During my medical training, we internal medicine doctors used to kid our dermatology colleagues:
“There’s not much to being a dermatologist. If it’s dry, moisten it; if it’s moist dry it; and if all else fails, put some steroid cream on it.”
And I might add, “If it looks funny, biopsy it”.
I’ve long said that what skin needs is not fancy potions applied externally; rather, healthy skin requires a lube job from within. Like with fish oil, borage oil, tocotrienols, astaxanthin, collagen and vitamin D.
But lately, some promising research about innovative natural topical treatments for skin has caught my eye:
Melatonin is one of them. Underappreciated is melatonin’s role beyond supporting sleep and rejiggering circadian rhythm when challenged by jetlag. It’s also a potent antioxidant.
It turns out that skin cells are extraordinarily rich in mitochondria, responding to the energy and protein synthesis demands of constant epidermal turnover. Surprisingly, their mitochondria produce large amounts of melatonin.
It turns out that melatonin topical application might confer skin benefits. According to a recent review:
“Topically applied melatonin may penetrate the stratum corneum and form a depot there due to its distinct lipophilic chemical structure. The application of melatonin on the skin is a very good option for retarding the aging process and reducing the hallmarks of skin aging. The cutaneous application of melatonin is efficacious and safe way to improve the clinical signs of aging (wrinkles, TEWL [Transepidermal water loss, an objective measurement of skin integrity] and hydration, skin roughness, sagging, etc.). Clinically, it is better to apply melatonin at nighttime when the skin permeability is higher and because melatonin can mimic its endogenous production and effects.”
What about oral melatonin? The authors conclude: “Orally supplemented melatonin appears in rather low levels in the blood due to prominent first-pass degradation in the liver, thus limiting skin access.” They add:
“With its pleotropic protective function of the skin, melatonin, with its proven beneficial anti-aging properties, could be considered as a therapeutic candidate for retarding skin aging and reversing cutaneous aging signs. Therefore, endogenous intracutaneous melatonin production, together with topically applied exogenous melatonin, is expected to provide the most potent defense system against cutaneous photodamage and multiple other pathological conditions that produce oxidative stress (e.g., in chronic skin inflammation, such as atopic dermatitis). Additionally, topical melatonin can be used for the treatment of androgenic alopecia in women.”
i.e., What’s good for the skin, by logical extension, is likely to be helpful for the scalp.
And while on the theme of skin mitochondria, one of the proven ways to rev them is via exposure to near-infrared light. In contrast to the Ultraviolet B portion of the sun’s light spectrum, red light—even below the threshold of human visual perception—generated by exposure to sunlight or to artificial infrared lighting, has been shown to confer skin benefits:
“Our results further suggest that IR radiation may result in beneficial effects on skin texture and wrinkles by increasing collagen and elastin in the dermis through stimulation of fibroblasts . . . it may have some use as a supportive method in the treatment of photo-aged skin.”
A plethora of devices are now marketed attempting to harness this potential—even red light diode-equipped scalp caps—but it remains unclear what precise frequencies, intensities or duration of exposure work best.
Urolithin A is another promising compound for topical application. Known as the active ingredient in Mitopure®️—one of our sponsors—its claim to fame is, as with melatonin and infrared, mitochondrial support. By enhancing mitophagy—the editing process by which defective mitochondria are eliminated—urolithin A supports cellular energy metabolism. Why not apply that principle to skin?
And, indeed, that’s what researchers have explored. A 2023 review (“Topical application of Urolithin A slows intrinsic skin aging and protects from UVB-mediated photodamage: Findings from Randomized Clinical Trials”) found that:
“Taken together, these clinical studies support the topical use of Urolithin A to manage and prolong skin health longevity by acting at the cellular level, supporting collagen structure, reducing wrinkle appearance and protecting against photoaging.”
Timeline, the maker of Mitopure®️, offers a variety of skin care products delivering urolithin A.
CBD (cannabidiol) applied externally has demonstrated its ability to address minor injuries; I sometimes use it to soothe sore muscles and joints. It also boasts distinct anti-inflammatory properties. While acknowledging the paucity of large, high-quality trials, Japanese researchers have concluded:
“Cannabidiol has attracted growing attention in the cosmetic industry, with an increasing number of CBD-containing skincare products on the market in recent years . . . Available in vitro and in vivo evidence suggests that CBD has anti-oxidant, anti-inflammatory, moisturizing, anti-acne, wound-healing, and anti-aging properties.”
CV Sciences, one of our sponsors, offers a variety of topical CBD products.
Epigallocatechin gallate (EGCG) is a polyphenol found in green tea, now a popular antioxidant supplement.
A 2018 review found:
“ . . . these results suggest that EGCG might be used as a cosmetic ingredient with positive effects on skin hydration, moisture retention, and wrinkle formation, in addition to radical scavenging activity.”
A prescription form of topical EGCG (Sinecatechins 15% ointment, trade name Veregen®) is even approved for external application for the treatment of genital and peri-anal warts caused by HPV.
Collagen is the ground substance that holds moisture and provides elasticity in connective tissue throughout the body. Its utility for retarding skin aging has been extensively studied:
“ . . . collagen is considered crucial for skin health because both photo-aging and intrinsic aging decrease its presence in the body . . . Both oral and topical collagen can contribute to reducing or delaying skin aging.”
Brightcore Nutrition, one of our sponsors, offers collagen masks as well as high-quality oral collagen.
Resveratrol has been proposed as an anti-aging elixir, but the efficacy of oral supplementation for extending longevity has been challenged by recent negative trials. Nonetheless, its potent natural antioxidant properties make it a candidate for topical application. A recent reviewconcluded:
“ . . . it protects the skin against the harmful effects of type B ultraviolet radiation, which is the main factor in the skin aging processes. It also enhances collagen synthesis by activating the oestrogen receptor and reduces wrinkles. In damaged tissues, it accelerates skin regeneration and healing by activating, among others, VEGF [vascular endothelial growth factor].”
Grapeseed extract, rich in proanthocyanidins, has been studied for its ability, in a topical form, to promote surgical wound healing:
“ . . . its anti-inflammatory and anti-microbial properties are effective.”
An evaluation of a proprietary form of grapeseed extract found:
“Clinical assessment of E-AGSE showed that it reduces the appearance of wrinkles, brightens the skin, and boosts hydration.”
Pycnogenol®️, a patented maritime pine bark extract, is an alternate source of proanthocyanidins. Its protective effects on brain, circulatory system, eyes, and joints have been validated by multiple studies. In a double-blind placebo-controlled trial:
“Pycnogenol®’s effects on the skin of 78 urban outdoor workers was investigated. Water loss of the skin during the hot summer season was significantly reduced by 14% with Pycnogenol® supplementation for three months and only by 5% with placebo. Accordingly, skin elasticity was shown to be improved by 13% after supplementation, compared to an increase of 1% in the placebo group.”
While this was a study of oral supplementation, as is the case with many of the above skin agents, there’s ample rationale for incorporation of Pycnogenol®️ in topical formulations as part of an “inside-out” strategy for skin protection.
Exosomes are all the rage in pricey skin care formulas these days, so I decided to take a look.
They are tiny vesicles—essentially miniscule “baggies”—that package proteins for intercellular transport. These proteins convey information that regulate various cell functions, including growth, repair and autophagy. Exosomes are a hot topic in research; their regenerative potential has even been proposed as a way of forestalling Parkinson’s Disease.
An extensive review details the way specific exosomes harvested from mesenchymal, bone marrow, umbilical or adipose tissue stem cells can help skin:
“Exosomes have many beneficial effects for skin care as they contain various biological molecules that can help to promote skin repair and regeneration . . . Exosomes are able to deliver various bioactive compounds into the skin cells, which can effectively delay skin aging and inhibit photoaging signatures . . . Exosomes can be delivered to skin through various invasive and non-invasive methods. In the non-invasive treatment exosomes are incorporated into topical creams, serums, oils, and masks to cover and protect skin.”
The challenge for consumers is to sort through the hype and discern which exosome products deliver bona fide benefits; many offerings may tout a smattering of exosome-like ingredients as window dressing for pricey potions of little efficacy. Exosomes are also a premium offering at luxury cosmetology clinics and longevity spas, with little regulation. But rest assured, exosomes are a hot topic in research these days, and there are sure to be refinements. Stay tuned!
Add all the above to previously-acknowledged topical skin stalwarts like vitamins C, E, retinol vitamin A, hyaluronic acid, coconut oil . . . and you have a lot of natural options for skin rejuvenation!