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Nick Norwitz MD PhD

@nicknorwitz

Jan 6

5 Things to Know About Cholesterol-Lowering Drugs 🧵

1/6) Statins are the go-to prescription — but with baggage.
They can:
👉Deplete GLP-1
👉Cause insulin resistance
👉Trigger muscle pain/damage and potentially muscle loss

These risks aren’t often mentioned, but they should be part of a real cost-benefit analysis.

🔗 to the letter at the end, including all hyperlinked references

2/6) Lp(a) and Drug Effects
👉PCSK9 inhibitors = tend to lower Lp(a)
👉Statins = tend to raise Lp(a)
This often-overlooked detail could matter a lot depending on your individual risk profile.

3/6) Ezetimibe blocks cholesterol absorption in the gut — both dietary and recirculated. Liver compensates by increasing LDL receptors.

Its effects are usually modest compared to statins and PCSK9 inhibitors, but if you're low-carb/high-fat you’re naturally recirculating more cholesterol + bile.

Thus, if you’re low-carb, ezetimibe becomes a much more powerful tool for ApoB and LDL lowering.

Read 6 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 5

Creatine Explained: How One Molecule Boosts Muscle and Brain Health 💪🧠🧵

1/11) Creatine is one of the most extensively studied performance-enhancing supplements in the world of exercise science and nutrition.

And yet, despite its popularity, few people truly understand how it works or what its full range of effects might be.

So, let’s break down what you need to know about creatine.
💪Muscle Hypertrophy Mechanisms
💪Brain Health
💪Protocols

2/11) There are several mechanisms through which it can support muscle growth (a.k.a. hypertrophy):

First, Satellite Cell Activation

When muscle fibers grow, they require additional nuclei to manage the increased protein production.

Unlike most cells, which contain only one nucleus, muscle cells are multinucleated. These extra nuclei come from satellite cells—a type of muscle stem cell.

Combined with resistance training, creatine stimulates satellite cell activity, which helps supply growing muscle fibers with the extra nuclei they need to expand.

In simpler terms: creatine makes it easier for your muscles to grow by helping recruit and integrate new cellular “command centers” (nuclei) into the muscle fibers.

3/11) ii. Cell Volumization: Creatine draws water into muscle cells, increasing intracellular hydration.

This “cell swelling” is more than just cosmetic—it acts as a signal that stimulates protein synthesis.

Over time, this contributes to an increase in muscle mass.

Read 11 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 3

Never get Alzheimer’s Disease: The NAD+ Breakthrough

1/9) This graph hints at a potential breakthrough in Alzheimer’s disease.

It shows that NAD+, a key energy carrier in the brain, is depleted in Alzheimer’s—but preserved in cognitively healthy brains.

Restoring it may not just protect memory—it might reverse dementia.

2/9) What is NAD+? NAD+ is an essential energy carrying molecule in the brain.

Most major energy metabolism pathways (carb burning via glycolysis, fat burning via beta oxidation, TCA/Kreb cycle, mitochondrial metabolism) rely on NAD.

When NAD drops, the brain fails.

3/9) In Alzheimer’s, NAD+ levels don’t just drop—they correlate with a core Alzheimer’s biomarker: phospho-tau.

Even more intriguing: some people have Alzheimer’s pathology (amyloid)… but if their NAD+ is high, they don’t tend to develop dementia.

This suggest NAD+ could be a resilience factor in the aging brain… So… what happens if you restore NAD+?

Read 9 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 2

Escape the Black Hole of Sugar Cravings

1/4) Why can some people say no to dessert, while others feel pulled toward sugar like it's a black hole?

It's NOT a failure of willpower.

🦷But before we start, tell me: do you have a sweet tooth? What's your dietary Achilles' heel?

2/4) Human data show that levels of a nutrient sensor, FFAR4, are reduced in diabetes, are negatively associated with fasting blood sugar, and are even linked to metabolic health in mendelian randomization studies.

3/4) The researchers dissect a fascinating cascade whereby this nutrient sensor alters the microbiome to change GLP-1 and FGF-21 signaling to alter brain signaling and sugar cravings.

Sugar cravings aren't about willpower. THey're about metabolism.

Read 4 tweets

Nick Norwitz MD PhD

@nicknorwitz

Dec 30, 2025

How Lp(a) Really Causes Heart Disease

1/9) New study finds that high Lp(a) increases the risk of death from CVD by as much as 230%.

Since Lp(a) is thought to be genetically determined, some people think if you have high Lp(a), you’re screwed.

🚨But I don’t think so...

2/9) The researchers studied 1,027 patients with advanced coronary artery disease who were undergoing cardiac surgery.

The conventional view is that Lp(a) and related molecules promote atherosclerosis by physically sticking to the artery wall, infiltrating it, and essentially “seeding” plaque.

But there’s more to the story…

3/9) The researchers found that patients with higher Lp(a) also had higher levels of a molecule called “superoxide” (O2×).

And no, despite the name, it’s not Superman of the molecular world. It’s not a hero—it’s a villain.

O2× is a reactive oxygen species. It fuels oxidative stress and inflammation—core pathologies that can drive atherosclerosis.

Read 9 tweets

Nick Norwitz MD PhD

@nicknorwitz

Dec 28, 2025

1/6) A study published in Atherosclerosis found that 37% of individuals with “optimal” LDL (<70 mg/dL) still had measurable atherosclerosis.

That’s not a trivial number—but it does require nuance.

The first objection is familiar: a single LDL measurement may not reflect lifetime exposure.

Maybe these people lowered LDL later in life after years of higher levels?

But all participants were untreated—no lipid-lowering medications.

That makes it more likely that most had lifelong low LDL. Yet 37% still had atherosclerosis on CAC or carotid ultrasound.

🔗 Link to details at the end
PMID: 29751286

2/6) To be fair, this was modestly lower than the overall prevalence in the cohort (49%).

But a 12% relative difference, while not nothing, is a surprisingly small payoff compared to improving factors like blood sugar control or insulin sensitivity.

The punchline: across two diverse, untreated cohorts, having “optimal” LDL did not prevent atherosclerosis.

Not even close.

3/6) This is not to say LDL or ApoB don’t matter at all for anyone—it’s to say they’re only a small part of the puzzle. Yet LDL and ApoB dominate the cardio conversation, while risk factors related to global metabolic dysfunction—are consistently marginalized.

Why?

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More from @nicknorwitz

Nick Norwitz MD PhD

Nick Norwitz MD PhD

Nick Norwitz MD PhD

Nick Norwitz MD PhD

Nick Norwitz MD PhD

Nick Norwitz MD PhD

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