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Nick Norwitz MD PhD

@nicknorwitz

Dec 17, 2022 • 10 tweets • 5 min read • Read on X

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@Nature

🚨New paper in @Nature reveals link between #microbiome & #exercise motivation!🧠🐁

👉Provides foundational insight that could lead to dietary practices & supplements to promote exercise motivation

Video:

@hubermanlab
#dopamine

1/ Thread🧵👇

2/ The study in question is a mouse study, as you can really perform these fine mechanistic study in animal models

Data show that genetics variation among mice was a minor contributor and the variations in microbiome composition were more important for physical performance...

3/ To show the microbiome mediates the effects, they knocked out the microbiome with antibiotics in high-performer mice and the result was an impairment physical performance by 50%! (2a)

By contrast, microbiome transplant could enhance performance.

4/ Progressed to test hypothesis that motivation to exercise accounted for effect of microbiome on physical performance

Found that exercise ⬆️ dopamine levels (controls motivational state) AND exercise-induced ⬆️ in DA could be blunted w/ antibiotics to destroy microbiome

@hubermanlab

5/ Figure shows DA levels are NOT impacted in the basal state w/ antibiotic treatment but that antibiotics do prevent the rise in DA following exercise – consistent with the possibility that microbiome dysfunctioncould impact motivational states related to exercise
@hubermanlab

6/ Zooming fwd so as not to get tedious, by blocking elements of pathways or activating elements, the team demonstrated there is an axis whereby certain bugs produce metabolites that activate neurons that signal to DA motivational centers in the brain to want to exercise

7/ Specifically, the most potent gut derived metabolites were fatty acid amines, such as N-oleoylethanolamide (OEA) (5e), which – for the super nerds out there – is a lipid that acts on the endocannabinoid pathway and is structured based on oleic acid, a monounsaturated fat

8/ The scientists were even able to show that gastric infusions of (OEA) recapitulated the effects of dopamine increase and improved exercise motivation/performance, and that more OEA correlated with more running (5g)

9/ These data spell out a story showing a strong link between the microbiome and exercise motivation

By better understanding these pathways, we could create dietary protocols or probiotics that could make us want to move our bodies more, improving personal and public health

10/ Plug again for 5 min video overview & Happy Saturday!

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More from @nicknorwitz

Nick Norwitz MD PhD

@nicknorwitz

Mar 31

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.

3/7) Furthermore, on a glucose tolerance test, DAS-treated mice showed: Lower total glucose and much lower insulin levels

This is evidence of improved insulin sensitivity.

Read 7 tweets

Nick Norwitz MD PhD

@nicknorwitz

Mar 28

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…

3/5) The sleep-deprived animals also accumulated more inflammatory immune cells inside their arteries — the very cells that drive plaque formation and instability.

Below you can see a quantification of the immune cells (three types) in the arteries of sleep deprived animals (green) versus healthy controls.

Read 5 tweets

Nick Norwitz MD PhD

@nicknorwitz

Feb 19

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.

3/6) When the ECM breaks down — due to aging, injury, or stress — it leaves behind fragments. These aren’t just passive debris.

Many of them act as bioactive signaling molecules known as “matrikines.”

Read 6 tweets

Nick Norwitz MD PhD

@nicknorwitz

Feb 5

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.

3/5) Mechanistically, this makes sense. Microplastics can drive oxidative stress, chronic neuroinflammation, and vascular injury—three core pillars underlying dementia.

Read 5 tweets

Nick Norwitz MD PhD

@nicknorwitz

Feb 1

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.

3/4) And—despite better drugs and relentless focus on LDL as the biomarker cardiology loves to hate—CVD remains a top killer.

That shouldn't be acceptable. Big problems demand hard conversations—and honest autopsies on where we’ve gone wrong in medicine.

If we’re serious about orphaning cardiovascular disease, we must target the metabolic dysfunctions beneath the surface—the ones that often get overlooked and left in the shadows.

Read 4 tweets

Nick Norwitz MD PhD

@nicknorwitz

Jan 24

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?

3/8) Take, sucralose, for example.... It has been shown in human-controlled studies in certain contexts (co-ingested with carbohydrates) to promote insulin resistance.

TL;DR: Don’t chase David Bar with a banana.
More in letter:

Read 8 tweets

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