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@DaveKeto

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Nick Norwitz MD PhD

@nicknorwitz

Oct 15

1/6) How Fructose Hijacks the Liver to Fuel Cancer (Link in 6/6)

Quote: “In all cases, diets supplemented with high-fructose corn syrup resulted in faster tumor growth compared with control diets.”

This includes melanoma, breast, and cervical cancers. What’s going on is ‘sneakier’ than you might think? Let’s break it down 🧵👇

2/6) Cancer is a master hijacker. In this case, it co-opts the liver. When the liver gets fructose, it turns it into molecules that cancer cells repurpose into specific phosphatidylcholines—key building blocks for cell membranes.

Fructose → liver → raw materials for cancer’s construction project.

3/6) But this isn’t just about fructose—it’s about how molecules we eat aren’t passive.

And, it’s why I can’t stand the phrase “empty calories.”

That phrase implies calorie-containing molecules (e.g. fructose) are neutral unless they come with nutrients. But that’s empty thinking. Here’s why...

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Nick Norwitz MD PhD

@nicknorwitz

Oct 14

DON'T DRINK Again Until Your Read THIS 🍺🍷🧠

(1/8) Sleep Deprivation Mimics Drunkenness on a Molecular Level — Here’s What That Really Means (Link in 8/8)

A paper in PNAS that provides a stunningly deep dive into how a lack of sleep and alcohol hijack the brain through the exact same pathway.

Stick with me. I'll break down why society's acceptance of "burning the midnight oil" is so dangerous.

(2/8) When I first opened this paper, I was struck by a simple thought: we socially accept exhaustion but demonize drunkenness.

We praise the all-nighter but would be horrified if a surgeon showed up to the OR after a few drinks. The data in this paper reveals just how backward that thinking is.

It turns out that both states flip the very same master “dimmer switch” in the brain. This switch is governed by a key molecule called adenosine, and it explains why the cognitive impairment from sleep loss is so severe.

(3/8) So let me break down that dimmer switch.

Think of adenosine as your brain's 'sleep pressure' gauge. As your cells burn energy all day, adenosine is the metabolic exhaust—it slowly builds up, pushing you toward rest. Normally, sleep is the cleanup crew that clears it all out.

But when you pull an all-nighter, that cleanup crew never arrives.

Adenosine builds and builds, cranking down your brain's dimmer switch.

Here's the kicker: alcohol is like a master key that lets a stranger into the control room to do the exact same thing. Two different paths, one identical outcome of cognitive impairment.

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Nick Norwitz MD PhD

@nicknorwitz

Oct 11

Cholesterol Confessions of an MD PhD Lean Mass Hyper-Responder. (link at the end)

1/7) I gave my cardiologist a heart attack. Well—not literally. But when a cardiologist sees an LDL cholesterol of 574 mg/dL, their eyes bug out like they’re a human-sized fruit fly.

And I understand why.

That number is higher than anything most doctors have seen in their entire careers. And it’s scary. It is.

It rivals levels found in “homozygous familial hypercholesterolemia,” a rare genetic disorder—occurring in ~1 in a million—that can cause fatal heart attacks in children as young as eight.

But I don’t have familial hypercholesterolemia.
Something very different is going on inside my body…

2/7) Today’s letter is an overdue ~3000-word essay on:
🩸My lipid levels
🩸Background on people like me
🩸Disclosure on my personal choices
🩸What I'm doing next
staycuriousmetabolism.substack.com/p/im-a-harvard…

Warning: It’s intense. And it’s only the beginning.

Caution: Please do not take this as medical advice or even the suggestion of such. Instead, my purpose is providing discloses it to reveal how I think, not what to think.

Note: The back half of the letter is currently only available for premium subscribers. For now, I’m reserving the most complex and intense details for a smaller, highly committed audience. Call it an intellectual stress test.

3/7) Still, at a high-level here in this thread, I want to reinforce a few points:

🚨First, people like me – lean mass hyper-responders (LMHR) on ketogenic diets – are unlike any other population ever studies with high LDL and ApoB.

🧬Our lipid levels are NOT the result of a congenital genetic lipid disorder (like familial hypercholesterolemia). And, generally, LMHR are in excellent metabolic health.

For these reasons, it’s in appropriate to extrapolate from the existing “preponderance of evidence” any certain claims with respect to cardiovascular risk to people like me.

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Nick Norwitz MD PhD

@nicknorwitz

Oct 7

🚨Low-Carb Gaslighting: How THIS Became “Keto” Science (link at the end)

1/8) What if you could live on a diet of Reese’s Peanut Butter Cups, lose body fat, and improve your health?
It sounds absurd—and it is.

But the absurdity of that thought experiment highlights a persistent misunderstanding about ketogenic and low-carb diets.

In today’s letter, I step through four shocking examples of low-carb and keto gaslighting—ultimately building to answer the question: why are these diets so grossly misunderstood.

@AKoutnik @janellison @realDaveFeldman @metcoalition @Metabolic_Mind @bschermd @TuitNutrition @BiggestComeback @BenBikmanPhD @thelowcarb_rd

2/8) Study 1: Skews the Truth with “Scores”

Take as our first example, recent study that was touted as “proof” online that low-carbohydrate diets don’t help—or can even exacerbate—diabetes.

At first, the headlines seem compelling, if for no other reason than the American Diabetes Association “seal of approval.”

But what did the researchers actually measure? What did they call “low-carb?”

This was a nutritional epidemiology study based on food-frequency questionnaires. Participants self-reported their diets, and researchers divided them into quintiles (fifths) according to carbohydrate intake. They then assigned each group a “low-carbohydrate score” relative to the others.

3/8) Here’s the problem… The lowest-carb group across multiple cohorts was still eating ~40% of calories from carbohydrates.

That’s not low-carb—it’s about the same carb proportion you’d find in a Reese’s Peanut Butter Cup.

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Nick Norwitz MD PhD

@nicknorwitz

Oct 5

Food is Medicine. Why Are We Poisoning Patients?

1/4) This is a plate of food at the hospital.

They say a picture is worth a thousand words. But I’d argue the fact that a wealthy, advanced Western society feeds its sick like this says more than all the words in the English language.

So, we must ask: Why do we do this?

And, how do we dig ourselves out of this sticky situation?

2/4) Honestly, the “why” is simple can be summed up in a words: ignorance.

I don’t believe those trays of food are driven by malice. I think it’s a genuine lack of understanding about just how harmful meals like these can be—especially for the metabolically vulnerable.

We toss around and consume misleading terms “empty calories,” phrases that distort biological reality.

On this example, nutrients that calories – carbohydrates (fructose, glucose), fats (stearic acid, linoleic acid, butyric acid), etc. – aren’t just passive carriers of vitamins and minerals; they are active biological signals with direct effects on your metabolism, mitochondria, and immune system.

3/4) For example, the photos I mentioned earlier. Each was a meal given to patients with some form of glucose dysregulation during the COVID pandemic.

And, in fact, we know how high blood sugar alters immunity and increases risk of severe COVID or risk of death from COVID: Let me inject you with some knowledge:

💉Hyperglycemia (high blood sugar) causes mitochondrial dysfunction.
💉Unhealthy mitochondria increase the production of reactive oxygen species (ROS), leading to oxidative stress.
💉This results in the oxidation of fragile lipids (fats), a process called lipid peroxidation (LPO).
💉 LPO, in turn, leads to the degradation of STAT4, a protein that regulates gene expression and the differentiation of CD4+ T-cells—key players in antiviral immune defense.
💉This sequence ultimately leads to impaired immune response and higher morbidity and mortality in those with T2D and poor glycemic control.

In short: Chronically high blood sugar weakens your immune system at the cellular level.

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Nick Norwitz MD PhD

@nicknorwitz

Oct 4

The Gut Molecule Makes Blood Less “Clotty” (New Research) 🔗 in 8/8

1/8) Imagine your blood as a river, delivering life to every organ downstream. A heart attack is a dam—a single clot that blocks that river, starving your heart or brain until it begins to die.

A new paper in @NatureCVR (PMID: 40217125) has identified a key molecule from our gut that keeps this river flowing.

Stick with me. I’ll break down these data.

2/8) Researchers compared patients with coronary artery disease (CAD) to healthy controls and found a stark deficiency.

The CAD patients had significantly lower levels of a particular bile acid called Deoxycholic Acid (DCA).

They also had fewer of the specific gut microbes responsible for producing it, revealing a potential link between a missing microbe and a missing protective molecule.

3/8) What is the functional consequence of low DCA?
In plain English: their blood was clottier.

The study showed a direct inverse correlation between DCA levels and platelet aggregation.

The ultimate consequence?

In their four-year follow-up data, higher DCA levels were linked to a lower risk of heart attack, stroke, or death (adjusted hazard ratio = 0.43).

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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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