Highly bioavailable hyaluronic acid for superior joint function

Hyluronan were first commercially available in 1942 when Endre Balazs applied for a patent to use the product as a substitute for egg white in baked products. It has since been used for a variety of purposes and has recently received much attention as a cosmetic product and as a treatment to improve joint mobility and reduce pain associated with arthritic conditions. “Hyal Joint” from AOR contains sodium hyaluronate, a low molecular weight and highly bioavailable form of hyaluronic acid. Hyaluronic acid’s capacity at improving joint mobility comes from it’s presence in the synovial fluid, a viscous substance found in joints. The synovial fluid acts as a lubricant and shock absorber. It forms a thin layer at the surface of cartilage, reducing friction, facilitating movement and providing nourishment.

What is Hyaluronic acid?
Hyaluronic acid is a cementing and protective substance found in the synovial fluid and connective tissue of movable joints. Hyaluronic acid is a naturally occurring substance that has a high water affinity. It is essential for joint mobility. Like chondroitin sulphate and glucosamine it is a mucopolysaccharide, a polysaccharide with a protein attachment. It’s utility in joint dysfunction comes from its viscoelastic and pseudoplastic properties. Simply put, hyaluronic acid forms a thick gel that lubricates and protects joints. Hyaluronic acid is found throughout the body but high concentrations are found in the skin, vitreous humour and synovial fluid.

Hyaluronic acid to protect articulations
Normal synovial fluid contains 3-4 mg/ml of hyaluronic acid. Hyaluronic acid helps protect joints by augmenting the viscosity of the synovial fluid, by increasing the elasticity of the cartilage found in joints and because of its anti-inflammatory effect. Recent studies have shown that serum hyaluronic acid levels are a useful marker for the activity and severity of rheumatoid disease. In animal models, hyaluronic acid significantly reduced the production of nitric oxide, a free radical involved in cartilage degeneration and joint inflammation. Supplementation with hyaluronic acid reduces pain and improves function in patients with osteoarthritis of the knee. These effects are thought to be attributable to the return of a more normal synovial fluid, improved viscoelasticity, improved cartilage biosynthesis, anti-inflammatory and analgesic effects. It is no surprise that sodium hyaluronate has been used in several countries since 1987 to treat osteoarthritis. Hyaluronic acid also promotes wound healing; it is thought that its cementing ability allows room for white blood cells, which increases the speed of recovery. It is used topically as an analgesic, in skin care products to moisturize the skin and in eye drops to reduce ocular discomfort.

Research Studies
• Studies show that the hyaluronic acid content in osteoarthritic cartilage is greatly reduced and that hyaluronic acid supplementation lessens pain and improves function in patients with osteoarthritis of the knee.
• Hyaluronic acid was shown to exert anti-inflammatory activity through its effect on nitric oxide, a molecule that is pivotal in synovium inflammation, cartilage and meniscus degeneration.
• Animal studies have shown that a formula containing niacinamide and hyaluronate was effective at reducing paw swelling.
• Hyaluronic supplementation also allowed for faster healing times of open wounds in rats. The group receiving hyaluronic acid healed 10 days faster than the control group. Hyaluronic supplementation also inhibited scar formation.
• Serum hyaluronic acid levels were shown to be a useful marker for the activity and severity of disease activity in rheumatoid arthritis patients.
• In vitro studies have clearly demonstrated that the presence of hyaluronic acid in has a stimulatory effect on chondrocyte metabolism. In other words, hyaluronic acid increases the activity of the cells responsible for cartilage production and maintenance.

Why Hyaluronic Acid?
There have been concerns about the absorption of hyaluronic acid. Given its structure, it is possible that what is absorbed is not sodium hyaluronate but some of its derivatives. It is thought that those metabolites reach the tissues. This is especially true for oral supplements containing larger molecules of hyaluronic acid. “Hyal-Joint” is a formulation specific for oral use and of lower molecular weight. A lower molecular weight means that the molecules are smaller which makes the product much more absorbable. It is produced specifically for the nutrition of synovial joints and is supported by several clinical studies showing its effectiveness. Hyaluronic acid is widely distributed in the body and it is one of the most potent “water holders” found in the human body. Its capacity at binding water is impressive and up to 6 liters of water may be bound per gram of hyaluronic acid.

“Hyal joint” is a highly absorbable hyaluronic acid supplement particularly useful for joint dysfunction. It has been shown to reduce pain and improve function in arthritic conditions and should be included in any treatment focused on improving joint mobility.

References

• Lu L, Leng Y, Cnen Y. An experiment study on wound healing with exogenous hyaluronic acid. Zhonghua Zheng Xing Wai Ke Za Zhi. 2000 Jan;16(1):30-3. Chinese.

• Metabolic Engineering of Hyaluronic Acid Production. Retrieved Oct 17, 2005 from: http://www.cheque.uq.edu.au/research/bioengineering/research/Metabolic_Engineering/HA.html

• Akmal M, Singh A, Anand A, Kesani A, Aslam N, Goodship A, Bentley G. The effects of hyaluronic acid on articular chondrocytes. J Bone Joint Surg Br. 2005 Aug;87(8):1143-9.

• Moskowitz RW. Hyaluronic acid supplementation. Curr Rheumatol Rep. 2000 Dec;2(6):466-71. Review.

• Williams JM, Zhang J, Kang H, Ummadi V, Homandberg GA. The effects of hyaluronic acid on fibronectin fragment mediated cartilage chondrolysis in skeletally mature rabbits. Osteoarthritis Cartilage. 2003 Jan;11(1):44-9.

• Louthrenoo W, Kongtawelert P, Sivasomboon C, Sukitawut W. Correlation between serum hyaluronan and disease activity and severity in Thai patients with rheumatoid arthritis. J Med Assoc Thai. 2001 May;84(5):622-7.

• Takahashi K, Hashimoto S, Kubo T, Hirasawa Y, Lotz M, Amiel D. Hyaluronan suppressed nitric oxide production in the meniscus and synovium of rabbit osteoarthritis model. J Orthop Res. 2001 May;19(3):500-3.

Copyright © 2005, Advanced Orthomolecular Research

Tolerability and short-term effectiveness of hylan G-F 20 in 4253 patients with osteoarthritis of the knee in clinical practice.
Curr Med Res Opin. 2005 Aug;21(8):1261-9. 
Kemper F, Gebhardt U, Meng T, Murray C.

OBJECTIVE: To determine the tolerability and short-term effectiveness of hylan G-F 20 (Synvisc) in patients with symptomatic osteoarthritis (OA) of the knee in standard clinical practice.
RESEARCH DESIGN AND METHODS: Over 800 orthopedic surgeons in Germany recorded adverse events (AEs) for approximately five consecutive patients each following 3 weekly intra-articular hylan G-F 20 injections. Patients assessed their pain on a 4-point scale before and 3 weeks after the first injection. Potential risk factors for local AEs and possible predictors of short-term effectiveness of hylan G-F 20 were explored with logistic regression.
RESULTS: 4253 patients were treated with 12699 injections by 840 physicians at 720 sites. Local, treatment related AEs (n = 302) were reported in 180 patients (4.2% of patients; 2.4% of injections). The most frequently reported AEs were joint effusion (2.4% of patients), joint swelling (1.3%), arthralgia (1.2%), joint warmth (0.6%), and injection site erythema (0.3%). Most AEs were mild (21.4%) to moderate (40.3%) in nature. One patient experienced a serious AE of severe swelling and synovial fluid accumulation judged as possibly treatment related. Patients < 70 years old, patients with a longer time since diagnosis, and those previously treated with visco-supplementation were more likely to experience a local AE. Pain significantly (p < 0.0001) decreased 3 weeks after the first injection compared with before treatment. Potential predictors of hylan G-F 20 short-term effectiveness were being underweight, male gender, shorter time since diagnosis, and severe baseline pain.
CONCLUSIONS: In this population of 4253 patients treated with hylan G-F 20 for OA knee pain, the overall incidence of local, treatment-related AEs was low and consistent with those reported in the current US product labeling and previously published studies. Additionally, short-term effectiveness was confirmed.


The effects of hyaluronic acid on articular chondrocytes.
J Bone Joint Surg Br. 2005 Aug;87(8):1143-9.
Akmal M, Singh A, Anand A, Kesani A, Aslam N, Goodship A, Bentley G.

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors.Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes.There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism.

Copyright © 2005, Advanced Orthomolecular Research