EGF structure

Microneedling & EGF

Prompted by the question  (see below) posted by reader Holly as a comment to our post entitled Bioeffect EGF Controversy, we invited our highly respected colleague Dr. Lance Setterfield, guru of all things microneedling and related skin care topics, to join us here at BFT.  He brings a new and  different perspective  to the science that interests us.  All the more fun because science shines best when it is debated, to bring out the fine points of what is (and often what is not) known.  Take it over DrLance….

“What do you think about micro needling / roller while using EGF? Does that alter what layer the EGF works at? I see this on the web used together. I also see it used for alopecia (needling) with serums so isn’t that the opposite of losing hair over time with EGF use? Is it the combo used together that changes the dynamics? I’ve never used any of them – just curious about micro needling for wrinkles and what I should use on the face while needling. I don’t want to use something unsafe. Thanks.”

On the surface (no pun intended), this may seem fairly straightforward, but it is extremely complex.  The question above presupposes that EGF in a skin care product works to begin with.  I am not saying thatEGF activated EGFR one could not get a result, but all the planets have to be aligned, so to speak.  Unfortunately, the skin care industry tends to oversimplify things and explain them in scientific ways so as to add credibility to a concept, but in essence it is mostly marketing spin to sell a product.  This is particularly true when it comes to stem cells, growth factors, and cytokines because they are new buzz words, and, together with gene therapy, represent the future of skin care.  The stakes are high.

Epidermal Growth Factor was one of the first growth factors to be isolated from a number of sources, e.g. plants, E-Coli, etc., and added to skin care products.  It is probably the most common growth factor in products today.  The marketing premise starts here:

EGF is a growth factor that is essential in the regulation of cell growth, proliferation, differentiation, and survival. It promotes synthesis of DNA, RNA, hyaluronic acid, and Hydroxyproline.

So far, so good.  But this is where the wheels fall off. Here are the issues.

  1. microneedling-pen-roller1. Considering things in isolation: 

EGF does not accomplish these things in isolation.  Think of it this way.  If growth factors and cytokines are signaling molecules that facilitate communication between cells, EGF is the area code in a phone number, but if you don’t punch in all the other numbers, you won’t make contact and there will be no outcome.  Not all phone calls have a happy ending either.  Once you get through, there may be other factors involved that can result in a negative outcome.  EGF is one of those growth factors that can work for good (rejuvenation) or bad (cancer), and much of the outcome depends on the balance or imbalance of many other factors.

 

  1. 2. Bio-mimicry:

Growth factors and cytokines bind to receptors to accomplish outcomes.  In other words, they are like keys that turn things on and off.  They have to fit the keyhole exactly.  The question becomes whether or not growth factors derived from plant cells are identical to those from human cells?

  1. 3. Quantity:Balance

Outcomes are dose-dependant.  Do all cosmetic products contain enough EGF to make a difference?

  1. 4. Balance of nature:

Are all the other elements that combine with EGF in any scenario present in quantities that represent a synergistic balance?  For instance, too many pro-inflammatory growth factors and cytokines will lead to premature aging, scarring, or even cancer.

  1. 5. Deductions based on a name:

Studies show that EGF results in cell growth, proliferation, differentiation, and survival.  But one study showed that “when cultured at 37 degrees C, keratinocytes formed a well-differentiated epidermis whether EGF was present or not.” [1]   Yet another study showed:  “Short-term growth of keratinocytes in a chemically defined medium demonstrated that neither EGF nor IGF-I alone could support significant keratinocyte spreading or proliferation, but that a combination of EGF with IGF-I or high-dose insulin could.” [2]

Thus, cell activity may be due to other factors besides the obvious.

  1. 6. Self-Regulatory via biofeedback mechanisms:

“EGF induces DUSP’s which are phosphatases that limit the EGF signal transduction in a feed-back loop.” [3]   So, at what point does too much of a good thing become a bad thing, especially in the context of needling where natural EGF is released in significant amounts?

  1. 7. EGF may induce or suppress the same genes:

EGF influences about 1100 genes.  Meta-analysis shows about 520 genes are induced while 580 are suppressed by EGF treatment in human epidermal keratinocytes.  44 are both induced and suppressed, depending upon the timeline of the treatment. Which outcomes will prevail depends on additional EGF-independent signals affecting the keratinocytes.  [3]

egf-bomber-creamWith regards to the question about EGF treatment for alopecia, again, it is a combination of factors that dictates outcome.  One study used EGF in isolation, injected in angora rabbits to facilitate an increase in depilation.  The mechanism of action involves inhibition of mitoses within the cell population of the follicle bulbs causing follicle regression. [4]

Other studies, however, show epidermal growth factor functions as a biologic switch that is turned on and off in hair follicles at the beginning and end of the anagen phase.  In addition, EGFR (Epidermal Growth Factor Receptor) signaling is indispensable for the initiation of hair growth. [5 Patients that are treated with EGFR inhibitors for cancer may develop alopecia [6], confirming the positive effect that EGF can have on hair growth.  The positive results seen with needling and PRP for hair restoration, however, are predominantly due to the activity of other growth factors and cytokines. This study pertaining to adipose stem cells showed “VEGF controls hair growth and follicle size by angiogenesis in a VEGF transgenic mouse model (30). In addition, PDGF and its receptors are important in follicular development, and PDGF isoforms induce and maintain the anagen phase in murine hair follicles (27). IGF-I also up-regulates hair follicle growth in various systems.” [7]

As to your question about what to use on your face that is safe to combine with needling, this is a topic too vast to embrace in this format of discussion. I address these concerns in a section of “Concise Guide to Dermal Needling – Expanded Medical Edition” (Pages 64-77) and excerpts can be viewed here:  http://www.needlingguide.com/book/lance book

In summary, listing individual ingredients on a skin care product label to create a distinctive difference disregards the complexities of biochemistry, which is borne out by the reality that we struggle to get results in our clinical practices despite the amazing advances in science.

–DrLance

References:

[1]  Epidermal growth factor and temperature regulate keratinocyte differentiation.  Ponec M1, Gibbs S, Weerheim A, Kempenaar J, Mulder A, Mommaas AM.

Arch Dermatol Res. 1997 May;289(6):317-26

[2]  Synergistic Effects of Epidermal Growth Factor (EGF) and Insulin-Like Growth Factor I/Somatomedin C (IGF-I) on Keratinocyte Proliferation May Be Mediated by IGF-I Transmodulation of the EGF Receptor  Jeffrey F Krane, Daniel P Murphy, D Martin Carter and James G Krueger Journal of Investigative Dermatology (1991) 96, 419–424; doi:10.1111/1523-1747.ep12469799

[3]  Profiling and metaanalysis of epidermal keratinocytes responses to epidermal growth factor. Miroslav Blumenberg.  Published online: 8 February 2013

[4]  Epidermal growth factor (EGF) facilitates depilation of the Angora rabbit.  G.P.M. MOORE, R.-G. THÉBAULT J. ROUGEOT and P. VAN DOOREN  Ann. Zootech.,  1987, 36 (4), 433-438

[5]  Epidermal Growth Factor as a Biologic Switch in Hair Growth Cycle*      Kingston K. L. Mak and Siu Yuen Chan.  First Published on April 24, 2003, doi: 10.1074/jbc.M212082200.  July 11, 2003 The Journal of Biological Chemistry, 278, 26120-26126.

[6] Nonscarring inflammatory alopecia associated with the epidermal growth factor receptor inhibitor gefitinib.  Julia E. Graves, MD, Beverly F. Jones, MD, PhD, Anne C. Lind, MD, Michael P. Heffernan, MD.  Journal of the American Academy of Dermatology  Volume 55, Issue 2, August 2006, Pages 349–353

[7]  Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion.  Byung-Soon P ark, Won-Serk Kim, Joon-Seok Choi, Hyung-Ki Kim, Jong-Hyun Won, Fumio Ohkubo, and Hirotaro Fukuoka. Biomedical Research 31 (1) 27-34, 2010

7 Comments

  1. Rena says:

    Dr Lance – from reading around the web it seems like everyone is using different products when dermal rolling. And different needles sizes. If I stay with small superficial needles (0.25) depth is it OK to use my usual skin care products at the time I needle? Thanks for helping us understand this.

    • drjohn says:

      DrLance is busy preparing for a visit to us here in the U.S., so I will answer your question and he can add/correct upon his return from exile.

      If you slather on your usual skin care product prior to or soon after needling you will allow absorption of considerably more that product to deeper layers than is possible when your skin protective barrier is intact. Even if you are at 0.25mm or less (so called cosmetic, as opposed to medical needling which is in the 0.5mm & above range) you are providing access to deeper layers of the epidermis where some fibroblasts and younger (less differentiated or toughened) keratinocytes (skin cells) reside. That can be a good thing (actives working to assist the effect of the needling) or it can be harmful (actives, or carriers/accessories in the products). Dr. Lance lists in his book a whole slew of potential troublemakers (he is gracious – I would have labelled them as noxious felons) including dyes, preservatives, fragrances and even common humectants and moisturizers). Even hyaluronic acid (HA – which we regularly inject into skin as fillers).

      Now, since the publication in a prominent medical journal a few months ago of a series of 3 cases where patients developed granulomas (nasty foreign body reaction) after dermarolling (using a vitamin C serum) doctors have become even more acutely aware of the potential problem. Which molecule in the serum was responsible is uncertain. Probably not the C itself, but one of the other ingredients (it’s hard to be allergic to an essential vitamin and still survive). So, we are all more cautious than ever. Actives, such as pure vitamins, metabolites, cell messenger & bioactives like cytokines, HA, etc. which are native to human skin, if present in a form & dose in physiologic or natural range, are presumed (in theory) to be just fine. But they need to be pure. No foreign stuff. No native (natural to human skin) stuff in concentrations or forms that could make it foreign by dint of being present in amounts too high to be physiologically usable.

      Unfortunately, there is another problem, created by the needling itself (although it is also doing good things by stimulating a wound healing cascade that leads to its therapeutic effects on skin). The side effect is a loss of protective skin barrier, temporarily, until the skin heals those little holes. It would be better to plug those holes to avoid problems with water loss than can itself damage the skin. Hyaluronic acid (at least the high molecular weight variety), being total natural to all layers of skin, provides one safe alternative (again – IF IT IS PURE & sterile & all that). Then you can talk about those other actives that help rather than hinder the positive effects of microneedling. Mind you, holes get naturally plugged to the point of safety within ~ 4 hours.

      Not sure of DrLance’s perspective on the matter, but to my mind another variable in the equation is age & skin health to begin with. If you are young with healthy skin, your probably don’t need a lot of extra help from chemical or bioactives. Your body will quickly move from a short inflammatory phase to an anti-inflammatory phase with rebuilding of skin & rejuvenation. And if you are not needling so frequently that inflammation becomes your chronic companion (you nightly “holey rollers” know who I mean). But if you are older that 35, have chronic sun damage, sensitive skin, have been using inflammatory skin creams or peels or such stuff, have problems with acne scars, prone to hyperpigmentation etc., then you are going to need all the help you can get. This shifts the risk/reward ratio ratio in favor of what could be called “microneedling helpers”.

      The problem becomes deciding which are safe and which are not. Read the book, or ask a professional who has read the book or taken the course. Maybe we need a “Safelist” of products. I’ve talked to Dr lance about that. I’m sure that would upset a lot of people. Since we at BFT aren’t overly shy about such things, we would be glad to publish it here.

      Dr Lance will review all this when he has time … he may disagree with some or all, we shall see.

      DrJohn

  2. Frances says:

    I’ve ordered Dr. Setterfield’s book because I’d really like to try derma rolling but in the meantime I have two questions – I’ve seen derma rollers for $15 and $150 – are some really better than others? also, since I’m also using ante age (serum and accelerator) do they have anything in them we shouldn’t be rolling in? thanks

    • drjohn says:

      Hi Frances. It’s an excellent question. I will give you my thoughts, and DrLance can give you his when he visits again (we are in Las Vegas together next week & I will prompt him.).

      On the dermaroller issue, there are most certainly some I have seen that are cheaply constructed in third world countries, and I worry about quality of construction. Some companies spend hundreds of thousands of dollars working with their pen devices to get it right. Others crank out knock off rollers with abandon.I have a particular concern about the metals (stainless steel and titanium) which can oxidize and leave behind metal nanoparticles which can cause local skin reactions. We don’t have a list of approved rollers, but would simply caution you to stick with reliable sources that have people you can talk to if you have questions, etc.

      On the AnteAge issue, there is now lots of real world experience now with the combination of AA and microneedling, and it is all positive. We have physicians and estheticians around the country reporting great results. However, DrLance and I agree that at the time of microneedling (and for a few hours after) to be totally cautious and prudent (while those punctures are not fully closed) we should keep it very simple. Only physiologic things should be used (things totally natural to the body), and only things that make sense because they are pro-healing, anti-fibrotic (non-scarring) and anti-inflammatory. For this reason Cellese has developed an AnteAge Microneedling Solution that contains only hyaluronic acid and stem cytokines/growth factors (the prime active ingredient in AnteAge). Then begin using the AnteAge serum twice daily after a few hours have passed, and the real work of regeneration gets started. I believe this product is being released next week. If you remind me then I will see that you get some.

  3. Frances says:

    Thank you! that sounds ideal – I now have my book so if Dr. Lance has anything to add on which derma roller that would be great!
    thanks

  4. Amber Borozny says:

    Hi there. My question is regarding body treatments with dermal needling. I have read Dr. Setterfield’s book and I do believe he says you can do body rolling but I can’t seem to find parameters. I plan on rolling with .25 or .3 (I have pretty oily skin) everyday with a copper peptide serum and .25 tret and then doing .5 once a month for my face. Do you know if there is something similar recommended for body treatments? I would like to treat for cellulite, wrinkly elbows and knees and some scars.
    Thanks so much in advance for any advice!!

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