Good evidence

Fermented Hyaluronic Acid

INCI: Lactobacillus Ferment, Saccharomyces Ferment Filtrate, Sodium Hyaluronate · also fermented HA, hyaluronic acid ferment filtrate, bioconverted hyaluronic acid

Hyaluronic acid fermented in our lab into a spectrum of sizes, so about a third of it is small enough to get past the surface and the rest holds water on top.

Why it is here

Size is the whole argument with hyaluronic acid. On Raman imaging of human skin, pieces between 20 and 300 kilodaltons crossed the outer layer and the large ones did not; in a 60-day trial, the 50 and 130 kilodalton sizes reduced wrinkle depth where larger sizes only hydrated. Fermentation gives Mixed Signals both jobs in one material.

Hyaluronic acid is a long-chain sugar that binds many times its weight in water, and skin itself breaks it into smaller fragments during repair. Our lab's fermentation does the same thing in a bioreactor with a Lactobacillus culture: the chain is cut into a range of sizes, roughly 46 percent above 1,000 kilodaltons, 19 percent between 100 and 1,000, 18 percent between 10 and 100 and 17 percent under 10, with a small fraction of peptides made by the culture along the way. The large fraction films the surface; the small fraction is in the range the human studies show getting in. In cultured skin cells the ferment also raised the cells' own hyaluronic acid synthesis by 61 percent, in our lab's assay.

The receipts

0.1 percent hyaluronic acid creams at 50, 130, 300, 800 and 2000 kDa all significantly improved hydration and elasticity against a vehicle over 60 days, and the 50 and 130 kDa sizes also significantly reduced wrinkle depth, attributed to better penetration of the smaller molecule.
Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. Journal of Drugs in Dermatology, 2011. randomized, vehicle-controlled, periocular, n = 76. PMID 22052267
Low molecular weight hyaluronic acid, 20 to 300 kDa, passed through the stratum corneum, while high molecular weight hyaluronic acid, 1000 to 1400 kDa, did not.
Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. Skin Research and Technology, 2016. Raman micro-imaging of human skin sections. PMID 25877232
Fermenting 1200 to 1300 kDa hyaluronic acid with Saccharomyces cerevisiae substantially reduced its molecular weight without changing its chemical structure, and the fermented material scavenged free radicals and raised superoxide dismutase and catalase activity in hydrogen-peroxide-stressed human skin fibroblasts through the Nrf2 pathway.
Saccharomyces cerevisiae fermentation of high molecular weight hyaluronic acid enhanced the antioxidant capacity in skin fibroblasts. Archives of Microbiology, 2025. in vitro, human skin fibroblasts. PMID 39979606

What the study actually did

Study: Pavicic T, Gauglitz GG, Lersch P, et al. Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. 2011.
Journal: Journal of Drugs in Dermatology 10:990-1000
Design: Randomized, vehicle-controlled, periocular, one formulation per eye
Subjects: 76 women aged 30 to 60 with periocular wrinkles
Concentration: 0.1% hyaluronic acid at 50, 130, 300, 800 or 2000 kDa
Duration: 60 days, twice daily
Outcome: Hydration and elasticity improved at all sizes; wrinkle depth reduced at 50 and 130 kDa

From our lab

Two peptides in one copper complex, a hyaluronic acid sorted by size, and the gentlest grade of niacinamide.

Our lab makes the copper complex as a pair: copper tripeptide-1 with Hexapeptide-11, a yeast-derived peptide with published work on the cell's own stress-defense switch. The hyaluronic acid is fermented in our bioreactors into a spectrum of sizes rather than one, because the human studies say size decides whether it gets past the surface. And the niacinamide is the low-flush grade, 20 parts per million nicotinic acid, the impurity that makes cheaper niacinamide sting.

1/3
Of the hyaluronic acid ends up under 100 kilodaltons after fermentation, the range the human studies show getting past the surface.*
+61%
More of their own hyaluronic acid made by skin cells exposed to the ferment.*
20 ppm
Nicotinic acid in our niacinamide, the flushing impurity. The gentlest grade made.

The signaling stack · Copper complex 1% and up; fermented hyaluronic acid 2 to 5%

INCI: Copper Tripeptide-1, Hexapeptide-11; Lactobacillus Ferment, Saccharomyces Ferment Filtrate, Sodium Hyaluronate; Niacinamide

*Our lab's tests of the ingredient: the size spectrum on the ferment itself, the synthesis figure in cultured skin cells.

Inside the lab

In practice

Typical use: 2 to 5 percent of a serum. The ferment is a solution, so the hyaluronic acid itself is a fraction of that.
Pairs with: Niacinamide, Copper Tripeptide-1, Glycerin
Keep apart from: Nothing. It is a humectant and gets along with everything.
Cautions: None notable. In very dry air, any humectant-heavy layer wants an occlusive over it, which is what Baby's Bottom is for.

Questions people ask

Is smaller hyaluronic acid always better?

No. The large sizes hold water on the surface, which is most of what people like about hyaluronic acid. The small sizes are the ones with the wrinkle-depth data. A spectrum does both, which is why we ferment rather than pick one size.

Is this the same as hydrolyzed hyaluronic acid?

Same goal, different route. Hydrolysis cuts the chain with acid, enzymes or heat to a target size. Fermentation lets a culture do it, which yields a spread of sizes plus the peptides the culture makes. Ours is fermented, and the label says so.