"Science" behind copper peptides
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free skin care · Mon Apr 19, 2010 4:41 am

Well I'm grateful for this thread, as I'm not a scientist or anything and my knowledge of science is limited, but on reading Josee's posts, I think its clear that this isn't so much a ganging up on Dr Pickart, but just a simple questioning about the products he sells/makes and the data that he uses to back his products.

To me, they were marketed as being antiaging. I even got advice at one point that my sun who is in his mid twenties and suffering from acne should use CP serum. Which I got him to doing and his spots did start clearing up. But the real eye opener to me is a fair enough point that I think many have made which is that the studies behind CPs are actually in relation to wound/scar healing and not necessarily skin aging. I can understand people saying that wrinkles are skin damage no matter how you put it, but this doesn't answer the question of if there are any actual studies that are proven that they are antiaging rather than skin repairing. Also Nanci mentioned in another thread that she wouldn't consider CPs are being suitable for someone under 30 - and thats an important thing I think to take note of, as that wasn't what was suggested to me for my son.

I've seen CPs recommended to many people on their forum, and so I wonder if this is a fact that perhaps we should be acting on (i.e. no CPs if under 30), but then find that Avalange was in her 30's and began using it and Dr P said why is she using it to also be an indicator that perhaps CPs aren't for everyone. Seems that they work well for some people and not so well for others, and theres nothing major in that, as even Retin A works well for some and not for others.

free skin care · Mon Apr 19, 2010 5:15 am

TheresaMary wrote:

To me, they were marketed as being antiaging. I even got advice at one point that my sun who is in his mid twenties and suffering from acne should use CP serum. Which I got him to doing and his spots did start clearing up.

If CPs are not recommended for people under 30, I think it might have been a special case.

If you go to the Skinbiology website, there's a tool to help you select the products you need.

http://reverseskinaging.com/gettingstarted.html

In the first page, it asks you what do you want the products for. And the answers it gives are:

a. Skin remodeling / Products to reverse the aging process

b. Hair renewal / Products to improve hair growth

So I think they are certainly marketed as anti-aging products.

Then they ask for your gender, skin type, and finally your age. In the age category it has 3 options that say this

a. Young: resilient with great elasticity. Under 30
b. Aging: Fine lines are present; skin is starting to lose its elasticity. Age: over 30
c. Sensitive: You react to most products with redness / inflammation. Products tend to burn, tingle, or sting when you apply them.All ages

So I think in general it is safe to say that the products ARE recommended for people under 30.

I hope this helped.

free skin care · Mon Apr 19, 2010 5:28 am

I think that CPS are strong products and as with any strong product, the side effects may be more severe. Judging from the reports of both great improvements as well as alarming deterioration in skin condition, obviously it does affect the skin in a lot of people, no matter whether there are any studies or not to show this. However, the "remodelling" process is not "intelligent" enough to rework your skin the way that you want in all cases. So for some, it is good but for others it is not good. It can be a double-edged sword.

free skin care · Mon Apr 19, 2010 6:13 am

Josee

This is a post of Nanci (of NCN proskincare who is one of their official sellers) of CP products:

NCN wrote:

No, I wouldn't suggest CP to anyone under 30 unless they were trying to reduce scars and/or stretchmarks. And I agree with you on sunscreen being an anti-aging product, that's why I mentioned CPs ability to inhibit UV rays. In my opinion (not Dr. Pickart's), the sun is the #1 cause of aging.

Then you have Avalange who got the response from Dr Pickart as to why was she using CPs (and she was in her 30's and had good skin to begin with). So its a bit suspect to why some people get told yes they can be used, and others don't. I trust Nanci - she's a doll and always been very helpful but I must admit that when I ordered CPs from her I didn't tell her they were for my son, as didn't think it would make that much of a difference (but from her post above it obviously does!).

free skin care · Mon Apr 19, 2010 6:17 am

If possible, could we go deeper into the skin remodeling aspect of the CP's? I am not understanding how a topically applied product is capable of causing "uglies" or "bringing up damage" in the skin. (I know that with Retin A a person can breakout for a while or it can cause dryness/flakes, but it does not cause sagging, nor do the glycolic acid products.) And, is this process strictly with the gen 2 (skinbiology) or does it also happen with gen 1 (GHK-cu)?

free skin care · Mon Apr 19, 2010 7:54 am

This is an article that attempts to explain (in layman's terms) how the copper peptides are thought to work:

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

I quote the more relevant parts:

"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. It also promotes the synthesis of elastin, proteoglycans, glycosaminoglycans and other components of skin matrix. Other important effects of GHK-Cu include the ability to regulate the growth rate and migration of different types of cells; significant anti-inflammatory action; and the ability to prevent the release of oxidation-promoting iron into the tissues."

And a possible explanation of the "uglies":

"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 quantify these risk."

I believe the studies that demonstrate possible benefits were done using 1st generation CPs (and mostly for wound healing rather than anti-ageing as pointed out in previous posts). There are no good studies on 2nd generation CPs which is why this thread escalated.

The "uglies" are based on individual reports by various people on their personal experience using 1st generation and 2nd generation CPs, mostly on bulletin boards and forums (such as this one) rather than being the subject of scientific publications. CPs are not FDB-regulated drugs therefore there is no formal mechanism for reporting and compiling statistics on adverse reactions and we have no way of knowing what is the actual incidence of side effects.

free skin care · Mon Apr 19, 2010 8:08 am

rileygirl wrote:

If possible, could we go deeper into the skin remodeling aspect of the CP's? I am not understanding how a topically applied product is capable of causing "uglies" or "bringing up damage" in the skin. (I know that with Retin A a person can breakout for a while or it can cause dryness/flakes, but it does not cause sagging, nor do the glycolic acid products.) And, is this process strictly with the gen 2 (skinbiology) or does it also happen with gen 1 (GHK-cu)?

The "bringing up damage" is basically the way of explaining why skin might look bad for some time.

There are different reasons why a certain substance might make the skin look not good for a certain period of time:

a. Dehydration. A substance might cause dehydration of the skin so it will look more wrinkled, dull, etc, etc.
The dehydration can be due to many reasons. It can be because the cells themselves loose water, or it can be because the substance disturbs the skin barrier. Anything that disturbs the skin barrier can cause transepithelial water loss (TEWL)

b. Increased cell turn-over. As basal cells start multiplying quicker, the top layer starts shedding more and can transiently become a little thicker. Hence the flaking and dry look.

c. Irritation

d. Exfoliation

In the case of CPs the "uglies" could be due to exfoliation caused by the LacSal, the CPs themselves could have an irritation/exfoliation property, or the CPs could increase cell turn over, or... anything of the above.

In the case of second generation copper peptides (SGCP), there are 4 studies studying TEWL and 3 of them found that, in wounded skin, it actually helped reduce TEWL. I don't know how SGCP could act on uninjured skin, but I tend to believe it would not disrupt them stratum corneum and not increase TEWL. However, many products that contain SGCP also contain other substances that could increase TWEL. I don't know about FGCP.

free skin care · Mon Apr 19, 2010 9:04 am

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.

free skin care · Mon Apr 19, 2010 9:37 am

Thanks for those excerpts, Josee. Very helpful to me. I have never been convinced by the explanation that CPs bring up damaged skin to the surface if used too aggressively and that's what causes the "uglies." The description sounds more like a form of skin damage caused by the agent itself than something latent being brought out, to me at least.

CPs, like other powerful cosmeceuticals, appears to have the ability to change the skin, for good in some cases, for not-so-good in others. It's precisely because of its efficacy--and the flipside of its potential to cause problems--that I appreciate having good, independent scientific evidence to evaluate whether to use or to avoid CPS. For now, I'm staying on the sidelines. The risks for me outweigh the potential benefits. (And, given this thread and its history, let me say explicitly that my personal choice to wait till there is more objective science showing that CPS and safe and effective is not an insult to anyone who chooses to use them or an attack on anyone who sells them. Just my personal choice.)

free skin care · Mon Apr 19, 2010 12:07 pm

m1rox wrote:

This is an article that attempts to explain (in layman's terms) how the copper peptides are thought to work:

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

I quote the more relevant parts:

"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. It also promotes the synthesis of elastin, proteoglycans, glycosaminoglycans and other components of skin matrix. Other important effects of GHK-Cu include the ability to regulate the growth rate and migration of different types of cells; significant anti-inflammatory action; and the ability to prevent the release of oxidation-promoting iron into the tissues."

And a possible explanation of the "uglies":

"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 quantify these risk."

I believe the studies that demonstrate possible benefits were done using 1st generation CPs (and mostly for wound healing rather than anti-ageing as pointed out in previous posts). There are no good studies on 2nd generation CPs which is why this thread escalated.

The "uglies" are based on individual reports by various people on their personal experience using 1st generation and 2nd generation CPs, mostly on bulletin boards and forums (such as this one) rather than being the subject of scientific publications. CPs are not FDB-regulated drugs therefore there is no formal mechanism for reporting and compiling statistics on adverse reactions and we have no way of knowing what is the actual incidence of side effects.

This same quote from SmartSkincare has been around for awhile & has come up on the SB Forum several times. The reason that this is in layman's terms is because as far as anyone could find, the owner of SmartSkincare may very well be just that -a layman – an advertising salesman for skin product reviews.

That may explain why what he states is false & inaccurate. And would further explain where his lack of understanding chemistry may stem from.

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

Quote:

Dr. Pickart had the following to say about this statement - His original response is found at:
http://healthyskin.infopop.cc/eve/forums/a/tpc/f/727002...780055604#6780055604

"These type of comments are rather ignorant and not supported by chemical studies or tests in animals and humans. The comments are from people who have never published papers on skin and are very ignorant of chemistry and biochemistry.

Because the SRCPs were originally intended for clinical use, there were a great number of safety studies in animals and humans. Even at high SRCP concentrations, we never observed skin irritation or inhibition of skin repair. If the copper complexes were oxidizing tissue, then there would have been tissue inflammation.

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.

Furthermore, it is impossible for free copper ion to exist in the system. The binding affinities of peptides for copper ion are so high that for every molecule of free ionic copper, there are at least 1000 billion bound copper ion bound to the peptides. The amount of free copper is unmeasurable and of no consequence.

People do have some problems when treating skin around the eyes. This is very thin skin and is often damaged by make-up and make-up removers. The problem is trying to push the changes too fast. No one every had long lasting problems.

The writer at smartskincare never seems to have published papers on skin renewal.If he has data to support his contentions, then he should publish the findings in scientific journals."
-Dr. Loren Pickart

This has come up in other threads in the forum and it is a completely unfounded statement.

Best Wishes,
-Skin Biology

free skin care · Mon Apr 19, 2010 12:31 pm

Star Model wrote:

Furthermore, it is impossible for free copper ion to exist in the system. The binding affinities of peptides for copper ion are so high that for every molecule of free ionic copper, there are at least 1000 billion bound copper ion bound to the peptides. The amount of free copper is unmeasurable and of no consequence.

I don't know when Dr. Pickart wrote this post but it is certainly either outdated or inaccurate. I think it was in the 90s when I first read about trace elements and free copper.

Free copper DOES exist and it IS measurable. Excess free copper is the basis of Wilson's disease.

McMillin GA et al. Direct measurement of free copper in serum or plasma ultrafiltrate.Am J Clin Pathol. 2009 Feb;131(2):160-5.

Some excerpts from the paper:

Copper is an essential element and a critical component of many metalloenzymes. However, excess copper, particularly the free (ie, not bound to proteins) fraction, may lead to tissue injury due to pro-oxidant effects and depletion of antioxidant reserves. It is estimated that less than 5% of the total copper concentration circulates independent of binding proteins such as ceruloplasmin. Thus, the concentration of protein-free copper is very low relative to the total serum copper concentration. As a result, a clinically significant change in the free copper concentration may not be detected through measuring total copper concentrations alone. Indeed, the total serum or plasma copper concentration is generally insensitive to detection of copper overload.

The most dramatic example of copper overload is Wilson disease (WD), wherein a defect in ATP7B, the gene that codes for the primary transporter responsible for copper elimination, leads to excess copper in circulation and accumulation of copper in tissues. Copper excess is also associated with cancer, preeclampsia, dilated cardiomyopathy, inflammation, biliary obstruction, Alzheimer disease, and total parenteral nutrition

Free copper concentrations represent the active, potentially toxic fraction of copper in circulation. The most dramatic clinical example of copper overload is WD. Owing to impaired elimination of copper and resultant accumulation of copper observed with WD, it is logical that the concentration of free copper would be elevated, and determination of the free copper level may assist in the diagnosis and monitoring of WD. Herein, a method for the determination of the free copper concentration is presented and its validation for clinical use described.

He is right though that most copper is bound to proteins (including enzymes). But this could be problematic too because if you have a complex like GHK-Cu (or the second generation) that is quickly broken in vivo, then that free copper will bind to some other protein. And that other protein + copper might be one of the many reactions in which copper generates free radicals or has some other adverse effect.

Star Model wrote:

The writer at smartskincare never seems to have published papers on skin renewal.If he has data to support his contentions, then he should publish the findings in scientific journals."
-Dr. Loren Pickart

I could not agree more with him. If people have data to support their contentions, they should publish their findings in peer-reviewed scientific journals.

free skin care · Mon Apr 19, 2010 12:57 pm

Here are more articles measuring free copper:

- Clin Chim Acta. 2004 Jul;345(1-2):113-21.

- J Neural Transm. 2000;107(3):321-9.

- Neurology. 2009 Jan 6;72(1):50-5.

- Ann Clin Biochem. 1993 Nov;30 ( Pt 6):545-9.

- Clin Chem. 1990 Jun;36(6):860-4.

There are lots more on Medline:
http://www.ncbi.nlm.nih.gov/pubmed

free skin care · Mon Apr 19, 2010 1:48 pm

Dr. Pickart has written to me in response this thread:

From Dr. Pickart:

Quote:

In real science, there is a honored rule called "Peer review". It means that another person commenting on your work is expected to have a similar education and experience in this field of study. It is impossible to discuss complicated topics with persons uneducated and
untrained in a given scientific discipline.

Dr. Pickart has published 17 review articles on copper peptide actions and many patents and research papers on copper complexes plus two papers more that will be published late in 2010. He has a BA in Chemistry and Mathematics from the University of Minnesota and a PhD in Biochemistry from UC San Francisco - one of the very top biochemistry departments in the world.
Look at: www.skinbiology.com/copperpeptideregeneration.html.

If anyone has questions on technical matters, you can ask Dr. Pickart
directly at drpickartchat@skinbiology.com.

* moderated

free skin care · Mon Apr 19, 2010 4:37 pm

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?

Also, regarding the 4 studies, only 3 showed results. One showed no results. And "inflammation and healing" were not outcomes. The outcomes were:

- For 3 papers, TEWL (transepithelial water loss). TEWL is used regularly to asses integrity of skin barrier. In one of the papers Dr. Pickart refers to, it states:

Quote:

TEWL may be a signal for the recovery of barrier function (33). We utilized the measurement of TEWL as a recovery index of skin barrier function on chemically damaged skin in man.

In another of these papers, it states:

Quote:

A chemical eliciting a high TEWL response is not necessarily erythematogenic, while another chemical may cause intense inflammation but not harm the water barrier, etc.

So TWEL is not necessarily a measure of inflammation. It is though used to measure skin barrier function. This is the function of the stratum corneum, the outermost layer of the skin that's composed of dead keratinized cells. So it also does not tell us what is happening in the deeper (and "alive") parts of the skin

- One paper measured TEWL, VS (a visual scale roughly measuring erythema and edema, which are signs of inflammation), BFV (skin blood flow volume) and color (measure with colorimeter)

color is usually used to measure erythema. And BFV is usually used to measure cutaneous inflammation

This paper found significant difference between the placebo and the cream in TEWL, visual score and color.

There was no difference on BFV.

The visual score difference is not clinically significant because the scale goes 1-on-1 point and the difference is half point or less.

There is another problem with the 4 papers and that is that they did not used "repeated measures" statistical analysis. This was something that was not used too much at the time of the papers (1998-1999). This is because, in subject X, a value on T2 will be dependent on the value of T1. So because of that standard errors can be artificially small if one doesn't account for the longitudinal data and can have something seem "statistically significant" when in reality it is not.

free skin care · Mon Apr 19, 2010 6:26 pm

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

free skin care · Mon Apr 19, 2010 6:53 pm

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

For quite some time, I have been asked my opinion related to the benefits of using copper peptides for skin rejuvenation. While these products have enjoyed widespread popularity, there had not been sufficient medical evidence to convince me of their efficacy. Results from recent studies have made me take a second more serious look at the use of Copper Peptides in skin rejuvenation. Up until recently, while this agent has been widely used in the cosmetic market, there was little supportive medical evidence. However, I have been pleased with newly published information and have personally added Copper Peptide therapy into my own skin rejuvenation process.

The Science Behind The Molecule:

New studies are compelling regarding the effectiveness of copper. In addition to copper being a well-known antioxidant, the ability to help stimulate collagen formation is a second very important issue when it comes to repairing as well as preventing aging skin changes. 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.

In the skin, copper helps to:

Stimulate Collagen Formation, diminishing fine lines and firming the skin.
Stimulate Elastin Formation, cutting down on sagging and fine lines.
Stimulate the formation of the extracellular cement between cells, thus improving skin strength, cutting down on fragility.
Stimulate the formation of GAGS (glycosaminoglycans). This helps to thicken the dermis resulting in a lessening of sagging and helps firm the skin.
Increase blood vessel formation and oxygenation within the skin.
Act as a potent antioxidant by stimulating the enzymatic function of Superoxide Dismutase.

The typical American's daily diet contains less than 1mg of Copper. RDA requirements are actually 2mg a day. Even with adequate intakes, the amount of a nutrient in the diet does not always correspond with its ability to not only reach the skin but do so in an active state. Vitamin C is the most well known example. Excess amounts of Vitamin C in the diet are simply eliminated by the body, preventing higher dosages to reach the skin. This necessitates the use of topical Vitamin C for skin rejuvenation purposes.

Simply applying copper to the skin does not guarantee its ability to adequately reach the cells and stimulate appropriate cellular functions. A peptide naturally found in human skin and tissue called GHK (glycyl-L-histidyl-L-lysine) binds cooper molecules, allowing them to arrive in an active state where needed. This peptide is chemically synthesized in the laboratory, so this means that the Copper Peptide complex known as Prezatide Copper Acetate is capable of being used for skin rejuvenation.

How To Incorporate Copper Into Your Regimen

Remember, that no single product is the complete answer to skin rejuvenation at this time. So by combining proven "active" agents, you should be able to achieve a more complete rejuvenation of the skin. Your approach to skin rejuvenation would be to exfoliate away the thickened epidermis and treat the underlying epidermal and dermal cells with other "actives". This does not mean that you must do anything grossly irritating to the skin in order to improve your skin. And of course, many people have very sensitive skin that precludes the use of agents such as vitamin A derivatives of glycolic acids.

Consider using products like glycolic acids (for instance, MD Formulations Facial Lotion or Cream, Peter Thomas Roth Glycolic Acid 10% Moisturizer with Glycolic Acid and Vitamins A, and E) and/or vitamin A products (Neova Retinol ME 0.30%, Afirm or Tretinoin) to thin the epidermal layer. If using both, (glycolic acids and vitamin A derivatives), it is traditional to use them on alternating evenings. As the upper eyelids are taboo for most product lines, use the Neova Eye Therapy nightly. You may then use products like Cellex-C and Neova, again used on alternate mornings to help stimulate your fibroblast activity, which results in collagen formation and other important dermal elements as a morning routine. You're also giving yourself a good dose of antioxidant therapy at the same time. Do not apply vitamin C products (like Cellex-C or SkinCeuticals) at the same time as copper containing products (Neova) as the vitamin C can neutralize the copper. However, you may certainly apply them at the same time to different areas of the skin. For instance, using Neova Eye Therapy or Neova Advanced Perfecting Elixir on the upper eyelids while applying Neova Therapy Mattifying Serum to the remainder of the face. Just because the Neova Night Therapy Cream has the name "Night" in it, you may always consider using it at another time of day. A helpful hintif you have oily skin or rosacea, you should opt to use the Neova Refining Eye Lift, which has a lighter texture. If you are on the dryer side, you may find that using the Neova Body Therapy is an ideal way to help restore hydration to your body. You may even want to use it more than once a day if necessary in place of a regular body moisturizer.

In this manner, you are treating 2 different aging skin issues. Thickening epidermal skin creates a dull, lifeless appearance. Thinning of the dermal layer leads to wrinkle formation, sagging, and of course increased bruising and overall skin fragility. Remember that many products actually have more than 1 active function, which helps enhance results. For instance, Vitamin A helps with collagen formation in addition to its exfoliating functions. So you end up with a bonus in functionality. Neova acts both as an antioxidant to help prevent aging skin changes while helping stimulate collagen and elastin formation within the dermis.

Copper Peptides have become an accepted item in the fight against aging skin. I euphemistically call copper the "blue gold" of the skin. It is certainly an important trace element in skin rejuvenation.

Thank you for taking the time to read my newsletter. I hope you have found it informative.

Audrey Kunin, M.D.

http://www.dermadoctor.com/article_Copper-Peptides_103.html

free skin care · Mon Apr 19, 2010 7:08 pm

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.

free skin care · Mon Apr 19, 2010 7:10 pm

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.

free skin care · Mon Apr 19, 2010 7:34 pm

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

free skin care · Mon Apr 19, 2010 8:11 pm

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.

I think Dr. Kunin wrote something similar to this (or this) in 2007 so she must be talking about the Neutrogena trials and the Abdulghani paper.

Quote:

New studies are compelling regarding the effectiveness of copper. In addition to copper being a well-known antioxidant, the ability to help stimulate collagen formation is a second very important issue when it comes to repairing as well as preventing aging skin changes. 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.

This is the Abdulghani paper (from a pilot study). It's almost impossible to get (it's definitely not available online). I'm trying to get the librarian to get it for me. I want to see the paper to see if the results were significant or not. I tend to think they were not significant because the pilot study did not lead to a full study and also because of something Dr. Maibach said on the latest peer-reviewed review on copper peptides (2009):

Abdulghani et al. revealed its enhanced but insignificant anti-ageing effects when compared with tretinoin, Vitamin C and melatonin.

In the review (Role of topical peptides in preventing or treating aged skin, Int.J.Cosm.Sci.31(5)327-345), Dr. Maibach cites the five in vivo studies that exist regarding HCK-Cu (FGCP) and anti aging. Four of those studies are the Neutrogena studies and then one is the Abdulghani one.

He then talks about some of the benefits GHK-Cu has shown in cell cultures and animal wound models: promoting extra large collagen aggregates degradation in scars, regular collagen synthesis in normal skin, elastin, proteoglycans and glycosaminoglycans production, growth rate and migration of different cell types and anti-inflammatory and antioxidant responses.

He does not evaluate the in vitro studies that showed effects vs. studies that did not show effect (e.g. one study shows increase of MMP, other shows decrease of MMP). He also does not address safety concerns although he does say that trials are needed to determine correct "dose" with safety.

He concludes:
High quality randomized double-blind active-controlled large trials are needed to calculate exact effect sizes of main topical peptides or proteins to reach to these conclusions (i) whether they are effective enough to be approved, (ii) whether they can be utilized as an equivalent to current recommended treatments for ageing skin and (iii) at what doses they have maximum efficacy with acceptable safety profile.

To conclude I believe that:

a. There are not enough published studies to affirm (or deny) an antiaging effect of copper peptides, either first or second generation

b. In vivo animal wound studies have suggested that FGCP promotes wound healing

c. Human studies regarding wound healing have found mixed results

d. In vitro data has shown conflicting results

f. There are testimonials of people who believe they have benefited from CPs, other have not benefited, others have claimed adverse effects.

I think that while we wait for new studies which will hopefully highlight good results, people have enough information to make an informed decision and decide whether to take the plunge or not.

free skin care · Mon Apr 19, 2010 8:15 pm

Josee wrote:

I think that while we wait for new studies which will hopefully highlight good results, people have enough information to make an informed decision and decide whether to take the plunge or not.

Agreed!

free skin care · Mon Apr 19, 2010 8:20 pm

bethany wrote:

Josee wrote:

I think that while we wait for new studies which will hopefully highlight good results, people have enough information to make an informed decision and decide whether to take the plunge or not.

Agreed!

I agree, as well. Thanks so much Josee for starting this thread so we can each make our own informed decision on whether CP's are right for us or not.

free skin care · Wed Apr 21, 2010 9:12 am

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

free skin care · Wed Apr 21, 2010 9:38 am

Thanks Josee. That was very interesting. It's a pity they didn't follow up the subjects for a longer period of time. Perhaps using both tretinoin and FGCP would cover the bases of increase in both types of pro-collagen. This is what quite a few people are doing already empirically.

free skin care · Wed Apr 21, 2010 9:55 am

Josee wrote:

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

Here's the exact quote from the SB website;

"A clinical study which compared the effect on the skin's production of collagen after using creams containing copper-peptides, vitamin C, or retinoic acid (retin-A) Twenty volunteers applied the various creams to their thighs daily for one month. New collagen production was determined by studying skin biopsy samples using immunohistological techniques.

The study found, that after one month, copper-peptides had the most significant effect on collagen production. Significant increases in collagen production were found in 70% of the persons treated with copper-peptide creams, 50% of the persons treated with the vitamin C cream, and 40% of the persons treated with retinoic acid."

And this SB link contains info on "all published studies"; (I knew I remembered reading that "70%" somewhere also.) Anyway, interesting reading for anyone who might have missed it;

http://www.skinbiology.com/copperpeptideregeneration.html#cosmetic

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