In Regards to the 4mg Reta Glucagon Myth

[tubby]

Amber and I are friends IRL so I might shoot her a text on that. She's tried to discuss reta and metabolic affects on Reddit but with Reddit being what it is, the responses were predictable and not at all constructive to the discussion.

Your ketosis observations are interesting. Because I've been on LCHP for several years, my ketones usually hover in the 0.3-0.5 mmol range (as opposed to being LCHF where I would get as high as 3.0, but as I was actively losing large amounts of bodyfat that tracks). When I first started reta, say, the first 3 weeks, my ketones got up to 1.2 mmol but have since gone back to baseline LCHP levels, but I'm also sitting at 15.4% BF and 19.9% BMI with 113lb lean mass, so I'm running out of fat to burn. Hence my approaching titrating schedule to microdosing for the OCD benefits I've experienced.

But yes, I agree that Amber would provide a great deal of value to the conversation, as she's the most level-headed, analytical person I know. Her brain is very intimidating at times 🙂

There are a few places on Reddit where you can sometimes have a decent conversation, but I'd agree that it's tough to find. I don't poke my head in there much, but have been a fan of /r/saturatedfat in the past. It was initially a place to discuss Brad Marshall's (fire in a bottle) theories which started with something dubbed the croissant diet (which was ultimately a stearic acid maximization diet, although there was a lot more nuance than just that). I think that's largely been abandoned (although the studies underpinning it and much of the thought that evolved with it was really interesting). In the last couple years, HCLPLF has been discussed quite a bit there, but the real value is that it's mostly populated by people who have dabbled in a lot of different "fringe" dietary spaces so instead of everyone being a zealot for one particular diet and turning into an echo chamber, there's a very diverse range of viewpoints that get discussed in a fairly respectful way. And there is a certain irony in a space that started out maximizing saturated fat intake, evolving towards a high-carb diet preference. Although, that becomes slightly less ironic when one digs beneath the surface and realizes that a high-carb diet is probably the most fool-proof way of minimizing PUFA fat stores (and maximizing saturated fat stores) in one's body.

That's useful to see you had a similar experience in regards to ketones and reta as I did. Will be interesting to see how my body responds when I'm back down at a BMI of 27 on reta and if there will be any surprises in regards to ketosis there. I have a theory that at lower BMIs reta might actually make it harder to slip into ketosis: The thinking is that you're effectively forcing your body to cope with a higher glucagon (even if it's fake glucagon) load and the only way that it will be able to do that will be an increase in insulin, which in theory should make ketosis "harder." If that were true, that would mean reta would actually be less effective than tirz once you get below a certain BMI (a tipping point, if you will), as the glucagon agonist would work against you at that point. However, reta leading to significantly greater average weight loss than tirz (at equivalent dosing) seems to disagree with my theory.... unless it turns out that most never get to a low enough weight to reach that tipping point or other metabolic factors dominate and nullify my theory (very possible).

 

[octopusthorpe]

There are a few places on Reddit where you can sometimes have a decent conversation, but I'd agree that it's tough to find. I don't poke my head in there much, but have been a fan of /r/saturatedfat in the past. It was initially a place to discuss Brad Marshall's (fire in a bottle) theories which started with something dubbed the croissant diet (which was ultimately a stearic acid maximization diet, although there was a lot more nuance than just that). I think that's largely been abandoned (although the studies underpinning it and much of the thought that evolved with it was really interesting). In the last couple years, HCLPLF has been discussed quite a bit there, but the real value is that it's mostly populated by people who have dabbled in a lot of different "fringe" dietary spaces so instead of everyone being a zealot for one particular diet and turning into an echo chamber, there's a very diverse range of viewpoints that get discussed in a fairly respectful way. And there is a certain irony in a space that started out maximizing saturated fat intake, evolving towards a high-carb diet preference. Although, that becomes slightly less ironic when one digs beneath the surface and realizes that a high-carb diet is probably the most fool-proof way of minimizing PUFA fat stores (and maximizing saturated fat stores) in one's body.

That's useful to see you had a similar experience in regards to ketones and reta as I did. Will be interesting to see how my body responds when I'm back down at a BMI of 27 on reta and if there will be any surprises in regards to ketosis there. I have a theory that at lower BMIs reta might actually make it harder to slip into ketosis: The thinking is that you're effectively forcing your body to cope with a higher glucagon (even if it's fake glucagon) load and the only way that it will be able to do that will be an increase in insulin, which in theory should make ketosis "harder." If that were true, that would mean reta would actually be less effective than tirz once you get below a certain BMI (a tipping point, if you will), as the glucagon agonist would work against you at that point. However, reta leading to significantly greater average weight loss than tirz (at equivalent dosing) seems to disagree with my theory.... unless it turns out that most never get to a low enough weight to reach that tipping point or other metabolic factors dominate and nullify my theory (very possible).

Ah, yes - I know Brad. My best friend is a fan of his dietary experiments and yes, did the croissant diet, as well as some "heavy-cream centric" approaches suggested by @exfatloss (not a fan of his - he's rather keto-jaded), and the latest low vit A schools of thinking - he's far more adventurous and experimental than I am in terms of diet. 😆

 

[tubby]

Ah, yes - I know Brad. My best friend is a fan of his dietary experiments and yes, did the croissant diet, as well as some "heavy-cream centric" approaches suggested by @exfatloss (not a fan of his - he's rather keto-jaded), and the latest low vit A schools of thinking - he's far more adventurous and experimental than I am in terms of diet. 😆

You're missing out on life if you don't follow exfatloss. It's about 50:50 on if I'll agree with his overall assessments, but he documents what he does so well that it's a pleasure to read and he's kind of the poster child for not being afraid to try an "extreme" diet.

Have to say Brad is one person I kind of hope doesn't get into reta, simply because it might be the end of him trying to invent and rationalize new dietary concepts. Then again, he'd probably have some interesting insights too if he did.

 

[octopusthorpe]

You're missing out on life if you don't follow exfatloss. It's about 50:50 on if I'll agree with his overall assessments, but he documents what he does so well that it's a pleasure to read and he's kind of the poster child for not being afraid to try an "extreme" diet.

Have to say Brad is one person I kind of hope doesn't get into reta, simply because it might be the end of him trying to invent and rationalize new dietary concepts. Then again, he'd probably have some interesting insights too if he did.

In all fairness, exfatloss and I got into a bit of a keto feud in my early keto days where he devolved into pure ad hominem, so I have a natural bias. That and his negatively-charged delivery (every methodology he disagrees with is a "-tard") keeps me from seeking to find the value in his work. But I'm with you on being curious on what Brad would discover on a reta experiment. He's a good egg.

 

[tubby]

In all fairness, exfatloss and I got into a bit of a keto feud in my early keto days where he devolved into pure ad hominem, so I have a natural bias. That and his negatively-charged delivery (every methodology he disagrees with is a "-tard") keeps me from seeking to find the value in his work. But I'm with you on being curious on what Brad would discover on a reta experiment. He's a good egg.

In ex's defense, he regularly refers to himself as a ketard as well and I'd agree that he's a little rough around the edges that way. I do love that he created a graphical representation of his heavy cream diet in pyramid form. I think my favor for him really just stems from him being the only guy I know crazy enough to find a diet where the vast majority of it involves consuming heavy cream, all day long, without limit, and demonstrates it to be a highly successful weight loss diet that he loses ~100 pounds on. That's a Norwitz-level gimmick right there and a great keto "convincer" for those who doubt the underlying mechanism!

But yeah, hopefully in time more folks from that community will wander over, as it would be fun to see what interesting conversations could evolve.

 

[kj4otu]

If you're trying to see the differences in average results, I'd recommend going back to the plot in the OP. It's going to be harder to see the difference in averages in waterfall plots.

Well, that's the point of averages, smoothing so you can see trend differences. Which are there but smaller once above 4mg. Def dif between 1 and 4 though.

 

[Jfrick11]

There’s actually a lot in this post that is more scientifically grounded than the usual GLP-1 forum mythology, Well done you 😉

This was by far, my favorite the part:

unchanged glucagon levels at low dose may actually reflect balancing effects rather than absence of glucagon agonism

That’s a sophisticated point.
People often assume:
“lab value unchanged” = “drug not doing anything”

But endocrine systems are feedback loops. A receptor agonist can absolutely be exerting biologic activity while measured endogenous hormone levels look “normal” because the body compensates.

That’s legit physiology reasoning.

 

[tubby]

unchanged glucagon levels at low dose may actually reflect balancing effects rather than absence of glucagon agonism

That's kind of fun to see what I assume is my OP translated to (I'm guessing) Spanish and then translated back to English. I'm honestly kind of surprised the translation properly carried the concept over and didn't change the meaning along the way.

 

[Omxxl]

Good post, and hearing of the dirty argument, but I believe that it is important to have some of these things because at the end of the message that this float is "the same dose as mine," and this is the stamp of all of this in practice.
Sobre lo del mito de los 4 mg:
The reason is that the concrete cifra de 4 mg comes from a reading a poco perezosa de la phase 1 de Coskun et al. (2022), and that extrapolar dose is unique to a weekly accumulation and does not have much pharmacokinetic feeling. Hasta ahí de acuerdo. But then I decided that the glucose component "is active" at 0.5 or 1 mg every week, but the propios datos do not respond to all. The fact that the test shows that the net effect on the serum glucose is practically zero or includes only a positive dose of low doses, and indeed, it is explained as it is explained (GLP/glucagon balance, individual sensitivity, etc.), means that the differential component is marginally affected by it. ese rango.
Point 3 (insulin/glucagon balance):
This is the part where the most recent argument is present, and it is the part he believes to be the strongest argument in the post. It is true that serum glucose is detected because a GLP-1 RA is elevated in basal insulin and the body compensates for glucose. Eso lo entiende muy poca gente. However, this is also a double-layered arm for your argument: if a low dose of glucose agonism does not compensate for the natural induction of GLP, then in practice the clean effect on gas energy, hepatic lipolysis and the preservation of fatty acids (that es donde reta presuntamente brilla frente a tirze) va a ser pequeño. The "equilibration" is still good in the real metabolic output terminals and therefore "nothing is too much of a problem".
About “falsified glucose”:
The analogy is well to explain, but it does add something. The agonism of the glucose receptor at the hepatic level is where it returns its different effects: an increase in energy levels, an improvement in the hepatic lipid profile, and the famous preservation of masa magra which is seen in the DEXA curves. These effects are based on the dose-dependency of the form that is based on Jastreboff's phase 2 data. If you see in the graph that you have misadjusted, the difference between 4 mg and 8-12 mg in weight per 48 weeks is not linear, but it is trivial: it is -17.8% vs -24%. This is 6-7 points that cannot be explained alone by more GLP.
What you have to say about the experience:
Personally, I did not pass 2.5 mg per week and the results were spectacular, even more so when he hoped to get the shot. Body composition, room, energy, all in line with what is promised. As if in the practical plan it is enough to acquire that no falta llegar a 4 mg for very good results, and much less in Alguien that starts from a moderate weight and has a decent response to the compuesto. The idea that "for 4 mg deduction is more likely" is clearly false if it is believed to pass into the heart of real people.
Donde sí creo que hay que tener cuidado es en vender la idea contraria, que es que es que es que es que es que es que es que es que es que la dose n'importanta o que el componente glucagon arde igual en todo el rango. The data suggested that you scale, and the interesting pregunta no es "¿4 mg es mágico?" (no lo es), otherwise "what is the minimum dose effective for each profile?". And it's probably more likely that it's more likely that people will take care of it, even if it's all people with less resistance to insulin, it's just like that in point 2.
In summary: taking 4 mg does not contain magic or the minimum obligatorio, in order to minimize the importance of the dose-response in the different component of the drug.

 

[Dmac12]

It can def be different for different people. I'm on 1mg, going on 11 weeks now. Started at 328, down 25lbs (7.6%, well ahead of the trial stats for 1mg) and have lost 4 inches in waist, so I would say for me 1mg is doing pretty well with visceral fat as well. Granted I am also eating differently and working out 3 times a week. It all adds up.

Ya, when I was larger and before these drugs came out just a slight change in diet and increase in activity saw huge results. It's good to see you aren't trying t speed run things. I suspect the Reta isn't contributing that much at this point and its more on your personal effort, good job. It will get more difficult and that's when you'll need the increased dose or maybe you won't. I got to a good place(-100lbs for 8 years) before GLP1s were a thing but after getting in a bit of a rut and putting on 40lbs I decided why make things hard on myself. I'm glad I did because not only has it helped with the weight loss but It eliminated the osteoarthritis in my hips and knees to nothing. I haven't had to take an Ibuprophen since shortly after starting which makes it a lot easier to be active.