Crushed Leptin: What's the move?

[ChemBB]

Weight loss has stalled dramatically recently. Scale isn't budging, and I do 1.5hrs resistance + 30m cardio at 135BPM HR daily.
Calories are 2,500-2,900 generally, at 195lbs 5'6, probably 12-14% BF

300mg Test
4iu GH
10mg Tirz + 3mg Sema

This doesn't make any sense to me, so I get leptin tested:


Now what?
We know depleted leptin in athletes reduces TDEE by ~20%.
It also places a ton of stress on the HPTA -- cortisol, T3/T4/TSH, sex hormones

I still have to drop 18lbs more to compete, and I have 24 weeks to do it.
Start taking 25-50mcg T3 + dieting harder?

It seems like Cagrilintide (amylin), and something called "celastrol" (which I've never heard of) might be effective too?

https://joe.bioscientifica.com/view/journals/joe/241/3/JOE-18-0606.xml#d3651583e1906

The second group of molecules induce weight loss in hyperleptinaemic animals even when administered alone, suggesting that they restore leptin signalling and resensitise obese mice to their endogenous hyperleptinaemia. Such molecules include amylin, predominantly secreted from the pancreatic β cells but also produced by hypothalamic neurons (Le Foll et al. 2015), and pramlintide, an amylin analogue in clinical use for the treatment of diabetes. ... Amylin also exerts a direct effect in enhancing leptin signalling via activation of the ERK/MAPK pathway on POMC neurons (Lutz et al. 2018). Glucagon-like peptide-1 (GLP-1) also increases central leptin action and appears to exert its anorectic effects synergistically with leptin.

Heat shock protein 90 (HSP90) inhibitors display leptin sensitiser properties (Desarzens et al. 2014, Ozcan et al. 2017). At least some HSP90 inhibitors were shown to induce weight loss in DIO mice but had a blunted effect in ob/ob or db/db mice. Some of these HSP90 inhibitors are natural compounds, such as celastrol and gambogic acid, which have pleiotropic effects including PTP1B inhibitory and anti-inflammatory activities (Tan et al. 2017).

CYS (Cite Your Sources)

Isola, V. et al. (2023). Weight loss induces changes in adaptive thermogenesis in female and male physique athletes. Applied Physiology, Nutrition, and Metabolism, 48(4), 414-423.
Kairaitis, R. et al. (2023). Dietary, Body Composition, and Blood Leptin Variations in Fit-Model Female Athletes During the Pre-Competition Period. Nutrients, 15(18): 3981.
Helms, E. et al. (2014). Evidence-based recommendations for natural bodybuilding contest preparation: nutrition and supplementation. J. ISSN, 11, 20.
Pardue, A. et al. (2017). Case Study: Unfavorable but Transient Physiological Changes During Contest Preparation in a Drug-Free Male Bodybuilder. Int J Sport Nutr Exerc Metab, 27(6), 550-559.
Hinkle, W. et al. (2013). Leptin Repletion and Reduced-Weight Maintenance: Effects on Neural and Endocrine Responses. PLOS ONE, 8(3): e59114.
Hislop, M. et al. (1999). Effects of anabolic-androgenic steroid use or gonadal testosterone suppression on serum leptin concentration in men. Eur J Endocrinol, 141(1), 40-46.
Peos, J. et al. (2021). Continuous versus intermittent dieting (ICECAP trial). Med Sci Sports Exerc, 53(8), 1685-1698.
Peos, J. et al. (2021). A 1-week diet break improves muscle endurance during an intermittent dieting regime (secondary analysis of ICECAP). PLOS ONE, 16(2): e0247292.
Rossow, L. et al. (2013). Natural bodybuilding competition preparation and recovery: a 12-month case study. Int J Sports Physiol Perform, 8(5), 582-592.
Rosenbaum, M. et al. (2002). Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and thyroid hormones. J. Clin. Endocrinol. Metab, 87(5), 2391-2394.
Trexler, E. et al. (2014). Metabolic adaptation to weight loss: implications for the athlete. J. ISSN, 11, 7.
Chan, J. et al. (2003). The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J. Clin. Invest, 111(9), 1409-1421.
jn.nutrition.org

 

[ChemBB]

I went from eating 2,500kcal of entirely clean food to 5,000kcal of 2,500kcal clean + 2,500kcal icecream just to see what would happen

It seems to have made zero difference, waking up slightly lighter each day

I give up on trying to understand human metabolism

 

[Avies48]

I went from eating 2,500kcal of entirely clean food to 5,000kcal of 2,500kcal clean + 2,500kcal icecream just to see what would happen

It seems to have made zero difference, waking up slightly lighter each day

I give up on trying to understand human metabolism

Almost compared to the sugar diet… but still including good foods, seems odd

 

[chrysler]

Do a thyroid panel and introduce T4 at 100 mcg per day.

HGH depletes T4 because it accelerates T4 to T3 conversion in the body. Supplementing with T4 is synergistic with HGH and might get you out of you stall.

 

[Avies48]

How to Increase Leptin Levels (From a Dietitian)

We’ve asked a qualified health care professional to provide medical advice on how to boost your leptin, and here’s what we’ve learned. Read on to find out more.

totalshape.com

How to Stimulate a Leptin Response in Your Body: 12 Steps

Leptin is a protein made by fat cells to regulate energy levels. This hormone does its task by telling the brain when you are satiated, or "full," allowing your body to use energy at normal levels. When leptin is released the feeling of...

www.wikihow.health

How to Increase Leptin, Your Fat-Burning Hormone

Leptin is the "starvation hormone" because it notifies your brain if you have eaten enough and your calorie intake is sufficient. Learn how to increase it and fight leptin resistance with the right diet, exercise types, lifestyle changes and more.

draxe.com

 

[anon55]

If you can handle financially metreleptin go for it!

 

[eery]

Going hard on a cut and pushing cortisol and everything hard tends to have your body figh tback and hold on to ..everything. But it usually gives once you chill out and give it some rest, recovery and time, thats where refeeds can be helpful in my experience, coupled with the increased glycogen you get which helps maintain training intensity and quality more.

you might just have to give it time and you'll have a big "woosh".

look into the woosh effect ala lyle mcdonald.

anyway, eat less and/or do more cardio, consider a replacement amount of t3/t4 to keep your metabolism at as much of a baseline as possible, maximize recovery, sleep, hydration and all of that.

 

[SubparMarioBro]

It seems like Cagrilintide (amylin), and something called "celastrol" (which I've never heard of) might be effective too?

https://joe.bioscientifica.com/view/journals/joe/241/3/JOE-18-0606.xml#d3651583e1906

Hyperleptinaemia (those studies) and hypoleptinaemia (your labs, almost) are two entirely different things.

 

[ChemBB]

I just went from 190 -> 220lbs over the span of 6 weeks, and my leptin hasn't budged.

T3/T4/TSH are all in range, cortisol is low rather than high

Must be the GLP-1's or something, I've been taking 2.3mg Reta a week during this bulk for insulin sensitivity

 

[syuri]

I just went from 190 -> 220lbs over the span of 6 weeks, and my leptin hasn't budged.

T3/T4/TSH are all in range, cortisol is low rather than high

Must be the GLP-1's or something, I've been taking 2.3mg Reta a week during this bulk for insulin sensitivity

View attachment 362279

shocked your cortisol is low even off 2-ish mgs of reta. my cortisol has spiked and has stayed spiked off 1mg unfortunately. sorry about your situation though.

 

[hooligansluck]

The best ways, Ive always break through plateaus is a 3 day fast then low carb with moderate fats for 2-4 weeks, then slowly introduce carbs.

 

[dinfaralt]

increase cardio or eat less or do a refeed to reset.

honestly, you run out of options and need refeeds more often than not when you're leaning out for competition.

ive spoken with a few guys that compete and they plan their last 20 weeks crazy, going all the way down to 1800/2000 calories, refeed 4-6 weeks in repeat.

adding crazy amount of steps. 20-30k steps a day burns the fat off in my experience. never got down to 5% max 7-8%