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ascent
Iron
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Hello, I will be discussing GHRP-2 and a study I have found on it, as well as a principle I call the AUC Threshold Effect.
Link to the Study - It is a 2014 study done on pre-pubertal children. *1
Study Goal: Assess whether or not GHRP-2 increase height-growth in children.
Study Design:
"This study included 84 facilities throughout Japan and involved 126 children (81 males, 45 females) who fulfilled the following criteria: 1) prepubertal boys aged ≥4 to <10 yr old, and prepubertal girls aged ≥4 to <9 yr old; 2) a height SD score of –2 SD or less and peak GH levels of 6 ng/ml or less in at least 2 GH stimulation tests using insulin, glucagon, arginine, clonidine or L-DOPA (4); 3) an increased in the serum GH level to at least 9 ng/ml more than 30 or 45 min after administration in a preliminary test in which the subjects were administered an intranasal GHRP-2 spray (50 μg in those with a body wt of less than 20 kg, and 100 μg in those with a body wt of 20 kg or more). All subjects had been diagnosed as having idiopathic GHD"
"Subjects were enrolled by a double-blind method into 3 groups; that is 44 were included in the placebo group (group P: 30 males, 14 females), 41 were included in the GHRP-2 low dose group (group L: 25 males, 16 females), and 41 were included in the GHRP-2 high dose group (group H: 26 males, 15 females)"
"The subjects in group P received a placebo, while those in the other two groups were administered the intranasal GHRP-2 spray twice a day, in the morning before meals and in the evening before bedtime; for these two groups, subjects with a body wt of less than 20 kg were administered 50μg (group L) or 100μg (group H), and those with a body wt of 20 kg or more were administered 100 μg (group L) or 200 μg (group H)."
TLDR:
1. Study Population
- Prepubertal Boys: ages 4-9, Prepubertal Girls: ages 4-8.*2
- All diagnosed with Idiopathic GHD (growth hormone deficiency), and short stature.
- All children confirmed responsive to the peptide, ensuring a rise of at least 9ng/ml.
2. Groups
Group P: Given a placebo, 30m, 14f, (2.14 ratio mtf) | Placebo spray given.
Group L: Given a low-dose. 25m, 16f, (1.56 ratio mtf) | 50mcg given if below 20kg, 100mcg if more.
Group H: Given a high-dose. 26m, 15f, (1.73 ratio mtf) | 100mcg given if below 20kg, 200mcg if more.*3
The children were given the spray in the morning before meals, and before bed, pretty much all parameters (height, weight, etc.) were measured at 4 weeks, 12 weeks, 24 weeks and 48 weeks.
This is the before-treatment outline, obviously there is some variation between the groups, but its not bad.
Results
Well, I'm just going to summarize with quotes, but basically there was no height gain.
--
"Of the 126 subjects, 44, 40 and 40 subjects in groups P, L and H, respectively, completed the 48-wk treatment period. None of the subjects reached puberty during the treatment period. The values that were determined are not shown separately for boys and girls, since no differences in measured values were observed between them.""
Peak serum GH concentration, as you can say as time goes on it seems as if the high-dose seems to lower similar to the low dose, maybe showing it slowly natural production, or possibly blunting growth hormone response.
"At baseline, the mean peak serum GH values were 4.5 ng/ml in group P, 13.2 ng/ml in group L, and 26.4 ng/ml in group H, and thus significant differences were observed among the 3 groups. After 24 wk of treatment, the mean peak serum GH values were 3.4 ng/ml in group P, 10.7 ng/ml in group L, and 17.8 ng/ml in group H, and thus significant differences were also observed among 3 groups at this time point. However, the mean peak GH values of groups L and H gradually decreased, and after 48 wk of treatment, the mean peak serum GH values were 4.0 ng/ml in group P, 12.0 ng/ml in group L, and 14.6 ng/ml in group H; thus no significant difference was observed between groups L and H"
Growth velocity does not change, if it does it is probably statistical.
"are shown in Fig. 3. During treatment, the mean growth rates in groups P, L and H were 5.4 cm/ yr, 5.2 cm/yr and 5.1 cm/yr, respectively, and thus no significant differences were observed; no promotion of the growth rate was observed as result of treatment. After 48 wk of treatment, the height SD scores in groups P, L and H were –2.18 SD, –2.35 SD, and –2.24 SD, respectively, and thus no significant differences were observed among"
"3 groups: also no significant change in height SD score was observed in any of the 3 groups as result of treatment. Adverse events were reported for 76 subjects (60.3%), and most of the adverse events were accidental such as acute upper respiratory tract inflammation, tonsillitis and otitis media; adverse events that were judged by the investigator as “possibly related” or “probably related” included borborygmus (in 3 subjects) and epistaxis, decreased blood pressure and eosinophilia (in the same subject)."
"However, the AUC was found to be much smaller during treatment with the intranasal GHRP-2 spray in group H (16.3 ± 10.0 ng/ml•h) than that during treatment with subcutaneous GH injection (230 ± 7.0 ng/ml•hr) (6)"
---
This is saying that despite there being a high spike, the total area under the curve, was just too small to achieve down-stream affects, and it adds a new puzzle-piece of the understanding of how to achieve highest growth from a GH Secretagogue/mimic, it introduces something I like to call the AUC Threshold Effect.
Understanding why it doesn't increase height:
Take a look at this graph of a normal 8 year old.
What we see is that he has what I like to call a standard gh profile, he has several pulses at night, we see a good decent amount of space underneath the graphs line, or the area under the curve (AUC). When there is significantly high GH, the GH begins to flood the system, binding to the proper receptors, and the total AMOUNT & DURATION of such a high bodily-saturation of growth-hormone determine how effectively hepatocytes activate downstream signaling pathways, leading to increased production of IGF-1. It is this sustained IGF-1 output during the night, along with the pulsitivity (which avoids receptor downregulation & desensitization) that allows for normal height growth, and when GHRP-2 was used, the pulse created wasn't enough to actually cause those downstream effects.
READ THIS, TLDR:
basically for a GHRP or GH secretagogue to be effective, you need to cause a pulse in growth hormone or elevate it enough to which the liver's hepatocytes are activated properly and produce a significant amount of igf-1, pretty much saying you have to have a balance of high enough gh, and length that the gh is elevated. the bodies natural system of pulses works excellently, and any heightmaxxing protocol should be fine-tuned to mimic the pulse and aoc system. this also means ghrp-2 is cope because while it can produce a very high pulse of gh, it just doesnt last long enough to have the desired effects.
--
*1: Pre-pubertal children are the best way to see if a secretagogue or any drug increases height, as growth plates are fully open and growth is driven by the GH to IGF-1 axis without confounding hormones altering it (sex hormones primarily.)
*2: The combination of the 2 genders may cause statistical and biological variability.
*3: Yeah this is pretty flawed jfl, mg/kg model mogs
other notes:
no the study does not take into account intranasal bioavailability, so the dosages are practically halved, which is honestly shit
--
Lmk what yall think. mb for shit formatting.
Link to the Study - It is a 2014 study done on pre-pubertal children. *1
Study Goal: Assess whether or not GHRP-2 increase height-growth in children.
Study Design:
"This study included 84 facilities throughout Japan and involved 126 children (81 males, 45 females) who fulfilled the following criteria: 1) prepubertal boys aged ≥4 to <10 yr old, and prepubertal girls aged ≥4 to <9 yr old; 2) a height SD score of –2 SD or less and peak GH levels of 6 ng/ml or less in at least 2 GH stimulation tests using insulin, glucagon, arginine, clonidine or L-DOPA (4); 3) an increased in the serum GH level to at least 9 ng/ml more than 30 or 45 min after administration in a preliminary test in which the subjects were administered an intranasal GHRP-2 spray (50 μg in those with a body wt of less than 20 kg, and 100 μg in those with a body wt of 20 kg or more). All subjects had been diagnosed as having idiopathic GHD"
"Subjects were enrolled by a double-blind method into 3 groups; that is 44 were included in the placebo group (group P: 30 males, 14 females), 41 were included in the GHRP-2 low dose group (group L: 25 males, 16 females), and 41 were included in the GHRP-2 high dose group (group H: 26 males, 15 females)"
"The subjects in group P received a placebo, while those in the other two groups were administered the intranasal GHRP-2 spray twice a day, in the morning before meals and in the evening before bedtime; for these two groups, subjects with a body wt of less than 20 kg were administered 50μg (group L) or 100μg (group H), and those with a body wt of 20 kg or more were administered 100 μg (group L) or 200 μg (group H)."
TLDR:
1. Study Population
- Prepubertal Boys: ages 4-9, Prepubertal Girls: ages 4-8.*2
- All diagnosed with Idiopathic GHD (growth hormone deficiency), and short stature.
- All children confirmed responsive to the peptide, ensuring a rise of at least 9ng/ml.
2. Groups
Group P: Given a placebo, 30m, 14f, (2.14 ratio mtf) | Placebo spray given.
Group L: Given a low-dose. 25m, 16f, (1.56 ratio mtf) | 50mcg given if below 20kg, 100mcg if more.
Group H: Given a high-dose. 26m, 15f, (1.73 ratio mtf) | 100mcg given if below 20kg, 200mcg if more.*3
The children were given the spray in the morning before meals, and before bed, pretty much all parameters (height, weight, etc.) were measured at 4 weeks, 12 weeks, 24 weeks and 48 weeks.
This is the before-treatment outline, obviously there is some variation between the groups, but its not bad.
Results
Well, I'm just going to summarize with quotes, but basically there was no height gain.
--
"Of the 126 subjects, 44, 40 and 40 subjects in groups P, L and H, respectively, completed the 48-wk treatment period. None of the subjects reached puberty during the treatment period. The values that were determined are not shown separately for boys and girls, since no differences in measured values were observed between them.""
Peak serum GH concentration, as you can say as time goes on it seems as if the high-dose seems to lower similar to the low dose, maybe showing it slowly natural production, or possibly blunting growth hormone response.
"At baseline, the mean peak serum GH values were 4.5 ng/ml in group P, 13.2 ng/ml in group L, and 26.4 ng/ml in group H, and thus significant differences were observed among the 3 groups. After 24 wk of treatment, the mean peak serum GH values were 3.4 ng/ml in group P, 10.7 ng/ml in group L, and 17.8 ng/ml in group H, and thus significant differences were also observed among 3 groups at this time point. However, the mean peak GH values of groups L and H gradually decreased, and after 48 wk of treatment, the mean peak serum GH values were 4.0 ng/ml in group P, 12.0 ng/ml in group L, and 14.6 ng/ml in group H; thus no significant difference was observed between groups L and H"
Growth velocity does not change, if it does it is probably statistical.
"are shown in Fig. 3. During treatment, the mean growth rates in groups P, L and H were 5.4 cm/ yr, 5.2 cm/yr and 5.1 cm/yr, respectively, and thus no significant differences were observed; no promotion of the growth rate was observed as result of treatment. After 48 wk of treatment, the height SD scores in groups P, L and H were –2.18 SD, –2.35 SD, and –2.24 SD, respectively, and thus no significant differences were observed among"
"3 groups: also no significant change in height SD score was observed in any of the 3 groups as result of treatment. Adverse events were reported for 76 subjects (60.3%), and most of the adverse events were accidental such as acute upper respiratory tract inflammation, tonsillitis and otitis media; adverse events that were judged by the investigator as “possibly related” or “probably related” included borborygmus (in 3 subjects) and epistaxis, decreased blood pressure and eosinophilia (in the same subject)."
"However, the AUC was found to be much smaller during treatment with the intranasal GHRP-2 spray in group H (16.3 ± 10.0 ng/ml•h) than that during treatment with subcutaneous GH injection (230 ± 7.0 ng/ml•hr) (6)"
---
This is saying that despite there being a high spike, the total area under the curve, was just too small to achieve down-stream affects, and it adds a new puzzle-piece of the understanding of how to achieve highest growth from a GH Secretagogue/mimic, it introduces something I like to call the AUC Threshold Effect.
Understanding why it doesn't increase height:
Take a look at this graph of a normal 8 year old.
What we see is that he has what I like to call a standard gh profile, he has several pulses at night, we see a good decent amount of space underneath the graphs line, or the area under the curve (AUC). When there is significantly high GH, the GH begins to flood the system, binding to the proper receptors, and the total AMOUNT & DURATION of such a high bodily-saturation of growth-hormone determine how effectively hepatocytes activate downstream signaling pathways, leading to increased production of IGF-1. It is this sustained IGF-1 output during the night, along with the pulsitivity (which avoids receptor downregulation & desensitization) that allows for normal height growth, and when GHRP-2 was used, the pulse created wasn't enough to actually cause those downstream effects.
READ THIS, TLDR:
basically for a GHRP or GH secretagogue to be effective, you need to cause a pulse in growth hormone or elevate it enough to which the liver's hepatocytes are activated properly and produce a significant amount of igf-1, pretty much saying you have to have a balance of high enough gh, and length that the gh is elevated. the bodies natural system of pulses works excellently, and any heightmaxxing protocol should be fine-tuned to mimic the pulse and aoc system. this also means ghrp-2 is cope because while it can produce a very high pulse of gh, it just doesnt last long enough to have the desired effects.
--
*1: Pre-pubertal children are the best way to see if a secretagogue or any drug increases height, as growth plates are fully open and growth is driven by the GH to IGF-1 axis without confounding hormones altering it (sex hormones primarily.)
*2: The combination of the 2 genders may cause statistical and biological variability.
*3: Yeah this is pretty flawed jfl, mg/kg model mogs
other notes:
no the study does not take into account intranasal bioavailability, so the dosages are practically halved, which is honestly shit
--
Lmk what yall think. mb for shit formatting.
