Nick Norwitz MD PhD

What if we’ve been focusing on the wrong cholesterol marker all along?
Link: staycuriousmetabolism.substack.com/p/the-untold-st…


For decades, cardiology has focused on a simple mantra: “Lower LDL and ApoB to reduce heart disease risk.”

But there’s a paradox. Even though cardiovascular disease is a leader killer—people with genetically low LDL and ApoB don’t necessarily live longer.

Enter ApoC3—a small protein that regulates how your body clears triglycerides. 

People with mutations that reduce ApoC3 have better fat metabolism, lower cardiovascular risk, and—most strikingly—longer lifespans. Centenarians are more likely to carry these mutations, despite having similar LDL and ApoB levels to everyone else.


In today's letter, I’ll walk through practical, evidence-based ways to reduce ApoC3 and improve metabolic health—tools that could add years to your life and life to your years.


Check the link above for the deep-dive.

#cardiovascularhealth #ApoB #ApoC3 #metabolism #metabolichealth #staycurious

1 day ago | [YT] | 383

Nick Norwitz MD PhD

BPC-157: The Peptide Everyone Is Talking About
Link: staycuriousmetabolism.substack.com/p/peptides-what…

Following the GLP-1 wave, few compounds are generating as much buzz as BPC-157 (Body Protection Compound-157).

In preclinical research, this peptide has shown intriguing effects on tissue repair, inflammation, and recovery.

A recent systematic review highlights impressive results in animal models and suggests probable safety.

But here’s the critical reality check: there are no rigorous human clinical trials.

The entire human literature consists of a small, uncontrolled study of 12 people with knee pain—11 reported improvement. That’s it.

Meanwhile, public enthusiasm has exploded. In 2024 alone, 10s of millions of videos tagged BPC-157 flooded TikTok and YouTube.

The gap between hype and evidence couldn’t be wider.

That said, "absence of evidence isn't evidence of absence." And, mechanistically, BPC-157 and its cousins are interesting!

If you want the full peptide deep dive click the link above.

#BPC157 #metabolism #peptides #GLP1 #staycurious

3 days ago | [YT] | 552

Nick Norwitz MD PhD

Ezetimibe (Zetia) for Alzheimer's Disease?!
Link: staycuriousmetabolism.substack.com/p/this-study-co…

A fascinating study suggests ezetimibe—a widely used, relatively benign cholesterol-lowering drug—may help reduce Alzheimer’s risk via a mechanism that is entirely unexpected.

Alzheimer’s disease and related dementias are driven in part by protein misfolding and aggregation.

One intriguing interaction occurs between 14-3-3, a scaffolding protein with a horribly boring name, and hexokinase, an enzyme involved in metabolism.

In Alzheimer’s brains, these proteins clump together, particularly in memory-critical regions like the hippocampus.

Researchers ran a hypothesis-naive screen of FDA-approved drugs to disrupt this interaction. (They were not looking for benefits of cholesterol medications).

Ezetimibe raised its hand.

Ezetimibe disrupted the 14-3-3–hexokinase interaction and was associated with less amyloid, less tau, and improved autophagy, the cell’s cleanup and recycling system.

The team then examined existing human data: among ezetimibe users, the incidence of Alzheimer’s and related dementias during follow-up was ~8-fold lower.

As always, these findings come with important caveats, which I unpack in the full letter—along with what I’m personally considering and why.

Click the link above to read the full letter and join our booming StayCurious Metabolism community.

P.S. I have no - ZERO, Zilch - conflicts with pharma.

#AlzheimersResearch #Neuroscience #DrugRepurposing #BrainHealth #AgingResearch #PrecisionMedicine #MetabolicHealth #MedicalScience #TranslationalResearch #StayCurious

5 days ago | [YT] | 675

Nick Norwitz MD PhD

The Big New Statin Study (Lancet) has a Big Blind Spot
Link: staycuriousmetabolism.substack.com/p/the-big-new-s…

A major new study just dropped two days ago in a top journal, The Lancet. The headlines are loud:

“Millions more” people should be taking statins

This study pooled 19 placebo-controlled randomized trials (123,940 participants) to assess whether statins causally drive 66 feared side effects.

True most outcomes didn’t cross the threshold for “statistical significance”—and that word is doing a lot of work.

Many effects, including weight gain and metabolic changes, trend toward harm (including dose response relationships).

That’s not a biological all-clear; it’s statistical semantics.

Click the link above.

#StayCurious #EvidenceBasedMedicine #Statins #MedicalResearch #ScientificNuance #HealthData #CriticalThinking #MetabolicHealth #HeartHealth

1 week ago | [YT] | 678

Nick Norwitz MD PhD

This Graph Changed How I Think about Dementia...
Link: staycuriousmetabolism.substack.com/p/this-graph-ch…

Microplastics are accumulating in the human brain—rapidly.

Over the past ~8 years, levels of microplastics in brain tissue have increased by roughly 50%.

But that’s not the most concerning part...

Brain microplastic levels are consistently much higher in individuals with dementia compared to those without dementia. 

See on the graph how the dementia cases (purple) needed a whole Y-axis break... 
And the relationship is incredibly consistent!

Researchers propose that the exponential rise in environmental micro- and nanoplastics may be driving a parallel increase in plastic accumulation in human brain tissue.

While correlation does not equal causation, it’s important to recognize that randomized controlled trials are neither ethical nor feasible in this context.

Check out the link above for the deep dive.

#microplastics #brainhealth #brainenergy #dementia #inflammation #longevity #microbiome

1 week ago | [YT] | 410

Nick Norwitz MD PhD

Peter Attia is hiding something—But it’s not what you think…
Link: staycuriousmetabolism.substack.com/p/peter-attia-i…

He’s hiding a graph.

In a letter that appears to be responding to my work (a case I outline clearly in the full piece), Peter challenges a study we've reviewed on this channel showing statins slash GLP-1 levels in humans... yet this key figure is excluded.

He even pulls other panels from the same figure (Figure 1) showing LDL and total cholesterol reductions, cites 36 references… and somehow leaves out the only truly relevant graph.

It’s hard to imagine that’s an accidental omission.

It’s like asking someone to watch all the Star Wars movies but leaving out the Jedi.

For someone who claims to be a champion of "nuance and accuracy" this conspicuous omission is truly hard to reconcile.

Click the link about for the full letter.

#Statins #GLP1 #MedicalTransparency #ScientificIntegrity #EvidenceBasedMedicine #PatientCenteredCare #MetabolicHealth #ClinicalResearch #HealthCommunication #OpenScience

1 week ago | [YT] | 1,054

Nick Norwitz MD PhD

Cholesterol Debates in the Era of Medical Mistrust
Link: staycuriousmetabolism.substack.com/p/cholesterol-d…

This graph highlights a striking comparison: the Hazard ratio coronary heart disease associated with insulin resistance score (LP-IR) versus LDL cholesterol.

The difference isn’t subtle—insulin resistance carries more than a 14-fold higher relative risk. (With 1.0 marking neutral.)

And yet, LDL continues to dominate the conversation.

Why? Because it’s easier to lower, easier to measure, and comes with highly profitable pharmacologic solutions.

The statin industry alone generates over $20 billion per year. And we’d be naïve to think financial incentives don’t shape clinical focus.

But if we truly want to reduce cardiovascular disease on a population level, we need to confront the metabolic dysfunctions driving the disease process.

We need to ask: What have we missed? What needs to change? And what might we uncover if we shift our attention toward the deeper mechanisms at play?

Now, let’s not end the conversation here... click the link above to today's newsletter.

#cholesterol #ApoB #statins #hearthealth #staycurious

2 weeks ago | [YT] | 484

Nick Norwitz MD PhD

A New Heart-Health medication may hold promise for Alzheimer’s prevention... and Lp(a)
Link: staycuriousmetabolism.substack.com/p/the-medicatio…

In a recent analysis, the new-generation CETP inhibitor, obicetrapib, appeared to halt progression of p-tau217, a key blood-based biomarker of Alzheimer’s disease.

In the study, the placebo group showed a 5.71% increase in p-tau217 over one year.

In contrast, among those at highest genetic risk—ApoE4 carriers—the obicetrapib group showed no increase at all.

It’s like Alzheimer’s pathology hit a brick wall!

For a deep dive into these data, check out today's StayCurious Newsletter, linked above.

#ApoE4 #dementiaprevention #brainhealth #brainenergy #Alzheimersdisease #CEPT #obicetrapib #staycurious

2 weeks ago | [YT] | 401

Nick Norwitz MD PhD

This actually BLEW MY MIND! A striking brand-new study (Feb, 2026) in Cell reveals a surprising biological twist: proteins secreted by cancer cells may help protect against Alzheimer’s disease. 
Link: staycuriousmetabolism.substack.com/p/hijacking-can…

For years, data have hinted that people with a history of cancer have a lower risk of Alzheimer’s—but this was often dismissed as a statistical artifact. This research suggests something deeper is going on.

In animal models, multiple cancers (lung, prostate, colon) reduced amyloid plaques in the brain.

Moreover, when researchers treated Alzheimer’s mice with proteins secreted by cancer cells—without tumors—amyloid dropped and memory improved.

The key molecule turned out to be cystatin C, which is also elevated in many human cancers. It activates brain immune cells via the TREM2 pathway, helping clear toxic amyloid.

This isn’t a treatment yet—but it’s a powerful reminder that biology is full of unexpected connections.

If you’re interested in the deeper science and **Practical, Evidence-backed ways to support brain health,** check out the link above.

#AlzheimersResearch #Neuroscience #AgingScience #BrainHealth #Biotech #MedicalBreakthrough #HealthInnovation #ScienceCommunication #Longevity #StayCurious

2 weeks ago | [YT] | 476

Nick Norwitz MD PhD

Exercise doesn’t just build muscle—it changes how muscle ages.
Link: staycuriousmetabolism.substack.com/p/the-aging-mus…

New research in PNAS reveals a fascinating muscle paradox that reshapes what we think exercise really does inside the body.

To understand the paradox, meet mTOR—the big, fat red “grow” button for muscle.

It drives protein synthesis and growth.

So, with aging + muscle loss, you’d expect less mTOR, right?

WRONG!

Paradoxically, mTOR activity actually increases in aging muscle. So, we’re hitting the grow button harder… but still losing muscle mass. What gives?

Turns out mTOR has a dark side. While it builds muscle, it also shuts down cleanup + renewal pathways like autophagy. Too much mTOR for too long = cellular clutter, damage, and muscle quality decline.
Here’s the beauty: Exercise is the fix.

Yes, it spikes mTOR in the short term (to stimulate growth).

But over time, it suppresses chronic mTOR overactivation, restoring the cleanup crew.

So, exercise gives you the best of both worlds:
✔️ Growth
✔️ Renewal
✔️ Better muscle quality with age

And that’s not just good for your biceps—it’s good for your lifespan and healthspan.

Now, do you want to dive deeper into how muscles age and how to protect them as you age?

👉 Comment “Curious” and I’ll send you the full deep dive, included high-yield tips to keep your muscles healthy with age

There’s also a free signed Forever Stronger Playbook giveaway! No paid promotion or ads. Just added value for you!

#Longevity #MuscleHealth #ExerciseScience #mTOR #HealthyAging #StrengthTraining #Autophagy #Healthspan #ResearchInsights #LifelongStrength #LinkedInScience

2 weeks ago | [YT] | 658