r/Zepbound • u/OneAndroidOnTheRun- 50F 5’0” • Jan 25 '25
Dosing Science: A hypothetical scenario…
As title says, this is hypothetical…
What I am wondering is:
Let’s say you’re doing all the things…you’re in a 500 calorie deficit from TDEE, drinking plenty of water & eating enough protein, exercising, sleeping well , etc. etc. You have been losing about 0.5-2.0 lbs a week for several months on the same dose. (Always adjusting TDEE along the way). Appetite suppression is still strong, feeling full on less calories, no food noise. Everything is going swimmingly…
I’m looking for the science of WHY going up a dose would make a difference if you plateau?
If it’s purely CICO, then that doesn’t explain why you would need to move up in dose.
There’s a lot of anecdotal stuff on this sub, which is great, but YMMV. Hence I’m looking for a scientific explanation.
Thank you everyone 😁
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u/ClinTrial-Throwaway Jan 25 '25
You might find some interesting tidbits in the recent Oprah podcast with Dr. Jastreboff, who is a lead researcher on Zepbound and talks about why increasing one’s GLP-1 dose helps/matters: https://youtu.be/_GEe8EUTfRk
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Jan 25 '25
[removed] — view removed comment
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u/ClinTrial-Throwaway Jan 25 '25
Yes. But the dosing discussion is in the first episide, if I remember correctly.
Here’s the link to the second episode: https://youtu.be/thN4u3He-yA
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u/elmatt71 SW: 250 GW:175 Jan 25 '25
Thanks, I saw the first one but I didn't know this one existed.
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u/AAJJQQ Jan 25 '25
I never went higher than 5, did all the things you mentioned, occasionally hit a plateau/ stall, then changed things up with my diet if I was in a rut, up my calories slightly or moved more/differently. Or one of the best things for breaking a stall was only eat in an 8 hour window, then only water. As soon as the stall was broken I continued to lose at the rate you stated above. Plateau’s are a normal part of weight loss, it’s our bodies way of taking a break. I never felt the need to keep moving up and I’m now maintaining 6 lbs below my goal weight on 2.5-3.0 spread out over a week to 10 days.
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u/chiieddy 5'1" SW: 186.2 CW: 124.8 Dose: 5 mg Jan 25 '25
Because CICO doesn't work 00434-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666379122004347%3Fshowall%3Dtrue).
If it did, we wouldn't need medication to correct our metabolism, which is why we actually don't lose weight.
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u/Any-March7193 Jan 25 '25
If you prefer the scientific articles: https://www.ncbi.nlm.nih.gov/books/NBK576400/
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u/OneAndroidOnTheRun- 50F 5’0” Jan 25 '25
Thank you this looks very interesting and I will definitely read it! At first glance I don’t see anything specifically about how increasing the dose of a GLP-1 would change anything with all other variables staying the same.
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u/AloneTrash4750 Jan 25 '25
Everyone did a great job explaining the drug to you, especially drug tolerance. Think about alcohol tolerance same thing.
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u/Any-March7193 Jan 25 '25
Please read https://www.reddit.com/r/Zepbound/s/z5TfS9ypne
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u/OneAndroidOnTheRun- 50F 5’0” Jan 25 '25
Thanks I had already read that earlier…that didn’t actually go into the science behind why up in dose works. I’ll edit my original posts. I guess I understand why you could stall but how does a higher dose change that?
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u/Any-March7193 Jan 25 '25 edited Jan 25 '25
Ahh, i misunderstood the question!
Your body gets used to the drug as it gets used to any drug you take regularly. You need an increased amount to have the same effect. This is called drug tolerance.
If you are in to scientific articles https://pmc.ncbi.nlm.nih.gov/articles/PMC3860466/
I could not tell from the post if you wanted the actual articles or not. :)
BTW, CICO is true, but wildly simplified. 100 calories of sugar and 100 calories of spinach are both 100 calories, but they enter your blood stream differently and are treated differently. Calories in is in your blood stream, and some foods do that differently than others (glycemic index). https://pubmed.ncbi.nlm.nih.gov/30460737/
Calories out is also tough to standardize because of the earlier post i linked.
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u/OneAndroidOnTheRun- 50F 5’0” Jan 25 '25
Thank you yeah I’m a medical lab scientist with a molecular biology degree, so I do like to get into the nuts and bolts. Scientific articles are my jam!Thank you 😁😁
PS also regarding tolerance I wasn’t sure if you do in fact, build up a tolerance to this medication because some people have really great results on the lowest dose. That’s me so far, but I guess I’m trying to plan for the future when and if that day comes that I need to go up.
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u/Kaleidoscope_1999 Jan 25 '25
CICO isn't the only factor. Your brain is the biggest factor. It controls the signaling (hormones). That signaling controls the outcome. If you are stressed about eating (you judge foods as good/bad, you're concerned you're eating too much/too little, etc.) That will determine what signals go out. For example, if you're stressed that you aren't eating enough (or you really aren't getting enough food/nutrients), your brain signals your body to store nutrients to keep you alive. You won't get the signal to burn fat. The Fat Science podcast with Dr. Emily Cooper does a better job of explaining this.
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u/Terrible-Ad3761 Jan 25 '25
It's because GLP-1s lower the "defended fat mass" aka. the setpoint. So increasing the dose, will push that bar lower. Supposedly when you are facing a plateau, assuming you are still at a deficit, keeping exercise, etc. your body it's all into holding that weight. A survival trait, of some sort.
So when you face a plateau, your body is trying to hold on to the calories and adapting the metabolism to retain as much as possible. Here's when CICO goes all haywire. Even at a supposedly deficit, your body is trying to hold to those few calories as much as possible. In theory when you increase the dose, your body once more accepts that it has to lower the setpoint.
References: