Can One Peptide Reduce Visceral Fat and Promote Longevity? 🧵

1/5) Tesamorelin is a peptide shown in randomized controlled human trials to reduce visceral fat by ~20%.

But that may be one of its least interesting effects.

Stick around to the end for the big reveal… 2/5) Tesamorelin is a growth hormone-releasing hormone (GHRH) analog.

Rather than supplying growth hormone directly, it nudges your pituitary to release more of your own.

That can:

• Support lean muscle
• Reduce visceral fat
• Improve body composition

But there's more.

How to Hack a 7-Day Fast in 24 Hours

1/5) What happens when you fast for 7 days?

Not what I expected.

In a remarkable study published in Nature Metabolism, researchers put 12 healthy volunteers through a 7-day water-only fast and used advanced proteomics to track 2,923 circulating proteins simultaneously.

What they found was surprising—and suggests some people may stop fasting just before many of the benefits begin. 2/5) During the first two days, the body performed a fuel switch.

Proteins involved in fat transport and ketone production surged as participants transitioned away from glucose dependence. Basic. That’s fasting 101.

But the most interesting changes hadn't started yet… The real shift didn't begin until Day 3.

Do Statins Cause Alzheimer’s: The Uncomfortable Nuanced Truth

1/5) Can statins cause Alzheimer’s disease and dementia? The honest answer is more complex than people give it credit for.

There are data suggesting statins can impair cognition. There are also data showing neutral effects, and even potentially protective effects. That contradiction requires resolution, not echo chambers.

Take a 2012 study in patients with pre-existing cognitive decline:

• Removing statins for 6 weeks improved cognition
• Re-challenging with statins for 6 weeks worsened cognition

Sounds alarming. But that’s not the whole story. 2/5) Many studies and meta-analyses find: no cognitive harm, neutral effects, or even potential protection against dementia

So, what’s going on? The answer likely lies in the interaction between:

• The pleiotropic effects of statins and
• Individual host physiology

Context matters. (Shocker)

Most Americans are metabolically unhealthy.

They have endothelial dysfunction and chronic inflammation.

On THAT metabolic background, statins may improve: endothelial function, blood flow, and inflammation Potentially benefiting both heart AND brain.

The Longevity Molecule is Garlic Nobody Saw Coming 🧛‍♂️🧄

1/4) Look at these two graphs.

LEFT: This what happens to circulating levels of something called “eNAMPT” with age in humans. It drops.

eNAMPT is a form of the enzyme NAMPT packaged into tiny extracellular vesicles (e) that travel throughout the body.

Why does that matter?

NAMPT is critical for producing NAD+, a molecule essential for energy metabolism, DNA repair, and countless other biological processes.

RIGHT: This shows what happens when researchers treat animals with eNAMPT-containing vesicles.

Lifespan increases by roughly 10%.

But here's where the story takes a surprising turn... Garlic!?! 2/4) In a 2026 paper published in Cell Metabolism, researchers connected a compound found in aged garlic extract—called S1PC (1)—to this longevity pathway.

Specifically, S1PC stimulates fat cells to release eNAMPT (2). What happens next is pretty wild.

eNAMPT travels to the brain (3), increases NAD+ levels, and ultimately contributes to improvements in muscle function, strength, and frailty measures in aged animals (4).

What's more, in a randomized, double-blind, placebo-controlled trial in humans, supplementation with S1PC from aged garlic extract increased circulating eNAMPT levels.

The effect was particularly evident in adults over 40 who were not clinically underweight.

In other words, the mechanism appears to translate from mice to humans.

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...

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.

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.

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—