Nick Norwitz

I accidentally supercharged my metabolism with sardines 🐟⚡
Link: staycuriousmetabolism.substack.com/p/the-weird-ant…

After sharing my Sardine Diet experiment, one unexpected side effect stood out: I became oddly cold-resistant.

Imagine standing shirtless in a Boston winter and feeling... fine. Almost comfortable.

Strange? Yes. But also grounded in biochemistry.

As I dug into the literature, a fascinating pathway emerged.

It turns out metabolically active brown fat can convert omega-3s into a signaling molecule called 12-HEPE. This molecule ramps up thermogenesis (heat production), pulls glucose into muscle, and boosts energy expenditure.

It’s a cold-adaptation mechanism—but fueled by omega-3s, not just temperature.

In humans, activating this pathway pharmacologically led to a surge in 12-HEPE and increased glucose uptake into brown fat—a metabolic shift toward heat.

There are also data showing that obesity is a 12-HEPE-deficient state.

Interesting… 🤔

There’s a lot more to unpack—including the full study data and some surprising insights from my own experiment.

If you’re interested in:
👉 The metabolic power of brown fat
👉 Why omega-3s may do more than just fight inflammation
👉 What cold exposure teaches us about fat-burning…

Check out the full letter (linked above).

#Metabolism #Longevity #HealthTech #SelfExperimentation #NutritionScience #Omega3 #BrownFat #GlucoseMetabolism #FunctionalMedicine

10 hours ago | [YT] | 326

Nick Norwitz

Want to get your Omega-3s to your brain, not your fat? Listen up…
staycuriousmetabolism.substack.com/p/why-omega-3-s…

Most Omega-3 supplements are a "letter with no address."

The Paradox: We know that eating fatty fish is associated with lower rates of Alzheimer’s and better cognitive longevity. 

Yet, clinical trials with Omega-3 supplements often yield disappointing results.

Why the disconnect? It comes down, at least in part, to biochemistry.

The form of the molecule dictates the destination. Most supplements provide Omega-3s as triglycerides, free fatty acids, or ethyl esters.

But the brain prefers a specific form: Lyso-DHA (DHA bound to phospholipids).

The Mechanism (MFSD2A): The brain has a specific transporter called MFSD2A.

“Normal” DHA: Like mailing a letter with no address. It doesn't get past the blood-brain barrier efficiently. It ends up in your fat cells (adipose tissue).

Lyso-DHA: This is the "Express Courier." It has the code to unlock the MFSD2A transporter and get straight into the neuron.

The Data: In comparative studies, Lyso-DHA was shown to more than double brain DHA levels, while free DHA was preferentially sent to fat (adipose) tissue.

TL;DR: Form matters.

Check the link above for the full deep dive

#Alzheimers #ApoE4 #Omega3 #BrainHealth #Neuroscience #Biohacking #Longevity #DHA #NutritionScience

2 days ago | [YT] | 336

Nick Norwitz

We know that poor metabolic health is linked to higher rates of anxiety and depression. But the key question remains: Is this association causal?
staycuriousmetabolism.substack.com/p/how-metabolic…

New research going to print this week in Cell Host & Microbe suggests the answer is "YES"—and identifies the specific molecule responsible.

The study focuses on a bacterial metabolite called imidazole propionate (ImP).

We already knew ImP is elevated in people with Type 2 diabetes and heart disease.

But this new paper shows that ImP can cross the blood–brain barrier and physically alter the brain's stress circuitry. The mechanism is fascinating and terrifying:
👉 Metabolic disease disrupts the gut microbiome.
👉 Specific bacteria produce excess ImP.
👉 ImP travels to the hypothalamus (the brain's control center).
👉 It alters gene expression and neurotransmitter balance.

Check out the full deep dive (linked above) for the data + a 'special announcement' about our new Mental Health-Metabolic Health company, NeuroVitals.

#metabolichealth #microbiome #mentalhealth #newscience #staycurious

4 days ago | [YT] | 228

Nick Norwitz

The LDL Illusion... We might be measuring the wrong marker...
Link: staycuriousmetabolism.substack.com/p/the-ldl-illus…

When I was a kid, I figured out that drinking really hot chocolate right before my mom took my temperature could fake a fever.

The thermometer said "sick." But I was perfectly healthy.

In medicine, we call this a surrogate marker. And a new massive meta-analysis suggests we might be falling for the "hot chocolate" trick when it comes to LDL Cholesterol and Statins.

The New Science:

A review published in the European Heart Journal analyzed 20 Randomized Controlled Trials (RCTs) including 194,686 participants.

🤔 The researchers asked a simple question: Does the magnitude of LDL reduction predict the reduction in cardiovascular risk?

🫨 The answer: Not really.

Here is the data breakdown:

The Statistic: They looked at r2 (which tells you how well one number predicts another).

The Result: The r2 for LDL-C on major adverse cardiovascular events ranged from 0 to 0.1.

The Translation: Reducing LDL-C more didn't necessarily mean reducing heart attacks more.

But wait—This is where the nuance lives (and why headlines often fail us).
In these trials, statins did reduce cardiovascular events. But if the LDL drop wasn't the predictor, what was?

The likely answer is a complex set of effects on the background of metabolically unwell patients.

Statins don't just lower cholesterol. They are also anti-inflammatory and improve vasodilation (blood flow). In a metabolically unhealthy population (which is most of us), these effects might be the real heroes, while LDL gets all the credit.

We have built a massive industry on a surrogate that, in isolation, might just be hot chocolate.

Read more by clicking the link above. And remember... sharing is caring :).

#metabolichealth #LDL #cholesterol #medicalresearch #newstudy #statins #cardiology

5 days ago | [YT] | 444

Nick Norwitz

Can a Keto Diet Treat Inflammatory Bowel Disease?
Link: staycuriousmetabolism.substack.com/p/a-keto-diet-c…

I went from being destroyed – bleeding out my butt a dozen times with inflammatory bowel disease, emaciated and physically and psychologically wrecked, back to being a happy healthy human.

But my experience isn’t validated by the “gold standard” randomized controlled trial literature.

What I did isn’t “standard of care.” Why?

It’s not because it didn’t work. It saved my life.

It’s because the system we have doesn’t incentivize the sort of research needed to translate my experience into standard of care.

The next best thing is to try to understand what happened to me (and to others) through a deeper understanding of physiology. That’s the real topic of today’s letter.

In today’s letter, I break down: The data from a paper in Cell & tips for optimizing an anti-inflammatory diet (including fermented foods and specific fats).

Check out the link above for more

#ketodiet #metabolichealth #staycurious #IBD #guthealth #microbiome

1 week ago (edited) | [YT] | 282

Nick Norwitz

🎁 A Free Gift Guide for the Metabolically Curious 🎁
Link: staycuriousmetabolism.substack.com/p/saint-dr-nick…

Okay, this is a little out of character. Today, instead of breaking down a new Nature or Cell paper at StayCurious Metabolism, I made a holiday gift guide. (Don’t worry, you’ll still get your routine letters. This is a bonus!)

And not just any guide—these are picks that combine science, health, delight, and nerdy charm. A few come from close friends, scientists, and fellow obsessives.

Here’s a teaser of what you’ll find:

🎁 The best ‘bang for your buck’ health tool you should have
🎁 A heavy fitness upgrade that may lower your appetite
🎁 The $20 kitchen gadget my fav cholesterol researchers swear by
🎁 A piece of wooden neuro-art I just love
🎁 A wearable tool for heart-rate-based recovery training
🎁 A probiotic designed to bind and eliminate microplastics
🎁 The best board game ever (p <0.05)
🎁 The cozy creature that helps soothe chronic pain
🎁 A premium app that does what your doctor can’t

Whether you're shopping for a curious mind or quietly practicing the art of autologous gratitude (read: gifting yourself), this guide might just make your season.

Wishing you a joyful, nerdy, metabolically interesting holiday season.
— Dr Saint Nick, MD PhD

#giftguide #metabolism #microbiome #biohacking #holidayseason #healthtech #longevity #personalizedmedicine #guthealth #sciencegifts #StayCurious

1 week ago (edited) | [YT] | 105

Nick Norwitz

"Fiber is good for you" is lazy science, and I have the data to prove it.
staycuriousmetabolism.substack.com/p/fiber-is-good…

A randomized controlled crossover trial published out of Stanford illustrates exactly how fiber is not a monolith and why individual context matters.

The study was incredibly high-resolution. They collected thousands of data points across genetics, proteomics, metabolomics, lipidomics, and clinical labs—even tracking "fart frequency" to build a complete metabolic phenotype.

They compared distinct fibers.

The results exposed a massive divergence in biological response across groups and across individuals.

*Liver Damage*

One fiber, at high doses, increased a liver damage marker, ALT.
The reaction was severe enough that researchers halted inulin supplementation for those individuals out of safety concerns. The other had no such effect.

*What about Cholesterol?*

One fiber slashed LDL like a katana through butter. The other didn’t.

And the mechanism by which this fiber did so is far more complex and interesting than simply blocking cholesterol absorption. It “trojan horsed” other molecule(s) into the body.

This isn’t a fiber is evil or fiber is wonderful story. That story lacks complex characters. It’s boring. And it’s wrong.

The story I’m going to tell you is FAR more interesting and useful. Click the link above to the full deep dive.

#MetabolicHealth #GutHealth #NutritionScience #PrecisionNutrition #MedicalResearch

1 week ago | [YT] | 389

Nick Norwitz

A Junk Food Binge Can Scar the Brain.
Link: staycuriousmetabolism.substack.com/p/this-study-ch…

I just read a controlled human trial in Nature Metabolism that proves a junk food binge does something far worse than add a few inches to your waistline.

It leaves a "metabolic scar" on your brain.

Researchers took 29 healthy, young men and split them into two groups. One group consumed a "high-calorie" diet loaded with chips, brownies, and junk food for just five days.

Most people focus on the scale, but in this study, the high-calorie group saw no significant increase in body weight.

However, inside their bodies, the story was different. Liver fat spiked by a striking 64% (from 1.55% to 2.54%) and brain blood flow decreased significantly to the hippocampus and fusiform gyrus.

These brain regions are essential for memory, learning, and self-control. They are the parts of your brain that "put the brakes" on impulsive eating. When blood flow drops, those regions go quiet.

Simultaneously, the brain developed specific insulin resistance. It lost the signal to "stop eating."

The binge rewired the brain to crave more while physically weakening the willpower to resist. It’s a vicious biological cycle.

Click the link above for the full deep dive.

#MetabolicHealth #Neuroscience #NutritionScience #PublicHealth #InsulinResistance #NewResearch #BrainHealth

1 week ago | [YT] | 389

Nick Norwitz

How Berberine Lowers Cholesterol: Blew My Mind!
Link: staycuriousmetabolism.substack.com/p/how-berberine…

The nutraceutical berberine has been all the rage. And I just found a paper in Nature Medicine that had my mind spinning.

It turns out, this compound lowers cholesterol via a mechanism completely different from statins or other medications, and the biology is fascinating.

For context, statins work by inhibiting an enzyme (HMG-CoA reductase), causing a state of "cholesterol starvation" inside the liver. → The liver senses this depletion.→This turns on the gene for LDL receptors, pulling more cholesterol from the blood.

Effective? Yes.

But it comes with baggage: mitochondrial disruption, insulin resistance, diminishing GLP-1 levels, etc.

But berberine does something totally different… It stabilizes the "instruction manual" for making LDL receptors.

Normally, the mRNA transcript (the instructions for making LDL receptors) is shredded by your cells after about 1 hour.

Berberine stabilizes this transcript.

It makes the instructions stick around for over 3 hours (a ~3-fold increase).
The result? The liver has more time to build LDL receptors.

In human trials, this translated to a 25% drop in LDL-C and a 35% drop in triglycerides (in patients not on other meds), often with improved metabolic health markers (triglycerides, glucose, etc.)

Mechanisms matter. They tell us about tradeoffs and downstream effects.
I’m currently running an N=1 crossover experiment on myself to test this.

See Link Above for the Deep Dive!

#berberine #cardiovascularhealth #ApoB #LDL #cholesterol #statins #staycurious

2 weeks ago | [YT] | 532

Nick Norwitz

Microplastics increase your risk of heart attack and death by 350%. (Wait for it...)

Link: staycuriousmetabolism.substack.com/p/microplastics…

In a landmark study published in the New England Journal of Medicine, researchers examined arterial plaques from 257 patients. 

They found that 58.4% of these patients had microplastics embedded directly inside their arterial plaque.
The consequences were massive.

Those with plastic in their arteries had a 350% higher risk of cardiovascular death, stroke, or heart attack.

The pathology suggests that jagged plastic particles irritate immune cells (macrophages) inside the artery, creating a "hostile" inflammatory environment that makes plaque more likely to rupture.

Click on the link above to get the deep dive... and the solution (a new microplastic-binding probiotic I'm helping to develop and now using myself)

#microplastics #cardiovascularhealth #microbiome #hearthealth #metabolism #staycurious

P.S. I dad acquire an actual heart for demonstration purposes… although I thought I’d get in trouble for stealing a human heart from the lab… so we have a cow heart.

2 weeks ago | [YT] | 390