Nick Norwitz

5 Things You Should Know About Cholesterol-Lowering Medications
Link: staycuriousmetabolism.substack.com/p/a-concise-mas…

1. Statins aren't benign.
While widely prescribed, statins can have significant off-target effects — including GLP-1 depletion, insulin resistance, and potential muscle pain/damage. 

These aren't guaranteed, but they're under-discussed and should be part of any responsible risk-benefit conversation.

2. PCSK9 vs Statins — effects on Lp(a)

If lipoprotein(a) is on your radar (as it should be), it’s worth noting: PCSK9 inhibitors tend to reduce Lp(a) vs Statins may actually increase Lp(a).

3. Ezetimibe works by blocking cholesterol absorption in the gut — not just from food, but from endogenous recycling.

This mechanism becomes particularly relevant for people on low-carb, high-fat diets, who naturally circulate more cholesterol and bile acids.

In those cases, ezetimibe can punch above its weight.

4. Bempedoic acid: is a newer drug targets just upstream in the cholesterol synthesis pathway versus statins — but acts specifically in the liver.

Because of this tissue specificity, it may avoid the muscle-related side effects common with statins, offering a tolerable alternative for many.

5. Berberine: not a medication per se, but mechanistically interesting
Though not a prescription drug, berberine can lower LDL by up to 25%. Its mechanism? Stabilizing mRNA transcripts (the ‘blueprints’) for LDL receptors in the liver.

This is just the beginning. Click the link above for the Deep Dive.

#Cholesterol #CardiometabolicHealth #HealthcareInnovation #PrecisionMedicine #Pharmacology #PreventiveCardiology #MetabolicHealth #Longevity

1 day ago | [YT] | 559

Nick Norwitz

A Brand New Study may reshape how we think about Alzheimer’s disease.
Link: staycuriousmetabolism.substack.com/p/never-get-alz…

Researchers found that NAD+—a key molecule involved in brain energy metabolism—is consistently depleted in Alzheimer’s brains.

Strikingly, people with amyloid pathology but high NAD+ levels often remain cognitively intact.

In two Alzheimer’s mouse models, restoring NAD+ through a NAMPT-activating compound reversed memory loss, reduced amyloid and tau, calmed neuroinflammation, and even repaired the blood–brain barrier.

Parallel molecular patterns were observed in human brain tissue, suggesting this biology translates.

👉 The best part? NAD+ levels can also be supported safely and naturally through targeted lifestyle interventions.

In today’s letter, I break down the study, the mechanisms, and actionable steps anyone can take. Click the link above for the deep dive!

#brainhealth #NAD #staycurious #metabolism #longevity #educational

4 days ago | [YT] | 702

Nick Norwitz

HAPPY NEW YEAR! 

Here are your Metabolism Highlight Reel: Fan Favorites from StayCurious Metabolism in 2025

Link: staycuriousmetabolism.substack.com/p/the-2025-meta…

Thank you for being part of this StayCurious Rocketship. 🚀

#staycurious #metabolichealth #metabolism #educational

6 days ago | [YT] | 412

Nick Norwitz

New study: Lp(a) may increase cardiovascular death risk by 230%. But does that mean you’re doomed by your genes?
Link: staycuriousmetabolism.substack.com/p/the-hidden-me…

Not necessarily—and I’m willing to bet my heart on it.

Researchers studied 1,027 patients with advanced coronary artery disease undergoing surgery.

Those with high levels of lipoprotein(a), or Lp(a), had significantly higher risk of death. The conventional thinking?

Lp(a) physically sticks to arteries and seeds plaque.

But this study found something deeper: high Lp(a) was also linked to higher levels of superoxide (O2×)—a highly reactive molecule that fuels inflammation and oxidative stress in arteries.

Here’s the kicker: Lp(a) appears to deplete an enzyme's cofactor needed for nitric oxide production... without it, the enzyme instead makes more O2×.

The result?

A vicious cycle: Less nitric oxide → more oxidative stress → more damage → higher risk.

That helps explain the dramatic jump in cardiovascular risk among high Lp(a) patients.

But here’s why I’m still optimistic: Understanding the mechanism opens the door to intervention.

In the full letter, I’ll share dietary strategies to help defuse this biological bomb. Link above.

#hearthealth #lpa #cardiovascularhealth #metabolichealth #staycurious

1 week ago (edited) | [YT] | 509

Nick Norwitz

A study published in Atherosclerosis reported 37% of individuals with “optimal” LDL cholesterol (all <70, mean 57 mg/dl) had measurable atherosclerosis.
Link: staycuriousmetabolism.substack.com/p/beyond-ldl-re…

That’s not a trivial number—but it does deserve careful interpretation. (Click the link.)

The larger point is that, in clinical practice, LDL and ApoB often dominate the conversation, while markers of metabolic dysfunction—more powerful factors in the pathogenesis of cardiovascular disease—receive far less attention.

This is not 'proportional' or patient-centered medicine. Why does this imbalance persist?

If you’re interested in a deeper dive—what biomarkers may matter more than LDL-C, and what targets make sense in context—click the link above.

#ApoB #LDL #cardiovascularhealth #metabolichealth #staycurious

1 week ago | [YT] | 562

Nick Norwitz

“Young blood” isn’t just science fiction. It might be mitochondrial medicine.
Link: staycuriousmetabolism.substack.com/p/can-young-blo…

A study in Nature Aging shows that small extracellular vesicles (sEVs) from young blood extended lifespan in mice by 12%, while also rejuvenating fertility, brain function, and physical performance.

What are sEVs?

They’re tiny, bubble-like particles released by cells into the bloodstream—think of them as biological delivery packets, carrying proteins, RNA, and lipids that help cells communicate and regenerate.

🔬 In the study, old mice injected with sEVs from young mice:
✅ Lived longer
✅ Had better aerobic fitness (VO₂)
✅ Nearly doubled sperm quality and litter size
✅ Regained brain volume in areas tied to memory
✅ Showed stronger bones and better mobility
✅ Improved mitochondrial energy output (ATP)

And here’s the kicker: these benefits aren’t limited to mouse-to-mouse transfers…
In the full breakdown, I’ll cover:

→ The underlying mechanism
→ What this means for human aging
→ What might be actionable now

Link Above

#youngblood #longevity #staycurious #metabolism #mitochondria

1 week ago | [YT] | 498

Nick Norwitz

🔥“How do you increase your metabolism?” It’s a billion-dollar question—literally.
Link: staycuriousmetabolism.substack.com/p/how-to-increa…

And today’s letter is dedicated to answer that questions, but without dangerous drugs or gimmicks… just practical advice to move the needle.

Here’s a nibble…

A landmark Science study overfed participants by 1,000 calories/day for 8 weeks. The result? A 10-fold difference in fat gain between individuals. 🤯
So, what made the difference?

The answer: NEAT — Non-Exercise Activity Thermogenesis.

NEAT includes all the small, spontaneous movements we make during the day: fidgeting, standing, pacing, walking while on the phone.

Some people increase NEAT dramatically when overfed—becoming “jittery furnaces.” Others slump into “sentient throw pillows.”

The best part? You can nudge your NEAT.

Here are 3 practical tips:

✅ Use a standing desk – Even a cheap adjustable stand promotes subtle movement.
✅ Anchor movement to habits – Pace during phone calls, do calf raises while coffee brews, walk after meals.
✅ Get a dog (or borrow one) – Daily walks = effortless NEAT. Bonus points if it’s a puppy.

That’s just the beginning. Want more practical ways to make fat loss easier (including a dietary hack to make you poop out Calories)?

Check out the letter, above.

#metabolism #calories #weightloss #fatloss #staycurious

2 weeks ago | [YT] | 529

Nick Norwitz

Can nattokinase reverse atherosclerosis?
Link: staycuriousmetabolism.substack.com/p/nattokinase-t…

Few supplements generate as much buzz—or confusion—as nattokinase, an enzyme derived from natto, the Japanese fermented soybean dish.

A 16-year observational study of 29,000 people found that those in the highest quartile of natto consumption had a 25% lower risk of cardiovascular death—even after adjusting for other variables.

But here’s the kicker: this effect wasn’t linked to soy in general. No benefit was seen with soy protein or other soy foods. The signal was specific to natto. Let that ferment for a second.

Why? Possibly because of nattokinase, an enzyme produced during fermentation by Bacillus subtilis.

In another study with over 1,000 participants, a daily dose of 10,800 units of nattokinase for a year led to measurable regression of atherosclerosis.

Mechanistically, nattokinase exerts triple action:

✅ Anti-thrombotic (reduces clotting)
✅ Anti-hypertensive (lowers blood pressure)
✅ Antioxidant (fights oxidative damage)

In today’s Stay Curious newsletter, we unpack the human data, RCTs, mechanisms, dosing, and safety.

👉 Check it out (link above)

#natto #nattokinase #hearthealth #metabolichealth #metabolism

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2 weeks ago | [YT] | 677

Nick Norwitz

Could high-fat cheese lower dementia risk? 🧠🧀
Link: staycuriousmetabolism.substack.com/p/high-fat-chee…

A brand-new paper just followed 27,670 people for 25 years and found something surprising: higher intake of high-fat cheese—but not low-fat cheese—was associated with a lower risk of dementia.

That’s brie-lliant news… but how Gouda are the data?

First, some context. This wasn’t a randomized controlled trial—you simply can’t randomize people to high-fat vs. low-fat diets for decades (and being stuck in the low-fat arm for 25 years sounds cruel).

So yes, this is observational nutrition science, which always warrants caution.

That said, the study did several things right. Instead of relying on a single 24-hour dietary recall (yes, some studies really do that), the researchers used:
👉 A 168-item food frequency questionnaire, plus...
👉A 7-day consecutive food diary, plus...
👉A 45–60 minute dietary interview

🧠 The Headline Finding: There was a 13% reduced risk of dementia in people eating >50g/day of high-fat cheese compared to those eating <15g/day.

There was a similar association for high-fat cream.

However, low-fat dairy—including low-fat cheese and cream—was not associated with any reduced risk of dementia.

This is where most people will stop—and that’s fine.

But if you want the deeper nuance, this is where things get interesting. In the full letter, linked above, we review:
👉 Patterns that are easy to miss but reveal a much bigger truth
👉The role of genetics, specifically ApoE4
👉 My top dietary tips for Alzheimer’s prevention

#dementia #cheese #dairy #saturatedfat #brainhealth #healthydiet #staycurious

2 weeks ago | [YT] | 553

Nick Norwitz

To supplement or not to supplement? That is the question.
Link: staycuriousmetabolism.substack.com/p/inside-my-sup…

It’s a controversial one. In health and fitness circles, there’s a common view that optimal human health comes from living in an evolutionarily compatible way.

Our ancestors didn’t pop pills to be healthy—so why should we?

There’s wisdom in aligning with our evolutionary biology. But taken too far, that perspective is short-sighted for two key reasons.

First, the environment we live in today is radically different from the one our ancestors evolved in.

Modern soil depletion, chronic stress, artificial light, ultra-processed foods, and the pervasion of microplastics are not ancestral variables. In some cases, thoughtful supplementation may help compensate for modern deficits and dysfunctions.

Second, our goals don’t align with evolution’s priorities.

Evolution optimizes for reproduction, not longevity or quality of life. Most of us aren’t trying to have 12 kids and die at 50—we’re trying to live long, fulfilled lives on our own terms. In that context, supplementation can be a tool to support healthspan, and possibly lifespan.

So yes—I’m pro-supplement. But only when it’s targeted, intentional, and individual-specific.

I get a lot of questions about the supplements I personally take, which is the purpose of today’s newsletter for those interested. A quick caveat: my routine is not set in stone. It’s constantly evolving. Think of this less as “do what I do” and more as “how I think about supplementation.”

That said, I will share products I genuinely use and trust, along with the rationale behind them, for your consideration.

See link above

#supplementation #omega3 #brainhealth #guthealth #microplastics #staycurious

2 weeks ago | [YT] | 374