Hyaluronic Acid (HA) - what is it and how can it help your joints?

By Jason Theodosakis, M.D., M.S., M.P.H., FACPM   "Dr. Theo"

In the 1990s, arthritis and related conditions passed up heart disease as the number one cause of disability in America. Since that time, the prevalence of arthritis has increased even further and will continue to do so in the foreseeable future.

According to the CDC, one in three adults are now affected by an arthritis related condition. For those who are affected, quality-of-life often declines. Pain, stiffness and inflammation can lead to decreased voluntary activities, such as exercise or recreational endeavors. This indirectly results in a host of conditions including: depression, obesity, heart disease, diabetes, work or relationship problems, among many others. For most people, life is just not as enjoyable with arthritis.

The good news is that the high prevalence of arthritis has led to increased awareness and increased research efforts.  New treatment options have become available which allow for improvement in pain and function while having a better safety profile compared to earlier treatments.

In the 1990s, the first available hyaluronic acid (abbreviated as “HA”) products became available as injectable agents for osteoarthritis of the knee. These were, and are still today prescription items which are administered by physicians in a series of three to five weekly injections. Injectable hyaluronic acid is well-established as a safe therapy for osteoarthritis and is part of the American College of Rheumatology guidelines for treating osteoarthritis of the knee. After a series of injections, over half of the patients receiving HA have persistent improvements in pain and function lasting up to a year. By providing long-lasting relief, osteoarthritis patients can often avoid the dangers associated with over-the-counter or prescription anti-inflammatory drugs.

Receiving an injection inside the joint however is something that most people do not take lightly. It's an invasive procedure that involves pain and some risk -- a small chance of introducing an infection in the joint. Costs can be a factor, especially if insurance doesn't pay as the labor and materials for a series of injections can approach $1,500. It's also inconvenient to have to return to the doctor to receive the full series of injections, or repeat injections, if necessary.

Recently, oral forms of hyaluronic acid, which are nonprescription and sold as dietary supplements, have become available. The benefits of an oral formulation compared to injections are obvious: lower cost, no pain, lower risk, and improved convenience. In the past couple of years, research on oral HA has been steadily increasing and has vaulted this product into the limelight.  

What is HA and what is its role in the joints?

HA is a naturally occurring family of extremely large molecules that are contained in many tissues in our bodies. HA molecules have both structural and functional effects. For instance, HA is one of the components it gives our tissues flexibility. Your eyeballs, for instance are “squishy” mainly because of their high HA content. Same goes for the cartilage in your joints.

Joint cartilage, called articular cartilage in medicine is a glistening, smooth, translucent whitish colored living tissue that provides both a low friction environment for movement and shock absorption to protect the bones from fracturing with activity. HA serves as a backbone which connects charged molecules, such as chondroitin sulfate. Groups of these charged molecules tend to repel each other - think of the way like poles of two magnets help keep the magnets away from each other. This electromagnetic repelling effect is a critical function of healthy cartilage. It gives joint cartilage its special properties. Joint cartilage is so special in fact, that nothing man-made can currently approach the performance of this remarkable tissue. Joint cartilage is also very prevalent in the body as it caps the ends of the most bones in our 230 different joints.

Other structures make up the joints besides bones and cartilage. Bones are held together by ligaments and muscles are attached to bones by tendons. Surrounding the joint is a watertight, fibrous joint capsule which itself has several functions. Specialized cells called synoviocytes, which line the interior portion of the joint capsule, produce the synovial fluid, a thick, clear substance that looks and feels like raw egg white. Synovial fluid provides lubrication to the cartilage, increases the effectiveness of shock absorption and allows for the exchange of nutrients and waste products between the inside of the joint (which has no blood supply of its own). The joints have their own specialized system for exchanging nutrients and waste products.  This is in contrast to most tissues of the body (which are filled with small blood vessels called capillaries).

The joint capsule has other functions as well. For instance, it is loaded with blood vessels and nerves. These nerves send signals to the brain detailing the position of the joints in three-dimensional space. This type of information helps us walk with our eyes closed, for instance. The joint capsule can also be a source of pain due to disease or injury.

This is where hyaluronic acid finally comes into the picture. HA is the principal, functional component of synovial fluid. HA is responsible for giving synovial fluid its thick, viscous properties which are vital to normal joint function. HA molecules produced naturally in the body are extremely large in size, but are not completely uniform, some HA molecules are longer than others, and are often coiled up in various patterns to form complex structures. The size of these molecules is characterized by units of measures called Daltons, a description of molecular weight. In general, the higher the molecular weight, the larger the molecule. From pharmaceutical industry research, we know that the larger sized HA molecules (500,000 Daltons and up) result in a greater physiologic response. If the molecules are too small or are too large, this response will not be triggered in the same manner.

The consequences of insufficient HA in the 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, since 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 two-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.

The chemical effects of insufficient HA in the joints are still being elucidated. Researchers are discovering new mechanisms by which HA helps relieve pain and improve function in patients with osteoarthritis. The prevailing theory is that HA molecules of a certain size and geometric configuration can attach to binding sites on cells within joints. Once this attachment is made, a cascade of molecular events occur within the cells. For instance, HA molecules appear to inhibit some of the enzymes which help degrade components in the joint and some of the chemicals that lead to inflammation. HA is an anti-inflammatory, but its mechanism differs from that of over-the-counter or prescription anti-inflammatory drugs. HA molecules also appear to disrupt some of the nerve impulses that transmit pain signals from the joint to the brain. In addition, HA molecules can stimulate the cells that line the joint capsule and trigger those cells to manufacture more hyaluronic acid.

What are the differences in the various forms of hyaluronic acid?

The source of oral forms of hyaluronic acid sold as dietary supplements come from three general categories: low purity animal extractions mixed with collagen, fermentation from bacteria, or concentrated extraction from avian cartilage. The original pharmaceutical forms of injected hyaluronic acid were all derived from the latter category so it makes sense that this is also the optimal form for dietary supplements. Low purity animal extractions mixed with collagen and are undesirable because of the low concentration of hyaluronic acid (usually 10% or less). To get an adequate quantity of hyaluronic acid, one needs to take a significant volume of this material. It's also questionable whether the biologic activity of this source of hyaluronic acid compares with the others. Hyaluronic acid derived from fermentation from bacteria is devoid of some of the natural, active components found in the concentrated extractions from avian cartilage. Perhaps this helps explain the result of an internal,  comparison study between a fermented HA versus a concentrated extractions from avian cartilage. When exposed to a culture of living synovial cells, the concentrated extraction from avian cartilage was twice as efficacious at stimulating production of more HA compared to the fermented product, even though the concentrations of each product was the same (200 mcg/ml). This might translated into a more effective product or allow manufacturers use lower doses, making the concentrated extractions from avian cartilage more economical. The final main difference in the various forms of HA related to the world-wide experience of the different sources. The concentrated extractions have been utilized extensively in the clinic and in large human studies (some of long-duration), in the pharmaceutical community.

Hyal-Joint® brand of oral Hyaluronic Acid supplementation

Manufacturers choose different raw materials based on a number of factors, but too often price is their main consideration. This trend is likely to change as research compares the biologic activity of different raw material sources. As is the case with most dietary supplements, there are some raw materials that are better studied, more biologically active, and more likely to yield positive effects.  Hyal-Joint® appears to be the “best in breed” of the oral hyaluronic acid products for dietary supplementation. It is a concentrated extraction from avian cartilage that also has other, naturally active components.  It's been studied in laboratory experiments, indicating anti-inflammatory effects. There's also documented absorption in an animal model, and a positive, pilot clinical study in humans. Perhaps most interesting, is data from a veterinary study involving oral administration of Hyal-Joint® to horses. In this study, horses were given 250 mg of Hyal-Joint® daily for eight weeks. At the end of the study, and subsequently four weeks later, increased levels of hyaluronic acid were noted in the joint fluid of the horses. This is very interesting because it not only indicates absorption of this oral HA product, but also an effect in the target tissue -- in this case the joints. This effect has been corroborated in the lab. Hyal-Joint® is a potent stimulator of endogenous HA in synovial cells. Further animal and human testing is underway.

Besides the ongoing research, the suggested dose of how joint in humans is another bright spot for manufacturers trying to limit the size of their dietary supplements. The human clinical trial utilized only 80 mg per day. The trial is underway using a 40 mg dose and some manufacturers will add 20 mg to joint health supplements containing other active components such as glucosamine and chondroitin. More information is available at www.Hyal-Joint.com