Some demographic expert has probably already enlightened you with the statistic that every seven seconds, someone in the U.S. is having a 50th birthday. This reality conjures up a vivid image of a rushing stampede (with a lot of buying power, I might add) to shop for those "look good, feel good" products. Such promises may be delivered in anti-wrinkle cream, weight loss products, fitness and spa memberships or herbs that may even help you remember what you forgot you were going after.

Meanwhile, all of this rushing around may wreak dreadful havoc on the joints. Of those aged 50+, 80% currently experience some form of joint discomfort (Sloan, 1999). This is reflected in consumer reports compiled by health trend experts. For instance, a recent survey shows that 73% of Americans are "very" or "somewhat" concerned over joint pain/arthritis (Applied Biometrics, 1998). These consumers are so concerned, in fact, that more than $1 billion is spent on unproven arthritis remedies. Other surveys show that one third of Americans believe herbals can help treat arthritis (Gallup, 1998). This strong belief in alternative choices outside of the traditional pharmacological approach has pushed U.S. sales of joint pain-related dietary supplements to just under $750 million (Decision Research, 1998).

'Wear & Tear' Market Drivers
Currently nearly 40 million people in this country experience some form of arthritis or joint inflammation (NIH, 1998). The potential causes of this painful inflammation, however, differ from one form of arthritis to another. Although this can include a simple injury from exercise, the more prevalent forms are osteoarthritis and rheumatoid arthritis. Osteoarthritis, the most common form affecting 12.1% of the U.S. population, is a condition where cartilage that lines the joints "wears away," allowing the bones to brush against each other. Rheumatoid arthritis, or chronic swelling of the joints, is the next common form and affects almost 10% of the U.S.

Regardless of the form, the impact on days of restricted activity or days lost from work make it the leading cause of industrial absenteeism. Some financial experts estimate that it costs the U.S. economy 1% of the gross national product or $35 billion per year in medical care and lost wages. Over the next several years, this cost is expected to multiply over 2.5 times, reaching $95 billion.

An estimated $45 billion is spent annually in the U.S. on treating diseases associated with being overweight. With obesity on the rise and more than half of American adults currently overweight or obese, this will have its own impact on joint pain. Experts say that being overweight increases the load placed on the joints, which could possibly speed up cartilage wear and tear. According to Johns Hopkins Arthritis Center, being only 10 pounds overweight increases the force on the knee by 30-60 pounds with each step. Population studies have shown a relationship of being overweight as a factor in developing osteoarthritis of the knee (Anderson, 1988).

In addition to the personal choices of exercise and diet, there are literally hundreds of products targeting consumers with joint pain. Claims cover the gamut of relief from severe inflammation or loss of mobility to aches and stiffness associated with the strains of exercise. So as consumers are deciding between a conventional route of prescription drugs or OTC products like aspirin or shopping in the alternative aisle of dietary supplements, companies are fighting for their dollars by continuing to develop and position new or improved ingredient combinations.

On the prescription front, the pharmaceutical industry is battling over several billion dollars for cox-2 drugs, a purported breakthrough treatment for arthritis. The dietary supplement industry, on the other hand, continues to clamor over a market approaching $1 billion, with special formulations of glucosamine and chondroitin taking the lead. It doesn't stop there, as more offerings have entered the fray, leveraging ingredients like MSM, shark cartilage, curcuminoids, boswellic acid and gingerol extracts as well as new claims on the more familiar antioxidants, omega-3 fatty acids and gelatin.

"Tylenol" and other acetaminophen brands are generally the first line of defense for osteoarthritis. They are used alone or in combination with other pain-relievers, i.e. nonsteroidal anti-inflammatory drugs (NSAID's) such as "Advil," "Aleve" or "Motrin." Individuals who may not experience relief from acetaminophen or whose stomachs cannot handle the commonly used NSAID's may benefit from a new class of NSAIDs called cox-2 drugs.

Cox-2 drugs, so-called because they act on the enzyme cyclooxygenase-2, are touted to be the next big breakthrough in the treatment of arthritis. According to the Johns Hopkins Arthritis Center, these new drugs appear to be as effective as NSAID's in managing the pain and inflammation of arthritis without severe gastrointestinal bleeding, side affects of longer term use of some current drugs.

Given the market potential, its not surprising that drug makers are lining up to get a piece of the action. Monsanto and Pfizer are co-marketing "Celebrex," a cox-2 drug already estimated to reach sales of $1 billion in 1999 and quadruple in sales by 2002. In its first three weeks on the market, roughly 142,000 new prescriptions were written, making it the second best launch ever after Pfizer's "Viagra." Merck's "Vioxx" is anticipating similar results and is expected to get FDA approval sometime this year. The competitive landscape is heating up as Abbott Laboratories has acquired U.S. marketing rights to the cox-2 drug "Mobic." Abbott will sell the drug along with its maker, Germany's Boehringer Ingelheim GmbH.

The 'Miracle Combo' Is Only A
Supermarket Or Website Away
When standard medication and exercise programs fail to provide any relief, individuals are seeking new options from the expanding alternatives market. The media blitz in early 1997 brought "Cosamin DS," a patented glucosamine and chondroitin combination, into the limelight. New York Times columnist Jane Brody shared her personal experience of joint relief from its use in her "Personal Health" column. The awareness was further heightened by features released in mainstream magazines such as Time as well as the New York Times bestseller The Arthritis Cure, which discusses "the medical miracle that can halt, reverse and may even cure osteoarthritis."

Nutramax Laboratories, Baltimore, MD, the producer of Cosamin DS, patented the synergistic effect of the combination of glucosamine and chondroitin on cartilage matrix enhancement. The product is a double strength formula offered through licensed health care professionals and behind the counter at pharmacies. Product literature states that "Cosamin DS provides the raw materials that are essential for the synthesis of synovial fluid and the complete cartilage matrix including collagen, hyaluronic acid and various modified sugar chains of the glucoaminoglycans."

You don't have to look too hard to find products containing glucosamine and chondroitin on supermarket, drug store and health food shelves or on the Internet. The popularity among consumers is sparking more competition with products like "Osteo-Bi-Flex," "Arth-X Plus," "Inholtra," "Joint Modulators," "Joint-EZ" and many others. Rexall's Osteo-Bi-Flex is poised to deliver $100 million in 1999 revenues. In fact, according to analysts, Osteo-Bi-Flex is the number two best selling nutritional supplement in the U.S. food, drug and mass market and achieved its position after just eight months on the market, with only 45% ACV (all commodity value) distribution (Adams, Harkness, & Hill, 1999). Rexall was granted the exclusive license in the U.S. and Canada to market the Nutramax patented combination as Osteo-Flex 450. Given product proliferation from other companies, Nutramax has filed patent infringement lawsuits in U.S. District Court for the District of Maryland against a number of companies that it alleges have sold its patented formula without authorization.

This is not a completely new approach in joint relief. Recognizing that glucosamine, a modified sugar produced in the body, plays a role in cartilage resiliency, researchers began looking into its potential affects in the 1950's. By the 60's, some European physicians used glucosamine sulfate to relieve arthritic pain in the form of intramuscular injections. Germany seems to be leading the way here as several drugs have been prescribed to osteoarthritic patients for the past 25 years as injectable purified components of cartilage ("Arteparon" and "Rumalon"). These drugs were shown to slow the progression of arthritis. Arteparon has been approved in the U.S. and renamed as "Adequan" for veterinary use to treat joint problems in horses.

Given this advancement, research continued primarily outside the U.S. evaluating different forms, including the more convenient oral form. An Italian laboratory demonstrated through radiolabeling that glucosamine sulfate appeared in the blood an hour after ingestion and has a unique attraction to the cartilage tissue. Several clinical trials conducted outside the U.S. have continued to show symptom relief including an increase in joint mobility for some individuals. Human trials are currently underway in the U.S. and Canada.

Many products are adding to this dynamic duo with a combination of ingredients. Irwin Naturals/4Health, Inc., Culver City, CA, announced in March that it has closed its deal to acquire Inholtra for $13.25 million, giving them the rights to the joint pain relief product sold under the same "Inholtra" brand name. The product was featured on the TV news show Hard Copy highlighting glucosamine sulfate, n-acetyl-D-glucosamine, chondroitin sulfate, EPA, DHA, borage oil, vitamins A& E and manganese. The company is expected to realize additional EBITDA and income of $2 million because of the unique clinical effectiveness and U.S. patent supporting it.

From Horses To Humans:
Sulfur Supplements
The comfort of the spa includes the inviting sulfur springs sought for the relief of chronic pain. Sulfur is a critical component of specific amino acids such as methionine and cysteine. Methionine is an essential amino acid that combines with other amino acids to form specific proteins that become primary constituents of enzymes, hormones and other compounds that drive biochemical activity. As a result, a variety of sulfur-based supplements have been developed with messages like "to promote healthy tissue and cells." It was not surprising to some involved in this line of research that sulfur concentration in arthritic cartilage was reported to contain significantly less sulfur than levels in normal cartilage (Rizzo et. al., '95). Although several sulfur-based products are on the market, two of the more popular ones include DMSO and MSM.

In March 1980, DMSO (dimethyl sulfoxide) was highlighted on an episode of 60 Minutes as a tremendous pain reliever through the account of a person who had suffered severe pain for over two years as a result of a car accident (Jacob et al., '99). According to those involved in DMSO development, the impact of that feature sparked the start of a $1 billion DMSO market in the 80's for help in the reduction of inflammation.

As DMSO research has continued, more attention has been focused on its breakdown product, MSM or methyl-sulfonyl-methane. MSM is currently used by the equine industry to decrease inflammation in geriatric horses. The success of its use has driven researchers to develop a form suitable for human consumption. According to a news release from MSM supplier Carolwood Corporation, "MSM has been used by athletes to relieve strained muscles and overextended joints. In addition to reducing cramping, a recent study showed that the recovery time in marathon runners given MSM dropped 75%" (McCartney, '99). The press release goes on to report that "a recent study of 12 osteoarthritis patients treated with "Lignisulmsm" found that they experienced a comparable level of pain relief to another group treated with 2400 mg of Motrin, but without side effects."

Ayurvedic Practices Use Some Of The Oldest Compounds To Combat Inflammation
Some of the oldest natural anti-inflammatory agents have been used in ayurvedic medicine. According to Mark Sysler, Vice President-Sales for Sabinsa Corporation, Payson, UT, the Western culture has been slow to adopt these practices from India; however, over the past 5-10 years, Western science is validating their use in areas such as "joint relief." In fact, the company's fastest growing products are in this arena.

For instance, curcuminoids of the spice tumeric from the ginger family are widely recognized for their antioxidant properties. These compounds have also been shown to have a similar action to that of aspirin, given their ability to prevent the synthesis of enzymes that participate in the synthesis of inflammatory substances derived from arachidonic acid. When the anti-inflammatory properties of curcumin were tested in a double-blind clinical trial in rheumatoid arthritis patients, curcuminoids produced significant improvement with the effects comparable to phenylbutazone, a prescription drug used for inflammation (Deodhar et al., 1980). Given curcuminoids' mechanism of action, research is being planned to compare their efficacy with that of the new cox-2 drugs.

"Boswellin" is another offering with promise from Sabinsa (Majeed et al., 1995). The products contains boswellic acids from Boswellia serrata, a large, branching deciduous tree that grows in the hilly parts of India. The gum resin exudate containing essential oils, terpenoids and gum has been used in the ayurvedic system for rheumatism and other disorders. These herbs have primarily been researched in the medical communities of Europe and Asia demonstrating an ability to improve joint pain. As interest in this arena continues and more research is validated in the U.S., these products are expected to gain even more acceptance.

Last But Not Least: New Twist On The More Familiar
Fish oil supplements are widely available on the market today. More recently, the omega-3 fatty acids EPA and DHA derived from fish oil have been included in joint relief combination products. Omega-3 fatty acids have been shown to help reduce inflammation by countering the effects of prostaglandins, therefore suggesting that increased intake of rich sources of omega-3 fish found in salmon, anchovies, tuna or mackerel may help to manage inflamed joints. In the early 1980's, research suggested that fish oil supplements would benefit patients with rheumatoid arthritis (Kremer, et al., 1985, 1990). As more research has been conducted, not all clinical improvements have been statistically significant and the impact of their use may be modest.

On another familiar front, Nabisco's "Knox" gelatin team launched a new version of the product as the dietary supplement "Knox NutraJoint." The ingredients include a combination of gelatin, vitamin C and calcium with emphasis for its use for physically active people who have joint stress due to extra weight. The product literature states that it "helps maintain flexible joints and healthy bones the nutritional way."

There does not seem to be any end in sight for new entries into this growing category. From a profitability perspective, companies will be looking for protected positions to minimize dilution of margins, given broad participation in products such as glucosamine. At the same time, there appears to be an opportunity to lessen the confusion with respect to the efficacy and number of ingredients being offered for managing joint relief pain. Both of these factors will shape the future of the joint pain market. NW

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About the Author:
Dondeena Bradley, Ph.D. is a Program Manager in the Global Nutrition & Health Group at the Campbell Soup Company, Camden, NJ. Dr. Bradley's seven years experience in the nutrition arena includes nutrition research & development at M&M/Mars and managing the commercial development of specialty fat ingredients at the Stepan Company.