Lost 31 Pounds And Stalled? Don't Raise The Dose | Weekly Q&A #16

All right, this week's gun that we're showing is my new Benelli M2G1, pretty fucking sweet. Now let's talk about the question that matters most this week, which is what to do when you lose 31 pounds on retatrutide and then the scale stops moving.

The instinct is to raise the dose, because that is what the clinical trials did, and the trials incrementally increase the dose over time, and that works until it doesn't.

What's actually happening at that stall has almost nothing to do with the drug losing potency and almost everything to do with what an extended calorie deficit does to your thyroid.

Before I get into the fix, you need the whole chain in front of you, because the piece most people look at is the piece that tells you the least.

Your thyroid produces T4 and a small amount of T3, and TSH is the signal from your pituitary telling the thyroid how hard to work, so when a doctor checks your thyroid he usually checks TSH and maybe T4 and calls it a day.

Thyroid is producing T4 and T3, but most of the T3 that's produced isn't actually happening at the thyroid. Most of the T3 in your body is converted at the liver and some in the kidneys, where an enzyme strips an iodine atom off T4 and turns it into the active form.

T3 is the active form of the thyroid hormone that's influencing your metabolism. It's what sets how much energy your cells burn at rest, which is the number that determines whether a given calorie intake produces weight loss or produces nothing.

Here's where the deficit comes in. That same T4 molecule can have a different iodine atom removed instead, and what you get is reverse T3, which fits the same shape but doesn't activate anything.

And what you're looking at is not necessarily shut down of the thyroid, but understanding that there's an increase in the production of reverse T3 at the liver rather than the production of T3, which is passively reducing your body's ability to burn fat.

This is not new science. Burman and colleagues demonstrated back in 1980 that caloric restriction shifts T4 metabolism away from T3 and toward reverse T3, which is the same conversion shift showing up in every long dieter I see.

That's not influencing your metabolism, right? Think of reverse T3 for the thyroid as the same as SHBG for testosterone, right? My testosterone levels can be through the fucking ceiling and I can still feel like crap if my SHBG levels are also elevated because the SHBG is preventing that testosterone from binding to the androgen receptors.

So you can sit there with a lab report where TSH is where it should be, T4 is where it should be, everything looks great on paper, and your reverse T3 is through the ceiling, and nobody checked it because reverse T3 is almost never on a standard panel.

The research on incretin mimetics like retatrutide and tirzepatide found TSH actually dropped as weight came off while free T4 didn't change, and a large review of hypothyroid patients found those who lost more than five pounds on a GLP-1 saw their TSH fall by about 0.36 to 0.55 on average.

Which tells you the thyroid changes are coming from the deficit and the lower body weight, not from the drug damaging anything.

And this matters for dose decisions, because when you raise retatrutide on top of an already suppressed metabolism, you're deepening a deficit that your body has already responded to by lowering the burn rate. You get more appetite suppression and more downregulation at the same time.

Worth noting the dose escalation data is real. Jastreboff and colleagues in the New England Journal of Medicine in 2023 ran retatrutide up to 12 milligrams and saw mean weight reduction of 24.2 percent at 48 weeks, so the drug does keep working at higher doses in a trial population that is being escalated on a schedule from the start.

The question is whether you're the person in that trial or the person who has already been in a deep deficit for four months and whose thyroid has quietly adjusted.

And in most cases, the thing that's going to fix this stall is reverse dieting your way back up to maintenance calories over a 12-week period.

Then you hold at those maintenance calories for about four to six weeks before you start incrementally decreasing again. When you reverse diet back up, your thyroid gets functioning correctly again, you start seeing more meaningful T3 conversion at the liver, T3 gets back within a normal range, and things start to turn on again.

Before GLP-1 drugs existed, it was realistic for me to expect one to two pounds of weight loss per week, and that number hasn't changed just because the appetite suppression got better. Don't run an extreme deficit for longer than 12 to 16 weeks max, period. The faster you lose the weight, the less sustainable that is for you long-term.

The same deficit logic shows up in a completely different question I got this week, which is about growth hormone secretagogues and IGF-1 not moving.

Your pituitary is the gatekeeper to the production of growth hormone, and CJC and tesamorelin are GHRH analogs, meaning they replicate the growth hormone releasing hormone signal your hypothalamus normally sends to the pituitary. The pituitary pulses growth hormone, growth hormone goes to the liver, and the liver converts it into IGF-1.

Why? Well, because IGF-1 is a building signal, aka, we're going to go and repair, build more muscle, more tissue, etc. Well, if you're in an extreme deficit, your body shut down, and your body's trying to hold on to resources, the last thing it's going to do is create a hormone that's going to trigger the growth or expenditure of surplus resources.

Moller and Jorgensen laid this out in Endocrine Reviews in 2009, describing how growth hormone's direct action drives lipolysis while the IGF-1 arm of the system carries the anabolic signal, which is why the two effects can separate under the right conditions.

Yes, you're going to get a meaningful increase in growth hormone production, but the secondary benefit, which is that IGF-1 conversion, is going to be blunted.

Estrogen is the other big lever on that conversion, and it's probably the most impactful one. If you're on TRT with an aromatase inhibitor, or you're running a SERM like clomiphene, you're blunting the conversion of GH to IGF-1 at the liver.

Age stacks on top of both. You're on the decline when it comes to the production of new tissue, which means that you have to work even harder to get the result, especially after 55.

What I suggest you do either way is, before you start these types of growth hormone-related peptides, you get your lab work done, get a baseline of what your IGF-1 is, then go for six to eight weeks, and then when you draw your labs, if you're doing the peptide, make sure you get that blood drawn about four hours or so after you've done your shot, and that's going to be sufficient time for your body to produce the GH, and then subsequently convert it to IGF-1.

If you don't see any meaningful increase in IGF-1 levels, and you're eating, and your estrogen is where it needs to be, then that probably means that your pituitary isn't as responsive, in which case it would probably be a better approach to look at growth hormone directly, and this kind of lends us to our next question, which is, my IGF-1 went from 110 to 150 on CJC and ipamarylin, is that response a normal swing? And this is for a man, he said he started at 110 and went to 150, okay, so for context, that's about a 36% increase, so I suppose that's good, but the other thing to consider is the fact that 110 as a middle-aged man is a pretty low IGF-1 level to start.

There is a lot more of this inside the free community, and it is genuinely free, so if you want somewhere to ask the follow-up question the men's group is here: https://www.skool.com/jh-iron-forge-brotherhood/about

Research: Burman 1980 (PMID 7419689); Jastreboff 2023 (PMID 37366315); Moller 2009 (PMID 19240267); Falutz 2008 (PMID 18690162).

References

Dalmasso et al., Gastroenterology, 2008. PMID: 18061177. https://pubmed.ncbi.nlm.nih.gov/18061177/

Burman et al., Journal of Clinical Endocrinology and Metabolism, 1980. PMID: 7419689. https://pubmed.ncbi.nlm.nih.gov/7419689/

Jastreboff et al., New England Journal of Medicine, 2023. PMID: 37366315. https://pubmed.ncbi.nlm.nih.gov/37366315/

Falutz et al., New England Journal of Medicine, 2008. PMID: 18690162. https://pubmed.ncbi.nlm.nih.gov/18690162/

Moller et al., Endocrine Reviews, 2009. PMID: 19240267. https://pubmed.ncbi.nlm.nih.gov/19240267/

Skorupskaite et al., Human Reproduction Update, 2014. PMID: 24615662. https://pubmed.ncbi.nlm.nih.gov/24615662/