Joint Supplements Controversy
In this issue, we discuss one of the hottest, and most controversial, areas of supplementation on the equine market--glucosamine, chondroitin sulfate, and other oral supplements for horses with signs of osteoarthritis or degenerative joint disease. These products are among the most successful classes of nutraceutical supplements currently available for horses--although "successful" doesn't necessarily mean "effective."
Despite the fact that many of these products escape regulation as drugs by means of clever packaging and vague claims, and despite the fact that they're far from inexpensive, oral "joint" supplements are a huge hit among the owners and trainers of performance horses.They're absolutely flying off the store shelves, helped along by a powerful marketing machine that bases its advertising mainly on anecdotal claims of horses regaining ease and fluidity of movement and a return to top performance. Savvy advertising has implied that the "chondroprotective" effects these supplements are supposed to have assist an older horse with established symptoms of DJD, and they might help keep a younger horse from developing symptoms. Meanwhile, manufacturers vie for your market share by altering the recommendations for dosages or combinations of ingredients, or for the mode of administration (right now, liquid supplements are trendy), or by talking confusingly about features like molecular weight.
For the consumer, this makes choosing the "right" supplement a real crapshoot. Since most of us aren't scientists, it comes down to which product has the most convincing name and the most eye-catching packaging.
Despite this minefield of consumer misinformation, chances are you've tried at least one kind of oral joint supplement on your horse. If not, you certainly know someone who swears by a particular brand, and swears it made a difference to her horse's health or performance. But the hard, unvarnished truth of it is that oral joint supplements still have very little proof of efficacy behind them, even after having been on the North American market for more than a decade.
There's ample evidence that they do no harm, and there's some evidence that they might have a beneficial effect in other species (most notably humans and dogs). But even those results are controversial, because they're often based on studies in which there was no control group (a group taking a placebo instead of the supplement); or they only examined the raw "active" ingredient in a commercial supplement rather than the whole supplement itself.
Furthermore, very little scientific study has been done on these products specifically in horses. Horses aren't humans or dogs; some of their physiological processes are significantly different, so it's risky to extrapolate from other species. The result is that we don't know very much about how oral joint supplements might operate in the equine body, or if they are even absorbed when taken orally!
Many manufacturers are perfectly content with this scenario--after all, their products are selling like gangbusters purely on the strength of anecdotal claims. Why should they sink big money into research?
Let's take a hard look at the questions surrounding oral joint supplements, then you can make up your own mind. But first, let's make sure we understand the rationale behind them.
Arthritis: A Short Course
A normal equine joint functions with the aid of synovial fluid (a viscous liquid about the consistency of egg whites) that helps lubricate the joint. Synovial fluid is a nutrient-rich brew that contains proteins, enzymes, water, leukocytes, and the key ingredient sodium hyaluronate, which is responsible for the fluid's elastoviscous qualities. Sodium hyaluronate (formerly known as hyaluronic acid) is a negatively charged glycosaminoglycan (GAG)--more simply put, a sugar chain--that arranges itself in complicated coils, adapting to the pressure changes in the joint capsule as the horse moves. It assures the unhindered passage of metabolites to and from the joint, and serves as a stabilizer and shock absorber for the structures that are undergoing continual mechanical stresses.
Cartilage, the other main shock-absorbing component of a joint, coats the ends of each bone. It's made up of a web of collagen fibers, with cells called chondrocytes scattered along the matrix. Chondrocytes produce giant proteoglycan molecules (that resemble microscopic bottle brushes) that bind the GAGs; the GAGs in turn extract and loosely hold large amounts of positively charged water molecules.
Unfortunately, cartilage is one of the body's most primitive structures. It has no blood or nerve supply of its own, so it has little or no ability to repair itself. As a result, although cartilage performs admirably under normal conditions, it only takes a 5% to 10% overload of work stresses to begin the process of cartilage breakdown. The wear and tear of hard work, uneven or unyielding footing, poor conformation, or any number of other factors might trigger the deterioration of cartilage, which is where osteoarthritis begins. Although the horse notices no pain and continues to work with no observable lameness, havoc is ensuing inside his joints.
As soon as cartilage cells begin to erode, the cells of the synovial membranes respond by cleaning up the debris--a classic inflammatory response. The process of breaking down and removing the foreign bodies from the area changes the chemical makeup of the fluid in the joint, introducing excess fluids and a greater concentration of destructive enzymes and prostaglandins into the closed space. This destroys the lubricating GAGs. The synovial fluid begins to lose viscosity, becoming less like egg whites and more like water.
The chondrocytes eventually suffer from a compromised nutrient supply, can't keep up with repairs, and the cartilage develops pits, holes, and fissures, opening the bone ends to direct trauma. The bone responds with a defense that only causes further destruction--it lays down new bone to strengthen the surface (a process called sclerosis) and extend its margins (bone spurs and osteophytes). In its final stages, if left unchecked, arthritis causes fusing of equine joints.
In the 1960s, our only veterinary defenses against this destructive process were anti-inflammatories (such as Bute and corticosteroids) and rest. Then someone got the bright idea of replacing some of the natural constituents of joint fluid and/or cartilage, in the hope that the body could use those building blocks to restore normal function and halt the destructive cascade. Such substances would act in a chondroprotective fashion, altering the progression of arthritis and perhaps even reversing it.
One of the first such products to be made available was injectible sodium hyaluronate (aka "Hylartin-V," and a host of other brand names), which first went into widespread use around 1970. It was a revolutionary advance, often promoting the production of natural sodium hyaluronate within the joint. But its intra-articular administration was tricky. Eventually, it was found that intravenous injection worked, with the medication somehow finding its way to the injured joint to increase the viscosity of the synovial fluid, inhibit damaging enzymes, and encourage the body to manufacture more of its own sodium hyaluronate.
Polysulfated glycosaminoglycan (PSGAG), or Adequan, was launched in North America in 1984. In many cases it was more effective than sodium hyaluronate in reversing arthritic lameness and inflammation. PSGAGs can be administered by injection directly into the joint, or by intramuscular injection--but it's not cheap, and most horses require a course of injections over a period of weeks or months before they show improvement.
About a decade ago, the manufacturers of joint supplements took the ingredients needed for healthy joint function and put them in a handy jar rather than an intimidating syringe. Suddenly, this was available to the average horse owner, and administering it was as user-friendly as mixing a little powder with your horse's grain. Considering that most performance horses show signs of joint aches and pains, the idea immediately was embraced by the equestrian community.
What's In Them?
The two active ingredients found in oral joint supplements are likely familiar names to you by now, but their modes of action might not be as familiar. Here's some background on the role these naturally occurring chemicals might play.
Sometimes bound to sulfates, sometimes to hydrochloride (there's considerable debate as to which is better), glucosamine is one of the constituents of GAGs and proteoglycans in the joints, as well as an essential ingredient in most of the body's connective tissues, including tendons, ligaments, skin, hooves, heart valves, blood vessels, cell membranes, and so on. It's also a component of sodium hyaluronate. With-out enough glucosamine, the horse has no hope of healing damaged cartilage.
Providing glucosamine to joint cells, in theory, stimulates them to produce more GAGs, including sodium hyaluronate. It's important to note that glucosamine is a small molecule that is water soluble, so it can travel across membranes fairly easily.
This is a type of glycosaminoglycan (GAG) required for the formation of proteoglycans in joint cartilage. Supplementing this molecule might decrease the activity of destructive enzymes by binding with them and inactivating them, thus slowing the process of degradation in a diseased joint. It also might play a role in stimulating the body to produce more sodium hyaluronate and provide additional substrates (most importantly, sulfur) for the formation of a healthy joint matrix.
It's important to note that chondroitin sulfate is a very large and unwieldy molecule when compared to glucosamine, and there are questions about how well it passes through the intestinal cell walls.
In her book, Equine Supplements and Nutraceuticals: A Guide to Peak Health and Performance Through Nutrition, Eleanor M. Kellon VMD, makes this analogy: "A comparison would be how easy it is for you to swallow whole a strand of spaghetti (glucosamine) compared to a hair brush (chondroitin sulfate)."
Chondroitin sulfate can be extracted only from animal cartilage or connective tissue. Most often, it's derived from bovine tracheal tissue, which is a waste product from the meat packing industry. But there are many supplements that, rather than extracting purified chondroitin sulfate, offer the whole unpurified tissue in freeze-dried form in the hope that it might supply other useful GAGs.
Shark cartilage is one of these; extract of perna mussel (a type of sea mollusc) and/or sea cucumber are two others. While it's true that such products might offer some additional fatty acids and trace minerals when compared to purified chondroitin sulfate, you should ask yourself what the environmental im-pact of harvesting mus-sels or sharks purely for an equine joint supplement might be. Extracts of bovine tracheal cartilage likely contain the same trace ingredients at a lower cost to the ecosystem.
In the hope of improving absorption levels or otherwise boosting the performance level of the two key ingredients, manufacturers often add nutrients to oral joint supplements. Among those you're likely to see are methylsulfonylmethane (MSM), a source of organic sulfur (which is important in helping the body form a strong collagen matrix); copper, manganese, and zinc, and vitamin C. Whether these additives have any serious impact on a product's efficacy is unproven.
It's also unclear whether combining glucosamine and chondroitin sulfate in a single supplement provides any synergistic effect. In a paper published in the Alternative Medicine Review in 1998, Gregory S. Kelly, ND, wrote, "Although glucosamine sulfate and chondroitin sulfates are often administered together, there is no information available to demonstrate the combination produces better results than glucosamine sulfate alone."
Keep in mind that some oral joint supplements might contain anti-inflammatory additives, especially herbal ones like devil's claw. These can act to reduce the pain of arthritis without actually treating the disease--so they can tempt an owner into believing a healing effect is occurring from the glucosamine and/or chondroitin sulfate when in fact the horse might be feeling less discomfort while the destructive degeneration continues!
Do They Work?
That's the $64,000 question. While the idea of supplying more of what a healthy joint needs to function seems like a good idea, it's debatable whether offering those substances orally is an effective way to go. William Moyer, DVM, Professor of Large Animal Medicine and Surgery at the College of Veterinary Medicine, Texas A&M University, urges owners to employ some critical thinking before they plunk down their hard-earned dollars for oral joint supplements.
"As I see it, there are three main issues to consider," he says." First, can the product be absorbed across the intestinal wall, or is it destroyed by stomach acids before it can get there? Second, even if it is absorbed, can it get to the joint where it's needed? Third, even if it gets to the joint, does the body use it?"
The issue of absorption is a big one. Radio-labelling experiments have indicated that glucosamine sulfate is well-absorbed in humans (up to 87% after oral administration), but there's no good data available at the moment to reflect its absorption rate in horses. There's also considerable debate as to whether glucosamine hydrochloride or sulfate is the preferred form for an oral supplement. Although both probably are easily absorbed, the sulfated form contains less actual glucosamine by weight than the hydrochloride form. On the other hand, glucosamine might work better in the presence of more sulfur.
Chondroitin sulfates, because of their much larger molecular size, are generally considered to be poorly absorbed, with estimates ranging from 0% to about 13% (although one Japanese study reported a 30% absorption rate). The remainder of the chondroitin sulfate probably is digested into smaller constituents which then are absorbed. Further breakdown occurs in the liver after the particles reach the bloodstream. These individual components might have a beneficial effect if and when they reach arthritic joints, but we don't know for sure. If you choose to go with a chondroitin-source product like whole freeze-dried shark cartilage or perna mussel, remember that there's no data concerning the absorption rates of the active product from these, but that it probably makes the job of absorption that much more difficult than with a "purified" product.
David Frisbie, DVM, PhD, MS, Dipl. ACVS, an assistant professor of equine orthopedic research at Colorado State University in Fort Collins, Colo., has performed a number of in vitro studies in which chunks of equine cartilage are grown in a culture medium and manipulated to simulate arthritic changes found in intact joints by the addition of destructive proteins (such as interleukin-1).
"It's a way to use fewer horses in our research and get faster results," he notes. He and his team have examined the effects of both glucosamine-based products, and those based on chondroitin sulfates, on in vitro cultures. "We bathe the cartilage in a 'soup' containing the product, and watch for changes in the interleukin-1 over a period of seven to 10 days," he explains. "We're looking to see whether the product blocks the arthritic process. We've tried different concentrations (of both glucosamine and chondroitin sulfate) separately, then various concentrations combined, hoping to get some answers as to the ideal proportion and concentration of these medications needed for the best results. That's where we are now--taking steps toward getting answers, but we're not there yet. Once we have a clearer direction, the next step is to design studies on real horses."
While Frisbie's studies have provided encouraging early data to merit further study, he freely admits that in vitro studies do nothing to answer the question of absorption.
"In order to study absorption effectively, you need to tag the products with a radio-isotope and follow its progress through the body. Some studies of this nature are going on at the University of Guelph at the moment, but it's been complicated by the fact that it's quite difficult to tag these sorts of molecules."
Studies on live horses continue to be scarce because, as Moyer explains, "horses aren't food animals, so the government has no interest in providing funding, even though the horse industry is big business in the United States. Universities are dependent on the generosity of private funding for their research, and unfortunately the amount of money the industry puts back into research and development is incredibly small. We're all vying for the same dollars, and most people have no idea how expensive research is. For example, if I were to design a statistically valid study on the effect of oral joint supplements, I'd need a herd of 1,000 horses with identical arthritic lesions, performing identical activities, for three years."
In contrast, many of the existing studies quoted in the marketing literature and the slick brochures either are based on small sample groups, had no control group compared, relied on customer reports of improved attitude or performance (nebulous qualities at best), or compared horses with very different activity levels or degrees of DJD. The result has been that for every study which purports to demonstrate the efficacy of oral chondroitin sulfate and/or glucosamine in horses, there's another one that refutes it.
Further frustration comes from the fact that there are so many combinations and dosages of oral joint supplements available that, as Frisbie says, "It's tough to know where to start!" He agrees that in many cases there's been very little industry support for studies proving efficacy. "We've been approached more than once by manufacturers who initially wanted studies done, then withdrew at the last minute. What we really need is private foundation funding, but that, of course, is hard to secure. I'm aware of some suppressed studies as well, especially in small animals--studies which showed little efficacy, or didn't show the product in a positive light.
"Often there's no consistency as to quality control. There are still a lot of things that need to be brought into the light."
Moyer is less enthusiastic. "Not only is there very little scientific benefit proven for any of these oral products, there's absolutely no regulation as to purity." An article by Mark A. Anderson, DVM, MS, in the September 1999 issue of Compendium concurs. In the article, entitled "Oral Chondroprotective Agents: Evaluation of Products (Part II)," Anderson notes, "...70% of products analyzed for glucosamine and chondroitin sulfate did not meet label claims. Even when a product does contain the stated amount, quality and grade of the labeled compound may not be specified. For example, glucosamine and CS are available in a variety of grades of raw product. The studies that have evaluated the safety and efficacy of these two compounds used pharmaceutic-grade material; products using lower-grade material may not achieve similar results.
"Veterinarians should study labels to ensure that the exact amounts of active ingredient are listed and the labels are easy to understand. Labels that are not easy to read can often be deceptive if not examined closely. Products that combine metric and apothecary systems should be questioned because calculating dosages be-comes difficult.
"When evaluating non-drug oral products, veterinarians must base their selection decisions on their knowledge of the compound's safety and efficacy and the manufacturer's reputation."
The Bottom Line
The claims might be sincere, but in the real world it's devilishly difficult to isolate the variables and determine that, without a doubt, it was the oral supplement that did the trick. Perhaps old Champion's routine didn't change an iota except for the addition of the supplement to his diet--but then again, perhaps his turn-out routine changed, or he's being worked on softer footing, or his new farrier adjusted the angles of his hind feet by more than a degree, or that it got colder, or warmer, or whatever. Outside of the research environment, it's practically impossible to make only one change in a horse's life at a time.
Moyer emphasizes, "Joint damage is inevitable for any athlete. The only way you can avoid it is not to participate. From the standpoint of someone who's worked with lame horses for 30 years I can tell you that, despite all these so-called advances we've made in treating arthritic changes, racehorses are now making fewer starts and having shorter careers. If these products work so well, why aren't horses lasting longer?
"The marketplace is appealing to people who are looking for anything that might make a difference," he concludes. "But we're just not seeing improvement across the board."
Frisbie is a little more sanguine. "There's no good evidence that (oral joint supplements) work in horses. The scientific proof is just not there, though it will get done eventually. Anecdotally, there's some evidence, at least in humans, but it's a potency game. If you rated treatments for equine arthritis from a scale of 1 to 10, corticosteroids might be a 10 (in terms of fighting inflammation), Adequan might rate a five or a six, and the oral products might earn a two or a three."
With so many products, all suggesting difference dosages and frequencies of administration, it's tough to make any solid recommendations as to which product an owner might choose to use, he says.
There's also the economic point of view to consider. "Steroids are the cheapest way to go," Frisbie says, "and it's usually a one-time thing. Injections of Legend or Adequan are expensive, and you usually need a series of them, which may have to be repeated. But the oral products, given over a period of months or years, aren't any cheaper, and you may or may not see any benefit. Most people would be better served working with their veterinarians to choose the most appropriate way to medicate their horses, than by just choosing an oral supplement off the shelf."
If you're using an oral joint supplement on your horses and feel it's making a difference, chances are you aren't going to change your mind. But I hope at least you've been encouraged to examine your choices more closely and be less willing to believe the claims. There's still much more research to be done before we can say with certainty that oral joint supplements do--or do not--have a place in the treatment of the arthritic horse.
About the Author
Karen Briggs is the author of six books, including the recently updated Understanding Equine Nutrition as well as Understanding The Pony, both published by Eclipse Press. She's written a few thousand articles on subjects ranging from guttural pouch infections to how to compost your manure. She is also a Canadian certified riding coach, an equine nutritionist, and works in media relations for the harness racing industry. She lives with her band of off-the-track Thoroughbreds on a farm near Guelph, Ontario, and dabbles in eventing.
POLL: University Equine Hospitals