Thread by @stevemagness

In the health & performance world, we often get lost on the pathways.

Fasting, cold showers, etc. activates mTOR, AMPK, PGC-1a, etc. Then we assume it works.

Pathways are important. But they are easy to activate.
We need to worry about functional adaptations.

A quick primer:

With fasting, exercise, etc. it's simple

You are applying a stressor & hoping to get an adaptation

What adaptation you get depends on the strength & direction of the stimulus

Stimulus ->Body is embarrassed, signal to adapt -> pathway ->genetic response -> functional adaptation

Take fasting... Is it a cure all? Nope.

It's just a mild stressor that sends a message of "Hey we are going without energy for a while", so your body starts sending a message to get a bit more efficient.

Low energy-->activate PGC-1a--> mitochondria shifts to adapt to it.

But here's the thing... activating a pathway is easy.

The key is does it lead to functional change?

Does PGC-1a lead to mitochondria increases is step one.
Step two is does that lead to functional changes in something meaningful? Not just a marker, but something important.

The charts below get at this process. They are from work I did 10 years ago, but the ideas hold.

To really know if something works and how it does. We need to understand from the bottom to the top. From stimulus to functional adaptation.

Often, we just know pieces.

Let me give an example. HIF-1 is the pathway for responding to altitude. Simplified

1. Low O2 (hypoxia)-->
2. HIF-1 pathway activation -->
3. EPO expression -->
4. Red Blood Cell ⬆️ -->
5. ⬆️ Total Hemoglobin Mass-->
6. ⬆️ In endurance capacity

Traveling on a plane (lower O2 for ~hours) can activate HIF-1 pathway. But it stops there.

Sleeping in an altitude tent for ~8hrs for weeks: Gets you to EPO expression & maybe RBC...but stops there.

To get functional ⬆️ in endurance: 10-12hrs+ a day in hypoxic tent for months.

Point being. Activating the pathway is easy.

You need the right stimulus for long enough to get to what really matters. The functional shift in endurance performance.

Which gets us back to the original point of this thread...

Whenever we obsess over a pathway, I get wary.

That's not the vital part. The key is does the stimulus you apply lead to a functional change!

Let's go back to fasting: It's a stimulus. It activates some energy pathways.

What's it take to get to functional change?

Fasting may get you there.

But...it's a very crude and narrow one. There's little way to vary it (to keep getting adaptation) besides fasting longer...

You can activate the same pathways, in a much more varied and robust way through other mechanisms.

For instance, if mitochondria adaptations are your thing.

There is a near-endless supply of endurance stimuli you can use in exercise that are more robust, stronger stimuli that lead to functional adaptations.

From short intervals to long walks & everything in between.

That doesn't mean I'm against fasting.

If that's your choice of stressor, that is sustainable. Go for it.

Let's just not get lost in pathway madness. There are many many important pathways. They interact. They can be activated in a variety of ways.

For any intervention, ask these questions:

What adaptation are you looking for?
What stimuli lead to those adaptations?
How much and in what direction does the stimulus need to be applied to get to functional adaptation?

We can get really complicated.

But any stressor that embarrasses the body, telling it that isn't quite strong, efficient, capable, etc. enough starts the cascade.

It's the right dose, at the right time, over a prolonged period that leads to adaptation.

It's a lesson I learned along time ago in coaching.

Scientists- Obsess over the pathway, the mechanism, how it occurs

Coaches- Obsess over what makes them faster/stronger (i.e. functional result)

In an ideal world, we figure out all, understanding from the bottom to the top