Question: Have you noticed ATX causing extreme lethargy in people? @Drew Donaldson talks about it, he said he hates the compound and I went up to 300 mg and got super lethargic and brain fog too. Thank you @Josh Large for sending this to me. Answer: Yes, I have noticed people reporting lethargy and brain fog, but what is being experienced is not ATX “causing” those effects in isolation. What you are describing is exactly what happens when redox state, timing, dose, lifestyle context, and signal balance are not respected. This is not a compound failure. It is a signaling and systems failure, and it is entirely predictable once you understand the underlying biology. At a cellular level, ATX strongly biases signaling toward AMPK activation. AMPK is the cell’s energy stress sensor. It turns on when ATP availability drops or when the cell is told that energy scarcity exists. When AMPK is activated, it suppresses energy-expensive processes, including mTOR-driven protein synthesis, growth, and repair, while increasing pathways involved in efficiency, substrate conservation, and survival. This is adaptive when the signal is brief, well-timed, and followed by recovery. It becomes maladaptive when the signal is strong, prolonged, or layered on top of an already stressed system. When someone pushes the dose to 300 mg, especially while under-eating, fasting, training hard, sleeping poorly, or operating under high psychological stress, the body is already leaning toward an energy-conservation state. Adding a strong AMPK signal on top of that tells the cell that energy scarcity is not temporary, but ongoing. The cell responds logically by reducing output. This includes lowering mitochondrial ATP throughput, decreasing neuronal firing rates, reducing neurotransmitter synthesis, and downshifting overall metabolic demand. Subjectively, this feels like lethargy, brain fog, low motivation, and mental dullness. Redox biology is central to this experience and is often completely ignored. Mitochondria do not just need substrates like glucose or fatty acids; they need a stable redox environment to move electrons efficiently through the electron transport chain. If oxidative stress is high and reducing capacity is low, electron flow becomes inefficient and ATP production suffers. AMPK activation in this redox-unstable environment further reduces energy demand as a protective mechanism. The brain, which has the highest energy demand per gram of tissue, is usually the first place people notice the consequences. Brain fog is a redox and energy throughput problem, not a toxicity signal.

I just got some and would like to know what a good starting dose is as a general mitochondrial dose.

https://open.spotify.com/episode/2fprUVF1byUiJheLu8K7I8?si=GHKmiEoZSZyT1W3iUpcwBA @Drew Donaldson and @Anthony Castore cover great topics here and most importantly apply common sense to peptides, small molecules and more. "Minimum effective dose" is the take home message. Great job fellas!

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