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"Science" behind copper peptides

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Josee
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Tue Apr 13, 2010 8:56 pm      Reply with quote
OK I did not want to hijack "sunscreen" the thread any further so I decided to start a new thread.

I do hope we can have a good and fruitful discussion and abstain from engaging in ad hominems with other posters which do not provide really any information regarding the topic at hand.

I claimed that there is no evidence that the second generation of copper peptides has any anti-aging effect. I also contend that the website makes unsubstantiated claims and selectively quotes medical literature to prove a point.

So I asked for references. And I was told they were 4 studies. The 4 studies Dr. Pikart cites can be found here on his website: http://reverseskinaging.com/studies15.html

The website claims:
"Four independent, placebo-controlled double-blinded clinical studies at the University of California at San Francisco have given statistically significant positive results that our products markedly accelerated the rate of skin regeneration and reduced skin irritation after severe skin damage. Dr. Howard Maibach, who directed the studies, is one of the the world's leading dermatologists with over 60 books and over 1,350 papers on the topic."

Just from the start there are some poblems:

- Dr. Maibach has over 1200 papers but not ON THE TOPIC of skin regeneration or copper peptides. His research specialty (as per his website) is: Dermatotoxicology, dermatopathology and percutaneous penetration.

- The studies did not assess the "rate of skin regeneration". The studies assessed TEWL which is transepitelial water loss. It is used many times to measure the integrity/function of the stratum corneum. It is not synonym of skin regeneration. In fact, there are substances (and cosmetics) who diminish the TEWL yet impair skin regeneration. One study also measured a visual score (VS), skin blood flood volume (BFV) and skin color.

- The damage was not "severe". This were clinical trials done in healthy volunteers so as it is obvious, you can't cause severe damage to volunteers for clinical trials.

- One study did not find any significant difference, yet that is conveniently not mentioned in the website

- No study discusses clinical significance. Things can be statistically significant but not clinically significant. For e.g. I can have a large sample size. In one sample size the average height is... 1.65 m and in the other the average height is 1.64. I do my statistical tests and I find that the 2 populations are statistically significan different with p<0.05. Now... is really the difference between 1.65 and 1.64 important or relevant? Probably not. That's why in clinical research is always better to report the confidence interval as opposed to simply the p-value. The thing is that the purposes of this studies was to mainly evaluate their models of irritation more than to test a particular agent. So the did not report confidence intervals since they were not really that interested in clinical significance but in the ability of their model to detect differences.
For more information of p-value, you can read:
Dtsch Arztebl Int. 2009 May; 106(19): 335–339)

Acta Paediatr. 2008 Aug;97(Cool:1004-7. Epub 2008 May 7.

In there it states: " It is good practice for authors of research articles to report CIs with their estimates instead of just p-values as p-values are less informative and convey no information on clinical importance."

Now... on to the studies....

1) Zhai, Chang, Singh, Maibach, Contact Dermatitis, 40, 1999, 205
Sample size = 14
Study on the effect of topical copper on contact dermatitis. Copper peptide improved TEWL, skin color and VS more than placebo starting on day 8-10. BFV showed no significant difference. Clinical significance not discussed


2) Zhai, Poblete, Maibach, Int. J. Dermat., 37, 1998, 386
Sample size= 6
Study on the effect of topic copper on skin irritation (measured by TWEL). The study found NO EFFECT.
"Our data showed that there was no statistical difference between the topical agent and stripped skin during the barrier function repair process. The results indicate that topical application had no adverse effect on repair"

3) Zhai, Leow, Maibach, Clin. Exp. Derm., 23, 1998, 11.
Sample size = 6
Study on the effect of copper peptide on skin barrier after irritation by acetone (measured by TWEL). The study found a positive effect of copper peptide vs. placebo. Clinical significance not discussed.

4) Zhai, Leow, Maibach, Skin Res. Tech., 4, 1998
Sample size = 6
Measure TWEL after detergent irritation and copper peptides. They found an effect of copper peptides. Clinical significance not discussed.

So... what can conclude after reading this articles? One can conclude that a solution containing copper peptides may help accelerate water barrier function. Do these studies provide any evidence that the copper peptide studies "regenerate skin", or have any antiaging function whatsoever? NO.

Are the website claims misleading? In my opinion YES, but each one has different standards on when to classify something as misleading.

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m1rox
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Wed Apr 14, 2010 6:30 am      Reply with quote
Did Josee mention that her supervisor also published some studies on copper peptides? Perhaps there is some water under the bridge between these researchers and Dr. Pickart?

However, I do not think that we can dismiss what she puts across as she does have valid points to make. I know there are some who are very loyal to Dr. Pickart and have benefitted from his products but she should have a chance to present her points of view as well.

As we know, medicine is as much an art as a science and scientific studies don't always do justice to a specific product. Unlike the big companies like Proctor and Gamble, etc. the small companies do not have the money and resources to carry out large clinical studies to validate their product. Just because there is no proper scientific study done on the 2nd generation copper peptides doesn't mean that they don't work and (hopefully) the testimonials of some of you are genuine (not aided by the company) and there really is some benefit that can be gained by using them. Of course, one wouldn't expect them to work for everyone as each individual's condition is different.
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Wed Apr 14, 2010 9:39 am      Reply with quote
I am not a scientist, but my closest friend from college grew up to be a biochemist, now a professor at a major NY university. We had a few discussions back in the day and I (the MBA) was surprised at her antipathy for commercial applications of science. I didn't agree with it, but I understood. She didn't believe any research should have commercial purposes, and in her ideal world, all funding would come from generous people who wanted to advance knowledge, not from profiteering corporations big or small.

So that is one end of the science/research spectrum, the pure scientist who disdains entrepreneurs.

Another facet to consider is that research itself is not only expensive but often extremely limited. So if I am trying to test the results of copper peptides, say, I must carefully select my subjects and then apply a measured amount of product to a carefully delineated piece of skin. Months or (more likely) years later, you can enumerate results for that very specific process...but that may or may not tell you what happens in the 1001 scenarios that differ from your controlled experiment (eg wound vs wrinkle). So it is absolutely understandable if cosmetic companies don't do hard core testing except to ensure safety. It isn't necessary. Customers buy results, not the science.

Moreover, those of us who have been around for a few decades have seen much-touted research disproven, and last year's marvel become next year's carcinogen. M.Ds once touted the health benefits of cigarettes and xrays were a cure for acne.

My point: though I love to read research as much as the next curious soul, it's not a make-or-break for me, especially when the research doesn't pass my straight face test. Research provides a circumscribed bit of data than may or may not lead me to buy a product. And I don't think there's ever been any product that has been proven to work 100% of the time, so even the most thoroughly researched products may not be my cuppa.

I have been using the second gens for a few months, but as far as I can tell, no one else is using them as aggressively as I am. And I am okay with not knowing if this protocol has been researched and proven effective. If I decide it's not working for me, I'll try something else. The world of remedies is vast and expanding all the time.
Josee
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Wed Apr 14, 2010 1:51 pm      Reply with quote
Hello... wow it seems there's a lot of interest on this... it's great!

Some clarifications are in order (I guess):

a. For those who frequent the "EDS Lounge", you know that I'm a pain sometimes. I do tend to be skeptical of things (read my rant about multivitamins? Smile ) and I voice my opinion. So this "copper peptides" thread is no different from the other many opinions that I have had on other threads to which people have strongly disagreed with me. I do hope we can agree to disagree in a civil way without imputing "evil intention" or anything like that to each other

b. I have no idea why this came up but to make it very clear... I have no connections at all whatsoever with any cosmetics or pharmaceutical company or lab, nor do I work or have ever worked for a cosmetic or pharmaceutical company or lab. I have never received any money from any pharmaceutical or cosmetics company or lab.
The research I do has to do with evidence-based medicine, health technology assessment and public health.
I am not an expert at all in dermatology, cosmeceuticals or anything like that. Like most of you, I have an inquiring mind which has led me to read up on cosmeceutical, cosmetic procedures, etc, etc.

c. I really like the field of evidence-based medicine and I push in every way I can to make sure that decisions are made based on evidence. I truly DO NOT LIKE IT when people and/or companies make claims that cannot be substantiated or that can mislead people. This applies to every field, from politics to health care!

d. KNOWLEDGE IS POWER. I can't stress this enough. There is no perfect "potion" for skin. Most cosmeceuticals have little research behind it. But knowledge is POWER. Because... as long as you KNOW... then you can make informed decisions.
I myself have bought stuff because "a friend tried it an it worked great!" So what? There's nothing wrong with that! I realize that there's no "real" evidence but I still take the plunge!


So... to end, there is a lot written on EDS about the potential benefits of copper peptides, the theories behind how it works, etc, etc. I am not interested in that, not because it's not interesting but because that info is already out here. I am interested in seeing what hard, peer-reviewed research is out there regarding copper peptides and then do claims based strictly on that.

As bethany said in this thread, the fact that there might not be evidence today about something working does not mean it doesn't work. It just means there's no evidence.

All the best,
Josee

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m1rox
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Wed Apr 14, 2010 7:36 pm      Reply with quote
Although a wound is not a wrinkle, the products that help to heal wounds could well help to reduce wrinkles if they stimulate collagen production. I would be disappointed if the comparison between copper peptides and retinoids is not over a longer period of time (eg one to two years). As we all know, within a period of one month, retinoids do have a tendency to make skin look worse before it gets better and I don't think a one month time scale is fair to compare these products. The skin improvements with retinoids take months and there are also long term benefits.
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Thu Apr 15, 2010 4:17 am      Reply with quote
It is interesting to note that several people who use CPs on this forum have had a filling in of acne scars. Old acne pits, that have actually filled in and become smooth, healthy skin. It is also interesting to note that many people have experienced significant change in their aged skin. While a wound may not look like a wrinkle, the skin does feel sun damage and moisture loss are indeed wounds. There is a structural change in DNA when the skin is sun damaged, and the loss of the ability to regulate moisture, collagen and the like are treated by the body as a disease or wound issue - the body attempts to compensate.
While I worked in a lab and was involved in formulations, I would never consider myself capable of second guessing doctors (the SkinBio site refers to dozens, all involved in various studies) or the actual experience of those who use the products, who, I am sure have conducted their own research.
I my self have experienced impressive results and find the tone of this thread somewhat insulting.
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Thu Apr 15, 2010 6:16 am      Reply with quote
I always struggle with understanding this Avalange, as I was told they were suitable for antiaging for my son (who was 26).... and know that others have said they are antiaging topicals also - but on looking at the forum, I can't ever find Dr Pickart mentioning this. I know from reading a message of your's before, when SkinBio questioned him over what was happening with you, he apparently said "Why would you be using this", but I thought you heard that through a third party and not direct from Dr P himself. Did you actually get a message from Dr Pickart not to use CPs for antiaging purposes. I really would love to get to the bottom of this, as it does worry me as my son is using them after that conversation and has been for a couple of months now, but I don't want him ruining his skin or getting the kind of results you got so if I can help him avoid that - I think he'll be a happier son! If its alright with you - I might ask Dr P on the forum (if thats ok?).

avalange wrote:
cps were marketed to me as having anti-aging properties, but in my correspondence with Dr. Pickart he steadfastly denied that anyone without major damage to repair should be using his products. there's a double standard there, and i think he would do well to quell our fears and confusions by clarifying his own scientifically-informed position on how best his products should be used.

--avalange
Josee
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Thu Apr 15, 2010 9:41 am      Reply with quote
m1rox wrote:
Well, Neutrogena did buy over Procyte...
I presume they did their due diligence on the product and would have had enough scientists and MDs to evaluate it before purchasing.

Therefore I think the 1st generation copper peptides even though more expensive are probably "safer" to use


Yes, I think every product goes through basic toxicology and mutation testing, which does not mean that the product could not have adverse effects on the long run.

But this is for every single product out there and the reason some of today's "poisons" were yesterday's "miracle cures".


m1rox wrote:

As someone already mentioned, just because there's no reported studies in peer-reviewed journals doesn't mean the product doesn't work. It seems to have effects as some of the forum members will attest.


I absolutely agree with this. My MAIN MAJOR "beef" is about CLAIMS.

There are A LOT of small companies that sell their products in a very honest way. They present whatever little evidence they have on the subject and then rely on mouth-to-mouth and on customer's reviews. This is how I have successfully bought a lot of stuff. I took the risk... and it paid off!

However when people make grandiose claims about a product without having sound science behind, then I have a problem. And when people selectively quote papers, state things in a way that gives one impression when in reality the truth is different, and try to pass that as "science", then I have a bigger problem. And then when someone says "I'm not like big companies that give you shady science and hype" while doing just that... then it's a huuuge problem for me.

And for me the obvious problems with this are:

a. I think it's not honest and it's misleading.

b. People have only limited money and time to dedicate to their skin care. So they need to make choices. And by reading misleading information they might spend their money in one place when it would have been more useful to spend it in another.
For e.g. one of the obvious choices for anti-aging is tretinoin cream (Retin A, Renova). It's the one that has the most science behind it, and today it would be considered the "gold standard" kind of thing. Now if someone makes a claim that product XYZ is BETTER than Retin A and without the side effects, then... that's a pretty serious claim, don't you think? I for sure would jump ship, esp. given the irritation that RetinA sometimes give me. However, if there's nothing really substantive behind that claim.... then... it's pretty annoying because people might not buy RetinA to buy XYZ.
Now if people realize that really there's not much behind XYZ but they still want to give it a try, then it's a good , informed choice. And if in the end it turns out that XYZ works better for them than RetinA... then even better!!!

But I think that WE, people who work hard to make our money, deserve nothing but total transparency and honesty with no "sweet talk" about products. Sadly total transparency and honesty are the exception and not the rule in every industry Sad
Thus it is usually up to us, and consumer groups, to try to do some research on our own to reach our own conclusions.

All the best,
Josee

PS: BTW, this doesn't only happen with companies. When I was doing my MSc a looong time ago we were randomizing rats to 2 diets. The diets were supposed to be equal in everything except for calcium content. Well... it turns out that once the lab messed up and the diet low in calcium was also low in protein. This posed a huge problem because protein content also had been shown to alter what we were studying. So I said that the whole thing should be discarded and we should start over. My supervisor at the time said no and he went ahead and published the paper without saying a word about the problem with the protein. I obviously withdrew my name from the paper and ran away from him as fast as possible! Still he continued publishing until some years later he was kicked out for an unrelated reasons (used grant money for personal reasons)

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Thu Apr 15, 2010 12:00 pm      Reply with quote
Josee wrote:


Yes and that dermatologist is quoting the only seemingly independent, peer-reviewed, clinical PILOT study done on copper peptides.


I'm not sure why you draw that conclusion. I read that piece and it says:

"Results from recent studies [plural!] have made me take a second more serious look at the use of Copper Peptides in skin rejuvenation...I have been pleased with newly published information."

Josee, you say:

"My MAIN MAJOR "beef" is about CLAIMS."

and I think therein lies the problem.

When I look at the skinbio website, the impression I get is not that it's a Clinique that's trying to snow me with extravagant "science-backed" promises, but rather that it's a pretty amateurish effort -- like a lot of websites, not that easy to navigate, with info not always presented in the most coherent way.

You could probably post some pages and say "see, he's making a claim here" but I'd say you're taking bits of the website out of context. My impression again is that Pickart (never met him or communicated with him) leans more toward the art side of the science spectrum. He'll throw in snippets of info that fascinate him, but he doesn't have the inclination to do it in an organized fashion, or in a manner that would pass rigid scientific scrutiny. For the same reason, he's not the type that publishes his findings/present at conferences.

I don't think he is a snake oil salesperson (as are so many we see in this industry) but that is my unscientific gut impression.

There is so much we don't know--I am willing to take a leap of faith here and see if the products work. As an anecdotal aside, I am pretty sure that aspirin never underwent any clinical trials. It worked; there was a market. The rest is history.
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Thu Apr 15, 2010 2:28 pm      Reply with quote
Star Model wrote:

There is plenty of evidence that CPs work in rebuilding skin, that is why so many are using them to do the most difficult task which is "beyond curing the wrinkle" – they are using them for "scar reduction".


I think we're just going to have to agree to disagree on this one. I guess some people (like yourself) may believe that there is plenty of evidence and other people (like myself) believe that there is not. We don't need to agree.

Star Model wrote:

And actually wrinkles are likes scars in a sense, so that is why others with "no scars" are using them. CPs heal wounds without forming scars. That is one of its biggest assets in my opinion. CPs suppress the scar forming protein which allows the wound to heal clean, free & clear of new scar formation. Like 1st generation CPs, they are regenerative in that sense unlike anything else.


Not really. Scars are formed because fibroblast over proliferate and over produce collagen I.

Wrinkles are formed because collagen breaks down.

So if I want a cream to prevent scarring, I wouldn't mind if it has quite a bit of MMP/TIMP imbalance activity because I do want some of the collagen to break down to prevent the scar.

However, I certainly do not want much MMP activity for wrinkle treatment! So something can be good for wound healing but not for wrinkle prevention.

Also for wrinkle prevention/improvement I'd like something that stimulates both the production of collagen III and I, not just I.

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Thu Apr 15, 2010 3:16 pm      Reply with quote
Josee wrote:
Quote:
However, I certainly do not want much MMP activity for wrinkle treatment! So something can be good for wound healing but not for wrinkle prevention.


MMP & CPs are not the same thing, so you can't compare the 2.


Josee wrote:
Quote:
Also for wrinkle prevention/improvement I'd like something that stimulates both the production of collagen III and I, not just I.


So keep on looking. GHK stimulates Collagen I/ CPs - III. That is why some people use both - alternating their products. It is a good idea, really. But if you need an "All-In-One" you're going to have to continue your search.
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Thu Apr 15, 2010 3:36 pm      Reply with quote
rileygirl,

i'm sorry, i think I misunderstood the motivations behind your post. I apologize for my crabby mood, which most certainly affected how I read your question.
let's carry on, and learn.


--avalange

rileygirl wrote:
avalange wrote:
hi rileygirl,

i think i've made it quite clear that i was looking for the most up-to-date anti-aging active for my skin. when i tried cps there was a long-standing thread on the subject and its anti-aging, "firming," "pore-refining," and "rejuvenating" qualities were being touted. i visited the sb forums, other forums, and knew about the "uglies," which is why i decided to try the 2nd gen cps, which were supposed to be gentler and cause less issues.

i love skincare and always want to be abreast of the latest technology and actives. i take full responsibility for my decision to try cps, but it's quite odd that you would question me for wanting to try them.
This, from the sb forum:
Quote:
Copper peptides - Skin treatment products to help tighten facial skin, improve skin texture, improve skin tone, and improve skin complexion.


Why wouldn't someone want to use a product apparently backed by the latest research that promises such results?

--avalange



Thanks, Avalange. I was not sure if you had a particular skin condition/issue.

I understand exactly what you are saying and agree with you. The skinbiology website Does seem to promote the CP's for anti-aging and I see no mention on their site for how old one must be to try their products.

In my opinion, if copper peptides are going to be compared to Retin A and topical C (along with the statement on the skinbiology website that CP's performed better than either one of the above) then Most people, I would think, would come to the same conclusion - that CP's Are for anti-aging and not just for "damaged" skin.

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Fri Apr 16, 2010 5:17 am      Reply with quote
m1rox wrote:
Does anybody know the difference between the 1st and 2nd generation copper peptides? Why can the 2nd gen ones be used with acids and not the 1st gen?


The 1st generation uses a particular tripeptide (GHL). The second generation uses a mix of peptides.

The claim (I have not seen evidence regarding the claim but I have not really looked much) is that GHL-Cu is unstable and reacts with acids and that the second generation is more stable and does not react with acids.

DarkMoon wrote:

It's all very confusing even here at times the term CP is used for either 1st or 2nd gen. I have difficulty keeping them straight. I also thought acids were a no no with any CP as it's the copper is what's reactive to acids, but I wouldn't be surprised to hear I have that one wrong also?
Rolling Eyes


All the discussion in this thread (except for the first post) is regarding FIRST GENERATION. I think we didn't discuss second generation because there isn't any research out there regarding them (except the 4 papers I referenced in the first post).

Whether any CP reacts with acids or not will depend on the "strength" of the bond of the Cu to the peptides, the shape of the complex (i.e. where the Cu is located), and the peptides, etc. So some complexes can react "slower" and thus not be degraded so fast, or sometimes not react all.

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Fri Apr 16, 2010 5:28 am      Reply with quote
Josee

I want to thank you for starting this thread, as it is providing us with interesting questions for sure regarding CPs, and certainly I'm learning from your questions which I think are well thought out and although I'm not scientific, I understand what your asking and when reading them I find myself thinking the same thing!

Theresa
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Fri Apr 16, 2010 5:47 am      Reply with quote
TheresaMary wrote:
I just ordered the Super CP serum. Im not sure whether its first generation, second generation - as if you look at their website they don't label their products as either.


TheresaMary, that is the 2nd gen CP's. The only 2 products that Dr. Pickart sells that are 1st gen are the Super GHK Cream or Serum. All the others on his site are 2nd gen.
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Fri Apr 16, 2010 7:21 pm      Reply with quote
OK... It's time to take a new direction!

I'm thinking we can, instead of analyzing in general the science behind CPs, analyze the evidence behind different claims (e.g. antioxidant properties, collagen production, etc, etc.) Because then we might be able to isolate some effects where there is good science and some other effects where more needs to be done.

Also, I see there's a lot of confusion between first and second generation of copper peptides, so I propose a nomenclature.

First generation copper peptides = GHK-Cu or GHL-Cu, or 1CP

Second generation copper peptides = P-Cu (considering the fact that it's a mix of peptides), or 2CP

So if we all use these terms, then there will be less confusion.

The first effect I'd like to research is "antioxidant properties". We should look for published studies in peer-reviewed journals. We can include in vitro studies as long as we clarify that. Although in vitro are problematic because often results in vitro don't happen in vivo, at least it's something to give us hope Smile

Also...it's important that the references are reference to ACTUAL studies. Sometimes in journals, different doctors write their opinions, which is good, but it's not studies.

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Sat Apr 17, 2010 9:14 am      Reply with quote
I just want to thank Josee for starting this post! CP's have been a mystery that have befuddled me for years! I too believe that knowledge is power and that we have the right to discuss all products and question anything that we put on our face! As for me, I have tried the SkinBio CP Serum (regular strength) and it was a disaster for me! Now I have pretty good skin to begin with. No wrinkles to speak of except for a few small fine lines in the crow's foot area. I wanted to try to use the CP Serum to get rid of those & just as a general antioxidant & anti-inflammatory & MMPi. My skin is super sensitive & has a tendency to flare up to the point that no matter what I use it either makes me dry out, or I get these tiny little bumps on my forehead & cheeks. Not pustules, but just skin-colored bumps. My doctor said it was not rosacea or any skin condition and to use Dove soap! Rolling Eyes

Anyway, I started using the SkinBio CP serum & within a month my skin just went crazy. It got these dry, rough patches, My undereye area got all crepey & wrinkly. Honestly, I never thought that a skin care product could do this to someone's skin. I contacted SkinBio & someone from their customer service wrote me back & told me it was my sun damage coming to the surface & to just keep using it & exfoliate by using more acids & to abrade the rough areas with a toothbrush before applying the CP Serum so it can penetrate better. I was appalled! Shock First of all, I don't think that you should have to wirebrush your face in order for a product to work. Secondly I don't have a lot of sun damage. I live in an area where we get maybe 80 sunny days a year. I never go outside without using sunblock & I am not a "sun person" anyway. I can't deal with the heat, so I stay inside in the summer a lot, or stay in the shade.

Anyway, when I wrote back to them I told them all of this. I got another reply that was the complete opposite of the first suggestion. This time I was told that unless I have skin tags or scars or moles that I want to remove that I shouldn't even be using CP's! That they are not intended for healthy, intact skin. Umm...OK. So then why are they being sold as an anti-aging breakthrough? They told me to get the Super GHK-Cu Serum (which was twice the price for 1/2 the amount of product), as that is better for sensitive skin types. So I tried it (I was deperate to get rid of the rough patches). I let my skin alone for a while before I started the GHK-Cu though & I didn't have any problems with it. It took a while for my skin to get back to normal & then I must say that it didn't look any better than before I tried the CP's. Anyway, I stopped using the GHK-Cu on a regular basis because it got to be too expensive & I really didn't see any improvements.

I too find Dr. P to be full of contradictions. I've been to their forum a few times & his asnwers to questions are short & rude IMHO. I have also noticed a defitinite double-standard. He trashes every other skin care line out there & says not to use anything that is not supported by placebo-controlled, double blind, peer reviewed studies, but then his products don't meet those criteria either.

I see nothing wrong with us discussing our experiences with CP's (either positive or negative), and although I don't have any experience in science either, I'd be happy to contibute what I can to this subject, as it is a topic that interestes me. Thanks again Josee!
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Mon Apr 19, 2010 9:04 am      Reply with quote
m1rox wrote:


[i]"The mechanism of copper peptide action is relatively complex. GHK-Cu induces the degradation of "extra-large" collagen aggregates found in scars and promotes the synthesis of smaller more regular collagen found in normal skin.


Disclaimer: all this post pertains to first-generation copper peptides. There is no published research regarding second generation so we can't discuss it. In this post, first generation copper peptides = FGCP

I do know that there are in vitro studies that show that FGCP stimulate the secretion of MMP, an enzyme that degrades collagen. They do not degrade only "extra-large" collagen aggregates.

In cell cultures there was a stimulation of collagen. However the same stimulation was obtained by adding just the peptide (i.e. without the copper) (FEBS Lett. 1988 Oct 10;238(2):343-6). In animal wound models, there was also stimulation of collagen I.

The problems with the studies are:

a. In the cell culture, the medium was void of MMP (Matrix metalloproteinases). So if (hypothetically) FGCP overall degraded more collagen than built it (ie. the MMP stimulation was greater than the collagen stimulation), this study would not have shown that since there was no MMP

b. In the wound healing, one must take into account the difference between wound healing and regular skin.
When someone has a wound, a very complex and big inflammatory cascade starts. This inflammation recruits lots of cells, including fibroblast who secrete collagen I like crazy and thus form a scar.
So a substance that stimulates MMPs is good because we do want collagen to be deposited, but not so much that it will cause a scar.
But in unwounded skin, the signals to deposit collagen are not as strong, so something stimulating MMPs might not be good.
To add to the confusion, FGCP have also been shown stimulate TIMP (Tissue inhibitor of metalloproteinases), which inhibit MMP.
The KEY then... is to figure out how all these enzymes balance on uninjured skin. Because the overall balance can be degradation (which we don't want!!!), or generation (which we want) Smile


m1rox wrote:
Other important effects of GHK-Cu include the ability to regulate the growth rate and migration of different types of cells;


Yes there are lots of studies who have used FGCP in cell cultures and have seen that it promotes growth.
However, it is not clear whether it promotes the growth of fibroblast. A study on cell cultures indicated that it did not, although it could be due to the low duration of incubation (FEBS Lett. 1988 Oct 10;238(2):343-6.)

The other thing is that growth factors that are not "selective" can help grow good things and bad things (e.g. cancer cells). FGCP are also used as growth factors for cancer cell lines. However, as I always say, whatever happens on a cell culture is not necessarily representative of what happens in vivo.


m1rox wrote:

[i]"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.


This is an extremely tricky issue. There are studies that have shown a weak superoxide dismutase (SOD) activity, while others have shown no SOD activity (Adv Exp Med Biol. 1990;264:79-84). Yet other studies have shown production of free radicals associated with FGCP (Chembiochem. 2007 Jul 23;8(11):1317-25.) This production of free radicals in vitro has to do with the redox cycling of GHK-Cu more than the "concentration".

To add more to the confusion... no one really knows exactly what happens with the GHK-Cu (FGCP). To begin with, absorption is not high. Then how it is absorbed... it's still up for discussion. Skin models have shown that it is absorbed BOTH as GHK-Cu and separately (i.e. Cu on one hand, GHK on the other). Then if Cu is absorbed freely, there's more concern because free Copper is involved in many processes that generate free radicals. In addition, the stability of the peptide in plasma is very low, which means that the GHK protein degrades very quickly. As it degrades so quickly, it is hard to know whether it has enough time to do anything, and also whether it can also contribute to the generation of free radicals because then copper would also be free.
In one study, GHK was completely hydrolized after one hour (Int J. Pept. Prot.Res. 41, 1993. 561-566). The study states: "Despite these interesting activities, the instability of GHK in plasma, common to all physiological peptides, may preclude the maintenance of signficant tissue concentrations when administered either topically or intradermally". In another, GHK showed a half life period of 16 min (Biochim Biophys Acta. 2001 May 3;1526(2):199-210.)

I think there are quite a few wound healing studies in animals that have showed anti-inflamatory and healing properties. However, how that translated into long-term use in uninjured skin is something that is not clear. It is the same thing for many drugs. And anti-cancer drug might have XYZ effects however I think most of use would use caution before using it in a healthy person.

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Mon Apr 19, 2010 6:26 pm      Reply with quote
Josee wrote:
Star Model wrote:

Posted by SkinBio from Dr. Pickart regarding this exact same claim which I found on the SB Forum:

Quote:

In published, placebo-controlled human studies by Howard Maibach at UCSF, we tested creams as strong as Super Cop 2X and found both strong healing and anti-inflammatory actions.


I am confused. I thought Super Cop was the strongest of all CPs??? Because on the studies that Dr. Pickart refers to they used "Repair and Restore" which I always thought was less strong than Super Cop 2X. Does anyone know about this?


Here is the list of product strengths:
Quote:

Most all Skin Biology products have as the main active ingredient Skin Remodeling Copper-Peptides (SRCPs) and thus all have strong skin remodeling action. But if we had to categorize product strength, here is what the list might look like from mildest to strongest:

- Super GHK-Copper Serum
- Super GHK-Copper Cream
- CP Night Eyes: Premier
- CP Night Eyes: Regular
- Protect & Restore Day Cover
- Protect & Restore Classic
- Protect & Restore High Retinol
- Protect & Restore Body Lotion
- Protect & Restore BND Cream
- BioHeal and Regular CP Serum
- TriReduction Cream
- Super CP Serum
- Skin Signals Solution
- Super Cop Cream
- Super Cop Cream 2X-Extra Strength

(Please keep in mind above list is not an absolute rule of strengths)
http://www.skinbio.com/faqpage.html

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Mon Apr 19, 2010 7:34 pm      Reply with quote
alexes wrote:
This is the same article I gave a link to on page two, and although the study is not referred to, or even named, it was summarily dismissed for being a pilot study. I am confused by that.


rileygirl wrote:
Bethany, do you know the date of when Dr. Kunin wrote that? She seems to be talking about the same study Josee mentioned earlier in this thread. I am guessing on that, but the study Josee had talked about compared the 3 ingredients, but only for 30 days.


I don't know when she wrote it, but it looks like she was referring to the Neutrogena studies (which we already established are not independent studies) on the FGCPs.

Quote:
GHK Copper Peptides

Studies are compelling regarding the effectiveness of copper when combined with a GHK protein peptide (GHK-CU). A study performed upon 20 volunteers showed that after 30 days, the formation of ProCollagen, a precursor of Collagen, increased 70% (shown by skin biopsy) compared with 50% formation from Vitamin C and 40% due to Tretinoin, respectively. This means that GHK Copper Peptides are highly effective in the skin rejuvenation process.

A peptide naturally found in human skin and tissue, GHK (glycyl-L-histidyl-L-lysine), binds copper molecules, allowing them to arrive in an active state where needed. This peptide is now chemically synthesized in the laboratory. Known as Prezatide Copper Acetate (Neova or Osmotics Blue Copper), it is capable of being used by the skin.

Three interesting studies performed by James Leyden, M.D. of the University of Pennsylvania (and sponsored by Neutrogena) were presented at the March 2002 American Academy Meeting which determined the effectiveness and benefits that GHK Copper Peptides provided in skin rejuvenation. One also compared the GHK Copper Peptide to retinol while another compared it to Vitamin K (for eye region). The GHK Copper Peptide gave impressive results in both studies with little irritation.

http://www.dermadoctor.com/article_Skin-Rejuvenation-Part-2_201.html


At the end of the day, I think that this thread DID prove to be beneficial.

- There are some strong followers here on EDS that have given testimonials for what CPs have done for their skin, as well as some instances where CPs were not the best option (and one size seldom fits all!)

- There are not a lot of studies for CPs as it relates to anti-aging/skin renewal, though there are some for wound healing.

- Most studies thus far seem to be on First-Gen CPs, and hopefully the ones coming out in 2010 will be on 2nd-Gen CPs.

- Slow and steady (and weak!) is the best CP approach for optimizing success and minimizing the Uglies.

- Between this thread and the testimonial/reviews threads, there should be more than enough info for people to decide on whether CPs are right for them.

- There are lots of skincare options out there, and people just need to keep learning and trying stuff until they find something that works for them. But people do make decisions differently...some rely on others' experiences, while others want studies. And both options/discussions should be respected.


Did I miss anything? Very Happy

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Wed Apr 21, 2010 9:12 am      Reply with quote
bethany wrote:
I just found this article where Dr. Audrey Kunin is now recommending CPs based on some "recent studies" though she doesn't reference them.

Quote:
Copper Peptides

A study performed upon 20 volunteers showed that after 30 days, the formation of ProCollagen, a precursor of Collagen, increased 70% (shown by skin biopsy) compared with 50% formation from Vitamin C and 40% due to Tretinoin, respectively. This means that Copper Peptide is a highly effective agent in the skin rejuvenation process.


I finally found the paper

This is the only peer-reviewed clinical study published on first generation copper peptides and skin aging (there isn't any for second generation)

I think because this paper is quite hard to come by (I had to submit a special request @ my university to get them to find it) most people that have quoted it have not actually read the paper so there are some misquotations.

It's not that Tretinoin had a 40% increase in collagen, and CP 70%.

The study is a non-randomized study, but the evaluator was blinded. The paper was partially sponsored by Revlon (one of the authors works for Revlon) but I don't think that is of much consequence.

20 people applied creams to their thighs (2 creams per person). Some people applied tretinoin and Vitamin C, others applied FGCPs and melatonin (not together, but in different spots).

They don't mention all the ingredients of the creams Sad


They did follow up at one month.


The results are:

a. Out of the 20, 4/10 had a visible increase in procollagen I using tretinion, 5/10 in the Vitamin C group, 5/10 in the melanin group, and 7/10 in the FGCP group (that's where people get the 70% and 40% from)

They don't say whether the increase was statistically significant or not, or whether one of the compounds increased it more or not. In the picture they have on the paper, the procollagen I staining by tretinoin is obviously much stronger than the CP staining.

I suspect this is why Dr. Maibach called the collagen increase "insignificant"

b. They measured Ki67 which is a measure of keratinocyte proliferation (which some would say it's a sign of skin regeneration). Only tretinoin showed a significant increase in Ki67

c. They measured dermal CD3+ (sign of inflammation). Only tretinoin and Vitamin C decreased CD3+

I think it is a little encouraging because, even though we don't know whether the increase in procollagen I was statistically or clinically significant, at least coupled with some animal and cell culture models is a sign that maybe first generation copper peptides do increase collagen I.

It would be nice to see longer follow-ups to assess long-term effects and safety and see if they have any effect in collagen III (which tretinoin does)

I hope this helped Smile

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Wed Apr 21, 2010 6:38 pm      Reply with quote
rileygirl wrote:
Josee, thanks for finding the complete study. I am curious what your thinking is on the 1st gen CP's now, and will you be trying the gen1 CP's?


Mmm... I think that I'm a little more disappointed because I had a little bit of hope that this study showed a significant difference. If they don't say that it was significant, it means it wasn't (if you have a positive result, you don't forget to mention it!).

I think for me the main issue is that there are no studies that show that FGCP does anything for uninjured skin (i.e. improve wrinkles, collagen, etc, etc).

The only in vivo studies are on injured skin which is quite different from regular skin, and even then large FDA human trial failed. There are some things that happen during wound healing that I wouldn't want to happen to my skin in a continuous way.

Even though a cell culture study showed that CPs activate TIMPs, the fact that CPs activate metalloproteinases (MMPs) is quite concerning to me because I would like to stay away from things that have the potential to degrade collagen.

Also, the fact that GHK-Cu is rather unstable is also of concern to me because I don't want free copper running around my skin or my system giving it the opportunity to engage in some free-radical producing reaction.

I am also a special case because I do have a family history of Alzheimer's and so given the potential role of GHK-Cu on Abeta agreggation and free radical generation with the subsequent neuronal death... obviously concerns me.

There are a lot of people who had fantastic results with GHK-Cu which for me would be the best motivator to try them. However, there are people who had horrible effects and have quite dramatically claimed that the treatment ruined their skin and that it took over a year to go back to normal, even though they started with very diluted CPs.

So... given the fact that I'm not 100% sure on the safety or efficacy + people that have had severe adverse reactions... at least personally for me, it's not worth the risk.

If anything, I'd be more willing to try the GHK alone, without the copper, since it has also shown to increase collagen in fibroblast, does not have MMP activity, does not have any link to Alzheimer's, etc.

Again, I do know that some people have had positive life changing results with these CPs; in this case I'm just not willing to take the plunge.

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Fri Apr 23, 2010 2:02 pm      Reply with quote
bethany wrote:

Editing to add:
Josee, based on what you know now, what do you think is the BEST way for people to use CPs if they choose to do so? I saw some improvement on my pigmentation, so I know there can be some benefits, but the question is how to mitigate any risk.


I think if someone's curious enough, one should maybe try to do a split face trial. So in one half of the face the only difference would be just putting copper peptides (just the copper peptides, not the copper peptide creams that also have retinol, etc.).

Now I'm sure lots of people don't have the patience for that so what I would do is...

a. Use first generation
b. Start slow. Although people who have started slow have had bad reactions as well, the manufacturer recommends starting slow so I would just do it
c. I would use it for as little as possible
d. I would use it separate from any acid. In fact, I would try using a slightly neutral toner (to up the natural acid Ph of the skin) because it's better for absorption of the complex (but I would make sure I don't start getting any bad reactions like pimples from upping the Ph).
e. I would be VERY vigilant on any "uglies" episode. I think people use the "there are uglies which is damage coming up" as a metaphor to help people understand because in reality that does not happen biologically.

Biologically you have the epidermis that renews constantly. So the only thing that can "come out" is just epidermal things basically which are sunspots but that's pretty much it. The "dryness" that people see while using Retin-A for example, is due to the keratolytic activity of the Retin-A. Because of the keratolysis, the stratum corneum starts peeling and thus we see the appearance of the skin as "dry" and... well you know the rest. But then with more use keratinocytes start reproducing faster, we develop tolerance to having a thinner epidermis, etc, etc. and our skin looks better. Also because of the keratolysis is that some people see the "purging".

But that is about it. All the damage of the collage from wrinkles, scars, etc. is on the dermis so it is biologically impossible for that to "come out". If there's any collagen remodeling it occurs within the dermis, it's reabsorbed within the dermis and that's it.

So if I started seeing anything more than some drying, I would stop the use immediately.

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Fri Apr 23, 2010 5:37 pm      Reply with quote
I’ve been following this discussion with a great deal of interest. I haven’t contributed too much because I have scientific dyslexia. However, I do have a few comments I’d like to make.

With regard to scientific studies on cosmetics: Wouldn’t it be wonderful if there was actual proof that the cosmetic creams that we spend our hard earned money on were actually going to deliver the over-the-top promises they make? Realistically though, cosmetic products are not subject to the rigorous testing and control that pharmaceutical products undergo. Even cosmeceuticals (which are supposed to contain a higher percentage of actives and usually have a doctor’s name attached to them) also fall into the category of “cosmetic”. This means that they don’t actually make any biological changes to the body. If the actives are at a high enough percentage to actually make biological changes, then they would be classified as a pharmaceutical and be subject to medical testing. This is something that cosmetic companies want to avoid as claims like “a visible difference to wrinkles in 30 days” would have to be substantiated.

So I would ask, are there any scientific studies for Valmont and other high-end products? How do they justify charging $600 for a jar of face cream? At least Dr Pickart is prepared to stand behind his research and products and sell them at a reasonable price point. I’m afraid I have a very cynical view of the skin care industry and view most lines as very expensive snake-oil. And what annoys me about scientific studies is that you can find one for whatever stance you wish to take (a bit like quotes out of the Bible!) But I would like to see some anti-aging products controlled in the same manner as pharmaceuticals - then, perhaps, they would be worth the money - instead of just paying for marketing and packaging.

With regard to it being biologically impossible for hidden damage to be brought to the surface of the skin, there are a few members on this thread that are currently trialling The Wonderbar (an incredibly expensive bar of soap that also purports to do this. Users are expected to endure something called “the healing crisis“ before their skin improves). At present, people are experiencing mixed results - and, of course, there are no scientific studies to support the Wonderbar’s claims and no explanation for its exorbitant cost.

On a personal level, I’m also somewhat sceptical of “The Uglies”. I have never had a real problem with CPs but I have stopped and started using them several times because I’ve convinced myself that The Uglies have set in. Realistically however, I appear to get The Uglies at about 3 pm every day (regardless of what product I’m using). I’m of the opinion that we spend way too much time gazing into magnifying mirrors searching for flaws that weren’t there yesterday. I wouldn’t be surprised if most uglies are brought about by doing way too much to our skin and drying it out excessively.

Lastly, I’d like to make a comment on the “mean girls” attitude and Dr Pickart bashing. As I’ve pointed out, I do use CPs, but I have no problem whatsoever with people such as Josee asking perfectly acceptable questions and putting forward her opinions on the subject. I’m always interested to hear anyone else’s viewpoint and she has raised some interesting issues. There has been a trend on the Forum lately to chastise and vilify people for asking questions and drawing attention to what they see as errors or misinformation. Personally, I have no issue with people expressing their opinions as long as they do so in a polite manner - it all makes for interesting discussion.

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Fri Apr 23, 2010 7:39 pm      Reply with quote
Keliu wrote:

With regard to it being biologically impossible for hidden damage to be brought to the surface of the skin, there are a few members on this thread that are currently trialling The Wonderbar (an incredibly expensive bar of soap that also purports to do this. Users are expected to endure something called “the healing crisis“ before their skin improves).


I have to believe that people that are creating these terms do it in a metaphorical way to help others understand.

Biologically, the dermis and the epidermis are separated by a membrane and dermal elements do not go up the epidermis. That is just basic histology and you will not find one single paper, article or book that claims otherwise.

This would be the same as saying... "I'm putting this cream on my face and it's making my face greasy because it brings the subcutaneous fat up" Rolling Eyes That just does not exist.

Melasma, hyperpigmentation, age spots are in the epidermis so sometimes, as the skin renews the layers that have those spot do go up (since that's how the skin naturally renews, the bottom layers divide and push other layers up) and so when those cells dehydrate and die it can make the sun spots a little more pronounced. That is also what happens when, for e.g. you do IPL. IPL targets the cells with melanine, kills them, they get dehydrated and for a little they seem "darker". Also if you have a keratolytic effect, your skin will look drier. But that's about it... not much else is going on in the epidermis. All the rest of the things, the sagging, the collagen, etc... are on the dermis and the dermis CANNOT come out to the epidermis.

Now you got me curious about this "healing crisis" so I asked in the other thread... will see!

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