Benefits of Low & High Molecular Weight Hyaluronic Acid?

Benefits of Low & High Molecular Weight Hyaluronic Acid?


Hyaluronic acid (HA) is a naturally occurring substance in the human body, found in high concentrations in the skin, connective tissue, and eyes. It plays a crucial role in retaining moisture, supporting skin health, and improving joint function. In recent years, HA has gained popularity as a dietary supplement and a topical agent for skincare. This blog will explore the benefits of low molecular weight (LMW) and high molecular weight (HMW) hyaluronic acid in dietary supplements and topical applications, supported by human randomized controlled trials (RCTs) from top journals.

Benefits of Low Molecular Weight Hyaluronic Acid

Low molecular weight hyaluronic acid is characterized by smaller molecules, which can penetrate the skin and tissues more effectively than their high molecular weight counterparts. This property makes LMW HA particularly beneficial for certain therapeutic applications.

  1. Improvement in Joint Pain and Function:

    • Supraspinatus Tendinopathy: A study comparing LMW HA with physiotherapy for supraspinatus tendinopathy found that LMW HA was more effective in reducing shoulder pain at rest and during activities, and in improving shoulder motion and quality of life (Rezasoltani et al., 2021).
    • Osteoarthritis of the Knee: In another study, LMW HA injections showed similar efficacy to high molecular weight HA in reducing pain and improving function in patients with advanced osteoarthritis of the knee (Karatosun et al., 2005).
  2. Skin Health and Wrinkle Reduction:

    • Wrinkle Reduction: Oral intake of LMW HA has been shown to reduce wrinkles and improve skin condition significantly. A study found that after 12 weeks, participants taking LMW HA exhibited better wrinkle reduction and skin suppleness compared to a placebo group (Oe et al., 2017).

Benefits of High Molecular Weight Hyaluronic Acid

High molecular weight hyaluronic acid consists of larger molecules, which are primarily used for their viscoelastic properties, making them suitable for joint lubrication and surface hydration in topical applications.

  1. Joint Health and Pain Relief:

    • Knee Osteoarthritis: HMW HA injections have demonstrated significant benefits in reducing pain and improving knee function in patients with osteoarthritis. Studies have shown that HMW HA provides long-term relief, improving both pain and functional scores significantly (Kirchner & Marshall, 2006).
    • Chronic Bronchitis: HMW HA has been used subcutaneously to reduce the number of infectious exacerbations in patients with chronic bronchitis, potentially by enhancing cellular host defense mechanisms (Venge et al., 1996).
  2. Skin Health and Hydration:

    • Topical Applications: Topically applied HMW HA is known for its excellent moisturizing properties and ability to form a protective barrier on the skin. This helps in retaining moisture and improving skin elasticity. Although direct RCT evidence for topical application is limited, the general consensus in dermatological practice supports these benefits.

Combining Dietary Supplements and Topical Applications

Combining both oral and topical forms of hyaluronic acid can offer comprehensive benefits by supporting skin health from within and protecting the skin's surface. Oral supplements can provide systemic hydration and improve skin elasticity, while topical applications can target specific areas for hydration and protection.


Both low molecular weight and high molecular weight hyaluronic acid have unique benefits when used in dietary supplements and topical applications. LMW HA is particularly effective for deeper tissue penetration, making it suitable for joint health and skin wrinkle reduction. On the other hand, HMW HA excels in providing joint lubrication and surface hydration for the skin. Combining both forms can offer a holistic approach to enhancing skin and joint health.


  1. Rezasoltani, Z., Esmaily, H., Dadarkhah, A., Rousta, M., Mohebbi, R., & Vashaei, F. (2021). Low Molecular-weight Hyaluronic Acid Versus Physiotherapy for the Treatment of Supraspinatus Tendinopathy: A Randomized Comparative Clinical Trial. The Journal of the American Academy of Orthopaedic Surgeons

  2. Karatosun, V., Unver, B., Gocen, Z., & Sen, A. (2005). Comparison of two hyaluronan drugs in patients with advanced osteoarthritis of the knee. A prospective, randomized, double-blind study with long term follow-up. Clinical and experimental rheumatology

  3. Oe, M., Sakai, S., Yoshida, H., Okado, N., Kaneda, H., Masuda, Y., & Urushibata, O. (2017). Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period. Clinical, Cosmetic and Investigational Dermatology.

  4. Kirchner, M., & Marshall, D. (2006). A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee. Osteoarthritis and cartilage.

  5. Venge, P., Pedersen, B., Håkansson, L., Hällgren, R., Lindblad, G., & Dahl, R. (1996). Subcutaneous administration of hyaluronan reduces the number of infectious exacerbations in patients with chronic bronchitis. American journal of respiratory and critical care medicine.