There Are Only 3 Ways To Increase Your IGF-1 (How To Pick The Right One)
Your pituitary gland is not a simple on/off switch. It is more like a thermostat that is constantly reading signals from your blood, adjusting output, and defending a set point that your body has decided is appropriate for you. Understanding that thermostat is the whole reason the three categories of growth hormone compounds work so differently from each other.
Here is the full chain first, because without it the rest of this will not make sense.
Your hypothalamus releases something called GHRH, which stands for growth hormone-releasing hormone, and its job is to signal your pituitary to produce and release growth hormone. Growth hormone then travels to your liver, where it triggers the production of something called IGF-1, which is insulin-like growth factor 1, and IGF-1 is the molecule that actually does most of the downstream work: building tissue, burning fat, supporting recovery. When IGF-1 climbs high enough, it signals back to the hypothalamus to release somatostatin, which is essentially a brake on the whole system, and pituitary output slows down. That feedback loop is the key to understanding why each category hits a different ceiling.
Category one, the GHRH analogs, which includes Tesamorelin, CJC-1295, and Sermorelin, work by mimicking your body's own GHRH signal. You inject the peptide, your pituitary responds by releasing more growth hormone, your liver converts that into IGF-1, and IGF-1 rises. The important thing here is that the feedback loop is still intact. As IGF-1 climbs, somatostatin rises to match it, and the system self-corrects. That is what the video means by a built-in ceiling. You are working within the system, not bypassing it.
Clinical trials on Tesamorelin give you a concrete sense of what that ceiling looks like in practice. In a 2007 trial published in the New England Journal of Medicine, HIV-positive patients with excess visceral fat received Tesamorelin at 2 milligrams daily for 26 weeks. IGF-1 levels rose significantly but stayed within what would be considered a high-normal physiological range, and visceral fat decreased by roughly 15 percent compared to placebo. The feedback loop allowed the system to respond, but it also prevented IGF-1 from climbing into territory the body did not permit.
That visceral fat result is worth slowing down on, because there is a common belief that Tesamorelin has some unique fat-burning mechanism that other growth hormone compounds lack. The belief is understandable because almost all the clinical trials for Tesamorelin specifically measured visceral fat as the primary endpoint, which is what it was developed and approved to treat. What those trials actually showed, though, is that growth hormone in general drives lipolysis, which is the breakdown of stored fat, most aggressively in the depots that have the highest concentration of GH receptors, and visceral fat has a higher density of those receptors than subcutaneous fat does. Research from Johannsson and colleagues in 1997 showed the same visceral fat reduction in abdominally obese men treated with pharmaceutical HGH, with abdominal fat mass dropping significantly alongside improvements in glucose and lipoprotein metabolism. The mechanism is the same. The trial population just happened to be different.
Category two is exogenous growth hormone, which is pharmaceutical HGH injected directly. When you do this, growth hormone is no longer coming from your pituitary in response to an internal signal. It is coming from outside the feedback loop entirely. Your IGF-1 can climb past what your body would naturally permit because somatostatin is responding to the IGF-1 level, not suppressing a pituitary that is already bypassed. This is also why stacking GHRH analogs on top of exogenous HGH does not accomplish what people hope it will. Research from Rosenthal and colleagues demonstrated that exogenous growth hormone suppresses GHRH-induced GH secretion in normal men, meaning the pituitary is already being dampened by the negative feedback from elevated IGF-1, so adding Tesamorelin or CJC on top of an HGH protocol is paying for a signal the pituitary is no longer responding to.
The tradeoff with exogenous HGH is not just cost, though cost is real. It is also the ongoing need to monitor IGF-1 through bloodwork, because without the body's own thermostat doing the correcting, the only feedback mechanism you have is the blood test. Too high and you start seeing the risks associated with chronically elevated IGF-1. Too low and you are not getting the intended effect. The tool is more powerful precisely because the safety system has been removed.
Category three, IGF-1 LR3, removes even more of the system. You are not stimulating growth hormone. You are not waiting for the liver to convert anything. You are injecting the downstream effector molecule directly. IGF-1 LR3 is a modified version of IGF-1 that has been engineered to resist binding proteins, which means more of it stays in its active, unbound form and it remains active in the body for a longer window than standard IGF-1. Research by Chapman and colleagues found evidence that it is free, unbound IGF-1, rather than the protein-bound fraction, that drives the suppression of pituitary GH release, which means IGF-1 LR3's resistance to binding proteins also makes its suppressive feedback significantly more potent. That is one reason why receptor desensitization becomes the limiting factor. If you run it continuously, the receptors that respond to IGF-1 downregulate, meaning the same dose produces less effect over time, which is why six to eight week cycles followed by time off are the standard approach for people who use it.
The practical decision between the three categories comes down to what ceiling you are working toward. If your goal is restoring growth hormone output to something close to a healthy physiological range, supporting sleep quality, body composition, and recovery without going above what the body would naturally allow, a GHRH analog is the right tool. It is the lowest intervention and the one most consistent with the body's own regulation. If your goal is sustained IGF-1 above your natural ceiling for an extended period, exogenous HGH is the path, with the understanding that bloodwork is not optional. If you have a specific short-term goal that requires direct IGF-1 activity and you are willing to cycle appropriately and monitor closely, IGF-1 LR3 is the most direct tool available.
None of these change the fundamental requirement for a calorie deficit if fat loss is the goal. Growth hormone accelerates lipolysis, meaning it speeds up the rate at which fat is mobilized from storage, but mobilized fat still has to be used for energy rather than redeposited. The hormone is the accelerant. The deficit is the fire.
The three compounds are not a hierarchy where more powerful is always better. They are three different entry points into the same signaling chain, and which one makes sense depends entirely on where in that chain you need the intervention to happen.
References
- Falutz J, Allas S, Blot K, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S. (2007). Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med 357(23):2359-70. DOI: 10.1056/NEJMoa072375
- Stanley TL, Grinspoon SK. (2015). Effects of growth hormone-releasing hormone on visceral fat, metabolic, and cardiovascular indices in human studies. Growth Horm IGF Res 25(2):59-65. DOI: 10.1016/j.ghir.2014.12.005
- Moller N, Jorgensen JO. (2009). Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 30(2):152-77. DOI: 10.1210/er.2008-0027
- Hashimoto Y, Kamioka T, Hosaka M, Mabuchi K, Mizuchi A, Shimazaki Y, Tsunoo M, Tanaka T. (2000). Exogenous 20K growth hormone (GH) suppresses endogenous 22K GH secretion in normal men. J Clin Endocrinol Metab 85(2):601-6. DOI: 10.1210/jcem.85.2.6377
- Rosenthal SM, Hulse JA, Kaplan SL, Grumbach MM. (1986). Exogenous growth hormone inhibits growth hormone-releasing factor-induced growth hormone secretion in normal men. J Clin Invest 77(1):176-83. DOI: 10.1172/JCI112273
- Chapman IM, Hartman ML, Pieper KS, Skiles EH, Pezzoli SS, Hintz RL, Thorner MO. (1998). Recovery of growth hormone release from suppression by exogenous insulin-like growth factor I: evidence for a suppressive action of free rather than bound IGF-I. J Clin Endocrinol Metab 83(8):2836-42. DOI: 10.1210/jcem.83.8.5040
- Johannsson G, Marin P, Lonn L, Ottosson M, Stenlof K, Bjorntorp P, Sjostrom L, Bengtsson BA. (1997). Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. J Clin Endocrinol Metab 82(3):727-34. DOI: 10.1210/jcem.82.3.3809
Join the free community:
Men: Iron Forge Brotherhood
Women: Powerhouse Fitness
If this is the kind of information you want access to on a daily basis, the community is free and there are full courses on training, nutrition, hormones, and supplementation inside. You can ask questions and post your own labs and get feedback from me and from the community.