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Nick Norwitz MD PhD

@nicknorwitz

Jun 7

How To Optimize Sleep to Clean the Brain

1/6) Sleep is critical for clearing metabolic waste out of your brain. But few people know how to optimize this process.

So today we're breaking it all down: a masterclass on the glymphatic system (link at the end) and how your brain cleans itself while you sleep.

Let's start with the fundamentals: what is the glymphatic system?

Most of your body has two major vessel systems:
👉Blood vessels → deliver oxygen and nutrients
👉Lymphatics → remove waste

But your brain, despite being one of your most metabolically active organs, lacks the conventional lymphatic system.

So how does it take out the trash?

2/6) The answer is the glymphatic system.

Unlike lymphatics, it isn't a dedicated network of vessels. During sleep, blood vessels in the brain constrict slightly, creating channels through which cerebrospinal fluid flows.

Think of it as a nightly shower for your brain, washing away metabolic debris that accumulated during the day.
Why does this matter?

Because when glymphatic clearance becomes impaired, metabolic waste can accumulate in the brain.

Over time, this is thought to contribute to brain metabolic dysfunction, cognitive decline, and potentially neurodegenerative diseases like Alzheimer's.

Which brings us to the next question...

3/6) When does glymphatic clearance occur?

Primarily during deep sleep.

That means one of the best ways to support your brain's waste-removal system is to improve deep sleep—without sacrificing REM sleep.

One interesting tool...

Read 6 tweets

Nick Norwitz MD PhD

@nicknorwitz

May 26

Most Promising Molecules that Fight Alzheimer’s (New Science)

1/12) Here are five molecules that might protect the brain against Alzheimer’s based on new 2025 – 2026 science.

Lock in. This one goes deep!

2/12) The first is lithium.
• Across geographies, higher trace lithium levels in drinking water are associated with lower Alzheimer’s rates.
• Brains with Alzheimer’s disease show lower lithium levels.
• And lithium inhibits a protein (GSK3β) that plays a central role in promoting Alzheimer’s.

3/12) There may even be a vicious cycle.

Research suggests amyloid pathology in Alzheimer’s can sequester lithium, lowering available levels → which may promote more pathology → more sequestration → and downward spiral towards dementia.

Read 12 tweets

Nick Norwitz MD PhD

@nicknorwitz

May 16

The Heart Supplements I Recommend to Family 🧵 👇

1/7) I have astronomically high cholesterol (>700 mg/dl) and high Lp(a) (194), but my arteries are perfectly clear. I mean perfect! 0 mm³ of any measurable plaque upon expert read and AI-guided quantification of my coronary CT angiogram—a finding that left several cardiologists stunned.

2/7) And although I'm young, at levels like mine, this is still stunning. The only historical comparator group are those with a 1-in-1,000,000 genetic condition: homozygous familial hypercholesterolemia (hoFH). Now, I don't have this hoFH. These children typically get severe advanced atherosclerosis and even a heart attack as young as age 8 or 10.

In fact, I have far more lifetime exposure than these children, yet my arteries could not be more perfect.

3/7) I'm not going to chalk up my good cardiovascular health to any supplement one singular aspect of my health routine. Nothing beats being overall metabolically healthy and eating and living well.

Nevertheless, my personal story has inspired a curiosity in readily available natural compounds that can improve heart health. Today's deep dive letter is a result of my obsessive fascination in heart health—a synthesis of tens of thousands of written words and hundreds of papers that I've gobbled up over time.

Let me give you a taste…

Read 7 tweets

Nick Norwitz MD PhD

@nicknorwitz

Apr 30

The Peptide Proven to Cut Visceral Fat (In RCTs) 🧵

1/6) There is a peptide proven in multiple double-blinded, placebo-controlled randomized controlled trials to reduce visceral fat.

It’s called tesamorelin. (link at the end)

2/6) Tesamorelin is an analog of growth hormone–releasing hormone, a hormone released by the brain that signals the pituitary to release growth hormone.

Its main advantage over growth hormone is that it stimulates the body’s natural release of growth hormone, rather than adding a non-physiologic dose that doesn’t align with biological rhythms.

3/6) To give you just a taste of data: in a landmark 2007 New England Journal of Medicine study, patients with HIV on antiretroviral therapy and excess abdominal fat were given 2 mg of tesamorelin or placebo for 26 weeks.

Visceral fat decreased by ~15% in the tesamorelin group, while it increased in the placebo group. Subcutaneous fat did not change, and there was no loss in lean mass.

*Nuance note: Historically, the patient population studied has been patients with HIV taking antiretroviral therapy. Why? These therapies can cause visceral fat gain. So these patients aren’t biologically unique to HIV—they’re just a particularly vulnerable population in which these drugs have been assessed and FDA-approved.

Read 6 tweets

Nick Norwitz MD PhD

@nicknorwitz

Apr 28

After 7 Years, I Changed My Mind on Cholesterol Meds (Or Did I?)

🚨You'll want to read this one all the way though. Link at the end🚨

1/7) After seven years of living with astronomically high cholesterol, I’ve decided to start two medications. Not statins, but ezetimibe and bempedoic acid.

But that’s NOT the real story. The real story is WHY… and it has nothing to do with cholesterol🤨🤔...

Quick preface: “cholesterol-lowering drugs” are named for one effect, not their full biological impact.

Molecules don’t respect our labels. These drugs can influence multiple systems, including metabolism and brain health.

And in this case, they likely do.

2/7) Take ezetimibe. Beyond lowering LDL, evidence suggests it crosses into the brain and influences neurobiology.

Specifically, is disrupts the interaction between 14-3-3 and hexokinase, reducing protein aggregation.

Full video:

3/7) That means less amyloid, less tau, and even improved autophagy.

Even more interesting: retrospective analyses have found up to an ~8x lower risk of Alzheimer’s in patients on ezetimibe.

Not causal. Not definitive. But a signal worth paying attention to—especially in the right context.

Read 7 tweets

Nick Norwitz MD PhD

@nicknorwitz

Apr 25

1/5) Here are four things statins do in your body.

First: A human controlled trial found statins reduced GLP-1 levels by 50% in 16 weeks.

The clinical implications aren’t fully clear—but the fact this isn’t discussed is a disservice to science and to patients.

2/5) Statins disrupt mitochondrial function.

They reduce CoQ10 synthesis (a key electron carrier) and directly inhibit Complex IV in the electron transport chain. These are biochemical effects—but they matter for informed decisions.
staycuriousmetabolism.substack.com/p/the-mitochon…

3/5) Statins are sexist. Women face higher risk of muscle pain, potential muscle loss, and statin-induced diabetes.

Why? An extra X chromosome—and a gene affecting fatty acid (DHA) synthesis. Less DHA → worse mitochondrial function + higher blood sugar.
staycuriousmetabolism.substack.com/p/the-x-factor…

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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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