Efficacious Antioxidants and Vitamin C: A Novel Free Radical Defense Approach

Among existing needs is the well-established field of skincare, where decade-by-decade advancements look like leaps along a trail that has literally been trod for thousands of years. Yet, the science behind skincare is often suspect because regulatory rules do not require the same scientific rigor as drugs and medical devices are subject to. A recent study¹ in the Journal of Cosmetic Dermatology elucidates the groundwork for and rationale behind a potentially game changing formulation in the fight against free radical damage with two experiments. The combination of antioxidant actives consists of a variety of proven players, as well as a vitamin C derivative sodium salt which, in contrast to the oft utilized vitamin C/L-ascorbic acid variants, preserves rather than inhibits the presence and neogenesis of elastin.

Alan Widgerow, MBBCh, MMed, division chief of research for the Center for Tissue Engineering at the University of California Irvine (Irvine, Calif.) is lead author of the article. “Any dermatologist can tell you that a large volume of reactive oxygen species is generated on a daily basis stemming from photodamage and other stressors that are applied to the skin, wear and tear, and other extrinsic causes, resulting in free radical damage which the body is constantly combatting,” he explained. “Vitamin C, a backbone of cosmeceutical preparations, was the first original quencher of these reactive oxygen species. So, it has taken a key leading role in cosmeceuticals over the years – even as many alternative antioxidants have emerged – in our efforts to bolster and maintain skin health.”

While the community has always regarded vitamin C as a stimulant of collagen and a solid antioxidant, which it is, nobody had looked at what happens with elastin, a vital element within the extracellular matrix. “Research began to surface suggesting that the traditional vitamin C, L-ascorbate, was causing damage to elastin, and nobody had looked at vitamin C from that perspective,” Dr. Widgerow continued. “This caught our attention and generated a lot of interest. We also noticed a discovery out of Canada that vitamin C sodium salt derivatives actually conserved elastin. So, first we set out to validate an antioxidant formulation we created using recognized antioxidants known to be powerful, plus this elastin-conserving vitamin C, versus a similar formulation with traditional vitamin C. Once we validated that the formulations had equivalent antioxidant effects, we subjected an ex vivo skin model – three skin explants from facelift procedures – to each topically administered formulation to compare the effect of each on elastin.”

Detailed in the study text are the extensive formulations. Differing only in the vitamin C used, the evaluated preparations were applied to treat human skin cultures for 48 hours before being subjected to oxidative stress – a dose of 13 J/cm2 ultraviolet (UV) radiation – then retreated and incubated for another 24 hours (total 72 hours of treatment). According to the study, the generation of free radicals was then semi-quantitatively measured. The result was a firm demonstration of strong efficacy, but more importantly, equivalence between the two formulations in their ability to fight the effects of free radicals.

During the ex vivo skin model experiment, plastic surgeons donated the skin used. “This was unique because the explant skin was real, photodamaged skin which is a perfect model for examining exactly what effect these formulations would have on collagen, elastin, etc.,” Dr. Widgerow said. “It was our belief that the preparation with the vitamin C sodium salt derivative would perform better as far as elastin preservation was concerned.” After the explants were subjected to topical treatment with the formulations daily for 7 days, the skin underwent immunofluorescent staining, followed by software analysis of captured images. The results were striking. “We did find that in fact, the traditional L-ascorbate did create a moth-eaten appearance in the elastin. In other words, it seemed to actually degrade some of that elastin, whereas the preparation with the sodium ascorbate we were using seemed to conserve the elastin.”

This led to the next step, a deeper evaluation of the sodium ascorbate formulation, in a more recent study in press, to see if it might actually stimulate elastinogenesis. Dr. Widgerow stated that the preliminary results appear to be extremely favorable. “We seem to have a breakthrough here, where we go one better with sodium ascorbate and preserve – or even stimulate – elastin, when for a long time we have been having a deleterious effect on elastin with our vitamin C based topicals. So, it is an ideal combination for an antioxidant formulation because it has efficacy in the antioxidant sphere, it stimulates collagen, and it stimulates elastin. And that is beautiful. What’s more, we are not only looking at potential applications in normal skincare, which it should work wonderfully for, but also in a post-procedure adjunctive role. The possibilities are exciting, to say the least.”

Reference:

1. Widgerow, AD, Ziegler, ME, Garruto, JA, Shafiq, F. Antioxidants with Proven Efficacy and Elastin-Conserving Vitamin C – A New Approach to Free Radical Defense. J Cosmet Dermatol 2023; 22: 3320–3328.

Editor’s Note: The original article Antioxidants with Proven Efficacy and Elastin-Conserving Vitamin C – A New Approach to Free Radical Defense, is open access and available online at: https://pubmed.ncbi.nlm.nih.gov/37853849/

Gender-Affirming Facial Surgery: Adult 3D Facial Morphology Differences

With the more normalized acceptance of fluidity in gender identity, comes an unsurprising concurrent rise in demand for what has been termed gender-affirming facial surgery (GFS). Making a face more masculine or feminine plays a key role in the expression of a new gender choice. The fundamental aspects of facial appearance that characterize masculinity or femininity are basically understood and defined subjectively, but there is little objective data to drive surgical decision making in these cases. Emerging technology is being adapted to meet this developing need. A recent study¹ published in Facial Plastic Surgery & Aesthetic Medicine elucidated the use of digital imaging and software analysis to provide a more objective approach to better defining, in three dimensions (3D), what surgical interventions would shift a given face toward a more masculine or feminine ideal. In other words: Objectively, what makes a face more masculine or feminine?

“We have not seen robust objective facial data in the 3D realm,” said Rahul Seth, MD, an author of the above-mentioned article from the Division of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology-Head and Neck Surgery at University of California San Francisco (San Francisco, Calif.). Dr. Seth also practices at Golden State Plastic Surgery (Walnut Creek, Calif.). “Although there is a reasonable amount of data in the two-dimension (2D) realm, the question of facial femininity versus masculinity is a fundamentally three-dimensional assessment. We knew there was a lot to be gained in growing that overall understanding. Through previous research, we have begun to understand that certain areas of the face are more influential in the brain’s perception and categorization of somebody’s gender, but understanding in 3D how the face and its regions display sex-characteristics was less understood.”

Study authors selected a subset of 1,573 facial surface scans of healthy subjects from a much larger U.S.-based repository of 3D facial scans and demographic information (collected between 2009 and 2014). For inclusion, facial scans were to be of subjects 20 years of age or older at the time of imaging with no known congenital facial abnormalities or history of facial trauma/facial surgery. Also, gender was self-identified as either female or male and confirmed via genetic analysis of saliva samples. In order to reduce confounding variables, only participants of European-Caucasian ancestry were included. Each scan was then landmarked by trained human observers according to a scientifically-validated system of 24 landmarks. The magnitude of differences in various aspects between male and female faces was then determined by software. “Simply put, we took 3D facial scan data and used mathematical software analysis to reveal the type and magnitude of facial differences between males and females.” The key to this is geometric morphometrics (GM), a series of mathematical operations which translates nuisance biometric scanning differences into interpretable, and thus practically representable, information. “GM is a science for understanding how different 3D points relate to one another. It is a complicated process, but we can boil it down to three characteristics: Size, shape and form (a combination of size and shape),” Dr. Seth explained.

Results were extraordinary. While the article itself provides and dives more deeply into the details, the differences that drive our perception of gender account for only 6% of facial shape variance, but 30% of facial form variance, when objectively analyzed. “We think of prominent features such as the area between the eyes, the prominence of the brow, or shape of the nose to portray gender, but there are many more subtle differences that, together, help make the whole face more masculine or feminine,” he continued. “This kind of information may help surgeons optimize intervention for GFS. The possibilities this enables compelled us to form a company (Deep Surface AI in Calgary, Alberta, Canada) and build a Health Insurance Portability and Accountability Act (HIPAA) compliant commercial software platform to help the community with visual representations and software morphing. This may provide practical, datadriven guidance for making the face look better, younger, or more towards a specific gender.”

As supplementary information to guide understanding, software-generated visual representations were then manipulated using this data to morph a face toward more masculine and feminine extremes. This is demonstrated by the example in Figure 1 (Figure 3 from original paper). The use of morphing technology to visualize potential changes in a digitally scanned patient face is a common practice, but there is a challenge – and a responsibility – in translating what may be generated on a computer screen into what is surgically achievable. “Facial morphing includes the conceptualization, visualization and explanation of the proposed changes, all of which lead up to inform surgical execution,” Dr. Seth noted. “It is up to the surgeon to use technology responsibly in the consult, to know what they can and cannot do as a surgeon, and to accurately represent these realities to the patient in any case, before they undergo surgery.”

In the seemingly large sample size, the distinct lack of ethnic diversity was a notable limitation of the study, but necessary at that stage of the game, according to Dr. Seth. “We had to limit the study to lend a more homogeneous analysis and make things a bit simpler at first. Within the facial data we worked with, there is a broader representation of ethnic variety. We do have an expanded dataset which we expect to publish in the future.” A sneak peek at that information? “Our data for this study we are discussing now suggests, among other things, that our perception of gender-related facial differences is much more profound than the actual objective differences,” he asserted. “We still have more work to do with the expanded dataset, but similarly, the objectively measured differences due to ethnicity are much less significant than our perception of them would suggest. Overwhelmingly, and simply put, we are much more alike than different.”

Reference:

1. Bannister JJ, Juszczak H, Aponte JD, et al. Sex Differences in Adult Facial Three-Dimensional Morphology: Application to Gender-Affirming Facial Surgery. Facial Plast Surg Aesthet Med 2022;24(5):363–368.

Editor’s Note: The original article Sex Differences in Adult Facial Three-Dimensional Morphology: Application to Gender- Affirming Facial Surgery, is open access and available online at: https://pubmed.ncbi.nlm.nih.gov/35357226/