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.

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:

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…

If you're worried about Alzheimer's disease, you need to know this about Omega-3s 👇

1/8) If you want to avoid Alzheimer’s, you need to understand these critical facts about fat metabolism in the brain.

Let’s start with this graph.

It shows how biomarkers change over the course of developing Alzheimer’s—from normal cognition, to mild cognitive impairment, to full-blown dementia.

The first thing to decline is lipid metabolism. But here’s the good news: that decline may be preventable. (link at the end) 2/8) The most important fat for the brain is DHA, a long-chain omega-3 fatty acid.

DHA makes up around 40% of the fatty acids in the gray matter of your brain.

It supports neural structure, reduces inflammation, improves brain glucose metabolism, and even helps clear metabolic waste like amyloid.

Eating 1000 Sardines Gave Me THIS Superpower
(New 2026 Findings!)

1/8) I ran a self-experiment where I ate 1000 sardines in a month.

Sure, it made me stink—but it also gave me one epic superpower. Let me explain. 🧵 (link at the end)

We all know sardines make your breath stink and that they’re nutrient-dense.

That’s basic.

But eating that many sardines changed me. It gave me a “superpower” that had my inner Marvel nerd activated—and my scientist brain scrambling to explain it.

Eventually, I found those data. 2/8) It was new paper in a top journal turned confusion into clarity and left me in awe of how much we’re still uncovering about human physiology.

The superpower…

Full deep dive link: staycuriousmetabolism.substack.com/p/why-stinking…

Citrus Bergamot for Cardiovascular Health

1/5) One meta-analysis of controlled human trials found that citrus bergamot extract lowers triglycerides, increases HDL, and lowers LDL — to a substantial degree.

But that’s not all... (link at the end) 2/5) More interestingly, one trial showed that while bergamot decreased small dense LDL, it increased‘large, fluffy’ LDL.

This shift towards a preponderance of large LDL vs small LDL is a metabolic fingerprint of improved metabolic health.

1/7) Is garlic the new metformin?

A strange new 2026 study suggests compounds in garlic might:
👉Extend lifespan (11.4% in animals)
👉 Improve insulin sensitivity (lower glucose and insulin levels)
👉Reduce fatty liver & reduce inflammation

Let’s break down this bizarre but compelling research. 2/7) Garlic is rich in diallyl sulfides (DAS) — sulfur compounds that increase hydrogen sulfide (H₂S) levels. H₂S acts like a hormone: it diffuses through membranes, triggering cellular pathways across the body.

Researchers fed mice a diet enriched with DAS, leading to an 11.4% increase in lifespan, more than double the effect of metformin.

How Sleep Deprivation Causally Drives Atherosclerosis

1/5) It’s well established that poor sleep is associated with an increased risk of cardiovascular disease.

But the big question has always been: How… Exactly?

Impressive research published in Nature — one of the world’s top scientific journals — reveals a fascinating biological mechanism. (link at the end) 2/5) To test for a causal connection between sleep deprivation and atherosclerosis (the buildup of plaque in arteries), researchers sleep-deprived mice genetically predisposed to developing atherosclerosis.

Compared to well-rested healthy control mice, the sleep-deprived mice developed significantly more atherosclerotic plaque (quantified on the right).

But that’s not all…

1/6) Let’s make this quick, because you don’t have much time…

New research suggests aging isn’t what we thought it was.

It’s not a passive decay process… it’s more like a violent molecular explosion!

Allow me to explain…
2/6) The scaffolding beneath your skin, made of collagen, elastin, and other proteins is called the “Extracellular Matrix” (ECM).

Over time, that matrix weakens. But according to new science, aging isn’t just a slow collapse.
It’s a BOOM!

But understanding this BOOM may open a path to stopping it.

As a Neuroscientist, this Graph changed how I think about Dementia Risk Factors

1/5) Microplastics are accumulating in the human brain at an alarming rate. Over the past ~8 years, brain microplastics have increased by ~50%.

But that’s not the worst part…

Consistently, microplastic levels in the brain are much higher in people with dementia (purple) than in those without dementia.

The association is so massive the graphs needs a Y-axis break! 2/5) The researchers behind this work hypothesize that the exponentially increasing concentrations of micro- and nanoplastics in the environment are driving a parallel increase in plastic accumulation in the human brain.

True—correlation ≠ causation. But you cannot do randomized controlled trials here. It’s neither ethical nor feasible.

And when an association is this large—and reverse causality is unlikely—it demands serious attention.

Cholesterol Debates in the Era of Medical Mistrust

1/4) This graph shows the hazard ratio for coronary heart disease associated with insulin resistance score (LP-IR) versus LDL cholesterol.

It’s not even close. Insulin resistance dwarfs LDL—with a >14-fold difference in relative risk. 2/4) So why does LDL get all the attention?

Simple: It’s easy to manipulate—and highly profitable.
The statin industry alone generates over $20 billion annually. It would be naive to pretend financial interests don’t shape medical priorities.

That’s not a conspiracy theory. It’s acknowledgement of incentive structures that ultimately dictate the spotlight of research, guidelines and medicine.

Protein-Maxing and the Illusion of Nutritional Progress

1/8) David Bar is the world’s most hyped protein bar—boasting ~75% of Calories From Protein (CFP) and the tagline “only what’s necessary.”

But how does it stack up? Let's have a dispassionate discussion...🧵👇 (link in 8/8) 2/8) Formulation: I’d give it a 3/10.

Despite the “only what’s necessary” claim, it contains two artificial sweeteners (Ace-K and sucralose) and the controversial artificial fat EPG.

Seems like inconsistent messaging at the very least. But what about these ingredients?

🚨👉What if a diet that lowered your cholesterol… increased your risk of death? (link at the end)

1/12) That’s what a forgotten a double-blind, randomized controlled trial from the 1970s seemed to show.

It tested whether swapping saturated fats for unsaturated fats would improve heart health.

Results?

The group that lowered their cholesterol... died more often. And the lower their cholesterol went, the higher their risk of death.

And if you think you’ve heard this story before (including a proper assessment of the counterarguments and deeper nuances—you haven’t…) 2/12) The Minnesota Coronary Experiment was a randomized controlled trial conducted between 1968 and 1973 that enrolled 9,423 men and women across six mental hospitals and one nursing home.

The power of this approach—though ethically questionable by today’s standards—was that researchers could truly blind and control patients’ diets with remarkable accuracy

A Nuance Hidden in a Historic Statin Trial (link in 12/12)

1/12) Medicine is supposed to treat individuals, not populations averages. And yet, the imprecision remains, like an intellectual cancer.

So, let’s look back at one of the most pivotal studies in cardiovascular history: the 4S trial, an see what is reveals when we stratify but just two biomarkers: TG and HDL

(And if you think you know where this goes, you're in for at least one plot Twist... 🚭) 2/12) According to cardiologists, the 4S trial is widely regarded as the study that launched the statin era.

4S was a randomized, double-blind, placebo-controlled study that enrolled 4,444 participants established coronary heart disease.

Patients were assigned to receive either simvastatin (20–40 mg daily) or a placebo and followed for 5.4 years.

The headline findings were that the statin (simvastatin) significantly reduced overall and cardiovascular mortality.

But there’s another part of the story—

Dr @PeterAttiaMD recently published an article entitled, "Pitting facts against sensationalism regarding the role of LDL cholesterol in ASCVD"

1/9) Peter opens with a quote: “We must admit that our opponents in this argument have a marked advantage over us. They need only a few words to set forth a half-truth; whereas, in order to show that it is a half-truth, we have to resort to long and arid dissertations.” ― Frédéric Bastiat

I could not agree more.

That's the purpose of today's letter... to discuss Where's the Nuance, Really?!

Specifically, where is the nuance on Longevity, Cholesterol and ApoB?

What follows is a teaser for a 25 page, 4000 word "long and arid dissertations" -- linked in 7/9 🔗

Punchline: When talking about deceptive simple messaging and biased narratives, medicine should look in the mirror as well.

Let's begin... 2/9) Here's where I want to start: The three dumbest words in medicine are: “Lower is better.”

This refers to lowering LDL cholesterol or ApoB.

It’s medical clickbait—seductive, oversimplified, and deeply devoid of nuance.

“You are going to die young.”

1/8) The first time I heard those six words, they were jarring. I was 23.

The insult that provoked that perceived threat was a single number on a lab report: my LDL cholesterol (LDL-C).

After I started a ketogenic diet (June 1, 2019), my LDL-C more than tripled from 95 mg/dl to 321 mg/dl.

Link at the end... 2/8) The logic was straightforward:

If I allowed my LDL-C levels to remain in the stratosphere, I would inevitably develop cardiovascular disease and die of a heart attack—young.

The question is this: Does LDL—or more accurately, ApoB—kill?

It sounds like an easy question. But it isn’t.

🚨The New Dietary Guidelines Are Internally Inconsistent

1/7) Publicly, RFK Jr. says “we’re ending the war on saturated fat.” The iconic food pyramid has been flipped, with butter and beef now at the top.

But read the actual guidelines, and you’ll find the exact same restriction: saturated fat still capped at 10% of daily calories. No change.

(People may not like this thread or the linked long-form letter. But I'm not here to pander or choose political sides. I'm here to seek the clarifications I know Americans want and to 'tough love' this step in the right direction into a proper leap...)

cc @RobertKennedyJr @HHSGov 2/7) How can one recommend:
👉Cooking with butter and tallow
👉Eating full-fat dairy three times a day
👉Prioritizing red meat…

🚨Yet still limit saturated fat to 10% of calories? That’s not an opinion. The math doesn’t math?!

Full Breakdown: staycuriousmetabolism.substack.com/p/the-new-diet…

1/10) No word yet from 'Dr' Johnson. So, I've decided to use this as a springboard to deeper learning.

Quick review: in a recent Twitter exchange between @chamath and @bryan_johnson, Bryan proclaimed: “Definitely do not stop statins.”

Today, we deconstruct common logical missteps that could lead to this misguided medical mandate.

A 🔗 to the full letter is at the end.

This won't be shallow reaction content, but an opportunity to dive deep... 2/10) Main Point #1: Causality is Overrated

Just because a molecule or biomarker plays a causal role in a disease process does not mean it is sufficient to cause disease.

More importantly, it does not mean intervention is the prudent path.

The presence of a “causal” variable does not ensure disease nor is the treatment benign.

Can TUDCA Really Slow Atherosclerosis? 🫀

1/6) The bile acid and supplement, TUDCA, has the potential to reduce atherosclerosis.

And it appears to do so not by lowering cholesterol, but by reducing inflammation inside arteries. (Red = fatty deposits in arteries)...🔗 in 6/6 2/6) In atherosclerosis, macrophages in the artery wall take up too much oxidized LDL.

This can trigger *ER stress* and activate inflammation, pushing the macrophages into *foam cells* that are a cause and hallmark of atherosclerosis.

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.

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.