anthroLift

Des(1–3)IGF-1

tl;dr Des(1-3)IGF-1 is a form of IGF-1 found in the brain but also works for muscle development. It is very potent. Some studies show it be 10x the potency of full IGF-1. There is also a controversial theory regarding it’s creation during exercise that I think is false.

Names: Des(1–3)IGF-1, IGF-1 DES 1-3, des(N)IGF-1, IGF-1 DES, R3-IGF-1, desamino-(1-3)-IGF-1

Introduction

Des(1–3)IGF-1 is a smaller version of insulin-like growth factor 1 (IGF-1). It has been truncated to have 3 less amino acids than IGF-1. The full name “desamino(1-3)” is a really fancy way of saying the removal of 3 amino acids.

This change allows it to bind less to Insulin-like Growth Factor-Binding Proteins (IGFBPs). IGFBP are the proteins that IGF-1 can bind to instead of the IGF-1 receptors in a cell. This inhibits the effects of IGF-1 by preventing it from binding to cells to cause growth. But with an up to 20-50x less adhesion to IGFBP123 this means more des(1–3) to cause more IGF activity in cells.456

More effective than base IGF-1

The bottom line on this change? One study found des(1–3)IGF-1 to have 10 times the potency for stimulating hypertrophy over IGF-1.7

As we’ve seen with IGF-1 LR3, changes to the base IGF-1 molecule affect it’s half-life. Des(1-3)IGF-1 is a very brief molecule that has a half-life of under 5 minutes in humans.8 This very short life means dosing has to be precise.

Muscle Growth and Repair

Evidence:

Effect:

Des(1–3)IGF-1 is highly anabolic

As expected from any IGF-1 peptide, des(1-3) is anabolic and used by muscles for growth and recovery. It has been shown to be as effective as IGF-1 for muscle growth9 and 2.5x as potent for reversing catabolic states.10 These effects are found again comparing IGF-1 to des(1-3)IGF-1, with des(1-3) being better at lower doses.11

Another study finds it highly effective compared to IGF-1 in reducing the rate of muscle protein breakdown.12 This is because it’s anti-catabolic effects are helpful for keeping muscle mass during catabolic states like dietary protein restriction13 or renal failure.14

The best explanation is that because des(1-3) does not bind to IGFBPs as much, it is able to take action at the cellular level more effectively. Des(1-3) simply does a better job in times of muscle stress when negative catabolic effects are damaging muscle tissue.

Other Benfits

This peptide’s main strength is in it’s anabolic properties. Since it is similar to full IGF-1, des(1-3) has a host of other effects in the body. It plays a role in bone growth and repair,15 smooth muscle survival,16 and stomach/gut growth specifically.171819 It does have a few other uses in the brain, but studying this is difficult.

Here’s how it does for our areas of interest:

TBI and Brain Health

Evidence:

Effect:

Created in the brain and works with nuerons

Des(1-3) offers some level of neuroprotection for the brain. A very early study found it to be the form of IGF-1 that the human brain uses locally.20 It wasn’t until 2 years later the peptide was named specifically. But in general the IGF series is active in brain growth21 and helping brain damage.22

Directly related to TBI, des(1-3) is found to help the “life-threatening negative nitrogen balance” present in polytrauma (accidents involving multiple organ system damage) often accoympaning the cause of TBI.23

This peptide has other brain benefits besides TBI. Des(1-3) is found to be better than full IGF-1 at protecting after stroke related brain injuries.24 It is also effective at promoting neural growth25, better at keeping nuerons alive26, and preventing apoptosis in some neurons to keep them alive even longer.27

PTSD

Evidence:

There are studies or reports of using des(1-3) for PTSD.

Alzeimher’s Disease

Evidence:

Effect:

Might offer some protection

IGF-1 is found to prevent cell death in Alziemer’s disease. Des(1-3) is found to offer similar effects, but at no better or worse levels.2829 But while research is continuing30 there is one problem. As you age there are less IGF-1 receptors in the brain. This age related decline in numbers makes it difficult to explore the effects IGF-1 or des(1-3).31

Wound Repair

Evidence:

Effect:

Des(1-3) is found to be ineffective at wound repair when compared to normal IGF-1 bound to IGFBP.32 It appears that des(1-3) by itself is not enough to start the biological tissue repair process. The Binding Protein + IGF-1 combination is necessary.

Nerve Repair

Evidence:

There is no direct link between peripheral nerve growth and this peptide. All nervous system related studies for des(1-3) are related to the brain. This makes sense given that it’s found there.

Downsides

Cancer link like any IGF-1

Des(1-3) is very capable of causing organ growth33 and cell differentiation.343536 In many cases it is better than full IGF-1 at causing this growth.37 There is a fine line though and after a certain point des(1-3) was toxic to budding cells.38

The downside of this faster growth, of course, is helping cancer cells grow as well.39 Des(1-3) is found to stop cancer cells from dying.40

Lactic Acid and Des(1-3) Theory

Evidence:

In Author L. Rea’s book Chemical Muscle Enhancement he floats a theory about endogenous production of des(1-3) during workout. He claims that the lactic acid in your muscles cleaves IGF-1 into the des(1-3) form. He also claims that the lactic acid present deforms the IGF-1 receptors in such a manner that only des(1-3) can bind. Because IGF-1 cannot bind in such a catabolic environment, the endogenous des(1-3) is made to protect your muscles temporarily.

It’s a beautiful and elegant theory. Intuitively, the process makes sense because it is similar to endegenous MGF/IGF-1EC creation. xxxx link me here

Rea’s theory sounds good but there’s one problem…

But: he offers zero citations, studies, or evidence for this process. Unfortunately we can’t ask him. Rea passed away in 2016 and his is the only work I can find describing the role of lactic acid and IGF-1 for muscles. His theories and works are controversial - to put it mildly.

Normally I would reject these claims since they aren’t cited. Sadly, his claims from Chemical Muscle Enhancement have wormed their way into every single webpage or forum post as holy fact on the nature of des(1-3). If you’ve done more than a few minutes of searching you’ve seen his claims.

I’ll do my best to step through his claims:

Part 1 Most athletes have heard of IGF-1 (insulin like growth factor-1) and the amazing anabolic effects it has been reported to have upon Protein based tissue such as muscle. Des (1-3) IGF-1 is over 10 times (1000%) more anabolic than IGF-1. Now that is amazing!! IGF-1 is actually produced from both insulin and growth hormone in the Liver and other tissues. IGF-1 is made up of 70 amino acids in a chain. Well, when a clever chemist removes the last 3 amino acids in the IGF-1 chain (the N-terminal tri-peptide) it becomes Des (1-3) IGF-1 and 1000% plus more anabolic. Why?

True

Some of the earliest human studies found des(1-3) to be 10x as potent for hypertrophy.41

Part 2 IGF-1 circulates through our blood stream and tissue 24 hours a day, 7 days a week. Unfortunately, most of the IGF-1 is inactive because it is bound by another Protein called (get this) IGF-1 Binding Protein-3, or IGF-1-BP-3 for short. Since bound hormones can not fit into and trigger a receptor-site, the majority of circulating and muscle IGF-1 can not trigger an anabolic stimulus. Like tons of cellulite in a ***** movie (who watches those?) there is little good stuff happening. However, when IGF-1 is altered and becomes Des (1-3) IGF-1 the binding Protein IGF-1-BP-3 can not bind to it and it is totally active.

True

IGF-1 is indeed bound mostly by IGFBP3. Des(1-3) does have minimal BP activity, but not enough to affect bioavailability by any large degree.42

Part 3 Another reason Des (1-3) IGF-1 is so potent is its unique ability to fit into lactic acid altered IGF-1 receptor sites. (YUP) When we train we burn carbohydrates as a fuel to make cellular ATP. When cells switch to this ATP pathway, the by-product is Lactic Acid. This is of course the cause of most of the burn we feel during intense or higher rep sets. Well, the lactic acid build-up is called acidosis, and it destroys the shape of some receptor-sites for period of time. Therefore some anabolic/anti-catabolic hormones have difficulty merging with their respective receptor- site and triggering a response (such as even unbound IGF-1). Not so with Des (1-3) IGF- 1, the super growth factor. It fits into the IGF-1 receptor-site even after acidosis. Des (1- 3) IGF-1 is unbound, over 10 times more potent than IGF-1, and it picks receptor-site locks. Too bad it has only a few minute active-life.

Unproven

Indeed, you make lactic acid as a result of ATP production. There is a form of acidosis occurring, but it is not the direct effect of lactate build up and it is not metabolic acidosis.43 Receptors do change shape, and acidosis is capable of making other cells change shape.44 Full metabolic acidosis is capable of affecting IGF-1 receptors.45 Seldin and Giebisch’s research into kidneys46 shows that in chronic acidosis there are less IGF-1 receptors expressed in muscle. But: that is in a chronic long-term condition, and the effect is not switched on or off as quickly as working out does in Rea’s theory.

The claim that this local non-metabolic acidosis temporarily deforms the IGF-1 receptors is possible, but presented with no proof. There are simply no studies of exercise or lactate changing the IGF-1 receptor in such a way. Same with the claim of des(1-3) being able to fit the deformed receptor - no existing research comparing IGF-1 to des(1-3) has shown any difference in the IGF-1 receptor affinity.

Part 4 Did you know that our body’s make Des (1-3) IGF-1 naturally? Most un-informed individuals claim other wise, but it is true. When an athlete trains lactic acid builds up in muscle tissue. As we know, there is always IGF-1 / GH present in the blood stream and tissues (including muscle) from prior work-outs and other metabolic factors. That lactic acid burn triggers IGF-1/GH secretion from both prior and present work-outs. Unfortunately, lactic acid destroys some of the IGF-1 present in muscles being trained. But wait, this is good too!

Unproven

The main point here is that lactic acid destroys IGF-1. Trying to search for this only brings up circular claims from the book itself. There are no links or studies of IGF-1 being destroyed by lactic acid, lactate, or acidosis. Full blown metabolic acidosis is proven to cause a “significant decrease in serum IGF-1 concentration”47 but not by destroying the molecule. Rather, acidosis causes hGH resistance so IGF-1 isn’t made in the first place. IGF-1 is of course capable of being destroyed, but is not a particularly fragile molecule.4849

Parts 5 Lactic acid also cuts (truncates) the last 3 amino acids off the 70 amino acid chain of “some” of the surviving IGF-1 and creates Des (I-3) IGF-1. So acidosis increases GH/IGF-1 production in the Liver, “unbinds” IGF-1 locally in the muscle being trained (burned), destroys some of the IGF-1, and converts some IGF-1 into Des (I-3) IGF-1. Huh, good deal. And the synthetic form of this super anabolic stuff is beginning to show up on the black market more frequently.

Unproven/False

This is the main part of the des(1-3) + lactic acid theory. The same action (lactic acid buildup) that causes a catabolic environment also creates the anabolic agent. But he gives no proof or citation. There are no studies or research anywhere else that suggest this is what goes on. It is even possible that the formation of des(1-3) is not necessary for muscle growth, and it’s occurrence just simply occurs sometimes with no greater purpose.50

Is there any way Rea’s idea could be true?

To play Devil’s Advocate here how it could work:

  1. “Proteolysis” is the technical term for what happens when a protein is broken down into it’s component amino acids. So stripping the three amino acids off IGF-1 would create des(1-3)IGF-1 through proteolysis.

  2. We do see this happening: Des(1-3) is capable of being made by many different enzymatic means51 or through proteolysis.5253

  3. This process is also more effective in acidic conditions5455 such as the 6.4-6.6 pH levels present during exercise.56

  4. This part requires a logical leap. The lactic acid present quickly finds the local free IGF-1 (which is likely less than 5% of the total IGF-1 in your body) and cleaves it. Your muscle (with it’s somehow deformed IGF-1 receptor) can now take the des(1-3) for protection. This receptor then does not deform again. The bound des(1-3) also does not undergo further cleavage into des(1-4,5,6)57 - ignoring the claims that IGF-1 would somehow become unbound by the lactic acid, but des(1-3) would not. This process continues until the pH levels go back to normal.

I guess it’s possible. But, more likely, Rea made this up. Which sucks because it’s a great theory and very elegant.

But all reference studies for proteolysis and IGF-1 are how the body uses proteolysis to destroy the binding proteins, not IGF-1 itself. (585960, etc) This is more consistent with how the endocrine system works.

The other claims are false. Des(1-3) is created only on free IGF-1, not from bound IGF-1.61 Local acidosis in a muscle does not directly signal back to the liver to create more IGF-1/GH. GH does not come from the liver. IGF-1 release is triggered by GH, which is released in a pulsatile manner on a circadian rhythm 62 by the pituitary gland.

What’s the takeaway?

All in all I don’t believe his lactic acid theory - mainly because Rea was known for making many incredible claims but not giving any proof. The best way to test would be on IGF-1 that has been bathed in lactic acid at 6.5 pH. If there’s no des(1-3) present the theory is proven false.

Regardless of if you believe his theory, you have to admit it has infiltrated everywhere. I’ve seen some pretty bad misunderstandings from it.

Leads to even more confusion

A common misconception is that lactic acid itself makes des(1-3) more effective, or that des(1-3) is only active with lactic acid. His theory only says the lactic acid simply creates the environment for des(1-3) to be created.

He also never claims that lactic acid alter des(1-3) further or change it’s structure. It also doesn’t “bind to lactic acid receptors” in the muscle. There are no such things. Des(1-3) binds to the IGF-1 receptors. Also, the des(1-3) doesn’t swoop in and overtake any bound IGF-1 - the two don’t knock each other off receptor sites.63

I am also working on exploring the reasons for des(1-3) to even exist. Of all IGF-1 desamino forms it is the best for bioavailability, but 99% of the work on this peptide is just measuring it’s effects - no one seems to asking WHY it exists.

Dosage

Patents

Pricing

Pubchem doesn’t seem to have an entry for Des(1–3)IGF-1. Sigma-Aldrich does not seem to sell it, but some other high end suppliers have it starting anywhere from $50-$250 for 20mcg, with bigger orders being around the same price as peptide sites.

Peptide site pricing is around $110-$120 for 1-1.2mg.

Legality

This is a good time to point out my standard disclaimer: I am not a doctor or a lawyer. I made this site to help in my own research of the human endocrine system, and to find any new treatments for PTSD and Traumatic Brain Injury. I’m not making any medical or legal claims about any drug here besides what medical studies are showing and what people are self-reporting they use.

Each country and state is free to make their own scheduling on substances so it’s up to you to check. At the time of writing Des(1–3)IGF-1 didn’t appear on the DEA list.

WADA specifically bans the IGF-1 class as a whole. They prohibit at all times:

  • Insulin-like Growth Factor-1 (IGF-1), and its analogues

The NCAA bans as a class “Peptide Hormones and Analogues” naming “Growth hormone (hGH); human chorionic gonadotropin (hCG); erythropoietin (EPO); IGF-1; etc.” Des(1–3)IGF-1 being a form of IGF-1 would fall under this ban.

References

  1. Ross, M, G L Francis, L Szabo, J C Wallace, and F J Ballard. 1989. “Insulin-Like Growth Factor (IGF)-Binding Proteins Inhibit the Biological Activities of IGF-1 and IGF-2 but Not Des-(1-3)-IGF-1.” Biochemical Journal 258 (1) (February 15): 267–272. doi:10.1042/bj2580267. http://dx.doi.org/10.1042/bj2580267. ↵
  2. ROGHANI, MONIREH, CLAUDINE LASSARRE, JÜRGEN ZAPF, GUILHERME POVOA, and MICHEL BINOUX. 1991. “Two Insulin-Like Growth Factor (IGF)-Binding Proteins Are Responsible for the Selective Affinity for IGF-II of Cerebrospinal Fluid Binding Proteins*.” The Journal of Clinical Endocrinology & Metabolism 73 (3) (September): 658–666. doi:10.1210/jcem-73-3-658. http://dx.doi.org/10.1210/jcem-73-3-658. ↵
  3. Gill, R. 1996. “Biosensor Measurement of the Binding of Insulin-Like Growth Factors I and II and Their Analogues to the Insulin-Like Growth Factor-Binding Protein-3.” Journal of Biological Chemistry 271 (24) (June 14): 13948–13952. doi:10.1074/jbc.271.24.13948. http://dx.doi.org/10.1074/jbc.271.24.13948. ↵
  4. G L Francis, S E Aplin, S J Milner, K A McNeil, F J Ballard, and J C Wallace. Insulin-like growth factor (IGF)-II binding to IGF-binding proteins and IGF receptors is modified by deletion of the N-terminal hexapeptide or substitution of arginine for glutamate-6 in IGF-II. Biochem J. 1993 Aug 1; 293(Pt 3): 713–719. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1134424/ ↵
  5. Bagley CJ, May BL, Szabo L, et al. A key functional role for the insulin-like growth factor 1 N-terminal pentapeptide. Biochemical Journal. 1989;259(3):665-671. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1138570/ ↵
  6. M Ross, G L Francis, L Szabo, J C Wallace, and F J Ballard. Insulin-like growth factor (IGF)-binding proteins inhibit the biological activities of IGF-1 and IGF-2 but not des-(1-3)-IGF-1. Biochem J. 1989 Feb 15; 258(1): 267–272. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1138350/ ↵
  7. John Ballard, F., John C. Wallace, Geoffrey L. Francis, Leanna C. Read, and Frank M. Tomas. 1996. “Des(1–3)IGF-I: a Truncated Form of Insulin-Like Growth Factor-I.” The International Journal of Biochemistry & Cell Biology 28 (10) (October): 1085–1087. doi:10.1016/1357-2725(96)00056-8. http://dx.doi.org/10.1016/1357-2725(96)00056-8. ↵
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  13. Tomas, F. M., S. E. Knowles, P. C. Owens, L. C. Read, C. S. Chandler, S. E. Gargosky, and F. J. Ballard. 1991. “Effects of Full-Length and Truncated Insulin-Like Growth Factor-I on Nitrogen Balance and Muscle Protein Metabolism in Nitrogen-Restricted Rats.” Journal of Endocrinology 128 (1) (January 1): 97–105. doi:10.1677/joe.0.1280097. http://dx.doi.org/10.1677/joe.0.1280097. ↵
  14. Insulin-like growth factor I and its variant, des(1-3)IGF-I, improve nitrogen balance and food utilization in rats with renal failure. Martin AA, Tomas FM, Ballard FJ, Read LC. Miner Electrolyte Metab. 1992; 18(2-5):264-8. [PMID:1465072] https://www.ncbi.nlm.nih.gov/pubmed/1465072 ↵
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