Nick Norwitz MD PhD

Master Your Nervous System to Improve Your Heart Health

Deep dive here: staycuriousmetabolism.substack.com/p/how-to-master…

There’s a connection between your brain and your heart that you can leverage to improve your heart health.

In human studies, activating this system has been shown to improve heart rhythm and measurably reduce inflammatory molecules in the blood, like TNF-alpha.

And this has been demonstrated in not one, but several controlled human studies.

But the converse can also be dangerous. Outbursts of anger, for example, have been associated with a nearly fivefold increase in heart-attack risk in the hours that follow. And even simply recalling an anger-provoking experience can temporarily impair blood vessel function.

In today’s letter, we get into a masterclass on how to use your nervous system to improve your heart health.

1 day ago | [YT] | 248

Nick Norwitz MD PhD

A diet made people 2.5 years biologically younger.

Deep dive here: [open.substack.com/pub/staycuriousmetabolism/p/how-…](open.substack.com/pub/staycuriousmetabolism/p/how-…)

Not younger-looking. Younger by a blood test that predicts mortality better than your birthday does.

It took 15 days of eating. And there was no association with weight loss.
It's called the fasting mimicking diet.

The premise is simple: fasting triggers deep metabolic changes, but you often need several days straight of water-only fasting to see the major changes.
So, researchers asked: could you eat just enough to stay sane, while your body still thinks it's fasting? Turns out, yes.

The protocol: ~5 days of low-calorie, low-protein, higher-fat eating (~1,000 kcal/day). Then back to normal. That's one cycle.

So, what happened when people did 3 cycles over 3 months?

Three 5-day cycles of the fasting mimicking diet over three months decreased biological age by a median of 2.5 years.

And a second independent trial found nearly the same thing.

Notably, while there was a decrease in weight and liver fat, the decrease in biological age was not associated with how much weight anyone lost. Losing more weight didn't predict more benefit.

So, what’s going on? And what are the lasting effects?

Today’s letter linked above is a deep dive into the Fasting Mimicking Diet:

The effects on longevity, heart disease, and cancer risk

Who is most likely to benefit, and why

Exactly how to build a Fasting Mimicking Diet yourself, and on a budget

#FastingMimickingDiet #BiologicalAge #Longevity #MetabolicHealth #AntiAging

4 days ago | [YT] | 398

Nick Norwitz MD PhD

🚨 Very Exciting Announcement!

We’re officially releasing My Digital Mind at StayCurious Metabolism Substack.

🔗 staycuriousmetabolism.substack.com/cc/ask-nick

But let me give you a little context.

Over the past year, StayCurious Metabolism has grown from its infancy to become a top bestseller on Substack and, by far, the most often #1 Top Rising Science newsletter on the platform. In fact, we’ve spent more time at #1 on the Rising Science leaderboard in 2026 than all other science newsletters combined.

🫵 And that’s all thanks to you, your enthusiasm, and your curiosity.

But as we’ve scaled, one of the challenges I’ve faced as a creator is the limitation of my own time. As much as I’d love to respond to every comment, answer every question, and correspond with each of you personally, there simply aren’t enough hours in the day.

So, we’ve been working on something special.

We’ve partnered with Delphi to create a digital version of my mind, trained on my entire body of work.

That includes >300 letters, >500 videos, dozes of papers, posts, and thousands of hours of podcast content.

In fact, it's trained on >4.5 million words of my original work, which is more than All the Harry Potter Books and all the Lord of the Rings Trilogy combined times three! And it's growing every day!

This isn’t just a random chatbot.

It’s a digital facsimile of my brain, built around my scientific interests, research, explanations, and perspectives, that you can interact with at your leisure.

Want to explore a topic from one of my letters? Ask a follow-up question about a video? Dig deeper into the science of metabolism, nutrition, or longevity?

Now you can.

And unlike me, my digital mind doesn’t need to sleep!

📢 Built With You, for You

We first launched this tool to our founding members about a month ago, giving them early access to help us beta-test the experience.

The feedback has been phenomenal.

“I used Delphi like I would Claude and ChatGPT. I thought Delphi had better depth in terms of mechanism of action. It really helped me understand a nagging shoulder injury that I have. I like the idea that the outputs are tied to Nick’s knowledge base. Feels more nuanced.”

“I get trustworthy information and perspectives highly relevant to my health and well being that I can’t get anywhere else.”

“The interaction during the commentary was what I would expect from a knowledgeable and caring clinician.”

And this is just the beginning.

As my body of work grows, so will the knowledge and functionality of this tool. And the more you use it, the more feedback we’ll have to continue refining and improving the experience.

My hope is that it becomes an increasingly useful resource for exploring the science, revisiting ideas, and satisfying your curiosity whenever inspiration strikes.

🫂 The Human Touch Isn’t Going Anywhere

Let me emphasize one thing: StayCurious Metabolism will never lose its human touch.

I’ll still be here, writing letters, engaging in the comments, and sharing the science that excites me.

But as our community continues to grow, I want to find new ways to make this experience more personal, not less.

And that’s what my digital mind is all about.

It’s a way to give you greater access to my body of work, help you explore the questions that matter to you, and make our growing library of scientific content more interactive and accessible.

🙌 Give It a Whirl!

Premium members (net cost less than 67 cents per 3,000 word deep dive) get unlimited access. Free subscribers get a free trial.

I look forward to continuing to learn, explore, and grow together.

5 days ago | [YT] | 253

Nick Norwitz MD PhD

Every once in a while, I read a paper that actually changes what ends up on my dinner plate. This was one of those papers, recently published in Nature Aging. And the food in question is a mushroom—a very particular one.

But let’s start with a nutrient: Ergothioneine.

Deep dive here: open.substack.com/pub/staycuriousmetabolism/p/the-…

Ergothioneine is a sulfur-containing amino acid with antioxidant and anti-inflammatory properties. Interestingly, its levels also decline with age, paralleling the gradual loss of antioxidant defenses that occurs as we get older.

In fact, some researchers have even proposed classifying ergothioneine as a “longevity vitamin” or “stress vitamin.”

In this new study in Nature Aging, researchers looked at 1,082 middle-aged adults and found that higher ergothioneine tracked with better cognition, and the direction held for total brain volume, hippocampal volume, and future Alzheimer's risk.
But the more practical question is what sets your level?
But what are the best dietary sources?

Today's deep dive covers: the specific mushroom I'm adding to my diet, how to cook it so you don't wash the ergothioneine down the drain, a full recipe, the gut microbes involved, and the common medication linked to lower ergothioneine and poorer cognition.

Check the deep dive linked above.

#brainhealth #alzheimersdisease #staycurious #mushroom

6 days ago | [YT] | 123

Nick Norwitz MD PhD

This might be the strangest GLP-1 finding I’ve come across all year.

Deep dive here: staycuriousmetabolism.substack.com/p/glp-1-drugs-t…

Researchers studied the brain’s hunger neurons, expecting GLP-1s to switch them off. It did the opposite. The GLP-1 (semaglutide) switched them “ON.”

A drug famous for killing appetite activated the very cells that drive hunger!?

So, what are we missing?

Quick background. Deep in your hypothalamus sits a cluster called AgRP neurons. They’re part of your brain’s hunger alarm. So, the logic writes itself: a drug that kills hunger should shut these cells down.

Except that’s not what happened.

A new Yale study in PNAS tested it directly. They engineered mice with impaired AgRP neurons, then gave them the GLP-1 semaglutide. Normal mice: steady, sustained weight loss.

But when you impaired the AgRP “hunger” neurons, weight loss started… stalled… then rebounded all the way back to baseline.

If the GLP-1 couldn’t turn “ON” the hunger neurons, the weight came back. Weird?!

How can we reconcile this? It seems impossible.

In today’s deep dive linked above we review:

•⁠ ⁠The mechanisms and data
•⁠ ⁠Why this hits women differently (it’s hormone-dependent)
•⁠ ⁠How to keep your fat-burning engine running after you stop the drug

#GLP1 #WeightLoss #HungerNeurons #MetabolicHealth #NutritionScience

1 week ago | [YT] | 19

Nick Norwitz MD PhD

Why You Can’t Focus

Deep dive here: staycuriousmetabolism.substack.com/p/why-you-cant-…

You sit down to work and your mind bolts. Phone. Instagram. YouTube. You can’t even finish one video. We joke “my ADHD is acting up.”

But fascinating research in Cell suggests we might be stumbling onto something real: some “attention problems” may be sleep problems wearing a disguise.

Today, we delve into the science.

A little primer:
Stimulants like Ritalin and Vyvanse have been prescribed for ~90 years on one assumption: they turn up the brain’s “attention machinery.”

But when a team at Washington University conducted fMRI brain scans on nearly 12,000 kids, and then adults on and off a stimulant, to watch what the drugs actually do inside the brain… what they found surprised me.

The attention networks were untouched.

What lit up instead: the brain’s arousal and reward systems.

That might seem like an esoteric purely academic distinction. But it’s not.

It helps resolve key paradoxes in the field.

For example, have you ever considered these are stimulants… but they’re often used to treat hyperactivity in patients with ADHD.

That doesn’t make sense. Why use a stimulant to treat hyperactivity and an attention defect? That’s like prescribing three shots of espresso as a sleep aid. Unless it’s not actually an attention problem at all.

Or another paradox: there’s a U-shaped curve for stimulants and performance. Give stimulants to a high-performer, and their performance actually suffers. If stimulants were just boosting attention, this wouldn’t make any sense.

In today’s deep dive, we’ll unpack the latest science and practical takeaways, whether you have ADHD, are raising a child with ADHD, or occasionally find yourself, like me, sleep-deprived and unable to focus.

Check the full breakdown linked above.

#ADHD #BrainHealth #SleepScience #Neuroscience #MentalPerformance

1 week ago | [YT] | 10

Nick Norwitz MD PhD

Do you ever feel like your doctor hates you?

Deep dive here: staycuriousmetabolism.substack.com/p/do-you-ever-f…

You ask questions and they’re met with defensiveness. You leave appointments unsatisfied.

I’ve been there.

But the truth is your doctor rarely hates you. Rather, it can feel that way when they don’t know what to do with you.

They’re pressed for time, only learn so much in medical school, and when you don’t fit the mold, when you’re what’s known as a “medical zebra” rather than a commonplace diagnosis, a medical horse, frustrations emerge.

They don’t hate you. Instead, they don’t understand you.

The solution is to move to the driver’s seat. Take responsibility and control of your own health, which does not mean discarding your doctor, but seeing them as a partner, not a master.

That’s what we explore in today’s free letter linked aboved.

#PatientAdvocacy #HealthEmpowerment #DoctorPatientRelationship #MedicalZebra #HealthLiteracy

1 week ago | [YT] | 0

Nick Norwitz MD PhD

Could a nutrient made by gut bacteria make your bones stronger? The answer appears to be: Yes.

Deep dive here: open.substack.com/pub/staycuriousmetabolism/p/a-ma…

In a study published in Cell Metabolism, researchers demonstrated that when mice had their gut microbiomes wiped out with antibiotics and then mechanically loaded their bones through treadmill running, the bones failed to get stronger as they normally would. This is fascinating, but the researchers took it a step further…

When they stratified the mice according to how strongly their bones responded to mechanical loading—that is, how much stronger their bones became with exercise—they found high- and low-responder mice.

What made the high responders stand out was an abundance of bacteria belonging to the family Lachnospiraceae. But what signal were these bacteria actually sending to make bones stronger?

The answer is L-citrulline. L-citrulline sets off a cascade of events, ultimately helping bones "hear" the signal generated by exercise.

Supplementing L-citrulline improved the bones' response to mechanical loading. In effect, each impact made the bones stronger.

More bone bang for the bacteria buck!

This is just one fascinating example. If you want to learn more, check out today's masterclass on how to build stronger bones.

Check the deep dive linked above.

#BoneHealth #GutMicrobiome #LCitrulline #ExerciseScience #StayCurious

1 week ago | [YT] | 228

Nick Norwitz MD PhD

Could Peptides Restore Our Natural Anti-Cancer Defenses?

Deep dive here: open.substack.com/pub/staycuriousmetabolism/p/coul…

Cancer risk doesn’t rise with age simply because mutations accumulate. It also rises because the systems designed to detect and eliminate abnormal cells begin to fail.

One of the most important of these systems is immune surveillance — your immune system’s ability to identify and destroy potentially cancerous cells before they become clinically meaningful tumors.

And this process is happening constantly.

Your body contains ~30 trillion cells, each repeatedly copying billions of DNA letters. Mistakes are inevitable.

The remarkable thing is not that cancer exists, it’s that our bodies suppress it as effectively as they do.

That’s why researchers are becoming increasingly interested in the thymus gland, which helps train key immune cells involved in cancer defense.

Studies suggest individuals with healthier thymuses have lower mortality, improved cardiovascular health, and lower cancer risk.

This raises a fascinating question:
Could certain peptides and bioregulators help restore aspects of thymic function and immune surveillance as we age?

In today’s deep dive, we explore:
• Vilon and thymic peptides
• Immune rejuvenation
• GHRH analogs and thymic regeneration
• Practical tools you can use today, and future directions

Check the full breakdown linked above.

#Peptides #CancerResearch #Longevity #ImmuneHealth #Biohacking #HealthyAging #MetabolicHealth #PreventiveMedicine #Biotech #Thymus

2 weeks ago | [YT] | 260

Nick Norwitz MD PhD

Scientists just found a new Alzheimer’s Doom Loop.

Deep dive here: staycuriousmetabolism.substack.com/p/a-new-alzheim…

The paper, just published in Neuron, reveals a previously unknown way that phosphorylated tau—one of the hallmarks of Alzheimer’s disease—may drive neurodegeneration.

Here’s the mechanism: Phosphorylated tau doesn’t just form neurofibrillary tangles.
It also binds directly to Complex I of the mitochondrial electron transport chain, triggering a process called reverse electron transport.

The result?

Less energy production
More oxidative stress
More neuronal damage

But it gets worse…
This creates a vicious cycle.

More phospho-tau → more reverse electron transport → more oxidative stress and NAD⁺ depletion → those changes activate enzymes—including GSK-3β—that produce even more phospho-tau.

And the spiral continues. A biological doom loop.

So, the obvious question is: Can you break it?

The researchers showed that you can!

In the full deep dive, I also cover:
The mechanism and solutions
The three tools I use today
What this means for your brain


Check the link above for the full breakdown.

#AlzheimersResearch #BrainHealth #Neuroscience #Mitochondria #TauProtein

2 weeks ago | [YT] | 425