Still hiding from pigment issues? There’s a new deep-science approach. | BareFacedTruth.com

Still hiding from pigment issues? There’s a new deep-science approach.

Abnormality in pigment is one of the most common topics readers inquire about on BFT. Most frequently it has to do with hyperpigmentation that results from an inflammatory insult (PIH) or hormonal flux (melasma or “mask of pregnancy”), but many readers have sought information as to how they can lighten or “brighten” their general complexion.

This post provides information about new approaches to managing pigmentation issues, something your hosts have been working on for a considerable time. We will examine this work and the novel multi-prong approaches incorporated into these new and unique products.

For those who wish to learn the basics about pigment issues, we suggest you visit our earlier BFT blogs on the subject.

https://barefacedtruth.com/2013/05/25/melasma-melanin-and-mosaicism/

https://barefacedtruth.com/2013/06/14/postinflammatory-hyperpigmentation/

Disclosure:

The management of aesthetically displeasing skin pigmentation is changing. To describe it, we must discuss work performed by the team at Cellese Regenerative Therapeutics over the past couple of years. Regular readers of BFT know that DrJohn and DrGeorge wear day hats as principals of Cellese. 

Pigment Basics Revisited

Melanin is an evolutionary protective pigment whose skin function is as a barrier against ultraviolet (UV) solar radiation. All races have similar numbers of melanin producing cells located within the stratum basalis of the epidermis. Skin color differences result from the pigment content and characteristics of the melanosomes produced by the melanocytes.

Caucasian skin has the smallest amount of pigment and smallest melanosomes; darkly pigmented skin has larger, wider and denser melanosomes. Inflammation from any source, including damage from UV radiation, is a potent stimulus for increased melanin production. Darker Fitzpatrick skin types are more prone to develop aesthetically displeasing hyperpigmentation.

As a general rule, melanosomes produced by melanocytes are expelled and subsumed into nearby keratinocytes. The melanin-laden keratinocytes slowly migrate to the skin surface where they are eventually sloughed off, a process that takes four to six weeks.

Melanogenesis takes place within the melanosomes, catalyzed by the enzyme tyrosinase. Inhibitors of this enzyme have long been mainstay ingredients in depigmenting products, the most well-known of which is hydroquinone. This approach, however, addresses only one of the several processes involved in melanin production, deposition and disposal.

Differences Between Epidermal and Dermal Pigmentation

During embryogenesis, melanocytes are genetically programmed to eventually settle in the lowest region of the epidermis (basal layer), just above the dermal-epidermal junction that separates the epidermis from the dermis. Typically, about one in every ten cells in this layer is a melanocyte, with a ratio of one melanocyte to thirty keratinocytes, which is the predominant cell of the epidermis. Epidermal pigmentation occurs from keratinocyte uptake of melanosomes produced by melanocytes.

As melanocytes (actually the precursor cell, the melanoblast) transit the dermis to the epidermis, some may finally reside within the dermis. Epidermal and dermal melanocytes appear to be biologically different populations. Dermal and epidermal melanocytes participate differently in pigmented lesions. The table below describes the role each layer plays in specific pigmentation scenarios.

Type of Pigmentation Surface (i.e. Epidermal) Deep (i.e. Dermal)
Brown birthmarks, café au lait spots No Yes
Normal tanning Yes No
Prolonged tanning Yes Yes
Freckles Yes No
Age spots No Yes
Melasma Yes Yes
PIH from injuries (burns, cuts, abrasions, etc.) Yes Yes

The illustration below demonstrates the pigment deposition patterns of common skin lesions.

It’s a fact of life that dermal pigment is more difficult to remove than epidermal pigment. Topical products are less able to penetrate to deeper skin layers, although microneedling can be of significant benefit. Pigmented spots that don’t readily respond to topical brightening treatments are likely to involve the dermis.

Multiple Pathways Involved in Melanin Production, Dispersal and Disposal

As was the case when we launched our hair growth products, we approached pigmentation from a deep-science perspective, knowing that melanogenesis is but one part of a complex multi-step pigmentation process. Several other pathways are involved. The steps below can each be addressed to reduce pigmentation.

  1. Inhibit tyrosinase activity and co-factors
  2. Promote tyrosinase degradation
  3. Down regulate gene expression that promotes melanogenesis
  4. Inhibit the pro-melanogenetic effects of UV
  5. Inhibit melanosome transfer from melanocyte to keratinocyte
  6. Increase exfoliation of pigmented keratinocytes
  7. Counter the inflammation stimulus of UV and other stresses

Our Approach

Your hosts have formulated products with active ingredients that influence each of these pathways. A daily-use topical product with all ingredients, and a microneedling solution with those that are physiologically compatible when used in conjunction with 1.0 mm medical needling. The products affect pathways involved in melanogenesis, keratinocyte melanin uptake and cellular exfoliation.

 

Active ingredients and mechanisms of action in daily-use topical:

Active Ingredients and mechanisms of action in microneedling topical:

Clinical Study

Products were tested in a 90-day randomized study of thirty-one participants aged 30 to 70 years of age of both genders with Fitzpatrick skin types I to V. Using a zero to five-point scoring system, a skincare specialist analyzed before and after high-resolution photos with different wavelengths of light. Using the same scoring system, each participant also completed subjective questionnaires at the beginning and end of the trial. Photo analysis and questionnaires confirmed significant and safe brightening and improved appearance of undesired facial pigmentation, regardless of its cause.  Participant satisfaction was extremely high. No adverse events were reported during the study.

 

Slow & Steady

Treatment of abnormalities of facial pigmentation requires a slow steady approach as overzealous treatment can have devastating consequences. As an example, experience with higher doses of hydroquinone has repeatedly shown it is possible to end up with pigment abnormalities that are significantly worse than the original problem. The most severe pigment problems occur in people with skin that is especially prone to darkening, higher Fitzpatrick skin types. Gradual cautious lightening is preferable to inadvertent injury that can be counterproductive and worsen the problem.

The products tested function to affect the seven pathways of skin pigmentation: -melanocyte stimulation and control, melanin synthesis and production, melanin uptake and dispersal, and cellular exfoliation – using multiple gentle yet effective physiologic “nudges.”

Additional information will soon be available at anteage.com.

 

References:

 

Ebanks J, Wickett R , Boissy RMechanisms Regulating Skin Pigmentation: The Rise and Fall of Complexion Coloration. Int J Mol Sci. 2009 Sep; 10(9): 4066–4087.

Arndt, K.A. and Fitzpatrick, T.B.Topical use of hydroquinone as a depigmenting agent.JAMA 194(9), 965967 (1965).

Ando H, et al. Melanosomes Are Transferred from Melanocytes to Keratinocytes through the Process of Packaging, Release, Uptake and Dispersion. Journal of Investigative Dermatology. Volume 132, Issue 4, April 2012, 1222-1229

Serre C, Busuttil V, Botto JM. Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation.  Int J Cosmet Sci. 2018 Aug;40(4):328-347.

Pillaiyar T, Namasivayam V, Manickam M, Jung SHl Inhibitors of Melanogenesis: An Updated Review. J Med Chem. 2018 Sep 13;61(17):7395-7418.

Bissett DL et al. Reduction in the appearance of facial hyperpigmentation by topical N-acetyl glucosamine. J Cosmet Dermatol 2007 Mar.6(1):20-6

Ebrahimi B, Naeini FF. Topical tranexamic acid as a promising treatment for melasma. J Res Med Sci. 2014 Aug; 19(8): 753-757

Yun WJ et alEpidermal growth factor and epidermal growth factor signaling attenuate laser-induced melanogenesis. Dermatol Surg. 2013 Dec; 39(12): 1903-11

Yokota T, Nishio H, Kubota Y, Izogushi M,  The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Res. 1998 Dec; 11(6) 355-61

 

 

 

 

 

4 Comments

  1. Maya N says:

    I have been using AnteAge cleanser, serum, and accelerator for about a month now. I am loving the improvement in tone, texture, fine lines, and PIH, but I have noticed small bumps/pimples popping up all over my face that I cannot attribute to anything else – diet, hormones, etc. I am not using any other products except for my usual makeup (which is rare these days as I’m trapped at home) and occasionally a glycolic face wash. It’s frustrating because the products do seem to be helping my fine lines and pigment issues, but then I am getting these small little bumps that are offsetting the aesthetic benefits. The bumps are not true whiteheads… they don’t even appear to be clogged pores… they’re almost like very very tiny blisters?! Is this a natural side effect? The good news is that even if I pick at them (which I know I shouldn’t), they do seem to heal very quickly.

    Thanks so much. I love the product otherwise but just am not sure what’s going on with the bumps or if this is common within the first month or so of use.

    • drgeorge says:

      A few people have minor issues when they first begin using our products, especially people who have not used products with true active ingredients. And our Serum/Accelerator products have more actives than any other brand of which we are aware. The increased rate of cellular proliferation and turnover takes a period of time for your skin to establish a new “set point”. As that occurs, the phenomenon you are experiencing can occur. Don’t fret, it will resolve. A reasonable approach may be to gently “scrub” the skin with an exfoliative cleanser or even a very mildly abrasive glove. Older layers of skin will accelerate the rate at which the slough off and the problem should resolve.

      FYI, To get the same number of active ingredients typically requires purchase of many different kinds of products. Several years ago DrGeorge was interviewed by a Los Angeles television program interested in our approach to hi-science skincare. They priced the many different actives, not including the bone marrow stem cell conditioned media, and came up with a total that approached $1000!

  2. mike says:

    I’m looking into ordering the AnteAGE home microneedling kit with 0.25 mm roller. I’m a 32-year-old male with a history of acne and some light to moderate scarring, which have improved significantly over the years. What are your thoughts on using this roller for the purpose of product penetration and collagen production? How frequently is it suggested to use your microneedling kit? I am currently using tazorac .01% concentration. What would be the appropriate regime for using micronneedling and tazorac? Also, what is your professional opinion on using a microneedling pen for home use?

    • drgeorge says:

      The home microneedling kit and 0.25 mm dermaroller can be of significant benefit to improve appearance. The 0.25 mm needle length is long enough to enhance product penetration but not long enough to do significant trauma to the dermis. Medical needling uses needles 0.5 mm and longer and results in pinpoint bleeding in most people. Longer needles are needed for thicker areas of skin on the face and elsewhere, especially if the intent is to reduce scarring or the appearance of striae. Pigmentation also requires longer needles. The AnteAGE kit includes Microneedling Solution, the penetration of which is enhanced with even shallow needling. Some of the ingredients have published proof of enhanced collagenesis so one can expect improved appearance with regular use. Two or three times a week is typical.

      Tazorac is the brand name for tazarotene, a retinoid (vit A derivative) prescribed as a treatment for acne and psoriasis. Tazorac creme is used to help reduce fine facial wrinkles and certain types of pigmentation. Concentrations approved by the FDA include 0.001%, 0.005% and 0.01%. We see no contraindication for applying with 0.25 mm needling although as a general rule, especially with deeper needly treatments, we recommend products that contain only physiologic ingredients i.e. those found naturally in the skin such as is contained in the AnteAGE brand. Do be observant for any evidience of allergy or sensitivity reactions, however, until you are certain there are no obvious negative effects. Let us know how it goes.

      The question of home use of a microneedling pen has too many issues to give you a recommendation. Pen quality, needle length and material, method of keeping equipment hygenic and clean, and possibility of cross-contamination if used by more than one person are all considerations that must be addressed. We’ll stay agnostic on this one. Needling pens are the domain of licensed estheticians (shallow needling only). Medical needling is performed by nurse practitioners, physicians and properly supervised nurses.

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