Hyaluronic Acid (Sodium Hyaluronate)
Hyaluronic Acid (Sodium Hyaluronate) — evidence, uses & status

Class: polysaccharide
Synonyms: HA
sodium hyaluronate
hyaluronan
low molecular weight HA (LMW-HA)
high molecular weight HA (HMW-HA)
INCI: Hyaluronic Acid
INCI: Sodium Hyaluronate
Function tags: skin appearance (cosmetic)
hydration
humectant
barrier support
plumping (appearance)
Overall evidence grade: A
WADA prohibited: no
Last updated: 2026-07-21

In brief: Hyaluronic acid (HA) is a naturally occurring polysaccharide that binds up to a thousand times its weight in water. As a topical cosmetic ingredient, HA reliably improves skin hydration (Grade A) and — at lower molecular weights — the appearance of fine lines and elasticity (Grade B). Higher MW forms sit on the surface; lower MW forms penetrate deeper. Effect is primarily humectant and surface-focused, not regenerative; HA does not build collagen or replace retinol, but it partners well with almost every other active. Injectable crosslinked HA is a separate medical-device category and outside the cosmetic scope.

## Identity

a large, negatively-charged **glycosaminoglycan** (polysaccharide) composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. Occurs naturally throughout the body, most abundantly in skin, joints, and eyes. In skin, HA is a major component of the extracellular matrix and dermal ground substance, holding water and maintaining tissue turgor. Endogenous HA declines with age. Used topically as sodium hyaluronate (the sodium salt, more stable in cosmetic formulations) in molecular weights ranging from ~10 kDa (very-low, deeply penetrating) through 2,000+ kDa (very-high, surface-forming).

## Development & history

- Isolated by **Karl Meyer and John Palmer in 1934** from bovine vitreous humor.
- Commercial cosmetic use began in the 1980s.
- Injectable dermal fillers (crosslinked HA) approved in the early 2000s (Restylane 2003, Juvederm 2006).
- Topical multi-molecular-weight formulations emerged in the 2010s and are now standard in premium skincare.
- Today HA is one of the most-used cosmetic ingredients globally, present in serums, creams, sheet masks, and post-procedure products.

## Mechanism (as proposed)

a humectant that binds water and holds it near the skin surface. High-molecular-weight HA forms a film on the stratum corneum, reducing transepidermal water loss and giving a smooth, plumped surface. Low-molecular-weight HA can penetrate into the upper epidermis, delivering hydration deeper and — per multi-MW clinical trials — reducing the appearance of fine lines. Very-low-MW HA fragments may signal to skin cells, though this is more relevant in wound-healing contexts than topical cosmetic use. HA is not enzymatically active on collagen or elastin — the appearance benefits come from hydration and surface effects, not from remodeling the extracellular matrix.

Evidence grades by outcome:
outcome: Topical: skin hydration (all molecular weights)
grade: A
base: Multiple placebo-controlled trials at 0.1% across MW range (50–2000 kDa); 2024 JCAD multi-weight formulation study; consistent effect across MW
effect: Measurable immediate and sustained increase in skin hydration (corneometry); onset within 30 minutes
caveat: Effect is humectant and surface-focused; depth depends on molecular weight and formulation
outcome: Fine lines and wrinkle appearance (LMW-HA 50–130 kDa)
grade: B
base: Pavicic 2011 RCT (n=76, periocular, 60 days, 5 MW compared); LMW-HA showed significant wrinkle depth reduction
effect: Visible reduction of wrinkle depth after 4–8 weeks with low-molecular- weight formulations
caveat: Effect smaller than retinoids or injectables; multi-weight formulations combine surface hydration with deeper penetration
outcome: Skin elasticity and appearance of firmness
grade: B
base: Pavicic 2011; multi-weight formulation trials
effect: Measurable improvement over 30–60 days
caveat: Modest effect; depends on formulation, MW, and delivery system
outcome: Barrier function / TEWL reduction
grade: B
base: Multiple controlled trials; multi-weight formulation studies
effect: Reduction in transepidermal water loss
caveat: Effect modest; primarily via humectant film and superficial hydration
outcome: Oral supplementation for skin hydration and wrinkles
grade: B
base: 2025 meta-analysis of 7 RCTs; Nature Scientific Reports 2025 RCT n=150 with 1.8 MDa sodium hyaluronate
effect: Statistically significant improvement in hydration, elasticity, and wrinkle depth
caveat: Outside cosmetic topical scope; not a claim for a topical serum; effect sizes modest
outcome: Injectable dermal fillers (crosslinked HA, e.g. Restylane, Juvederm, Profhilo)
grade: A
base: Decades of clinical use; multiple RCTs and systematic reviews
effect: Immediate volume restoration; effect lasts months
caveat: Medical device territory, not cosmetic; requires practitioner and falls outside 1223/2009 cosmetic scope
outcome: "Holds 1,000 times its weight in water" skin-hydration advantage
grade: D
base: Marketing claim
caveat: The 1,000:1 ratio is a laboratory property of the raw polymer measured under ideal humidity, not a measurement made in skin. Human trials measured corneometry hydration, and it improves; none measured the ratio in skin, and none showed hydration scaling with it
outcome: "Fills wrinkles from within" needle-free filler equivalence
grade: F
base: Marketing claim
caveat: Topical trials measured wrinkle depth and appearance improving through surface smoothing of hydrated upper layers. Volume restoration is documented only for crosslinked hyaluronic acid injected into the dermis, a separate medical-device category; no human study shows a topical reaching the dermis or adding volume from within
outcome: Safety (topical)
base: Decades of widespread cosmetic use across all molecular weights
effect: Very well tolerated
caveat: Occasional dryness in low-humidity environments if used without occlusive layer (humectant can pull water outward when air is dry)

Legal status:
region: INT
status: Lawful cosmetic ingredient
note: Topical Hyaluronic Acid and Sodium Hyaluronate are lawful cosmetic ingredients globally, including EU (Regulation (EC) 1223/2009). CosIng- listed. No concentration ceiling. Injectable crosslinked HA (dermal fillers) are medical devices under separate regulation (EU MDR 2017/745) and are not sold as cosmetics.

Cosmetic claims:
allowed: for the appearance of hydrated, plumper-looking skin
helps improve the look of dryness
supports a smooth, comfortable-feeling skin surface
for the appearance of a more supple, refreshed-looking complexion
forbidden: treats dry skin
repairs the skin barrier
restores dermal volume
builds collagen
reverses aging
fills wrinkles from within
regenerates skin

Note: Hyaluronic Acid and Sodium Hyaluronate are lawful cosmetic ingredients worldwide. Vallydia uses multi-molecular-weight HA in cosmetic serums with appearance-only claims. Reference science below includes topical cosmetic studies, oral supplementation trials, and injectable filler trials; only the topical cosmetic use is relevant to the sellable product.

Sources:
Pavicic T, et al. Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol. 2011; 10(9):990-1000.
Draelos ZD, et al. Clinical Evaluation of Next-generation, Multi-weight Hyaluronic Acid Plus Antioxidant Complex-based Topical Formulations. J Clin Aesthet Dermatol. 2024.
Nobile V, et al. Oral intake and topical application of hyaluronic acid ameliorates skin aging signs: efficacy results of a placebo-controlled in&out trial. Cosmetics. 2025; 12:52.
Oral sodium hyaluronate improves skin hydration, barrier function and signs of aging: a randomized, double-blind, placebo-controlled trial in 150 healthy adults. Sci Rep. 2025.
Meta-analysis (2025). Oral hyaluronic acid supplementation efficacy in skin hydration, elasticity, and wrinkle depth reduction. J Drugs Dermatol.
Zhang R, Yaqoubi M, et al. The Effect of Local Hyaluronic Acid Injection on Skin Aging: A Systematic Review and Meta-Analysis. J Cosmet Dermatol. 2024; PMC11731322.