Hyaluronic Acid Reduces Joint Friction
This natural polymer acts to lubricate joints
that are vulnerable to the ravages of osteoarthritis
By Will Block
What’s a nice molecule like you doing in a joint like this?
— W. Block
othing—not a piece of Teflon, not even a puff of air—can rub against another object without generating some friction, however slight. Friction comes in many guises. The friction between tire and road keeps your car from sliding wildly out of control. The friction of a bow across a violin string can make heavenly sounds. Perhaps you awake in the morning from the friction of your cat’s tongue on your face. The wind and waves generate friction on everything they touch, slowly but surely wearing away even the hardest rocks.
The feathery friction of a lover’s caress can make your heart race. That increases the friction generated as your blood roils through your heart and rushes out through your arteries (friction makes the sounds heard through your doctor’s stethoscope). The friction generated as the chyme in your stomach churns about helps with digestion; and that embarrassing gurgling sound (wonderfully named borborygmus) that usually happens at the wrong time is caused by the friction of gas or fluid moving around in there. The friction of air molecules passing over your vocal chords makes them vibrate, giving voice to your thoughts. There is even friction in your brain every time you move, as the 3-pound organ slides about, just a little, inside its protective housing.
Within normal bounds, friction is a necessary and often desirable phenomenon. Undue friction, however, is another matter, and in one case it can become intolerably painful: bone on bone. What a pity that Mother Nature didn’t see fit to provide us with Teflon-capped bones to prevent the pain of osteoarthritis (the most common form of arthritis). Give her credit, though, for trying to keep our joints properly lubricated and happy by providing slippery, spongy cartilage and synovial fluid (more on that below). It’s not her fault that they tend to deteriorate with age. (Well, actually it is her fault, but let’s try not to make her angry, OK?)
Friction . . . Knees . . . Bad Combination
When you think of joint problems, which joint comes to mind first? Right—the knee. Considering that our knees are the most complex of all our joints and that they take a tremendous pounding even during ordinary daily activities, such as walking, it’s hardly surprising that they’re ground zero for injury and degenerative joint diseases. Oh, the pain caused by deteriorating knees! Some people would give an arm and a leg to be rid of it. (Hey, wait a minute . . .)
It’s not just knees, though. Hands and hips are commonly afflicted, as well as the all-important spine. Almost every joint can suffer to some degree, but our feet, curiously, are not very susceptible. Despite enormous effort, the pharmaceutical industry has been largely unsuccessful in doing anything for osteoarthritis sufferers except to alleviate their symptoms to varying degrees, primarily with NSAIDs (nonsteroidal anti-inflammatory drugs), such as aspirin, acetaminophen, ibuprofen, and naproxen.* That’s a major benefit, of course, but it pales in comparison with the prospect of curing the disease, or at least retarding its progress.
Glucosamine Can Improve Joint Function
Paradoxically, the only agent that has been definitively shown to improve the course of osteoarthritis rather than merely to alleviate its symptoms is a nutritional supplement, glucosamine, which is an amino sugar found naturally in our bodies. It’s a precursor to an important class of complex carbohydrates called glycosaminoglycans (formerly called mucopolysaccharides). These are large polymers that play a central role in the formation of cartilage and synovial fluid; the latter is the clear gelatinous fluid that serves to lubricate our joints, tendon sheaths, and bursae. [Glucosamine is safe for diabetics, by the way. A study has shown that, used properly, the amino sugar does not adversely affect glycemic control, i.e., it has no appreciable effect on blood sugar (glucose) levels.]
Glucosamine, which appears to help repair and build cartilage, is a prescription drug in many European and other countries. Most of the evidence for its efficacy has been obtained with the sulfate salt, but the hydrochloride salt is believed to be effective as well. It’s referred to as a structure-modifying agent, which means that it actually changes the joint structure, in ways that may improve joint function for a long time.
Excellent Results in Glucosamine Studies
In a superbly designed Belgian study published in 2001, glucosamine sulfate supplementation (1500 mg/day for 3 years) was found to halt the physical deterioration of arthritic knees, as indicated by precise radiographic measurements of the joint space between the bones (see “Landmark in Osteoarthritis Research Validates Glucosamine Sulfate” in the April 2001 issue of Life Enhancement). As a “bone-us,” the treatment provided significant relief from the patients’ pain and stiffness.
In a similar Czech study published in 2002, essentially the same results were observed, adding weight to those of the first study (see
“Glucosamine Sulfate Scores, Again, Against Arthritis,” March 2003). And in 2004, the Belgian and Czech researchers collaborated in yet another study showing positive results (see
“Postmenopausal Women Benefit from Glucosamine,” September 2004).
Chondroitin Sulfate Can Be Beneficial Too
Also believed to be effective against osteoarthritis, particularly when used in combination with glucosamine, is chondroitin sulfate, which is a structural component of cartilage.* Chondroitin sulfate is a glycosaminoglycan (the most prevalent one of all); hence it’s a polymer, unlike glucosamine, which is not. As is true of most polymers, chondroitin sulfate’s chain length is highly variable—and so, therefore, is its molecular weight, which reflects the total number of atoms in the molecule. This variability can affect both the physical and chemical properties of the compound, and hence its biological activity.
The combination of chondroitin sulfate with glucosamine sulfate or glucosamine hydrochloride has been used in some scientific studies; others have used chondroitin sulfate alone (see
“Supplements Put the Brakes on Osteoarthritis,” December 2003). The results have been somewhat ambiguous, with some studies showing a benefit, particularly for chondroitin sulfate of relatively low molecular weight, and others showing none. What is clear, however, is that chondroitin sulfate may be beneficial and is certainly not harmful; thus it makes sense to use it together with glucosamine and other potentially beneficial substances.
Hyaluronic Acid Bathes and Lubricates Our Joints
One such substance is hyaluronic acid, the largest of all the glycosaminoglycans. This polymer, which is found in all animals, acts as a binding and lubricating agent and shock absorber throughout the body. It’s found abundantly in skin (and it’s a common ingredient in skin-care products) and connective tissues.
Hyaluronic acid is also an important component of articular (joint) cartilage, and it’s the principal constituent of synovial fluid, which bathes and lubricates all our synovial joints. A synovial joint is a moving joint (not all joints move) in which the opposing bony surfaces are covered with a layer of cartilage within a membrane-lined cavity that is filled with synovial fluid and is reinforced by a fibrous capsule and ligaments. Together, the articular cartilage and synovial fluid act as a shock-absorbing cushion, keeping the ends of our bones at a safe distance from each other. (See the sidebar for how this works.)
Shocking Facts About Hyaluronic Acid
The word hyaluronic comes from the Greek hualos, meaning glass, and ouron, meaning urine; hence, hyaluronic acid means a glassy substance associated with urine. Bet you didn’t know that, or that hyalophobia is a morbid fear of glass objects—a condition that definitely does not afflict people who are prone to hyalophagia, the eating or chewing of glass. (There is no behavior so bizarre as not to have been given a fancy technical name.)
But why glass? Why urine? Hyaluronic acid (also known as hyaluronan) was first discovered in the vitreous humor—the clear, watery fluid that fills the eyeball behind the lens. Vitreous means glassy (our eyes are, after all, transparent), and so does the prefix hyalo-. As for the urine angle, read on, and you’ll see.
As mentioned in the article, hyaluronic acid (HA) is a glycosaminoglycan, and it’s the largest known member of this class of polymers. It’s composed of repeating units of a particular disaccharide (a two-sugar molecule) in extremely long, unbranched chains. Each such disaccharide pair (a dimer) consists of glucuronic acid and N-acetylglucosamine.
Glucuronic acid is a glucose derivative that reacts with many foreign chemicals as well as with the natural breakdown products of normal body constituents to form compounds called glucuronides, which are excreted in the urine (a-HA!). N-Acetylglucosamine is a derivative of glucosamine (which is a derivative of glucose) and is a constituent not only of HA but also of many members of the class of compounds called glycoproteins.
A molecule of HA can contain up to a few tens of thousands of the disaccharide dimers. In human synovial fluid, the average molecular weight of the HA is about 3–4 million daltons (atomic mass units), representing about 7,700–10,300 dimers. (By comparison, the molecular weights of water and glucose molecules are 18 and 180 daltons, respectively.)
Much of our cartilage consists of the triple-helical protein collagen, which provides structure and tensile strength, as well as huge molecular complexes called proteoglycans, which are composed of chemically bound proteins and glycosaminoglycans. The principal proteoglycan, called aggrecan, serves as our joints’ primary shock absorber. How does it do that?
Well, the protein part of aggrecan consists of three globular domains, the surface features of which permit the binding of two glycosaminoglycans, namely, chondroitin sulfate and keratan sulfate, between them. Together, these entities constitute aggrecan. But one end of the aggrecan can also bind to yet another glycosaminoglycan, namely, hyaluronic acid, anywhere along the length of the HA molecule. When large numbers of aggrecan molecules do so, the result is an immense complex, up to several micrometers in length, in which HA serves as the molecular backbone, with all the aggrecan “ribs” projecting outward from it.
Now, the molecular structure of glycosaminoglycans allows them to attract and hold countless water molecules through electrostatic forces and weak chemical interactions called hydrogen bonds, which are easily formed and broken. The water-holding capacity of these glycosaminoglycans is so great that, when they’re incorporated into the molecular complex described above, the complex can hold up to 50 times its own weight in water.
This enables the complex to cushion the effects of physical impacts, such as the compressive forces generated when our feet hit the ground while walking or running. Upon impact, water is squeezed out of the glycosaminoglycans, and when the compressive force dissipates, the water rebinds to these thirsty molecules.
And that is why—assuming you don’t have arthritis—you don’t have to shout “Ouch!” every time you take a step. You can thank your hyaluronic acid and chondroitin sulfate, among others (including glucosamine, which is a precursor to the glycosaminoglycans).
Have you cracked your finger joints lately? Here’s what happens. When the two parts are pulled away from each other, the joint capsule expands, but the synovial fluid can’t, so a partial vacuum is formed. Gases dissolved in the fluid quickly form a bubble that bursts with a cracking sound. It’s called cavitation, and it’s harmless.
Oral Hyaluronic Acid for Osteoarthritis?
Osteoarthritis occurs when the cartilage—especially in a weight-bearing joint—erodes with age and the wear and tear of physical activity. As the cartilage becomes soft, frayed, and thinned, its Teflon-like properties diminish, and frictional forces build, aggravating the condition. Eventually, there is bone-on-bone contact, and real friction—and major pain.
Can hyaluronic acid (HA) help alleviate this condition? Some researchers think it can—and not just by injection into the knees (a therapy called viscosupplementation, which has been in use since the early 1990s). During the last five years, oral ingestion of HA has been studied in both animals and humans, with some promising results. (The animals, in this case, were not limited to the usual mice and rats; they also included dogs and even thoroughbred racehorses, in which lameness can mean the loss of big bucks.)
Rats Absorb It, and Phospholipid Seems to Help
Recently a team of researchers in China investigated the “oral” absorption of hyaluronic acid by healthy rats—“oral” because the rats did not actually ingest the HA; instead, it was administered intragastrically, as a solution deposited in their stomachs via syringe. HA was given in three forms: (1) by itself; (2) as a physical mixture with a phospholipid (lecithin, aka phosphatidylcholine) to aid in its absorption; and (3) as a chemically bound complex, called Haplex, of HA and the phospholipid (PL).
Blood was drawn at intervals after the treatment to determine the HA concentration. The results showed a significant absorption of HA, peaking at about 7 hours. In general, the mixture of HA and PL was somewhat better absorbed than HA alone, and the Haplex was absorbed somewhat better than the mixture. In the control group, which received only saline solution, the HA levels did not change.
Rabbits Get It in the Knees
The Chinese researchers speculated that, in addition to facilitating the absorption of HA via the gastrointestinal tract, phospholipids might also enhance HA’s effects in the synovial fluid. Hints that this might indeed occur had been obtained several years earlier by Japanese researchers, who investigated the combined use of high-molecular-weight HA and PL by injection into the knees of rabbits in which severe degeneration of the articular cartilage had been surgically induced.
After a number of in vitro studies had shown promising results in this area, this was the first in vivo study. The objectives were to determine: (1) whether HA would effectively lubricate the rabbits’ knee joints and prevent further degeneration of the articular cartilage; (2) whether the HA-plus-PL mixture was superior to HA alone in this regard; and (3) whether HA of a higher molecular weight—2,000,000 daltons (atomic mass units)—was better than HA of a “conventional” molecular weight (800,000 daltons).
The results were generally disappointing—the benefits seen were small and, for the most part, not statistically significant—but they were also encouraging in the sense that there was a small but measurable tendency for the HA-plus-PL mixture to produce better results than were obtained with HA alone. Curiously, despite prior evidence that high-molecular-weight HA was generally superior to low-molecular-weight HA in lubricating qualities, this study showed no significant difference between the two samples used.
High Molecular Weights Are Generally Better
More recently, however, another Japanese group reviewed the literature in this area and performed experiments of their own to determine the effect of HA’s molecular weight on the elastic properties of articular cartilage. In both cases, they found that molecular weights of a few million daltons were superior to those in the range of hundreds of thousands of daltons. (Recall that for chondroitin sulfate, low molecular weights appear to work better; go figure.)
It may not be coincidental that over a human lifetime, the average molecular weight of the HA in our articular cartilage declines markedly, from about 2,000,000 daltons to about 300,000 (on the other hand, the amount of HA in our joints increases). With that decline come the degenerative changes that lead eventually to arthritis—either osteoarthritis or rheumatoid arthritis (HA has been found to be beneficial in treating the latter disease as well).
Pain, Pain, Go Away . . . and Don’t Come Back
There’s nothing like pain to concentrate the mind. It can be a distracting annoyance or a force so strong as to overwhelm one’s ability to do much of anything besides trying to avoid or alleviate it. Arthritis victims know all too well that their knees can ache even while they’re sitting down, and stabs of pain can strike like lightning bolts out of the blue, just from making a wrong move.
Friction is the culprit. We cannot make it disappear, but we can, to a significant degree, hold it at bay with glucosamine, chondroitin sulfate, and hyaluronic acid, and possibly a few other agents as well. Considering the stakes, it’s worth any effort to preserve and protect the mobility in our precious joints.
- Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Arch Intern Med 2003;163:1587-90.
- Huang SL, Ling PX, Zhang TM. Oral absorption of hyaluronic acid and phospholipids complexes in rats. World J Gastroenterol 2007;13(6):945-9.
- Kawano T, Miura H, Mawatari T, Moro-Oka T, Nakanishi Y, Higaki H, Iwamoto Y. Mechanical effects of the intraarticular administration of high molecular weight hyaluronic acid plus phospholipid on synovial joint lubrication and prevention of articular cartilage degeneration in experimental
osteoarthritis. Arthritis Rheum 2003;48(7):1923-9.
- Kato Y, Nakamura S, Nishimura M. Beneficial actions of hyaluronan (HA) on arthritic joints: effects of molecular weight of HA on elasticity of cartilage matrix. Biorheology 2006;43:347-54.
Will Block is the publisher and editorial director of Life Enhancement magazine.