments and deeper nuances—you haven’t…)

2/12) The Minnesota Coronary Experiment was a randomized controlled trial conducted between 1968 and 1973 that enrolled 9,423 men and women across six mental hospitals and one nursing home.

The power of this approach—though ethically questionable by today’s standards—was that researchers could truly blind and control patients’ diets with remarkable accuracy

3/12) The researcher tested whether swapping saturated fat for vegetable oil rich in unsaturated fat would reduce heart disease and death.

Butter was replaced with margarine rich in polyunsaturated fat, leading to a diet much lower in saturated fat and higher in unsaturated fat, particularly linoleic acid.

Compared to the baseline hospital diet:
👉 Linoleic acid intake increased by 288%
👉 Saturated fat intake decreased by 51%

Read 12 tweets

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.

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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

Nick Norwitz MD PhD

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