This article, from C&T's upcoming February 2025 edition, compares the efficacy of a bio-retinoid from microalga with that of retinol and bakuchiol to reverse signs of photoaging in vitro. Its efficacy, safety and skin-soothing effects vs. retinol and bakuchiol are also explored in clinical trials.
In the sprawling landscape of skin care innovations, few ingredients have garnered as much attention and acclaim as retinol. Renowned for its potent anti-aging properties, retinol has been a cornerstone of skin care routines worldwide, promising to diminish wrinkles, refine texture and impart a youthful radiance to the complexion.
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This article, from C&T's upcoming February 2025 edition, compares the efficacy of a bio-retinoid from microalga with that of retinol and bakuchiol to reverse signs of photoaging in vitro. Its efficacy, safety and skin-soothing effects vs. retinol and bakuchiol are also explored in clinical trials.
In the sprawling landscape of skin care innovations, few ingredients have garnered as much attention and acclaim as retinol. Renowned for its potent anti-aging properties, retinol has been a cornerstone of skin care routines worldwide, promising to diminish wrinkles, refine texture and impart a youthful radiance to the complexion.
Despite its proven efficacy in combatting the signs of aging, retinol comes with a well-known laundry list of potential side effects that can deter even the most dedicated skin care enthusiasts. From redness and flaking to increased sensitivity and dryness, the journey to youthful skin can often feel like a trade-off between visible results and comfort. Furthermore, retinol's instability presents a formidable challenge for skin care formulators, requiring sophisticated stabilization techniques to maintain its potency and efficacy.
Consequently, in recent years, bakuchiol has emerged as a promising alternative to retinol in the skin care industry. Bakuchiol, derived from the seeds of the Psoralea corylifolia plant, has been shown to offer a compelling alternative. Its efficacy is often said to be comparable to retinol and it is known to be particularly efficient at treating acne-prone skin.
However, it comes with issues as well, as readers may know. Bakuchiol can impart a strong color when added to products, posing a formulation challenge. The availability of high-quality bakuchiol also remains limited. Nonetheless, bakuchiol's rise in popularity underscores the growing demand for effective yet gentle alternatives to traditional retinol formulations.
In response to the limitations of traditional retinol1 and bakuchiol, researchers turned to nature in search of alternative solutions. Among the most promising recent discoveries is a “bio-retinoid” derived from a sustainable strain of Chlorella vulgaris microalgaa. The ingredient is powered by marine apocarotenoids from xanthophyll, a class of compounds found in certain microalgae.
These apocarotenoids bear striking structural similarities to retinoic acid, the active form of vitamin A in skin, allowing them to bind to and activate retinoid receptors. Combined with a proprietary delivery system, the structural analogues can penetrate the skin to target specific receptors and deliver visible improvements, e.g., in wrinkles, texture, tone and overall appearance.
The present article provides a brief background on retinoids and retinoic acid receptors before delving into the bio-retinoid’s activities. In vitro studies compare the efficacy of the ingredient with that of retinol and bakuchiol for anti-aging and skin-brightening benefits. Clinical trials also assess the bio-retinoid’s safety and efficacy in comparison with retinol and bakuchiol.
Retinoids, Retinoic Acid Receptors and Marine Apocarotenoids
The transformative potential of the novel bio-retinoid hinges on understanding the structure of retinoids and their interaction with Retinoic Acid Receptors (RARs). Retinoids, including retinoic acid, consist of a cyclic end group, a polyene side chain and a polar end group that is crucial for engaging RARs expressed throughout the skin. Three RAR isoforms — α, β and γ — exhibit distinct expression patterns, with α and γ mainly in the epidermis and β in the dermis. The activation of RAR receptors by retinoic acid is what regulates genes linked to cell differentiation and proliferation.
Traditionally, first- and second-generation retinoids bind flexibly to multiple receptors. Third-generation retinoids are less flexible and interact with fewer receptors. Trifarotene, a fourth-generation retinoid, selectively binds to the RAR-γ receptor. Recent studies2 highlight that receptor selectivity allows for a more targeted therapeutic effect, requiring lower retinoid concentrations. This addresses some of the challenges with conventional retinoid therapies, especially for sensitive skin.
In contrast, retinol is a first-generation retinoid with the potential to bind to multiple receptors. This can cause the irritation for which retinol is well-known – also known as retinol burn or retinoid dermatitis. Notably, research shows2, 3 that RARα and RARγ receptors, particularly in the stratum corneum, play crucial roles in retinol burn development. They promote skin inflammation, disrupt barrier function and induce growth arrest and apoptosis upon retinoic acid stimulation.
As described earlier, central to the bio-retinoid of interest are marine apocarotenoids derived from microalgae xanthophyll. They bear structural similarities to retinoic acid (see Figure 1 below), the active form of vitamin A in the skin, which allows them to bind to and activate retinoid receptors with precision. Notably, these apocarotenoids exhibit a high degree of selectivity, primarily targeting RARβ, which supports skin-modeling benefits. This selectivity likely stems from their unique molecular structure, which complements the binding pocket of RARβ more precisely than other RAR subtypes. This structural complementarity allows these compounds to achieve targeted activation of RARβ, potentially leading to more specific skin-modeling effects with reduced off-target interactions. This activation was explored in vitro as follows.
In vitro Materials and Methods: RARβ Selectivity, Anti-aging
Test ingredient: As noted, the active fraction of the bio-retinoid is encapsulated in a proprietary delivery system of pharmaceutical-grade liposomes coated with a marine biopolymer (derived from the same microalgae). This structure is designed to ensure the actives reach their target receptors in the skin intact, maximizing their efficacy and stability while also minimizing the risk of degradation or any irritation.
Selective receptor activation: The modulation of the RARβ receptor was validated through a cell-based nuclear receptor profiling assayb. This assay employed an engineered UAS-bla HEK 293T cell line expressing RARα, RARβ or RARγ to evaluate the action of the active ingredient. The assay uses a technologyc incorporating a mammalian-optimized beta-lactamase reporter gene (bla) combined with a FRET-enabled substrate. This provides a sensitive detection method for assessing specific receptor activation by measuring changes in the blue/green fluorescence ratio. Such comprehensive profiling provided valuable insights into the specificity and potency of the active ingredient's interaction with RARβ and the other retinoic acid receptors.
Results (see Figure 2, below) demonstrated the bio-retinoid selectively activated the RARβ receptor in a dose-dependent manner. This selective binding ensures the precise modulation of gene expression, promoting the skin-remodeling and rejuvenation benefits associated with potent retinoids while also minimizing potential side effects caused by RARα and RARγ activation.
Effects on anti-aging, skin-benefit targets: Additional in vitro studies compared the effects of 1% bio-retinoid with those of 1% bakuchiol and 0.15% pure retinol on anti-aging targets including: hyaluronic acid (HA), collagen synthesis and MMP-1 expression, melanin production and cell proliferation.
Hyaluronic acid production in human dermal fibroblasts culture supernatants were measured by the enzyme-linked immunosorbent assay (ELISA) method. Collagen synthesis was measured in a dermal skin model by immunohistochemistry analysis of Collagen I and III. In this same in vitro study, the supernatant of the cell culture served as the medium for quantifying MMP-1 levels using the ELISA method.
Another separate in vitro study was conducted on human epidermal melanocytes. At the end of the experimental time, the cells were used for the determination of melanin content with a fluorimetric commercial kit. Lastly, yet another in vitro study was carried out using human skin fibroblasts to evaluate the ingredient’s cell proliferation activity, monitored using MTT-assay.
The results showed the novel bio-retinoid at 1% outperformed both retinol at 0.15% and bakuchiol at 1% for all variables, increasing HA production, cell proliferation and collagens I and II, and decreasing MMP-1 and melanin (see Table 1, below).
Clinical Efficacy for Anti-aging, Skin Benefits
To evaluate the in vivo efficacy and safety of the bio-retinoid, three clinical studies were conducted to compare its efficacy versus retinol, versus bakuchiol and in combination with retinol versus retinol alone.
Bio-retinoid versus retinol: Two test creams – comprising water (aqua), coco-caprylate/caprate, glycerin, phenoxyethanol, ethylhexylglycerin, sodium acrylate/sodium acryloyldimethyl taurate copolymer, hydrogenated polydecene, trideceth-6, sorbitan laurate and disodium EDTA – were developed containing either 2% bio-retinoid or 0.3% pure retinol (= 2% commercial retinol). Thirty subjects applied both products, one to each side of their faces, for 56 days. Evaluations were made for photoagingd, e and hyperpigmentationf, g after 7, 14, 28 and 56 days of test cream application (see Table 2, below). Examples of the bio-retinoid’s effects against hyperpigmentation are shown in Figure 3, below.
Bio-retinoid versus bakuchiol: Another double blind, randomized study using the same base cream compared the bio-retinoid’s efficacy against that of bakuchiol (> 99.8% pure) in acne-prone skin. In this case, 30 participants with acne-prone skin applied a test product containing 1% bio-retinoid and 1% bakuchiol each to one side of the face for 28 days. Assessments were made – for frequency and severity of breakouts, as clinically evaluated by a dermatologist; sebum contenth; pore sizee; skin moisturej; and skin rednessk – after 7, 14 and 28 days (see Table 3 below).
Considering the observed improvement in hydration, the skin-soothing effects of the bio-retinoid versus bakuchiol were compared, dermatologically measured by overall skin redness as indicator of irritation. As Figure 4, below, shows, after 14 days of treatment and measured by clinical assessment, overall skin redness decreased by 84% with the bio-retinoid, versus a 23% decrease with bakuchiol.
Bio-retinoid + retinol blend versus pure retinol: Finally, a third clinical study was carried out to determine the effects of the bio-retinoid + low-dose retinol, compared with retinol alone. The goal was to determine whether the two could act synergistically, leveraging each other’s strengths and mitigating irritation potential while also respecting the regulatory limits set on retinol.4
In this case, 30 participants applied the same base cream containing either 1% bio-retinoid + 0.1% pure retinol blend or 0.5% pure retinol alone, each to one side of the face for 28 days. Measurements were made for photoagingm, n, hyperpigmentationf, g and skin tolerabilityp after 7, 14 and 28 days of use (see Table 4, below).
Considering the potential for retinol irritation, the soothing effects of the blend versus pure retinol also were tested, again as indicated by skin redness (see Figure 5, below). The images takenp showed the blend reduced redness while retinol alone increased redness after only one application.
Taken together, the combined bio-retinoid + low-dose retinol improved the skin parameters evaluated (i.e., wrinkle depth, firmness and elasticity) better than retinol alone, and without increased redness (i.e., irritation). Subjects additionally reported, in a self-assessment conducted after 56 days of use, that they experienced smoother, plumper skin with visibly reduced fine lines and wrinkles and no irritation (not shown).
Discussion and Conclusion
These findings mark a significant advancement in skin care, promising:
- effectiveness,
- safety and
- innovation.
By providing a viable alternative to traditional retinol that delivers similar results without the common side effects, the bio-retinoid highlighted here could redefine anti-aging skin care standards.
Not only does it open up new options for consumers seeking gentle yet effective skin care, it serves as a genuine retinol alternative, aiding brands in meeting regulations while maintaining or enhancing performance – and if used in combination with retinol, potentially retaining its label claim. The bio-retinoid ultimately offers a path to a brighter, more radiant future for skin of all ages.
Footnotes
a Algaktiv RetinART (INCI: Water (Aqua) (and) Propanediol (and) Algae Oligosaccharides (and) Xanthophylls (and) Lactic Acid) is a product of Algaktiv.
b Conducted by SelectScreen Cell-Based Nuclear Receptor Profiling Service
c GeneBLAzer
d R0 and R2 parameters by Cutometer and skin profilometry
e Pore size and wrinkle depth by PRIMOS 3D
f ITAº value by spectrophotometer/colorimeter
g Clinical evaluations by a dermatologist
h Sebumeter
j Corneometer
k Mexameter 18
m R0 and R2 parameters by Cutometer
n Wrinkle depth by PRIMOS 3D
p RBX RED VISIA imaging and self-assessment
References
1. Kawczak, P., Feszak, I., Brzeziński, P. and Bączek, T. (2024, May 10). Structure-activity relationships and therapeutic applications of retinoids in view of potential benefits from drug repurposing process. Biomedicines, 12(5) 1059; doi: 10.3390/biomedicines12051059. PMID: 38791021; PMCID: PMC11117600.
2. Gericke, J., Ittensohn, J., Töröcsik, D., et al. (2013). Regulation of retinoid-mediated signaling involved in skin homeostasis by RAR and RXR agonists/antagonists in mouse skin. PLoS ONE, 8(4) e62643; https://doi.org/10.1371/journal.pone.0062643.
3. Chapellier, B., Mark, M., ... Chambon, P., et al. (2002, Jul 1). Physiological and retinoid-induced proliferations of epidermis basal keratinocytes are differently controlled. EMBO J, 21(13) 3402-13; doi: 10.1093/emboj/cdf331. PMID: 12093741; PMCID: PMC125394.
4. CTPA. (2024, Jul 11). 9 Cosmetic ingredient bans/restrictions in the EU: Kojic acid, 4-MBC, retinol, arbutin and more. Cosmetics & Toiletries. Available at https://www.cosmeticsandtoiletries.com/regulations/regional/news/22913539
