In recent years, a variety of new active/hero ingredients have been shown to perform better than the old standbys in a variety of dermatological conditions. This is extremely exciting news as most of these ingredients are all-natural and have limited downsides/side effects, if any.
Anti-Aging: Retinol is Being Challenged
Retinoic acid (tretinoin) has compelling evidence of efficacy, but it must be prescribed and it has many downsides (a “break-in” period, photo-sensitivity, PM application only, inability to pair well with other actives) and many women (and men) do not tolerate it well, resulting in irritation and redness. Retinol is the light-duty version of retinoic acid (no Rx needed and ~1/3 the potency), but the same downsides exist. Pregnant and lactating women should avoid both.
Y100 is a newly introduced hero ingredient (brought to you by YuvaBiosciences) that is all natural. When loaded into Z-pods (which provides sustained delivery of the Y100, up to 24 hours), the dynamic duo has similar efficacy levels of retinoic acid and three times the efficacy level of retinol (~60% reduction in wrinkles and ~55% improvement in elasticity vs. about 20% on both for retinol). The Y100-loaded Z-pod has no known downsides, however: It is for all skin types and all skincare regimens (i.e., no pairing issues) … plus no irritation, AM and/or PM application, vegan, and pregnancy/lactation safe. The statistically significant data were from a split-face-designed double-blind study with 35 subjects conducted by Eurofins in Poland.
Acne: Evidence for NAD and Nitric Oxide (N.O.)
NAD (nicotinamide adenine dinucleotide) is starting to be recognized as a possible player in acne. NAD is a dinucleotide, meaning it's composed of two nucleotides linked together: One nucleotide contains adenine, and the other contains nicotinamide (aka niacinamide), a form of vitamin B3. It is anti-inflammatory; it inhibits melanosome transfer; and it reduces sebum.
Supporting data are from a 2024 split-face, double-blind randomized controlled trial from Thailand of 40 patients with mild-to-moderate acne vulgaris. The addition of a moisturizer containing niacinamide to a standard acne regimen (5% benzoyl peroxide plus 0.1% adapalene gel) produced a statistically significant reduction in total acne counts at 8 weeks compared with the control group.
Nitric oxide, on the other hand, is a tiny molecule that our bodies make (but less and less as we age); it is anti-inflammatory and anti-microbial. Novan Inc. showed in a Phase 3 study that a sustained-release version of N.O.—by itself—can significantly reduce acne counts.
Atopic Dermatitis (AD): Barrier Repair a Cornerstone
Biologics are now used for severe cases of AD, but this is overkill for mild-to-moderate cases. In AD lesions, ceramide levels are reduced, and the carbon-chain lengths of certain ceramide classes become shorter.
Recently, urea and NAD have been shown to increase the biosynthesis of ceramide and help replenish and restore the skin’s moisture barrier.
The new wonderkind on the block is the aforementioned Y100-loaded Z-pods. The Y100 restores mitochondrial function, and the Z-pods—100% comprised of amorphous silica—make up for the body’s decreasing ability to make its own silica, which is required to maintain collagen and a proper skin-barrier function. In addition, silica is a powerful adsorbent, so it works to increase the water content of the stratum corneum, also contributing to an optimized skin barrier function.
Melasma: Hydroquinone Alternatives
A prescription-only cream containing fluocinolone acetonide (a corticosteroid), hydroquinone, and tretinoin is FDA-approved for moderate-to-severe melasma and is considered reasonably effective. But satisfactory results can take many months and breaks in use are urged due to possibly dangerous side effects associated with long-term continuous use.
During these breaks, new-kids-on-the-block actives such as cysteamine, which has demonstrated reductions in Melasma Area and Severity Index (MASI) scores, and thiamidol should be considered.
Thank you to Medscape and Randy Dotinga for their 9/11/2025 online article, “Which Cosmeceuticals Are Backed Up by Research?”