Why are we (the collective “we”) not talking about Cardarine more? It’s effective, and it’s cheap as hell, win win IMO. I get that these peptides, small molecules and whatnot are the hot topic nowadays, rightfully so, but why isn’t Cardarine in that discussion? I’ve personally seen good results with using carnitine and Cardarine together, and now I’m looking at bringing in SLU and the other mitochondrial players. How would I use Cardarine along with carnitine, SLU, mots c, etc.? I’ve used carnitine and Cardarine pre training with good success, but like all of us here, I want to keep improving Like I mentioned, I’ve used carnitine and cardarine pre training (substrate session) thinking that I’ll spare muscle glycogen, therefore improving performance, by enhancing fat usage and stimulating PGC-1 in a training environment would help make sure those new mitochondria are exposed to that environment. But if I’m looking to build my glycolytic system, maybe that’s not the best approach, and keep those players on more metabolic days? @Anthony Castore

I’ve talked about this a few times before, but I know there are still plenty of questions around it so I wanted to take another shot at clearly explaining the reasoning behind my answer. The case against higher doses of SLU-PP-332 starts with first principles: this compound works as a signaling cue, not a substrate to be “pushed” toward saturation. In cell systems and animal models, SLU-PP-332 appears to activate the estrogen-related receptor (ERR) program with PGC-1α coactivation, shifting transcription toward fatty-acid oxidation, oxidative phosphorylation, and mitochondrial quality control. That kind of pathway is amplifier biology: a small receptor-level nudge fans out into many downstream genes and post-translational switches. In such networks, more ligand does not linearly equal more benefit; it often crosses into different biology entirely, including compensatory braking and desensitization. Think of it like tapping a conductor’s baton to set tempo versus throwing a bigger baton at the orchestra. The first coordinates; the second creates noise and reflexes you didn’t intend. A key downstream branch of the ERR/PGC-1α program is modulation of uncoupling proteins. Mild, context-appropriate uncoupling in UCP2 and UCP3 can lower electron pressure, trim reactive oxygen species, and improve metabolic flexibility under load. But pushing the axis hard increases the probability of off-site expression and activity in UCP4 and UCP5, which are enriched in neurons and glia. Excess uncoupling in those tissues risks local ATP shortfall where energy security is non-negotiable. In brain and autonomic circuits, too much leak across the inner mitochondrial membrane can force compensatory hypermetabolism to maintain voltage, distort calcium handling, and disturb neurotransmission timing. At the organism level, that looks like brain fog, dysautonomia, sleep fragmentation, and reduced stress tolerance exactly the systems you don’t want to pay for marginal fat-loss gains. Mechanistically, high-dose signaling also raises the odds of maladaptive redox and substrate partitioning. ERR/PGC-1α drive beta-oxidation and electron delivery to the respiratory chain. If you layer that on top of exercise, fasting, thyroid augmentation, or catecholamine tone, you can overshoot electron influx relative to complex-level throughput, increasing retrograde signaling and forcing the cell to dump potential as heat via uncoupling. At low dose this can be hormetic and helpful. At high dose, it can flatten the ATP/ADP ratio, trigger AMPK hard, suppress mTORC1 anabolics, and blunt hypertrophy. In muscle, that shifts toward more oxidative phenotype at the expense of contractile remodeling; in the heart, it risks energetics imbalance that the sinoatrial node and conduction system must buffer beat-to-beat.

Exercise-induced lactate has turned out to be one of the most elegant examples of how the body’s energy and communication systems are woven together. For decades it was treated as a metabolic leftover, the acid that made your muscles burn. We now know that lactate is not waste at all it is a messenger and a fuel that links the contracting muscle to the brain, the immune system, and even gene expression. When you move hard enough that your breathing deepens and your legs start to ache, you are not just conditioning your heart; you are triggering a cascade of molecular conversations that teach your brain to grow new connections. During exercise, muscle cells switch from fully aerobic metabolism using oxygen to burn glucose in their mitochondria to a hybrid mode in which some glucose is converted to lactate through the pathway called glycolysis. Glycolysis is fast but inefficient, breaking a six-carbon sugar into two three-carbon molecules of lactate while regenerating a small amount of ATP, the universal energy currency. Instead of staying trapped in the muscle, lactate diffuses out through transport gates known as monocarboxylate transporters (MCTs). Think of these as commuter trains carrying lactate from working muscle into the bloodstream. Once in circulation, lactate levels can rise from a resting value of about 1 millimole per liter to 8–15 mmol/L during intense work, enough to change the chemistry of nearly every tissue. One of lactate’s first destinations is the brain. Astrocytes star-shaped support cells that wrap around neurons also produce lactate locally when neurons fire rapidly. They shuttle it to neurons through the so-called astrocyte-neuron lactate shuttle. In this system, astrocytes act like neighborhood bakeries turning stored glucose into lactate pastries that neurons can eat immediately. Neurons then oxidize lactate back to pyruvate, feeding it into the tricarboxylic acid (TCA) cycle and the electron transport chain in mitochondria to make large amounts of ATP. This direct fuel line keeps neurons firing efficiently when demand spikes, such as during learning or memory formation.

Join me for our October Live Q&A on Saturday, October 25 at 12:00 p.m. EST. We’ll dig into peptides, mitochondrial medicine, training and recovery design, and real-world protocol troubleshooting. Bring your questions (big or small), wins, sticking points, and labs or metrics you want decoded. Come ready to learn, take notes, and leave with clear next steps you can use the same day. To submit a question in advance, reply to this post with “Q&A” at the top and a concise summary of your question; live questions will be taken in order after pre-submissions. Save the date, invite a friend who’d benefit, and I’ll see you Saturday at noon. Here is the link to watch the replay of the Q&A thank you everone for joining and thank you for sending your questions in! https://us06web.zoom.us/rec/share/pcj7EkP9JA9hgj2SIcHeiFFgml4klErn_CRj33Nbb10OM0gmzh7itR_vKyHGXXwd.Cs3mioaqFw2jbYHe?startTime=1761407862000 Passcode: e4T2tR!l

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