Hyaluronic Acid

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    Last Updated: September 5, 2023

    Hyaluronic acid (HA) is a large polysaccharide that is found naturally throughout the body and in high concentrations in the skin, the joint fluid, and the eye. It plays a role in many important bodily functions, including wound healing, joint lubrication and ovulation. As a supplement, it is most frequently used for joint health, to treat dry eyes, and in anti-aging products for the skin.

    Hyaluronic Acid is most often used for .

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    3,691 participants in trials and 12 meta-analyses

    What is hyaluronic acid?

    Hyaluronic acid is a mucopolysaccharide that is part of a family called the glycosaminoglycans. These long-chain sugar molecules appear naturally in cell membranes throughout the human body, and help with hydration of tissues and other important cell functions. For supplementation, hyaluronic acid may be produced using animal sources, but can also be isolated from fermented bacteria.[4]

    What are hyaluronic acid’s main benefits?

    HA is useful in several branches of medicine. Ophthalmologists use it in the treatment of dry eye syndrome,[2] orthopedics specialists use it for different types of arthritis and joint pain,[5][6][7] and aesthetic practitioners use HA in fillers.[8] It seems to have potential in other areas, too, such as wound healing and the treatment of burns.[9][10] In all of these applications, HA helps with hydration, lubrication, and tissue regeneration. High-molecular-weight HA is produced in healthy cells. Molecular weight is measured in daltons, which is the unit used to express the weight of atoms and larger molecules. A high molecular weight for HA is above 2000 kilodaltons (kDa). High-molecular-weight HA is associated with anti-inflammatory effects, and seems to slow down immune responses.[11] Other potential uses that are being looked into include alopecia treatments, regeneration of nerves in peripheral neuropathy, and use of HA in vascular grafts to help with healing.[12][13]

    What are hyaluronic acid’s main drawbacks?

    Since hyaluronic acid is found within the body and is naturally produced in the cell walls, it is biocompatible and rarely causes any adverse effects. In products made from animal sources, the potential for an allergic reaction exists, but is unlikely.[10][4] One potential drawback of endogenous HA is that cancer cells may also produce high-molecular-weight HA. In these cells, the regenerative properties of HA support tumor growth by improving blood supply and can even protect the tumor from anticancer drugs. Some cancer treatments therefore include hyaluronidase to break down HA so that the medication can reach the tumor.[4] At very low molecular weights, measured as 40 KDa and below, HA can be a sign of stress and may be associated with inflammation.[10]

    How does Hyaluronic Acid work?

    HA is a large hydrophilic molecule. When it is released from cells, it binds water, and this helps with hydration of the cells. It also attracts fluid into the synovial fluid of the joints and the vitreous fluid in the eye, hydrating and lubricating these areas. When it is produced by cells, HA is a long molecule with a high molecular weight. In this form, it binds to certain proteins produced by the immune system, such as IL-8, and prevents autoimmune responses and inflammation.[10]

    What are other names for Hyaluronic Acid

    Note that Hyaluronic Acid is also known as:
    • Hyaluronan
    • Hyaluronate (as sodium or potassium salt)

    Dosage information

    For oral supplementation, the recommended dosage is 120 mg per day, with supplements usually available in either 60 mg or 120 mg tablets.[1]

    For dry eye treatments, drops are usually available in 0.3% solutions, although they may be effective from as low as 0.1%.[2]

    Topical creams and serums range from 0.1% to 0.3% HA concentrations, and will contain a mixture of high- and low-molecular-weight HA.[3]

    Examine Database: Hyaluronic Acid

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    Frequently asked questions

    What is hyaluronic acid?

    Hyaluronic acid is a mucopolysaccharide that is part of a family called the glycosaminoglycans. These long-chain sugar molecules appear naturally in cell membranes throughout the human body, and help with hydration of tissues and other important cell functions. For supplementation, hyaluronic acid may be produced using animal sources, but can also be isolated from fermented bacteria.[4]

    What are hyaluronic acid’s main benefits?

    HA is useful in several branches of medicine. Ophthalmologists use it in the treatment of dry eye syndrome,[2] orthopedics specialists use it for different types of arthritis and joint pain,[5][6][7] and aesthetic practitioners use HA in fillers.[8] It seems to have potential in other areas, too, such as wound healing and the treatment of burns.[9][10] In all of these applications, HA helps with hydration, lubrication, and tissue regeneration. High-molecular-weight HA is produced in healthy cells. Molecular weight is measured in daltons, which is the unit used to express the weight of atoms and larger molecules. A high molecular weight for HA is above 2000 kilodaltons (kDa). High-molecular-weight HA is associated with anti-inflammatory effects, and seems to slow down immune responses.[11] Other potential uses that are being looked into include alopecia treatments, regeneration of nerves in peripheral neuropathy, and use of HA in vascular grafts to help with healing.[12][13]

    Is hyaluronic acid effective as an anti-aging supplement?

    HA is often used in aesthetics in the form of topicals, tablets or injectables. A recent study suggests that oral intake of HA could improve skin hydration and wrinkles, with differences most notable on the face.[14][1] However, long-term studies are needed to determine whether these effects are long-lasting. If not, lifelong supplementation could be necessary.

    Several studies support the use of HA in topical treatments to reduce wrinkles and skin dryness and to improve skin elasticity. HA seems to improve the appearance of wrinkles and helps to hydrate the skin. High-molecular-weight HA is not able to penetrate the deeper skin layers, but does help to hydrate the outer layer of the skin. Low-molecular-weight HA can move into the deep layers, helping with hydration and elasticity. With this in mind, most products combine multiple molecular weights of HA into a serum. Since low-molecular-weight HA works on the deeper skin layers and does not cause inflammation in topical form, it seems to be the most effective option.[15] While more research is needed to support these claims, so far, the evidence looks promising for topical HA products.[3] Injectable HA is a better-known product, as it is commonly used for facial fillers. These are injected into the skin to improve the appearance of wrinkles. HA is ideal for this procedure because it is hydrating, it helps with healing, and it is produced by the body naturally and so is unlikely to produce any side effects.[16]

    Are hyaluronic acid eye drops good for dry eyes?

    Dry eyes are caused by a lack of tear production or fast evaporation. One method for managing the systems is to use “artificial tear” products—eye drops that can lubricate eyes. Hyaluronic acid (HA) has been investigated as a component of artificial tear products due to its ability to bind to ocular surface cells, enhance wound healing, and reduce the viscosity of the overall fluid.[17]

    A 2021 meta-analysis of randomized, controlled trials on participants with dry eye syndrome compared eye drops containing HA with eye drops not containing HA, including many artificial tear products with other ingredients.[2] Hyaluronic acid improved tear production relative to saline and some artificial tear products, but not all artificial tear products. The same was true of tear break-up time and Ocular Surface Disease Index, while an analysis comparing HA products to those without HA didn’t find a difference for Corneal Fluorescein Staining Score. Trials where HA is compared to artificial tear products are often confounded with other ingredients that make it difficult to discern the efficacy of HA. A 0.3% HA solution appeared to be the most effective relative to saline, though the evidence doesn't allow us to say that this dose is the best with much certainty. Doses as low as 0.1% have seen some benefit and may be useful as an addition to multi-ingredient artificial tear products, though much more research with the proper study design is needed to evaluate the ideal formulae.

    What are hyaluronic acid’s main drawbacks?

    Since hyaluronic acid is found within the body and is naturally produced in the cell walls, it is biocompatible and rarely causes any adverse effects. In products made from animal sources, the potential for an allergic reaction exists, but is unlikely.[10][4] One potential drawback of endogenous HA is that cancer cells may also produce high-molecular-weight HA. In these cells, the regenerative properties of HA support tumor growth by improving blood supply and can even protect the tumor from anticancer drugs. Some cancer treatments therefore include hyaluronidase to break down HA so that the medication can reach the tumor.[4] At very low molecular weights, measured as 40 KDa and below, HA can be a sign of stress and may be associated with inflammation.[10]

    How does Hyaluronic Acid work?

    HA is a large hydrophilic molecule. When it is released from cells, it binds water, and this helps with hydration of the cells. It also attracts fluid into the synovial fluid of the joints and the vitreous fluid in the eye, hydrating and lubricating these areas. When it is produced by cells, HA is a long molecule with a high molecular weight. In this form, it binds to certain proteins produced by the immune system, such as IL-8, and prevents autoimmune responses and inflammation.[10]

    Update History

    References

    1. ^Oe M, Sakai S, Yoshida H, Okado N, Kaneda H, Masuda Y, Urushibata OOral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period.Clin Cosmet Investig Dermatol.(2017)
    2. ^Yun-Jung Yang, Won-Young Lee, Young-Jin Kim, Yeon-Pyo HongA Meta-Analysis of the Efficacy of Hyaluronic Acid Eye Drops for the Treatment of Dry Eye SyndromeInt J Environ Res Public Health.(2021 Mar 1)
    3. ^Bravo B, Correia P, Gonçalves Junior JE, Sant'Anna B, Kerob DBenefits of topical hyaluronic acid for skin quality and signs of skin aging: From literature review to clinical evidence.Dermatol Ther.(2022-Dec)
    4. ^Salwowska NM, Bebenek KA, Żądło DA, Wcisło-Dziadecka DLPhysiochemical properties and application of hyaluronic acid: a systematic review.J Cosmet Dermatol.(2016-Dec)
    5. ^He WW, Kuang MJ, Zhao J, Sun L, Lu B, Wang Y, Ma JX, Ma XLEfficacy and safety of intraarticular hyaluronic acid and corticosteroid for knee osteoarthritis: A meta-analysis.Int J Surg.(2017-Mar)
    6. ^Khan M, Shanmugaraj A, Prada C, Patel A, Babins E, Bhandari MThe Role of Hyaluronic Acid for Soft Tissue Indications: A Systematic Review and Meta-Analysis.Sports Health.(2023)
    7. ^Mao B, Peng R, Zhang Z, Zhang K, Li J, Fu WThe Effect of Intra-articular Injection of Hyaluronic Acid in Frozen Shoulder: a Systematic Review and Meta-analysis of Randomized Controlled Trials.J Orthop Surg Res.(2022-Mar-03)
    8. ^de la Guardia C, Virno A, Musumeci M, Bernardin A, Silberberg MBRheologic and Physicochemical Characteristics of Hyaluronic Acid Fillers: Overview and Relationship to Product Performance.Facial Plast Surg.(2022-Apr)
    9. ^Voigt J, Driver VRHyaluronic acid derivatives and their healing effect on burns, epithelial surgical wounds, and chronic wounds: a systematic review and meta-analysis of randomized controlled trials.Wound Repair Regen.(2012)
    10. ^Marinho A, Nunes C, Reis SHyaluronic Acid: A Key Ingredient in the Therapy of Inflammation.Biomolecules.(2021-Oct-15)
    11. ^Ferreres G, Pérez-Rafael S, Torrent-Burgués J, Tzanov THyaluronic Acid Derivative Molecular Weight-Dependent Synthesis and Antimicrobial Effect of Hybrid Silver Nanoparticles.Int J Mol Sci.(2021-Dec-14)
    12. ^Abatangelo G, Vindigni V, Avruscio G, Pandis L, Brun PHyaluronic Acid: Redefining Its Role.Cells.(2020-Jul-21)
    13. ^Zerbinati N, Sommatis S, Maccario C, Capillo MC, Di Francesco S, Rauso R, Protasoni M, D'Este E, Gasperina DD, Mocchi RIn Vitro Hair Growth Promoting Effect of a Noncrosslinked Hyaluronic Acid in Human Dermal Papilla Cells.Biomed Res Int.(2021)
    14. ^Tzu-Fang Hsu, Zi-Rong Su, Yao-Hao Hsieh, Ming-Fu Wang, Mariko Oe, Ryosuke Matsuoka, Yasunobu MasudaOral Hyaluronan Relieves Wrinkles and Improves Dry Skin: A 12-Week Double-Blinded, Placebo-Controlled StudyNutrients.(2021 Jun 28)
    15. ^Farwick M, Gauglitz G, Pavicic T, Köhler T, Wegmann M, Schwach-Abdellaoui K, Malle B, Tarabin V, Schmitz G, Korting HCFifty-kDa hyaluronic acid upregulates some epidermal genes without changing TNF-α expression in reconstituted epidermis.Skin Pharmacol Physiol.(2011)
    16. ^Signorini M, Liew S, Sundaram H, De Boulle KL, Goodman GJ, Monheit G, Wu Y, Trindade de Almeida AR, Swift A, Vieira Braz A,Global Aesthetics Consensus: Avoidance and Management of Complications from Hyaluronic Acid Fillers-Evidence- and Opinion-Based Review and Consensus Recommendations.Plast Reconstr Surg.(2016-Jun)
    17. ^Lyndon Jones, Laura E Downie, Donald Korb, Jose M Benitez-Del-Castillo, Reza Dana, Sophie X Deng, Pham N Dong, Gerd Geerling, Richard Yudi Hida, Yang Liu, Kyoung Yul Seo, Joseph Tauber, Tais H Wakamatsu, Jianjiang Xu, James S Wolffsohn, Jennifer P CraigTFOS DEWS II Management and Therapy ReportOcul Surf.(2017 Jul)

    Examine Database References

    1. Dermatitis Severity - Tai RZ, Loh EW, Tsai JT, Tam KWEffect of hyaluronic acid on radiotherapy-induced mucocutaneous side effects: a meta-analysis of randomized controlled trials.Support Care Cancer.(2022-Jun)
    2. Joint Pain (General) - Shen D, Chen M, Chen K, Wang T, Lu L, Yang XEfficacy of hyaluronic acid after knee arthroscopy: A systematic review and meta-analysis.J Rehabil Med.(2018-Nov-07)
    3. Postoperative Adhesions - Liu YR, Liu B, Yang BP, Lan Y, Chi YGEfficacy of hyaluronic acid on the prevention of intrauterine adhesion and the improvement of fertility: A meta-analysis of randomized trials.Complement Ther Clin Pract.(2022-May)
    4. Postoperative Adhesions - Dou Y, Yu T, Li Z, Wang J, Jiang Y, Liu YShort- and Long-term Outcomes of Postoperative Intrauterine Application of Hyaluronic Acid Gel: A Meta-analysis of Randomized Controlled Trials.J Minim Invasive Gynecol.(2022-Aug)
    5. Joint Pain (General) - Ebad Ali SM, Farooqui SF, Sahito B, Ali M, Khan AA, Naeem OClinical Outcomes Of Intra-Articular High Molecular Weight Hyaluronic Acid Injection For Hip Osteoarthritis- A Systematic Review And Meta-Analysis.J Ayub Med Coll Abbottabad.(2021)
    6. Joint Pain (General) - Mao B, Pan Y, Zhang Z, Yu Z, Li J, Fu WEfficacy and Safety of Hyaluronic Acid Intra-articular Injection after Arthroscopic Knee Surgery: A Systematic Review and Meta-analysis.Orthop Surg.(2023-Jan)
    7. Joint Pain (General) - Tang JZ, Nie MJ, Zhao JZ, Zhang GC, Zhang Q, Wang BPlatelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: a meta-analysis.J Orthop Surg Res.(2020-Sep-11)
    8. Joint Pain (General) - Mao B, Peng R, Zhang Z, Zhang K, Li J, Fu WThe Effect of Intra-articular Injection of Hyaluronic Acid in Frozen Shoulder: a Systematic Review and Meta-analysis of Randomized Controlled Trials.J Orthop Surg Res.(2022-Mar-03)
    9. Joint Pain (General) - He WW, Kuang MJ, Zhao J, Sun L, Lu B, Wang Y, Ma JX, Ma XLEfficacy and safety of intraarticular hyaluronic acid and corticosteroid for knee osteoarthritis: A meta-analysis.Int J Surg.(2017-Mar)
    10. Joint Pain (General) - Zhao J, Huang H, Liang G, Zeng LF, Yang W, Liu JEffects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis.BMC Musculoskelet Disord.(2020-Apr-11)
    11. Wound Healing - Voigt J, Driver VRHyaluronic acid derivatives and their healing effect on burns, epithelial surgical wounds, and chronic wounds: a systematic review and meta-analysis of randomized controlled trials.Wound Repair Regen.(2012)
    12. Dry Eye Symptoms - Yun-Jung Yang, Won-Young Lee, Young-Jin Kim, Yeon-Pyo HongA Meta-Analysis of the Efficacy of Hyaluronic Acid Eye Drops for the Treatment of Dry Eye SyndromeInt J Environ Res Public Health.(2021 Mar 1)