A MEDICAL FOOD
Progressive loss of muscle beginning subtly as early as twenty-five years of age affects every person over the course of their adult lives. Spontaneous and progressive muscle weakness with actual loss of lean body mass accelerates over time resulting in frailty, loss of functional mobility and independence as well as increased risk for development of intrinsic disease (1 – 3). Thus, sarcopenia is an important cause of morbidity and mortality as we age. However, it is potentially reversible through appropriate changes in life style, exercise and regular use of anabolic food complements such as Sarcotropin.
Contributing factors to muscle loss during aging include physical inactivity, improper nutrition, decline in hormones, insufficient micronutrients and other catabolic factors. Thus, in addition to a moderate regimen of resistance exercise, sarcopenia can also be effectively managed with protein-energetic substances that are anabolic to the muscles of aging adults. Sarcotropin was specifically formulated to oppose the causal molecular deficiencies underlying age-related muscle loss.
Recognizing the anabolic value of human growth hormone (hGH), the first pituitary hormone to decline during aging (4), selection of Sarcotropin ingredients capable of increasing that specific hormone has received significant attention. In this regard, secretagogues that directly stimulate pituitary somatotrophs to produce and secrete hGH are particularly effective. One such molecule is growth hormone releasing peptide-2 (GHRP-2; DAlaDßNalAlaTrpDPheLysNH2) an analog of the endogenous gastrointestinal (GI) peptide, ghrelin (5) that displays comparable activity in vivo (6). In addition to its ability to increase hGH production and secretion, GHRP-2 also exhibits other ghrelin-like properties that are potentially valuable for therapeutic application. Some of these include stimulation of appetite, growth and muscle mass in children and adults (7 - 10) as well as control of gastric motility and secretion, modulation of pancreatic and immune functions, glucose metabolism, cardiovascular performance, sleep and behavior (see 6). Furthermore, because of their small size and structural resistance to digestion by proteolytic enzymes, GHRP-2 is orally bioavailable making it even more suitable for therapeutic application (11 - 12).
In addition to GHRP-2, additional active ingredients in Sarcotropin include ß-hydroxy ß-methyl-butyrate (HMB), Vitamin D, and extract of Mucuna pruriens. While GHRP-2 increases lean body mass, ß-hydroxy-ß-methyl butyrate (HMB), a metabolite of leucine inhibits proteolysis of newly synthesized muscle protein (13).
.Vitamin D plays an essential role in muscle growth and development (14) and in regulating muscle contractility. On the other hand, Vitamin D deficiency is associated with a loss of muscle strength (15) and function (14.) and an increased risk of falling (16.). However, there is evidence that these deficits can be improved by vitamin D supplementation supporting a putative role for vitamin D in preventing sarcopenia (17).
Mucuna pruriens, also called velvet bean or cowitch, is a legume the extracts of which are used for a variety of purposes including treatment of diseases, development of muscle mass and enhancement of growth hormone and testosterone secretion. Its endocrine effects result from the action of L-DOPA, a naturally occurring amino acid that increases brain dopamine which in turn enhances pituitary growth hormone production and release (18, 19).
Based upon these complementary anabolic effects on muscle and the body in general, the ingredients found in Sarcotropin oppose development of sarcopenia, which is perhaps the most significant threat to health and vitality that occurs during aging.
Extensive review of the endocrine and toxicology literature has failed to identify any report(s) of general or reproductive toxicity nor of carcinogenicity for GHRP-2 in animals or humans. In fact, many peer-reviewed publications make anecdotal comment that the peptide is safe for human use and without side effects even when administered at relatively high daily doses for a year or longer (8 - 10). To further ensure the safety of GHRP-2, a literature search of ghrelin side effects was performed to determine if pathophysiological effects might result from the influence of GHRP-2 on ghrelin target sites including the stomach, GI tract, pancreas, heart and brain. However, none were found suggesting that the molecule is free from side effects. Support for this view derives from a report that pre-pubertal children weighing on average 45 kg, received 900 µg GHRP-2 orally, twice daily for eight months without experiencing any adverse effects (8). Similarly, it was well tolerated when administered intranasally for as much as two years (10). Finally, a series of toxicological studies were commissioned by Prosoma, to determine the safety profile for GHRP-2. When tested for acute oral toxicity (LD50), the peptide was found to be safe at 2000 mg/kg when administered to Wistar rats as two divided dose within a one hour interval. Hence it was declared to be GHS-5 or a very safe category. Furthermore, after repeated oral administration of GHRP-2 for 90 days, there were no adverse effects observed in any parameters of study and a No Observed Adverse Effect Level (NOAEL) for the test article was found to be 50 mg/kg. When converting Animal Dose in mg/kg to Human Equivalent Dose (HED), regulatory guidelines recommend that when HED is based upon rat NOAELS, either divide the animal dose by 6.2 or multiply it by 0.16 (20). Based upon this recommendation, a NOAEL for human clinical application of GHRP-2 would be approximately 8 mg/kg. Heretofore, the highest therapeutic dose administered orally to human beings for as long as one year was 0.9 mg/kg twice daily (or 1.8 mg/kg/day). It has been administered intranasally for twice as long without any evidence of side effects (10). While effective in stimulating growth hormone for realization of its intended clinical benefits, the risk of dose-related adverse events occurring at the therapeutic doses was non-existent. Furthermore, doses as low as 4 mg orally or 1 mg subcutaneously per day which are currently being used to sustain lean body mass during aging are equivalent (based upon a 60 kg human being) to only 0.07 or 0.02 mg/kg/day, respectively.
Using the bacterial reverse mutation assay (AMES test), GHRP 2 was non mutagenic up to dose of 2 mg/ml. The results of mammalian bone marrow micronucleus study and bone marrow chromosome aberration test of GHRP 2 in Swiss albino mice indicated that the peptide is non-genotoxic and non-mutagenic up to 2000 mg/kg/day when administered for two consecutive days. Thus, animal studies of general, cytotoxicity and genotoxicity were all negative indicating that GHRP-2 has a high margin a safety. Full reports on the results of these pre-clinical toxicity tests are on file and available for review at the archives of ProSoma LLC, Clearwater, FL.
Thus, the absence of publications reporting side effects in human subjects receiving GHRP-2 is not surprising. In conclusion, the findings of studies reported herein, taken in conjunction with a history of three decades use in human subjects without a single report of toxicity in the peer-reviewed literature, support the view that the peptide is safe and effective for treatment of age-related sarcopenia as a component of medical foods or nutritional supplements.
The metabolite of leucine, ß-hydroxy ß-methyl butyrate (HMB) is included in the Sarcotropin formula because of its ability to decrease muscle protein catabolism. Because evidence of toxicity has not been linked to the molecule, there are no bans or restrictions on its use in food supplements. While leucine the precursor of HMB is known to be safe and effective, extremely high doses, well beyond those used in the Sarcotropin formula may cause symptoms of reduced blood sugar as a result of its ability to stimulate insulin secretion (21). Nine studies designed to evaluate HMB safety in which humans found it to be safe for use as an ergogenic (performance enhancing) aid that benefits cardiovascular/general health and improves perception of well-being (22). The studies were from 3 to 8 weeks in duration, included both males and females, young and old, exercising or non-exercising subjects. Organ and tissue function was assessed by blood chemistry and hematology; subtle effects on emotional perception were measured with an emotional profile test and tolerance of HMB was assessed with a battery of 32 health-related questions. HMB did not adversely affect any surrogate marker of tissue health and function. Furthermore, the effects of HMB on surrogate markers of cardiovascular health suggests that it may decrease the risk of heart attack and stroke.
The Mucuna prurients plant has demonstrated little toxicity; however, when administered at very high doses to experimental animals it may cause birth defects. Thus, the product should not be used during pregnancy (11).
As one of the safest substances known to man, vitamin D toxicity is very rare. In fact, people are at far greater risk of vitamin D deficiency than they are of vitamin D toxicity (23). However, as with all substances that are capable of affecting bodily functions, extremely high doses can cause toxicity. For example, hypervitaminosis D is a condition that occurs after taking very high doses of vitamin D that causes abnormally high levels of calcium in the blood (24). However, such toxicity occurs at doses more than ten times higher than that found in the Sarcotropin formula.
Toxicities of the inactive ingredients (preservative and water) used in the Sarcotropin formulation have been previously reported and are generally regarded as safe for use at the dosages employed.
Finally, clinical studies were recently completed on the Sarcotropin formulation. The results showed the product is effective in its claims and safe for human consumption. Thus, Sarcotropin has been shown to lack side effects and that if any adverse events are reported, they should be of no greater severity or frequency than those occurring spontaneously by chance.
A total of 94 male and female healthy subjects were enrolled of which 53 were male (56.38 %) and 41 were female (43.62 %). Of these, 75 subjects completed the study. Out of the 75 on-study subjects, 50 (M - 29 and F - 21) were in the treatment group whereas 25 subjects (M - 13 and F - 12) were in the placebo group. Nineteen subjects were discontinued from the study for personal reasons and/or due to adverse events.
The mean age of all subjects on treatment ranged from 40 to 68 years with a mean of 48.89 ± 0.992 years, mean height 163.56 ± 1.25 cm and mean weight of 71.67± 2.07 kg. The mean age of all subjects in the placebo group ranged from 40 to 62 years with a mean of 49.50 ± 1.24 years, a mean height of 159.57 ± 4.02 cm and mean weight at 72.60 ± 3.86 kg.
Insulin-like growth factor-1 (IGF-1) was significantly increased from 103.54 ± 1.94 ng/mL at baseline to 111.40 ± 2.01 ng/mL at day 45. Levels further increased to 120.47 ± 2.10 ng/mL after 90 days of treatment. In contrast, there were no significant changes in IGF-1 levels in subjects receiving placebo.
Body Mass Index (BMI) and total body water did not change significantly in either treatment or placebo groups during the course of study.
Total body fat was significantly decreased in the treatment group from 34.46 ± 1.23 % at baseline to 32.54 ± 1.04 % on day 45 and to 31.31 ± 1.11 % at the end of treatment. The decrease in body fat after 45 days of treatment was 5.57% and after 90 days it decreased 9.14%. Visceral fat decreased in the treatment group from 11.84 ± 0.66 % at baseline to 10.62 ± 0.66 % on day 45 and to 10.15 ± 0.67 % after 90 days of Sarcotropin administration. Visceral fat was reduced by 10.3% and 14.27% after 45 and 90 days of treatment, respectively. There were no changes in total or visceral body fat within the placebo group.
Muscle mass was significantly increased from 41.88 ± 1.28 Kg at baseline to 44.13 ± 1.24 Kg at the end of the 90 day treatment period. Lean body mass increased by 5.37% after 90 days treatment with Sarcotropin in comparison to placebo which was not associated with change in muscle mass.
Forced vital capacity (FVC) significantly increased by 16.61% after 90 days of Sarcotropin treatment. FVC was significantly increased from 71.84 ± 3.18 % at baseline to 73.60 ± 3.52 % on day 45 and to 83.77 ± 3.70 % on day 90. There were no changes in FVC in the placebo group throughout the course of study.
Favorable changes were measured in the treatment group for bone mass and grip strength but these did not reach the level of statistical significance. No changes in bone mineralization or cardiovascular compliance were noted in either group. It is possible that longer treatment periods are required to gain positive effects for these clinical parameters.
Changes in Quality of Life (QoL) were measured using standardized questionnaires that were completed by all subjects at baseline and on days 45 and 90 of study. The questionnaire consisted of 15 questions that could be answered on a graded scale of 1 – 5. A lowering score trend was considered to reflect improvement in QoL. The score was reduced in treated subjects from 36.4 at baseline to 31.1 and 25.9 on days 45 and 90, respectively. These changes represented a 28.85% reduction on day 90 in the treated group. In comparison, the mean score was reduced from 37.6 to 34.1 on day 45 and to 31.5 at day 90. This represents a 16.22% reduction in the placebo group. Thus, there was a significant improvement in QoL for both the groups but the effect occurred in 96% of those receiving Sarcotropin as compared with only 60% of those receiving placebo. Of those showing improvement, most remarked about having increased energy, improved work ability/capacity, increased confidence, improved physical fitness, increased resistance towards illness, increased sleep duration and overall feelings of happiness. A few of subjects reported having reduced back pain and ankle pain while others remarked about improvement in skin texture and radiance.
Changes in pancreatic function as evaluated using the Intravenous Glucose Tolerance Test (IGTT) suggested that insulin sensitivity was increased in the treatment group. This conclusion is indicated by the fact that mean glucose levels were in the normal range at base line before glucose administration, but spiked significantly by one minute afterward. Thereafter, blood glucose returned by normal levels within two hours. A similar profile occurred after 30 days on study both in treated and placebo subjects. However, insulin levels were 24.62 % and 32.94 % lower at 1 hour and 2 hours, respectively, after glucose administration in the treatment group as compared to 3.4 % and 7.25 % lower in the placebo group. Despite the lower insulin levels in the treated individuals, their blood glucose levels were comparable to those in the placebo group suggesting the Sarcotropin increased insulin sensitivity.
A total of twenty adverse events were reported from 94 enrolled subjects. Of those possibly related to treatment as determined by the physician in charge included soft stool, drowsiness, upset stomach and menstrual irregularity. Unrelated events as determined by the physician in charge included itching, increased osteoarthritis problems and joint pain. Of the individuals reporting such adverse events, five were discontinued from the study of their own accord or by the doctor’s order. No clinically significant changes in biochemical or hematological parameters were noted except that total platelet count was increased in treatment group. However, the values were well within the normal range and therefore not considered to be clinically relevant.
There were neither unexpected adverse events nor serious adverse events reported during the course of this study.
Finally, clinical studies were recently completed on the Sarcotropin formulation. The results of this study demonstrate that Sarcotropin is safe and effective for improving body composition and quality of life in humans that are middle-aged and beyond. Statistically significant increases in lean body mass suggest that the product has value in opposing sarcopenia; the loss of muscle that underlies much of the adverse effects of aging on health, vitality and quality of life. Sarcotropin has been shown to lack side effects and that if any adverse events are reported, they should be of no greater severity or frequency than those occurring spontaneously by chance.
A full copy of this Clinical Study is on file in the archives of ProSoma, LLC, Clearwater, Florida, USA
Because of the need to use Sarcotropin appropriately in concert with other medical therapies for opposing maladaptive effects of aging on body composition and for reducing risks of developing age-related disorders, the product is only available to those who are under supervision of a health care professional. To determine if Sarcotropin will be of benefit in a program designed to sustain health, vitality and good quality of life in your patients during aging, and/or for information on ordering this important medical food go to www.sarcotropin.info
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