# Efficacy and Safety of Amino Acid–Enriched Hyaluronic Acid in Facial Rejuvenation: A Systematic Review and Meta‐Analysis

**Authors:** Maite Mosteirin, Ava Guila Ardila, Raúl Gil Calomarde, Gonzalo Mariscal

PMC · DOI: 10.1111/jocd.70741 · Journal of Cosmetic Dermatology · 2026-02-22

## TL;DR

This study finds that hyaluronic acid enriched with amino acids improves skin appearance and thickness, with a good safety profile for facial rejuvenation.

## Contribution

The study provides a systematic evaluation of amino acid–enriched hyaluronic acid for facial rejuvenation, combining efficacy and safety data.

## Key findings

- Treatment significantly reduced wrinkle severity and improved aesthetic appearance.
- Dermal thickness and cell viability were significantly increased post-treatment.
- Adverse events were reported but not statistically significant.

## Abstract

Skin aging, marked by wrinkles, volume loss, and reduced hydration, has driven growing interest in minimally invasive aesthetic treatments to restore skin quality and appearance. This study aimed to evaluate the efficacy and safety of an injectable formulation combining hyaluronic acid (HA) and amino acids (AA) for facial rejuvenation in adults.

A systematic review and meta‐analysis was conducted according to the PRISMA guidelines using PubMed, EMBASE, Scopus, and the Cochrane Library. Eligible studies compared HA + AA complexes with conventional HA or a placebo. The primary efficacy outcomes were changes in wrinkle severity (WSRS), aesthetic improvement (GAIS), skin thickness, and epidermal growth factor (EGF)‐positive cell viability. Safety was assessed by adverse event reporting.

This meta‐analysis included 11 studies that met the inclusion criteria. A significant reduction in wrinkle severity was observed on WSRS following treatment (MD, 2.15; 95% CI, 2.00–2.30; p < 0.0001). Global aesthetic improvement demonstrated a marked enhancement at 3 months (MD = 3.13; 95% CI = 1.94–4.33; p < 0.00001). Dermal thickness significantly increased post‐treatment (MD = −0.42 mm; 95% CI = −0.55 to −0.30; p < 0.00001). Cell viability improved significantly (MD = −24.00; 95% CI = −25.16 to −22.84; p < 0.00001). There was a statistically significant difference in adverse events (RR = 5.20; 95% CI = 0.53–50.77; p = 0.16).

Amino acid–enriched hyaluronic acid improves wrinkle severity, dermal thickness, and cell viability, enhancing overall skin aesthetics. Larger prospective studies are needed to confirm these findings.

## Full-text entities

- **Genes:** EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}
- **Diseases:** edema (MESH:D004487), pain (MESH:D010146), GAIS (MESH:C538175), inflammatory reactions (MESH:D007249), volume loss (MESH:D016388), cytotoxicity (MESH:D064420), Wrinkle (MESH:D019773), erythema (MESH:D004890), tenderness (MESH:D063806), granulomas (MESH:D006099)
- **Chemicals:** DVS (MESH:C009873), polysaccharide (MESH:D011134), PEG (MESH:D011092), proline (MESH:D011392), BDDE (MESH:C014376), glycine (MESH:D005998), HA (MESH:D006820), water (MESH:D014867), AA (MESH:D000596), ACHA (MESH:C050057), 1,4-Butanediol Diglicil Ether (-), ROS (MESH:D017382), lysine (MESH:D008239)
- **Species:** Meleagris gallopavo (common turkey, species) [taxon 9103], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12926521/full.md

## References

20 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926521/full.md

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Source: https://tomesphere.com/paper/PMC12926521