Hi All

Background:
I don’t eat/avoid foods with gluten, lectins, cassein, soy nor histamines. If I slip, I don’t get into shock but its still not very pleasant (pains, emotions), but I sometimes do for getting dopamine or pmdd or stress reasons.

Issue:
Now I started micro/nano dosing (.14mg) mounjaro (glp-1) and for the first time in a long time, I got reflux a few times. I want to nip this in the proverbial b* before it becomes a real issue and it forces me to stop the glp-1.

Question:
I take a lot of supplements in alignment with a longevity specialist/dr but for whatever reason I don’t have any digestive enzymes.. so I thought I ask in here as you might take smth that fits my needs.

Hi all

Starting this for inflammation and hence very low. I have it all ready at home, kiwipen at 2.5mg and Ultra-fine pen needles. I also got this calculator https://getdosewise.com so so far, so good.

Idea is to start with .14mg, which equals 3 clicks.

But - I read smth about the first 2 clicks do not contain anything ?

Can someone clarify this for me ?

Many thanks

There’s a hormone your muscles release when you do intense exercise.

In 2012, harvard university found something. They called it Irisin. After iris the greek messenger goddess.

In a literal sense, it carries the signal from your muscles to your brain.

And that message is.

Build.

What it does

In animal studies, when irisin reaches the hippocampus, the part of your brain tied to memory it activates pathways that increase a protein called BDNF.

BDNF is what helps build new connections, keeps neurons alive, and supports the creation of new ones.

It’s basically part of your brain’s maintenance system.

In humans, this pathway seems to exist too.

But it’s not clean.

A lot of it is stitched together from animal work and indirect human data. The direction is pretty clear. The size of the effect isn’t.

Still, the idea holds:

Your muscles, send a signal that appears to keep your brain itself intact.

What triggers it

Intensity.

That part shows up again and again.

A 2024 study looking at this pathway found a pattern. At lower effort, the signal is weak or inconsistent. As intensity goes up, the response becomes more reliable.

It’s not a clean switch.

But it leans one way:

Push harder = stronger signal.

Walking still helps your brain.

So does light movement.

They just don’t seem to drive this specific pathway very hard.

If you want this muscle to brain signal, you probably have to go past comfortable.

Cold exposure

Cold seems to tap into part of the same system.

A 2014 study showed that cold exposure increases circulating irisin in humans.

Same hormone but different trigger.

What has not been proven yet, but may in the future.

That cold - BDNF - better cognition chain in humans.

The overlap in pathways is real.

The interesting thing is If you can't train hard due to various reasons, there might be another way to get part of this signal to the brain.

Where the irisin story went wrong

Early on, most of the hype came from mouse studies.

Those studies used doses far higher than anything a human body produces.

Then came the measurement issue.

Early human studies used an antibody test that was not specific, they picked up on the wrong proteins.

So the numbers looked bigger than they actually were.

In 2015, researchers used mass spectrometry, a much more accurate method to measure irisin in humans.

Here's what they found:

Sedentary people: around 3.6 ng/ml
People who train: around 4.3 ng/ml

That’s a real difference.

But not so huge.

Nowhere near what the early headlines suggested.

So the honest version looks like this:

The hormone is real.
The pathway is real.
The effect in humans exists but it’s modest.

Which means exercise matters.

But it’s not the whole picture.

The other problem

Even when the pathway is there, it doesn’t operate on its own.

Insulin resistance lowers BDNF.
Chronic inflammation lowers it.
High cortisol lowers it.
Oxidative stress lowers it.

So the people who may need this signal the most…

often have the weakest response to it.

That’s the bottleneck.

The second pathway

Your brain doesn’t rely only on muscles.

It can generate its own signal.

Cognitive challenge, done properly can increase BDNF without any muscle involved.

No sweat needed. Just difficulty.

Push your brain hard enough, and it responds.

The trial most people missed

The ACTIVE trial.

2,802 adults over 65.

Started in the late 90s.

They were split into groups:

• memory training
• reasoning training
• speed-of-processing training
• or nothing

Each group trained for about 5-6 weeks.

Some got follow up booster sessions about a year later, and again at three years.

Then they waited.

For twenty years.

The follow up came out in 2026.

Researchers looked at medical records for just over 2,000 of the original participants.

Most had died by then. Average age: mid 80s.

The result:

The speed-of-processing group that got boosters had about a 25% lower risk of dementia over 20 years.

Roughly 40% developed dementia versus 49% in the control group.

Memory training didn’t show a clear effect.

Reasoning training didn’t either.

Speed training alone wasn’t enough.

Only the combination short training plus reinforcement over time made a difference.

This is one of the few long term randomized trials showing any reduction in dementia risk.

Not drugs.

Not supplements.

Not diet.

Training.

Done in a specific way.

And not Wordle.

Not Sudoku.

Not the generic brain apps.

This was adaptive training that got harder as people improved.

Two pathways

Most people are using neither very effectively.

One pathway is physical:

Intensity → irisin → BDNF

The other is cognitive:

Adaptive challenge → BDNF

Most people walk
and do light puzzles.

Both are fine.

They just don’t seem to push either system very far.

What to do

If you’re young and healthy:

Push intensity.

Sprints. Intervals. Heavy lifting.

Cold exposure can help, but it’s secondary.

Check your vitamin D.

Low levels may reduce FNDC5 — the protein that turns into irisin.

Which means the same effort could give you less return.

If you’re older or can’t train hard:

The cognitive pathway has stronger long term outcome data.

Not casual games.

Adaptive training that forces you to improve.

And it probably needs to be repeated over time.

If you’re in the middle:

Use both.

TLDR

Your brain needs repeated growth signals.

Modern life strips most of them away.

We move, but not intensely.
We think, but not deeply.
We stay comfortable.

Exercise gives you one signal.

Cognitive challenge gives you another.

Irisin exists.

It was identified in 2012.

It’s measurable in humans.

Its role in brain health is promising — but still being worked out.

Most people have never heard of it.

Now you have.