Peptides
CJC-1295 & Ipamorelin Blend (10mg)
Ipamorelin and CJC-1295 are both considered to be growth hormone secretagogues. Ipamorelin is a synthetic pentapeptide,(1) and CJC-1295 peptide consists of 29 amino acids.(2) Ipamorelin appears to fall into a category of peptides classified as growth hormone secretagogues (GHSs). These are peptides that are assumed to stimulate the release of the growth hormones, however are not considered growth hormone releasing peptides themselves. On the other hand, CJC-1295 has also been suggested by researchers to stimulate the release of growth hormone, primarily by mimicking the actions of the naturally occurring growth hormone-releasing hormone (GHRH). Both Ipamorelin and CJC-1295 peptides have been assigned by researchers to this class, studied for similar potential actions and apparently differing only in terms of their half-life and pharmacokinetic profiles. Overview CJC-1295 & Ipamorelin peptides both are suggested by researchers to augment the levels of the growth hormones through a possible triggering of the anterior pituitary gland. Scientists consider that once triggered, growth hormones may be naturally secreted, maintaining levels of growth hormones in the organism.(3) CJC-1295 peptide is a tetrasubstituted version of GHRH 1-29, developed to represent the shortest functional sequence of GHRH. GHRH 1-29 consists of the first 29 amino acids of the native GHRH peptide, and may potentially stimulate growth hormone production in pituitary gland cells, called somatotrophs. The peptide has four amino acid substitutions in its structure, which scientists suggest may enhance its activity and resistance towards proteolytic enzymes. More specifically, the amino acids which are replaced appear to be the 2nd, 8th, 15th, and 27th amino acids. Owing to these substitutions, the peptide might be able to bind covalently to blood albumin, with trace amounts possibly able to bind to fibrinogen and immunoglobulin G (IgG). As a result, the apparent half-life of the peptide may increase from 10 mins to 30 mins.(4) This may lead to elevated levels of plasma growth hormone and insulin-like growth factor 1 (IGF-1). CJC-1295 might also be linked with the purported drug affinity complex (DAC) element, which may attach to plasma proteins. In particular, the DAC element in CJC-1295 alludes to the connection of N-epsilon-3-maleimidopropionamide derivative of lysine at the C-terminal end. Merging the tetrasubstituted amino acid chain and the DAC element, CJC-1295 appears to display enhanced pharmacokinetics yet retains a comparable attraction to the GHRH receptors in the pituitary gland, similar to natural GHRH.(5) More specifically, researchers comment that when the peptide was “selected for further pharmacokinetic evaluation, where it was found to be present in plasma beyond 72 h.” Ipamorelin is a man-made pentapeptide, also known as NNC 26-0161, that is believed to associate with a specific receptor in the pituitary gland cells, termed the growth hormone secretagogue receptor (GHS-R1a). These receptors are considered to be located in the hypothalamus. Moreover, GHS-R1a is often referred to as the ghrelin receptors because ghrelin seems to be its primary natural ligand. Ipamorelin appears to stand out from other GHSs as a potentially more selective compound, which may possibly stimulate the release of GH levels by somatotroph cells without also increasing other hormones produced by the anterior pituitary gland, such as prolactin. When the peptide blend, sometimes also called the peptide stack, is presented in combination, research studies typically report that the Ipamorelin exerts initial action, exhibiting some sign of impact within the first two hours of presentation, and as it starts to wean off, the CJC-1295 peptide may gradually supplement action.(6) Chemical Makeup Molecular Formula: CJC-1295: C152H252N44O42 Ipamorelin: C38H49N9O5 Molecular Weight: CJC-1295: 3367.9 g/mol Ipamorelin: 711.8 g/mol Other Known Titles CJC-1295: CJC-1295 NO DAC; Mod GRF 1-29 Ipamorelin: NNC 26-0161 Research and Clinical Studies CJC-1295 & Ipamorelin Blend and Half Life Determination Clinical studies have been conducted on test subjects to determine the half life of and individual pharmacokinetic profiles of the two peptides. In one late 1990s study,(6) a clinical trial was conducted on eight male test subjects with a concentration escalation design. The level of growth hormones was monitored after every instance of peptide presentation. At the end of the study, it was suggested by the researchers that there was a single episode of growth hormone release with the highest peak at 0.67 hours, after which there was an exponential decline up to negligible concentrations of the compound. This study concluded that the Ipamorelin peptide appeared to exhibit a short half-life of 2 hours, after which the potential action appears to begin to decline. CJC-1295, by contrast, appears to have a much longer half-life. Researchers comment that a single introduction of the peptide may upregulate growth hormone production by somatotrophs for prolonged periods of time, thus apparently contributing “to an overall increase in [growth hormone] secretion … by 46%” and also potentially upregulating its main anabolic mediator insulin-like growth factor-1 (IGF-1) by 45% on average.(7) Another publication also observes that CJC-1295 may potentially upregulate “[growth hormone] concentrations by 2- to 10-fold,” and estimates that the half-life of the peptide ranges between 5.8 – 8.1 days.(8) CJC-1295 & Ipamorelin Blend General Research In this early 2000s study,(7) a clinical trial was conducted on male test subjects aged between 20 and 40 years old. Test subjects were divided into two groups; one group was presented with the placebo and the other with the peptide. Blood was sampled from the subjects one week before and after the presentation of CJC-1295 peptide (and placebo) to monitor the levels of growth hormone pulsatility. At the end of the study, it was suggested that CJC-1295 contributed to a 7.5-fold increase in the growth hormone pulsatility levels as compared to that of the placebo. Apart from apparently affecting the synthesis of growth hormone, scientists also suggest that CJC-1295 may interact with the survival and proliferation of the cells that synthesize it - the somatotroph cells in the anterior pituitary gland.(9) In one study on murine models, the authors commented that "CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images.” To exert these apparent effects, CJC-1295 appears to interact with specific binding sites on the GHRH receptor protein, leading to conformational changes in the receptor structure and potentially initiating a cascade of molecular events. The binding appears to activate intracellular signaling proteins that potentially act as molecular toggles.(10) These proteins are often referred to as G-proteins, which, upon activation, might drive the generation of secondary messengers like cyclic adenosine monophosphate (cAMP) or inositol trisphosphate (IP3.(11) Secondary messengers such as cAMP may set in motion protein kinases, enzymes believed to alter distinct proteins. These kinases possess a modulatory capacity for cellular activities and might phosphorylate transcription regulators, or proteins overseeing gene modulation. Once phosphorylated, these transcription regulators could migrate into the nucleus of somatotroph cells, possibly impacting genes associated with growth hormone formation.(7) On the other hand, Ipamorelin appears to interact with the anterior pituitary gland cells via the N-terminus of GHS-R1a, which has binding sites that appear to recognize specific sequences in the secretagogue. When Ipamorelin meets this receptor, it may attach in a non-permanent way through forces like hydrogen bonds and forces between molecules called van der Waals forces. This attachment might make the receptor change its shape, which could start cell signals, mainly those involving G-proteins. GHS-R1a might work with a specific part of G-proteins called Gαq/11.(12) A main process started by GHS-R1a involves an enzyme called phospholipase C (PLC). Gαq/11 interacts with PLC, which may split a fat-like molecule, phosphatidylinositol 4,5-bisphosphate (PIP2), into two messaging molecules: IP3 (Inositol trisphosphate) and DAG (Diacylglycerol). IP3 appears to attach to places on a cell part called the endoplasmic reticulum, causing calcium ions (Ca2+) to be released. Also, DAG might turn on an enzyme called protein kinase C (PKC), which may add phosphate groups to other signaling molecules. All these steps might end with the ‘turning on’ of proteins that help release growth hormone from certain cells in the pituitary gland.(13) CJC-1295 & Ipamorelin Blend and Nitrogen Balance The apparent synergistic action of CJC-1295 and Ipamorelin on the production of growth hormone by the somatotroph cells in the anterior pituitary gland appears to result in a positive nitrogen balance and potential increase in lean mass in test models. In a particular study, investigators sought to probe the metabolic capabilities of Ipamorelin within the context of certain hepatic markers related to alpha-amino-nitrogen processing during an artificlaly triggered catabolism. The team evaluated the liver's ability to produce urea-N (CUNS), a potential metric of nitrogen processing within the liver. They examined the observable levels of messenger RNA (mRNA) linked to enzymes of the urea cycle in the liver, gauged the overall nitrogen equilibrium, and postulated the nitrogen quantities in different organs. It was proposed that Ipamorelin might have led to a 20% decline in CUNS, in contrast to the catabolic condition that was artificially prompted by the researchers. Moreover, it could have conceivably decreased the manifestation of urea cycle enzymes, reinstated nitrogen equilibrium, and theoretically adjusted or enhanced the nitrogen values in organs.(14) CJC-1295 & Ipamorelin peptide blend is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. doi: 10.1530/eje.0.1390552. PMID: 9849822. https://pubmed.ncbi.nlm.nih.gov/9849822/ Lucie Jette et al, hGRF1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long Lasting GRF Analog, ResearchGate, January 2005. Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. doi: 10.1530/eje.0.1390552. PMID: 9849822 https://pubmed.ncbi.nlm.nih.gov/9849822/ The Discovery of Growth Hormone-Releasing Hormone: An Update https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2826.2008.01740.x Jetté, L., Léger, R., Thibaudeau, K., Benquet, C., Robitaille, M., Pellerin, I., Paradis, V., van Wyk, P., Pham, K., & Bridon, D. P. (2005). Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology, 146(7), 3052–3058. https://doi.org/10.1210/en.2004-1286 Gobburu JV, Agersø H, Jusko WJ, Ynddal L (September 1999). “Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers”. Pharmaceutical Research. 16 (9): 1412–6. doi:10.1023/A:1018955126402 Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006 Dec;91(12):4792-7. doi: 10.1210/jc.2006-1702. Epub 2006 Oct 3. PMID: 17018654. https://pubmed.ncbi.nlm.nih.gov/17018654/ Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006 Mar;91(3):799-805. doi: 10.1210/jc.2005-1536. Epub 2005 Dec 13. PMID: 16352683. https://pubmed.ncbi.nlm.nih.gov/16352683/ Alba, M., Fintini, D., Sagazio, A., Lawrence, B., Castaigne, J. P., Frohman, L. A., & Salvatori, R. (2006). Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. American journal of physiology. Endocrinology and metabolism, 291(6), E1290–E1294. https://doi.org/10.1152/ajpendo.00201.2006 Martin, B., Lopez de Maturana, R., Brenneman, R., Walent, T., Mattson, M. P., & Maudsley, S. (2005). Class II G protein-coupled receptors and their ligands in neuronal function and protection. Neuromolecular medicine, 7(1-2), 3–36. https://doi.org/10.1385/nmm:7:1-2:003 Newton, A. C., Bootman, M. D., & Scott, J. D. (2016). Second Messengers. Cold Spring Harbor perspectives in biology, 8(8), a005926. https://doi.org/10.1101/cshperspect.a005926 Yin, Y., Li, Y., & Zhang, W. (2014). The growth hormone secretagogue receptor: its intracellular signaling and regulation. International journal of molecular sciences, 15(3), 4837–4855. https://doi.org/10.3390/ijms15034837 Bill, C. A., & Vines, C. M. (2020). Phospholipase C. Advances in experimental medicine and biology, 1131, 215–242. https://doi.org/10.1007/978-3-030-12457-1_9 Aagaard, N. K., Grøfte, T., Greisen, J., Malmlöf, K., Johansen, P. B., Grønbaek, H., Ørskov, H., Tygstrup, N., & Vilstrup, H. (2009). Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 19(5), 426–431. https://doi.org/10.1016/j.ghir.2009.01.001 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
CJC-1295 DAC (5mg)
CJC-1295 DAC is a peptide that researchers posit may function similarly to growth hormone-releasing hormone (GHRH), potentially increasing the endogenous production of growth hormone (GH) within the organism. The CJC-1295 DAC peptide is a synthetic 29 amino acid analog of GHRH.(1) It is the shortest functional analog of GHRH that still has the potential capacity to trigger GH release from the somatotroph cells in the pituitary gland. Moreover, 4 of the original 29 amino acids in this fragment are substituted in CJC-1295 DAC, to possibly improve the pharmacokinetics of the peptide and prolong its half-life. The DAC component is a biochemical complex that may further increase the half-life of the peptide. This phenomenon might be ascribed to the alleged capability of the DAC to bind to proteins present in plasma. More precisely, the DAC component appears to entail the attachment of a lysine derivative, identified as N-epsilon-3-maleimidopropionamide, to the C terminus of CJC-1295 DAC. Integrating this modified amino acid sequence with the DAC component might conceivably enhance the pharmacokinetics of CJC-1295 DAC, extending its half-life to approximately 8 days. Simultaneously, it appears to maintain a significant affinity for GHRH receptors, similar to the affinity exhibited by CJC-1295 without DAC.(2) This does not imply that CJC without DAC has no relevance or use in present day research. For example, CJC-1295 without DAC & Ipamorelin blend has been studied for its suggested synergistic potential, as combining GHRH analogs with peptides that appear to activate the ghrelin receptors in the pituitary gland. It is also posited to result in greater GH-synthesis response from the somatotroph cells.(3) Overview CJC-1295 DAC is recognized by many names: CJC-1295, CJC-1295 with DAC, DAC:GRF, long-acting GHRH analog, and synthetic GHRH analog. Theoretically, as the peptide is considered a releasing factor for growth hormone, CJC-1295 DAC has been studied for its potential role in: The reduction of fat mass by using fat cells as an energy source. It may lead to increased muscle mass via the promotion of protein synthesis. Since growth hormone is considered to promote bone growth and improved joint and connective tissue, CJC-1295 DAC peptide may potentially improve bone mass and thereby reduce the risk of damage. Studies have suggested that GHRH may support the centers in the nervous system for sleep, and potentially this action may be mirrored by analogs like CJC-1295 DAC.(4) Chemical Makeup Molecular Formula: C152H252N44O42 Molecular Weight: 3367.95 g/mol Other Known Titles: Tetrasubsituted GRF 1-29 with DAC Research and Clinical Studies CJC-1295 DAC Peptide Mechanism of Action Researchers conducted two clinical studies in 2006 to examine the action of CJC-1295 DAC. In the first study, CJC-1295 DAC or a placebo was presented in one of four ascending concentrations. In the second study, CJC-1295 DAC was presented repeatedly at a single concentration. According to the results, after the introduction of CJC-1295 DAC, there appeared to be an increase in GH and insulin-like growth factor-1 (IGF-I) levels among the research models.(5)CJC-1295 DAC is thought to elevate levels of IGF-1 by increasing growth hormone production, which in turn may bind to receptors on liver cells, potentially triggering a cascade of intracellular signaling processes. This binding might activate the Janus kinase-signal transducer and activator of the transcription (JAK-STAT) signaling pathway. Subsequently, the activated STAT proteins might migrate to the nucleus, where they may attach to specific DNA sequences considered to be response elements, potentially resulting in the transcription of the IGF-I gene. It is theorized that the IGF-I produced in liver cells may be transported to various target tissues. Additionally, it is believed that many tissues possess GH receptors, which, upon activation, may lead to the production of IGF-I within the tissues themselves. IGF-I is considered a potent hormone that may play a key role in promoting growth, suggesting it mediates many growth and anabolic effects of growth hormone. It is hypothesized to encourage cell growth and proliferation, as well as the enlargement and strengthening of tissues and organs, possibly aiding in protein synthesis and cellular expansion. Preliminary exposure to CJC-1295 DAC in experimental models has been suggested to significantly affect average growth hormone levels, with studies reporting an apparent increase of 2- to 10-fold for 6 days or possibly longer. Moreover, CJC-1295 DAC has been suggested to lead to dependent increases in average IGF-I levels by 1.5- to 3-fold for about 9–11 days, with suggestions that IGF-I levels may remain high for at least two weeks in experimental models. Following repeated exposure to CJC-1295 DAC, average IGF-I levels appear to remain elevated above baseline for up to 28 days. Notably, data suggests a cumulative effect following repeated exposure of the compound.(5) In 2006, another group of scientists assessed the GH pulsatility after a single occurrence of CJC-1295 DAC. They found out that there appeared to be an increase of about 50% in mean GH secretion and IGF-I levels after a single presentation of CJC-1295 DAC.(6) Researchers have suggested that the peptide might contribute to an increase in peak growth hormone levels by as much as 7.5 times in the models studied.(6) It seems that CJC-1295 DAC may interact with certain binding sites on the growth hormone-releasing hormone (GHRH) receptor protein. This interaction may lead to changes in the receptor's structure, potentially triggering a series of molecular processes. This interaction is believed to stimulate specific intracellular signaling proteins, often referred to as G-proteins.(7) Upon activation, these proteins may promote the production of secondary messengers, such as cyclic adenosine monophosphate (cAMP) or inositol trisphosphate (IP3), which are considered to play crucial roles in cellular signaling pathways.(8) Secondary messengers, including cAMP, are thought to activate protein kinases, which are enzymes considered capable of modifying specific proteins. These kinases are considered able to regulate cellular functions by phosphorylating transcription regulators, the proteins responsible for controlling gene expression. Once phosphorylated, these transcription regulators are speculated to move into the nucleus of somatotroph cells, where they might influence the genes involved in the production of growth hormone. This intricate cascade of events highlights the potential of CJC-1295 DAC to modulate growth hormone levels through a complex network of molecular interactions. Additional animal studies were conducted to evaluate the potential of CJC-1295 DAC. One study evaluated murine models presented with either the peptide or a placebo. The researchers concluded that exposing the murine models daily CJC-1295 DAC might completely normalize growth. Another finding was that CJC-1295 DAC presented every 2 or 3 days appeared to produce intermediate results, indicating a probable interval-dependent action.(9) Furthermore, this study suggests that CJC-1295 DAC might potentially impact body composition, seemingly by increasing muscle tissue hypertrophy while not impacting, or even possibly reducing, fat tissue levels. The murine models in this study appeared to have a deletion of the GHRH gene (referred to as GHRHKO); observations suggested that CJC-1295 DAC may boost GH synthesis, leading to a beneficial alteration in body composition. Exposure to CJC-1295 DAC in these GHRHKO murine models appeared to preserve normal levels of lean mass, unlike in models that were not exposed and exhibited suboptimal lean mass levels. Furthermore, the amount of subcutaneous fat mass stayed consistent with control levels in all groups associated with the peptide, whereas GHRHKO murine models without CJC-1295 DAC exposure exhibited signs of increased fat levels. This indicates that CJC-1295 DAC might positively affect muscle and bone structure without promoting an increase in fat accumulation. Additionally, the study noted a possible increase in pituitary RNA and GH mRNA levels following CJC-1295 DAC exposure, suggesting an enhanced presence of somatotroph cells—those believed to produce growth hormone in the pituitary gland. The authors commented that "CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images.” (9) CJC-1295 DAC Peptide Half-life In its original form, CJC-1295 DAC uses a technology referred to as Drug Affinity Complex (DAC).(1) Contrary to GHRH, which is considered to boast a half-life of approximately 7 minutes, researchers report CJC-1295 without DAC to exhibit a longer half-life of 30 minutes due to its truncated 29 amino acid fragment, and 4 of the original amino acids in this fragment are replaced. Alterations to the peptide structure, specifically at the 2nd, 8th, 15th, and 27th amino acid positions, are thought to potentially improve the peptide's stability against breakdown by the enzyme dipeptidyl peptidase-4. These alterations are detailed as follows: At the 2nd position, L-alanine is substituted by D-alanine, a change believed to bolster resistance against enzymatic degradation. At the 8th position, asparagine is replaced with glutamine, a modification that might reduce the risk of asparagine rearrangement and amide hydrolysis. The substitution of glycine with alanine at the 15th position is theorized to enhance the peptide's bioactivity. The alteration from methionine to leucine at the 27th position is considered to potentially prevent methionine oxidation. These modifications aim to enhance the peptide's resilience and functional efficacy by mitigating enzymatic degradation and improving stability under physiological conditions. In addition, the half-life of the peptide appears to be additionally extended to 6-8 days due to the DAC technology.(10) CJC-1295 DAC Peptide Ancillary Studies In 2005, a clinical study aimed to evaluate the mechanism of action of CJC-1295 DAC in models of immunodeficiency virus (HIV) associated with visceral obesity. In this study, the models would be presented with CJC-1295 DAC for 3 months, followed by a 6-week follow-up period. However, this study was terminated during recruitment, and no related results were posted.(11) According to a 2009 Norwegian study, a compound was submitted for analysis to evaluate whether it contained prohibited substances or not. The researchers of the Norwegian Doping Control Laboratory and School of Pharmacy reported that this substance was CJC-1295 DAC. In their published article they concluded that "CJC-1295 DAC is a releasing factor for growth hormone".(1) CJC-1295 DAC peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Henninge J, Pepaj M, Hullstein I, Hemmersbach P. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug Testing and Analysis. 2010 Nov-Dec;2(11-12):647-650. DOI: 10.1002/dta.233. Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005 Jul;146(7):3052-8. doi: 10.1210/en.2004-1286. Epub 2005 Apr 7. PMID: 15817669. Sinha DK, Balasubramanian A, Tatem AJ, Rivera-Mirabal J, Yu J, Kovac J, Pastuszak AW, Lipshultz LI. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Transl Androl Urol. 2020 Mar;9(Suppl 2):S149-S159. doi: 10.21037/tau.2019.11.30. PMID: 32257855; PMCID: PMC7108996. Steiger A, Holsboer F. Neuropeptides and human sleep. Sleep. 1997 Nov;20(11):1038-52. PMID: 9456470. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006 Mar;91(3):799-805. doi: 10.1210/jc.2005-1536. Epub 2005 Dec 13. PMID: 16352683. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006 Dec;91(12):4792-7. doi: 10.1210/jc.2006-1702. Epub 2006 Oct 3. PMID: 17018654. Martin, B., Lopez de Maturana, R., Brenneman, R., Walent, T., Mattson, M. P., & Maudsley, S. (2005). Class II G protein-coupled receptors and their ligands in neuronal function and protection. Neuromolecular medicine, 7(1-2), 3–36. https://doi.org/10.1385/nmm:7:1-2:003 Newton, A. C., Bootman, M. D., & Scott, J. D. (2016). Second Messengers. Cold Spring Harbor perspectives in biology, 8(8), a005926. https://doi.org/10.1101/cshperspect.a005926 Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1290-4. doi: 10.1152/ajpendo.00201.2006. Epub 2006 Jul 5. PMID: 16822960. Van Hout MC, Hearne E. Netnography of Female Use of the Synthetic Growth Hormone CJC-1295: Pulses and Potions. Subst Use Misuse. 2016 Jan 2;51(1):73-84. doi: 10.3109/10826084.2015.1082595. Epub 2016 Jan 15. PMID: 26771670. ClinicalTrials.gov, A service of the US National Institutes of Health. Available at: http://clinicaltrials.gov/ct2/show/NCT00267527 (27 June 2010). Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Sermorelin (5mg)
Sermorelin is a 29 amino acid peptide, the shortest synthetically developed peptide that may potentially induce biological activity at the receptors for the growth hormone-releasing hormone (GHRH).(2) Sermorelin polypeptide is an analog of the GHRH factor consisting of GHRH (1-29 acid)-amide. Due to this structural and functional mimicry, Sermorelin has been studied across multiple branches of scientific research involving growth hormone deficiency models.(3) It was in the early 1980s that the action of Sermorelin, classified as a growth hormone-releasing fragment GHRF (1-29) amide, was first explored. Several research studies were conducted on rats where exogenous GHRF (1-29) amide was introduced in conscious and anesthetized rats. It was observed that the presence of GHRF appeared to stimulate the pituitary gland and promote growth. Following this theory, Sermorelin and similar compounds have become the subject of further research in growth hormone deficiency models.(4) Overview Sermorelin is suggested to be a growth hormone analog constituting the first 29 amino acids out of the usual 44 amino acids found in growth hormone-releasing hormone (GHRH). Researchers posit that Sermorelin binds with the GHRH receptors found on the pituitary gland and suggest further that the synthetic peptide may stimulate secretion of growth hormone (hGH). Thus, Sermorelin is believed to maintain the fundamental function of GHRH, possibly stimulating the GHRH receptors in the pituitary gland and leading to sporadic release of growth hormone despite its reduced amino acid sequence. This mechanism is thought to result in increased levels of insulin-like growth factor-1 (IGF-1), primarily recognized for its role in the anabolic actions of growth hormone. The estimated half-life of Sermorelin is around 11 to 12 minutes. A major potential advantage of the peptide is that due to its apparent GHRH receptor specificity, it may not induce any significant change in the levels of other endocrine markers such as prolactin, insulin, cortisol, glucose, or thyroid hormones.(6) Chemical Makeup Molecular Formula: C149H246N44O42S Molecular Weight: 3357.93 g/mol Other Known Titles: GRF 1-29 Research and Clinical Studies Sermorelin and GHRH Receptors Sermorelin is thought to interact with GHRH receptors through complex molecular mechanisms, possibly triggering various cellular signaling pathways. It is hypothesized that upon binding to the GHRH receptor, Sermorelin may alter the receptor's structure, potentially initiating a series of intracellular signaling events.(12) Some researchers propose that Sermorelin might enhance the production of cyclic adenosine monophosphate (cAMP) in specific cells. This enhancement may occur through the activation of adenylate cyclase, which is suggested to convert ATP into cAMP. Higher levels of cAMP might lead to the activation of protein kinase A (PKA), a key enzyme in cellular signaling processes. PKA might phosphorylate various target proteins, thereby initiating further cellular responses. The potential activation of the GHRH receptor by Sermorelin, along with the ensuing cAMP-PKA signaling cascade, is thought to possibly promote the secretion and distribution of growth hormone (hGH) from somatotroph cells in the pituitary gland. The secreted hGH is also believed to contribute to the synthesis of insulin-like growth factor-1 (IGF-1).(12) Sermorelin Peptide and Growth Velocity Researchers reported positive results in the idiopathic GH deficiency when Sermorelin was presented to underdeveloped animal models. Increased growth and height velocity rate was observed within 12 months of consistent, continuous peptide presence. These elevated levels were reported to be sustained for an average of 36 months after continuous presence.(7) Sermorelin Peptide and Anabolic Research Outcomes Preliminary findings from one investigation indicate that Sermorelin may lead to an 82% enhancement in average growth hormone levels, with actions persisting for approximately two hours.(13) A separate study conducted over 16 weeks hypothesizes that Sermorelin might elevate growth hormone levels by as much as 107%, and increase IGF-1 levels by about 28%.(14) The research further suggests a possible increase in lean body mass of approximately 2.78 lbs (1.26 kg), with no significant change in fat mass. These actions are tentatively attributed to the peptide's capacity to boost growth hormone levels, and in turn, IGF-1, which is considered a potential anabolic agent influencing growth hormone activity. The most noteworthy outcomes identified by the researchers include observations that there was “a gain of 1.26 ± 0.52 kg (P < 0.05) in LBM” and that “skin thickness increased significantly.” Sermorelin Peptide and Lipodystrophy Scientists carried out a controlled clinical study involving 31 HIV-positive subjects with lipodystrophy, to investigate the potential impact of Sermorelin.(8) All 31 subjects were divided into two groups, where one was presented with Sermorelin, and the other group with a placebo for 12 weeks. Following the study, it was suggested by the research team that growth hormone levels appeared significantly increased in Sermorelin subjects as compared to the ones given a placebo. Levels of insulin-like growth factor (IGF-1) had apparently increased – resulting in increased lean body mass in the peptide group. Abdominal visceral fat and the ratio of trunk to lower extremity fat were reported by the researchers to be significantly reduced. There was no other reported change in the glucose or insulin levels.(8) Sermorelin Peptide and Cognition In the early 2000s, clinical research studies were conducted with 89 subjects between 68 and 69 years of age to explore the correlation (if any) between tapering growth hormone release and impaired cognition. Scientists consider that with increasing age, levels of growth hormone naturally decline, which may result in reduced physiological functions, including cognition (i.e. ability to collect, process, and recollect information). Following the introduction of Sermorelin, it was observed that there was an apparent improved performance in the Wechsler Adult Intelligence Scale (WAIS) – i.e. improved IQ levels, picture arrangement tests, and verbal tests - amongst the test subjects.(9) Sermorelin Peptide and Tumor Cells A clinical study was designed where 1,018 glioma subjects were presented with over 4,000 compounds each, and following each presentation, a DRS was determined for all compounds, for each subject. Following the results of the study, it appeared that the Sermorelin compound reportedly induced the most sensitivity in the test subjects. Upon analysis, it was suggested by the researchers that this may be due to the potential of Sermorelin to block the tumor cell cycles, thereby possibly preventing tumor cell proliferation.(10) Sermorelin Peptide and Hypogonadism Initial research into the peptide suggested that Sermorelin might be impactful in increasing lean mass. One study sought to explore if Sermorelin had potential in hypogonadism (which is considered to stem from additional fat mass). Test models were divided into two groups where one group was presented with Sermorelin followed by GHRH 1-40, with a one week interval between the two compounds, whereas the other group was given the same combination in reverse order. Following the study, it was reported by the researchers that for both groups, the Sermorelin appeared to stimulate the release of FSH and LH, which might stimulate testosterone production. This initial research spawned additional studies, including one clinical study that included 19 male subjects, 9 of whom were aged between 22 and 33 years of age, and 10 were aged between 60 and 78 years of age. The more elderly subjects were presented with one of two concentrations of Sermorelin for a period of 28 days, with an interval of 14 days in between the two instances. Testosterone levels in the elderly subjects reportedly increased after the presentation of Sermorelin; however, it should be noted that the levels were not statistically significant. Furthermore, researchers suggested that elevated levels of growth hormones, possibly induced by Sermorelin presence, appeared to be at peak during the night time, for all test subjects, as compared during the day.(11) Sermorelin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Garcia JM, Merriam GR, Kargi AY. Growth Hormone in Aging. [Updated 2019 Oct 7]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. https://www.ncbi.nlm.nih.gov/books/NBK279163/?report=reader Prakash, A, and K L Goa. “Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency.” BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy vol. 12,2 (1999): 139-57. https://pubmed.ncbi.nlm.nih.gov/18031173/ National Center for Biotechnology Information. "PubChem Compound Summary for CID 16129620, Sermorelin" PubChem Clark, R G, and I C Robinson. “Growth induced by pulsatile infusion of an amidated fragment of human growth hormone releasing factor in normal and GHRF-deficient rats.” Nature vol. 314,6008 (1985): 281-3. https://pubmed.ncbi.nlm.nih.gov/2858818/ Drugs at FDA: FDA Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020443 Junichi I. et al, Growth hormone secretagogues: history, mechanism of action, and clinical development, JSCM Rapid Communications Vol. 3 Issue 1, 09 February 2020. https://onlinelibrary.wiley.com/doi/full/10.1002/rco2.9 Prakash, A, and K L Goa. “Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency.” BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy vol. 12,2 (1999): 139-57. https://pubmed.ncbi.nlm.nih.gov/18031173/ Koutkia, Polyxeni et al. “Growth hormone-releasing hormone in HIV-infected men with lipodystrophy: a randomized controlled trial.” JAMA vol. 292,2 (2004): 210-8. https://pubmed.ncbi.nlm.nih.gov/15249570/ Vitiello, Michael V et al. “Growth hormone releasing hormone improves the cognition of healthy older adults.” Neurobiology of aging vol. 27,2 (2006): 318-23. https://pubmed.ncbi.nlm.nih.gov/16399214/ Chang, Yuanhao et al. “A potentially effective drug for patients with recurrent glioma: sermorelin.” Annals of translational medicine vol. 9,5 (2021): 406. doi:10.21037/atm-20-6561. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033379/ Sinha, Deepankar K et al. “Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males.” Translational andrology and urology vol. 9,Suppl 2 (2020): S149-S159. doi:10.21037/tau.2019.11.30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108996/ Zhou, F., Zhang, H., Cong, Z., Zhao, L. H., Zhou, Q., Mao, C., Cheng, X., Shen, D. D., Cai, X., Ma, C., Wang, Y., Dai, A., Zhou, Y., Sun, W., Zhao, F., Zhao, S., Jiang, H., Jiang, Y., Yang, D., Eric Xu, H., … Wang, M. W. (2020). Structural basis for activation of the growth hormone-releasing hormone receptor. Nature communications, 11(1), 5205. https://doi.org/10.1038/s41467-020-18945-0 Vittone, J., Blackman, M. R., Busby-Whitehead, J., Tsiao, C., Stewart, K. J., Tobin, J., Stevens, T., Bellantoni, M. F., Rogers, M. A., Baumann, G., Roth, J., Harman, S. M., & Spencer, R. G. (1997). Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism: clinical and experimental, 46(1), 89–96. https://doi.org/10.1016/s0026-0495(97)90174-8 Khorram, O., Laughlin, G. A., & Yen, S. S. (1997). Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. The Journal of clinical endocrinology and metabolism, 82(5), 1472–1479. https://doi.org/10.1210/jcem.82.5.3943 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
CJC-1295 (Mod GRF 1-29) & Hexarelin Blend (10mg)
CJC-1295 (no DAC) and Hexarelin are research peptides that have been studied by researchers in the interest of learning more about growth hormone synthesis by pituitary cells. Many relevant scientific observations have been drawn from such studies. Specifically, these peptides appear to interact with different receptors on anterior pituitary gland cells and stimulate the synthesis and release of this hormone. Rather than interacting via the same receptors, CJC-1295 (no DAC) and Hexarelin belong to different classes of research peptides that interact with pituitary cells via different receptors. Previous research has suggested that simultaneous activation of both receptor types may initiate synergistic actions; hence, the combination of CJC-1295 (no DAC) and Hexarelin may be of interest to scientists. Chemical Makeup Other Known Titles CJC-1295 (no DAC): Modified GRF 1-29 Hexarelin: Examorelin, P-23905, and MF-6003 Molecular Weight: CJC-1295 (no DAC):9 g/mol Hexarelin:05 g/mol Molecular Formula: CJC-1295 (no DAC): C152H252N44O42 Hexarelin: C47H58N12O6 Research and Clinical Studies CJC-1295 (no DAC) Interactions with GHRH Receptors CJC-1295 (no DAC) and Hexarelin appear to interact with pituitary cells via different receptors. CJC-1295 (no DAC) may interact with the cells via the GHRH receptor, which is posited to be the main type of receptor on these cells regulating growth hormone synthesis. Normally, these receptors respond to the endogenous growth hormone-releasing hormone (GHRH), which has a 44-amino-acid structure. Researchers believe CJC-1295 (no DAC) may mimic that structure. This is suspected in part because the peptide consists of the first 29 amino acids from GHRH with four specific modifications. The first 29 amino acids are posited to retain a GHRH-receptor affinity while being a shorter molecule. Specifically, this is considered by said researchers to be the shortest molecule that may stimulate growth hormone release via the GHRH receptors. To further support the potential of CJC-1295 (no DAC), the peptide bears four modifications, which, according to researchers such as Jette et al., involve the amino acids at positions 2, 8, 15, and 27.(1) Specifically, the modifications involve replacements at: At position 2, alanine is replaced with D-alanine, which may make the peptide less susceptible to common proteolytic enzymes. At position 8, asparagine is replaced with lysine, introducing an extra positive charge that may subtly change the surface charge and potentially support stronger interaction with the GHRH receptor.s At position 15, histidine is replaced with D-phenylalanine, adding a second D-amino acid that may further slow enzymatic degradation. At position 27, cysteine is replaced with N-methylglycine (sarcosine), which may hinder specific peptidases from rapidly dismantling the peptide backbone. This may allow the peptide to remain active for longer and to produce a more sustained receptor signal, possibly. Despite these changes, the downstream signaling is thought to resemble that of endogenous GHRH. The peptide is hypothesized to activate adenylyl cyclase, leading to the conversion of ATP into cyclic AMP (cAMP). Rising cAMP levels may then activate protein kinase A, which is proposed to phosphorylate targets that open voltage-dependent calcium channels on pituitary somatotroph membranes. The resulting calcium influx may trigger vesicle fusion and promote the release of stored growth hormone. Apart from upregulating growth hormone release, the peptide may also upregulate the overall capacity for growth hormone synthesis. An experiment by Alba et al. suggests the peptide "caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images.”(2) This pattern suggests that the peptide may also potentially support somatotroph number and GH gene transcription. Hexarelin Interactions with GHS-R1a Rather than a GHRH analog, Hexarelin has been referred to by experts as a growth hormone secretagogue (GHS). This is a class of peptides that react with pituitary cells via a different set of receptors called the growth hormone secretagogue receptors 1a (GHS-R1a). Experimental work undertaken in laboratory settings by Bowers et al. and Yin et al. has suggested that GHS-R1a is also the main receptor for ghrelin, also referred to as the hunger hormone.(3)(4) When Hexarelin binds to these receptors, it may trigger a signaling cascade that looks different from GHRH-type peptides. One potential pathway involves activation of phospholipase C, which may then generate two second messengers: IP₃ and diacylglycerol (DAG). IP₃ is thought to release calcium from intracellular stores. At the same time, diacylglycerol may activate protein kinase C. Higher intracellular calcium, together with PKC activation, is then posited to support growth hormone release from somatotroph cells. Thu, the peptide appears to induce the release of growth hormone by a different mechanism, potentially complementary to those of GHRH-analogs like CJC-1295 (no DAC). CJC-1295 (no DAC) & Hexarelin Potential on Hormone Synthesis Experiments suggest that the growth hormone release induced by CJC-1295 (no DAC) & Hexarelin from pituitary cells may surpass the peaks typically observed in control settings. For example, an experiment with CJC-1295 (no DAC) by Khorram et al. suggests that this kind of peptide may raise growth hormone output from pituitary cells by roughly 70–100% over a 12-hour window in laboratory settings.(5) The authors observed the most pronounced peak in the first two hours after exposure. In their report, 2-hour integrated growth hormone secretion seemed to rise approximately 6-fold from about 200–300 to roughly 1,100–1,600 µg/L·min. Growth hormone released in this way may then bind to GH receptors on peripheral cells and possibly drive IGF-1 production, which is viewed as a key downstream mediator of growth hormone’s anabolic actions. In that experiment, mean IGF-1 levels appeared to increase by around 27% after prolonged CJC-1295 (no DAC) exposure. Similarly, research by Imbimbo et al. has suggested that Hexarelin itself may drive an increase in growth hormone release from pituitary cells. Compared with a baseline near 3.9 ng/mL under placebo conditions, Hexarelin seemed to push peak growth hormone levels up to about 55 ng/mL, where the response plateaued. The maximal stimulus appeared within 30–40 minutes, followed by a gradual fall back toward baseline over about four hours, with an estimated half-life in the range of 50–60 minutes. This pattern suggests a strong but short-lived growth hormone pulse after Hexarelin exposure. The scientists also observed that "plasma glucose, luteinising hormone, follicle-stimulating hormone, thyroid-stimulating hormone” were unaffected. CJC-1295 (no DAC) & Hexarelin Synergistic Potential Currently, there are no experiments conducted in laboratory settings that have evaluated a combination of CJC-1295 (no DAC) & Hexarelin. Yet, the research that is available has investigated blends between Hexarelin and other GHRH-analogs, such as the full-length GHRH, from which CJC-1295 (no DAC) is derived at length. Notably, several studies by Arvat et al. evaluated GHRH and Hexarelin individually or in a blend, and suggest that when pituitary cells are exposed simultaneously to Hexarelin and GHRH, activating both types of receptors may exert synergistic actions.(7) When each compound was exposed to research models alone, Hexarelin appeared to generate a much larger growth hormone synthesis measured as an area under the curve (about 2,200.8 ± 256.9 µg/L·h) than GHRH by itself (around 792.2 ± 117.6 µg/L·h). However, when both were combined, the reported growth hormone area under the curve rose to roughly 4,259.2 ± 308.0 µg/L·h. This is higher than the sum of the two single-agent responses, which the authors interpreted as a true synergistic potential. Taken together, findings like this are often viewed by researchers as potentially suggestive that a GHRH-type peptide and a GHS like Hexarelin may provide a stronger pituitary GH signal when both receptor systems are engaged at the same time. CJC-1295 (no DAC) & Hexarelin blend is available for research and laboratory purposes only. Please review our Terms and Conditions before ordering. References: Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005 Jul;146(7):3052-8.DOI: 10.1210/en.2004-1286. Epub 2005 Apr 7. PMID: 15817669. Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1290-4. doi: 10.1152/ajpendo.00201.2006. Epub 2006 Jul 5. PMID: 16822960. Bowers CY. History of the discovery of ghrelin. Methods Enzymol. 2012;514:3-32. doi: 10.1016/B978-0-12-381272-8.00001-5. PMID: 22975043. Yin Y, Li Y, Zhang W. The growth hormone secretagogue receptor: its intracellular signaling and regulation. Int J Mol Sci. 2014 Mar 19;15(3):4837-55. doi: 10.3390/ijms15034837. PMID: 24651458; PMCID: PMC3975427. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem 82.5.3943. PMID: 9141536. Imbimbo BP, Mant T, Edwards M, Amin D, Dalton N, Boutignon F, Lenaerts V, Wüthrich P, Deghenghi R. Growth hormone-releasing activity of hexarelin in humans. A dose-response study. Eur J Clin Pharmacol. 1994;46(5):421-5. doi: 10.1007/BF00191904. PMID: 7957536. Arvat E, Di Vito L, Gianotti L, Ramunni J, Boghen MF, Deghenghi R, Camanni F, Ghigo E. Mechanisms underlying the negative growth hormone (GH) autofeedback on the GH-releasing effect of hexarelin in man. Metabolism. 1997 Jan;46(1):83-8. doi: 10.1016/s0026-0495(97)90173-6. PMID: 9005975. Arvat, E., Gianotti, L., Di Vito, L., Imbimbo, B. P., Lenaerts, V., Deghenghi, R., Camanni, F., & Ghigo, E. (1995). Modulation of growth hormone-releasing activity of hexarelin in man. Neuroendocrinology, 61(1), 51–56. https://doi.org/10.1159/000126827 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
NAD+ (100mg / 250mg / 750mg)
NAD+ is an acronym for Nicotinamide Adenine Dinucleotide, an endogenous nucleotide that is considered to regulate primary functions such as metabolism, energy production, and DNA repair. It is also considered to act as a secondary messenger via calcium-dependent signaling mechanisms, possibly serving as an immunoregulatory component.(1)(2) NAD+ is considered by researchers to be naturally synthesized via the de novo mechanism of converting the amino acid tryptophan through several enzymatic steps. Researchers posit that there are five components to NAD+ synthesis, including tryptophan, nicotinamide, nicotinic acid, nicotinamide riboside, and nicotinamide mononucleotide.(3) Once synthesized, research suggests it exerts over 500 enzymatic reactions and cellular processes(12) to aid metabolic activities. Essentially, it is suggested to act as a coenzyme in redox functions, converted to NADH (the energy-carrying form of NAD+), which may involve other metabolic pathways. Overview Researchers have suggested Nicotinamide Adenine Dinucleotide (NAD+) to act as a coenzyme, with three major classes of enzymes including: Deacetylase enzymes in the sirtuin class (SIRTs) Poly ADP ribose polymerase (PARPs) enzymes, and Cyclic ADP ribose synthetase (cADPRS) Research suggests that each class of enzymes interacts with NAD+ in the following possible respects: SIRTs may stimulate mitochondrial homeostasis, stem cell regeneration, loss of stem cells, and nerve degeneration. PARPs, composed of 17 different enzymes, may act alongside NAD+ enzymes and synthesize poly ADP ribose polymers, which may lead to genome stability. cADPRS include CD38 and CD157, which are considered to be key immunological cells. cADPRS appears to hydrolyze NAD+ and thereby may stimulate stem cell regeneration and DNA repair, which may be important for maintaining cell cycles. Researchers suggest the above-mentioned enzymes to be NAD+ dependent enzymes, possibly acting based on the presence of Nicotinamide Adenine Dinucleotide (NAD). Researchers suggest that should all three enzymes be dependent on NAD+, they may potentially compete amongst themselves for bioavailability. It has been posited that the potential function of SIRTs, for instance, may lead to reduced PARPs activity and, thereby, potentially lead to weakened systems. Hence, it may be critical to maintain a balance between the availability and consumption of NAD+ to obtain optimal potential impact.(5) Chemical Makeup Molecular Formula: C21H27N7O14P2 Molecular Weight: 663.43 g/mol Other Known Titles: nicotinamide adenine dinucleotide Research and Clinical Studies NAD+ Peptide and Productive Aging Researchers suggest that NAD+ has two key intermediates: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Studies have indicated that these intermediates may be potent agents for promoting 'productive aging.' In a study,(7) normal-aging mice were exposed to the NMN intermediate for 12 months. Following the study, the researchers suggested that NMN may promote NAD+ synthesis in the mice. Peptide exposure may have been the catalyst for the observed reduced weight gain, increased energy metabolism, enhanced physical activity, improved lipid profile, and other physiological impacts in the mice. NAD+ Peptide and Neurodegenerative Activity Scientists consider mitochondrial dysfunction to lead to various functional limitations in the electron transport chain and ATP (energy) synthesis, possibly resulting in various neurodegenerative diseases. A study(8) was conducted where aged mice were exposed to NMN, a NAD+ intermediate, for 3 to 12 months. The study's main aim was to evaluate the potential impact of the peptide on mitochondrial respiratory processes, for which fluorescent NMN protein was presented to the mice models. After peptide introduction, the mitochondrial oxygen consumption rates in the nerve and brain cells of the mice were studied. Upon analysis, it was suggested that mitochondrial functions had been restored in the aged mice, suggesting that NMN may be immediately utilized by the cells to produce NAD+, exerting a possible positive impact. NAD+ Peptide and DNA Repair After Ischemic Stress The main aim of this study(11) was to determine the neuroprotective potential of Nicotinamide Adenine Dinucleotide against ischemic stress induced in mice. For this study, ischemic stress was induced in the neuronal cultures in rats via deprivation of oxygen and glucose for about 2 hours. NAD+ was directly replenished into the culture medium before or after the induced ischemic stress. After 72 hours of introducing NAD+ into the cultures, it was reported by the researchers that the DNA base excision repair activity (DNA BER), cell viability, and oxidative DNA damage repair appeared to be significantly improved, irrespective of whether Nicotinamide Adenine Dinucleotide was added before or after inducing the ischemic stress. Indeed, NAD+ appears crucial for DNA integrity, with studies focusing on the enzyme poly(ADP-ribose) polymerase (PAR polymerase or PARP), which might depend on NAD+ for activating DNA repair. In the event of DNA damage, it is thought that PARP might be triggered, potentially attaching itself to the DNA's damaged parts. Researchers suggest that PARP might utilize NAD+ molecules to add ADP-ribose units to itself and other proteins in a process known as PARylation, potentially aiding in the attraction and activation of other DNA repair proteins and thereby assisting in repairing DNA damage.(15) This PARylation may lead to the formation of PAR chains, which might signal the DNA repair systems to identify and address DNA damage. PARP is also considered to have a role in detecting and mending single-strand DNA breaks. If NAD+ is confirmed as a necessary cofactor, PARP may be important in preserving genomic stability by initiating DNA repair mechanisms. However, this activity could also reduce NAD+ levels within cells, potentially affecting other NAD+-dependent processes like energy production and cellular signaling. It has been noted that DNA damage may cause a rapid increase in PAR synthesis, possibly using up significant amounts of NAD+. Consequently, researchers are exploring the idea that NAD+ depletion, triggered by PAR polymerase activation, might influence the NAD+/SIRT1 pathway, potentially affecting mitochondrial function, ROS production, DNA repair, and cell survival.(16) Consequently, the reintroduction of NAD+ in such settings may compensate for this and may be posited to support the process of DNA repair and cell survival. NAD+ Peptide and the Liver, Kidney Upon introducing experimental mice with the NAD+ peptide and stimulating an increase in Nicotinamide Adenine Dinucleotide levels up to normal concentrations, researchers suggested the peptide exhibited positive potential in preventing obesity and alcoholic hepatitis while possibly improving glucose homeostasis and overall liver function. When aged mice kidney cells were supplemented with NAD+, the results indicated that adding the peptide possibly promoted SIRTs activity, which exhibited neuroprotective potential against glucose-induced kidney cell hypertrophy. Furthermore, when presented with NMN, NAD+ intermediate, it appeared to promote neuroprotective impact against cisplatin-induced kidney injury.(12) NAD+ Peptide and Skeletal Function Upon presenting aged mice with NMN daily for 7 days, researchers suggested that the peptide possibly increased ATP production, reduced inflammation, and elevated mitochondrial functions.(13) The researchers considered this may have been due to the role that NAD+ appears to play in cellular respiration and energy production, specifically acting as a helper molecule in redox reactions, which may be vital to converting nutrients into energy. This process, known as cellular respiration, is thought to allow cells to produce usable energy through a series of steps, and NAD+ is believed to play a key role in two specific phases: glycolysis and the citric acid cycle (or Krebs cycle). In glycolysis, the initial breakdown of glucose into pyruvate is suggested to be produced by a small amount of ATP and NADH. Here, NAD+ is thought to accept electrons and a hydrogen ion from glucose, turning into NADH. This transformation might allow NADH to transport these high-energy electrons to a later stage of energy production. Following glycolysis, pyruvate is further broken down in the citric acid cycle, potentially releasing more energy. NAD+ is implicated in various reactions during this cycle, possibly accepting electrons and hydrogen ions to form NADH. These crucial steps are considered to happen directly within the mitochondria. The NADH formed during both glycolysis and the citric acid cycle is presumed to carry high-energy electrons to the electron transport chain, the last step of cellular respiration. At this stage, NADH may give up its electrons, creating an electrochemical gradient and a chain reaction that drives protons across the mitochondrial membrane. This action appears to lead to the combination of electrons and protons with oxygen to produce water, and the energy released during this process may be used to generate ATP through oxidative phosphorylation. As NADH relinquishes its electrons, it may be transformed back into NAD+, ready to assist in another glycolysis and citric acid cycle. This regeneration of NAD+ is considered to be crucial for the ongoing production of ATP, thus maintaining the cell's energy supply. NAD+ Peptide and Cardiac Functions Researchers have suggested Nicotinamide Adenine Dinucleotide deficiency may lead to reduced SIRT activity, which may in turn cause reduced energy production and aortic constriction. When mice were exposed to NMN 30 minutes prior to induced-ischemia, the peptide reportedly produced a cardioprotective function against ischemic injury.(14) NAD+ peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Schultz, Michael B, and David A Sinclair. "Why NAD(+) Declines during Aging: It's Destroyed." Cell metabolism vol. 23,6 (2016): 965-966. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088772/ Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. 2020 Apr;132:110831. doi: 10.1016/j.exger.2020.110831. https://pubmed.ncbi.nlm.nih.gov/31917996/ Johnson, Sean, and Shin-Ichiro Imai. "NAD + biosynthesis, aging, and disease." F1000Research vol. 7 132. 1 Feb 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795269/ Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell. 2004 May 14;117(4):495-502. https://pubmed.ncbi.nlm.nih.gov/15137942/ Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017). NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends in molecular medicine, 23(10), 899–916. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494058/ Harden, A; Young, WJ (24 October 1906). "The alcoholic ferment of yeast-juice Part II.--The coferment of yeast-juice". Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character. 78 (526): 369–375. https://royalsocietypublishing.org/doi/10.1098/rspb.1906.0070 Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016 Dec 13;24(6):795-806. https://pubmed.ncbi.nlm.nih.gov/28068222/ Long AN, Owens K, Schlappal AE, Kristian T, Fishman PS, Schuh RA. Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. BMC Neurol. 2015 Mar 1;15:19. https://pubmed.ncbi.nlm.nih.gov/25884176/ Safety & Efficacy of Nicotinamide Riboside Supplementation for Improving Physiological Function in Middle-Aged and Older Adults. https://clinicaltrials.gov/ct2/show/NCT02921659 Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. 2020 Apr;132:110831. https://pubmed.ncbi.nlm.nih.gov/31917996/ Wang S, Xing Z, Vosler PS, Yin H, Li W, Zhang F, Signore AP, Stetler RA, Gao Y, Chen J. Cellular NAD replenishment confers marked neuroprotection against ischemic cell death: role of enhanced DNA repair. Stroke. 2008 Sep;39(9):2587-95. https://pubmed.ncbi.nlm.nih.gov/18617666/ Rajman, Luis et al. "Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence." Cell metabolism vol. 27,3 (2018): 529-547. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342515/ Heer C, et al, Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity. Journal of Biological Chemistry. Volume 295, Issue 52, Dec 2020. https://www.jbc.org/article/S0021-9258(17)50676-6/fulltext Mehmel, Mario et al. "Nicotinamide Riboside-The Current State of Research and Therapeutic Uses." Nutrients vol. 12,6 1616. 31 May. 2020, doi:10.3390/nu12061616 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352172/ Leung A, Todorova T, Ando Y, Chang P. Poly(ADP-ribose) regulates post-transcriptional gene regulation in the cytoplasm. RNA Biol. 2012 May;9(5):542-8. doi: 10.4161/rna.19899. Epub 2012 May 1. PMID: 22531498; PMCID: PMC3495734. Croteau DL, Fang EF, Nilsen H, Bohr VA. NAD+ in DNA repair and mitochondrial maintenance. Cell Cycle. 2017 Mar 19;16(6):491-492. doi: 10.1080/15384101.2017.1285631. Epub 2017 Feb 1. PMID: 28145802; PMCID: PMC5384578. Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
GHRP-2 (5mg / 10mg)
GHRP-2 is a synthetic peptide made of five amino acids (pentapeptide) analogous to the endogenous neurotransmitter met-enkephalin.(1) Yet, the peptide appears to lack any neurotransmitter-like properties and instead appears to activate the receptors for the hormone ghrelin. Ghrelin is a naturally occurring hormone that is posited to regulate food intake.(11) Growth hormone-releasing peptide GHRP-2 may induce the secretion of growth hormone (GH) by apparently activating the ghrelin receptors on the pituitary gland, also termed as growth hormone secretagogue receptors (GHS-Rs). Overview of GHRP-2 Mechanisms Bovine studies have suggested that GHRP-2 peptide exhibits multifaceted impacts, but its main mechanism of action appears to involve the GHS-Rs. These receptors are naturally triggered by ghrelin and may be found in various parts of the nervous system and other tissues. In the nervous system, they are located in the hypothalamus and the pituitary, among other structures. When GHRP-2 appears to engage with GHS-Rs, it's believed that a structural transformation might be triggered upon attachment, possibly initiating intracellular signaling networks primarily mediated through G-proteins. The release of Gαq/11, a component of the G-proteins, might commence, potentially setting off subsequent signaling sequences. Phospholipase C (PLC) may split phosphatidylinositol 4,5-bisphosphate (PIP2) into secondary signaling molecules, IP3 and DAG (diacylglycerol). IP3 is thought to prompt the release of calcium ions. In contrast, DAG may activate protein kinase C (PKC), potentially heightening the signaling pathway and possibly facilitating the secretion of growth hormone from pituitary cells. Moreover, this process may also involve the activation of cyclic AMP (cAMP), which plays a crucial role in cellular signaling. Increasing cAMP levels may further enhance the signaling cascade, potentially boosting GH synthesis.(13)(14) Nevertheless, GHRP-2 appears to induce desensitization at these receptors immediately after exposure, potentially reducing sensitivity lasting a complete four hours before reversal.(5) By apparently activating the GHS-Rs on other parts of the nervous system, GHRP-2 might trigger a series of cellular events leading to the enhanced synthesis of hunger-promoting neuropeptides, namely Neuropeptide Y (NPY) and Agouti-related peptide (AgRP). These peptides are thought to be integral to the regulation of energy balance and the control of appetite. At the same time, GHRP-2 is believed to possibly inhibit the secretion of the appetite-reducing hormone, melanocyte-stimulating hormone (α-MSH), thus shifting the equilibrium towards increased hunger and encouraging dietary intake. Moreover, GHRP-2 might affect the mesolimbic reward system, a neural pathway associated with regulating the craving for food, via the activation of GHSR-1a receptors. This action might theoretically heighten the drive for food consumption, potentially through the activation of cyclic adenosine monophosphate (cAMP) pathways, further implicating GHRP-2 in the modulation of feeding behavior and reward-based eating. Chemical Makeup Molecular Formula: C45H55N9O6 Molecular Weight: 817.97 g/mol Other Known Titles: pralmorelin Research and Clinical Studies GHRP-2 Peptide and Growth Hormone Synthesis This study(7) was conducted to understand the action of two synthetic GHRPs, GHRP-2 and Hexarelin (HEX), on growth hormone, prolactin, adrenocorticotropic hormone (ACTH), and cortisol concentrations. Two groups of various stages of mature development were evaluated, and both groups experienced a higher GH increase compared to the physiological increase induced by native growth hormone-releasing hormone (GHRH). Unfortunately, GHRP-2 also may induce an apparent increase in the levels of ACTH and cortisol. Further studies have reported that exposure to GHRP-2 in laboratory settings may induce a significant increase in peak GH levels, mean pulsatile GH secretion by the anterior pituitary gland cells, and may potentially upregulate mediators of GH’s anabolic actions such as insulin-like growth factor-1 (IGF-1): In one trial, GHRP-2 was suggested to induce up to 181-fold higher spike in GH production by the anterior pituitary gland cells.(17) Another experiment posited that the peptide may induce a 47-fold increase in mean 2.5-hour pulsatile GH secretion by the anterior pituitary gland cells compared to placebo.(18) A third trial on prolonged GHRP-2 exposure reported that the peptide may have induced an apparent increase in GH levels between 3-fold and 5-fold. Moreover, IGF-1 levels apparently increased from an average of 100mcg/l at baseline to a plateau value of around 180mcg/l.(19) GHRP-2 Peptide and Appetite In one study,(2) two groups were evaluated, one following GHRP-2 exposure and the other with saline. They were then taken to a buffet meal to measure their food intake. The researchers reported that the GHRP-2 models ate an average of 36% more than the saline group, with each model reportedly exhibiting increased food intake when measured against their respective body weight. The researchers reported that the energy intake per kilogram of body weight increased up to 136.0±13.0 kJ/kg vs 101.3±10.5 kJ/kg for the placebo group. Furthermore, the GH levels also presented significant incremental increases in GHRP-2 models compared to saline. The levels of the hormone measured as “area under the curve” (AUC) increased up to 5550±1090 μg/L/240 min vs. 412±161 μg/L/240 min. The researchers concluded that “GHRP-2, like ghrelin, increases food intake, suggesting that GHRP-2 [may be] a valuable tool for investigating ghrelin effects on eating behavior.” GHRP-2 Peptide and Muscle Tissues Murine models of thermal injury have suggested that GHRP-2 may significantly decrease in proinflammatory markers such as IL-6 and E3 ubiquitin ligases (MuRF-1 and MAFbx), which are associated with muscle wasting in critical conditions. The authors also posited that the peptide may directly reduce total muscle protein breakdown in the experimental models, therefore suggesting a muscle-sparing action GHRP-2.(20) Case studies have also suggested that the peptide may induce muscle and weight gain.(21) GHRP-2 Peptide and Antioxidative Actions Studies indicate that GHRP-2 may display antioxidative potential, with researchers noting its possible affinity for CD36, a receptor thought to play a key role in capturing oxidized low-density lipoprotein (OxLDL). This interaction could potentially limit the cellular absorption of OxLDL, which is reputed to contribute to atherogenic processes. In experiments conducted on mouse models lacking the ApoE gene (ApoE(-/-)), GHRP-2 exposure over 12 weeks seemed to elevate circulating levels of IGF-I, with increases observed to be between 1.2 to 1.6 times the initial measurements. Additionally, a reduction of approximately 66% in circulating interferon-gamma levels was reported. Although GHRP-2's introduction did not appear to significantly alter the extent of atherosclerotic plaque coverage, it is suggested to have reduced superoxide production in the aorta, as indicated by dihydroethidium staining. Furthermore, GHRP-2 is reported to have notably decreased, by about 92%, the aortic gene expression of 12/15-lipoxygenase, and also diminished the aortic expressions of interferon-gamma and macrophage migration inhibitory factors. Observations in cultured aortic smooth muscle cells suggested that GHRP-2 may counter the production of peroxides triggered by OxLDL, prevent the suppression of the IGF-I receptor, and potentially block apoptosis. In macrophages exposed to OxLDL, GHRP-2 is hypothesized to reduce lipid accumulation, further illustrating its potential antioxidative and protective roles against proatherogenic agents.(15) GHRP-2 Peptide and Inflammation To further elucidate the potential action of GHRP-2 on oxidative stress and inflammation, a study on murine models with artificially induced acute lung injury suggested that exposure to GHRP-2 may reduce lung edema, neutrophil infiltration, and levels of pro-inflammatory cytokines. The peptide was also posited to have suppressed nuclear factor-kappaB activation, a major mediator of inflammation. The cascades that follow its activation often lead to tissue damage.(16) GHRP-2 Peptide and GH Deficiency The most common diagnostic tool for GH deficiency is the insulin tolerance test (ITT), which may cause contraindications. A study(8) aimed to explore the potential of GHRP-2 as a diagnostic resource for GH deficiency. The study evaluated research models first tested via ITT. Of these, the study indicated 77 models exhibited normal insulin tolerance and 58 exhibited GH peak levels of less than three. Post overnight fasting, all research models were presented GHRP-2. After 2 hours, their blood samples were collected and tested. Upon analysis, the researchers reported that the GH levels peaked after one hour of GHRP-2 in all cases. These results were reportedly reproducible upon repetition of the tests. An additional study(9) was conducted to research the diagnostic properties of GHRP-2 on still-developing research models of GH deficiency (GHD) in comparison to a conventionally-used compound. Research models of GHD were enrolled in this study, presented with at least one conventional compound, and later presented with GHRH and GHRP-2. All models were first given GHRP-2. When measured, the serum GH levels appeared to have significantly increased. Models who demonstrated a robust response to the peptide were then presented with GHRP-2 and GHRH in combination. All models exhibited an apparent positive response in their GH levels, according to the researchers. Combination Studies with TRH and GnRH This study(10) was conducted on research models of prolonged hypo-somatotropism, hypogonadism, or hypothyroid complications to evaluate the action of compounds of GHRP 2, Thyrotropin-releasing hormone (TRH), and Gonadotropin-releasing hormone (GnRH) with GHRP-2 alone and with GHRP-2 and TRH in combination. Over 5 days, one group was presented with a placebo, one group with GHRP-2 every hour, another group with GHRP-2 + TRH every hour, and the remaining group with GHRP-2 + TRH + GnRH every 90 minutes. Serum samples were collected on the first and last night of the study. After the results were analyzed, researchers suggested that the combination of GHRP-2 + GnRH + TRH induced the greatest apparent activation of growth hormones along thyroid stimulating hormone and luteinizing hormone axes, along with other possible metabolic effects. These actions were reported to be absent with GHRP-2 solo presentation and only partially seen with GHRP-2 and TRH combination. GHRP 2 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Garcia JM, Merriam GR, Kargi AY. Growth Hormone in Aging. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext. South Dartmouth (MA): MDText.com https://www.ncbi.nlm.nih.gov/books/NBK279163/ Laferrère, Blandine et al. “Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.” The Journal of clinical endocrinology and metabolism vol. 90,2 (2005): 611-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824650/ Bowers CY. History to the discovery of ghrelin. Methods Enzymol. 2012;514:3-32. doi: 10.1016/B978-0-12-381272-8.00001-5. PMID: 22975043. https://pubmed.ncbi.nlm.nih.gov/22975043/ Roh SG, He ML, Matsunaga N, Hidaka S, Hidari H. Mechanisms of action of growth hormone-releasing peptide-2 in bovine pituitary cells. J Anim Sci. 1997 Oct;75(10):2744-8. doi: 10.2527/1997.75102744x. PMID: 9331879. https://pubmed.ncbi.nlm.nih.gov/9331879/ Asad Rahim, Stephen M. Shalet, in Growth Hormone Secretagogues, 1999. Does desensitization to growth hormone secretagogues occur? https://www.sciencedirect.com/topics/medicine-and-dentistry/pralmorelin Furuta S, Shimada O, Doi N, Ukai K, Nakagawa T, Watanabe J, Imaizumi M. General pharmacology of KP-102 (GHRP-2), a potent growth hormone-releasing peptide. Arzneimittelforschung. 2004;54(12):868-80. doi: 10.1055/s-0031-1297042. PMID: 15646371. https://pubmed.ncbi.nlm.nih.gov/15646371/ Emanuela Arvat, Lidia Di Vito, Barbara Maccagno, Fabio Broglio, Muni F Boghen, Romano Deghenghi, Franco Camanni, Ezio Ghigo, Effects of GHRP-2 and Hexarelin, Two Synthetic GH-Releasing Peptides, on GH, Prolactin, ACTH and Cortisol Levels in Man. Comparison with the Effects of GHRH, TRH and hCRH, Peptides, Volume 18, Issue 6, 1997, Pages 885-891, ISSN 0196-9781, https://doi.org/10.1016/S0196-9781(97)00016-8 Chihara K, Shimatsu A, Hizuka N, Tanaka T, Seino Y, Katofor Y; KP-102 Study Group. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency. Eur J Endocrinol. 2007 Jul;157(1):19-27. doi: 10.1530/EJE-07-0066. https://pubmed.ncbi.nlm.nih.gov/17609397/ Pihoker C, Middleton R, Reynolds GA, Bowers CY, Badger TM. Diagnostic studies with intravenous and intranasal growth hormone-releasing peptide-2 in children of short stature. J Clin Endocrinol Metab. 1995 Oct;80(10):2987-92. https://pubmed.ncbi.nlm.nih.gov/7559885/ Van den Berghe G, Baxter RC, Weekers F, Wouters P, Bowers CY, Iranmanesh A, Veldhuis JD, Bouillon R. The combined administration of GH-releasing peptide-2 (GHRP-2), TRH and GnRH to men with prolonged critical illness evokes superior endocrine and metabolic effects compared to treatment with GHRP-2 alone. Clin Endocrinol (Oxf). 2002 May;56(5):655-69. https://pubmed.ncbi.nlm.nih.gov/12030918/ GHRP 2, GPA 748, Growth Hormone-Releasing Peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102 LN. https://link.springer.com/article/10.2165/00126839-200405040-00011# Phung LT, Sasaki A, Lee HG, Vega RA, Matsunaga N, Hidaka S, Kuwayama H, Hidari H. Effects of the administration of growth hormone-releasing peptide-2 (GHRP-2) orally by gavage and in feed on growth hormone release in swine. Domest Anim Endocrinol. 2001 Jan;20(1):9-19. https://pubmed.ncbi.nlm.nih.gov/11164330/ Yin, Y., Li, Y., & Zhang, W. (2014). The growth hormone secretagogue receptor: its intracellular signaling and regulation. International journal of molecular sciences, 15(3), 4837–4855. https://doi.org/10.3390/ijms15034837 Sinha, D. K., Balasubramanian, A., Tatem, A. J., Rivera-Mirabal, J., Yu, J., Kovac, J., Pastuszak, A. W., & Lipshultz, L. I. (2020). Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Translational andrology and urology, 9(Suppl 2), S149–S159. https://doi.org/10.21037/tau.2019.11.30 Titterington JS, Sukhanov S, Higashi Y, Vaughn C, Bowers C, Delafontaine P. Growth hormone-releasing peptide-2 suppresses vascular oxidative stress in ApoE-/- mice but does not reduce atherosclerosis. Endocrinology. 2009 Dec;150(12):5478-87. doi: 10.1210/en.2009-0283. Epub 2009 Oct 9. PMID: 19819949; PMCID: PMC2795722. Li, G., Li, J., Zhou, Q., Song, X., Liang, H., & Huang, L. (2010). Growth hormone releasing peptide-2, a ghrelin agonist, attenuates lipopolysaccharide-induced acute lung injury in rats. The Tohoku journal of experimental medicine, 222(1), 7–13. https://doi.org/10.1620/tjem.222.7 Veldhuis, J. D., Keenan, D. M., Bailey, J. N., Adeniji, A. M., Miles, J. M., & Bowers, C. Y. (2009). Novel relationships of age, visceral adiposity, insulin-like growth factor (IGF)-I and IGF binding protein concentrations to growth hormone (GH) releasing-hormone and GH releasing-peptide efficacies in men during experimental hypogonadal clamp. The Journal of clinical endocrinology and metabolism, 94(6), 2137–2143. https://doi.org/10.1210/jc.2009-0136 Veldhuis, J. D., & Keenan, D. M. (2008). Secretagogues govern GH secretory-burst waveform and mass in healthy eugonadal and short-term hypogonadal men. European journal of endocrinology, 159(5), 547–554. https://doi.org/10.1530/EJE-08-0414 Bowers, C. Y., Granda, R., Mohan, S., Kuipers, J., Baylink, D., & Veldhuis, J. D. (2004). Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women. The Journal of clinical endocrinology and metabolism, 89(5), 2290–2300. https://doi.org/10.1210/jc.2003-031799 Sheriff, S., Joshi, R., Friend, L. A., James, J. H., & Balasubramaniam, A. (2009). Ghrelin receptor agonist, GHRP-2, attenuates burn injury-induced MuRF-1 and MAFbx expression and muscle proteolysis in rats. Peptides, 30(10), 1909–1913. https://doi.org/10.1016/j.peptides.2009.06.029 Sigalos, J. T., & Pastuszak, A. W. (2018). The Safety and Efficacy of Growth Hormone Secretagogues. Sexual medicine reviews, 6(1), 45–53. https://doi.org/10.1016/j.sxmr.2017.02.004 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
LL-37 (5mg)
LL-37, also known as Cathelicidin, is a cationic peptide composed of 37 amino acids and is primarily found in neutrophils.(1) The peptide appears to be produced by the extracellular breakdown of the hCAP18 proteins caused by protease enzymes. Researched for its potential antimicrobial characteristics, the peptide appears to form agglomerates and lipid bilayers, which may prevent it from easily degrading and protect it from enzymatic action.(1) Overview Antimicrobial peptides are structured with the potential to fight against bacteria, fungi, and some virus strains. These peptides may interact with targets in a non-specific fashion, which supports researchers' belief that once the peptide is introduced, pathogens are unable to develop resistance against these peptides.(2) LL-37 is a α-helical peptide that scientists believe is required to maintain immunity against all microbes.(3) To understand the functioning of the peptide, a peptide model was created as part of a study(4) based on the assumption that the peptide might interact directly with the bacterial membrane. This study suggested that the peptide first interacts with the lipids on the bacterial membrane via electrostatic characteristics, followed by lateral diffusion and consequent assembly of the peptide on the membrane. This potential interaction may lead to membrane interference and degradation of the bacterial cell. Several other studies hypothesize how the peptide interacts with microbial membranes, including pore formation on the membrane(3)(5) and extreme membrane disruption caused by the peptide and lipid complexes.(6) These studies universally suggest that peptides have the potential to interact with the microbial membrane, leading to membrane breakdown. Chemical Makeup Molecular Formula: C205H340N50O53 Molecular Weight: 4493.34 g/mol Other Known Titles: CAP-18 Research and Clinical Studies LL-37 Peptide and Inflammatory Response The main aim of this study(7) was to determine the inflammatory potential of this peptide. Tissue culture was used, half without alteration and the other half with added U1 RNA. U1 RNA is a non-coding RNA released upon tissue injury. LL-37 peptide was then added to both cultures. Upon genetic analysis, it was suggested by the researchers that the culture that was given both U1 RNA and LL-37 peptide stimulated a reportedly significant response towards epidermal inflammation and defense response. The study proposes that the peptide might potentially enhance the immune system's response to damaged cells by influencing how self-nucleic acids (DNA and RNA) are recognized. This recognition is apparently facilitated when the peptide interacts with specific cellular receptors, including scavenger receptors (SRs), which may lead to clathrin-dependent endocytosis. This process appears critical for the subsequent activation of inflammatory pathways within the cells. Moreover, the study indicates that LL-37 might enable the binding of dsRNA (double-stranded RNA) to these scavenger receptors, which in turn might lead to a series of signaling events culminating in cytokine expression. Notably, the interaction between LL37 and scavenger receptors such as SR-A6 and SR-B1 may be essential for this process, as blocking these receptors with a competitive inhibitor like fucoidan or silencing their expression significantly reduced cytokine production. Another interesting aspect of the study is the hypothesis that LL-37 may modulate the immune system by potentially altering how intracellular signaling pathways, such as those involving Toll-like receptors (TLR) and the interferon regulatory factors, and may be activated in response to foreign nucleic acids. As detailed in the study, the involvement of clathrin-mediated endocytosis suggests that LL-37 may help orchestrate the entry of these immune-modulating molecules into cells, which is a vital step for triggering an immune response. LL-37 Peptide and Autoimmunity Models The main aim of this study(1) was to understand the role of LL-37 in models of autoimmunity such as psoriasis. This disease pathogenesis study suggested that endogenous peptide may form complex DNA, increasing interferon mechanisms and more inflammatory responses. This study theorized that LL-37 may be favorable for tissue and wound injury; however, in some cases, LL-37 levels appeared to indicate psoriasis presence. In fact, it might potentially exert anti-apoptotic actions on keratinocytes, which might be linked to the observed cellular proliferation in psoriatic lesions. LL-37 is a naturally occurring antimicrobial peptide that forms part of the immune system, playing various roles in immune responses. This action may potentially contribute to developing the thick, scaly skin that is a hallmark of psoriasis. While LL-37 has been implicated in promoting inflammation via type I interferon (IFN) pathways, it appears to simultaneously offer a protective action against the activation of the AIM2 inflammasome by cytosolic double-stranded DNA (dsDNA). Cytosolic dsDNA often triggers immune responses that may lead to inflammation. In cases where LL-37 forms complexes with DNA, these complexes seemingly do not promote the production of interleukin-1β (IL-1β), a pro-inflammatory cytokine, nor activate the inflammasome. This implies that LL37 might protect keratinocytes from the inflammatory responses typically triggered by the AIM2 inflammasome in the presence of dsDNA. This dual potential of LL-37 underscores its complex involvement in immune regulation and inflammatory processes. LL-37 Peptide and Arthritis The main objective of this study(1)(8) was to evaluate the potential of LL-37 in arthritic joints. A group of rats were used in this study,(8) with one control group and one group experimentally induced with rheumatoid arthritis. Upon inducing the condition, researchers reported an apparent increased regulation of rCRAMP, the rat analog of LL-37 peptide, in inflammatory cells. Researchers suggested that LL-37 peptide might further induce apoptosis of osteoblasts, thereby leading to decreased bone formation in the joints. This study suggested that increased LL-37 levels are characteristic of joint aches and arthritis and may potentially be used for diagnostic purposes. Besides these, study(1) has suggested that LL-37 elevation is seen in other inflammatory circumstances, such as arteriosclerosis. Scientists report that LL-37 activation and the consequent upregulation of interferons are characteristic of arteriosclerosis-induced cells. The researchers of this study suggested that the peptide may have potential as an immunomodulatory agent. LL-37 Peptide and Tissue Repair In this study,(9) mice presented with an anti-inflammatory compound were then presented with LL-37 to study the potential of this peptide on angiogenesis and wound healing. The researchers suggested that the peptide mice exhibited an apparent increase in vascularization and skin cell formation. This study suggested that LL-37 has the potential to induce endothelial skin cell proliferation and formation of tubule-like structures, which are both required in angiogenesis mechanisms. Further, the study indicates that LL37 possibly counteracts the activation of macrophages triggered by lipopolysaccharide (LPS), a component known to provoke immune responses. Furthermore, it seems to foster endothelial cell behaviors essential for wound healing, such as proliferation, migration, and the formation of tubule-like structures, all indicative of angiogenesis. Experiments on catabolism-induced murine models, utilizing both synthetic and recombinant forms of LL-37, suggest that exposure to the peptide may enhance vascularization and re-epithelialization. These observations collectively lead to the hypothesis that the peptide might be crucial in promoting wound regeneration, potentially through its actions on vascularization. LL-37 Peptide and Cancer Cells Studies(10) are ongoing to explore the potential of the peptide in cancer cell development. These studies have suggested that the peptide may inhibit gastric cancer cell proliferation by activating the bone morphogenetic protein signaling system. The main aim of this research was to consider the potential of LL-37 as an immunotherapeutic agent or consider the potential of LL-37 peptide as an adjuvant in eliminating cancer cells from the host system. CpG oligodeoxynucleotides are widely considered to be immunotherapeutic compounds as they appear to promote the tumor-suppressing activity. When presented with LL-37, researchers reported that the peptide LL-37 appeared to increase the CpG oligodeoxynucleotides sensitivity in lymphocytes. LL-37 Peptide and GI Tract LL-37 may potentially impact ailments associated with the gastrointestinal (GI) tract. There appears to be an increased expression of LL-37 in research models of gastrointestinal ulcers. This upregulation might be mediated through the activation of Toll-like receptor 3 (TLR-3) by its ligand, polyinosinic-polycytidylic acid (poly(I)). Poly(I) stimulation possibly enhances LL-37 expression by triggering intracellular signaling cascades involving proteins such as Toll/IL-1R domain-containing adaptor-inducing interferon (TRIF), tumor necrosis factor receptor-associated factor 6 (TRAF6), and transforming growth factor β-activated kinase 1 (TAK1). Owing to its antimicrobial potential, LL-37 may be capable of protecting GI mucosa from microbial damage.(12) The protective potential of this peptide in the gastrointestinal tract may involve its interaction with lipopolysaccharide (LPS), a component of bacterial cell walls. LL-37 may be able to suppress LPS-induced secretion of pro-inflammatory cytokines such as interleukin-6 (IL-6) and IL-8 in colonic subepithelial myofibroblasts (SEMFs), which possibly contributes to a protective action by moderating local inflammation. LL-37 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Kahlenberg, J Michelle, and Mariana J Kaplan. “Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease.” Journal of immunology (Baltimore, Md. : 1950) vol. 191,10 (2013): 4895-901. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836506/ Seil, M., Nagant, C., Dehaye, J. P., Vandenbranden, M., & Lensink, M. F. (2010). Spotlight on Human LL-37, an Immunomodulatory Peptide with Promising Cell-Penetrating Properties. Pharmaceuticals, 3(11), 3435–3460. h https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034075/ Zeth, Kornelius, and Enea Sancho-Vaello. “The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions.” Frontiers in chemistry vol. 5 86. 7 Nov. 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681987/ Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol. 2005 Mar;3(3):238-50. https://pubmed.ncbi.nlm.nih.gov/15703760/ Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW. Membrane pores induced by magainin. Biochemistry. 1996 Oct 29;35(43):13723-8. https://pubmed.ncbi.nlm.nih.gov/8901513/ Bechinger B, Lohner K. Detergent-like actions of linear amphipathic cationic antimicrobial peptides. Biochim Biophys Acta. 2006 Sep;1758(9):1529-39. https://pubmed.ncbi.nlm.nih.gov/16928357/ Takahashi, T., Kulkarni, N.N., Lee, E.Y. et al. Cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors. Sci Rep 8, 4032 (2018). https://doi.org/10.1038/s41598-018-22409-3 Hoffmann MH, Bruns H, Bäckdahl L, Neregård P, Niederreiter B, Herrmann M, Catrina AI, Agerberth B, Holmdahl R. The cathelicidins LL-37 and rCRAMP are associated with pathogenic events of arthritis in humans and rats. Ann Rheum Dis. 2013 Jul;72(7): https://pubmed.ncbi.nlm.nih.gov/23172753/ Ramos R, Silva JP, Rodrigues AC, Costa R, Guardão L, Schmitt F, Soares R, Vilanova M, Domingues L, Gama M. Wound healing activity of the human antimicrobial peptide LL37. Peptides. 2011 Jul;32(7):1469-76. doi: 10.1016/j.peptides.2011.06.005. Epub 2011 Jun 13. https://pubmed.ncbi.nlm.nih.gov/21693141/ Wu, W. K., Wang, G., Coffelt, S. B., Betancourt, A. M., Lee, C. W., Fan, D., Wu, K., Yu, J., Sung, J. J., & Cho, C. H. (2010). Emerging roles of the host defense peptide LL-37 in human cancer and its potential therapeutic applications. International journal of cancer, 127(8), 1741–1747. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930073/ Wang, C., Wang, S., Li, D., Chen, P., Han, S., Zhao, G., Chen, Y., Zhao, J., Xiong, J., Qiu, J., Wei, D. Q., Zhao, J., & Wang, J. (2021). Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds with One Stone. ACS infectious diseases, 7(6), 1545–1554. Kusaka; et al. Expression of human cathelicidin peptide LL-37 in inflammatory bowel disease. Clin Exp Immunol. 2018 Jan;19(11). Epub 2017 Sep 28. https://pubmed.ncbi.nlm.nih.gov/28872665/ Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Hexarelin (5mg)
Hexarelin is a growth hormone-releasing peptide (GHRP) that researchers consider may host a potential action parallel tothat of peptide GHRP-6.(1) Hexarelin, or Examorelin, is a synthetic peptide composed of six amino acids.(2) Regarding its mechanism of action, Hexarelin is believed to work by mimicking the naturally occurring peptide ghrelin, which contains 28 amino acids and is considered by scientists to stimulate the release of growth hormone (GH) and induce hunger. Several synthetic compounds, including Hexarelin, which appears to exhibit actions similar to those of ghrelin, were developed more than 25 years ago.(3) Since their development, continuous studies and research have been conducted to fully examine the actions and potential of these peptides. Overview Hexarelin is hypothesized to operate by imitating ghrelin's role in activating ghrelin receptors throughout the organism, notably those within the pituitary gland and hypothalamus. Known as growth hormone secretagogue receptors (GHS-Rs), more specifically the GHSR-1a, their stimulation may lead to the secretion of GH, positioning Hexarelin as a potential growth hormone secretagogue (GHS). This appears to be an alternative mechanism regulating the synthesis of GH by the anterior pituitary cells, compared to the direct stimulation of the hypothalamus via the native growth hormone-releasing hormone (GHRH). The GHSR-1a is found on the hypothalamus and pituitary gland and across various parts of the nervous system and other tissues. Thus, Hexarelin's action is posited to encompass both direct and indirect triggers of GH release, potentially impacting GHS-Rs in the pituitary and indirectly affecting the hypothalamus.(4) When Hexarelin engages GHS-Rs, it is hypothesized that it might cause a structural change, possibly activating intracellular signaling pathways that largely depend on G-proteins, such as the potential activation of protein kinase C (PKC), possibly amplifying the signaling pathway and facilitating GH release from pituitary cells. However, exposure to Hexarelin has also been posited to lead to transient receptor desensitization that may last for days or weeks.(5) Furthermore, Hexarelin has been posited to be unselective towards the apparent synthesis of GH, and researchers suggest the peptide may also induce the production of other pituitary hormones. Namely, these hormones may include the adrenocorticotropic hormone (ACTH) and prolactin.(6) In general, the upregulation of these hormones in experimental settings is undesired by researchers. Researchers note that Hexarelin's potential to activate GHS-Rs also in other nervous system areas might initiate cellular processes that increase the production of hunger-related neuropeptides, such as Neuropeptide Y (NPY) and Agouti-related peptide (AgRP). These are considered critical in managing energy balance and appetite control. Concurrently, Hexarelin might also reduce the secretion of the appetite-suppressing hormone, melanocyte-stimulating hormone (α-MSH), thus tipping the balance towards increased hunger and encouraging food intake. Hexarelin may also influence the mesolimbic reward system, associated with craving regulation for flavorful food, through potential GHSR-1a activation. This could theoretically amplify the motivation for eating, possibly by activating cyclic adenosine monophosphate (cAMP) pathways, thereby suggesting Hexarelin's potential role in altering feeding behavior and reward-driven eating practices.(7) Chemical Makeup Molecular Formula: C47H58N12O6 Molecular Weight: 887.05 g/mol Other Known Titles: examorelin Research and Clinical Studies Hexarelin Peptide and Growth Hormone Release A study(8) was conducted on three groups of research models at the adolescent, maturation, and elderly stages of development to evaluate the GH-releasing potential of the peptide. All models were presented with Hexarelin, GHRH alone, or GHRH combined with arginine. In adolescent models, the GH levels were reportedly elevated by GHRH + arginine combination, while GH levels did not appear to be raised by Hexarelin alone. On the other hand, Hexarelin appeared to induce higher GH levels than the increased GH levels induced by GHRH alone and GHRH + arginine combination in adolescent and mature models. In elderly models, Hexarelin reportedly induced higher GH levels in comparison to GHRH. However, the GH levels were reportedly lower than GHRH + arginine combination. These results suggest that Hexarelin may potentially elevate GH levels in adolescent and mature models. While it might increase GH levels in the elderly and adolescent groups, no significant effects were reported. Hexarelin Peptide and Potential GHRH Synergism The main aim of this study(9) was to determine the potential of Hexarelin on the GH1 murine tumor cell line, which may be insensitive towards GHRH. Furthermore, this study monitored the potential involvement of GHRH in the possible action of Hexarelin on the GH1 murine tumor cells. Hexarelin was presented in normal control murine pituitary cells and GH1 murine cells. Researchers reported that GHRH appeared to increase GH levels in the control rat cells without presenting any apparent effects on GH1 cells. Moreover, when presented with Hexarelin, GHRH appeared to cause no impact on GH release. These results suggest that GHRPs and GHRHs may act on two distinct sites, and GHRPs, such as Hexarelin, may have the potential to act on cells that are not sensitive to GHRH effects. Most importantly, the researchers commented, "In this latter cell model, GHRH and Hexarelin were [posited] to have additive stimulatory effects on GH secretion.” Thus, it may be suggested that due to the distinct pathways of GH-stimulation by Hexarelin and GHRH, they may have complementary action on the GH synthesis and potentially result in greater stimulation than either agent alone. Hexarelin Peptide and Cardiovascular Activity Studies(10) have suggested that the acute presentation of Hexarelin may induce positive inotropic activity in the cardiovascular system. When presented to research models, the peptide reportedly increased the left ventricular ejection fraction (LVEF), possibly without affecting blood pressure. When presented to research models of disrupted coronary artery flow, the Hexarelin reportedly exhibited the potential to increase cardiac output and arterial pressure without changing heart rate. Furthermore, when presented in ischemic rat hearts, Hexarelin appeared to have restored the electrophysiological properties of the heart cells, and inhibited cell apoptosis, thereby producing positive inotropic activity and potentially promoting heart cell survival.(11) Another study(12) was conducted in which Hexarelin was presented daily to murine heart cells that were experimentally induced to undergo myocardial infarction. The results suggested that the peptide had the potential to increase stroke volume and cardiac output while decreasing peripheral resistance. Hexarelin Peptide and Composition One study(13) aimed to determine the possible fluctuation of sex-based weight composition with the growth hormone-releasing potential of Hexarelin. This study evaluated the impact of Hexarelin exposure, and upon analyzing the test samples, researchers suggested that the stimulus of Hexarelin and the consequent peak growth hormone release appeared to be negatively correlated to fat mass. Increased fat mass may lead to a reduction in GH release following Hexarelin exposure. Gender reportedly exhibited no significant impact on GH release. Hexarelin Peptide and Muscle Tissue Preliminary experiments suggest that Hexarelin may have sparing effects on muscle tissue in research models exposed to catabolic conditions. Several such experiments have reported an apparent reduction in muscle mass loss and muscle strength loss, potentially due to the action of Hexarelin. For example, one of the studies suggested that a group of research models exposed to catabolic agents lost 12% muscle mass. In comparison, the addition of Hexarelin may have lowered that loss to 7%.(14) A similar experiment also commented that the peptide may have attenuated the reduction in strength levels associated with exposure to catabolic agents.(15) Hexarelin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Giustina A, Bonfanti C, Licini M, Ragni G, Stefana B. Hexarelin, a novel GHRP-6 analog, stimulates growth hormone (GH) release in a GH-secreting rat cell line (GH1) insensitive to GH-releasing hormone. Regul Pept. 1997 May 14;70(1):49-54. https://pubmed.ncbi.nlm.nih.gov/9250581/ National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 6918297, Examorelin. Retrieved August 19, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Examorelin Fabio Broglio et al, Ghrelin: Much more than a natural growth hormone secretagogue. Division of Endocrinology and Metabolism, Department of Internal Medicine; Division of Pathological Anatomy, Department of Biomedical Sciences and Oncology https://www.ima.org.il/FilesUploadPublic/IMAJ/0/56/28152.pdf Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol. 1996 Oct;135(4):481-8. https://pubmed.ncbi.nlm.nih.gov/8921832/ Rahim, A., O'Neill, P. A., & Shalet, S. M. (1998). Growth hormone status during long-term hexarelin therapy. The Journal of clinical endocrinology and metabolism, 83(5), 1644–1649. https://doi.org/10.1210/jcem.83.5.4812 Massoud, A. F., Hindmarsh, P. C., & Brook, C. G. (1996). Hexarelin-induced growth hormone, cortisol, and prolactin release: a dose-response study. The Journal of clinical endocrinology and metabolism, 81(12), 4338–4341. https://doi.org/10.1210/jcem.81.12.8954038 Bresciani, E., Pitsikas, N., Tamiazzo, L., Luoni, M., Bulgarelli, I., Cocchi, D., Locatelli, V., & Torsello, A. (2008). Feeding behavior during long-term hexarelin administration in young and old rats. Journal of endocrinological investigation, 31(7), 647–652. https://doi.org/10.1007/BF03345618 Bellone J, Bartolotta E, Sgattoni C, Aimaretti G, Arvat E, Bellone S, Deghenghi R, Ghigo E. Hexarelin, a synthetic GH-releasing peptide, is a powerful stimulus of GH secretion in pubertal children and in adults but not in prepubertal children and in elderly subjects. J Endocrinol Invest. 1998 Sep;21(8):494-500. https://pubmed.ncbi.nlm.nih.gov/9801989/ Giustina A, Bonfanti C, Licini M, Ragni G, Stefana B. Hexarelin, a novel GHRP-6 analog, stimulates growth hormone (GH) release in a GH-secreting rat cell line (GH1) insensitive to GH-releasing hormone. Regul Pept. 1997 May 14;70(1):49-54. https://pubmed.ncbi.nlm.nih.gov/9250581/ Mao, Yuanjie et al. “The cardiovascular action of hexarelin.” Journal of geriatric cardiology : JGC vol. 11,3 (2014): 253-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178518/ Ma Y, Zhang L, Edwards JN, Launikonis BS, Chen C. Growth hormone secretagogues protect mouse cardiomyocytes from in vitro ischemia/reperfusion injury through regulation of intracellular calcium. PLoS One. 2012;7(4):e35265. https://pubmed.ncbi.nlm.nih.gov/22493744/ Tivesten A, Bollano E, Caidahl K, Kujacic V, Sun XY, Hedner T, Hjalmarson A, Bengtsson BA, Isgaard J. The growth hormone secretagogue hexarelin improves cardiac function in rats after experimental myocardial infarction. Endocrinology. 2000 Jan;141(1):60-6. https://pubmed.ncbi.nlm.nih.gov/10614623/ Rahim A, O'Neill P, Shalet SM. The effect of body composition on hexarelin-induced growth hormone release in normal elderly subjects. Clin Endocrinol (Oxf). 1998 Nov;49(5):659-64. https://pubmed.ncbi.nlm.nih.gov/10197083/ Bresciani, E., Rizzi, L., Molteni, L., Ravelli, M., Liantonio, A., Ben Haj Salah, K., Fehrentz, J. A., Martinez, J., Omeljaniuk, R. J., Biagini, G., Locatelli, V., & Torsello, A. (2017). JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia. Endocrine, 58(1), 106–114. https://doi.org/10.1007/s12020-016-1184-2 Conte, E., Camerino, G. M., Mele, A., De Bellis, M., Pierno, S., Rana, F., Fonzino, A., Caloiero, R., Rizzi, L., Bresciani, E., Ben Haj Salah, K., Fehrentz, J. A., Martinez, J., Giustino, A., Mariggiò, M. A., Coluccia, M., Tricarico, D., Lograno, M. D., De Luca, A., Torsello, A., … Liantonio, A. (2017). Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia. Journal of cachexia, sarcopenia and muscle, 8(3), 386–404. https://doi.org/10.1002/jcsm.12185 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Tesamorelin & Ipamorelin Blend (8mg)
The Tesamorelin and Ipamorelin blend consists of two peptides that appear to share the potential to stimulate the growth hormone axis, albeit through differing mechanisms. This combination may synergistically activate the pituitary gland, which research suggests results in the release of endogenous growth hormone. The blend seems to offer a potential means to optimize growth hormone levels and may elicit effects on sleep, metabolic function, cognition, muscle tissue, lean mass, and lipid profiles.(1)(2) It is possible that the combination of Tesamorelin and Ipamorelin may yield a range of impacts, which may include improved deep sleep, reduced levels of triglycerides, visceral adipose tissue (VAT), and carotid intima-media thickness (cIMT), enhanced cognition, and possible overall optimization of metabolic function. This blend appears to present an opportunity to harness the synergistic actions of both to potentially augment natural growth hormone levels. Chemical Makeup(3)(4) Molecular Formula Tesamorelin: C221H366N72O67S Ipamorelin: C38H49N9O5 Molecular Weight Tesamorelin: 5136 g/mol Ipamorelin: 711.8 g/mol Sequence Tesamorelin: Unk-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2 Ipamorelin: H-Aib-His-D-2Nal-D-Phe-Lys-NH2 Other Known Titles Tesamorelin: (3E)-hex-3-enoylsomatoliberin Ipamorelin: Ipamorelin Acetate, Aib-His-D-2-Nal-D-Phe-Lys-NH2 Research and Clinical Studies Tesamorelin & Ipamorelin Blend and Growth Hormone Deficiency The Tesamorelin and Ipamorelin blend appears to exert its potential through distinct yet complementary proposed mechanisms of action. Tesamorelin, a growth hormone-releasing hormone (GHRH) analog, appears to act by binding to and activating the GHRH receptor on somatotrophs in the pituitary gland. This stimulation potentially triggers the synthesis and secretion of endogenous growth hormone (GH) in a pulsatile manner. By promoting GH release, Tesamorelin may possibly enhance lipolysis, reduce visceral adipose tissue, and also potentially improve glucose metabolism. Ipamorelin, a growth hormone secretagogue receptor (GHSR) agonist, by contrast, appears to activate GHSR in the hypothalamus and peripheral tissues, potentially leading to the release of GH. This peptide appears to exhibit a high selectivity for GHSR, potentially without interfering with other hormones. This GHSR activation by Ipamorelin may result in increased GH secretion, which, in turn, might promote protein synthesis, lipolysis, and insulin-like growth factor-1 (IGF-1) production, as suggested by researchers. When combined, the Tesamorelin and Ipamorelin blend may provide a synergistic impact by targeting different components of the growth hormone axis. Tesamorelin has been suggested to enhance GHRH-mediated GH release, while Ipamorelin has been suggested to directly stimulate GHSR to increase GH secretion. This dual action appears to amplify the overall GH, such as improved body composition, lipid profile, insulin sensitivity, and overall metabolic function in laboratory test models. By seemingly targeting the growth hormone axis through their supposed distinct mechanisms of action, Tesamorelin and Ipamorelin may collectively stimulate the pituitary gland, thereby potentially enhancing the release of endogenous growth hormone.(5) Tesamorelin & Ipamorelin Blend and the Pituitary Gland The Tesamorelin and Ipamorelin blend appears to exhibit some impact on the pituitary gland, a critical endocrine organ considered responsible for the regulation of growth hormone secretion. Studies suggest that Tesamorelin may specifically target the growth hormone-releasing hormone receptor (GHRHR), potentially activating the signaling cascade that leads to growth hormone synthesis and subsequent release. As per the researchers, “Tesamorelin is a synthetic growth hormone-releasing hormone that acts on the anterior pituitary gland to stimulate the endogenous growth hormone secretion.”(6) Studies suggest that the peptide may potentially cause a 69% increase in total growth hormone levels (apparently assessed via area under the curve - AUC) and a purported 55% increase in the mean pulse area of the growth hormone. The peptide was not reported to affect growth hormone pulse frequency or peak growth hormone levels.(7) Ipamorelin, on the other hand, studies suggest may act as a potent agonist for the growth hormone secretagogue receptor (GHSR), seemingly promoting growth hormone secretion.(8) As stated in the studies, “Ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of ipamorelin makes this compound a very interesting candidate for future clinical development.”(8) Ipamorelin may have exhibited a propensity to elevate growth hormone levels, potentially reaching heights of up to 80mIU/l (equivalent to an approximate concentration of 26.6ng/ml). When expressed as a percentage increase in comparison to a placebo (1.31mIU/l or 0.4ng/ml), this augmentation appears to surpass 60-fold.(9) When combined, these peptides appear to exert a synergistic action on the pituitary gland, which might result in enhanced growth hormone production. This proposed synergistic interaction between Tesamorelin and Ipamorelin may offer a promising avenue for research in optimizing growth hormone levels. Tesamorelin & Ipamorelin Blend and Lipodystrophy Research studies frequently indicate that lipodystrophy is often accompanied by insulin resistance, dyslipidemia, and an increased risk of cardiovascular complications. Clinical studies have suggested that Tesamorelin presentation in lipodystrophic test subjects might lead to a reduction in visceral adipose tissue (VAT) and improvements in insulin sensitivity and lipid profiles. Tesamorelin appears to act through the activation of the growth hormone-releasing hormone receptor (GHRHR), potentially stimulating endogenous growth hormone secretion and promoting lipolysis; and potentially preserving “abdominal subcutaneous adipose tissue, improving body image and lipids”.(10) Similarly, Ipamorelin has been reported to exhibit some promise in influencing adipose tissue metabolism. By combining Tesamorelin and Ipamorelin, it is hypothesized by researchers that the synergistic potential of these peptides may enhance the reduction of VAT and improve metabolic parameters in lipodystrophy test models.(10) Tesamorelin & Ipamorelin Blend and Type 2 Diabetes Preclinical and clinical studies have suggested that both Tesamorelin and Ipamorelin hold promise in improving glycemic control and mitigating the metabolic abnormalities associated with T2DM. Tesamorelin appears to stimulate endogenous growth hormone secretion, which has been long considered by scientists to enhance insulin sensitivity and glucose utilization. Ipamorelin studies also indicate that the peptide may influence glucose metabolism and insulin sensitivity. Combining Tesamorelin and Ipamorelin may provide complementary effects, which could also include reductions in hemoglobin A1c (HbA1c) levels, possible improvements in insulin sensitivity, and possible reductions in visceral adiposity in individuals with Type II Diabetes Mellitus.(11) Tesamorelin & Ipamorelin and Cognitive Improvement Studies have indicated that growth hormone and its secretagogues, such as Tesamorelin and Ipamorelin, might play a role in neuroplasticity, neuronal survival, and synaptic plasticity, all of which are considered critical for optimal cognitive performance. Preclinical research has further suggested that Tesamorelin introduction may improve memory and learning abilities, possibly through its proposed impact on neurogenesis and synaptic plasticity. Furthermore, Ipamorelin has been suggested to enhance spatial memory and cognitive function in animal models. The combined influence of Tesamorelin and Ipamorelin may potentially amplify these cognitive benefits through their complementary mechanisms of action. By stimulating the growth hormone axis and modulating neurotrophic factors, this blend holds promise in cognitive improvement research. Tesamorelin & Ipamorelin Blend and Muscle Density In one of the aforementioned scientific examinations, the potential effects of Tesamorelin on muscle tissue integrity were assessed utilizing computed tomography (CT) scans. The results posited that there might be a relationship between Tesamorelin and enhancements in muscle density and size. Interestingly, certain muscle groups, notably the rectus abdominis, psoas major, and paraspinal muscles, appeared to display more pronounced changes, which were typified by either an augmentation in muscle density and size or a diminution in fat content. Statistically, these changes were distinct when compared with placebo. Yet, while it is believed that Tesamorelin's mechanism might be interconnected with molecules such as IGF-1, the study found no significant linkage between IGF-1 level shifts and modifications in muscle dimensions or density.(6) In parallel, early explorations employing experimental frameworks have posited that Ipamorelin may potentially manifest actions akin to those observed with Tesamorelin in relation to skeletal muscle and bone structures. Yet, these observations are yet to be definitively corroborated. Delving deeper, it was suggested that Ipamorelin might interface with, and perhaps elevate, IGF-I concentrations. Such interactions seemed to correlate with a surge in muscle fiber dimensions, overall muscle volume, and consequently, a potential amplification in skeletal muscle robustness during this murine investigation.(12) Tesamorelin & Ipamorelin Blend and Bone Density Ipamorelin seems to have a positive impact on bone health, potentially stimulating bone formation and fostering an enhancement in bone mass. The research posited a possible augmentation in bone mineral content that could be related to Ipamorelin. Various murine trials have alluded to the favorable effects of Ipamorelin on bone tissue.(13) (14) One specific murine study delved into the effects of Ipamorelin on bone mineral content (BMC). The findings proposed that there might be a surge in the test animals’ body weight and BMC, possibly discerned through dual X-ray absorptiometry. Yet, when standardized for body weight variations, the BMC to body weight ratio appeared consistent. An in vitro examination also indicated that the rise in cortical BMC could be attributed to an enlarged bone area, while the volumetric BMD seems to be stable. Tesamorelin & Ipamorelin Blend on Appetite and Digestion The interaction of Ipamorelin with ghrelin receptors appears to have implications for appetite modulation, potentially leading to augmented weight gain. One investigation posited that subjects exposed to Ipamorelin observed a roughly 15% ascent in body weight. It is suggested that this compound might have selectively amplified fat pad weights in relation to total body mass. Consequently, dual-energy X-ray absorptiometry assessments could reveal a nuanced increase in body fat composition. Emerging data also hints that Ipamorelin might elevate serum leptin levels, a hormone integral to energy and appetite regulation. This prompts the scientific community to consider the possibility that heightened food consumption may play a role in the documented weight augmentation within the Ipamorelin cohorts.(15) In addition, activating the ghrelin receptor also appears to affect digestion. Thus, researchers delved into the possible effects of Ipamorelin on gastric functions compared to placebo, with a spotlight on its purported ability to expedite gastric emptying. To gauge this, they employed an intricate technique that tracked the residual radioactivity in the stomach 15 minutes after the introduction of a specific substance through intragastric gavage. It was posited that abdominal surgical interventions might have played a role in decelerating gastric emptying, a phenomenon seemingly prominent in the placebo control cohort. In contrast, Ipamorelin appeared to expedite this emptying process relative to the control group. These observations suggested the potential of Ipamorelin in augmenting the rate of gastric emptying.(16) Diving deeper, the team sought to unravel the effects of this compound on the contractile dynamics of gastric smooth muscles when exposed to acetylcholine and electrical field stimulation. Data hinted that surgical manipulations of the intestines might markedly dampen the contractile responses to both inducements. Yet, intriguingly, this inhibitory effect seemed to be mitigated when Ipamorelin was co-presented with ghrelin. This introduces the tentative proposition that Ipamorelin might not just enhance gastric muscle contractility, but also possibly counterbalance the repressive outcomes instigated by specific surgical measures. (16) Tesamorelin & Ipamorelin blend is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Adrian S, Scherzinger A, Sanyal A, Lake JE, Falutz J, Dubé MP, Stanley T, Grinspoon S, Mamputu JC, Marsolais C, Brown TT, Erlandson KM. The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV. J Frailty Aging. 2019;8(3):154-159. doi: 10.14283/jfa.2018.45. PMID: 31237318; PMCID: PMC6766405. https://pubmed.ncbi.nlm.nih.gov/31237318/ Clemmons DR, Miller S, Mamputu JC. Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial. PLoS One. 2017 Jun 15;12(6):e0179538. doi: 10.1371/journal.pone.0179538. PMID: 28617838; PMCID: PMC5472315. https://pubmed.ncbi.nlm.nih.gov/28617838/ National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 16137828, Tesamorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Tesamorelin National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9831659, Ipamorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Ipamorelin Rogério G. Gondo et al, Growth Hormone-Releasing Peptide-2 Stimulates GH Secretion in GH-Deficient Patients with Mutated GH-Releasing Hormone Receptor, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 7, 1 July 2001, Pages 3279–3283, https://doi.org/10.1210/jcem.86.7.7694 Adrian S, Scherzinger A, Sanyal A, Lake JE, Falutz J, Dubé MP, Stanley T, Grinspoon S, Mamputu JC, Marsolais C, Brown TT, Erlandson KM. The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV. J Frailty Aging. 2019;8(3):154-159. doi: 10.14283/jfa.2018.45. PMID: 31237318; PMCID: PMC6766405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766405/ Stanley TL, Chen CY, Branch KL, Makimura H, Grinspoon SK. Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men. J Clin Endocrinol Metab. 2011 Jan;96(1):150-8. doi: 10.1210/jc.2010-1587. Epub 2010 Oct 13. PMID: 20943777; PMCID: PMC3038486. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038486/ Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. doi: 10.1530/eje.0.1390552. PMID: 9849822. https://pubmed.ncbi.nlm.nih.gov/9849822/ Gobburu, J. V., Agersø, H., Jusko, W. J., & Ynddal, L. (1999). Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharmaceutical research, 16(9), 1412–1416. https://doi.org/10.1023/a:1018955126402 Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban G, Loughrey H, Marsolais C, Turner R, Grinspoon S. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010 Sep;95(9):4291-304. doi: 10.1210/jc.2010-0490. Epub 2010 Jun 16. PMID: 20554713. https://pubmed.ncbi.nlm.nih.gov/20554713 Clemmons DR, Miller S, Mamputu JC. Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial. PLoS One. 2017 Jun 15;12(6):e0179538. doi: 10.1371/journal.pone.0179538. PMID: 28617838; PMCID: PMC5472315. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472315/ Andersen, N. B., Malmlöf, K., Johansen, P. B., Andreassen, T. T., Ørtoft, G., & Oxlund, H. (2001). The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 11(5), 266–272. https://doi.org/10.1054/ghir.2001.0239 Johansen, P. B., Nowak, J., Skjaerbaek, C., Flyvbjerg, A., Andreassen, T. T., Wilken, M., & Orskov, H. (1999). Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 9(2), 106–113. https://doi.org/10.1054/ghir.1999.9998 Svensson, J., Lall, S., Dickson, S. L., Bengtsson, B. A., Rømer, J., Ahnfelt-Rønne, I., Ohlsson, C., & Jansson, J. O. (2000). The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. The Journal of endocrinology, 165(3), 569–577. https://doi.org/10.1677/joe.0.1650569 Lall, S., Tung, L. Y., Ohlsson, C., Jansson, J. O., & Dickson, S. L. (2001). Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochemical and biophysical research communications, 280(1), 132–138. https://doi.org/10.1006/bbrc.2000.4065 Greenwood-Van Meerveld, B., Tyler, K., Mohammadi, E., & Pietra, C. (2012). Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. Journal of experimental pharmacology, 4, 149–155. https://doi.org/10.2147/JEP.S35396 { "@context": "https:\/\/schema.org", "@type": "Product", "name": "Tesamorelin & Ipamorelin Blend (8mg)", "description": "Tesamorelin & Ipamorelin blend for sale (8mg). Purchase peptide blends at 99+% purity with unmatched customer service and free shipping.", "image": "https://www.painandanxietymeds.shop/wp-content/uploads/2023/06/Tesamorelin-Ipamorelin-6-2-MG-300x300.jpg", "offers": [ { "@type": "Offer", "priceCurrency": "USD", "price": "90", "availability": "https:\/\/schema.org\/InStock", "itemCondition": "https:\/\/schema.org\/NewCondition", "seller": { "@type": "Organization", "name": "painandanxietymeds.shop" }, "url": "https:\/\/www.painandanxietymeds.shop\/tesamorelin-ipamorelin-blend-8mg/", "hasMerchantReturnPolicy": { "@type": "MerchantReturnPolicy", "applicableCountry": "US", "returnPolicyCategory": "https:\/\/schema.org\/MerchantReturnNotPermitted" }, "shippingDetails": { "@type": "OfferShippingDetails", "shippingRate": { "@type": "MonetaryAmount", "minValue": 0, "maxValue": 9.25, "currency": "USD" }, "shippingDestination": { "@type": "DefinedRegion", "addressCountry": "US" }, "deliveryTime": { "@type": "ShippingDeliveryTime", "handlingTime": { "@type": "QuantitativeValue", "minValue": 1, "maxValue": 2, "unitCode": "d" }, "transitTime": { "@type": "QuantitativeValue", "minValue": 1, "maxValue": 5, "unitCode": "d" } } }, "priceValidUntil": "2027-12-20T15:11:59+00:00" } ], "url": "https:\/\/www.painandanxietymeds.shop\/tesamorelin-ipamorelin-blend-8mg/", "aggregateRating": { "@type": "AggregateRating", "ratingValue": 98, "bestRating": 100, "reviewCount": 524 }, "review": [] } Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.