SLU-PP-332 vs. ATX-304

Happy Wednesday!

A few days ago, I got a great question from a reader that I know several thousand people are wondering.

The question was:

SLU-PP-332 and ATX-340 are two game-changing compounds taking the research world by storm right now.

Both of these molecules are incredible.

But they work completely differently.

And that matters a lot when you’re thinking about stacking them.

So let’s break this down in a way that makes sense.

Why It Matters

Before we talk dosing or stacking, we need to zoom out.

Because most people think of exercise as “movement.” But physiologically, exercise is a molecular event.

It’s the body experiencing controlled stress that forces it to:

• Increase metabolic rate

• Burn fat more readily

• Expand mitochondrial capacity

• Improve insulin sensitivity

• Strengthen muscle

• Upgrade cardiovascular performance

Most people either can’t exercise enough to trigger these changes…or they can’t sustain it long enough to maintain metabolic health.

Age, injury, autoimmune issues, obesity, and modern life all get in the way.

This is where exercise mimetics become revolutionary.

Both SLU-PP-332 and ATX-304 flip key biochemical switches that mimic real exercise inside the cell, without needing mechanical output.

Not as a replacement for training, but as a way to give the body the benefits of training when training is limited.

So the real question isn’t “should you take both?”

It’s “What biological layer are you targeting?”

Because these two molecules target completely different layers of the exercise effect.

SLU-PP-332

SLU-PP-332 is what I call a transcriptional exercise mimetic.

It binds the estrogen-related receptors (ERRα/β/γ), which are NOT estrogen receptors. They are mitochondrial gene-expression controllers.

Published data shows SLU-PP-332:

• Increased treadmill endurance by 70% in mice

• Increased distance by 45%

• Shifted muscles toward oxidative, fatigue-resistant fibers

• Caused obese mice to gain 10× less fat

• Dropped body weight without appetite suppression

• Dramatically improved glucose + insulin sensitivity

This is long-arc remodeling.

Real mitochondrial upgrade.

A genetic rewrite of your metabolic machinery.

Think of it like telling your muscles:

“You are an endurance athlete now. Build the engine to match.”

It changes the metabolic blueprint, the way training does, but from the inside out.

This becomes very important when we answer whether you should stack it with ATX-304.

ATX-304

ATX-304 (formerly O304) is not working on the genome.

It works on your fuel gauge.

ATX-304 is a pan-AMPK activator, and AMPK is the enzyme that turns on when:

• You’re low on energy

• You’re fasting

• You’re training

• Your muscles need more glucose

• Your cells need to burn fat

• Your body needs to improve blood flow and vascular dilation

In humans (yes, ATX-304 has human data):

• Fasting glucose dropped

• Insulin resistance improved

• Microvascular blood flow increased

• Blood pressure decreased

In animals:

• Liver fat and fibrosis dropped

• Total fat mass dropped

• Fat oxidation increased

• Cardiac output improved

• Kidney stress reduced

• Age-related insulin resistance reversed

It flips the metabolic switch that says, “Burn energy, stop storing energy.”

So now we ask the big question…

Should You Take SLU-PP-332 + ATX-304 Together?

Mechanistically?

Yes, these two stack beautifully.

Not because they “double” the same pathway.

But because they target completely different metabolic levers.

SLU-PP-332 = The Builder

It rewrites the metabolic blueprint.

It upgrades muscle fiber type.

It increases mitochondrial machinery.

It raises basal endurance metabolism.

ATX-304 = The Switch

It tells the cell to burn fat.

It increases glucose uptake.

It lowers blood sugar.

It triggers energy expenditure on demand.

In metaphor form:

SLU-PP-332 installs a bigger engine.

ATX-304 steps on the gas pedal.

This is why the stack makes sense for fat loss:

• One improves your capacity to burn fat

• The other increases your actual fat oxidation

• One improves endurance machinery

• The other improves metabolic turnover

• One is structural

• One is functional

They are complementary, not redundant.

Downside?

One thing I want to be absolutely clear about is that SLU-PP-332 is not a “more is better” molecule.

Because it works at the transcriptional level and rewires endurance gene expression, using too high a dose for too long can push the body into an overtrained metabolic state (aka mitochondria overspin).

Think of it like forcing the “endurance athlete program” too aggressively.

In animal models, excessively high ERR activation can theoretically lead to mitochondrial stress, excessive fatty-acid oxidation, and unintended muscle remodeling.

This doesn’t mean SLU is dangerous per se. It means it should be used intelligently, cyclically, and at the right dose, the same way you would cycle periods of high-intensity endurance training. More is not better.

On the other hand, ATX-304 operates at the AMPK level, which is the same energy-sensing pathway activated by fasting, caloric restriction, and exercise.

AMPK activation is one of the most consistently validated longevity pathways across species. ATX-304, when used correctly, is something I personally see as a long-term metabolic and healthspan compound, not something you have to cycle aggressively.

SLU = powerful but cyclical

ATX = sustainable and longevity-focused

Use each for what it’s best at, and you’ll stay on the right side of the metabolic curve.

Dosing

For SLU-PP-332, research models often used higher relative dosing, but for humans, 250–1000 mcg/day is the typical experimental range.

Some people go higher, but in my experience, that can cause a buildup of ROS much faster.

If you have never used SLU-PP-332, start LOW and go SLOW.

For ATX-304, early human trials used 50-300 mg/day orally, depending on formulation and bioavailability.

One trial had users take 1000mg daily and there were no adverse effects.

Based on my practical experience using it, I like 200–400 mg/day.

ATX-304 is dose-responsive, and you do NOT want to mega-dose AMPK activators (just like you wouldn’t megadose metformin).

Stacking Recommendation

When stacking both, experimental protocols generally look like:

• SLU-PP-332: 250–500 mcg/day

• ATX-304: 200–400 mg/day

This keeps you on the “exercise mimetic” side of the curve, not the “too much metabolic stress” side.

Final Thoughts

The future of fat loss and metabolic health is going to be multi-pathway.

Not one compound.

Not one receptor.

Not one lever.

GLP-1s reduce appetite.

Exercise mimetics improve energy expenditure.

Mitochondrial peptides improve cellular resilience.

Thyroid optimization improves basal metabolic rate.

Testosterone improves body composition.

Everything works together.

And when you zoom out, SLU-PP-332 and ATX-304 are simply two compounds to activate different arms of the “exercise signal” successfully.

One rewires the muscle to be more oxidative.

The other flips the cellular energy-use switch.

When used responsibly and experimentally, they could become some of the most powerful metabolic compounds the longevity world has ever seen.

Best,

Hunter Williams