Hyaluronic acid, a natural component in Halevox™ HA products

Hyaluronic acid (HA) is one of the major constituent of articular cartilage extracellular matrix and synovial fluid1. HA is a biopolysacharide – it consists of a number of sugar molecules bonded together into a long chain1.

HA is a crucial structural component of the synovial joint as it acts as a lubricant, shock absorber, filler, and metabolic agent2. OA in animal development diminishes the lubricating and shock absorption abilities of synovial fluid mainly by degradation of naturally produced HA3.

Viscosupplementation, so intra-articular injection of HA, is a scientifically and clinically approved practice for reducing joint pain in animals , improving the functional condition of OA-affected joint, protecting cartilage, and finally delaying progression of the disease4.

Intra-articular mechanism of action

  • HA restores viscoelastic properties of OA-affected synovial fluid thus improving lubrication
  • HA induces synthesis of natural hyaluronic acid thus contributing to recovery of joint homeostasis1
  • HA binds to special receptors – CD44 on cartilage and synovial cells to support matrix production2 and inhibit inflammation
  • HA affects OA-related nerve oversensitivity and reduces hyperalgesia3
  • HA diminishes inflammatory processes by reduction of proinflammatory mediators’ production and action4

Optimal chains length  

Only high molecular weight HA is fully biologically functional

  • Only optimally high molecular weight HA possesses the ability to protect against articular cartilage damage by restoring  joint lubrication and joint homeostasis1
  • Only optimally high molecular weight HA can reduce OA-related pain5
  • Only  HA with optimally high molecular weight HA can reduce OA-related inflammation processes6
  • Only optimally high molecular weight HA can protect articular cartilage from OA-related degenerative changes and show clinical benefits7
  1. Murray CJ, , Memish ZA. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2197-223
  2. Felson DT. Clinical practice. Osteoarthritis of the knee. N Engl J Med. 2006 Feb 23;354(8):841-8. doi: 10.1056/NEJMcp051726. Erratum in: N Engl J Med. 2006 Jun 8;354(23):2520.
  3. Balazs EA, Watson D, Duff IF, Roseman S. Hyaluronic acid in synovial fluid. I. Molecular parameters of hyaluronic acid in normal and arthritis human fluids. Arthritis Rheum. 1967 Aug;10(4):357-76.
  4. Creamer P, Sharif M, George E, Meadows K, Cushnaghan J, Shinmei M, Dieppe P. Intra-articular hyaluronic acid in osteoarthritis of the knee: an investigation into mechanisms of action. Osteoarthritis Cartilage. 1994 Jun;2(2):133-40.
  5. Smith MM, Ghosh P. The synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment. Rheumatol Int. 1987;7(3):113-22.
  6. Chow G, Nietfeld JJ, Knudson CB, Knudson W. Antisense inhibition of chondrocyte CD44 expression leading to cartilage chondrolysis. Arthritis Rheum. 1998 Aug;41(8):1411-9.
  7. Pozo MA, Balazs EA, Belmonte C. Reduction of sensory responses to passive movements of inflamed knee joints by hylan, a hyaluronan derivative. Exp Brain Res. 1997 Aug;116(1):3-9.
  8. Takahashi K, Goomer RS, Harwood F, Kubo T, Hirasawa Y, Amiel D. The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1beta(IL-1beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis. Osteoarthritis Cartilage. 1999 Mar;7(2):182-90.
  9. Gomis A, Pawlak M, Balazs EA, Schmidt RF, Belmonte C. Effects of different molecular weight elastoviscous hyaluronan solutions on articular nociceptive afferents. Arthritis Rheum. 2004 Jan;50(1):314-26.
  10. Gotoh S, Onaya J, Abe M, Miyazaki K, Hamai A, Horie K, Tokuyasu K. Effects of the molecular weight of hyaluronic acid and its action mechanisms on experimental joint pain in rats. Ann Rheum Dis. 1993 Nov;52(11):817-22.
  11. Altman RD, Bedi A, Karlsson J, Sancheti P, Schemitsch E. Product Differences in Intra-articular Hyaluronic Acids for Osteoarthritis of the Knee. Am J Sports Med. 2016;44(8):2158-2165. doi:10.1177/0363546515609599