Community Research Retatrutide dosing-Micorodose vs 1x per week

[s.gentz]

Came across this video. Thought it was interesting. Would live to know other s thoughts on the topic

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Takeaways


Goes straight to your hypothalamus (your brain’s central command center).

It specifically targets something called Pro-opiomelanocortin (POMC). When these neurons get activated, they release Alpha-melanocyte-stimulating hormone (a-MSH), a neuropeptide that binds to Melanocortin 4 (MC4R), a G-protein-coupled receptor in your brain that plays a crucial role in regulating energy balance and appetite.

This is the biochemical equivalent of slamming down the off switch on your appetite.

It suppresses Neuropeptide Y (NPY), which is the most powerful hunger-signaling molecule that your body produces.
full. Reprogramming your brain’s definition of hunger.

It binds to GLP-1 and GIP, you know these receptors on the beta cells, which trigger G-protein coupled receptor cascades that skyrocket intracellular cyclic AMP (cAMP), this amps up glucose-dependent insulin secretion.

These processes only occur when glucose is high; no more wild spikes.

While simultaneously telling the alpha cells to stand down, shutting down all unnecessary glucagon output.

The best part is, this happens in your liver. Reta binds to glucagon receptors on hepatocytes (cells) in your liver. Cyclic AMP (cAMP) activates Protein kinase A (PKA) which phosphorylates (a biochemical process where a phosphate group is added to a molecule, such as a protein or sugar) and activates hormone sensitive lipase HSL (a key intracellular enzyme that breaks down stored lipids, such as triglycerides and cholesterol esters, into free fatty acids and cholesterol, primarily in adipose tissue).

HSL is the enzyme that unlocks your fat cells, hydrolyzing stored triglycerides into free fatty acids, which you’re going to burn, and then it floods your bloodstream with all this fuel ready for oxidation to be used. Turning your body into a fat-burning machine.

1. microdosing myths

This triple agonism creates a self-reinforcing, very powerful feedback loop drastically reducing caloric intake, highly sensitizing insulin response, and maxing out basal energy expenditure.

Reta’s terminal half-life is approximately 144 hours about 6 days.

The Importance of Steady State Concentration

Requires a steady state concentration. (therapeutic equilibrium where the concentration in the bloodstream stays within a consistent range over time, rather than continuously building up or falling off)

The time to reach steady state is determined by half half-life. It takes four to five half-lives to reach 94 to 97%.

** 6 day half life = 24-30 days **

The weekly dosing interval is not arbitrary because the 7-day injection perfectly reinforces the plasma concentration just as it begins to decline from the previous dose. So it maintains that very crucial, very stable therapeutic plateau.

If you microdose, you can never go through the 4 to 5 half-lives to reach the 94 to 97% of steady state concentration, which means you’ll never get to the 24 to 30 day mark, which, for reta is required.

The fallacy of: “tiny doses every day because you get fewer side effects and you get the same benefits.”

For example, 0.1 milligrams daily versus 2.5 milligrams weekly means that the amount administered is likely less than the daily clearance rate, which we already learned is required.

You perpetually operate in what’s called the distribution phase. You’re trying to fill a bathtub with a thimble while the drain is wide open.

You never get to the therapeutic steady state that’s required for efficacy. Rewiring of the hypothalamic set point requires a very strong, sustained signal.

A weekly dose provides days-long signals that carve new fullness pathways into your brain’s neural architecture. A microdose is a weak, fleeting signal.

 

[toddthelineman]

Interesting. My 300lb buddy just started reta this week. His plan is .5mg 3x/wk. he’s on his second shot and he can tell it’s doing its thing at least. Curious how this thread evolves

 

[Mobster]

While we often talk about what is called 'off script use' when referring to many PEDs inc AAS we are still (kinda) using them for the same reasons they were created. By way of example increased nitrogen (protein) uptake, tissue repair and so on. When single source T wasn't what was wanted they created sus etc

With GLP's (all three of the main ones) they literally designed them for (among other things) what we want - fat loss. They also specifically designed them for (as per your reference) LONG half lives and to allow for those with bad 'keeping up the good habits' lifestyles to keep getting the benefits. This is especially true of Reta vs, say, Sema.

Now it's perfectly fine to look at things anew but this is less making a better wheel and more inventing one. It's been done lol

How it MIGHT be better for some users here is, arguably, NOT medically but more about how we use other PEDs (rarely run here solo) and other aspects of our fitness lifestyles.

There is some variation in doses, but as you've reiterated, it's not 1/5th. We often see meds dosing moved about in accordance with bodyweight, age and so on. But how many times have we seen people get a benefit from, say, 10mg vs the normal 200mg of Ibuprofen? Never

It does still suggest more research MIGHT be needed cos we ARE still seeing some positive results

 

[s.gentz]

Interesting. My 300lb buddy just started reta this week. His plan is .5mg 3x/wk. he’s on his second shot and he can tell it’s doing its thing at least. Curious how this thread evolves

While we often talk about what is called 'off script use' when referring to many PEDs inc AAS we are still (kinda) using them for the same reasons they were created. By way of example increased nitrogen (protein) uptake, tissue repair and so on. When single source T wasn't what was wanted they created sus etc

With GLP's (all three of the main ones) they literally designed them for (among other things) what we want - fat loss. They also specifically designed them for (as per your reference) LONG half lives and to allow for those with bad 'keeping up the good habits' lifestyles to keep getting the benefits. This is especially true of Reta vs, say, Sema.

Now it's perfectly fine to look at things anew but this is less making a better wheel and more inventing one. It's been done lol

How it MIGHT be better for some users here is, arguably, NOT medically but more about how we use other PEDs (rarely run here solo) and other aspects of our fitness lifestyles.

There is some variation in doses, but as you've reiterated, it's not 1/5th. We often see meds dosing moved about in accordance with bodyweight, age and so on. But how many times have we seen people get a benefit from, say, 10mg vs the normal 200mg of Ibuprofen? Never

It does still suggest more research MIGHT be needed cos we ARE still seeing some positive results

Personally I think people are micro dosing glp drugs because they are taking too high of a dose and they are trying to mitigate sides by not having the full amount of the drug hi you at once. If people would just be patient and use it as intended I think they could get away with using much less.
I’ve said this numerous times when new members ask. More is not better. The only thing taking more does is mess with digestion and make you feel like shit. These drugs were designed around a one week injection frequency and a specific dosing schedule for a reason.

 

[toddthelineman]

Personally I think people are micro dosing glp drugs because they are taking too high of a dose and they are trying to mitigate sides by not having the full amount of the drug hi you at once. If people would just be patient and use it as intended I think they could get away with using much less.
I’ve said this numerous times when new members ask. More is not better. The only thing taking more does is mess with digestion and make you feel like shit. These drugs were designed around a one week injection frequency and a specific dosing schedule for a reason.

You might be right! I need to reread your post and watch the video. Coincidentally, my friend called me this morning and said he was all twisted up this morning and that was after just his second shot. I know he got his reconstitution and dosing as intended because I helped him do it. He would be at 1mg total so far. He’s already not eating much, but still eating like shit. He’s a cable construction company owner like myself, but five years deeper into it, managing a lot, still working, etc. he thinks he needs to lose 30 pounds but really… like 100. He held fat even when he was a drug addict. His brother is 400 pounds and growing

 

[IronMarcus]

Takeaways


Goes straight to your hypothalamus (your brain’s central command center).

It specifically targets something called Pro-opiomelanocortin (POMC). When these neurons get activated, they release Alpha-melanocyte-stimulating hormone (a-MSH), a neuropeptide that binds to Melanocortin 4 (MC4R), a G-protein-coupled receptor in your brain that plays a crucial role in regulating energy balance and appetite.

This is the biochemical equivalent of slamming down the off switch on your appetite.

It suppresses Neuropeptide Y (NPY), which is the most powerful hunger-signaling molecule that your body produces.
full. Reprogramming your brain’s definition of hunger.

It binds to GLP-1 and GIP, you know these receptors on the beta cells, which trigger G-protein coupled receptor cascades that skyrocket intracellular cyclic AMP (cAMP), this amps up glucose-dependent insulin secretion.

These processes only occur when glucose is high; no more wild spikes.

While simultaneously telling the alpha cells to stand down, shutting down all unnecessary glucagon output.

The best part is, this happens in your liver. Reta binds to glucagon receptors on hepatocytes (cells) in your liver. Cyclic AMP (cAMP) activates Protein kinase A (PKA) which phosphorylates (a biochemical process where a phosphate group is added to a molecule, such as a protein or sugar) and activates hormone sensitive lipase HSL (a key intracellular enzyme that breaks down stored lipids, such as triglycerides and cholesterol esters, into free fatty acids and cholesterol, primarily in adipose tissue).

HSL is the enzyme that unlocks your fat cells, hydrolyzing stored triglycerides into free fatty acids, which you’re going to burn, and then it floods your bloodstream with all this fuel ready for oxidation to be used. Turning your body into a fat-burning machine.

1. microdosing myths

This triple agonism creates a self-reinforcing, very powerful feedback loop drastically reducing caloric intake, highly sensitizing insulin response, and maxing out basal energy expenditure.

Reta’s terminal half-life is approximately 144 hours about 6 days.

The Importance of Steady State Concentration

Requires a steady state concentration. (therapeutic equilibrium where the concentration in the bloodstream stays within a consistent range over time, rather than continuously building up or falling off)

The time to reach steady state is determined by half half-life. It takes four to five half-lives to reach 94 to 97%.

** 6 day half life = 24-30 days **

The weekly dosing interval is not arbitrary because the 7-day injection perfectly reinforces the plasma concentration just as it begins to decline from the previous dose. So it maintains that very crucial, very stable therapeutic plateau.

If you microdose, you can never go through the 4 to 5 half-lives to reach the 94 to 97% of steady state concentration, which means you’ll never get to the 24 to 30 day mark, which, for reta is required.

The fallacy of: “tiny doses every day because you get fewer side effects and you get the same benefits.”

For example, 0.1 milligrams daily versus 2.5 milligrams weekly means that the amount administered is likely less than the daily clearance rate, which we already learned is required.

You perpetually operate in what’s called the distribution phase. You’re trying to fill a bathtub with a thimble while the drain is wide open.

You never get to the therapeutic steady state that’s required for efficacy. Rewiring of the hypothalamic set point requires a very strong, sustained signal.

A weekly dose provides days-long signals that carve new fullness pathways into your brain’s neural architecture. A microdose is a weak, fleeting signal.

Wow, fascinating breakdown of Retatrutide! The point about steady-state concentration is key – microdosing likely won't achieve the sustained signaling needed to truly reprogram appetite & maximize fat-burning. The "bathtub with a thimble" analogy is perfect. Thanks for sharing!

 

[s.gentz]

You might be right! I need to reread your post and watch the video. Coincidentally, my friend called me this morning and said he was all twisted up this morning and that was after just his second shot. I know he got his reconstitution and dosing as intended because I helped him do it. He would be at 1mg total so far. He’s already not eating much, but still eating like shit. He’s a cable construction company owner like myself, but five years deeper into it, managing a lot, still working, etc. he thinks he needs to lose 30 pounds but really… like 100. He held fat even when he was a drug addict. His brother is 400 pounds and growing

People think these drugs are magic. They are just a tool to assist. You need to fix diet. Glp drugs react poorly with bad, fatty western diet.

 

[toddthelineman]

Well he keeps saying “it can’t work” but we see logs where it clearly does “work”. No matter how sternly he says it, I just a not smart enough to understand how, if you are getting it in there, it’s “never going to work”. I can imaaaaaaaagine that it could do more of what it’s intended to do if the doses are spread out. I can abstractly believe how that could be a thing. But to claim it can’t work when we see that it does… makes this a hard listen

 

[toddthelineman]

People think these drugs are magic. They are just a tool to assist. You need to fix diet. Glp drugs react poorly with bad, fatty western diet.

For sure! I’m working on it with him. Not that my diet is ideal especially for someone on reta. But it could be tweaked to work. He’s like my best friend and has pulled me out of the fire more than once. Excellent guy with just zero background on any of this

 

[toddthelineman]

Well he keeps saying “it can’t work” but we see logs where it clearly does “work”. No matter how sternly he says it, I just a not smart enough to understand how, if you are getting it in there, it’s “never going to work”. I can imaaaaaaaagine that it could do more of what it’s intended to do if the doses are spread out. I can abstractly believe how that could be a thing. But to claim it can’t work when we see that it does… makes this a hard listen

Ok ok. He’s saying that without giving the hypothalamus a full week to adapt, you’re not taking advantage of that feature, suggesting that one would not need to continue to take reta to avoid rebound weight gain. Well we will see. I always see examples of people trusting studies over experiments. Not being an academic, I’m more the opposite. For better or worse.

 

[NaturalChrisA]

Came across this video. Thought it was interesting. Would live to know other s thoughts on the topic

To view this content we will need your consent to set third party cookies.
For more detailed information, see our cookies page.

Accept third party cookies

Takeaways


Goes straight to your hypothalamus (your brain’s central command center).

It specifically targets something called Pro-opiomelanocortin (POMC). When these neurons get activated, they release Alpha-melanocyte-stimulating hormone (a-MSH), a neuropeptide that binds to Melanocortin 4 (MC4R), a G-protein-coupled receptor in your brain that plays a crucial role in regulating energy balance and appetite.

This is the biochemical equivalent of slamming down the off switch on your appetite.

It suppresses Neuropeptide Y (NPY), which is the most powerful hunger-signaling molecule that your body produces.
full. Reprogramming your brain’s definition of hunger.

It binds to GLP-1 and GIP, you know these receptors on the beta cells, which trigger G-protein coupled receptor cascades that skyrocket intracellular cyclic AMP (cAMP), this amps up glucose-dependent insulin secretion.

These processes only occur when glucose is high; no more wild spikes.

While simultaneously telling the alpha cells to stand down, shutting down all unnecessary glucagon output.

The best part is, this happens in your liver. Reta binds to glucagon receptors on hepatocytes (cells) in your liver. Cyclic AMP (cAMP) activates Protein kinase A (PKA) which phosphorylates (a biochemical process where a phosphate group is added to a molecule, such as a protein or sugar) and activates hormone sensitive lipase HSL (a key intracellular enzyme that breaks down stored lipids, such as triglycerides and cholesterol esters, into free fatty acids and cholesterol, primarily in adipose tissue).

HSL is the enzyme that unlocks your fat cells, hydrolyzing stored triglycerides into free fatty acids, which you’re going to burn, and then it floods your bloodstream with all this fuel ready for oxidation to be used. Turning your body into a fat-burning machine.

1. microdosing myths

This triple agonism creates a self-reinforcing, very powerful feedback loop drastically reducing caloric intake, highly sensitizing insulin response, and maxing out basal energy expenditure.

Reta’s terminal half-life is approximately 144 hours about 6 days.

The Importance of Steady State Concentration

Requires a steady state concentration. (therapeutic equilibrium where the concentration in the bloodstream stays within a consistent range over time, rather than continuously building up or falling off)

The time to reach steady state is determined by half half-life. It takes four to five half-lives to reach 94 to 97%.

** 6 day half life = 24-30 days **

The weekly dosing interval is not arbitrary because the 7-day injection perfectly reinforces the plasma concentration just as it begins to decline from the previous dose. So it maintains that very crucial, very stable therapeutic plateau.

If you microdose, you can never go through the 4 to 5 half-lives to reach the 94 to 97% of steady state concentration, which means you’ll never get to the 24 to 30 day mark, which, for reta is required.

The fallacy of: “tiny doses every day because you get fewer side effects and you get the same benefits.”

For example, 0.1 milligrams daily versus 2.5 milligrams weekly means that the amount administered is likely less than the daily clearance rate, which we already learned is required.

You perpetually operate in what’s called the distribution phase. You’re trying to fill a bathtub with a thimble while the drain is wide open.

You never get to the therapeutic steady state that’s required for efficacy. Rewiring of the hypothalamic set point requires a very strong, sustained signal.

A weekly dose provides days-long signals that carve new fullness pathways into your brain’s neural architecture. A microdose is a weak, fleeting signal.

Reta targets the brain's command center, impacting hunger and energy balance. It suppresses hunger signals, boosts insulin secretion when glucose is high, and shuts down unnecessary glucagon. Weekly dosing is key to maintain a steady state concentration for optimal results. Microdosing is ineffective.

 

[s.gentz]

Reta targets the brain's command center, impacting hunger and energy balance. It suppresses hunger signals, boosts insulin secretion when glucose is high, and shuts down unnecessary glucagon. Weekly dosing is key to maintain a steady state concentration for optimal results. Microdosing is ineffective.

 

[StrongZoeM]

Came across this video. Thought it was interesting. Would live to know other s thoughts on the topic

To view this content we will need your consent to set third party cookies.
For more detailed information, see our cookies page.

Accept third party cookies

Takeaways


Goes straight to your hypothalamus (your brain’s central command center).

It specifically targets something called Pro-opiomelanocortin (POMC). When these neurons get activated, they release Alpha-melanocyte-stimulating hormone (a-MSH), a neuropeptide that binds to Melanocortin 4 (MC4R), a G-protein-coupled receptor in your brain that plays a crucial role in regulating energy balance and appetite.

This is the biochemical equivalent of slamming down the off switch on your appetite.

It suppresses Neuropeptide Y (NPY), which is the most powerful hunger-signaling molecule that your body produces.
full. Reprogramming your brain’s definition of hunger.

It binds to GLP-1 and GIP, you know these receptors on the beta cells, which trigger G-protein coupled receptor cascades that skyrocket intracellular cyclic AMP (cAMP), this amps up glucose-dependent insulin secretion.

These processes only occur when glucose is high; no more wild spikes.

While simultaneously telling the alpha cells to stand down, shutting down all unnecessary glucagon output.

The best part is, this happens in your liver. Reta binds to glucagon receptors on hepatocytes (cells) in your liver. Cyclic AMP (cAMP) activates Protein kinase A (PKA) which phosphorylates (a biochemical process where a phosphate group is added to a molecule, such as a protein or sugar) and activates hormone sensitive lipase HSL (a key intracellular enzyme that breaks down stored lipids, such as triglycerides and cholesterol esters, into free fatty acids and cholesterol, primarily in adipose tissue).

HSL is the enzyme that unlocks your fat cells, hydrolyzing stored triglycerides into free fatty acids, which you’re going to burn, and then it floods your bloodstream with all this fuel ready for oxidation to be used. Turning your body into a fat-burning machine.

1. microdosing myths

This triple agonism creates a self-reinforcing, very powerful feedback loop drastically reducing caloric intake, highly sensitizing insulin response, and maxing out basal energy expenditure.

Reta’s terminal half-life is approximately 144 hours about 6 days.

The Importance of Steady State Concentration

Requires a steady state concentration. (therapeutic equilibrium where the concentration in the bloodstream stays within a consistent range over time, rather than continuously building up or falling off)

The time to reach steady state is determined by half half-life. It takes four to five half-lives to reach 94 to 97%.

** 6 day half life = 24-30 days **

The weekly dosing interval is not arbitrary because the 7-day injection perfectly reinforces the plasma concentration just as it begins to decline from the previous dose. So it maintains that very crucial, very stable therapeutic plateau.

If you microdose, you can never go through the 4 to 5 half-lives to reach the 94 to 97% of steady state concentration, which means you’ll never get to the 24 to 30 day mark, which, for reta is required.

The fallacy of: “tiny doses every day because you get fewer side effects and you get the same benefits.”

For example, 0.1 milligrams daily versus 2.5 milligrams weekly means that the amount administered is likely less than the daily clearance rate, which we already learned is required.

You perpetually operate in what’s called the distribution phase. You’re trying to fill a bathtub with a thimble while the drain is wide open.

You never get to the therapeutic steady state that’s required for efficacy. Rewiring of the hypothalamic set point requires a very strong, sustained signal.

A weekly dose provides days-long signals that carve new fullness pathways into your brain’s neural architecture. A microdose is a weak, fleeting signal.

Interesting video on Reta! The takeaway on steady-state concentration is key. Microdosing might seem appealing for side effects, but it sounds like you'd miss the therapeutic benefits. The analogy of filling a bathtub with a thimble is spot on! Gotta hit that 24-30 day mark.

 

[madcap71]

Micro-dosing for health benefits and mitigating sides is fine. Bigger bolus doses are better for appetite suppression and fat loss IME. 2x a week is the sweet spot for me

 

[s.gentz]

Micro-dosing for health benefits and mitigating sides is fine. Bigger bolus doses are better for appetite suppression and fat loss IME. 2x a week is the sweet spot for me

100% agree but if people are microdosing just to mitigate sides then chances are they are taking too much to begin with.
I think a lot of bad info is being given out on what a good starting dose is for GLP drugs. Tirzepatide and Semaglutide whether UGL or prescribed have dosing schedules that the drug companies have put out because that is how the drugs are supposed to be used. Unfortunately retatrutide is currently all UGL so there is not set dosing schedule but it's pretty well known that 1mg/wk to start is the correct dose. I see guys taking 3-4 mg/wk and need to microdose because of the sides. If they started on the recommended path they could take one or two shots a week and prob see the same or better response at a lower dose.

 

[s.gentz]

Micro-dosing for health benefits and mitigating sides is fine. Bigger bolus doses are better for appetite suppression and fat loss IME. 2x a week is the sweet spot for me

Honestly we should really have a sticky for the proper way to use each of these glp drugs. Lotta bad info being given out.

 

[madcap71]

100% agree but if people are microdosing just to mitigate sides then chances are they are taking too much to begin with.
I think a lot of bad info is being given out on what a good starting dose is for GLP drugs. Tirzepatide and Semaglutide whether UGL or prescribed have dosing schedules that the drug companies have put out because that is how the drugs are supposed to be used. Unfortunately retatrutide is currently all UGL so there is not set dosing schedule but it's pretty well known that 1mg/wk to start is the correct dose. I see guys taking 3-4 mg/wk and need to microdose because of the sides. If they started on the recommended path they could take one or two shots a week and prob see the same or better response at a lower dose.

Yep, I agree a lot of bad advice is being given on these. Problem is there's too many different sources of information and not a lot of verification around it. People here that the trials went up to 12mg and think it's a race to get there.

 

[s.gentz]

Yep, I agree a lot of bad advice is being given on these. Problem is there's too many different sources of information and not a lot of verification around it. People here that the trials went up to 12mg and think it's a race to get there.

Agree. That's why we need to be giving out the correct info. I've seen a lot of bad advice on here and affiliated sites about these drugs.

 

[madcap71]

Yep, I agree a lot of bad advice is being given on these. Problem is there's too many different sources of information and not a lot of verification around it. People here that the trials went up to 12mg and think it's a race to get there.

*people HEAR...

prep brain!

 

[LevButlerov]

Came across this video. Thought it was interesting. Would live to know other s thoughts on the topic

To view this content we will need your consent to set third party cookies.
For more detailed information, see our cookies page.

Accept third party cookies

Takeaways


Goes straight to your hypothalamus (your brain’s central command center).

It specifically targets something called Pro-opiomelanocortin (POMC). When these neurons get activated, they release Alpha-melanocyte-stimulating hormone (a-MSH), a neuropeptide that binds to Melanocortin 4 (MC4R), a G-protein-coupled receptor in your brain that plays a crucial role in regulating energy balance and appetite.

This is the biochemical equivalent of slamming down the off switch on your appetite.

It suppresses Neuropeptide Y (NPY), which is the most powerful hunger-signaling molecule that your body produces.
full. Reprogramming your brain’s definition of hunger.

It binds to GLP-1 and GIP, you know these receptors on the beta cells, which trigger G-protein coupled receptor cascades that skyrocket intracellular cyclic AMP (cAMP), this amps up glucose-dependent insulin secretion.

These processes only occur when glucose is high; no more wild spikes.

While simultaneously telling the alpha cells to stand down, shutting down all unnecessary glucagon output.

The best part is, this happens in your liver. Reta binds to glucagon receptors on hepatocytes (cells) in your liver. Cyclic AMP (cAMP) activates Protein kinase A (PKA) which phosphorylates (a biochemical process where a phosphate group is added to a molecule, such as a protein or sugar) and activates hormone sensitive lipase HSL (a key intracellular enzyme that breaks down stored lipids, such as triglycerides and cholesterol esters, into free fatty acids and cholesterol, primarily in adipose tissue).

HSL is the enzyme that unlocks your fat cells, hydrolyzing stored triglycerides into free fatty acids, which you’re going to burn, and then it floods your bloodstream with all this fuel ready for oxidation to be used. Turning your body into a fat-burning machine.

1. microdosing myths

This triple agonism creates a self-reinforcing, very powerful feedback loop drastically reducing caloric intake, highly sensitizing insulin response, and maxing out basal energy expenditure.

Reta’s terminal half-life is approximately 144 hours about 6 days.

The Importance of Steady State Concentration

Requires a steady state concentration. (therapeutic equilibrium where the concentration in the bloodstream stays within a consistent range over time, rather than continuously building up or falling off)

The time to reach steady state is determined by half half-life. It takes four to five half-lives to reach 94 to 97%.

** 6 day half life = 24-30 days **

The weekly dosing interval is not arbitrary because the 7-day injection perfectly reinforces the plasma concentration just as it begins to decline from the previous dose. So it maintains that very crucial, very stable therapeutic plateau.

If you microdose, you can never go through the 4 to 5 half-lives to reach the 94 to 97% of steady state concentration, which means you’ll never get to the 24 to 30 day mark, which, for reta is required.

The fallacy of: “tiny doses every day because you get fewer side effects and you get the same benefits.”

For example, 0.1 milligrams daily versus 2.5 milligrams weekly means that the amount administered is likely less than the daily clearance rate, which we already learned is required.

You perpetually operate in what’s called the distribution phase. You’re trying to fill a bathtub with a thimble while the drain is wide open.

You never get to the therapeutic steady state that’s required for efficacy. Rewiring of the hypothalamic set point requires a very strong, sustained signal.

A weekly dose provides days-long signals that carve new fullness pathways into your brain’s neural architecture. A microdose is a weak, fleeting signal.

I did watch the video, unfortunately lol but had to skip a bunch of parts to the things I wanted to hear. @s.gentz Of course I can make the same argument for testosterone, go pin 1 huge dose of 500mgs instead of splitting, you will saturate faster, that's partially true but there is a lot of fine tuning based on real life feedback that we need to do.
my view is that his “no microdosing” argument misses how pharmacokinetics and receptor signaling actually behave in practice. With a 6 day half-life, retatrutide maintains stable plasma levels even with smaller, more frequent injections, as long as total weekly dose remains consistent. Microdosing avoids the massive Cmax spike of full weekly dosing, reducing nausea, reflux, and fatigue while still reaching steady-state by day 24–30 just as a single dose would. The difference is smoother peaks, not loss of effect.
Anyone actually using a GLP1 will tell him that high doses 1x/week give a ton of sides, no matter if it's reta or semaglutide or tirzepatide etc.

A weekly 1x dose does produce higher short-term receptor saturation, but the GLP-1, GIP, and glucagon receptors do not require a constant supramaximal signal for hypothalamic remodeling. They respond to cumulative exposure over time. Microdosing distributes that exposure evenly, keeping plasma within the effective range and allowing receptor sensitivity to normalize without overstimulation and lower side effects.

Real world data from semaglutide, tirzepatide, and retatrutide logs and overall users I've talked to, shows that smaller, divided doses improve tolerance and adherence while maintaining efficacy once steady state is reached. For most guys, splitting the weekly total into 2–3 injections per week gives the same metabolic effect with fewer GI and appetite issues, which is far more sustainable long term.

@BeMe @HarleyGuy @vanlife_gymbum @toddthelineman @stevesmi @Pigsy @Mobster

 

[Pigsy]

It'll work with once a week, x 3 times a week daily. I dose everything i take daily. Just my preference

 

[vanlife_gymbum]

With a 6 day half-life, retatrutide maintains stable plasma levels even with smaller, more frequent injections, as long as total weekly dose remains consistent. Microdosing avoids the massive Cmax spike of full weekly dosing, reducing nausea, reflux, and fatigue while still reaching steady-state by day 24–30 just as a single dose would. The difference is smoother peaks, not loss of effect.

You are 100% correct @LevButlerov - anyone can easily prove this to themselves using a needle within a week.

The EOD dosing schedule you gave me fixed all my problems and side effects and I am grateful. I would have had to stop if I'd stayed with the one shot, the sides were intense and then it wore off before the next one, I don't want to have bigger shots to make up for that, you'll push your tolerance up way quicker doing that anyway. It's retarded.

Anyone actually using a GLP1 will tell him that high doses 1x/week give a ton of sides, no matter if it's reta or semaglutide or tirzepatide etc.

Fuckin' aye man - doesn't mean they'll be able to read it or listen tho

Heaps of drugs work like this, it's not a special case. I tried that with herion once, not recommended.

You really know your shit @LevButlerov - I'm glad I didn't keep that problem to myself for too long.

The source and mainstream sources of information all insisted on the one big shot.

 

[Allupfromhere]

@JimmyO187 we were just discussing this topic the other day werent we? Great timing for this thread @s.gentz

 

[HarleyGuy]

I did watch the video, unfortunately lol but had to skip a bunch of parts to the things I wanted to hear. @s.gentz Of course I can make the same argument for testosterone, go pin 1 huge dose of 500mgs instead of splitting, you will saturate faster, that's partially true but there is a lot of fine tuning based on real life feedback that we need to do.
my view is that his “no microdosing” argument misses how pharmacokinetics and receptor signaling actually behave in practice. With a 6 day half-life, retatrutide maintains stable plasma levels even with smaller, more frequent injections, as long as total weekly dose remains consistent. Microdosing avoids the massive Cmax spike of full weekly dosing, reducing nausea, reflux, and fatigue while still reaching steady-state by day 24–30 just as a single dose would. The difference is smoother peaks, not loss of effect.
Anyone actually using a GLP1 will tell him that high doses 1x/week give a ton of sides, no matter if it's reta or semaglutide or tirzepatide etc.

A weekly 1x dose does produce higher short-term receptor saturation, but the GLP-1, GIP, and glucagon receptors do not require a constant supramaximal signal for hypothalamic remodeling. They respond to cumulative exposure over time. Microdosing distributes that exposure evenly, keeping plasma within the effective range and allowing receptor sensitivity to normalize without overstimulation and lower side effects.

Real world data from semaglutide, tirzepatide, and retatrutide logs and overall users I've talked to, shows that smaller, divided doses improve tolerance and adherence while maintaining efficacy once steady state is reached. For most guys, splitting the weekly total into 2–3 injections per week gives the same metabolic effect with fewer GI and appetite issues, which is far more sustainable long term.

@BeMe @HarleyGuy @vanlife_gymbum @toddthelineman @stevesmi @Pigsy @Mobster

Agreed. Lev took the ball on the science of it so I'll go layman. It's all about getting to that steady state and how you want to get there. To dumb down his argument microdosing may cause you to lose some signaling that a bolus dose would provide but you don't lose the ability to reach a steady state it just might take longer as your doses are less "loud" when microdosing but over time both methods will get you there. The body doesn't just 'forget' to remodel because your doses aren't so loud day after day vs. one big scream once per week, it just might not get the hint as fast. You can ask a kid to make his lunch for tomorrow 100 times until he does or you can slam your fist down one time and say make your fucking lunch... either way he ends up at school the next day with his made lunch and that state of 'having lunch that day' gets reached. Hope that was layman'y enough to sort of wrap your mind around the fact he doesn't get to say "never" to microdosing.

Oddly enough I watched this today too it must be being pushed on the YT algorithm. I disagreed with him. I try and stay away from coaches who say "always" or "never" in these contexts.

Plus, if that moron would research anectodal reports of people who lost 80lbs using 2-4mgs microdosing he'd realize his use of the word "NEVER" all in caps and white and a different colour than the rest of the title just makes it clickbait.

 

[vanlife_gymbum]

It'll work with once a week, x 3 times a week daily. I dose everything i take daily. Just my preference

Hmmm that's an interesting point, I have been wondering why this keeps coming up again and again - do you think there's a possibility one of the real motives is to avoid more pins?

 

[vanlife_gymbum]

either way he ends up at school the next day with his made lunch and that state of 'having lunch that day' gets reached

Hahaha oh man that's gold

Oddly enough I watched this today too it must be being pushed on the YT algorithm. I disagreed with him. I try and stay away from coaches who say "always" or "never" in these contexts.

And give unsolicited medical advice they pulled out of their fucking ass.

 

[Pigsy]

Hmmm that's an interesting point, I have been wondering why this keeps coming up again and again - do you think there's a possibility one of the real motives is to avoid more pins?

Most of the time, one big dose is based on people's adhedense to stick to a dosing protocol. And less pinning, and sticking it out for the duration

 

[toddthelineman]

In the end it’s all just content. I’ve never seen that fella before, but he’s not the only Dr I’ve seen, online or in person, who speaks so confidently and condescendingly. People eat it up. Dr Todd Lee loves to talk like that. Keep listening and he’ll become much more reasonable.

 

[LevButlerov]

You are 100% correct @LevButlerov - anyone can easily prove this to themselves using a needle within a week.

The EOD dosing schedule you gave me fixed all my problems and side effects and I am grateful. I would have had to stop if I'd stayed with the one shot, the sides were intense and then it wore off before the next one, I don't want to have bigger shots to make up for that, you'll push your tolerance up way quicker doing that anyway. It's retarded.



Fuckin' aye man - doesn't mean they'll be able to read it or listen tho

Heaps of drugs work like this, it's not a special case. I tried that with herion once, not recommended.

You really know your shit @LevButlerov - I'm glad I didn't keep that problem to myself for too long.

The source and mainstream sources of information all insisted on the one big shot.

Good to hear you handled the sides properly. That switch to EOD retatrutide dosing keeps levels steady and proves the concept in real time, you did it right. @vanlife_gymbum

 

[vanlife_gymbum]

Good to hear you handled the sides properly. That switch to EOD retatrutide dosing keeps levels steady and proves the concept in real time, you did it right. @vanlife_gymbum

This is how methadone works too and it's important as it gets you exemptions from driving bans and stuff. Methadone in the recovery sense via a program aims to get you to 'therapeutic levels' I think it's called, I had to get peak and trough tests to prove it to the doctor else they adjust your dose down but if you dosed once a week you might die, three times a week you'd be high as fuck and nodding off and withdrawing some days, all bad for driving in a straight line.

But every 24 hours and the levels say stable. That's why people say methadone doesn't get tou high... it absolutely does if you dose it like that, double dose, etc, but when you reach therapeutic levels you're never high and never withdrawing and then they let you drive. Also if you miss more than three days they cut your dose in half.

 

[LevButlerov]

Agreed. Lev took the ball on the science of it so I'll go layman. It's all about getting to that steady state and how you want to get there. To dumb down his argument microdosing may cause you to lose some signaling that a bolus dose would provide but you don't lose the ability to reach a steady state it just might take longer as your doses are less "loud" when microdosing but over time both methods will get you there. The body doesn't just 'forget' to remodel because your doses aren't so loud day after day vs. one big scream once per week, it just might not get the hint as fast. You can ask a kid to make his lunch for tomorrow 100 times until he does or you can slam your fist down one time and say make your fucking lunch... either way he ends up at school the next day with his made lunch and that state of 'having lunch that day' gets reached. Hope that was layman'y enough to sort of wrap your mind around the fact he doesn't get to say "never" to microdosing.

Oddly enough I watched this today too it must be being pushed on the YT algorithm. I disagreed with him. I try and stay away from coaches who say "always" or "never" in these contexts.

Plus, if that moron would research anectodal reports of people who lost 80lbs using 2-4mgs microdosing he'd realize his use of the word "NEVER" all in caps and white and a different colour than the rest of the title just makes it clickbait.

Well said @HarleyGuy

 

[G-Merc 80]

I wasnt so much having side as it not blunting my hunger the way I was used to with Tirz, I moved to EOD based on your recommendation @LevButlerov which resolved the issue for me pretty quickly, I was on Tirz and doing weekly and found 1 to 2 days out I would want to go into pacman mode, but EOD with Reta I just dont have that at all; Micro dosing works for me but I find the read very interesting.

 

[Mobster]

One issue ignored by the 'it does work' side is that we're NOT talking about the obese or type II. We're discussing individuals already controlling what they eat, their activity levels and who hit the gym.

You only get a true picture by controlling the variables

 

[madcap71]

Paul Barnett has now said the same and due to his delivery alone, I'm more inclined to listen to him than the Thomas guy

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[LevButlerov]

Paul Barnett has now said the same and due to his delivery alone, I'm more inclined to listen to him than the Thomas guy

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Would be nice to get the screen shot of it or downloaded video, instagram is banned here wont work @madcap71 and I don't have social media lol it's poison.

 

[G-Merc 80]

Would be nice to get the screen shot of it or downloaded video, instagram is banned here wont work @madcap71 and I don't have social media lol it's poison.

Screenshots

 

[s.gentz]

Real world data from semaglutide, tirzepatide, and retatrutide logs and overall users I've talked to, shows that smaller, divided doses improve tolerance and adherence while maintaining efficacy once steady state is reached. For most guys, splitting the weekly total into 2–3 injections per week gives the same metabolic effect with fewer GI and appetite issues, which is far more sustainable long term.

I Agree with a lot of what you are saying but I also think people are taking way too much from the start and covering up the ill effects by microdosing which tells me they are never really getting to the levels of the amount of the drug they are taking or they would still be feeling the ill effects.
I've never seen a study that deal with microdosing these drugs but what is talked about in the video make a lot of sense. These drugs are all designed around a once weekly injection.
We are all experimenting with these drugs. Everyone's mileage will vary.

 

[s.gentz]

Anyone actually using a GLP1 will tell him that high doses 1x/week give a ton of sides, no matter if it's reta or semaglutide or tirzepatide etc.

Here is where the issue is. You should not be taking high doses until your body has acclimated to the lower doses. That is why pharm has designed these drugs with a titration schedule. I think a lot of people are missing that. They think more is better. It's just simply not the case.

 

[LevButlerov]

I Agree with a lot of what you are saying but I also think people are taking way too much from the start and covering up the ill effects by microdosing which tells me they are never really getting to the levels of the amount of the drug they are taking or they would still be feeling the ill effects.
I've never seen a study that deal with microdosing these drugs but what is talked about in the video make a lot of sense. These drugs are all designed around a once weekly injection.
We are all experimenting with these drugs. Everyone's mileage will vary.

You make good points here.
My view is that real user feedback, including logs and studies both point to the same thing. Retatrutide keeps stable levels once the half-life stacks, so splitting the dose 2–3 times weekly gives smoother receptor activity with less nausea and fatigue while keeping the same end result. That's kind of a drop the mic moment, no matter the dose the long half life is going to catch up, you follow? @s.gentz

The 1x weekly shot is for convenience, not better results. It's made for the obese and diabetics.
Smaller injections lower the peak load on GLP and GIP receptors, so the body adjusts easier, and once you reach steady state around week 4, the outcome is identical but far easier to tolerate.

Here is where the issue is. You should not be taking high doses until your body has acclimated to the lower doses. That is why pharm has designed these drugs with a titration schedule. I think a lot of people are missing that. They think more is better. It's just simply not the case.

You’re absolutely right that pyramiding up is critical before increasing dose. The clinical design from pharma companies starts with smaller amounts so the body can adapt to slowed gastric emptying and receptor binding, which prevents the harsh side effects that come with early high dosing. Or at least that's in theory, in practice I've seen almost any dose give sides.

The point of microdosing isn’t to skip the pyramid up, but to make the titration phase more tolerable. Dividing the same weekly amount lets guys reach the same effective dose with fewer GI issues, steadier blood sugar, and better adherence, especially during the first 2-6 weeks when side effects hit hardest.

I think this is a legit discussion, we should have more of these. EVO family respect your way @s.gentz for brining this forward.

 

[HarleyGuy]

Screenshots

Nice find. Gives us lots to talk about but microdosing still does work. I don't care about side effects so I'd pin once a week and let it ride until saturation but others need the slow steady state buildup.

 

[s.gentz]

You make good points here.
My view is that real user feedback, including logs and studies both point to the same thing. Retatrutide keeps stable levels once the half-life stacks, so splitting the dose 2–3 times weekly gives smoother receptor activity with less nausea and fatigue while keeping the same end result. That's kind of a drop the mic moment, no matter the dose the long half life is going to catch up, you follow? @s.gentz

The 1x weekly shot is for convenience, not better results. It's made for the obese and diabetics.
Smaller injections lower the peak load on GLP and GIP receptors, so the body adjusts easier, and once you reach steady state around week 4, the outcome is identical but far easier to tolerate.


You’re absolutely right that pyramiding up is critical before increasing dose. The clinical design from pharma companies starts with smaller amounts so the body can adapt to slowed gastric emptying and receptor binding, which prevents the harsh side effects that come with early high dosing. Or at least that's in theory, in practice I've seen almost any dose give sides.

The point of microdosing isn’t to skip the pyramid up, but to make the titration phase more tolerable. Dividing the same weekly amount lets guys reach the same effective dose with fewer GI issues, steadier blood sugar, and better adherence, especially during the first 2-6 weeks when side effects hit hardest.

I think this is a legit discussion, we should have more of these. EVO family respect your way @s.gentz for brining this forward.

I think there is an argument for using these drugs both ways but I have never seen any proof that one way is better/worse than the other. What the YT fellow says makes sense What i have seen is users taking too much and then thinking they are fixing the issue by microdosing. We have never seen studied that show how the body reacts one shot vs microdose. We only have anecdotal data from people that have used the drugs. I have used all 3 GLP drugs and always at 1 shot per week. The only time i have ever had GI issues is when i took too much or accelerated the dose too quickly. Of course we are all different and this is just my experience.
Forum members have stated they had issues with a single shot and went to micro to fix it. I would be interested to see what their initial dose was.

 

[Allupfromhere]

Nice find. Gives us lots to talk about but microdosing still does work. I don't care about side effects so I'd pin once a week and let it ride until saturation but others need the slow steady state buildup.

I microdosed when i first started on reta earlier this year, then to x3 weekly, then x2 and now one single injection and i definetely feel a difference in hunger reduction off one single dose now compared to multiple injections at the same dose. This is just me though..

 

[s.gentz]

but microdosing still does work.

It does work there is no doubt but we have no idea if it's better/worse than taking one shot for efficacy. Are people taking too much too soon and masking sides by micro? More is not better with these drugs.

 

[Allupfromhere]

It does work there is no doubt but we have no idea if it's better/worse than taking one shot for efficacy. Are people taking too much too soon and masking sides by micro? More is not better with these drugs.

This comment is fair!

 

[stevesmi]

retatrutide was designed to be pinned once a week. all the studies and trials they did that from Ely Lilly. the idea was that why should a diabetic or someone trying to lose weight have to inject something every single day or several times a day?
It has a long ester for a reason.

sustanon was also designed the same way but people still argue to pin it 3x a week or daily lol. it reduces sides they say.

whether you pin sust or reta daily or weekly. its still going to take weeks to reach peak concentrations in your body. so why waste injections?

 

[JimmyO187]

@JimmyO187 we were just discussing this topic the other day werent we? Great timing for this thread @s.gentz

We were bro…and the results are still split for once a week vs eod

I’ll still stand by the once a week over eod

 

[s.gentz]

whether you pin sust or reta daily or weekly. its still going to take weeks to reach peak concentrations in your body. so why waste injections

But the question here about GLP drugs is if you microdose do you actually reach full saturation at the level intended or are you reaching a steady state of a lower dose?
1mg week=X
does 1mg split =X or does it =Y?

 

[stevesmi]

But the question here about GLP drugs is if you microdose do you actually reach full saturation at the level intended or are you reaching a steady state of a lower dose?
1mg week=X
does 1mg split =X or does it =Y?

we don't know that for sure, i would say if someone were to try it both ways be their own guinea pig and see how it works for them.

for me i go once a week and that is what i recommend for my clients
i mean that is just the way the drugmaker intended it to be ran so i'm gonna trust that

 

[JimmyO187]

we don't know that for sure, i would say if someone were to try it both ways be their own guinea pig and see how it works for them.

for me i go once a week and that is what i recommend for my clients
i mean that is just the way the drugmaker intended it to be ran so i'm gonna trust that

I have more appetite suppression with 1 x weekly dose compared to M W F injections

 

[s.gentz]

I have more appetite suppression with 1 x weekly dose compared to M W F injections

I did to. With tirzep the suppression would taper a bit a day or so before my shot but not really a big deal. Was not in a steep deficit so didn't really bother me.

 

[madcap71]

Would be nice to get the screen shot of it or downloaded video, instagram is banned here wont work @madcap71 and I don't have social media lol it's poison.

Sorry I wasn't aware of that, for next time!

 

[Mobster]

Here is where the issue is. You should not be taking high doses until your body has acclimated to the lower doses. That is why pharm has designed these drugs with a titration schedule. I think a lot of people are missing that. They think more is better. It's just simply not the case.

@LevButlerov we'ver literally covered this multiple times. Even in the studies going on a dose, changing the dose etc would get issues such as nausea.

 

[ceo]

Came across this video. Thought it was interesting. Would live to know other s thoughts on the topic

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Takeaways


Goes straight to your hypothalamus (your brain’s central command center).

It specifically targets something called Pro-opiomelanocortin (POMC). When these neurons get activated, they release Alpha-melanocyte-stimulating hormone (a-MSH), a neuropeptide that binds to Melanocortin 4 (MC4R), a G-protein-coupled receptor in your brain that plays a crucial role in regulating energy balance and appetite.

This is the biochemical equivalent of slamming down the off switch on your appetite.

It suppresses Neuropeptide Y (NPY), which is the most powerful hunger-signaling molecule that your body produces.
full. Reprogramming your brain’s definition of hunger.

It binds to GLP-1 and GIP, you know these receptors on the beta cells, which trigger G-protein coupled receptor cascades that skyrocket intracellular cyclic AMP (cAMP), this amps up glucose-dependent insulin secretion.

These processes only occur when glucose is high; no more wild spikes.

While simultaneously telling the alpha cells to stand down, shutting down all unnecessary glucagon output.

The best part is, this happens in your liver. Reta binds to glucagon receptors on hepatocytes (cells) in your liver. Cyclic AMP (cAMP) activates Protein kinase A (PKA) which phosphorylates (a biochemical process where a phosphate group is added to a molecule, such as a protein or sugar) and activates hormone sensitive lipase HSL (a key intracellular enzyme that breaks down stored lipids, such as triglycerides and cholesterol esters, into free fatty acids and cholesterol, primarily in adipose tissue).

HSL is the enzyme that unlocks your fat cells, hydrolyzing stored triglycerides into free fatty acids, which you’re going to burn, and then it floods your bloodstream with all this fuel ready for oxidation to be used. Turning your body into a fat-burning machine.

1. microdosing myths

This triple agonism creates a self-reinforcing, very powerful feedback loop drastically reducing caloric intake, highly sensitizing insulin response, and maxing out basal energy expenditure.

Reta’s terminal half-life is approximately 144 hours about 6 days.

The Importance of Steady State Concentration

Requires a steady state concentration. (therapeutic equilibrium where the concentration in the bloodstream stays within a consistent range over time, rather than continuously building up or falling off)

The time to reach steady state is determined by half half-life. It takes four to five half-lives to reach 94 to 97%.

** 6 day half life = 24-30 days **

The weekly dosing interval is not arbitrary because the 7-day injection perfectly reinforces the plasma concentration just as it begins to decline from the previous dose. So it maintains that very crucial, very stable therapeutic plateau.

If you microdose, you can never go through the 4 to 5 half-lives to reach the 94 to 97% of steady state concentration, which means you’ll never get to the 24 to 30 day mark, which, for reta is required.

The fallacy of: “tiny doses every day because you get fewer side effects and you get the same benefits.”

For example, 0.1 milligrams daily versus 2.5 milligrams weekly means that the amount administered is likely less than the daily clearance rate, which we already learned is required.

You perpetually operate in what’s called the distribution phase. You’re trying to fill a bathtub with a thimble while the drain is wide open.

You never get to the therapeutic steady state that’s required for efficacy. Rewiring of the hypothalamic set point requires a very strong, sustained signal.

A weekly dose provides days-long signals that carve new fullness pathways into your brain’s neural architecture. A microdose is a weak, fleeting signal.

bros never understood the side effect thing. maybe people injecting too much if you getting side effects from bigger doses

 

[Allupfromhere]

But the question here about GLP drugs is if you microdose do you actually reach full saturation at the level intended or are you reaching a steady state of a lower dose?
1mg week=X
does 1mg split =X or does it =Y?

This is interesting, would the total weekly mg dose being the same not reach full saturation eventually regardless of administration schedual, seeing as though almost all of the total mg for the week would be injected within the half life of the drug?

 

[Allupfromhere]

bros never understood the side effect thing. maybe people injecting too much if you getting side effects from bigger doses

Yeah and i think this is what @s.gentz was saying... people starting on too high of a dose is the main cause of the impacting sides.

As in if someone started at lets say 500mcg-1mg 1x weekly and allowed that specific dose to saturate before increasing the dose any further then ones body would have already adjusted to potential sides before next increase.

Being able to utilise a smaller dose more effectively.

Rather then microdosing a higher dose sooner to manage sids effects on a mg level that they may not have actually needed to gain effect.

Im actually leaning towards agreeing with this somewhat, soley based on my personal experience and how i feel the effectiveness of the drug with both approaches.

Ill give an example for my experiance using it;
I have been running reta for most of the year for transparency, i reached a point of 3mg weekly spilt into 3 doses, once the effectiveness on hunger started to subside instead of increasing to a higher weekly mg dose i switched to 1 single injection for the total of 3mg and it was night and day difference with hunger reduction.

Both ways were the same weekly total keep in mind but the single full dose was more effective.

This leads me to my next question i ask myself.
Would i have actually needed to increase each time the effectiveness lowered when i was microdosing or could i have still had the benifits from a lower dose using a single injection and be utilising a lower dose then i currently am?

Side note though, i think everyone will agree that anything in this game will always be individually dependant response wise, so it makes it very difficult to judge whats best for everyone within narrow parameters.

 

[Ulter]

Came across this video. Thought it was interesting. Would live to know other s thoughts on the topic

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For more detailed information, see our cookies page.

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Takeaways


Goes straight to your hypothalamus (your brain’s central command center).

It specifically targets something called Pro-opiomelanocortin (POMC). When these neurons get activated, they release Alpha-melanocyte-stimulating hormone (a-MSH), a neuropeptide that binds to Melanocortin 4 (MC4R), a G-protein-coupled receptor in your brain that plays a crucial role in regulating energy balance and appetite.

This is the biochemical equivalent of slamming down the off switch on your appetite.

It suppresses Neuropeptide Y (NPY), which is the most powerful hunger-signaling molecule that your body produces.
full. Reprogramming your brain’s definition of hunger.

It binds to GLP-1 and GIP, you know these receptors on the beta cells, which trigger G-protein coupled receptor cascades that skyrocket intracellular cyclic AMP (cAMP), this amps up glucose-dependent insulin secretion.

These processes only occur when glucose is high; no more wild spikes.

While simultaneously telling the alpha cells to stand down, shutting down all unnecessary glucagon output.

The best part is, this happens in your liver. Reta binds to glucagon receptors on hepatocytes (cells) in your liver. Cyclic AMP (cAMP) activates Protein kinase A (PKA) which phosphorylates (a biochemical process where a phosphate group is added to a molecule, such as a protein or sugar) and activates hormone sensitive lipase HSL (a key intracellular enzyme that breaks down stored lipids, such as triglycerides and cholesterol esters, into free fatty acids and cholesterol, primarily in adipose tissue).

HSL is the enzyme that unlocks your fat cells, hydrolyzing stored triglycerides into free fatty acids, which you’re going to burn, and then it floods your bloodstream with all this fuel ready for oxidation to be used. Turning your body into a fat-burning machine.

1. microdosing myths

This triple agonism creates a self-reinforcing, very powerful feedback loop drastically reducing caloric intake, highly sensitizing insulin response, and maxing out basal energy expenditure.

Reta’s terminal half-life is approximately 144 hours about 6 days.

The Importance of Steady State Concentration

Requires a steady state concentration. (therapeutic equilibrium where the concentration in the bloodstream stays within a consistent range over time, rather than continuously building up or falling off)

The time to reach steady state is determined by half half-life. It takes four to five half-lives to reach 94 to 97%.

** 6 day half life = 24-30 days **

The weekly dosing interval is not arbitrary because the 7-day injection perfectly reinforces the plasma concentration just as it begins to decline from the previous dose. So it maintains that very crucial, very stable therapeutic plateau.

If you microdose, you can never go through the 4 to 5 half-lives to reach the 94 to 97% of steady state concentration, which means you’ll never get to the 24 to 30 day mark, which, for reta is required.

The fallacy of: “tiny doses every day because you get fewer side effects and you get the same benefits.”

For example, 0.1 milligrams daily versus 2.5 milligrams weekly means that the amount administered is likely less than the daily clearance rate, which we already learned is required.

You perpetually operate in what’s called the distribution phase. You’re trying to fill a bathtub with a thimble while the drain is wide open.

You never get to the therapeutic steady state that’s required for efficacy. Rewiring of the hypothalamic set point requires a very strong, sustained signal.

A weekly dose provides days-long signals that carve new fullness pathways into your brain’s neural architecture. A microdose is a weak, fleeting signal.

I won't shoot the message, but i will shoot the messenger. if this dude is really a doctor why is he buying views on youtube and trying to be some guru youtuber? seems like he should get off his high horse

 

[stevesmi]

I have more appetite suppression with 1 x weekly dose compared to M W F injections

yeah but it will absolutely still work microdosed and its hard to really know for sure because the setting where you were using it could have been different in each instance.
example with me the first month my appetite was super low. but more i stayed on the more it wasn't. so i could have switched to microdosing at month 2 and noticed the same thing. that is why legitimate studies would be something i would look at

anyway i don't know who that idiot is in the video and don't want to know, but i got half way through and instantly could tell he is a lying POS just trying to put out a clickbait video.

 

[s.gentz]

Both ways were the same weekly total keep in mind but the single full dose was more effective.

This is the whole point of this thread.

 

[s.gentz]

yeah but it will absolutely still work microdosed and its hard to really know for sure because the setting where you were using it could have been different in each instance.

. i don't know who that idiot is in the video and don't want to know, but i got half way through and instantly could tell he is a lying POS just trying to put out a clickbait video. i would steer way clear of that guys videos going forward IMHO

The point of the video was to bring up discussion. Most youtubers are idiots but some make good points. I see a bunch of people advocating for microdosing to "relieve sides" but in doing that are you still getting the same effectiveness taking 1mg in one shot or splitting 1mg into three shots. I'm in the 1mg taken 1 shot per week camp as the manufactures intended.
Are the people microdosing 3mg/wk getting the effectiveness of 3mg or are they really seeing the results of less MG absorbed and that's why the sides are lessened. That seems more like what is happening. I went from 1mg of retatrutide to 3mg after being on the 1mg for 10 weeks. I felt like absolute shit. Went down to 2mg and felt fine. I can grantee the same people who are starting 3mg microdosed are not getting the effectiveness of 3mg bolus. They would feel awful.
I'll preface this statement by saying most doctors are morons but I have spoken with a few people on sema and tirzep who have had gastric/nausea issues at any dose. No Dr. or wellness clinic has told any of them to split the dose. Do they know something we don't or are they just out of touch?

 

[stevesmi]

The point of the video was to bring up discussion. Most youtubers are idiots but some make good points. I see a bunch of people advocating for microdosing to "relieve sides" but in doing that are you still getting the same effectiveness taking 1mg in one shot or splitting 1mg into three shots. I'm in the 1mg taken 1 shot per week camp as the manufactures intended.
Are the people microdosing 3mg/wk getting the effectiveness of 3mg or are they really seeing the results of less MG absorbed and that's why the sides are lessened. That seems more like what is happening. I went from 1mg of retatrutide to 3mg after being on the 1mg for 10 weeks. I felt like absolute shit. Went down to 2mg and felt fine. I can grantee the same people who are starting 3mg microdosed are not getting the effectiveness of 3mg bolus. They would feel awful.
I'll preface this statement by saying most doctors are morons but I have spoken with a few people on sema and tirzep who have had gastric/nausea issues at any dose. No Dr. or wellness clinic has told any of them to split the dose. Do they know something we don't or are they just out of touch?

i think my main issue is none of the stuff he says in the video has validity. so i would throw it out the window on his points

on the dosing as i said earlier it was designed for once a week dosing. i sincerely believe that microdosing will not make a lick of difference. same goes for microdosing test cyp daily vs. weekly or any other long ester steroids. nebido can be injected once every 12 weeks for example so pinning it daily and microdosing tiny amounts instead of doing it all at once would not make any difference. you are still getting the same amount and it still wont peak in your system for a while.. the only thing you are doing is initiallly you would have less in your system. but over time it will balance out anyway.

 

[s.gentz]

i think my main issue is none of the stuff he says in the video has validity. so i would throw it out the window on his points

on the dosing as i said earlier it was designed for once a week dosing. i sincerely believe that microdosing will not make a lick of difference. same goes for microdosing test cyp daily vs. weekly or any other long ester steroids. nebido can be injected once every 12 weeks for example so pinning it daily and microdosing tiny amounts instead of doing it all at once would not make any difference. you are still getting the same amount and it still wont peak in your system for a while

The only issue is that we have no real data either way. Only anecdotal so we really can't advocate for anything other than what the manufacturers intend for us to dose it at.
I think the mechanisms are different between glp's and test so I don't really agree with that comparison but again, we have no idea.
We are all experimenting with our bodies and these drugs and they react differently in each of us.
The one thing that is curious is this:
You take 3mg bolus and reach steady state in X. You feel like total crap.
You micro 3mg over the course of a week so you would expect to reach steady state 6-7 days after the bolus. I think that if you are truly absorbing the 3mg dose the same in both instances you would still feel like shit either way. I highly doubt a week would make that huge of a difference in how you feel.

 

[JimmyO187]

yeah but it will absolutely still work microdosed and its hard to really know for sure because the setting where you were using it could have been different in each instance.
example with me the first month my appetite was super low. but more i stayed on the more it wasn't. so i could have switched to microdosing at month 2 and noticed the same thing. that is why legitimate studies would be something i would look at

anyway i don't know who that idiot is in the video and don't want to know, but i got half way through and instantly could tell he is a lying POS just trying to put out a clickbait video.

I’ve got the switch logged on here, diet the same, ped use the same just changed Reta frequency…I’m only one individual and that my experience…I’ve also reported the positive effects it had on my alcohol consumption

 

[2Thick]

this clown on this youtube video was busted a few years back for CHEATING in crossfit and was banned for 4 years. i mean how much of a tool do you have to be to cheat at CROSSFIT lol. and he isn't a real doctor and he sells $5000 packages to suckers. he is a grifter man. its just a clickbait video just don't even look at that guys videos again he is a tool job. the first 2 minutes of the video is self reflection on himself as a scammer.

 

[ROIDDERS]

this clown on this youtube video was busted a few years back for CHEATING in crossfit and was banned for 4 years. i mean how much of a tool do you have to be to cheat at CROSSFIT lol. and he isn't a real doctor and he sells $5000 packages to suckers. he is a grifter man. its just a clickbait video just don't even look at that guys videos again he is a tool job. the first 2 minutes of the video is self reflection on himself as a scammer.

i hate assholes like him. he fits the grifter image to a tee.
beard
bald head
tats
sells bunk programs
buys followers and pretends to be an expert when he is not

my advice to anyone in this thread is don't over think things. microdosing vs. injecting less often. in the end its going into your body either way. you do what you feel comfortable with

 

[JimmyO187]

i hate assholes like him. he fits the grifter image to a tee.
beard
bald head
tats
sells bunk programs
buys followers and pretends to be an expert when he is not

my advice to anyone in this thread is don't over think things. microdosing vs. injecting less often. in the end its going into your body either way. you do what you feel comfortable with

100%

See what feels best as the individual without being swayed just base it on personal experience

 

[ROIDDERS]

100%

See what feels best as the individual without being swayed just base it on personal experience

exactly no need to buy a program off some youtuber for thousands that is disgusting. wish those guys would get a real job for once

 

[madcap71]

bros never understood the side effect thing. maybe people injecting too much if you getting side effects from bigger doses

Too much too soon.
Delayed gastric emptying meaning my morning bowel movement was a bit later than normal, but that's subsided..I'm getting all the benefits within the sides and I have no need to up the dose

 

[vanlife_gymbum]

Would be nice to get the screen shot of it or downloaded video, instagram is banned here wont work @madcap71 and I don't have social media lol it's poison.

Fuck yeah @LevButlerov I love your zero tolerance stance on this. I've never logged into Facebook even once in my whole life. When I saw it in 2006 I thought "who the fuck would use their real name on the internet" but I was young back then and didn't realise how stupid people atcually are. Deleting youtube when I joined Evo also improved my life and mental health noticeably.

 

[G-Merc 80]

It does work there is no doubt but we have no idea if it's better/worse than taking one shot for efficacy. Are people taking too much too soon and masking sides by micro? More is not better with these drugs.

This has made me interested in moving to a single dose which i will now do from Wednesday, I am up to 2mg weekly

 

[s.gentz]

This has made me interested in moving to a single dose which i will now do from Wednesday, I am up to 2mg weekly

Report back on any changes. How long have you been on 2mg?

 

[toddthelineman]

i hate assholes like him. he fits the grifter image to a tee.
beard
bald head
tats
sells bunk programs
buys followers and pretends to be an expert when he is not

my advice to anyone in this thread is don't over think things. microdosing vs. injecting less often. in the end its going into your body either way. you do what you feel comfortable with

But he’s a doooooooctor

 

[LevButlerov]

Fuck yeah @LevButlerov I love your zero tolerance stance on this. I've never logged into Facebook even once in my whole life. When I saw it in 2006 I thought "who the fuck would use their real name on the internet" but I was young back then and didn't realise how stupid people atcually are. Deleting youtube when I joined Evo also improved my life and mental health noticeably.

EVO family is real, the social media is just made to suck down your endorphins @vanlife_gymbum

 

[LevButlerov]

this clown on this youtube video was busted a few years back for CHEATING in crossfit and was banned for 4 years. i mean how much of a tool do you have to be to cheat at CROSSFIT lol. and he isn't a real doctor and he sells $5000 packages to suckers. he is a grifter man. its just a clickbait video just don't even look at that guys videos again he is a tool job. the first 2 minutes of the video is self reflection on himself as a scammer.

Drop mic moment, exactly! why does anyone listen to him! @2Thick

 

[LevButlerov]

@LevButlerov we'ver literally covered this multiple times. Even in the studies going on a dose, changing the dose etc would get issues such as nausea.

Yes I heard you on a few podcasts talking about it

 

[vanlife_gymbum]

Side note though, i think everyone will agree that anything in this game will always be individually dependant response wise, so it makes it very difficult to judge whats best for everyone within narrow parameters.

Won't stop them playing doctor and telling people to change their dosing schedules and amounts from what already works and cease their medication based on shit they pulled out of their ass though.

 

[G-Merc 80]

Report back on any changes. How long have you been on 2mg?

Been on 2mgs for four weeks now, Will update here.

 

[2Thick]

Drop mic moment, exactly! why does anyone listen to him! @2Thick

found out he isn't even a doctor. i guess on youtube anyone can claim to be a doctor and buy followers. what a joke platform

 

[LevButlerov]

found out he isn't even a doctor. i guess on youtube anyone can claim to be a doctor and buy followers. what a joke platform

He's as much of a doctor as "DR" Tony huge

 

[Allupfromhere]

He's as much of a doctor as "DR" Tony huge

I remember that doco movie, "enhanced 2 the max" still cant believe people volunteered for that

 

[LevButlerov]

I remember that doco movie, "enhanced 2 the max" still cant believe people volunteered for that

He injected people with sarms, later they had an infection, later he had a murder in his house in Thailand he knew "nothing" about lol crazy stuff.

 

[Allupfromhere]

He injected people with sarms, later they had an infection, later he had a murder in his house in Thailand he knew "nothing" about lol crazy stuff.

Proper legit crazy lol

 

[LevButlerov]

Proper legit crazy lol

I don't want to pollute the thread with him but he's out there lol he was on the EVO podcast but the episode got pulled LOL!!!!

 

[Pigsy]

I don't want to pollute the thread with him but he's out there lol he was on the EVO podcast but the episode got pulled LOL!!!!

Time for DR Pigsy . I could be a fraud like these guys

 

[ceo]

Too much too soon.
Delayed gastric emptying meaning my morning bowel movement was a bit later than normal, but that's subsided..I'm getting all the benefits within the sides and I have no need to up the dose

bros i can see that being a benefit

 

[ceo]

Yeah and i think this is what @s.gentz was saying... people starting on too high of a dose is the main cause of the impacting sides.

As in if someone started at lets say 500mcg-1mg 1x weekly and allowed that specific dose to saturate before increasing the dose any further then ones body would have already adjusted to potential sides before next increase.

Being able to utilise a smaller dose more effectively.

Rather then microdosing a higher dose sooner to manage sids effects on a mg level that they may not have actually needed to gain effect.

Im actually leaning towards agreeing with this somewhat, soley based on my personal experience and how i feel the effectiveness of the drug with both approaches.

Ill give an example for my experiance using it;
I have been running reta for most of the year for transparency, i reached a point of 3mg weekly spilt into 3 doses, once the effectiveness on hunger started to subside instead of increasing to a higher weekly mg dose i switched to 1 single injection for the total of 3mg and it was night and day difference with hunger reduction.

Both ways were the same weekly total keep in mind but the single full dose was more effective.

This leads me to my next question i ask myself.
Would i have actually needed to increase each time the effectiveness lowered when i was microdosing or could i have still had the benifits from a lower dose using a single injection and be utilising a lower dose then i currently am?

Side note though, i think everyone will agree that anything in this game will always be individually dependant response wise, so it makes it very difficult to judge whats best for everyone within narrow parameters.

bros good points. but funny thing is reta not fda approved yet. so anyone who claim to be a guru/expert on it full of shit. everything we know on it either from trial studies or personal experience being shared

 

[ROIDDERS]

But he’s a doooooooctor

yeah imagine going to med school and instead of practicing medicine afterwards deciding to make a career putting out youtube videos all day and selling $5000 programs. a real doctor for sure

 

[s.gentz]

Yeah and i think this is what @s.gentz was saying... people starting on too high of a dose is the main cause of the impacting sides.

As in if someone started at lets say 500mcg-1mg 1x weekly and allowed that specific dose to saturate before increasing the dose any further then ones body would have already adjusted to potential sides before next increase.

Being able to utilise a smaller dose more effectively.

Rather then microdosing a higher dose sooner to manage sids effects on a mg level that they may not have actually needed to gain effect.

Im actually leaning towards agreeing with this somewhat, soley based on my personal experience and how i feel the effectiveness of the drug with both approaches.

Ill give an example for my experiance using it;
I have been running reta for most of the year for transparency, i reached a point of 3mg weekly spilt into 3 doses, once the effectiveness on hunger started to subside instead of increasing to a higher weekly mg dose i switched to 1 single injection for the total of 3mg and it was night and day difference with hunger reduction.

Both ways were the same weekly total keep in mind but the single full dose was more effective.

This leads me to my next question i ask myself.
Would i have actually needed to increase each time the effectiveness lowered when i was microdosing or could i have still had the benifits from a lower dose using a single injection and be utilising a lower dose then i currently am?

Side note though, i think everyone will agree that anything in this game will always be individually dependant response wise, so it makes it very difficult to judge whats best for everyone within narrow parameters.

This is a great example of the point of this thread. Sorry I didn’t see it sooner. There is too much noise in this thread now. Apparently it’s more interesting to disparage the YT guy than to discuss the valid points that are brought up.
Keep us updated on any changes. I knew there was something to this bit h from personal experience and from the way I see people taking larger staring doses with little to no sides. Further reinforces what I was trying to get across.

 

[madcap71]

Too much too soon.
Delayed gastric emptying meaning my morning bowel movement was a bit later than normal, but that's subsided..I'm getting all the benefits within the sides and I have no need to up the dose

That was meant to say all the benefits without the sides

 

[Allupfromhere]

This is a great example of the point of this thread. Sorry I didn’t see it sooner. There is too much noise in this thread now. Apparently it’s more interesting to disparage the YT guy than to discuss the valid points that are brought up.
Keep us updated on any changes. I knew there was something to this bit h from personal experience and from the way I see people taking larger staring doses with little to no sides. Further reinforces what I was trying to get across.

Thats all good brother, was a bit of side traffic comments rolling in when i posted it lol.
Will definetly keep things updated and posted here too.
As i mention im curious to see how long the effects will last at a full single dose taken once a week... if this approach does in in fact have more longer lasting efficacy, then i may have been wasting my money having to increase the previous doses when not actually needed

 

[s.gentz]

Thats all good brother, was a bit of side traffic comments rolling in when i posted it lol.
Will definetly keep things updated and posted here too.
As i mention im curious to see how long the effects will last at a full single dose taken once a week... if this approach does in in fact have more longer lasting efficacy, then i may have been wasting my money having to increase the previous doses when not actually needed

Last time I used retat I did 1x per week shot and never had to go higher than 2.5mg/wk. hunger was always under control.
I did tirzep about two years ago and one shot would taper a bit last couple days before the next shot but was nothing big.
For me tirzep just made me mentally not wanna put food in my mouth. Just felt full all the time.
Retat didn’t really control hunger the same way. It just made me feel not that hungry.
On both of if I ate too much or something overly fatty I def knew.
Looking forward to your update.

 

[Allupfromhere]

Last time I used retat I did 1x per week shot and never had to go higher than 2.5mg/wk. hunger was always under control.
I did tirzep about two years ago and one shot would taper a bit last couple days before the next shot but was nothing big.
For me tirzep just made me mentally not wanna put food in my mouth. Just felt full all the time.
Retat didn’t really control hunger the same way. It just made me feel not that hungry.
On both of if I ate too much or something overly fatty I def knew.
Looking forward to your update.

Thats exactly why i went for reta over tirz at the start.. i didnt want to not eat, still wanted to hit macros but just block everything else out. The more i looked into it reta had multiple other benifits over tirz anyway.

Will do brother, nice work on this putting this thread up

 

[2Thick]

He's as much of a doctor as "DR" Tony huge

i can tell you if i was a doctor i wouldn't be spending my life doing youtube videos. what a fkin loser. he probably failed 7th grade

 

[LevButlerov]

Evidence for 1 shot vs microdosing
@G-Merc 80 updated his LOG with new reta feelings
https://www.evolutionary.org/forums...comp-log-changing-my-life.106206/post-1862506

Thanks Brother, trying to keep consistent in pushing

The change in Reta schedule has made a big impact on bowel movement, I am no longer struggling with that, which is a big win, food noise is quiet consistently (no sudden pacman urges), BUT I believe starting off with Microdosing was the right thing for me at the time as it squashed the overwhelming food noise; side note blood glucose levels are on point! after a solid meal of carbs and protein I am clearing quickly down to 5.3 nmol/L within the hour. thank you @s.gentz for the interesting article and opening up that conversation.

HGH shift now has me falling asleep easier at night as well, so another big plus.

Without the yourself (@LevButlerov), @stevesmi, @Allupfromhere and the rest of the Evo families guidance I would not be where I am now in my journey, so a huge thank you.

 

[LevButlerov]

@madcap71 is using retatrutide 2x/week instead of 1x/week semi microdose due to hunger issues
https://www.evolutionary.org/forums/threads/summer-cut-cycle-log.109604/post-2088444

2x a week reta works out best for me because of the 5 day half life. I've tried pinning it M/W/F and once a week. Didn't notice much going M/W/F but once a week had me wanting to eat my own arm by the time my next pin was due