šØANNOUNCING: The StayCurious Heart Health Map!
š heartmap.staycuriousmetabolism.com/
Thank You! StayCurious Metabolism is Now Top 3 Overall Best-Selling Newsletter in Science on Substack Worldwide.
To celebrate this milestone, and the very beginning of our journey together (for thatās what this is), my partners at Hundred and I built something fun & interactive for you: The First StayCurious Metabolic Map, focused on Heart Health!
This web is a visual map of the StayCurious Heart Health deep dive we've done, showing how all the pieces connect.
How it works:
šEach node (circle) represents and links to a full deep-dive letter.
šThese are tagged by topic: E.g. statins, Lp(a), fasting, gut health, nutrients, etc.
šThe size of the node shows its popularity.
šClick any node to see a summary and its connections to other topics in the network.
šWatch the network evolve as we grow our knowledge base together!
This is my thank you to this community.
Consider it a "visual trophy" of how much weāve learned together. For new readers, itās a guide to explore. For long-time readers, itās a new way to see the big picture.
Best of allā¦
I see this as a prototype ā the first foundations for a bigger interactive learning tool.
So, my simple as to youā¦ try it out! Let me know:
(1) How youād like to see it evolve.
šWould you like video links?
šBuilt in quizzes?
šA community discussion board?
šA way to track what youāve read and whatās new?
The best way to make sure I see your comment is to leave it at the StayCurious Newsletter announcement.
šNewsletter Announcement staycuriousmetabolism.substack.com/p/the-intricateā¦
(2) Please share because Curiosity is a mind virus. I want you to spread it!
Here's to our continued pursuit of nuance in metabolic health. And thanks!
#hearthealth #cholesterol #staycurious #nuance #cardiovascularhealth #educational
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My Alzheimer's risk is 10-15x higher than average because I carry two copies of the ApoE4 gene variant. But research published in Molecular Therapy gives me hope.
staycuriousmetabolism.substack.com/p/new-hope-for-ā¦
This new study tested a fascinating "ApoE2 antidote" approach in mice engineered with the human ApoE4 gene.
The problem: How do you get a protective protein to the entire brain?
The solution: Researchers developed a new gene therapy method. They used an adeno-associated virus (AAV) to deliver the protective ApoE2 gene specifically to ependymal cells, which line the brain's fluid-filled ventricles.
These cells then acted like tiny factories, pumping the ApoE2 protein into the cerebrospinal fluid (CSF), which bathes the whole brain.
The results were stunning: This ApoE2 "bath" caused a ~33% reduction in dense core amyloid plaques.
Even more importantly, it quieted the significant neuroinflammatory responseāthe "blue haze" of microgliaāthat is a hallmark of Alzheimer's pathology.
Click the link above for the full deep dive on this new technology and my personal anti-Alzheimer's protocol.Ā
#brainhealth #brainenergy #ApoE4 #metabolichealth #staycurious
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The Serotonin Solution to IBS.
staycuriousmetabolism.substack.com/p/the-serotoninā¦
Have you ever dealt with bloating, constipation, or diarrhea? If so, congratulationsāyouāre part of the majority.
Irritable bowel syndrome (IBS) is becoming the norm.
But what actually causes IBS?
New research just published in Cell Reports uncovers a new mechanism.
It turns out that 95% of your body's serotonin originates in the gut, but it was thought to be made primarily by human cells.
This new study shows that specific gut microbes are also serotonin factories, producing serotonin that communicates directly with the gut's nervous system to regulate motility.
In mouse models a specific bacterial cocktail was shown to boost local (intestinal) serotonin and improve intestinal transit time.
And, when analyzing human samples, they found that levels of specific serotonin-producing bacteria were significantly lower in patients with IBS.
This discovery opens a new paradigm for IBS treatmentāmoving beyond symptom management toward precision microbiome interventions.
Click the link about to be taken to today's letter!
#IBS #guthealth #metabolichealth #microbiome #metabolism #staycurious
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āChronic stress literally biologically ages you, especially your brain.ā
Letter: staycuriousmetabolism.substack.com/p/social-stressā¦
This is the terrifying punchline of new research published in Nature Aging; however, this process isn't inevitable.
These new data reveal a precise mechanism.
After exposure to this stress, animals showed a sharp increase in ācellular senescence,ā (cellular āzombificationā) especially in the brain.
The study identified the pathway:
Stress ā DNA breaks + inflammation ā widespread senescence (the "zombie" state)
This confirms how psychosocial stress isn't just a "feeling"āit is a biological age accelerator.
But how do you fight it?
In the full deep dive (linked above), I break down the practical, science-backed tools to counteract stress-induced aging.
#stress #aging #healthyaging #longevity #metabolism #metabolichealth #nuance #medicaleducation #staycurious
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The True Story of the Cookie that Broke Cholesterol
Link: staycuriousmetabolism.substack.com/p/the-true-storā¦
Itās Day 3 of Nuance November and my 30th Birthday (11/3/1995)... so I decided to do something extra āfunā and a bit nostalgicā¦ a return to the (in)famous Oreo vs Statin Study (PMID: 38276308)!
Most of you now this story already, so I won't waste words on a preamble.Ā
But I will say, in this letter, I tell the story like never before.Ā
And, I tell you what's next...
#OreoVsStatin #Cholesterol #ApoB #LDL #staycurious
174 - 13
Creatine Mini-Masterclass: How Does it Really Work? And how do you maximize benefits for the muscle and the brain?
Link: staycuriousmetabolism.substack.com/p/creatine-explā¦
Todayās Newsletter (Day 2 of Nuance November!) is all about these questions and more!
Quickly, the muscle benefits of creatine are undeniable. A recent meta-analysis found that Creatine combined with resistance training has large benefits beyond resistance training alone:
ā
Increases lean mass by 2.5 lbs
ā
Reduces body fat by 1.6 lbs
šŖ Mechanistically, creatine works by:
š¹ Rapidly regenerating ATP (your cellsā energy currency)
š¹ Increasing muscle cell hydration (cell volumization)
š¹ Activating satellite cells (muscle stem cells)
š¹ Enhancing gene expression tied to muscle contraction
We delve into the mechanistic details in the newsletter.
Then, we dive into protocols including for muscle health and brain health!
Check the link above and dive deep with me!
#NuanceNovember #Creatine #ExerciseScience #MuscleGrowth #BrainHealth #FitnessScience
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Nuance November Day 1: The Black Hole of Sugar Cravings
staycuriousmetabolism.substack.com/p/the-metabolicā¦
Managing sugar cravings isnāt just about willpower.Ā
Fascinating research in Nature Microbiology identifies a gut receptor, FFAR4, that modulates our preference for sugar.
The cascade:
šFFAR4 boosts a microbe (B. vulgatus) that produces Vitamin B5.
šB5 increases GLP-1.
šGLP-1 signals the liver to make FGF21.
šFGF21 signals the brain to suppress sugar cravings.
See the full letter (link above), where I break down the actionable, science-backed ways to target this pathway. It might not be what you think.
#sugar #appetitecontrol #metabolism #sugarfree #metabolichealth #neuroscience #staycurious
217 - 8
This is exciting ā Nuance November kicks off tomorrow!
For the next 7 days - at StayCuriousMetabolism.com/Ā - weāll be sharing an unbroken streak of letters, each diving into a different aspect of metabolic health. From sugar cravings to gut health, brain function to heart health and an Oreo autopsy ā every letter is crafted to shift your thinking and challenge assumptions.
Itās going to be fun, educational, and ā as always ā nuanced.
And to make it even more exciting, weāre launching a giveaway and referral raffle, where you can win: Free months of premium subscriptions and more surprises.
All of this is part of the incredible community we're building together at StayCurious Metabolism ā which, thanks to your support, has become the #3 best-selling science publication in the world in just five months since my MD PhD graduation.
Thatās entirely because of you ā your curiosity, your enthusiasm, and the culture of thoughtful exploration youāve helped create.
Thank you.
Letās make this week one to remember.
ā Nick
As an aside, the midst of the streak will, on Nov 3, be my 30th birthday. So, if youāre on the fence about joining our StayCurious community and a birthday guilt trip will get you over the edge to trying a month-long trial or sharing your favorite Nuance November letterā¦
you know what to do (link above)
#staycurious #metabolism #metabolichealth #sciencebreakthroughs #nicknorwitz #medicaleducation #personalizedmedicine
206 - 7
āCalories Donāt Cause Obesity.ā
Today's Letter: staycuriousmetabolism.substack.com/p/calories-dontā¦
That sentence alone nearly broke Nutrition Twitter ā and triggered everything from trolls threatening to revoke my Harvard MDā¦ to DMs from other scientists offering, āwell, it appears vocalization of the word āc-a-l-o-r-i-e-sā is sufficient to put influencerās neurons into a caloric deficit.ā (Cue the laughter š¤£ )
But let me be clear:
š„ Itās not just a hot take.
š¤ Itās a critique of how we think about obesity.
Yes, a calorie is a legitimate unit of energy.
But confusing post-hoc arithmetic with biology is not just intellectually lazy, it's harmful.
In my latest StayCurious letter, I dig deep into:
ā
The data showing calorie intake can be uncoupled from fat gain
ā
The human RCTs and real-world variation that prove: Calories donāt ācauseā obesity
ā
Why āCalories In, Calories Outā is not just outdated ā itās holding us back
ā
And what we should focus on instead
Check out today's letter, linked above.
Note: Today's letter is for premium subscribers (cost less the $0.67 per letter). I'll also have a YouTube video eventually. The StayCurious Metabolism Substack community helps me scale across other platforms. So, big - HUGE - thank you to them. As of this morning, we're #3 in Best-Selling in Science on Substack overall/in the world (despite being quote young!), and are usually #1 in Rising Science on the platform. That's because YOU care about going deep, getting the nuances...
#metabolism #calories #obesity #metabolichealth #fatloss #staycurious
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Are Doctors Overprescribing Statins? (4 Studies)
*Link: staycuriousmetabolism.substack.com/p/weve-been-preā¦
New research published a few days ago in JACC: Cardiovascular Imaging suggests we need more precision.
The study found that while statins reduce risk of major adverse cardiovascular events (MACE) in patients with established heart disease, they showed no significant benefit for primary prevention in patients with minimal or no disease.
šØImportantly, this is NOT about just one study.Ā Consider this new study bait, inviting a broader conversation...
Other studies show consistent results & revealed other negative side effects of statins, including on diabetes risk, reducing GLP-1 levels and harming mitochondria.
The punchline: Itās time to move beyond just LDL numbers and use modern imaging to understand a patientās true risk. This is about using the right tool for the right job.
In the full letter (linked about) I review not one but four studies you should know.
My promise to you: Read this letter and in 10-15 minutes you'll learn more about statins than in 4 years of medical school.
#cholesterol #statin #ApoB #LDL #personalizedmedicine #staycurious
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MD, Harvard & PhD, Oxford & | My Motto is "Stay Curious" | Enthusiastic About All Matters Metabolic Health | Thanks for Learning with Me!
Please also follow at my Newsletter at "StayCuriousMetabolism.com" where you can find more deep dives into metabolism that will be worth your time and upgrade your health.
Disclaimer: While I am an MD PhD, this channel is intended to educate. It is not intended to provide clinical recommendations for any individual. Please contact your doctor or other clinical provider if you have questions about your care.
Joined 27 October 2013