Hyaluronic acid

Hyaluronic acid

Sodium Hyaluronate

Hyaluronic Acid is a naturally occurring glycosaminoglycan found in the extracellular matrix of human connective tissue, skin, and synovial fluid. In dermatology and skincare, it is recognized as one of the most effective humectants due to its exceptional ability to retain water—binding up to 1,000 times its weight in moisture. While endogenous levels of hyaluronic acid decline with age, topical and injectable forms are widely used to support skin hydration, barrier function, and elasticity.

Its efficacy varies depending on its molecular weight, with high-molecular-weight forms acting primarily on the skin surface and low-molecular-weight variants penetrating deeper into the epidermis. Hyaluronic acid is now a cornerstone in evidence-based cosmetic and dermatological formulations for treating dryness, fine lines, and loss of firmness, supported by extensive clinical research.

Hyaluronic acid

Manuela Valenti

Common Name

Hyaluronic Acid, Sodium Hyaluronate, HA

INCI

Hyaluronic Acid, Sodium Hyaluronate (salt form)

Extraction or Production Process

Originally sourced from animal tissues such as rooster combs, modern production of hyaluronic acid for cosmetic and medical applications is primarily via biotechnological fermentation using Streptococcus zooepidemicus, a non-pathogenic bacterial strain.

  1. Fermentation: Bacteria are cultured under controlled conditions to produce hyaluronic acid extracellularly.
  2. Purification: The fermented broth is filtered and purified to remove microbial residues and proteins.
  3. Precipitation and Drying: The purified HA is precipitated (commonly using ethanol or isopropanol), dried, and milled into a powder.
  4. Molecular Weight Control: Final processing may include enzymatic or acid hydrolysis to obtain different molecular weights, from high (HMW-HA) to low (LMW-HA) or even ultra-low molecular weight (ULMW-HA), each with different skin penetration characteristics.

Sources

  • Microbial fermentation using Streptococcus zooepidemicus or Bacillus subtilis
  • Historically extracted from animal cartilage or rooster combs (rare in current cosmetic formulations due to allergen and ethical concerns)

Country of Origin

  • Widely manufactured in Japan, South Korea, France, China, and the United States
  • Commercial-grade hyaluronic acid is produced for both medical (injectables, eye drops) and cosmetic industries

Function

  • Humectant: Binds up to 1,000 times its weight in water, increasing skin hydration
  • Skin Conditioning Agent: Enhances suppleness, reduces roughness, and improves skin texture
  • Barrier Support: Helps maintain stratum corneum integrity and reduces transepidermal water loss (TEWL)
  • Wound Healing Agent: In medical use, accelerates epithelial repair and regeneration

Properties

  • Molecular Weight Dependent Function:
    • High MW (1,000–2,000 kDa): Forms a protective film on the skin surface
    • Low MW (50–300 kDa): Penetrates more deeply, providing hydration in lower epidermal layers
    • Very Low MW (<50 kDa): May stimulate cytokine expression; controversial in long-term use due to potential for pro-inflammatory response
  • Non-comedogenic
  • Biocompatible and biodegradable
  • Colorless and odorless
  • Viscoelastic when dissolved in water

Benefits

  • Enhanced Skin Hydration: Proven in multiple clinical trials to increase hydration in the stratum corneum after topical application.
  • Reduction in Wrinkle Depth: Studies have shown that topical HA formulations (particularly LMW and cross-linked types) reduce wrinkle appearance and increase skin elasticity.
  • Improved Wound Healing: Facilitates keratinocyte proliferation and migration during tissue repair.
  • Improved Barrier Function: Reduces TEWL and improves epidermal resilience in both dry and aged skin.

Contraindications and Precautions

  • Generally well-tolerated, even in sensitive skin.
  • Rare cases of irritation or erythema have been reported, typically linked to formulation pH or preservatives rather than HA itself.
  • Very low molecular weight HA (<20 kDa) may trigger mild pro-inflammatory responses due to cytokine induction in some individuals; more research is ongoing
  • Product Stability: HA is hygroscopic and can degrade if not stored in air-tight, low-humidity, and light-protected packaging.
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    1. Papakonstantinou, Eleni, Michael Roth, and George Karakiulakis. “Hyaluronic Acid: A Key Molecule in Skin Aging.” Dermato-Endocrinology, vol. 4, no. 3, 2012, pp. 253–258. https://doi.org/10.4161/derm.21923
    2. Pavicic, Tatjana, et al. “Efficacy of Cream-Based Novel Formulations of Hyaluronic Acid of Different Molecular Weights in Anti-Wrinkle Treatment.” Journal of Drugs in Dermatology, vol. 10, no. 9, 2011, pp. 990–1000. https://pubmed.ncbi.nlm.nih.gov/21980732/
    3. Ghersetich, I., et al. “Hyaluronic Acid in Cutaneous Intradermal Therapy.” Journal of the European Academy of Dermatology and Venereology, vol. 22, no. 3, 2008, pp. 308–311. https://doi.org/10.1111/j.1468-3083.2007.02507.x
    4. Mine, Satoshi, et al. “Hyaluronic Acid Induces the Release of Inflammatory Cytokines from Fibroblasts.” Journal of Dermatological Science, vol. 64, no. 3, 2011, pp. 199–205. https://doi.org/10.1016/j.jdermsci.2011.09.009
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