IGF-1 LR3 (Insulin-like growth factor-1 long arginine 3)

IGF-1 - Insulin-like growth factor 1 (IGF-1) is a hormone that functions as the major mediator of growth hormone (GH)-stimulated somatic growth, as well as a mediator of GH-independent anabolic responses in many cells and tissues. IGF-1 is a small peptide (molecular weight 7647) that circulates in serum bound to high affinity binding proteins. IGF-1 is an unusual peptide in this regard since it is more than 99 percent protein-bound.

IGF-1 is synthesized by multiple mesenchymal cell types. As a result, there are two major mechanisms of IGF-1 regulation:

❖ IGF-1 which is synthesized in the liver and secreted into the blood is under the control of GH (growth hormone release stimulates the liver to produce IGF-1).
❖ Autocrine/paracrine IGF-1 is synthesized in peripheral tissues, such as bone. Its synthesis is controlled by GH and by factors that are secreted locally by the surrounding cell types. Some of the secreted autocrine/paracrine IGF-1 enters into the systemic circulation. Therefore, understanding the regulation of autocrine/paracrine synthesis of IGF-1 is necessary to interpret changes in serum IGF-1 concentrations.

IGF-1 exerts its effects via activation of the IGF-1 receptor [1]. This receptor is widely distributed, which enables blood-transported IGF-1 to coordinate balanced growth among multiple tissues and organs. In contrast, autocrine/paracrine IGF-1 can stimulate local, unbalanced growth independently of systemic GH. Examples of this type of growth regulation are wound healing and growth of the contralateral kidney after unilateral nephrectomy.

IGF-1 LR3 - is a synthetic protein and lengthened analog of human insulin-like growth factor 1 (IGF-1). It differs from native IGF-1 in that it possesses an arginine instead of a glutamic acid at the third position in its amino acid sequence ("arginine 3"), and also has an additional 13 amino acids, for a total of 83 amino acids (relative to the 70 of IGF-1). The results of these modifications are that IGF-1 LR3 retains the pharmacological activity of IGF-1 as an agonist of the IGF-1 receptor, has a very low affinity for the insulin-like growth factor-binding proteins (IGFBPs), and has improved metabolic stability. As a result, it is approximately three times more potent than IGF-1 and possesses a significantly longer half-life of about 20–30 hours (relative to IGF-1's half-life of about 12–15 hours).

We have the highest levels of IGF-1 during the pubescent years and the lowest levels during old age (and infancy). When IGF-1 along with GH decreases w/ age it triggers increased cellular cortisol, and sarcopenia, and causes decreased glucose sensitivity.

Clinical Pearls:
❖ We air on the side of caution with IGF-1 LR3 as too much IGF-1 has been linked to many cancers. Not as the cause of the cancer. The concern is if IGF-1 increases the proliferation of cells then we obviously do not want to exacerbate that in a patient who has cancer or a precancerous condition. The same goes for GH.
❖ Check IGF-1 levels during initial labs to get a baseline. If using IGF-1 LR3, or any growth hormone-releasing peptides we suggest performing follow-up labs every 3-4 months if you feel the need.
❖ MK-677 also stimulates IGF-1 production
❖ Even though we are not aiming to hit supraphysiologic levels of GH production or IGF-1 production it is best to check patient’s IGF-1 levels 3-4 times/year if they are taking growth hormone-releasing peptides.
➢ We have strategically designed the protocols to not be aggressive with these peptides, by not using them for prolonged periods without a break. Always exercise good clinical judgment.
❖ Be selective with which patient’s you are using this.

Customary Dosing:
❖ Inject 25-40mcg SubQ every other day (not available at this time coming soon)
❖ Current Advitam protocol:
➢ Males: 75mcg sublingual troche every other day x 4 weeks
➢ Females: 50mcg sublingual troche every other day x 4 weeks