Abstract
Oral hyaluronan has been reported to improve various aspects of skin physiology, but existing trials often lack methodological rigor, comprehensive outcome assessment, and diverse populations. This randomized, double-blind, placebo-controlled trial evaluated the effects of sodium hyaluronate (SH) supplementation at two daily doses on skin parameters in healthy Caucasian adults. A total of 150 participants were randomized to receive SH (1.8 MDa) at 60 mg/day (SH60), 120 mg/day (SH120), or placebo for 12 weeks. Facial hydration, transepidermal water loss (TEWL), sebum, elasticity, wrinkle depth, skin gloss, colorimetric parameters, epidermal thickness, dermal density, red areas, and pore size were assessed at baseline and monthly. Subjective skin condition was evaluated every two weeks, and components of natural moisturizing factor (NMF) in forearm skin were quantified by LC-MS/MS. SH120 significantly enhanced skin hydration and elasticity, while reducing TEWL, sebum, and periorbital wrinkle depth versus placebo. It also improved skin structure by increasing epidermal thickness, dermal density, and NMF levels. SH60 showed similar but more modest effects. No changes were observed for colorimetric parameters, red areas, pore size, or gloss. In conclusion, oral SH supplementation improved multiple aspects of skin physiology, supporting its use as a functional food ingredient with measurable benefits for skin health and healthy aging.Trial registration: ClinicalTrials.gov, NCT07065110 (retrospectively registered on 15 Jul 2025); EFSA (European Food Safety Authority) registry: EFSA202400027979 (prospectively filed on 06 Jun 2024).