Nick Norwitz MD PhD Profile picture
Sep 28 8 tweets 5 min read Read on X
The Oldest Woman (117) Had “High” Cholesterol 🩸— Here’s What That Really Means🤔(Link 🔗 in 8/8)

1/8) The world’s oldest woman just died. Before she passed, she pleaded, “Please study me.”

A new paper in Cell Reports Medicine (PMID: 39322234) just published provides a deep dive into her genes, metabolism and microbiome. What made this 117-year-old such a supercentenarian?

As a metabolism scientist, this is the kind of data I’d die for (figuratively speaking). Stick with me. I’ll break down what her biology really tells us about aging, and why we might be obsessed with the wrong biomarkers.Image
2/8) When I first read the paper, I noticed something odd.

The authors detailed her lipid profile (HDL, VLDL-TG, etc.) but her LDL-C and ApoB—the numbers most doctors obsess over—was nowhere in the main text.

I had to go hunting in the supplementary data. There it was, buried in a single line of Supplemental Figure 8B: elevated, and in the “red.” -- Granted, it wasn’t super high… but it wasn’t low either.

So what gives? Why was it not mentioned in the main text. I provide thoughts (not conspiracy theories) in the letter. But now I know I have your attention…

cc @realDaveFeldman @AdrianSotoMotaImage
3/8) Now for the next “paradox” - her telomeres 🧬😲

Telomeres are the protective caps on our chromosomes. Think of them like the plastic tips on a shoelace. The prevailing wisdom is that as they shorten with age, our health declines.

You’d expect a 117-year-old to have either freakishly long telomeres or be riddled with disease. Maria Morera had neither.

Her telomeres were tiny!!! I was expecting Godzilla telomeres and was met with chihuahuas exactly as short as you'd predict for her chronological age.

Yet, she was remarkably healthy. This is a crucial finding: telomere length may simply be a clock, not a direct measure of your healthspan.

cc @bryan_johnson, of interest?Image
4/8) So if it wasn't long telomeres, what set her apart?

Her mitochondria. As every high schooler knows, these are the “powerhouses in our cells,” and their decline is a key hallmark of aging.

Maria’s, however, were functioning like those of someone decades younger. The paper notes her mitochondria showed "not only preserved but also robust mitochondrial function."

cc @ChrisPalmerMD @MitoPsychoBioImage
5/8) The evidence for her low "inflammaging" status is compelling. Beyond her genetics, her bloodwork showed remarkably low levels of GlycA and GlycB—advanced biomarkers of systemic inflammation. 🔥

Summary so far: Genetics gave her an edge → leading to highly efficient mitochondria and a low inflammatory burden → which created a biological environment where factors like high LDL or short telomeres didn't lead to disease.Image
6/8) So, what about her lifestyle? For the last 20 years of her life, she ate a consistent diet that included a conspicuous amount of yogurt—three servings per day.

And the paper even specified the bacterial strains: Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus. She was also a heavy user of egg protein and olive oil.

I feel almost as if I designed her diet!

P.S. Smoked Maldon Salt Greek Yogurt is a 12/10
7/8) The clinical implications here are profound. Her case suggests that a state of low inflammation, a “highly engaged lipid metabolism,” and good mitochondrial health can grant resilience against factors we typically view as "bad." Yes, she was genetically gifted. But we can still turn her insights into action… What do we do with this knowledge?
8/8) In the rest of the letter (linked below), we turn these insights into action.

While you can't change your genes, you can support your mitochondria.

I break down her full meal plan, the specific U.S. yogurt brands I found that contain those exact bacterial strains, and actionable strategies — from fasting protocols to light exposure — that support the same mitochondrial resilience seen in this remarkable supercentenarian.

Premium subscribers get full access for less than 67 cents per letter. Read the full breakdown here → staycuriousmetabolism.substack.com/p/the-oldest-w…Image

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More from @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 🧵👇Image
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.Image
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...
Read 6 tweets
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.Image
(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.Image
(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.Image
Read 8 tweets
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…Image
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.Image
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.
Read 7 tweets
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_rdImage
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. Image
Read 8 tweets
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?Image
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.Image
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.Image
Read 4 tweets
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.Image
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).Image
Read 8 tweets

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