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Split Dosing GLP-1s: Why Smaller, More Frequent Doses Work Better
Do your research subjects experience a crash around day 6 or 7? It's a common pattern researchers observe... Days 1-4: Strong response. Minimal appetite signaling. Low food-seeking behavior. Days 5-6: Effects softening. Appetite signals returning. Day 7: Significant hunger response. Waiting on next administration. This isn't a flaw in the research protocol. It's basic pharmacokinetics. Here's what the data shows: Even with tirzepatide's ~5-day half-life, by day 7, circulating levels drop to roughly 60-65% of peak concentration. Receptor occupancy decreases proportionally. But what if you could maintain more stable levels throughout the research period? Same total weekly dose. Same mg. Just redistributed. → Reduced peak-related side effects → No end-of-week trough effects → More consistent receptor activation → Flatter concentration curve I wrote a deep dive breaking down: ✓ Why these compounds accumulate and why dose increases before week 4 skew results ✓ The math behind steady state ✓ Why clinical trials use once-weekly protocols (hint: it's about adherence, not optimization) ✓ Which research scenarios benefit from split dosing ✓ Practical protocols and considerations Full article with all the mechanisms 👇 https://open.substack.com/pub/derekpruski/p/split-dosing-glp-1s-why-smaller-more?utm_campaign=post-expanded-share&utm_medium=web Drop a comment if you've experimented with split dosing in your research—curious what others have observed.
Split Dosing GLP-1s: Why Smaller, More Frequent Doses Work Better
My Favorite Research Peptide for Sleep Support & Restoring Deep Sleep 😴
After trying DSIP with zero results, I found something that actually worked. Not a sleep "drug." Not another melatonin supplement. A peptide that works through an entirely different mechanism—one that's been studied for 35+ years (mostly in Russia) with some pretty wild implications beyond just sleep. The best part? The sleep improvements feel natural. No grogginess. No dependency. Just easier wind-down and better quality rest. What makes it different: It doesn't just knock you out like a sedative. It works by regulating your pineal gland and supporting your body's natural melatonin production. But that's just the beginning of what it does... The deeper mechanism involves something called telomeres (your cellular "aging clock") and an enzyme most of your cells don't produce anymore. I broke down the full science, mechanisms, research, and my lab rat's 15-day protocol in my latest deep dive. Read the full breakdown here: https://open.substack.com/pub/derekpruski/p/understanding-epithalon-the-longevity?r=4jq1x8&utm_campaign=post&utm_medium=web&showWelcomeOnShare=true Including: ✅ How it actually works (explained simply) ✅ Why telomeres matter for sleep AND longevity ✅ The research behind it ✅ Real-world 15-day protocol results ✅ Dosing and cycling protocols Worth a read if you're struggling with sleep or just curious about the intersection of peptides, longevity science, and cellular health. Drop a comment if you've tried this one—curious to hear your experiences. 👇
My Favorite Research Peptide for Sleep Support & Restoring Deep Sleep 😴
🔬 My Retatrutide Research Update: The Muscle Building Phase Game Changer
Alright community, it's time to share my experience with retatrutide in a muscle growth/bulking context. Let me break down the science AND my real-world results. Remember all of this info is for research purposes only, not medical advice, and do not copy. Understanding Retatrutide: The Triple Threat Retatrutide hits THREE different receptors. Here's what each one does: 🎯 GLP-1 Receptor: - Slows how fast your stomach empties - Reduces appetite through brain signaling - Helps your pancreas release insulin when you eat - Lowers glucagon (which normally raises blood sugar) 🎯 GIP Receptor: - Boosts insulin even more than GLP-1 - Improves how your body handles fat and nutrients - Reduces food intake through different pathways - Makes fat cells more insulin sensitive 🎯 Glucagon Receptor (THE KEY DIFFERENCE): - Increases your metabolic rate - Burns stored fat for energy - Reduces fat buildup in your liver - Helps preserve muscle during weight changes Why Reta Feels "Weaker" Than Tirzepatide Here's the thing: retatrutide's GLP-1 activation is intentionally weaker than tirz or sema. Why? Because glucagon normally increases appetite and blood sugar. So you need some GLP-1 to balance it out, but not so much that you kill your appetite completely. This is actually PERFECT for bulking. The gastric emptying is there, but way less pronounced. I've never gotten the same food noise reduction on reta compared to tirz. And that's exactly what you want when you're trying to EAT to grow. The "Eat More, Gain Less Fat" Phenomenon This is where it gets crazy. Here's what's actually happening: 1️⃣ Your Metabolism Runs Hotter Glucagon activation increases your metabolic rate by 5-10%. You're literally burning more calories doing nothing. 2️⃣ Your Body Burns Fat Preferentially Even when you're eating MORE, the glucagon component shifts your body to burn fat for fuel instead of storing it. You're in a surplus, but calories are being oxidized, not stored. 3️⃣ Better Nutrient Partitioning
🔬 My Retatrutide Research Update: The Muscle Building Phase Game Changer
🧠 PINEALON — THE “NEUROPROTECTIVE RESET” PEPTIDE
Daily Deep Dive: Pinealon is a short tri-peptide (Glu-Asp-Arg) that acts primarily on the central nervous system, specifically targeting neurons and mitochondrial health. It was originally developed in Russia for neuroprotection, anti-aging, and cognitive support, and it’s part of the same peptide family as Epitalon and Thymogen — small chains that regulate gene expression rather than directly build tissue. ⚙️ Mechanism of Action Pinealon works on a cellular regulatory level, meaning it doesn’t “stimulate” like caffeine or nootropics. Instead, it helps your cells function more optimally. Here's what’s happening under the hood: - Regulates gene expression in neurons related to oxidative stress resistance and DNA repair. - Enhances mitochondrial ATP production — improving overall neuronal energy efficiency. - Normalizes neurotransmitter balance, particularly GABA and glutamate, which can stabilize mood and focus. - Reduces lipid peroxidation and oxidative damage, offering long-term brain protection rather than short-term “stimulation.” - May influence melatonin and circadian rhythm regulation, due to its origin and activity in the pineal region. 💡 Potential Benefits - Improved mental clarity, focus, and memory retention - Reduced brain fog and fatigue - Better sleep regulation and recovery rhythm - May support mood stabilization and stress resilience - Neuroprotection during aging or high oxidative load (e.g., shift work, chronic stress, stimulant use) 🧪 Dosing (Research Context) Most human data comes from Russian studies and anecdotal research use: - Typical dose: 10mg per day - Frequency: Daily or 5 days on / 2 days off - Duration: 10–20 days per cycle - Route: Subcutaneous injection or oral capsule form (less bioavailability orally) Many use Pinealon as a “reset” peptide, often stacked with Epitalon or Cerebrolysin for synergistic cognitive and neuroprotective effects. 🧩 Common Stacks - Pinealon + Epitalon → longevity + circadian repair - Pinealon + Semax/Selank → cognitive performance + stress balance - Pinealon + Dihexa → neurogenesis + memory consolidation
🧠 PINEALON — THE “NEUROPROTECTIVE RESET” PEPTIDE
⚠️ Quick Reminder: Why Vendors Won't Answer Your Protocol Questions
Seeing a lot of frustrating DMs and comments about vendors not responding to reconstitution or dosing questions. Let me be clear about why: Research peptide companies legally CANNOT answer these questions. When you ask "how do I reconstitute this?" or "what should my research protocol be?" - you're implying human use. These companies operate under "research use only" licenses. The moment they provide guidance on human protocols, they're crossing a legal line that could shut them down entirely. Now I'm even seeing credit card processors won't allow vendors to respond to questions about cloudy peptides or peptides that gel up. This is getting even more restrictive - payment processors are cracking down hard on anything that could remotely imply human use. It's not that vendors are being unhelpful or ignoring you - it's a legal and financial liability they literally cannot take on. This is why this community exists. This is why we share information with each other. You're choosing to conduct your own research, which means YOU are responsible for educating yourself on: - Proper reconstitution techniques - Storage requirements - Research protocols - Safety considerations - What cloudy/gelled peptides mean Don't get upset with vendors for protecting themselves legally. Be smart, do your research, and take responsibility for your own decisions. Check the guides in the classroom section if you need help with the basics. 👊 Remember This Community Is All Anecdotal and Research Based. Not Medical Advice so DO Your OWN Research Please.
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