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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.

Read 6 tweets

Nick Norwitz MD PhD

@nicknorwitz

Nov 15

Microbiome Reset (Protocol)

1/6) If you’ve ever thought, “What if I just reset my microbiome?” Well, that’s what I want to help you do today.

But why even ask this question?

Let me back up—about 29 years—and share a bit of personal context.

As a newborn, I spiked a fever of 106°F. Out of caution, I was given powerful antibiotics.

Today, we better understand how critical early life is for microbiome development. Antibiotics like the ones I received can leave a lasting scar—even increasing risk for inflammatory bowel disease (IBD) later in life by ~500%.

Lo and behold, I did develop IBD—specifically, ulcerative colitis. It nearly killed me.

2/6) The truth is, our microbiomes are under constant assault—sabotaged daily by the booby traps of modern living.

From the moment you wake up and pour cereal into a bowl to the moment you collapse into bed, eyes glazed from “just one more” episode, our environments have drifted so far from nature’s blueprint that most of our microbiomes are evolutionarily unrecognizable.

So, what might a microbiome reset look like?

3/6) In today’s letter, we push the boundaries of science (and colon walls). We discuss:
👉A Step-by Step 4-Phase Guide
👉What to Avoid when you’re in microbiome in maintenance mode
👉Lifestyle inputs Beyond Food that shape your gut health.
staycuriousmetabolism.substack.com/p/how-im-rebui…

Read 6 tweets

Nick Norwitz MD PhD

@nicknorwitz

Nov 13

I just completed a month-long sardine diet.

1/5)The results were... surprising 😳
👉Body fat (7%)
👉Omega-3 levels, off the chart (literally, 25% higher than the visual scale goes and 2.7% above reference range)
👉Energy = Excellent (after some tweaks)
👉Cold Resistant. Maybe an impact of omega-3 on thermogenesis (via omega-3 derivatives, e.g. 12-HEPE)

2/5) The Rationale: Sardines are about as close to a superfood as one can get: packed with protein, omega-3, calcium, B12, CoQ10, creatine, etc.

They're like if a multivitamin had a baby with a protein supplement - but natural. So you can pretty much live off sardines

3/5) For the first several days I did only sardines. But then my energy dipped. So I adapted my 'sardine fast' into a sardine-based diet, supplementing with added fat - especially olive oil and MCTs.

This turned me into an energizer bunny and made the Sardine Diet sustainable for a full month.