Hyaluronic acid (HA), or hyaluronan, is a large molecule with a simple, repeating structure. Chemically, HA is a linear polysaccharide, a type of non-sulfated glycosaminoglycan, made up of alternating units of D-glucuronic acid and N-acetyl-D-glucosamine. This specific arrangement allows HA to be highly hydrophilic, meaning it has a powerful affinity for water. A single gram of HA can bind and hold several liters of water, creating a highly hydrated, gel-like substance.
The primary roles of this molecule stem from its capacity to retain moisture, provide lubrication, and offer structure. It acts as a natural shock absorber and lubricant in joint synovial fluid and is a major component of the skin’s extracellular matrix, maintaining tissue hydration and elasticity. Due to these functions, HA is a sought-after ingredient in cosmetic products, dermal fillers, and viscosupplementation for osteoarthritis. This widespread demand necessitates two distinct production methods: the body’s internal biological synthesis and large-scale commercial manufacturing.
The Body’s Natural Production of Hyaluronic Acid
The body’s production of hyaluronic acid is a dynamic, continuous biological process carried out by specialized enzymes. Synthesis occurs primarily on the inner surface of the cell membrane by integral membrane proteins called Hyaluronan Synthases (HAS). Humans possess three distinct isoforms—HAS1, HAS2, and HAS3—which create HA chains of varying molecular weights.
These HAS enzymes sequentially add two sugar precursor molecules, UDP-N-acetyl-D-glucosamine and UDP-glucuronic acid, to the growing HA chain. As the chain is built, it is simultaneously extruded through a pore in the cell membrane directly into the extracellular space. This process is most active in connective tissues; approximately half of the body’s total HA reserves are located in the skin, with high concentrations also found in the vitreous humor of the eye and joint synovial fluid.
Hyaluronic acid in the body is not static; it has a high turnover rate. An average adult carries about 15 grams of HA, and roughly one-third (about 5 grams) is broken down and resynthesized daily. This constant cycle of degradation and renewal is tightly regulated to maintain tissue structural integrity and hydration. The specific molecular weight of the HA produced determines its function; high molecular weight HA provides structural support, while lower weight fragments are often involved in cell signaling.
Commercial Manufacturing Through Bacterial Fermentation
Commercial production of hyaluronic acid for cosmetic and medical markets has evolved significantly. Historically, HA was extracted from animal tissues, such as rooster combs. This method resulted in high costs and risked contamination with animal proteins, which could trigger adverse immune reactions in human recipients and made the product less desirable for internal medical applications.
The modern industrial standard relies on microbial fermentation, a biotechnological process that produces highly pure, non-animal-derived HA. This method utilizes specific bacterial strains that naturally produce a hyaluronic acid capsule. Common organisms include certain species of Streptococcus, such as S. zooepidemicus. Genetically engineered strains of non-pathogenic bacteria like Bacillus subtilis or E. coli are also employed to enhance safety and yield.
The process begins by culturing the chosen bacteria in large fermentation tanks filled with a nutrient-rich broth containing sugar and nitrogen sources. During this growth phase, the bacteria synthesize and secrete the HA into the surrounding liquid medium. After incubation, the HA product must be meticulously separated from the bacterial cells.
The crude HA is harvested from the culture broth through filtration to remove the bacterial biomass. This is followed by a precipitation step, typically using organic solvents like isopropanol or ethanol, which causes the HA to solidify and separate from the liquid. Extensive purification steps, including ultrafiltration and activated carbon treatment, are then performed. This rigorous process removes all traces of bacterial proteins, endotoxins, and nucleic acids, ensuring the final product is a medical-grade material suitable for human injection or topical application.
A significant advantage of fermentation is the ability to control the final molecular weight of the HA. By adjusting fermentation conditions, such as pH, temperature, or precursor sugar concentration, manufacturers can steer production toward high, medium, or low molecular weight HA. This allows the product to be tailored for specific applications in cosmetics or medicine.
Dietary and Lifestyle Factors That Support HA Levels
While the body produces hyaluronic acid internally, external factors influence the efficiency of this process and the rate at which the molecule is degraded. Supporting natural HA levels involves dietary intake of necessary cofactors and protective lifestyle choices.
The enzymes responsible for HA synthesis require specific micronutrients to function optimally. For example, the HAS enzymes rely on divalent metal ions, such as magnesium, for their activity. Consuming a diet rich in mineral cofactors, including zinc and magnesium, supports the body’s natural production pathways.
Preventing the premature breakdown of existing HA is as important as supporting its synthesis. The enzyme hyaluronidase is responsible for degrading HA, and its activity can be inhibited by certain plant compounds. Flavonoids, such as naringenin found in citrus fruits, possess antioxidant properties that protect HA from free radical damage and may block hyaluronidase action.
Lifestyle factors, particularly sun exposure, also play a role in HA depletion. Exposure to ultraviolet (UV) radiation is a primary cause of accelerated HA degradation in the skin. Maintaining adequate hydration and protecting the skin from UV damage are practical ways to preserve the body’s natural HA reserves and support the regenerative cycle.