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Reversing copper peptide damage
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drtodorov
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Joined: 10 Dec 2004
Posts: 3177

PostPosted: Wed Jun 21, 2006 6:56 pm    Post subject: Reply with quote

I am not sure what is being quoted here, but it is clearly a misquote if someone is attemting to quote my words.

I never said that copper peptide oxidation was a problem. The problem might be, at least in theory, excessive MMP activation. CP are known to activate MMP. In fact, MMP activation is part of the mechanism thru which CP mediate skin remodelling.

I've always said that for most people copper peptides appear to be safe. However, the anecdotal reports of rare cases of side-effects should not be dismissed out of hand. One possible mechanism is the following. As I said, CP induce MMP (matrix metalloproteinases). Due to individual variability in induced MMP expression, in rare cases MMP production could be excessive and lead to side-effects, such as overshoot in connective matrix degradation. Unfortunately, to run a study testing this hypothesis would be laborious and expensive because you need to test a large sample to determine individual variability.

I don't specialize in copper peptides. I understand their mechanism of action to the degree a biochemist can understand research in a closely related field after reading research articles on it. I have not done CP studies in person and I never said I did. However, after receiving a number of anecdotal reports from users on significant side-effects, I felt that a remote possibily of such problems was at least worth a mention. Of course, anecdotal reports are not proof. But they may be a reason to conduct further research.

Of course, compared to Dr. Pickart, who has done decades worth of hands-on work with copper peptides, I am not an authority on this particular subject. On the other hand, I do not have a vested interest in commercial aspects of copper peptides either.


Last edited by drtodorov on Fri Jul 21, 2006 8:41 pm; edited 1 time in total
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sheellah



Joined: 20 Jun 2006
Posts: 22

PostPosted: Thu Jun 22, 2006 5:28 pm    Post subject: Reply with quote

Dr. Todorov, I again wrote to Dr. Pickart regarding your reply. This was his response also posted with his permission.

"SRCPs activate both proteases and anti-proteases. The only direct study of the effects on metalloproteinases concludes that GHK-copper decreases overall MMP activity in wounds in comparison to untreated wounds.

Canapp SO Jr, Farese JP, Schultz GS, Gowda S, Ishak A.M, Swaim SF, Vangilder J, Lee-Ambrose L, Martin FG, The effect of topical tripeptide-copper complex on healing of ischemic open wounds, Vet Surg. 2003 Nov-Dec;32(6):515-23. Result - GHK-Cu caused a significant decrease in wound area (64.5% GHK-Cu vs 28.2% control) by day 13. GHK-Cu also significantly lowered concentrations of TNF-alpha and MMP-2 and MMP-9."
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drtodorov
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PostPosted: Thu Jun 22, 2006 9:46 pm    Post subject: Reply with quote

Interesting. But this is not necessaarily a valid comparison because the biochemical environment of a wound is different from that of intact skin, i.e. a wound tends to have more inflammation mediators (such as TNF-alpha), oxygen free radicals and so forth. The baseline of MMP level will be higher in a wound. Therefore, from that study you cannot conclude that in the intact skin the balance of proteases/antiproteases will be the same after CP application. Besides, there's again an issue of individual variability.

Last edited by drtodorov on Sat Jun 24, 2006 2:13 am; edited 1 time in total
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PattiK



Joined: 09 Jan 2006
Posts: 11

PostPosted: Fri Jun 23, 2006 8:00 pm    Post subject: Reply with quote

I'm not sure what we a trying to prove here. Anyone who spends any amount of time on skin care forums - of which there are many - knows that there are plenty of people that have problems with CPs (i.e., anecdotal evidence). Even the skin bio forum is full of posts about dealing with "the uglies" the just don't seem to go away. Somewhere along the line Dr. Pickart lost his objectivity. It is true that copper peptides produce good results for some. But they produce bad results for others.
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merton



Joined: 12 Mar 2006
Posts: 80

PostPosted: Fri Jul 21, 2006 6:47 pm    Post subject: Copper Peptide GHK/MMP's and their enzymes Reply with quote

Assuming arguendo there are no non-self serving in vivo studies regarding this topic the person who believes (arguendo as well) that they are suffering from copper peptide damage is left with little hope. Or is he/she?

Quoting the several articles from this site and again assuming their validity for purposes herein:

"Caution: While moderate use of copper peptides stimulates collagen synthesis and has antioxidant effect (by stimulating the antioxidant enzyme superoxide dismutase), excessive use can have an opposite effect by increasing the levels of free copper and/or by triggering excessive production of metalloproteinases. Free copper promotes free radical damage and collagen breakdown leading to accelerated skin aging. Metalloproteinases can digest collagen and elastin, weakening the skin and causing sag. These problems do not seem to occur among the majority of copper peptide users. However, there are anecdotal reports indicating that such side-effects might happen with overuse or, rarely, even normal use in sensitive individuals. Ideally, a sufficiently large study is needed to better quiantify these risk."

See: http://www.smartskincare.com/treatments/copper.html

So the enemy appears to at least potentially be matrix metalloproteinases. In a different section we have this statement which was written prior to the release of the substance I refer to below (TIMP-2):

"But what can be done to inhibit MMP enzymes? Unfortunately, the development of practically useful MMP inhibitors by drug companies has met with only limited success so far. As of the time of this writing, the only MMP inhibitor available as a drug is doxycycline hyclate (Periostat), a compound that inhibits MMP-1 (a.k.a. type I collagenase). The approved use of doxycycline hyclate is periodontal disease, where it helps strengthen connective matrix in the gums. Theoretically, it may help to treat wrinkles if used topically, but studies are needed to determine safety and efficacy of such use."

See: http://www.smartskincare.com/treatments/mmpinhibitors.html

Not long ago an apparent synthetic version of human Tissue Inhibitor of Metalloproteinases 2 was released for topical cosmetic use.(TIMP-2) (there are 4 known TIMPs). According to the manufacturer TIMP-2 "potently inhibits almost all types of these MMP inhibitors . . ."

The statement "studies are needed to determine safety and efficacy of such use" is no doubt true. Large studies would be nicer. Independent studies approaches ascencion. But even designing a study on live humans is quite difficult when the most knowlegeable minds on the subject haven't yet quantified or qualified the problem in the first place.

The In vitro and Ex vivo tests revolve around the (arguably) somewhat related topic of test tube inhibition of MMPs and UVB irradiation of human explanted skin/collagen breakdown inhibition, respectively.

These certainly deserve notice and observation in light of TIMP-2 present availability.

This would seem to be the most promising item presently for Cu-GHK damage assuming such exists.

-merton
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drtodorov
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PostPosted: Fri Jul 21, 2006 8:48 pm    Post subject: Reply with quote

Do you have any links of references regarding that new "synthetic version of TIMP-2"? It sounds interesting...
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merton



Joined: 12 Mar 2006
Posts: 80

PostPosted: Mon Jul 24, 2006 6:54 pm    Post subject: Reply with quote

Hi Dr. Todorov,

I thought I emailed the pdf on this when it first came out. It appears to have been updated since then. If you go to this link and click on the small pdf box on the right it should download. As stated, only In vitro and Ex vivo studies are available thusfar. I've been compounding with a sample for several months:

http://www.centerchem.com/Capability.asp?CapabilityID=3340&Cat1ID=20&Cat2ID=10

I'll inquire whether there is more data available when I speak with them again.

-merton
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drtodorov
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PostPosted: Mon Jul 24, 2006 8:24 pm    Post subject: Reply with quote

Thanks. I looked at it. I think it is a reasonable and promising approach. One problems is that there were no real clinical studies so far and things often work better in the lab than in real life. Also, they are a bit vague as to how large a portion of natural TIMP-2 inhibitor their product uses. If they use a large peptide, then there is a penetration problem. They allegedly use liposomes to go around penetration hurdles, but liposomes to not have a great track record in real life skin care. So, I would like to see real clinical studies confirming that works. But it is definitely something to follow. And it is probably relatively safe to try if you are willing to try yet unproven treatments.
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merton



Joined: 12 Mar 2006
Posts: 80

PostPosted: Wed Jul 26, 2006 11:19 am    Post subject: Reply with quote

Hi Dr. Todorov,

Your point is well taken regarding the size of the TIMP-2 enzymatic polypeptide. It does not appear that there is any splicing whatsoever. The data indicates the synthetic version is identical to the endogenous homo sapien TIMP2 in toto. It is 220 amino acids in total. The molecular weight is 21,754 Da. There are 12 cysteine peptides which form 6 disulfide bonds. This would obviously reduce the maximum length in any given direction. However, despite the folding at these links, I, of course, concur that a 220 amino acid structure would generally be far to large for dermal penetration on its own.

But there is a caveat which you point out above. When researching the physical dimensions of TIMP-2, as opposed to molecular weight, I came across a company that has developed a large liposome that they propose In vivo testing has shown the transport of the also large superoxide dismutase molecule thru to the mid-level of the epidermis. This was news to me. I haven't kept up on liposome nanotech and found this rather thought provoking. I haven't yet looked up the MW of SOD yet. I found no report of the maximum diameter for TIMP-2.

Here is the link to Brookosme, the liposome manufacturer to which I refer re SOD:

http://www.archchemicals.com/Fed/PC/Docs/Brookosome_Brochure_v1.1.pdf

It will be interesting to see if this is the case with TIMP-2. If so then the question of whether this can perhaps benefit those who may be suffering adverse effects from Cu-GHK remains relevant.

-merton
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drtodorov
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PostPosted: Wed Jul 26, 2006 4:08 pm    Post subject: Reply with quote

Perhaps, but there have been many liposomal systems that looked good in the lab or early in vivo tests that never took off. In any case, it is reasonable to try putting TIMP-2 in a loposome and have, say, a 3-month study in real people, monitoring dermal parameters, wrinkle depth, skin matrix deposition and so forth. But for CP damage suffrers, this may be worth a try w/o waiting for such a study.
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kiwi



Joined: 17 Sep 2006
Posts: 2

PostPosted: Sun Sep 17, 2006 4:47 am    Post subject: cps Reply with quote

the side effects of cps are not rare at all, from reading the froums on the skin biology website, it seems a large proportion of the users have experienced these side effects of sagging skin, wrinkles 'crepieness' which they call the 'uglies', some find that it goes away if a break is taken from the cp products others contray to what Pickart says experience seemingly permanant damge, i my self am experiencing the 'uglis' from using the priducts and im just hoping it not permanent, at the moment im lookungto get some DMAE to see if that will help, something i find quite hypocritical about skin bio and dr Pickart is that he is always saying other companies do not publish clinical studies of their products and then claim they work miricals and false claims, well in my opinion he is no different as he has not published any studies on his second generation cps (the kind that are in his products) only on GU-CK cps (or whatever they are) wich are not the same as the kind in his products, the reason for not publishing he says is because it would cos millions to do the studies. this i think is an exageration adn even so you would think being a 'research company' as he claims they would be able to do the studies to publish especially with how successful his skin bio company seem to be at the moment
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