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Nick Norwitz MD PhD

@nicknorwitz

Dec 13

New Study: Person Study Finds Statin Use Associated Decline in Muscle Mass

1/6) A colleague of mine—a medical doctor—texted me recently: “I’m stopping my statin.”

The new paper referenced concludes: “Continuous statin use is associated with a decline in muscle function and mass over time (25% decline in grip strength and 73% decline in appendicular lean mass compared to never- users).”

Let’s discuss. (links in 5/6 and 6/6)

2/6) We’ll break this up by discussing the cross-sectional (single time point) and longitudinal (over time) results.

Cross-sectional analysis: In the fully adjusted model, adjusting for age, sex, education, smoking, BMI, activity score, diet quality score, high blood pressure, diabetes, and so on, statin use was associated with lower grip strength and lower appendicular lean mass.

3/6) Longitudinal Analysis: Statin Use Associated with Steeper Muscle Decline

Echoing the prior analysis, continuous statin use was significantly associated with accelerated declining grip strength and lean mass.

*Nuance note: For those with keen eyes, we discuss the y-intercept in the full letter

TL;DR: Statins use is linked to fasting muscular decline.

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Nick Norwitz MD PhD

@nicknorwitz

Dec 11

https://x.com/nicknorwitz/status/1988943850044366975

Sardines Accidentally Supercharged my Metabolism?(link in 8/8)

1/8) Now, I want to follow-up on one of the strangest findings from the Sardine Diet Experiment...

I became cold-resistant.

Taking off my shirt on an icy Boston winter day felt almost like a cool, soothing summer breeze.

It felt weird. It was unexpected. But it also makes sense... Let's discuss...

https://x.com/nicknorwitz/status/1988943850044366975

2/8) As a quick recap, I recently did a self-experiment that can be summarized in just two words: Sardine Diet. After a couple weeks on this extremely high omega-3 diet, I became conspicuously cold-resistant.

This was weird.

And I wanted to understand what might be happening. So, I dug into the literature.

3/8) Here's what could be happening...

Metabolically active brown fat can convert omega-3 fatty acids into a hormone called 12-HEPE.

12-HEPE stimulates thermogenesis in brown fat and ramps up glucose uptake into muscle as well.

This ultimately promotes heat production, cold adaptation, and energy expenditure.

Now, let’s get into some data…

Read 8 tweets

Nick Norwitz MD PhD

@nicknorwitz

Dec 9

The Best form of Omega-3 Matters (🔗 in 8/8)

(1/8) Alzheimer’s disease is personal for me. In my early 20s, I discovered I carry the ApoE4/4 genotype—placing me at the highest genetic risk. I was terrified. But over time, that fear shifted to a realization:
👉A genetic predisposition is a vulnerability, not a destiny.
👉 Our choices shape our health trajectory more than our genes ever could.

Today, I want to share a piece of that puzzle: The Omega-3 Paradox.

👉The Signal: Data clearly shows eating fatty fish lowers Alzheimer’s rates and boosts cognitive longevity.
👉The Failure: Yet, large clinical trials using Omega-3 supplements often fail to protect the brain.
👉The Question: Why?

One answer lies in a specific delivery mechanism most people—and many researchers—overlook.

Here is the science of getting Omega-3s into the brain. 🧵👇

(2/8) So, why do supplements often miss the mark? The answer is likely the form in which the Omega-3s are packaged.

When you eat seafood, you ingest Omega-3s in diverse forms, including phospholipids. However, most supplements on the shelf provide them in other forms, like triglycerides.

The Form Matters…

(3/8) The Form of Omega-3 Matters.

Think of it like this: Consuming DHA as a free fatty acid triglyceride is like mailing a letter with no address. It enters your system, but it doesn't know where to go. It rarely reaches the brain.

But if you have phospholipid-bound DHA? That’s like sending a letter via express courier, straight to the correct neuron. More specifically, the “express courier” form is called Lyso-DHA.

This specific form has special access to the brain through a transporter called MFSD2A.

Without the phospholipid "address," the DHA gets lost in transit.

Read 8 tweets

Nick Norwitz MD PhD

@nicknorwitz

Dec 7

How Metabolic Disease Feeds Emotional Eating 🧠🍩
(link at the end)

1/8) A brand new study (Dec 10, 2025) reveals how poor metabolic health can drive emotional eating.

Why this is important: There’s a known link between metabolic disease (obesity, diabetes, etc.) and mental health conditions (eating disorders, anxiety, depression).

But the causal relationships remain murky.

In uncovering the “how” we lay the groundwork for innovative solutions.

cc @Metabolic_Mind @janellison @TuitNutrition @ChrisPalmerMD @MitoPsychoBio @WilliamFurness @drjenunwin

2/8) The researchers behind the experiments took interest in ImP, which is known to be elevated in patients with metabolic conditions like diabetes (below)—and is linked to cardiometabolic disease.

*ImP levels are elevated in humans with type 2 diabetes (red) vs healthy controls (blue).

3/8) Given the link between metabolic diseases and mental health, the researchers set out to test a new hypothesis:

If you increase ImP, does that change the brain and behavior?

To do this, they fitted mice with a tiny pump that continuously delivered ImP at levels designed to mimic what’s seen in people with diabetes.

Afterward, they looked for neural changes and found a large shift in gene-expression programs within neurons tied to the stress response in the hypothalamus.

Those molecular changes lined up with behavior.

Read 8 tweets

Nick Norwitz MD PhD

@nicknorwitz

Dec 6

When The “Cholesterol Drop” Misses the Mark
(Links in 6/7 and 7/7)

1/7) Can we assume that how much LDL drops tells us how much cardiovascular risk is reduced?

A new meta-analysis in the European Heart Journal says, “No.”

In fact, it suggests the link between LDL-C reduction and actual cardiovascular outcomes is incredibly weak.

So, have we built a multi-billion-dollar industry on the assumption that hot chocolate equals real illness?

Let’s unpack that…

cc @realDaveFeldman @AdrianSotoMota @ApoDudz @DrEricRodgers @LDLSkeptic @AKoutnik @janellison @bschermd

2/7) This was an umbrella review of meta-analyses of randomized controlled trials.

In total, the review included 20 RCTs comprising 194,686 participants, with a median follow-up of 4.85 years.

So, what did they find?

In this study, the r² for LDL-C on major adverse cardiovascular events ranged from 0 to 0.1.

In other words, this calls into serious question whether LDL-C can be used as a surrogate for clinical outcomes in statin trials.

3/7) To better define r2 (pronounced “R-squared”)… it’s a number that tells you how well one thing predicts another. It ranges from 0 to 1 (or 0% to 100%):

r² = 1 means perfect prediction — knowing the first number tells you exactly what the second will be.

r² = 0 means no prediction — the first number tells you nothing about the second.

r² <0.1 ... is terrible!

It’s like trying to predict who will win the marathon based on who tied their shoes the tightest.

Read 7 tweets

Nick Norwitz MD PhD

@nicknorwitz

Nov 25

🚨How Berberine Lowers Cholesterol: Blew My Mind! (link at the end)

1/6) I just learned how berberine lowers LDL-C/ApoB, and the *mechanism* blew my mind.

Unlike statins, it doesn’t inhibit cholesterol synthesis, or harm mitochondria, and doesn’t worsen insulin resistance.

In fact, it improves features of metabolic health, while also lowering LDL and ApoB in a totally unexpected way.

Let’s break it down...

⚠️ Warning: This is a heart-health nerd's only zone. Proceed at your own risk, especially with 4/6.
@ApoDudz @lipo_fan @realDaveFeldman @AdrianSotoMota @LDLSkeptic @AKoutnik @janellison @bschermd @tyler_smith @Hundredhealth @DrPaulMason @robbwolf @reallyoptimized

2/6) First, contrast with statins. Statins inhibit cholesterol synthesis, creating a relative “cholesterol starvation” state in liver cells.

The liver compensates by ramping up LDL receptor expression, which pulls LDL particles out of the bloodstream. Effective—but not without tradeoffs, which can include off-target effects in other organs:

👉Mitochondrial impairment
👉Reduced CoQ10 synthesis
👉Lower GLP-1 levels
👉Insulin resistance

I’m not saying statins don’t have a place—but their mechanism of action has real biological costs.

3/6) Berberine diverges completely. In a hypothesis-naive screen of natural compounds, it stood out by boosting LDL receptors through a weird route.

TL;DR: it stabilizes the receptor’s mRNA “instructions,” extending receptor production from ~60 minutes to >3 hours.

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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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