HGH - timing and general issues - interesting findings

diskey · Nov 19, 2008

Hi guys, just tought I would share some info. I've gone through some research articles on hgh and found one article of particular interest:

"Exogenous 20K Growth Hormone (GH) Suppresses Endogenous 22K GH Secretion in Normal Men" Y. Hashimoto et al. 2000

It is of special interest since the experiment was done on 32 HEALTHY adults aged 20-31.

OK, the key findings which contradicts much of the hype around hgh:

*Exogenous hgh administration (sc) will not supress endogenous hgh production before 4 hours after administartion.

*IGF levels will raise slowly in 12 hours after administartion and then raise rapidly and reach a peak about 24 hours after administration.

*Exogenous hgh administration will supress endogenous hgh prduction for about 24 hours. This did even occur at small doses of 1-2iu a day.

*HGH is very dose dependant. A 10iu dose will give a ten fold increase in peak concentration levels of both hgh and igf-1. Also a bigger dose will not increase the supression time or peak times.

In regard to timining of hgh injections this would mean that the best time to inject your hgh is just before you go to sleep. That way you will still get your largest endogenous pulse, which accours about 2 hours after you go to sleep, and when that pulse is over, a little later in about 4 hours you hgh levelse will reach another peak from the hgh administration. The supression of your own hgh will be finished by the time you do your next injection the day after at the same time, so you will still get the deep sleep pulse the night after.

By taking your shots am you will supress all endogenous production of hgh the following nigth. Forget thinking that going up taking your shot 4am or 7am will help you not supress your own production, you will be shut down for 24 hours.

By doing several injections each day like am/afternoon you will shut down your own production completly(if you do ed shots)

The results also contradicts the theory of the hgh 3x blasting method popular for mass gaining. The key there is to maximize igf levels after training,
taking your shots pwo. The shots is supposed to be taken IM. Well first IM shots is not absorbed as good as sc shots, and you will get a somewhat better peak in concetration levels but a somewhat faster half-life time.

Anyway your igf levels will not peak before at least somewhere between 12-24 hours later and the whole dose will be less absorbed. The insulin levelse from your IM slin shot pwo will in no way have any synergy with a pwo hgh shot, because of the delayed increase in igf-1 levels. If you train mon-wed-fri with the 3x blast method your igf levels-1 will be at top the day after when your not training. It's quite important to see the difference between hgh peak time and igf peak time from hgh administration, as their are very different.

All in all bearing in mind that endogenous hgh production in healthy adults range from 0,5-1,5iu daily(I think), it is not that much you loose from beeing completly shut down. But even at larger doses of up to 10iu it should still be no loss of effect to take your hgh dose in one shot. If you take it before bed you igf levels will increase stadily the day after and be in high concetration when you train in the afternoon or evening.

All this assumptions are based on the article mentioned and there could ofcourse be other exmperiments showing different results, but at least this article have 16 citations(meaning that 16 other researchers have used the results from this article in their own articles)

Blade_HST · Nov 19, 2008

Except that synthetic HGH manufactured and sold today is the 22K, not the 20K as studied here....but some of the same issues are present so let's hope this leads to a good discussion.

GHRHs+GHRPs will increase endogenous release of all GH-kDa, and seems to be the optimal prescription for anti-aging and bodybuilding purposes.

JJDADOG · Nov 19, 2008

I take 2ius a day before work around 7:00-7:30 am... are you saying i should switch up and do it at night...

Thanks for the info

diskey · Nov 19, 2008

Blade_HST said:
Except that synthetic HGH manufactured and sold today is the 22K, not the 20K as studied here....but some of the same issues are present so let's hope this leads to a good discussion.

GHRHs+GHRPs will increase endogenous release of all GH-kDa, and seems to be the optimal prescription for anti-aging and bodybuilding purposes.

Hm, but should think the two are very similar. Why should 22k shut you donw less than 20k? When I think about it, would perhaps be hard to do any research on 22k exogenous effect on endogenous levels when they are the same.

Jarconis · Nov 19, 2008

I think this is why a lot of people are switching to EoD dosing

vadim_b1 · Nov 19, 2008

unless youre under 20 yrs old, your natural gh production will not really matter enough to make a difference IMO.

diskey · Nov 19, 2008

Jarconis said:
I think this is why a lot of people are switching to EoD dosing

Don't have time to dig it up, but by the way it is proven EOD is inferior to ED in regard to typical hgh benefits under the treatment. The only superior thing with eod protocol is that when you go off after a longer period you will recover your own production somewhat faster. 5/2 off or 6/1 will probably give the same recovery benefits (anyway this only applies to longer use like 1 year+). And don't forget that if you want to achieve near same results as ed from eod you must double the dose. So 5iu ed would have to be 10iu eod to compare. A lot of people decide on taking a daily dose say like 3iu, then they read up on the eod protocol and hear good things, then they further think that 3iu eod will give the same results, -well, no it won't. HGH is very dose dependant.

diskey · Nov 19, 2008

vadim_b1 said:
unless youre under 20 yrs old, your natural gh production will not really matter enough to make a difference IMO.

In the study above where the people where in their 20s, the peak from natural production was about 1:10 of the dose of exogenous dose of 0,01mg/kg bodymass. So something like 1iu for a 100kg male.

If you do higher doses like 5iu+ one should probably just forget completly about natural production. If you do 10iu daily perhaps splitting up to 2 injections of 5 would give nice high igf-1 throughout the day.

I also have the thought that fat loss from hgh, except for the spot reduction, is basically because of the increse in metabloism, which is mainly due to the increase in igf-1 levels (for those of you who have tried igf-1 lr3 you know how how hungry you get from that stuff), so what you would watch is the igf-1 levels not the hgh serum levels and times.

DatBtrue · Nov 20, 2008

diskey said:
... but at least this article have 16 citations(meaning that 16 other researchers have used the results from this article in their own articles)

No actually according to The Journal of Clinical Endocrinology & Metabolism, there are only three articles that cite Exogenous 20K Growth Hormone (GH) Suppresses Endogenous 22K GH Secretion in Normal Men , Yoshihide Hashimoto, The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 2 601-606. They are:

Systematic Review: The Effects of Growth Hormone on Athletic Performance, Ann Intern Med, May 20, 2008; 148(10): 747 - 758
Metabolic Effects of 20-Kilodalton Human Growth Hormone (20K-hGH) for Adults with Growth Hormone Deficiency: Results of an Exploratory Uncontrolled Multicenter Clinical Trial of 20K-hGH, J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1562 - 1571
Physiological and pharmacological regulation of 20-kDa growth hormone, Am J Physiol Endocrinol Metab, October 1, 2002; 283(4): E836 - E84

Now if you go pull those cited articles to see why they cited the original study here is what you find:

Cited article #1 "Systematic Review: The Effects of Growth Hormone..." made reference in the following phrase:

"Seven studies evaluated the use of a single dose of growth hormone. Of these, 3 studies provided growth hormone subcutaneously (35, 36, 38)" NOTE: 36 is a cite to the original article made simply to cite a study that use subcutaneous dosing.

Cited article #2 "Metabolic Effects of 20-Kilodalton Human Growth Hormone ..." made reference in the following phrase:

"Hashimoto et al. (16) have recently reported that single sc administration of 20K-hGH dose-dependently (0.003–0.1 mg/kg) increases serum IGF-I levels and stimulates lipolysis in normal subjects. Their results also showed that 20K-hGH administration significantly suppressed secretion of endogenous 22K-hGH." NOTE: the reference is primarily to define the characteristics of 20kDa (which makes up only 5 -10% of natural GH and 0% of synthetic GH).

Cited article #3 "Physiological and pharmacological regulation of 20-kDa..." made reference in the following phrases:

"Five separate studies were performed to investigate the physiological and pharmacological regulation of 20-kDa GH secretion (14-17, 20, 33)"

Elsewhere:

"It was previously reported that pituitary-derived 20-kDa human GH (hGH) was cleared more slowly than 22-kDa hGH in the rat (4). However, this has not been confirmed by a recent study in humans using recombinant 20-kDa hGH (13)"

And finally:

"These results are consistent with previous findings of Wu et al. (35) that the ratio of 22-kDa to total GH increased when recombinant GH was administered. Hashimoto et al. (13) have also shown that administration of 20-kDa GH reduced the levels of 22-kDa GH. Taken together, both GH isoforms are potent negative regulators of their own secretion."

None of those citations where made to support the conclusions you have drawn. You can not extrapolate patterns and levels that appear over the course of days, weeks and months based on a study using a single dose 24 hour dose.

jm425 · Nov 20, 2008

Thanks for the article diskey. It's very informative and also gives a good insight into when to take hgh. Good post.

diskey · Nov 20, 2008

DatBtrue said:
No actually according to The Journal of Clinical Endocrinology & Metabolism, there are only three articles that cite Exogenous 20K Growth Hormone (GH) Suppresses Endogenous 22K GH Secretion in Normal Men , Yoshihide Hashimoto, The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 2 601-606. They are:

Systematic Review: The Effects of Growth Hormone on Athletic Performance, Ann Intern Med, May 20, 2008; 148(10): 747 - 758

Metabolic Effects of 20-Kilodalton Human Growth Hormone (20K-hGH) for Adults with Growth Hormone Deficiency: Results of an Exploratory Uncontrolled Multicenter Clinical Trial of 20K-hGH, J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1562 - 1571

Physiological and pharmacological regulation of 20-kDa growth hormone, Am J Physiol Endocrinol Metab, October 1, 2002; 283(4): E836 - E84

Now if you go pull those cited articles to see why they cited the original study here is what you find:

Cited article #1 "Systematic Review: The Effects of Growth Hormone..." made reference in the following phrase:

"Seven studies evaluated the use of a single dose of growth hormone. Of these, 3 studies provided growth hormone subcutaneously (35, 36, 38)" NOTE: 36 is a cite to the original article made simply to cite a study that use subcutaneous dosing.

Cited article #2 "Metabolic Effects of 20-Kilodalton Human Growth Hormone ..." made reference in the following phrase:

"Hashimoto et al. (16) have recently reported that single sc administration of 20K-hGH dose-dependently (0.003–0.1 mg/kg) increases serum IGF-I levels and stimulates lipolysis in normal subjects. Their results also showed that 20K-hGH administration significantly suppressed secretion of endogenous 22K-hGH." NOTE: the reference is primarily to define the characteristics of 20kDa (which makes up only 5 -10% of natural GH and 0% of synthetic GH).

Cited article #3 "Physiological and pharmacological regulation of 20-kDa..." made reference in the following phrases:

"Five separate studies were performed to investigate the physiological and pharmacological regulation of 20-kDa GH secretion (14-17, 20, 33)"

Elsewhere:

"It was previously reported that pituitary-derived 20-kDa human GH (hGH) was cleared more slowly than 22-kDa hGH in the rat (4). However, this has not been confirmed by a recent study in humans using recombinant 20-kDa hGH (13)"

And finally:

"These results are consistent with previous findings of Wu et al. (35) that the ratio of 22-kDa to total GH increased when recombinant GH was administered. Hashimoto et al. (13) have also shown that administration of 20-kDa GH reduced the levels of 22-kDa GH. Taken together, both GH isoforms are potent negative regulators of their own secretion."

None of those citations where made to support the conclusions you have drawn. You can not extrapolate patterns and levels that appear over the course of days, weeks and months based on a study using a single dose 24 hour dose.

"These results are consistent with previous findings of Wu et al. (35) that the ratio of 22-kDa to total GH increased when recombinant GH was administered. Hashimoto et al. (13) have also shown that administration of 20-kDa GH reduced the levels of 22-kDa GH. Taken together, both GH isoforms are potent negative regulators of their own secretion."

This one supports the idea at least.

"It was previously reported that pituitary-derived 20-kDa human GH (hGH) was cleared more slowly than 22-kDa hGH in the rat (4). However, this has not been confirmed by a recent study in humans using recombinant 20-kDa hGH (13)",

rats absorb gh generally much faster than humans, so they give love validity to human use.

----

But to be honest I didn't know that 22k was the variant that was sold today. Do you know if there are any particular differences between those two(20k and 22k) except from a few different isoptops?

I didn't draw and conclusions, I recaped the study in the belief that 20K is the one sold. But then when you made me aware, I "assumed" that probably, and logically much reasanoble the two would be very similar in regard to topics discussed.

Nice you went through those citations, as you probably now many journals do not have all the citations that is actually used. It probably means that the article has been cited 3 times in that particular journal. Here are the rest of the 16 citations:

**broken link removed**

KillerStack · Nov 20, 2008

diskey said:
I also have the thought that fat loss from hgh, except for the spot reduction, is basically because of the increse in metabloism,

I think fat loss is due to increase in fat use for energy, instead of carbs. Lowered insulin sensitivity in fat cells is also a factor IMO.

As far as the original post I've said the same here for years. Like that igf-1 doesn't peak until a day later. Which is why I don't think timing matters hugely as long as you take it regularly.

DatBtrue · Nov 20, 2008

diskey; said:
But to be honest I didn't know that 22k was the variant that was sold today. Do you know if there are any particular differences between those two(20k and 22k) except from a few different isoptops?

The 20kDa is missing the amino acids that interact with the prolactin receptor. Studies have shown that 20kDa is just as anabolic as the 22kDa version. However it may bring about lower insulin resistance and lower levels of edema

Naturally the pituitary somatotrophs make and store both versions. Usually a blend is released with 90% being the 22kDa version and the other 10% being the 20kDa version. Immediately after exercise though the body seems to release more 20kDa.

The synthetic version that was made into a pharmaceutical is the 22kDa (full 191 aminos) version. There is no 20kDa synthetic yet available.

There are differences in how the two versions bind to the growth hormone receptor. The most interesting thing (to me) is that in high doses synthetic GH (22kDa) begins to clog up the receptors by two molcules trying to bind at the same time. This ends up having no effect and eliminating that receptor so the end result is that GH starts to become less effective.

20Kda doesn't have as strong a tendancy to behave this way at high dose. Pictures tell the story and the study with relevant parts highlighted is posted in my thread at AM **broken link removed**

diskey; said:
I didn't draw and conclusions, I recaped the study in the belief that 20K is the one sold. But then when you made me aware, I "assumed" that probably, and logically much reasanoble the two would be very similar in regard to topics discussed.

I know... but the essence of effectiveness doesn't come from creating chronically high dose levels of either GH or IGF-1.

The intracellular signalling (what happens after GH binds to a GH-receptor) is what is important because that is where the metabolic & proliferative events are mediated. As such these intracellular pathways need off time (or the absence of GH) to resensitize and be ready to go at full strength when the next GH wave occurs. This requires pulsation and troughs of low/no growth hormone.

Also it is not general liver synthesized circulating IGF-1 levels that are important. Rather it is IGF-1 that is created in muscle tissue & acts in that tissue. This is known as paracrine/autocrine or locally produced locally used. The muscle cell actually creates the IGF-1 and a pool sits in the cell cytoplasm before translocating to the cell surface and binding to its receptor.

After working out, the splice variant MGF is created in muscle cells.

It is GH levels that cause this local action to occur. Androgens aid the process.

So my simple point is that dosing synthetic GH needs to be done in such a way as to insure the latter and maximize the former.

Massive G and then others figured out that EOD dosing was better then ED dosing if building muscle tissue was the goal. They didn't know why ...they just figured it out.

The off time insures that the intracellular signalling pathways specifically Stat5b but also the modulating pathway that aids in proliferation, ERK1/2 are resensitized and ready to do things such as translocate to the nucleus of the cell and be involved in protein transcription once a wave of GH binds to a receptor and "flips the switch" to turn them on.