Fragment 176-191 & Mod GRF 1-29 & Ipamorelin Peptide Blend

Modified GRF 1-29 is a truncated version of Growth Hormone-Releasing Hormone (GHRH). Unlike GHRH, Mod GRF 1-29 is not a full-length peptide but rather a shorter version containing only 29 amino acids. In Mod GRF 1-29, four of the original amino acids have been modified, to enhance its stability. These modifications serve to make the molecule more resistant to degradation by dipeptidyl peptidase-4 (DPP-4) enzymes, which would otherwise break down the peptide structure. By reducing susceptibility to enzymatic degradation, these modifications may potentially increase the peptide’s half-life and improve its pharmacokinetics.⁽¹⁾

Ipamorelin is a synthetic pentapeptide, falling under the growth hormone secretagogue receptor (GHSR) agonist category. The peptide was derived from GHRP-1, which in turn is an analog of met-enkephalin, but potentially may not possess affinity to the opioid receptors. It appears to activate the ghrelin receptors (GHSR) which appear to trigger growth hormone synthesis.

Fragment 176-191, as the name implies, is a small ‘fragment’ of the growth hormone (hGH), also referred to as the “fat-burning peptide” for its potential in that area.⁽²⁾ Fragment 176-191 peptide, composed of 16 amino acids, including the last 15 amino acids from 177 to 191 found in hGH, has tyrosine added at the N-terminus (beginning). The peptide is also known as AOD 9604.⁽³⁾

Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and Lipolytic Action

The peptide in the blend that is believed to possess the most potent lipolytic (fat-breaking) action is likely Fragment 176-191. In one study,⁽²⁾ obese experimental murine models were subjected to the peptide for two consecutive weeks. After the completion of the study, it was noted that there appeared to be a significant reduction in the body weight of these murine models, including a reduction of excess body lipids. These results were deemed correlated to the increased concentration of the lipolytic ß3-AR receptors, indicating the peptides may work via the beta-adrenergic pathway. Further studies were conducted on the experimental mice with knocked-out lipolytic receptors. The peptide mice were reported to have experienced considerable weight loss, suggesting that the peptide may not depend on the lipolytic receptors to exert any action. Instead, it may possibly produce some fat-burning action via energy expenditure and fat oxidation. As per M Heffernan and his team, “this study demonstrates that the lipolytic actions of both hGH and AOD9604 are not mediated directly through the beta(3)-AR although both compounds increase beta(3)-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.” ⁽²⁾

Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and the Pituitary Gland

One review of the available literature⁽⁵⁾ suggested that these peptides appeared to yield various physiological changes, including “increase lean body mass, reduce fat mass, increase exercise tolerance and maximum oxygen uptake, enhance muscle strength, and improve linear growth…” in obese test models.⁽⁵⁾ While Fragment 176-191 was suggested to exert its potential action for weight loss via peripheral mechanisms, the aforementioned observation in the review are related to the apparent central action of peptides like Mod GRF 1-29 and Ipamorelin on the pituitary gland.

For example, Ipamorelin appears to work by potentially binding to the GHS-R1a receptor, also known as the growth hormone secretagogue receptor type 1a, which is found in the pituitary gland and the hypothalamus. Upon binding, this receptor activation may trigger a series of intracellular events that potentially culminate in the release of stored growth hormone from somatotroph cells (GH-producing cells) in the anterior pituitary. The apparent activation of the GHS-R1a receptor by Ipamorelin may lead to increased intracellular calcium ions through the phospholipase C pathway. The elevated calcium levels may prompt the secretory vesicles inside somatotropic cells to release growth hormone.

On the other hand, Mod GRF 1-29 appears to interact with the GHRH receptors on somatotrophs in the anterior pituitary gland. Upon binding to the GHRH receptors, Mod GRF 1-29 appears to instigate a cascade of intracellular signaling events. One of the key pathways activated appears to be the adenylyl cyclase pathway. Activation of this pathway may result in the conversion of ATP (adenosine triphosphate) into cAMP (cyclic adenosine monophosphate). This rise in cAMP appears to activate protein kinase A (PKA), which then may lead to the phosphorylation of various proteins, including voltage-dependent calcium channels on the cell membrane. The subsequent opening of these calcium channels potentially facilitates the influx of calcium ions into the somatotropic cells. Elevated intracellular calcium concentrations, in turn, appear to prompt the secretory vesicles inside these cells to release growth hormone into the bloodstream. It is posited that through this series of intracellular events that Mod GRF 1-29, upon binding to GHRH receptors, the peptide might facilitate the release and synthesis of growth hormone. The combination of Mod GRF 1-29 with certain growth hormone-releasing peptides like Ipamorelin, may potentially lead to a synergistic action, apparently amplifying the release of growth hormone.

Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and Fat Burning

In 2004, a clinical trial⁽⁶⁾ was launched, consisting of 300 obese test subjects. All these subjects were presented with the Fragment 176-191 peptide for 12 consecutive weeks. All subjects were divided into 6 groups – one group was presented with saline placebo, and the rest were given different peptide concentrations. After 12 weeks, when the subjects were examined, the group presented with the minor concentration appeared to exhibit the highest reduction in subject body weight (up to an average of 2.8 kilograms). Moreover, the trial also suggested that the peptide may have helped to improve these candidates’ cholesterol profiles and glucose tolerance levels. As per Chris Belyea, “The evidence from the trial is that over 12 weeks AOD9604 induces competitive weight loss with accompanying health benefits at a low dose and has superior tolerability.” ⁽⁶⁾

Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and Regeneration

In one 2015 study,⁽⁷⁾ 32 experimental rabbits were enrolled and divided into four groups of eight. All four groups were presented with placebo, Fragment 176-191 peptide, hyaluronic acid, or a combination of the peptide and hyaluronic acid. This study was conducted for approximately 7 weeks. After the completion of the study, all rabbits were examined for cartilage damage. Among all groups, the rabbits presented with the peptide and hyaluronic acid combination appeared to exhibit minor cartilage degeneration. The report concluded that “Intra-articular AOD9604 [administration] using ultrasound guidance enhanced cartilage regeneration, and combined AOD9604 and HA [administration] were more effective than HA or AOD9604 [doses] alone in the collagenase-induced knee OA rabbit model.” ⁽⁷⁾

Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend and Bone Mineralization

Considering the different peptides in the blend, Ipamorelin appears to be the one with a potential for improving bone mass and mineralization in experimental models. Preliminary experiments on murine models suggest that Ipamorelin may have mitigated the loss of muscle strength, which can occur in artificially-induced catabolic conditions.⁽⁸⁾ The researchers also commented that introduction of the peptide appeared to have increased bone mineralization in the murine models subjected to a combination of Ipamorelin and catabolism-inducing agents, in contrast to the control group receiving only catabolism-inducing agents.

Other trials on experimental murine models also suggest that Ipamorelin may elevate bone mineral content, pointing toward denser and more robust bone formation.⁽⁹⁾ The researchers utilized dual X-ray absorptiometry (DEXA) to observe the potential impact of Ipamorelin on bone mineral density in real-time, focusing on areas like the femur and L6 vertebrae. Post-research, the femurs of the murine subjects were analyzed using mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. The DEXA observations hint at a possible increase in tibial and vertebral BMC (bone mineral content) due to the peptide, differing from the control group. Additionally, the pQCT findings imply that the enhanced cortical BMC might stem from an expanded cross-sectional bone area, suggesting that the femur and L6 vertebrae could have seen heightened bone mineralization.

Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend and Appetite

Ipamorelin appears to activate the ghrelin receptors in the pituitary (GHSR1a) but may also trigger the receptors for ghrelin in other systems. Considering its potential impact on ghrelin receptors, Ipamorelin may enhance appetite, possibly leading to weight gain. Research indicates that Ipamorelin might have contributed to an approximate 15% increase in the body weight of murine models.⁽¹⁰⁾ Some theories suggest that Ipamorelin may have proportionally increased fat pad weights relative to total body weight, resulting in a noticeable rise in body fat, as detected by DEXA. Additionally, there are hints that Ipamorelin may have boosted serum leptin levels, a hormone associated with energy and appetite control. As a result, researchers theorize that murine models in the Ipamorelin groups could have consumed more food, leading to the observed weight gain.