Peptide therapy, or the use of specific peptides in treatment, has gained great popularity in recent years. This is due largely to the fact that these peptides are highly specific (i.e., only do what you want them to do) while also being well-tolerated and safe. As of January 2015, there were over 60 US FDA-approved peptide medications, 140 peptide drugs being evaluated in clinical trials, and 500 in pre-clinical development.
A synthetic analogue (AOD9604) of the lipolytic domain of human growth hormone (hGH) has been studied for its metabolic actions in obese Zucker rats. Daily treatment with an oral dose of AOD9604 of 500 microg/kg body weight for 19 days reduced over 50% (15.8 +/- 0.6 vs. 35.6 +/- 0.8 g) body weight gain of the animals in comparison with the control. The adipose tissues of the AOD9604--treated animals were found to have an increase in lipolytic activity. In contrast to chronic treatment with intact hGH, chronic treatment with AOD9604 showed no adverse effect on insulin sensitivity of the animals, as demonstrated with euglycemic clamp techniques. The results in the present study suggest that the analogue of the hGH lipolytic domain may have the potential to be developed into an orally usable and safe therapeutic agent for obesity.
The simple science of amino acids linked together, via peptide bonds, brings to life this now common word – “Peptides”. Used for a variety of health, fitness and anti ageing concerns, Peptides can help in many ways to promote fat loss, build lean muscle, assist with injury recovery, increase agility, and many other anti ageing benefits. Peptides are amino acid chains that act as messengers in the cellular world by telling your cells what to do. One of the world’s best kept secrets for optimal health is Human Growth Hormone (HGH). HGH is so instrumentally important that its decline as we age is directly related to our health and quality of life. Modern medicine is now recognising its decrease as a clinical syndrome called “Growth Hormone Deficiency Syndrome”. By stimulating your Growth Hormone levels back to a level that is clinically predicted for your age will allow your body to perform at its peak which allows you to feel youthful and rejuvenated.
Growth hormone releasing peptide (GHRP) 2 is a type of peptide therapeutic that mimics the effects of ghrelin, the “hunger hormone”. Ghrelin is a hormone that helps regulate appetite as well as energy distribution and rate of use, or metabolism. In the 1980’s, ghrelin was discovered to be the body’s natural ligand (or binding molecule) of the GHRP receptor in the anterior pituitary. This was a significant discovery, as it highlighted the role of ghrelin in hGH secretion and growth regulation. Modern biotechnology has used this knowledge to develop peptides that can be administered to mimic ghrelin’s hGH stimulation, but in a more targeted fashion. GHRP 2 is one such peptide, stimulating hGH secretion by 7-15 times, increasing appetite and meal initiation, while also decreasing fat mass and cholesterol. GHRP 2 is ideal for patients who are hypercatabolic, due to critical illness, cancer, AIDS, etc. It should be noted that GHRP 2 can also increase levels of prolactin, aldosterone, and cortisol.
For example, insufficient protein or calories can cause IGF-1 to plummet, while ample calories can cause IGF-1 to increase. For example, one study of women who fed with excess calories over and above their normal metabolic rate noted a 19% increase in IGF-1 after two weeks of overfeeding, with 46% of the weight gain from lean mass and 54% from bodyfat. Fasting insulin doubled in these women, and testosterone levels also significantly increased.
Growth Hormone Releasing Peptides (GHRP): include Ipamorelin, GHRP-2 and GHRP-6, peptides which stimulate the release of a hormone called "Ghrelin" in the stomach, which then in turn causes GH to be released. GHRP's cause a much more significant release of GH than do GHRH, meaning that mg for mg, a peptide like GHRP-6 is three times more potent than Modified GRF 1-29. However, when taken together, they become approximately ten times more potent than either one alone.
Django Nathan, a medical doctor with a degree in molecular biology and genetics, takes peptides because of his busy lifestyle: "Quite a few doctors I know are using them because they have so many beneficial effects and so few side effects. We're not elite athletes – we live rushed lives that can involve 70 hour weeks so staying fit and getting good sleep is essential – and peptides aid that."
For Growth Hormone (GH) to perform its anabolic (muscle building) affects it requires the presence of the body's most anabolic hormone: insulin. This is in contrast to GH related fat loss which requires insulin to be absent. However, since GHRP and fast-acting GHRH (Growth Hormone Releasing Hormone) products (i.e. Modified GRF 1-29) still need time to stimulate the body to release GH from the pituitary gland, the insulin spike must come after the injection and not before, otherwise the GH release will be blunted.
From the standpoint of protein synthesis and muscle repair, IGF-1 injections have also been shown to enhance the anticatabolic effects of insulin and to increase the protein synthesis normally induced by growth hormone. This is because, like insulin, IGF-1 encourages amino acid uptake into muscle cells, stimulates peripheral tissue uptake of glucose (which lowers blood glucose levels), and suppresses liver glucose production. That last fact is important and is actually why IGF-1 is even being considered as a diabetes-prevention drug. Insulin resistance can cause the liver to produce excess glucose, which then causes even more insulin insensitivity and can eventually result in type II diabetes, and IGF-1 can decrease the need for this type excessive insulin release.
You’ve already learned that sufficient protein intake (above 0.5g/lb of body weight) can assist with adequate IGF-1 and growth hormone production. Whey protein provides your body with a complete profile of necessary amino acids, including leucine. Leucine is an amino acid that promotes greater muscle protein synthesis and assists the body while gaining lean muscle mass and losing fat tissue simultaneously.
It is well known that hGH is associated with increased IGF-1 levels. IGF-1 may have a variety of undesirable effects, including an increase in cancer risk [22, 23]. In the studies discussed herein, IGF-1 levels were monitored in all long-term studies but did not reveal clinically significant differences between dose groups or placebo. Therefore the 5 SAEs that occurred in the 12 week treatment study (three in the AOD9604 20 mg group (basal cell carcinoma, moderate lipoma and squamous cell carcinoma), one in the 10 mg group (malignant melanoma) and one in the 5 mg group (breast cancer)) could not be attributed to increased IGF-1 levels. The Principal Investigator considered none of the reported SAEs to be “possibly”, “probably” or “definitely related” to the study medication. The rationale behind this judgment was that none of the cancer forms occurred in the highest dosage group (30mg AOD9604/day), therefore a dose effect can be excluded. Further examination of the SAE cases indicated that these subjects had neglected their personal medical care for a longer period of time, so that the higher incidence of cancer may well have occurred due to the natural incidence rate of cancer events in the population.
These peptides are inhibitors of a protein called myostatin. Myostatin is secreted by muscle cells and acts to essentially block the development of new muscle fibers and, thus, the development of lean muscle mass. In fact, individuals who have mutations in the gene coding for this protein have significantly more muscle mass and enhanced strength. The administration of follastatin peptides can generate enhanced muscle mass and strength, and has been found especially useful in patients suffering from muscle-wasting diseases or who have difficulty gaining muscle.
Strengths of our study include the serial physiologic assessments before and after bariatric surgery. The gastric bypass procedure ensured a large degree of weight loss (≈27% mean change in BMI), while the administration of normal saline provided an acute stimulus for eliciting acute natriuretic peptide responses. Thus, we were able to compare the relative effects of weight loss and saline infusion, with each individual serving as his or her own control. This study design minimizes confounding from sources of natriuretic peptide variation that might correlate with BMI. We performed the post‐surgical assessment 6 months after surgery to ensure that acute hemodynamic changes from surgery had resolved and patients had attained most of their expected weight loss. Mitral annular early diastolic (e′) velocity at the lateral annulus has been accepted as an index of diastolic function24, 25 and we had significant improvement in e′ suggesting improvement in myocardial relaxation. Our echocardiographic findings are in accordance with the recently published meta‐analysis demonstrating benefits of bariatric surgery on diastolic function.26
Like everything in life, you need to be careful. Too much of a good thing can be bad. Water and oxygen are essential for survival, however in excessive amounts be prepared to have ‘000’ on standby. The same principal is true for any drug or peptide. When used at the recommended dose, clinical trials have proven peptides to be effective with minimal side effects, if any. In addition, the body even has its own natural feedback mechanisms in place to downregulate high levels.
You will learn that no single method of using Ipamorelin is right or wrong, and there is more than one route (and dosage cycle length) you can choose, when you do incorporate Ipamorelin into your diet and exercise regimen. Regardless of how high or how long the dosage cycle is, you want to start off on the lower end when you are new to using Ipamorelin, or any growth hormone for that matter. Not only will this reduce the potential risk of experience the side effects, it also ensures your body will ingest the highest levels into the bloodstream. And, it will allow you to gradually increase the dosage and cycle lengths, in order to eventually get to the ideal levels which work best for your body, and for the intended/desired goals you are trying to achieve when using Ipamorelin daily.
This peptide is a modified fragment of hGH which contains the portion of the molecule that is believed to be responsible for hGH’s anti-obesity effects. The peptide has been shown to increase fat burning without the increase in blood sugar and growth rate that has been seen with hGH itself. AOD 9604 has been deemed safe for chronic use by the FDA, receiving Human GRAS status in 2014. In addition to its utility as an anti-obesity peptide, AOD 9604 has been shown to have very favorable cartilage repair and regenerative properties, especially when paired with peptide BPC 157.
If you are interested in using fat loss supplements to assist in your weight loss journey but have never used peptides before, don’t worry, our clinic doctor is available to answer any of your questions. To discuss any concerns, simply email your questions to firstname.lastname@example.org and our doctor and professional team will get back to you so you can be one step closer to starting your weight loss journey. Want to find out more information right now? Why not see if your questions have already been answered in our FAQs?
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Time line of collagenase, saline, HA and AOD9604 injection. Collagenase (0.25 mg) was injected in right knee twice on day 1 and 4, respectively. Normal saline 0.6 ml (group 1), HA 6 mg (group 2), AOD9604 0.25 mg (group 3), and AOD9604 0.25mg with HA 6 mg (group 4) were injected in the right knee at 4 weeks after the first collagenase injection. All rabbits were euthanized by CO inhalation at 4 weeks after injection of 4 different solutions.
As in the previous study there were no clinically relevant changes observed in safety laboratory parameters 24 hours following administration of AOD9604 or placebo. Similarly, there were no clinically relevant changes in vital signs (blood pressure, radial pulse rate and temperature) or ECGs recorded at any of the scheduled time points up to 24 hours post dose. There were no significant changes in glucose or IGF-1 levels following AOD9604 treatment compared with placebo.
3. Since actual HGH shuts down the body's natural pituitary gland, when you stop injecting it, your body's own ability to produce Growth Hormone is hindered and you will suffer a rebound of negative side effects such as fat gain, muscle loss and loss of skin tone/elasticity. This means you may end up doing yourself more harm than good. Since GH releasing peptides only stimulate your body's own natural production, there is no rebound negative effects if you stop usage.
With a blend of peptide and GH supplements, Ipamorelin can greatly help you in your weight loss endeavours. Using it with IGF-1 which is a natural growth hormone, can help you achieve even greater results. With lower dosage, you won’t increase muscle mass, your body will naturally decrease body fat levels, and you will begin to metabolize food faster, meaning you burn more calories in less time, for greater weight loss results.
Mean gross morphological and histopathological scores in Group 1 were significantly higher than those in Groups 2, 3, and 4 (p<0.05). Mean gross morphological and histopathological scores in Group 4 were significantly lower than those in Groups 2 and 3 (p<0.05). However, there are no differences between the mean gross morphological and histopathological scores of Groups 2 and 3 (Figures 4 and 5).
Lean C57BL/6J and obese (ob/ob) mice aged 12 wk were used in this study. There were 18 mice in each group, and they were divided into three treatment groups [saline (n = 6); AOD (250μ g/kg·d; n = 6); hGH (1 mg/k·d; n = 6)]. The animals were housed in the Departmental Animal Facility at a constant temperature and humidity in a 12-h light, 12-h dark cycle. Animals were injected with a single intraperitoneal dose of saline, AOD9604, or hGH at 0800 h each day for 14 d using a 1-ml syringe and 23-gauge needle. The body weights of the animals were recorded every second day along with food intake.
The company which developed it, Metabolic Pharmaceuticals, did have a small early study done which showed a small amount of fat loss at 1 mg per day but not really any other dosing. Measured effect was less at higher doses. In total the company did at least six studies. According to the lead researcher of five of the studies, Dr Gary Wittert, results were uniformly negative.
Comparing everything else is hard due to branding... don't want to start going into branding for obvious reasons. GH is incredible for fatloss but some brands add so much water it is hard to see the results to begin with. But due to the high serum and igf-1 from gh excellent results are to be had. Many factors come into play though which I am sure your well aware of. I think the ghrp's (2 and 6 for example) are excellent for fatloss if you keep up with the 4 daily injections in your research. Otherwise they are nowhere as effective due to the short peak times... so one must be organized and disciplined to get the full benefits.
The duration (treatment and follow up) of the individual studies depended on the type of study (supplementary data). The first three clinical trials were single dose treatments (METAOD001 - METAOD003); the longest was a phase IIb clinical trial (METAOD006) with a four weeks run-in phase, followed by a six months treatment phase and a 30 day follow-up phase.
The knee joints were dissected after euthanasia. The medial and lateral condyles of the femur and tibia were examined for gross morphological changes. The degree of cartilage degeneration on the lateral part of the femoral condyle was assessed using the scoring system devised by Yoshimi et al. . This area was assessed because the intra-articular collagenase injections had caused most damage at this area . Normal cartilage was scored as 0, softened cartilage as 1, fibrillated cartilage as 2, eroded cartilage as 3, ulcerated cartilage as 4, and loss of cartilage as 5.
As simple and basic as it is, eating less calories is much harder in practice than it sounds. Ask anyone who has ever gone on a diet before! Everyone knows if you want to lose weight, you need to eat less. It’s the first step of any legitimate diet and fitness program, but how much less, and what to eat remains a mystery to many dieters. Or, the results don’t come quickly enough and the dieter gives up before real results are experienced.
The effect of AOD9604 and hGH on β3-ARs in adipose tissue is believed to be a direct action of these compounds and not an effect secondary to the fat metabolism, given that both AOD9604 and hGH can influence β3-AR expression and function in a nonadipocyte human cell line (11). Hence, the β3-AR appears to be necessary for the chronic effectiveness of AOD9604 on lipolysis in BAT.
Background: The human growth hormone (hGH) has properties making it a potential candidate to treat obesity, however safety issues limit its long-term use. AOD9604 is a peptide fragment of the C-terminus of hGH (Tyr-hGH177-191), which harbors the fat reducing activity of hGH, without its negative effects. In this paper the safety data of AOD9604 obtained in clinical trials are summarized.
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