GH increasing igf levels, to what degree?

[GoneForever]

So its obvious after injecting gh it will increase igf levels for a certain period of time depending on dose. So lets take 2iu's, thats gonna keep igf elevated for roughly 3hours, then take 15iu's which will keep gh levels elevated for 24hours. Well here's my ?. How high are your igf levels going to be at a specifc dose and whats best for muscle gain? For example say you did 15iu's in one shot thats gonna keep your igf levels elevated for 24hours opposed to 15iu's split up into mulitple shots over a 24hour peroid resulting in the same time frame. It seems like with one bigger shot your igf levels will be extrememly high, much higher than smaller more frequent shots, so whats best for muscle growth? Do we really need elevated IGF levels all throught the day in smaller igf increases or would it be better to have massive spurts.

Say normal igf range is between 109-284ng/ml. Lets say after 2iu's your igf levels will be around 400 and then slowly start dropping back to normal after 3hrs. Then lets take a look at levels after 15iu's. What could they be? Maybe like 1000+ and then slowly start dropping.

 

[GoneForever]

i guess i should have worded this better

 

[jm425]

My igf levels were 900+ when I got them tested after doing 12ius of hyge. I take mine all at once pwo.

 

[DatBtrue]

...

It doesn't work like that. GH elevates IGF-1 in a delayed fashion. When a dose is given IGF-1 doesn't begin to rise for several hours and then it rises steadily over the next 24 hours.

See the following chart. Don't worry about the absolute level of IGF-1 shown because they only measured over a 24 hour period (for all but the highest dose which is shown on the 2nd chart.)

​

But IGF-1 will continue to rise into the next day and then when that next day dose is given it will rise further until it eventually settles into an elevated level that is sustained by continuous administration of GH.

It is like keeping a balloon a float by hitting it with a GH dose to keep it well above the floor.

​

Only the high dose GH was given each day and IGF-1 measured daily for a week. Here you can see it level off at day six at around an average of 800 ng/ml w/ at least one participant getting close to 1200 ng/ml.

 

[GoneForever]

So Dat, that chart is for a high dose everday correct. I plan to run 15iu's 3x per week. Would there be any benefit of using like 2iu's on off days to "keep the balloon afloat" as you say?

 

[DatBtrue]

So Dat, that chart is for a high dose everday correct. I plan to run 15iu's 3x per week. Would there be any benefit of using like 2iu's on off days to "keep the balloon afloat" as you say?

With 15ius EOD I am sure IGF-1 levels will remain elevated on the off day.

Remember that GH binds to a receptor on a liver cell and causes intracellular events that lead to transcription of genes for the making of IGF-1, which has to be made in pieces, assembled and eventually chaperoned from inside to the outside of the cell. These things take time...and IGF-1 is secreted slooowly...over the course of a day...

Then once IGF-1 (7.649kda in mass) is secreted most will become bound to a binding protein, the most beneficial of which for bodybuilding would be the binding to IGF-1 Binding Protein-3, which in turn binds to Acid Labile-Subunit (which circulates in abundance BECAUSE GH is responsible for its synthesis as well). This complex known as the ternary complex (150kda in mass) will prolong the half-life of IGF-1 from 10 minutes & of the IGF-1 Binding Protein-3's half-life of 30-90 minutes to that of 12-15 hours!

What does this mean?

From, Endocrinology in Clinical Practice by Philip E. Harris:

"This enables IGF-1 to remain in intravascular space for the steady delivery to the tissues, in contrast to the pulsatility of GH."

What are normal IGF-1 levels by age?

25-29 years of age 257 (127-387) ng/ml
30-54 years of age 212 (128-296) ng/ml
55+ years of age 196 (98-294) ng/ml

* Diagnostic Services Laboratories, Inc.​

So even when you experience a dip in IGF-1 levels over a 48 hour period of time it won't be an absolute drop and it certainly will remain well above normal.

Of course the question remains, do you want to jack IGF-1 levels constantly?

True IGF-1 has about 10-13% of insulin's activity which explains why those who have never used insulin go religious about IGF-1 LR3...

...but aside from that, the question remains...

...we spent time over some of the last few pages in my thread talking about protein synthesis & protein degradation as well as amino acid pools and we discussed what activity GH is responsible for and what activity IGF-1 is responsible for.

In addition it is my belief that all of this IGF-1 level stuff is serving as a proxy for measuring locally made, locally used IGF-1 (which we can not measure). So who cares about overall levels when what is important is muscle made & used levels.

But Dat if we can't measure the local stuff and the overall level is a proxy (or an indicator) of what is happening inside muscle then raising overall levels will correlate with muscle growth right?

Right. But I suspect... boy do I suspect that overall systemic levels could be supressed at the liver and still local production (in the muscle would be increase). That would be a lot safer & still give benefit.

I even saw a study that demonstrated that post-exercise circulating IGF-1 isn't even necessary. That if they eliminate receptors on muscle cells the muscle cell makes all the IGFs it needs internally and IGF never leaves the cell instead it activates protein synthesis and the like from within...perhaps translocating directly to the nucleus...

...thats what MGF ALWAYS does. So maybe IGF-1 isn't needed post-exercise at all. MGF is the splice variant that is created post-exericise that increases proliferation.

Remember I speculated and demonstrated w/ the study (on fibroblast growth factor) that IGF-1 (a differentiating factor) would just get in the way and hinder MGF's proliferative activity PWO. That IGF-1 would best exert its benefit at other stages...

Anyway...just some interesting stuff.

Back to your question? Sure 2iu could be used on off days and it would contribute to IGF-1 level elevation (i.e. keep the balloon higher).

Does it matter?

In your case (where we are talking about dips instead of drops back to baseline) I don't know. I suspect that it doesn't matter.

But I have discovered in my own body from my longevity research w/ alternate day fasting that drops of IGF-1 levels back to baseline hinder muscle preservation (and obviously gain).

Zero calories EOD drops IGF-1 back to baseline whereas just 15 - 20% of maintenance calories on "fast day" keep IGF-1 levels from dropping.

So dips are not as much of a concern as drops over a 48 hour period.

 

[GoneForever]

Wow dat, if your even in socal i'll book a table for 2 at ruth chris for us

 

[Blade_HST]

Very interesting posts, as usual, Dat.

I just wonder how administering 2IU GH every 3hrs with CJC+GHRP - say 5 times per day, would be any different in terms of inhibition vs. 10IU of GH in a single dose? Wouldn't the systemic IGF-1 elevation be equal in AUC? Or is inhibition more sensitive to amplitude vs. duration?

 

[DatBtrue]

Very interesting posts, as usual, Dat.

I just wonder how administering 2IU GH every 3hrs with CJC+GHRP - say 5 times per day, would be any different in terms of inhibition vs. 10IU of GH in a single dose? Wouldn't the systemic IGF-1 elevation be equal in AUC? Or is inhibition more sensitive to amplitude vs. duration?

Good question...and I have to go by memory here so don't hold me to it but...

Everyone understands that IGF-1 is synthesized in the liver BUT almost noone knows that it is also synthesized in the brain (hypothalamus) .

The inhibitory effects of IGF-1 on the hypothalamic release of GHRH are well established. However hypothalamic GHRH mRNA levels (i.e. synthesis) are resistant to systemic infusions of IGF-1 but responsive to direct infusion into the brain.

In other words IGF-1 is synthesized in the hypothalamus in response to various events and this inhibits GHRH. However administering IGF-1 or IGF-1 LR3 in the body systemically will have no direct effect on the brain and will not inhibit GHRH & thus GH.

Only to the extent that GH or other factors engender autocrine/paracine action of IGF-1 in the hypothalamus do we need to worry about inhibition from the source (i.e. hypothalamus). To the extent that this occurs (it is apt to be synchronized w/ GH pulsation).

Keep in mind that we overcome this (should it occur as a result of synthetic GH) by providing exogenous GHRH and using GHRP-6 to inhibit Somatosatin in the hypothalamus.

All of that is in the short-term.

The longer-term feedback results in IGF-1 stimulating the synthesis and release of Somatostatin (the inhibitory hormone).

IGF-1 also directly inhibits pituitary GH gene transcription. This means that less GH will be made and stored and available for the next pulse.

IGF-1 also inhibits at the pituitary "basal-, cAMP-, protein kinase C-, GHRH- and TRH-induced GH release." *

However "IGF-1 is...far less effective in inhibiting GH release than Somatostatin and [thus] may [in actual fact] only [directly] inhibit GH release from a subpopulation of GH cells that are not responsive to Somatostatin inhibition". *

So IGF-1 primarily exerts its effect indirectly by increasing somatostin's release and aiding its pituitary action.

With GHRP-6 we stop most of this action (at the pituitary and at the hypothalamus).

But even if you block Somatostatin (w/ GHRP-6, etc.), IGF-1 may still act directly on those other cells and inhibit GH-release. This is a weak action though and we know that GHRP-6 can overcome some of this direct action as well since it binds to cells in the pituitary and increases cAMP-induced GH release.

* Growth Hormone, Stephen Harvey, CRC Press 1995

Specific answer to your question.

???

I only have the understanding that 3 hour pulsation is entrained, burned into the way the body desires to do things. So duplicating it works...

See: http://www.professionalmuscle.com/forums/showpost.php?p=522247&postcount=662

Also I believe (but may be incorrect) that the pituitary (like the hypothalamus) may be primarily responsive to IGF-1 made locally...but I am not sure about that.

 

[DatBtrue]

You see we can be sloppy with some of this stuff because testosterone overcomes so much or makes up for deficiencies in protocols.

From, Testosterone Blunts Feedback Inhibition of Growth Hormone Secretion by Experimentally Elevated Insulin-Like Growth Factor-I Concentration, Johannes D. Veldhuis, Stacey M. Anderson, Ali Iranmanesh and Cyril Y. Bowers, The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 3 1613-1617, 2005, where they found:

"...supplementation of a high dose of Te in middle-aged and older men attenuates IGF-I feedback-dependent inhibition of nadir and peak GH secretion."​

​

The results of this study were confirmed in a recent study:

Testosterone Supplementation in Older Men Restrains Insulin-Like Growth Factor’s Dose-Dependent Feedback Inhibition of Pulsatile Growth Hormone Secretion, Johannes D. Veldhuis, Daniel M. Keenan, Joy N. Bailey, Adenborduin Adeniji, John M. Miles, Remberto Paulo, Mihaela Cosma and Cacia Soares-Welch, The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 1 246-254, 2009

Background: Pulsatile GH secretion declines in older men. The causal mechanisms are unknown. Candidates include deficient feedforward (stimulation) by endogenous secretagogues and excessive feedback (inhibition) by GH or IGF-I due to age and/or relative hypoandrogenemia.

Hypothesis: Testosterone (T) supplementation in healthy older men will restrain negative feedback by systemic concentrations of IGF-I.

Subjects: Twenty-four healthy men (ages, 50 to 75 yr; body mass index, 24 to 30 kg/m2) participated in the study.

Methods: We performed a prospectively randomized, double-blind, placebo-controlled assessment of the impact of pharmacological T supplementation on GH responses to randomly ordered separate-day injections of recombinant human IGF-I doses of 0, 1.0, 1.5, and 2.0 mg/m2.

Analysis: Deconvolution and approximate entropy analyses of pulsatile, basal, and entropic (pattern-sensitive) modes of GH secretion were conducted.

Results: Recombinant human IGF-I injections 1) elevated mean and peak serum IGF-I concentrations dose-dependently (both P < 0.001); 2) suppressed pulsatile GH secretion (P = 0.003), burst mass (P = 0.025), burst number (P = 0.005), interpulse variability (P = 0.032), and basal GH secretion (P = 0.009); and 3) increased secretory pattern regularity (P = 0.020). T administration did not alter experimentally controlled IGF-I concentrations, but it elevated mean GH concentrations (P = 0.015) and stimulated pulsatile GH secretion (frequency P = 0.037, mass per burst P = 0.038). Compared with placebo, T attenuated exogenous IGF-I’s inhibition of GH secretory-burst mass (P < 0.038) without restoring pulse number, basal secretion, or pattern regularity.

Conclusion: The capability of systemic T to mute IGF-I feedback on pulsatile GH secretion suggests a novel mechanism for augmenting GH production.​

 

[jrs]

I read a study stating that testosterone increases number of satellite cells. All of this is way above my head but it had me wondering, if high doses of AAS are used (androgens AND anabolics), how much elevation over baseline could one hypothetically see? I understand there are a ton of variables but let's break this down. Side by side, how do the following compare as far as healing, fat burning, and muscle building effects from GH?

Synthetic GH

Peptides

Testosterone/Other AAS

Baseline natural into middle age

 

[Blade_HST]

I'm always careful extrapolating time-courses (and obviously dosages) from rodent studies, but there is little doubt that we can entrain these GH pulses in humans as well. The question in my mind is whether we could consider 3hrs to be the minimum time between GH + peptides injections, or if we have to adhere to a strict schedule to get these benefits. I don't think most people have the opportunity to set a timer and inject at the exact 3:00hr mark (I know I don't).

Maybe that's not what you're saying but I seem to recall an earlier post where you said that every 3hrs was necessary (in the context of concurrent GH and peptide injections) and that every 4hrs would negate the effect?

I was thinking 1.5-2IU GH + 100mcg GRF 1-29 + 100mcg GHRP-6 morning/post-WO/pre-bed would be a good protocol, which should provide a very robust bodybuilding dose and be viable for most users vs. every 6-8 daily injections.

 

[DatBtrue]

I'm always careful extrapolating time-courses (and obviously dosages) from rodent studies, but there is little doubt that we can entrain these GH pulses in humans as well.

I don't have access to the full study, only the abstract BUT the dosage mentioned was not insulin units (iu) it was U (units). I don't know how they are defining it.

2iu is a bit arbitrary on my part. 1.5iu might be the proper dose...

The question in my mind is whether we could consider 3hrs to be the minimum time between GH + peptides injections, or if we have to adhere to a strict schedule to get these benefits. I don't think most people have the opportunity to set a timer and inject at the exact 3:00hr mark (I know I don't).

Yes... well since we are creating a pulse with GHRP-6 instead of waiting around for the next natural pulse...it is reasonable to guess that longer time periods will work.

Shorter time frames won't work obviously but longer time frames should.

Maybe that's not what you're saying but I seem to recall an earlier post where you said that every 3hrs was necessary (in the context of concurrent GH and peptide injections) and that every 4hrs would negate the effect?

From the study they found out of phase GH administrations stopped natural pulsation. But you bring up a good point, in that we are creating the pulse so every 4 hours wouldn't be "out of phase" in the way that the study defined it.

I was thinking 1.5-2IU GH + 100mcg GRF 1-29 + 100mcg GHRP-6 morning/post-WO/pre-bed would be a good protocol, which should provide a very robust bodybuilding dose and be viable for most users vs. every 6-8 daily injections.

Yes I like that. It is not far removed from what Lucian did w/ success.

You laugh but I was communicating w/ a guinea pig who is going to run 2iu of GH every 3 hours 6-8 times a day (w/o the peptides).

Practically speaking you are correct... I am curious to see how your plan works out because I think it will work out well. The best of both worlds.

 

[DatBtrue]

Side by side, how do the following compare as far as healing, fat burning, and muscle building effects from GH?

Synthetic GH

Peptides

Testosterone/Other AAS

Baseline natural into middle age

Don't really know how to answer your question. Not sure I understand it.

I'll pick at a few things. Lipolysis is a benefit of GH, meaning the breakdown & release of fat from cells into the bloodstream. So to maximize this effect you want insulin to be low while GH is active and then you want to be active to "burn" off the mobilized fats.

Taking GH haphazardly won't maximize fat loss.

GH is not really anabolic by itself. It becomes so with insulin (physiological or pharmacological) and testosterone.

GH is anti-catabolic by itself.

Peptides...well GH is a peptide, so is hepatocyte growth factor. You've probably never heard of it, but it is a growth factor that resides in muscle and when stretch overload occurs (such as extreme stretching) this causes the release of hepatocyte growth factor (HGF) into the medium and that released HGF stimulates nearby satellite cells to enter the cell cycle and join the muscle of the future party. Nitric oxide plays a role in this as well.

What is interesting is this occurs without IGF-1. Muscle growth occurs just fine w/ this mechanism & w/ IGF-1 receptors blocked... the proper intracellular pathways are activated.

As far as healing the following growth factors are involved and transported to sites of injury via platelets:

platelet-derived growth factor (PDGF)
vascular endothelial growth factor (VEGF)
transforming growth factor beta-1 (TGF-b1)
epidermal growth factor (EGF)
basic fibroblast growth factor (bFGF)
insulin-like growth factor-1 (IGF-1).
hepatocyte growth factor (HGF)​

So what was your question again

 

[jrs]

Don't really know how to answer your question. Not sure I understand it.

I'll pick at a few things. Lipolysis is a benefit of GH, meaning the breakdown & release of fat from cells into the bloodstream. So to maximize this effect you want insulin to be low while GH is active and then you want to be active to "burn" off the mobilized fats.

Taking GH haphazardly won't maximize fat loss.

GH is not really anabolic by itself. It becomes so with insulin (physiological or pharmacological) and testosterone.

GH is anti-catabolic by itself.

Peptides...well GH is a peptide, so is hepatocyte growth factor. You've probably never heard of it, but it is a growth factor that resides in muscle and when stretch overload occurs (such as extreme stretching) this causes the release of hepatocyte growth factor (HGF) into the medium and that released HGF stimulates nearby satellite cells to enter the cell cycle and join the muscle of the future party. Nitric oxide plays a role in this as well.

What is interesting is this occurs without IGF-1. Muscle growth occurs just fine w/ this mechanism & w/ IGF-1 receptors blocked... the proper intracellular pathways are activated.

As far as healing the following growth factors are involved and transported to sites of injury via platelets:

platelet-derived growth factor (PDGF)
vascular endothelial growth factor (VEGF)
transforming growth factor beta-1 (TGF-b1)
epidermal growth factor (EGF)
basic fibroblast growth factor (bFGF)
insulin-like growth factor-1 (IGF-1).
hepatocyte growth factor (HGF)​

So what was your question again

some things are complicated enough to me that i shouldn't be thinking about them so late at night. basically, how much would one be missing out on if they were to use only readily available anabolics and androgens? no peptides of any sort.

do you feel that, if somebody is NOT yet deficient in terms of growth hormone, they are still missing out on anabolism, fat loss, joint health, better sleep, etc in a significant amount? enough to warrant finding the money to use such things as gh/ghrp/slin in supra physiological doses if their goal is extreme size, strength, bodyfat levels?

 

[DatBtrue]

...how much would one be missing out on if they were to use only readily available anabolics and androgens? no peptides of any sort.

Very little if you are under 30 unless you have come close to a level of muscle mass that is very difficult to hold.

As far as diet and getting lean you can achieve that without peptides.

Most anabolic gains come from putting your body in a state where it wants to grow. That involves dieting down until you are very lean. In this state your body has lost the fat pad and said goodbye to a lot of aromatizing enzymes...

Proper (not over consumption) nutrition, proper workouts coupled with testosterone for a period of time will give you the majority of growth. Use of Leucine or stepping further forward insulin will push growth forward. Pharmaculogical doses are not required.

If you are not a competitor bodybuilding can be a healthy lifestyle, especially if you stay lean, get in good cardivascular shape and limit your steroid use to one 8 - 11 week run per year.

do you feel that, if somebody is NOT yet deficient in terms of growth hormone, they are still missing out on anabolism, fat loss, joint health, better sleep, etc in a significant amount? enough to warrant finding the money to use such things as gh/ghrp/slin in supra physiological doses if their goal is extreme size, strength, bodyfat levels?

If you are over 40 you need GH. One reason is that as you approach 50 you won't make much MGF PWO just from the workout. This limits muscle gains for older guys & gals.

Do everything correct as an older guy and you still won't gain unless you at least restore GH levels.

But assuming you are a young person with limited funds then the answer is NO! You aren't missing out on significant amount.

If you have limited funds then you can consider using insulin and high dose GH or high dose GHRH/GHRP on cycle only.

But generally the GH or GHRH/GHRP-6 are used year around and only ramped up on cycle.

As a young man you could easily use up 95% of your financial resources to attain 5% more gain.

I know a guy who is in his 20's. He does not have the funds to use expensive peptides but he loves inexpensive GHRP-6. He couples this with various things such as Arginine. He always doses prebed & I believe he also doses when he wakes up in the middle of the night.

That helps him get restoration and stay lean.

So we are talking about one 5mg vial a month. That costs $15 - $20per month. There is a big benefit to cost ratio here. Many young guys tell me they use it only for better sleep and that is worth it to them.

I notice you used the word extreme size & strength, etc.

A lot more goes into that then GH, but yes there comes a point where extreme requires GH & insulin.

For instance use of SEOs are necessary to attain a certain size and shape if you don't have pop & fresh musculature naturally...and yes they can and are used in every muscle in the body.

 

[jrs]

Thank you for your input.

Very little if you are under 30 unless you have come close to a level of muscle mass that is very difficult to hold.

As far as diet and getting lean you can achieve that without peptides.

Most anabolic gains come from putting your body in a state where it wants to grow. That involves dieting down until you are very lean. In this state your body has lost the fat pad and said goodbye to a lot of aromatizing enzymes...

Proper (not over consumption) nutrition, proper workouts coupled with testosterone for a period of time will give you the majority of growth. Use of Leucine or stepping further forward insulin will push growth forward. Pharmaculogical doses are not required.

If you are not a competitor bodybuilding can be a healthy lifestyle, especially if you stay lean, get in good cardivascular shape and limit your steroid use to one 8 - 11 week run per year.



If you are over 40 you need GH. One reason is that as you approach 50 you won't make much MGF PWO just from the workout. This limits muscle gains for older guys & gals.

Do everything correct as an older guy and you still won't gain unless you at least restore GH levels.

But assuming you are a young person with limited funds then the answer is NO! You aren't missing out on significant amount.

If you have limited funds then you can consider using insulin and high dose GH or high dose GHRH/GHRP on cycle only.

But generally the GH or GHRH/GHRP-6 are used year around and only ramped up on cycle.

As a young man you could easily use up 95% of your financial resources to attain 5% more gain.

I know a guy who is in his 20's. He does not have the funds to use expensive peptides but he loves inexpensive GHRP-6. He couples this with various things such as Arginine. He always doses prebed & I believe he also doses when he wakes up in the middle of the night.

That helps him get restoration and stay lean.

So we are talking about one 5mg vial a month. That costs $15 - $20per month. There is a big benefit to cost ratio here. Many young guys tell me they use it only for better sleep and that is worth it to them.

I notice you used the word extreme size & strength, etc.

A lot more goes into that then GH, but yes there comes a point where extreme requires GH & insulin.

For instance use of SEOs are necessary to attain a certain size and shape if you don't have pop & fresh musculature naturally...and yes they can and are used in every muscle in the body.

 

[GoneForever]

[QUOTE


From the study they found out of phase GH administrations stopped natural pulsation. But you bring up a good point, in that we are creating the pulse so every 4 hours wouldn't be "out of phase" in the way that the study defined it.



Yes I like that. It is not far removed from what Lucian did w/ success.

You laugh but I was communicating w/ a guinea pig who is going to run 2iu of GH every 3 hours 6-8 times a day (w/o the peptides).

Practically speaking you are correct... I am curious to see how your plan works out because I think it will work out well. The best of both worlds.[/QUOTE]

I dont understand? I thought taking GHRP6 with GH at the same time was no good.

 

[mixxin]

I think Dat said taking the GH 20 min after the GHRP is fine. Hence you get the natural pulse, let it peak, then the GH shot gives you another bang. If I read it correctly, it's fine if it's < 2iu.