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Happy Tuesday!
Today, I released a video breakdown of the AMPK-activating compound known as ATX-304.
This compound has been called an “exercise mimetic in a pill” because of the way it flips on the master metabolic switch in your body.
You can watch the video right now on Spotify here:
In today’s email, I would like to provide you with a detailed written breakdown of the topics covered in the video.
We’ll go into the backstory of ATX-304, how it works at the cellular level, what the science shows in both animals and humans, the results from clinical trials, the proper human dosing protocols, and finally who ATX-304 may be a good fit for.
Let’s dive in.
The Backstory of ATX-304
ATX-304 (originally known as O304 or OS-01) was discovered in Sweden about a decade ago by researchers searching for small molecules that could directly activate AMPK.
Unlike metformin, which weakly influences AMPK by complex I inhibition, ATX-304 was the first direct pan-AMPK activator to show strong preclinical results.
Early studies in obese and diabetic mice showed striking improvements in glucose tolerance, insulin sensitivity, fat mass, and even heart function.
This led to the first human trial in 2016–2017, where 65 type 2 diabetics on metformin were given ATX-304 for 28 days.
The results were published in JCI Insight and showed that the compound was safe, well tolerated, and effective at lowering glucose while improving blood flow.
Fast forward to today, and Cambrian Bio has taken the compound forward under the name ATX-304, and it’s being positioned as an anti-obesity, anti-aging, and metabolic health drug.
In other words, this is one of the closest things we have to a real pharmacological exercise mimetic.
Mechanisms
So how does this little molecule flip the exercise switch?
AMPK is the master energy sensor in the cell, activated naturally when energy is low (like during fasting or exercise).
Most drugs fail to activate it cleanly.
ATX-304 works differently.
It prevents dephosphorylation of AMPK at threonine-172, essentially locking it in the “on” position.
From there, downstream pathways light up:
Muscle glucose uptake increases without needing insulin.
Fat oxidation ramps up while fat synthesis is suppressed.
Autophagy is induced, clearing damaged proteins and organelles.
Vascular dilation improves blood flow via nitric oxide signaling.
It also acts as a mild mitochondrial uncoupler, increasing basal oxygen consumption and calorie burn by ~38% in cell models.
This dual action means ATX-304 mimics the metabolic effects of exercise at rest.
Think of it as tricking your body into acting like you’ve just done a fasted workout, without the workout.
Benefits
Because AMPK touches nearly every aspect of metabolism, the potential benefits of ATX-304 are broad. Here are the main categories backed by research:
Metabolic health: Improves insulin sensitivity, lowers fasting glucose, and reduces hyperinsulinemia.
Obesity and fat loss: Reduces fat mass rapidly in animal studies, preserving lean muscle.
Cardiovascular health: Lowers blood pressure, increases cardiac stroke volume, and improves microvascular perfusion.
Liver health: Protects against fatty liver (MASLD/NASH) by decreasing steatosis and fibrosis.
Kidney protection: Reduces serum creatinine and renal injury markers in cisplatin-induced AKI models.
Aging and longevity: Prevents age-related insulin resistance and preserves exercise capacity in older mice.
ATX-304 helps the body burn glucose and fat more efficiently, improves circulation, protects organs under stress, and supports healthy aging.
This is why it’s being called an “exercise pill” by many researchers.
Clinical Results
The most compelling evidence so far comes from the Phase IIa study in 65 patients with type 2 diabetes on metformin. After 28 days of 1000mg/day ATX-304:
Fasting plasma glucose dropped by –0.60 mM vs –0.10 mM with placebo (~11 mg/dL greater reduction, p=0.01).
Insulin resistance (HOMA-IR) improved by a statistically significant margin in the treatment group (p=0.0097).
Diastolic blood pressure decreased significantly, with a downward trend in systolic.
Peripheral muscle blood flow increased significantly on MRI perfusion scans.
Importantly, no serious adverse events or safety issues were reported.
In animals, the numbers are even more dramatic:
In fatty liver disease models, ATX-304 reduced total cholesterol by 45% (from 212 mg/dL to 143 mg/dL).
In AKI models, it cut serum creatinine by ~60% and kidney injury markers by two-thirds.
In aging mice, it reversed hyperinsulinemia and preserved exercise capacity equivalent to young controls.
These numbers show both statistical and clinically meaningful effects across multiple systems.
Dosing Protocols
In clinical trials, ATX-304 was given as a 1000mg oral suspension once daily.
However, new capsule formulations are being developed for easier use.
Based on the preclinical-to-human scaling and ongoing product development, the effective (and affordable) dose for humans is expected to be in the 100–300mg per day range.
Capsules are typically standardized to 100mg each, making the protocol simple:
Take 1–3 capsules daily (100–300mg).
Best taken first thing in the morning on an empty stomach, to mimic the natural fasting-induced AMPK activation.
This mirrors how your body would normally activate AMPK after an overnight fast and before exercise.
For most people, the sweet spot will be around 200mg/day, but dosing may depend on body weight and clinical goals.
Who Is ATX-304 For?
ATX-304 is not a magic pill, but it may be one of the most powerful tools we’ve ever seen for metabolic optimization and healthy aging.
It’s a great fit for:
People struggling with type 2 diabetes or prediabetes.
Those carrying excess body fat who want to preserve lean muscle while burning fat.
Individuals with fatty liver or early signs of metabolic dysfunction.
Biohackers and health optimizers looking for an exercise-mimetic longevity compound.
What can you expect?
Over time, improved blood sugar control, lower blood pressure, reduced fat mass, better endurance, and protection against metabolic stress.
In other words, many of the benefits of exercise and fasting.
Final Thoughts
ATX-304 represents a new class of compounds called exercise mimetics.
By directly activating AMPK across multiple tissues, it creates a metabolic environment that favors glucose uptake, fat oxidation, vascular health, and organ resilience.
The early data are extremely encouraging.
If future trials confirm these results over longer durations, ATX-304 could become a cornerstone therapy for obesity, diabetes, fatty liver, cardiovascular disease, kidney protection, and even aging itself.
And perhaps it could even be a better alternative to GLP-1s 🤷♂️
Time will tell, but at the very least, it will help complement the fat loss while preserving muscle.
Best,
Hunter Williams
P.S. If you want to snag some ATX to try for yourself, BioLongevity Labs offers this in their BioAmp product. You can get 15% off when you use code HUNTERW at checkout.
P.P.S. Further Reading (studies and sources):