The Myth of LR3 IGF-I ("IGF1-LR3")'s Long Half-Life

[sean1970ss]

I use it for advanced guys, with good results, but very differently from how it's used commonly. My protocol is proprietary. I edited this, because I would not actually apply LR3 IGF-I in your case.

I will get in touch! I really appreciate it sir! Sean

 

[dimethyl11]

LR3, yes. It adds up at the doses & frequencies you need to use for any significant effects. It's WAY more expensive than a moderately-high pharma rhGH dose, that is going to give you severalfold the results of LR3 if you're healthy (i.e., GH responsive).

I see a lot of people saying 4 weeks on 4 weeks off lr3, do you find this neccesary? Or is this another 'give the AR a chance to resensitize"

 

[Type-IIx]

I see a lot of people saying 4 weeks on 4 weeks off lr3, do you find this neccesary? Or is this another 'give the AR a chance to resensitize"

I don't see this as necessary because there's no known reason why its tachyphylactic effects would be any more profound than IGF-I's, for which yearslong treatment at a constant or relative dose is given to primary IGF-I deficient children with short stature.

RhGH sees substantial diminished potency at a constant dose that begins a trend decrement in ΔIGF-I between 4 & 5 mo. of continuous use and reaches a substantial decrement in GH response by month 9 (-42.73%) and yet guys still run rhGH year-round, and the same comment as for rhIGF-I's clinical use applies to rhGH with respect to short stature children.

I have all the horseshit saved that was written about LR3 IGF-I on BassKillerOnline, and it's just made up bro. That's where I think all of this bad information originated.

 

[dimethyl11]

I don't see this as necessary because there's no known reason why its tachyphylactic effects would be any more profound than IGF-I's, for which yearslong treatment at a constant or relative dose is given to primary IGF-I deficient children with short stature.

RhGH sees substantial diminished potency at a constant dose that begins a trend decrement in ΔIGF-I between 4 & 5 mo. of continuous use and reaches a substantial decrement in GH response by month 9 (-42.73%) and yet guys still run rhGH year-round, and the same comment as for rhIGF-I's clinical use applies to rhGH with respect to short stature children.

I have all the horseshit saved that was written about LR3 IGF-I on BassKillerOnline, and it's just made up bro. That's where I think all of this bad information originated.

Fantastic - thanks!!

 

[ZERaptor]

That's right, but I'd use rhIGF-I not LR3 in those cases, and in instances where GH response is low due to amenable health (e.g., liver, kidney disorders, prediabetes, obesity) or drug (e.g., trenbolone, estrogens) factors, try to ameliorate that first.

Does lower estrogen level increase or decrease liver hgh conversion to igf-1? So far what ive found is that lower estrogen levels are better (but not crashed levels)

 

[Type-IIx]

Does lower estrogen level increase or decrease liver hgh conversion to igf-1? So far what ive found is that lower estrogen levels are better (but not crashed levels)

Well, high estrogens lower IGF-I, but it does not follow that low estrogen levels increase it.

I'll describe the process by which T=[Aromatase]=>E2 negatively feeds back on IGF-I bioavailability:

E2 is a negative factor for IGF-I bioavailability. That is, once aromatization is very high, E2 feeds back negatively on IGF-I levels because of IGFBP-1, an IGF-I binding protein that is increased by estrogens and inactivates IGF-I in its active form.

E2, then, is not a positive factor for enhancing IGF-I. Rather, aromatization as a process is.

Estrogens increase IGFBP-1, reducing IGF-I bioavailability and unleashing GH secretion by feedback withdrawal. It's why women have higher GH levels than men by body surface area and are less sensitive per-mg to rhGH, and require dose increase (titrating up) when using exogenous estrogens: oral estradiol dramatically decreases IGF-I activity, and transdermal less so.

The result of increasing E2 by T dose is a sort of asymptotic shape to the curve of T/IGF-I in men. That is, at low levels of E2 (because low T & therefore aromatization), IGF-I activity is also low. As the E2 levels (because moderate/moderately-high T and therefore aromatization) increase, IGF-I does as well. Up to a point where E2 effects begin to inhibit (negatively feed-back on) IGF-I. Then the curve starts to taper off, increasing at a decreasing rate initially, and then negatively accelerating.

So, the task of maximizing IGF-I requires both the use of aromatizing androgen (e.g., T) and if using moderately-high/high/very-high T doses, then also using an aromatase inhibitor (AI) at a dose that doesn't totally abrogate (block) aromatase but rather shifts the inflection point (asymptote) to the right on the T/IGF-I curve. Moreover, AI compound selection is paramount. Exemestane does not directly decrease IGF-I (because its primary active metabolite is an androgen & it possesses a steroidal core), so it is a good choice for this task.

 

[tinypeter]

Was wanting to run some peptides but I hear such hit and miss stuff about them it makes me not want to now.

 

[Type-IIx]

Was wanting to run some peptides but I hear such hit and miss stuff about them it makes me not want to now.

Growth & Slin are peptides. Good ones.

 

[tinypeter]

Growth & Slin are peptides. Good ones.

Those are the only ones I've ran.
Green top hygetropins and humalin r from CVS.
This was 8 years or so ago.
Was say more towards, cjc, ghrp, lr3, tb500 all those new ones. Well i feel they are new. New to me lol

 

[tinypeter]

I know if you have good gh and use the slin right it's fucking crazy what it does.

 

[Itsdaboii]

By the law of large numbers, probably. It does have its uses in some cases, but it's less anabolic in human skeletal muscle (where it is equipotent to IGF-I) than slin or GH and the doses & frequencies at which they must be administered for any biologically relevant effect (typified by hypoglycemia) are tremendously expensive.

So which dose is effective? 1mg spread over the day? Higher then that?

 

[astral_essence]

LR3 IGF-I ("IGF1-LR3")'s biological half life is remarkably & profoundly short rather than long.

Its clearance from the blood depends primarily on IGFBP-3 levels, that are increased, probably dose-dependently, by rhGH. Nobody knows its estimated t1/2 in healthy adults, but it should be administered at least twice daily, if not more frequently.

From my notes (granted, it takes a bit more understanding that “it’s ‘Long’ R3, bro, lol”):

LR3 IGF-I is more potent than IGF-I when the peptides are given by injection, and particularly with twice daily injection due to its rapid clearance from plasma. [1]. The affinity for binding is four- to five- fold larger for LR3 IGF-I than IGF-I, and it is rapidly cleared from the plasma as a consequence of its resistance to binding to the IGFBPs. [1].

IGFBPs profiles & functions

- human skeletal muscle cells: abundant IGFBP-3; high affinity -BP-2 & -BP-4; -3, & -5 [3]

- fetal cells: <<IGFBP-3, -2 & no -4

- rat L6: IGFBP-4, -5, and -6

- rat C2: only IGFBP-5. [2].

IGFBPs modulate IGF activity by extending the half-life of the IGFs and by either potentiating or inhibiting binding of the IGFs to their receptors. [3].

From [3]:

Although muscle satellite cells were identified almost 40 years ago, little is known about the induction of their proliferation and differentiation in response to physiological/pathological stimuli or to growth factors/cytokines. In order to investigate the role of the insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system in adult human myoblast differentiation we have developed a primary human skeletal muscle cell model. We show that under low serum media (LSM) differentiating conditions, the cells secrete IGF binding proteins-2, -3, -4 and -5. Intact IGFBP-5 was detected at days 1 and 2 but by day 7 in LSM it was removed by proteolysis. IGFBP-4 levels were also decreased at day 7 in the presence of IGF-I, potentially by proteolysis. In contrast, we observed that IGFBP-3 initially decreased on transfer of cells into LSM but then increased with myotube formation. Treatment with 20 ng/ml tumour necrosis factor-alpha (TNFalpha), which inhibits myoblast differentiation, blocked IGFBP-3 production and secretion whereas 30 ng/ml IGF-I, which stimulates myoblast differentiation, increased IGFBP-3 secretion. The TNFalpha-induced decrease in IGFBP-3 production and inhibition of differentiation could not be rescued by addition of IGF-I. LongR(3)IGF-I, which does not bind to the IGFBPs, had a similar effect on differentiation and IGFBP-3 secretion as IGF-I, both with and without TNFalpha, confirming that increased IGFBP-3 is not purely due to increased stability conferred by binding to IGF-I. Furthermore reduction of IGFBP-3 secretion using antisense oligonucleotides led to an inhibition of differentiation. Taken together these data indicate that IGFBP-3 supports myoblast differentiation.


From the INCRELEX pamphlet:

Clearance of [IGF-I and its analogues] is inversely proportional to IGF binding protein-3 (IGFBP-3) levels.

Normal (healthy) clearance is 0.01 L/hr/kg (because normal concentrations of IGFBP-3, to which clearance is inversely proportional, is 3 micrograms/mL IGFBP-3).

From [4]:

rats; protocol: continuous subcutaneous infusion ~1.5mg * kg⁻¹ daily * 28 days (0.125μL*h⁻¹)

No significant effect of LR3 IGF-I on muscle contractile properties, mass, force capacity, nor specific force!

↓IGF-I (serum), ↓median myofiber CSA, indicating that IGFBP interaction is needed to maintain or augment muscle myofiber size, oxidative capacity!

_______________________

References:

[1] Tomas, F. M., Lemmey, A. B., Read, L. C., & Ballard, F. J. (1996). Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. Journal of Endocr inology, 150(1), 77–84. doi:10.1677/joe.0.1500077

[2] Crown, A. (2000). Characterisation of the IGF system in a primary adult human skeletal muscle cell model, and comparison of the effects of insulin and IGF-I on protein metabolism. Journal of Endocrinology, 167(3), 403–415. doi:10.1677/joe.0.1670403

[3] Foulstone, E. J., Savage, P. B., Crown, A. L., Holly, J. M. P., & Stewart, C. E. H. (2003). Role of insulin-like growth factor binding protein-3 (IGFBP-3) in the differentiation of primary human adult skeletal myoblasts. Journal of Cellular Physiology, 195(1), 70–79. doi:10.1002/jcp.10227

[4] Gehrig SM, Ryall JG, Schertzer JD, Lynch GS. Insulin-like growth factor-I analogue protects muscles of dystrophic mdx mice from contraction-mediated damage. Exp Physiol. 2008 Nov;93(11):1190-8. doi: 10.1113/expphysiol.2008.042838. Epub 2008 Jun 20.

Thank you for your contribution in regards to the above info.
Question for you based on the above is what are your thoughts in regards to DES-IGF?

Half Life? (Most available info up unto this point states 30mins)

Comparison to IGF-LR3 in terms of potency, efficacy, etc?

Thanks for your time in advance.
AE

 

[Type-IIx]

Thank you for your contribution in regards to the above info.
Question for you based on the above is what are your thoughts in regards to DES-IGF?

Half Life? (Most available info up unto this point states 30mins)

Comparison to IGF-LR3 in terms of potency, efficacy, etc?

Thanks for your time in advance.
AE

I just think people start wasting money when they start buying all these IGF fragments and analogues. LR3 IGF-I, rhIGF-I, rhGH; maybe, ipamorelin and Mod GRF (1-29). Those are the full plethora of agents with any particular use case for bodybuilding. The latter two, for women mostly.

 

[Superset007]

This is the primary reason why I always do my igf pre workout right before the gym. into the muscle I’m working out.

 

[astral_essence]

I just think people start wasting money when they start buying all these IGF fragments and analogues. LR3 IGF-I, rhIGF-I, rhGH; maybe, ipamorelin and Mod GRF (1-29). Those are the full plethora of agents with any particular use case for bodybuilding. The latter two, for women mostly.

FYI - Just came across this.

Study from 2021 seems to be supporting your original conclusions on IGF-LR3.

Same study detected what one could interpret as a much longer half life to Des-IGF in comparison.

Detection of LongR3 -IGF-I, Des(1-3)-IGF-I, and R3 -IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes - PubMed

Insulin-like growth factor-I (IGF-I) and its analogs LongR³ -IGF-I, Des(1-3)-IGF-I, and R³ -IGF-I are prohibited substances in sport. Although they were never approved for use in humans, they are readily available as black market products for bodybuilding and can be used to...

pubmed.ncbi.nlm.nih.gov

 

[BigLittleJoe2]

RhGH sees substantial diminished potency at a constant dose that begins a trend decrement in ΔIGF-I between 4 & 5 mo. of continuous use and reaches a substantial decrement in GH response by month 9 (-42.73%) and yet guys still run rhGH year-round, and the same comment as for rhIGF-I's clinical use applies to rhGH with respect to short stature children.

What research are these estimated declines in potency based on? Is the remedy to come off HGH completely for a period of time? If so, how long?

My understanding is that most top pros stay on HGH for years on end. Should they be doing something differently?

 

[Zonezack]

Why is DES unpopular?

 

[Type-IIx]

What research are these estimated declines in potency based on? Is the remedy to come off HGH completely for a period of time? If so, how long?

My understanding is that most top pros stay on HGH for years on end. Should they be doing something differently?

To be discussed at length in my book to be released by Christmas, Bolus: A Practical and Reference Guide for the Use of human Growth Hormone and GH Secretagogues! I've done a lot of work putting together all the data.

 

[mimo]

Dude you've been saying this for a while now. Any estimates on when it will be ready?

 

[Type-IIx]

Dude you've been saying this for a while now. Any estimates on when it will be ready?

Dec 16