there's been a lot of rumination on whether lr3igf-i is able to cause the gh gut so fashionable amongst pros today. i believe the science can lead us to categorically conclude "no", with two exceptions: concurrent use of GH, and oral use.
before we begin, note that rats are a terrible model for this because their gastrointestinal system differs from ours greatly. the porcine -- pig -- is probably the closest one we can ethically abuse. this is most important in terms of autocrine effects; rats produce most of their igf-i centrally, so systemic doses will lead to nice gut growth. this isn't necessarily true for us. not only that, but the doses used in the studies to generate maximal gut growth are on the order of 278mcg/day -- in a rat. which is slightly smaller than a human.
i've heard of an oral lr3igf-i preparation lately. i don't know how they've done it, but if they're relying on intestinal uptake, this turns out to be wonderfully local and will lead to very high concentrations in the intestines with little systemic effect. it'll probably get delivered pretty well though.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=11782919
http://ajpregu.physiology.org/cgi/content/abstract/270/5/R1085
http://ajpgi.physiology.org/cgi/content/full/277/3/G619
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=10484387
the main reason lr3igf-i is unlikely to cause intestinal growth is that the concentrations reached are below what is able to cause proliferation of various intestinal cells, much less optimum for growth. researchers have taken samples from a large number of human patients, put them on sponges, and doused them in large amounts of GH, IGF-I, and slin. you couldn't ask for a better study. binding proteins will be extremely negligible and probably nil.
http://gut.bmjjournals.com/cgi/content/abstract/40/1/57
at 50ng/ml, there was no growth rate increase at all over controls. by 400ng/ml, there was a big one.
another study looked at the effects on the smooth muscle part of the intestines:
http://ajpgi.physiology.org/cgi/content/full/286/3/G412
here the concentration used for growth was 100nM; given the 7.6kDa molecular weight of igf-i, this comes out to 760nm/ml.
looking at the actual pharmacokinetics of sub-q igf-i, we see 120 mcg/kg leading to a serum peak of 350mcg/L-ish. this is a huge dose but only leads to a concentration of 350ng/ml, and 99% is protein-bound.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7688671
it probably isn't that relevant to us though, because lr3igf-i has such different pharmacokinetics. so let's use HGH for a crude estimate, which is probably a lot closer:
http://moderntherapy.com/hgh/humatrope/
"The volume of distribution of somatropin after intravenous injection is about 0.07 L/kg."
so we'll take a 100kg bodybuilder and say there's about 7 liters of stuff this percolates into; pretty standard vss. we'd reach a rough serum/tissue concentration of 14ng/ml with a 100mcg dose.
some people have suggested lr3igf-i preferentially binds to intestinal receptors/accumulates in the gut, which is an excellent thing to look at. an important thing to remember is the fact that distribution of an igf-i flavour depends on the analog used, largely because of the distribution of binding proteins, which are used to capture free igf-i for local use. however, lamb studies have shown roughly 3-4% of a total iv dose accumulates in the gut:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7520931
"The net intestinal transfer of IGF-I, calculated as the sum of the proportions of infused tracer recovered from intestinal tissue, luminal contents and lymph, was 3.46 +/- 0.22% (S.E.M.) and 3.49 +/- 0.93% when infused at high and low specific activities respectively. The analogues differed from IGF-I with up to ninefold higher concentrations of free radiolabelled peptide in venous plasma of the perfused intestinal segment, and corresponding decreases in binding to the 30-50 kDa binding proteins. Notwithstanding these marked differences in the plasma levels of free peptide, net intestinal transfer was very similar for the three peptides, as was the extent of degradation in the intestinal tissue."
another study agrees:
http://joe.endocrinology-journals.org/cgi/content/abstract/128/2/197
though having it end up in brain makes me worry a little, especially since it causes growth here for laron's syndrome patients.
anyway, this is a fairly low uptake, which reflects the fact that drugs have a hard time passing from blood into the intestine. this makes it even less likely we'll see growth.
if we go back to the study published in gut, look at the concentrations of GH needed to achieve intestinal growth; combining this with insulin(albeit at ridiculous doses, though the slin dose didn't matter much for some reason) led to massive growth. note that with that 7L volume of distribution for GH, you might not be surprised if 20IU hit a concentration of .0028IU/ml in intestinal tissue. i'm too sleepy to check the distribution right now. there also seemed to be a somewhat linear increase with GH, so even small amounts of GH probably contribute some, whereas small amounts of IGF-I contribute none.
hopefully some of you bros can sleep more easily tonight.
before we begin, note that rats are a terrible model for this because their gastrointestinal system differs from ours greatly. the porcine -- pig -- is probably the closest one we can ethically abuse. this is most important in terms of autocrine effects; rats produce most of their igf-i centrally, so systemic doses will lead to nice gut growth. this isn't necessarily true for us. not only that, but the doses used in the studies to generate maximal gut growth are on the order of 278mcg/day -- in a rat. which is slightly smaller than a human.
i've heard of an oral lr3igf-i preparation lately. i don't know how they've done it, but if they're relying on intestinal uptake, this turns out to be wonderfully local and will lead to very high concentrations in the intestines with little systemic effect. it'll probably get delivered pretty well though.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=11782919
http://ajpregu.physiology.org/cgi/content/abstract/270/5/R1085
http://ajpgi.physiology.org/cgi/content/full/277/3/G619
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=10484387
the main reason lr3igf-i is unlikely to cause intestinal growth is that the concentrations reached are below what is able to cause proliferation of various intestinal cells, much less optimum for growth. researchers have taken samples from a large number of human patients, put them on sponges, and doused them in large amounts of GH, IGF-I, and slin. you couldn't ask for a better study. binding proteins will be extremely negligible and probably nil.
http://gut.bmjjournals.com/cgi/content/abstract/40/1/57
at 50ng/ml, there was no growth rate increase at all over controls. by 400ng/ml, there was a big one.
another study looked at the effects on the smooth muscle part of the intestines:
http://ajpgi.physiology.org/cgi/content/full/286/3/G412
here the concentration used for growth was 100nM; given the 7.6kDa molecular weight of igf-i, this comes out to 760nm/ml.
looking at the actual pharmacokinetics of sub-q igf-i, we see 120 mcg/kg leading to a serum peak of 350mcg/L-ish. this is a huge dose but only leads to a concentration of 350ng/ml, and 99% is protein-bound.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7688671
it probably isn't that relevant to us though, because lr3igf-i has such different pharmacokinetics. so let's use HGH for a crude estimate, which is probably a lot closer:
http://moderntherapy.com/hgh/humatrope/
"The volume of distribution of somatropin after intravenous injection is about 0.07 L/kg."
so we'll take a 100kg bodybuilder and say there's about 7 liters of stuff this percolates into; pretty standard vss. we'd reach a rough serum/tissue concentration of 14ng/ml with a 100mcg dose.
some people have suggested lr3igf-i preferentially binds to intestinal receptors/accumulates in the gut, which is an excellent thing to look at. an important thing to remember is the fact that distribution of an igf-i flavour depends on the analog used, largely because of the distribution of binding proteins, which are used to capture free igf-i for local use. however, lamb studies have shown roughly 3-4% of a total iv dose accumulates in the gut:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7520931
"The net intestinal transfer of IGF-I, calculated as the sum of the proportions of infused tracer recovered from intestinal tissue, luminal contents and lymph, was 3.46 +/- 0.22% (S.E.M.) and 3.49 +/- 0.93% when infused at high and low specific activities respectively. The analogues differed from IGF-I with up to ninefold higher concentrations of free radiolabelled peptide in venous plasma of the perfused intestinal segment, and corresponding decreases in binding to the 30-50 kDa binding proteins. Notwithstanding these marked differences in the plasma levels of free peptide, net intestinal transfer was very similar for the three peptides, as was the extent of degradation in the intestinal tissue."
another study agrees:
http://joe.endocrinology-journals.org/cgi/content/abstract/128/2/197
though having it end up in brain makes me worry a little, especially since it causes growth here for laron's syndrome patients.
anyway, this is a fairly low uptake, which reflects the fact that drugs have a hard time passing from blood into the intestine. this makes it even less likely we'll see growth.
if we go back to the study published in gut, look at the concentrations of GH needed to achieve intestinal growth; combining this with insulin(albeit at ridiculous doses, though the slin dose didn't matter much for some reason) led to massive growth. note that with that 7L volume of distribution for GH, you might not be surprised if 20IU hit a concentration of .0028IU/ml in intestinal tissue. i'm too sleepy to check the distribution right now. there also seemed to be a somewhat linear increase with GH, so even small amounts of GH probably contribute some, whereas small amounts of IGF-I contribute none.
hopefully some of you bros can sleep more easily tonight.
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