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Overall, there were no AEs that were deemed to be “definitely related” to the study treatment. The percentage of AEs that were deemed to be “probably” or “possibly related” to study treatment was similar among all treatment groups including placebo. The most common classes of AE deemed to be “probably” or “possibly”related to study treatment were gastrointestinal disorders (5.2% overall) and nervous system disorders (4.9% overall).
Prior studies have been largely observational, and based on measurement of natriuretic peptide levels collected in individuals with random salt intake. Because natriuretic peptide levels are dependent on loading conditions, more controlled physiologic data are needed. Accordingly, the aim of the current investigation was to study the natriuretic peptide axis in the context of a well‐controlled physiologic stimulus (intravenous saline infusion) in obese, otherwise healthy, individuals. This study design also enabled us to compare the relative effects of weight loss and intravenous saline infusion on circulating natriuretic peptide levels.
Steve Coggan, Chatswood, Sydney, “I am 48 and been weightlifting for 20 years. I have used CJC 1295 and Ipamorelin on their own and together, and have to say that when combining them they work better and faster. I have been using them for the past year, with 2 rest times. The combination of CJC 1295 Ipamorelin, is proving fantastic all round. Not only am I increasing muscle, my weight is down, but my skin is looking great. Some of the bags under my eyes have more or less gone. My missus thinks I look 10 years younger! Also, it has helped in the recovery of an injury to my knee after a fall. I have to say it isn’t cheap, but the results are worth it. CJC 1295 Ipamorelin side effects were few, just some headaches at first. You need to use it with a good diet and fitness regime for best results. I will definitely be continuing with it!”
Endurobol (GW501516): Classified under a group of drugs called peroxisome proliferator-activated receptor (PPAR) agonists, Endurobol’s potential abuse in athletes is based on animal studies that showed it could improve endurance, increase fat metabolism, improve glucose uptake in skeletal muscle tissue, and increase in muscle gene expression. At the moment, there is insufficient evidence for these sport performance outcomes in humans. Human side-effects are currently also unknown. Endurobol is prohibited both in and out of competition under WADA’s Prohibited List.
For the Anti-Aging crowd, we recommend choosing only 1 peptide, rather than a combination. The reason for this is that as you get older your GH levels decline rapidly and therefore you will benefit from any kind of GH increase meaning there is no need to overdo things with multiple peptides. If you wish to use more than one peptide, we recommend cycling a GHRP product (GHRP-6, GHRP-2 or Ipamorelin) every 3-6 months with CJC-1295 DAC for two reasons.
In the 80 years, scientists have searched different peptides and more particularly GHRH to discern what part was necessary to stimulate the pituitary response. Then in testing Sermorelin as a tool for the process of anti-agingthey found that it was the famous 1-29 chain that was responsible for stimulating the endocrine gland in question. Similarly, many studies have shown that this peptide was similar to GHRH and very well tolerated by the body.
Hey Elvia, do you think that using DAC for short periods of time at your proposed dose is still effective for fat loss? Say for four weeks at 4mg a week? I know peptides need to be used for awhile before effect can be seen. I was thinking about doing 4mg a week for 4 weeks with Injectable l-carnitine for my last 4 weeks before summer haha. In your experience is it worth it to spend the money on the DAC for such a short period?
Echocardiographic measurements obtained at pre‐ and post‐bypass visits are outlined in Table 2. Due to limitations in scanning windows and poor image quality, interpretable echocardiograms were obtained in 12 of 15 patients. Transmitral E increased from 76±19 cm/s at pre‐bypass to 83±19 cm/s at the post‐bypass surgery visit while no significant increase was noted in transmitral A. The mean intra‐individual change in transmitral E was 15 cm/s, with 95% confidence interval 3 to 26 cm/s. The increases in transmitral E were significant for the effects of saline (P=0.005) and surgery (P=0.002). There was also a significant increase in the early diastolic mitral annular velocity e′ (P=0.02 for effect of surgery). However, the E/e′ ratio did not change after surgery (Table 2). Left atrial diameter showed a trend towards decrease at the post‐bypass surgery visit (P=0.3).
Another way GH helps with fat loss is that it maintains blood glucose levels by inhibiting glucose uptake into peripheral cells, decreasing glucose oxidation for energy in the cells, and therefore increasing glucose production in cells from fat and amino acids (gluconeogenesis) (Copeland 1994, Ho 1996). The free fatty acids in the blood from lipolysis also partially block the insulin receptors on cell membranes, decreasing the effectiveness of insulin in triggering the removal of glucose from the blood, causing insulin resistance, or decreased insulin sensitivity. These all result in fat loss, especially from hard to move intra-abdominal fat stores (Johannsson 1997).
Within all clinical trials the subjects underwent physical examination. The vital signs were observed, laboratory parameters were analyzed (hematology; biochemistry, urinalysis, lipid analysis), and ECG were measured before and after treatment (or in between and follow-up depending on the duration of the study). All subjects were interviewed at each visit with regard to any adverse events (AEs) they had experienced since the previous visit. The causality of AEs (namely their relationship to trial treatment) was assessed by the Principal Investigator. Special attention was made to on the evaluation of Serious Adverse Events (SAE).
The increase in GH secretion due to IPAMORELIN (and other GHRP) leads to an increase in IGF-1 (thought to be the anabolic mechanism of GH). As we get older GH and subsequently IGF-1 decrease substantially. This decline is thought to be one of the major causes of the ageing process. By increasing these levels again there is increased collagen synthesis, promotion of lean muscle mass, bone strength, improved healing capability, improved sleep cycle, increased energy, repair and regeneration of internal organs, strengthening of joints/cartilage/connective tissue, and anti ageing effects on the skin.
200 to 300 mcg is typically the daily dosage which is recommended for the typical Ipamorelin user. It can be taken anytime during the day but is advisable to be used in the morning, as it will help you achieve the best results in such cases. Regardless of when you start your dosage, it is important to ensure you are taking it at the same time each day. And, for new users, it is best to stick to a one-a-day cycle.
CJC-1295 is basically a peptide hormone that acts similar to growth hormone releasing hormones (GHRH). Invented by a Canadian biotechnology company called ConjuChem, it is beneficial to athletes because it can bioconjugate with circulating albumin and increase the time it can be used for medical purposes. It achieves this by preventing degradation of its amino acids. With a single dose, it can remain in the body for quite a few days and can cause the growth hormone to be released many times per day. This reduces the frequency of injections needed.
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) used in the management of mild to moderate pain and inflammation in conditions such as dysmenorrhoea, headache including migraine, post-operative pain, dental pain, musculoskeletal and joint disorders such as ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis including juvenile idiopathic arthritis, peri-articular disorders such as bursitis and tenosynovitis, and soft tissue disorders such as sprains and strains. It is also used to reduce fever.
23 Pivovarova O, Gogebakan O, Kloting N, Sparwasser A, Weickert MO, Haddad I, Nikiforova VJ, Bergmann A, Kruse M, Seltmann AC, Bluher M, Pfeiffer AF, Rudovich N. Insulin up‐regulates natriuretic peptide clearance receptor expression in the subcutaneous fat depot in obese subjects: a missing link between CVD risk and obesity?J Clin Endocrinol Metab. 2012;97:E731–E739.CrossrefMedlineGoogle Scholar
The first was a double-blind, placebo-controlled, parallel group, multi-center study (5 Australian hospitals) (METAOD005). In this study 300 healthy obese males and females (BMI ≥ 35 kg/m2; Median BMI: 40 kg/m2, range: 35 to 67 kg/m2; 30 to 65 years old; 54% males and 46% females) were randomized to a 14-week period of daily oral dosing. The treatment period comprised a 2-week single-blind placebo run-in period followed by 12 weeks administration of either placebo or AOD9604 (1, 5, 10, 20 or 30 mg AOD9604 or placebo once daily; n =50 per group).
Specifically, T α 1 has been shown to enhance the function of certain immune cells called T and dendritic cells. This is very important to anyone with a depressed immune system or suffering from an infection, as these white blood cells play pivotal roles in the body’s defense process. T cells, for example, come in two forms: killer and helper T cells. Killer T cells are responsible for hunting down and destroying our body’s own cells that are cancerous or infected with bacteria or viruses. Helper cells work with the other cells of the immune system to orchestrate and carry out appropriate immune responses.
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.
There are several limitations of our study. Given the nature of our physiologic protocols, which required two large volume saline infusions in obese patients before and after surgery, our sample size was modest. Nonetheless, we were able to elicit significant relationships of all four natriuretic peptides (ANP, Nt‐proANP, BNP, and Nt‐proBNP) across a variety of salt conditions before and after surgical weight loss. Our study population consisted of primarily females. We do not believe from prior epidemiologic studies looking at resting natriuretic peptide levels in obese individuals12 that having more men in our cohort would have modified our findings. Prior epidemiologic studies do not suggest that gender modifies the association between obesity and natriuretic peptide concentrations. We did not examine short‐term changes in the natriuretic peptide system, as a physiologic assessment immediately after surgery would have been impractical and potentially confounded by post‐operative shifts in volume or nutrition. We also focused on surgical weight loss because weight loss with non‐surgical treatments is less consistent. Thus, we cannot exclude any surgery‐specific effects. Because the saline infusion was indexed to BSA, less saline was given at the post‐weight loss visit. This could have created a “conservative” bias, eg, toward observing a smaller natriuretic peptide response after surgery. Indexing was performed to ensure that the amount of saline relative to plasma volume was relatively constant. Lastly, we did not perform a complete assessment of the renin‐angiotensin‐aldosterone system and the sympathetic nervous system, all of which could also be primarily affected resulting in the observed responses of the natriuretic peptide system after weight loss and/or saline loading.
The effects of hGH and AOD9604 on fat metabolism may be mediated by an alteration in the expression of a lipolytic/antilipogenic gene. Theβ 3-AR is a major lipolytic receptor identified in rodent fat cells (18) that mediates its effects through G protein coupling to adenylate cyclase, generation of cAMP, and stimulation of PKA (19). This enzyme then phosphorylates proteins in the lipolytic cascade, including hormone-sensitive lipase (20). In BAT, the β3-AR stimulates uncoupling of the electron transport chain, enhancing the ability of mitochondria to generate heat in preference to ATP through the dissipation of the electron gradient (21). Mice that lack this receptor have lower rates of resting energy expenditure (0.0041 vs. 0.0047 kcal/min, P < 0.02) and lower rates of fat oxidation (0.00019 vs. 0.00030 g/min, P < 0.02) than control mice (data not shown).
Echocardiograms were performed before and after saline infusion at both the baseline and post‐gastric bypass surgery visits. Each subject had four echocardiograms in total during the entire study. Interpretations were made by investigators blinded to clinical status (before or after saline infusion, before or after surgery). The following standard measures were made on two‐dimensional (2D) images in each echocardiogram: interventricular septal and posterior wall thickness (IVS and PWT), left ventricular internal diameter at end‐diastole and end‐systole (LVID, LVIS) and left atrial anteroposterior diameter (LA Dia) in the parasternal view, left ventricular (LV) volumes using a modified Simpson's rule (apical 4 chamber and 2 chamber views), mitral inflow E and A velocities and E deceleration time, and mitral annular early diastolic (e′) velocity at the lateral annulus. We did not calculate left atrial volumes due to limited echocardiographic windows in severely obese patients. Estimation of left atrial filling pressure was obtained every 20 minutes during the second hour of the infusion by determining the ratio of the early diastolic mitral inflow velocity to the early diastolic mitral annular velocity.15
Abellan R, Ventura R, Palmi I, di Carlo S, Bacosi A, Bellver M, Olive R, Pascual JA, Pacifici R, Segura J, Zuccaro P, Pichini S. Immunoassays for the measurement of IGF-II, IGFBP-2 and -3, and ICTP as indirect biomarkers of recombinant human growth hormone misuse in sport. Values in selected population of athletes. J Pharm Biomed Anal. 2008 Nov 4;48(3):844-52. doi: 10.1016/j.jpba.2008.05.037.
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