Clinical Studies

Research Studies with HA


There are many Hyaluronic Acid products available now on the market. This review from the Journal of Applied Nutrition examines the different kinds of HA available and talks about their effectiveness. Not all Hyaluronic Acid is created equal. Keep in mind when reading this study that our patented Synthovial Seven®is high molecular weight HA in the 2.4-3 million Daltons!

“..dietary supplements containing HA are not equivalent due to the inherent properties of the three major types of HA commercially available as dietary supplement materials. Consumers and health care professionals need to be aware of the different types of HA and their very large differences in properties (even before ingestion). One source, hydrolyzed chicken sternal cartilage, is clearly unlike native HA, does not match the biological properties of native HA, and consequently should not be represented as HA to consumers on product labels…”

Click here to read the entire review.

Title of study: Supporting Knee Joints With Oral Hyaluronic Acid.

Chief Investigator: K. Dean Reeves, M.D., F.A.A.P.M & R. (Fellow of the American Academy of Physical Medicine and Rehabilitation). Human Subject Committee: Shawnee Mission Medical Center, Shawnee Mission Kansas (Greater Kansas City Area)

Purpose of study: This study is designed to compare the effects of Synthovial Seven® with a control treatment for patients with knee conditions. Link to Dr. Reeves Website- click here.

Layman’s Explanation: Synthovial Seven® is a pure form of hyaluronic acid. Hyaluronic acid is a special protein that is the normal lubricant in human joints. When present in a joint, even a joint with minimal or no cartilage, it can provide a cushion effect. Hyaluronic acid in our joints is a long and complex molecule, and makes a ball shape which resists compression. However, with inflammation or other conditions the complex hyaluronic acid molecule breaks down to smaller pieces and is not effective in keeping a ball shape. Therefore it cannot provide a cushion of protection in the joint. Hyaluronic acid is also found in all connecting tissues of the body such as ligaments and tendons where it performs special functions of lubrication and helps orient ligament and tendon fibers.

Title of study: Effect of Lubricant Composition on the Fatique Properties of Ultra High Molecular Weight Polyethylene (UHMWPE) for Total Knee Replacement (TKR)-

Investigating Team: Department of Bioengineering, Clemson University

ABSTRACT:Clemson University Fatigue failure of ultra high molecular weight polyethylene (UHMWPE) has been cited as the prevalent surface failure mechanism for total knee arthroplasty (TKA). Hence, it becomes imperative to simulate in-vivo conditions in in-vitro simulations. In this study. the hypothesis that the physiological environment influences the fatigue properties of the polymer was explored. The present study examined the effect of adding hyaluronic acid in varying clinical concentrations on the fatigue crack growth response of UHMWPE. A fracture mechanics approach was adopted to relate the fatigue properties of the polymer determined using the ASTM E 647, to the physiological environment. The fractured surfaces were characterized using scanning electron microscopy to evaluate the effect of lubricant viscosity on the fatigue failure mechanisms. The serum protein adsorption on the surface of the specimens was studied by Fourier Transform Infrared Spectroscopy. Rheological analysis indicated that the viscosity of the lubricants with the three concentrations of hyaluronic acid -2.22 g/l, 0.55 g/l and 1.5 g/l were representative of those found in osteoarthritic and rheumatoid arthritic diseased joints and in the periprosthetic fluids, respectively HA was found to significantly affect lubricant viscosity and wettability. These are environmental factors, which are theorized to directly affect the fatigue properties of the polymer, and can be directly related to the clinical environment as well. Results showed that the presence of HA in the bovine serum not only affects the crack initiation of the polymer, but also causes a significant shift of the linear crack growth regime compared to 50% bovine serum alone (t-test, a = 0.05). Key words: fatigue, FTIR, Hyaluronic acid, UHMWPE

Click here to Read Letter from Clemson University to Hyalogic specifically asking to use Synthovial Seven® because of the high molecular weight of our product. (.pdf file 25 KB)

Research with Episilk™ Premium Cream (Pure Hyaluronic Acid)

Chief Investigator:Dr. A. Bulent Tanman, Dermatologist, Elit Saglik Clinics Advisor: Prof. Dr. Ertugrul H. Aydemir, University of Istanbul, Faculty of Medicine, Cerrahpasa, Dept. of Dermatology

Excerpt from “Discussion About the Results “…According to the results, we can understand why hyaluronic acid is called a Natural Moisturizer of the Skin. Since Episilk Premium is a pure hyaluronic acid cream, I think it will help the patients to feel good; having much more smoother, shinier, moisturized skin and with improved wrinkles…”

Entire study results available in .pdf form- click to download(212 KB).

Title of study: Moleculaar and Rheological Characterization of Sodium Hyaluronate (HA) and Equine Synovial Fluid

Chief Investigators:Danielle Leiske, Willie E. (Skip) Rochefort of Oregon State University. This work is ongoing and this project was presented at the Society of Rheology Meeting in Lubbock, Texas in February 2005.

This is an excerpt from the introduction…
Sodium hyaluronate (also referred to as hyaluronic acid, or HA) is the largest molecular component of synovial fluid and contributes both viscous (lubricating) and elastic (shock-absorbing) properties that are important in \the lubrication and protection of cartilage. Hyaluronate (HA) is a polymer found in all parts of the body but is of particular importance in articular joints. The key to the viscoelastic behavior of synovial fluid is molecular weight and concentration of HA. Hyaluronate’s important role in joint lubrication has made it of particular interest in the biomedical field.

Certain types of joint diseases have been attributed to the breakdown of HA in the joint. Although the exact nature of the degradation of HA is not yet fully understood, it has been credited to the presence of deleterious enzymes and radicals. Any decrease in the size of HA molecules will result in a decrease of viscoelastic properties of synovial fluid, which could lead to cartilage damage. Viscosupplementation is a treatment developed to care for joint disease. It involves either intra-articular or intravenous injections of HA supplements to the diseased joint or patient. Initially this idea was developed to boost the viscoelastic properties of synovial fluid, however it was later realized that HA performs a biochemical role in joints in addition to its well described mechanical role. Nevertheless, the mechanical role of HA in joint fluid is important and worthy of study.

Hyaluronic acid is one of the most researched substances in medicine today and is backed by thousands of clinical trials in the fields of orthopedics and eye surgery. If you’d like to learn more about the benefits of hyaluronic acid, the following resources will provide you with a starting point for further research.

  1. Marshall KW. Viscosupplementation of HA: current status, unresolved issues and future directions. J Rheumatol 1998;25:2056-8.
  2. George E. Intra-articular hyaluronan. Ann Rheum Dis 1998;57:637-40.
  3. Wobig M, Bach G, Beks P, Dickhut A, Runzheimer J, Schwieger G, et al. The role of elastoviscosity in the efficacy of viscosupplementation for the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan. Clin Ther 1999;21:1549-62.
  4. Cohen MD. Hyaluronic acid treatment (viscosupplementation) for OA of the knee. Bull Rheum Dis 1998;47:4-7.
  5. Balazs EA, Denlinger JL. Viscosupplementation: a new concept in the treatment for the knee. J Rheumatol 1993;20(suppl 39):3-9.
  6. Weiss C, Balazs EA, St. Onge R, Denlinger JL. Clinical studies of the intraarticular injection of HealonR (sodium hyaluronate) in the treatment of human knees. symposium. Palm Aire, Fla., October 20-22, 1980. Semin Arthritis Rheum. 1981;11(suppl 1):143-4.
  7. Peyron JG. Intraarticular hyaluronan injections in the treatment of the knee: state-of-the-art review. J Rheumatol 1993;39(suppl):10-5.
  8. Henderson EB, Smith EC, Pegley F, Blake DR. Intra-articular injections of 750 kD hyaluronan in the treatment of the knee: a randomised single centre double-blind placebo-controlled trial of 91 patients demonstrating lack of efficacy. Ann Rheum Dis 1994;53:529-34.
  9. Lohmander LS, Dalen N, Englund G, Hamalainen M, Jensen EM, Karlsson K, et al. Intra-articular hyaluronan injections in the treatment of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Mulicentre Trial Group. Ann Rheum Dis 1996;55:424-31.
  10. Dougados M, Nguyen M, Listrat V, Amor B. High molecular weight sodium hyaluronate (hyalectin) for the knee: a 1 year placebo-controlled trial. Cart 1993;1:97-103.
  11. Marshall KW. Viscosupplementation: current status, unresolved issues and future directions. J Rheumatol 1998;25:2056-8.
  12. Listrat V, Ayral X, Paternello F, Bonvarlet JP, Simonnet J, Amor B, et al. Arthroscopic evaluation of potential structure modifying activity of hyaluronan (Hyalgan) in the knee. Cart 1997;5:153-60.
  13. Altman RD, Moskowitz R. Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patient’s knee: a randomized clinical trial. J Rheumatol 1998;25:2203-12 [Published erratum appears in J Rheumatol 1999;26:1216].
  14. Wobig M, Dickhut A, Maier R, Vetter G. Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the knee. Clin Ther 1998;20:410-23.
  15. Adams ME, Atkinson MH, Lussier AJ, Schulz JI, Siminovitch KA, Wade JP, et al. The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone. Cart 1995;3:213-25.
  16. Lussier A, Cividino AA, McFarlane CA, Olszynski WP, Potashner WJ, De Medicis R. Viscosupplementation with hylan for the treatment of: findings from clinical practice in Canada. J Rheumatol 1996;23:1579-85.
  17. Disla E, Infante R, Fahmy A, Karten I, Cuppari GG. Recurrent acute calcium pyrophosphate dihydrate arthritis following intraarticular hyaluronate injection. Arthritis Rheum 1999;42:1302-3.
  18. Maheu E. Hyaluronan in knee: a review of the clinical trials with hyalgan. Eur J Rheumatol Inflamm 1995;15:17-24.