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Oral Hyaluronic acid (HA) supplementation.

As our population has aged and become more overweight, and the impact of sport takes its toll, the prevalence of osteoarthritis (OA) has increased significantly. It is expected that this trend will continue in the foreseeable future.

For those affected with arthritis, their quality of life often declines. Pain, stiffness and inflammation can lead to decreased voluntary activities, such as exercise or recreational endeavours. This indirectly results in a host of conditions including depression, obesity, heart disease, diabetes, work and/or relationship problems, among many others. For most people, life is just not as enjoyable with OA. Osteoarthritis is a dynamic process that may progress episodically. It remains unclear what triggers the onset of the disease and its course cannot be reliably predicted. Its etiology is multifactorial and can include both systemic and local biomechanical factors. (1) Risk factors such as age, sex, trauma, overuse, genetics and obesity can all contribute to the injury process. Such risk factors can serve as initiators that promote abnormal biochemical processes involving the cartilage, bone and synovium, which, during a period of years may result in the characteristic features of OA. The good news is that the high prevalence of arthritis has led to increased awareness and greater research efforts. New treatment options have become available that allow for improvement in pain, function and inflammation while having a better safety profile compared with earlier treatments.

HA and Joint Function

Hyaluronic acid (HA) represents one of the main components of synovial fluid and contributes to its elasticity and viscosity. (2) It is well known that in osteoarthritic joints, the synovial fluid contains a lower concentration and molecular weight of HA than in healthy ones. (3) Thus, HA seems to play an important role in either joint function or OA treatment and prevention. And, for this reason, hyaluronans are used for the viscosupplementation of joints. In the joint disease, osteoarthritis, several things go wrong. The cartilage on the end of the bones slowly erodes, the bone underlying the cartilage changes (leading to bone spurs and pain) and the fluid in the joint changes in character. In severe osteoarthritis, the level of hyaluronic acid in the joint fluid may decrease by 75% or more. This can lead to both mechanical and chemical changes within the joint.

From a mechanical standpoint, as HA serves as a shock absorber and lubricator, it's no wonder that such a decrease in this important molecule results in adverse consequences such as a "creaking" or "grinding" sensation, pain or even something called "movie-goers knee." Movie-goers knee, which sounds funny but is a real medical condition, occurs when sitting with the knee bent at a sharp angle for a prolonged period of time without movement, such as sitting at a 2-hour movie or driving a car. Upon arising, a sudden, sharp, stabbing pain can occur in the knee. The pain usually goes away after walking a few steps as the remaining fluid in the knee coats the surfaces of the cartilage.

Synovial Fluid Role for HA

One of the most recent and remarkable advances in the field of osteoarthritis is understanding the relationship between inflammation of the synovial membrane and the acute symptoms experienced by osteoarthritis sufferers. This inflammation--termed synovitis--is directly correlated with the level of pain and dysfunction: low levels are usually associated with mild symptoms, and large amounts of synovitis are almost always associated with pain, swelling, warmth and dysfunction. About 50% of osteoarthritis sufferers experience synovitis-derived pain. A number of studies also suggest a relationship between synovial inflammation and the progression of structural damage.

Both clinicians and researchers can directly measure and quantify the level of synovitis. Diagnostic ultrasound and MRI scans provide precise information about the location and extent of synovitis. One form of HA, concentrated from avian origin (brand name Hyal-Joint), was recently studied to gauge its effects on treating people who were suffering from synovitis-derived osteoarthritis pain. Those who had taken 80 mg of Hyal-Joint oral HA daily had a rapid (1 month) and significant reduction in pain and an objective reduction in synovitis (as measured by ultrasound) compared with those who had taken 500 mg of acetaminophen per day. This kind of high quality evidence may signal a major new advance in osteoarthritis treatment. The dietary supplement, Hyal-Joint, is a natural extract of chicken comb with a high content of hyaluronic acid, hydrolysed proteins (mainly collagen) and other mucopolysaccharides. The clinical efficacy of Hyal-Joint has been demonstrated in a number of ways:

Reduced pain and improved quality of life: The results obtained in both in vitro and in vivo experiments done in animal models suggest that Hyal-Joint's effect on joint function may have an impact on the quality of life of patients with joint problems or osteoarthritis. Both effects were confirmed in a pilot study in patients with osteoarthritis of different degrees (grade ≥2 on the Kellgren/Lawrence scale). (4) This was a random, double-blind, placebo-controlled study involving 20 patients with osteoarthritis of the knee. Ten patients received Hyal-Joint (80 mg/d) and 10 received a placebo for 8 weeks. In both groups, the patients showed improvements in levels of pain, stiffness, functional subscales and overall WOMAC scores. However, the improvement was greater in the group treated with Hyal-Joint than in the placebo group. Similarly, when the SF-36 quality of life survey was evaluated, the patients treated with Hyal-Joint showed significant improvements compared with the placebo group on different subscales (physical role and body pain).

Reduction of synovial effusion and inflammation in 1 month: Hyal-Joint was demonstrated to be particularly effective for the treatment of patients with OA/synovitis. In an observational retrospective cohort study involving 71 consecutive outpatients with knee OA, the evolution of synovial effusion and pain were studied during a period of 6 months. (5) The course of synovitis was measured in the suprapatellar recess using ultrasonography (US) equipment with a high frequency linear array. The maximal synovial thickness and effusion depth were measured in millimetres using the longitudinal scale (clinical synovial effusion was defined as present in results ≥4 mm). It was noted that treatment with Hyal-Joint reduced the prevalence of patients with clinical synovial effusion compared with treatment with paracetamol at an analgesic dose (500 mg/d). Interestingly, the results were statistically significant from the first month of treatment. Similarly, joint pain assessed using the Huskisson's scale decreased more quickly during the study in the Hyal-Joint group compared with the paracetamol one, showing that pain and synovial effusion are strongly correlated. Although these results need to be confirmed in a prospective double-blind placebo-controlled clinical trial, the evidence suggests that Hyal-Joint could be a useful tool for the treatment of OA coursing with synovitis. The specific effect that Hyal-Joint has on the evolution of synovitis implies that the product could theoretically delay the onset of OA (synovitis is considered to be an independent risk factor of OA progression). (6)

Regulation of HA metabolism in synovial fluid: The results obtained in vitro were confirmed in two in vivo studies done in different animal models. In a double-blind, placebo-controlled study conducted in young horses diagnosed with osteochondritis dissecans, treatment with Hyal-Joint oral supplements for 60 days reduced the level of synovial effusion and, as a result, increased the concentration of hyaluronic acid in the synovial fluid. (7) In a study in rats in which osteoarthritis had been induced, the administration of Hyal-Joint significantly reduced inflammation, the destruction of cartilage and bone reabsorption. A modulating effect of Hyal-Joint on the endogenous synthesis of hyaluronic acid was observed in arthritic rats; treatment with Hyal-Joint made it possible to maintain the concentration and speed of synthesis of hyaluronic acid at the same levels as in healthy rats, thereby preventing abnormalities in HA metabolism associated with acute joint inflammation. (8)

Reduced use of pain relievers: Reduced joint inflammation and the regulation of HA metabolism results in the control of joint pain.2 As a result, the use of drugs to control pain should be significantly reduced in individuals treated with Hyal-Joint. The overall results clearly suggest that treatment with Hyal-Joint is safe, well tolerated and should be taken into account as a new tool for the treatment of OA.


(1.) C.J.L. Murray and A.D. Lopez, "The Global Burden of Disease," World Health Organization (Geneva, Switzerland, 1996).

(2.) H. Bothner and O. Wik, "Rheology of Hyaluronate," Acta Otolaryngol. 442, 25-30 (1987).

(3.) E. Balazs, "The Physical Properties of Synovial Fluid and the Specific Role of Hyaluronic Acid," in A.J. Helfet (Ed.), Disorders of the Knee (J.B. Lippincot, Philadelphia, Pennsylvania, USA, 1982) pp 61-74.

(4.) D.S. Kalman, et al., "Effect of a Natural Extract of Chicken Combs with a High Content of Hyaluronic Acid (Hyal-Joint) on Pain Relief and Quality of Life in Subjects with Knee Osteoarthritis: A Pilot Randomized Double-Blind Placebo-Controlled Trial," Nutr. J. 7, 3 (2008).

(5.) I. Moller, D. Martinez-Puig and C. Chetrit, "Oral Administration of a Natural Extract Rich in Hyaluronic Acid for the Treatment of Knee OA with Synovitis: A Retrospective Cohort Study," Clinical Nutrition Suppl. 4(2), 171 (2009).

(6.) P. Conhagan, et al., "EULAR Report on the Use of Ultrasonography in Painful Knee Osteoarthritis. Part 2: Exploring Decision Rules for Clinical Utility," Ann. Rheum Dis. 64, 1710-1714 (2005).

(7.) J.U. Carmona, et al., "Effect of the Administration of an Oral Hyaluronan Formulation on Clinical and Biochemical Parameters in Young Horses with Osteochondrosis," Vet. Comp. Orthop. Traumatol. 22(6), 455-459 (2009).

(8.) V. Castillo, et al., "Effects of Oral Administration of Hyal-Joint[R] in 17 Day Rat Developing Type II Collagen Arthritis," Osteoarthr. and Cartil. 18(2), S244-S245 (2010).

For more information

Cristina Martinez

Product Manager


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Title Annotation:bone and joint health
Author:Martinez, Cristina
Publication:Nutraceutical Business & Technology
Article Type:Report
Geographic Code:1USA
Date:Jan 1, 2011
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