I hope everyone had a fantastic weekend! We’ve got some exciting updates this week, and I wanted to bring everything together in one post for simplicity. First, big news the Kenetik Pro Buyers Club is officially launching! If you’ve been curious about trying the supplement I personally rely on the most, ketone esters, now’s your chance. I’m thrilled to be able to offer both access and savings. I’ve put together a thread that breaks down everything you’ll need—how to order, how many bottles you’ll likely go through in a month, and pricing details. Next, a quick clarification on the upcoming free webinar. This one is going to pull back the curtain on my own protocol and thought process. You’ll get the full, no-holds-barred breakdown of what I take, why I take it, and how I pair it with training, nutrition, and lifestyle strategies. My goal is to help you see things through a systemic lens so you can craft protocols that are more precise and effective. I want this to be fun, transparent, and useful and I’ll say up front, I’m learning every day right alongside you. Feedback (positive or critical) is always welcome. My plan is to make this a monthly feature, including not just my own protocols but also other people’s, so we can grow as a community of protocol designers together. Finally, a huge thank-you to Kassem Hanson of N1. He’s been an incredible resource for me personally and for our community. I’m currently enrolled in his program design mentorship, and if you want to learn the N1 approach, I can’t recommend their online and in-person seminars enough. They teach customization and critical thinking in a way that resonates whether you’re brand-new or decades into this field. Kassem generously edited the SLU webinar from Saturday, and I’ll be posting the recording soon for anyone who couldn’t attend. I’ll also be sharing the slides here, so if you haven’t received them by email, keep an eye out for the link. Link to webinar reply Thank you all so much for your support and for the energy you bring to this community. Everything we’re building here is possible because of each of you. Please don’t hesitate to reach out if there’s something you’d like to see more of, or if you have suggestions on how I can serve you better. I’m here for you guys!

Has anyone heard about this peptide before? Sounds promising as it’s orally active. https://onlinelibrary.wiley.com/doi/10.1002/dmrr.70056

This whole “six-stage agonist” idea reads like a playground contest where six-year-olds are trying to one-up each other without thinking through the consequences. One kid says, “I can eat the most candy,” the next says, “Well I can stay up all night,” another brags, “I can ride my bike with no hands,” and pretty soon the game spirals into chaos everybody competing, nobody coordinating, and the end result is a bunch of sick, cranky kids. That’s exactly what happens when you try to bolt GLP-1, GIP, glucagon, IGF-1, Klotho, and myostatin inhibition together into a single product. Each of these signals has real, powerful effects on metabolism, growth, and cellular resilience, but they pull in opposite directions, act on different timelines, and demand very different dosing windows. Instead of synergy, you create noisy cross-talk that leaves the body trying to follow six conflicting orders at once. True optimization doesn’t come from piling on more levers or chasing the newest shiny receptor target it comes from respecting the intelligence of the cell, reducing signal noise, and using surgically precise interventions at the right time and in the right tissue. A “GLP-1 + GIP + glucagon + IGF-1 + Klotho + anti-myostatin” cocktail is mechanistically incoherent because it stacks pathways that biochemically push in opposite directions, on different clocks, in different tissues. GLP-1R and GIPR are Gs-coupled incretin receptors that raise cAMP/PKA and potentiate β-cell insulin secretion, slow gastric emptying (GLP-1), and alter CNS appetite; GCGR is also Gs-coupled but in hepatocytes it spikes cAMP/PKA to drive glycogenolysis and gluconeogenesis, directly opposing the glucose-lowering aim of the incretins and serine-phosphorylating IRS1 to blunt insulin signaling in liver. IGF-1R is an RTK that activates IRS→PI3K→AKT→mTORC1 and MAPK/ERK to promote hypertrophy and nutrient storage, while soluble Klotho evolved as a longevity brake: it partners with FGF23 for phosphate/Vit-D control and independently dampens IGF-1/insulin signaling and shifts cells toward FoxO-mediated stress resistance and autophagy i.e., the biochemical opposite of sustained mTORC1 drive. Myostatin inhibition removes SMAD2/3 repression at ActRIIB, disinhibiting satellite cells and mTORC1 in muscle; pair that with IGF-1 and you push strong anabolism in myofibers, but the liver is simultaneously being told by glucagon to export glucose and lipids while adipose receives a GIP signal that favors storage so partitioning gets noisy. Add hard constraints from pharmacology: receptor stoichiometry and PK don’t line up. IGF-1 (IGFBP-bound) has long half-life and broad tissue exposure; GLP-1/GIP need DPP-4 protection and act over minutes to hours; glucagon clears fast but hits liver immediately; Klotho’s effects are slow, endocrine, and context-dependent; anti-myostatin requires sustained exposure for weeks to remodel transcription. One fixed dose can’t simultaneously achieve the right receptor occupancy across these targets: the concentration that meaningfully engages IGF-1R will overshoot GLP-1R CNS effects; the dose that meaningfully inhibits myostatin in skeletal muscle will not “time-match” the brief hepatic cAMP bursts from glucagon; and any hepatic PKA surge will antagonize the insulin/IGF-1 signaling you need for clean glycogen and protein synthesis. Think of it like six foremen shouting conflicting orders on a construction site: IGF-1 and anti-myostatin demand “build muscle now,” Klotho says “slow growth and repair the scaffolding first,” GLP-1/GIP say “bring in insulin and store nutrients,” glucagon yells “ship the materials back out of the warehouse,” and the clock for each foreman runs at a different speed. The “peer-reviewed” reality is that the only reason GLP-1/GIP/GCGR tri-agonists can work in trials is because they are engineered single peptides with tuned receptor bias and potency ratios to achieve a net, phase-appropriate phenotype; bolting on IGF-1, Klotho, and anti-myostatin as separate levers breaks that balance and guarantees asynchronous, tissue-mismatched signaling. The likely story arc is predictable: week 1 you feel appetite suppression and see scale weight drop from GLP-1 physiology while hepatic glucagon spikes make glucose swing; by week 2–4 IGF-1 and anti-myostatin start pushing muscle protein synthesis but collide with hepatic PKA-mediated insulin resistance and GIP-biased adipose storage, so nutrient partitioning becomes erratic; by weeks 4–8 Klotho’s brake on IGF/insulin signaling and phosphate/Vit-D shifts muddy recovery and mitochondrial quality control, leaving you with jittery glycemia, inconsistent pumps, GI side effects, possible edema or mineral issues, and a plateau where fat isn’t reliably falling and muscle isn’t cleanly accruing. Instead of a symphony you get six instruments in different keys, different tempos, and different rooms the score reads “recomp,” but the sound is chaos.

Monthly Q&A is Wed, Sept 24th at 12pm EST! Peptides, mitochondria, training, recovery, redox, nutrition nothing off limits. Can’t make it? It’s recorded. Send your questions ahead & I’ll tackle as many as possible. Don’t miss this one! Anthony Castore is inviting you to a scheduled Zoom meeting. Topic: Anthony Castore's Zoom Meeting Time: Sep 24, 2025 12:00 PM Eastern Time (US and Canada) Join Zoom Meeting https://us06web.zoom.us/j/3374982270?pwd=df4BMZNo1LubZaVOX40y7ApApJMNh1.1&omn=86062393294 Meeting ID: 337 498 2270 Passcode: 12345 --- One tap mobile +13052241968,,3374982270#,,,,*12345# US +13017158592,,3374982270#,,,,*12345# US (Washington DC) Join instructions https://us06web.zoom.us/meetings/86062393294/invitations?signature=ifWS2d8Nthqfmi1D1qiFFAu-MxuZwFKHQvHy7dxGD68