Joint-Health Ingredients for Dietary Supplements: Coming ‘round the Bend


Supplements to keep joints healthy.

Tim Hammond knows that today’s seniors are a breed apart. “While baby boomers age,” says the director of sales and strategic relations, Bergstrom Nutrition (Vancouver, WA), “their hearts stay young.” Having it all doesn’t seem too much for them to ask, either, “from participating in a favorite sport to keeping up with the grandkids,” he adds. “And they don’t want to let the aches and pains of aging slow them down.”

But aches and pains-especially in the joints-are more than just inconveniences for energetic elders. They’re a genuine public health problem. According to the U.S. Census Bureau’s 2006 National Health Interview Survey, one in three Americans reported experiencing joint pain within the previous 30 days. “And it is likely,” says Nena Dockery, technical support for ESM, Stratum Nutrition (St. Charles, MO), “that the numbers are even higher now.”

Which is why joint-health supplements pose such an intriguing prospect. If they can provide relief and an alternative to invasive treatments whose costs can outweigh their benefits, they may make life better for individuals as well as the nation. But the key to their success lies in sound science and in formulating only with those ingredients proven to work.


Taking a Bad Turn

Our everyday lives are practically engineered to encourage joint trouble. Sherry Torkos, BSc, Phm, author of The Canadian Encyclopedia of Natural Medicine and a spokesperson for Proprietary Nutritionals Inc. (Kearny, NJ), notes that joint pain “can be an occasional or chronic problem. It can arise from injury to the joint, overexertion from exercise or sports, heavy lifting, or a person’s occupation, such as being a carpet layer.”

It also accompanies age-and the throng of Americans hitting retirement right now certainly helps account for the widespread incidence of joint pain. So, too, does obesity, as a growing mass of Americans finds itself carrying around…well, a growing mass. As Torkos says, “Extra weight adds burden to the joints. With over two-thirds of our population classified as overweight or obese, it is not surprising that joint problems are a common issue.”

Joint pain can arise from medical conditions more serious than daily wear and tear, too, as with rheumatoid arthritis, an autoimmune disorder that leads to pain and the loss of joint tissue, says Anurag Pande, PhD, vice president of scientific affairs, Sabinsa (East Windsor, NJ). Gout is another joint disorder, wherein excess deposits of uric acid, especially in the foot, cause intense pain, Pande says.


The Osteoarthritic Cascade

Perhaps the most familiar cause of joint pain is osteoarthritis, which can afflict its sufferers at a surprisingly young age. As Dockery points out, “Though we normally think of joint problems beginning around age 50, it is estimated that up to 90% of Americans have some features of osteoarthritis by the time they are 40.”

The symptoms progress slowly at first, as cartilage-the flexible connective tissue that serves as our joints’ natural shock absorber-starts losing elasticity and resilience. “As a result,” Dockery says, “the surrounding ligaments and tendons stretch and become more prone to injury.” This sets off a cascade of inflammation, stiffness, and pain, after a while of which “the bones in the joint start rubbing together, further wearing down the entire region and resulting in a diagnosis of osteoarthritis,” Dockery says.



Knees take the biggest brunt, thanks to the weight they bear and the work they do; the shoulder joints, hips, fingers, and toes are also liable. But wherever it strikes, osteoarthritis, like so many other causes of joint pain, “is a question of inflammation,” says Jamie Spell, managing director, Nutraceuticals International Group (Paramus, NJ). “Inflammation is the base of pain.”

Alas, inflammation is a routine condition of our era, observes Steve Holtby, president and CEO, Soft Gel Technologies Inc., (SGTI; Los Angeles). A diet that favors omega-6 fatty acids over omega-3s is one reason, he says, as is a lack of the antioxidants that can neutralize pro-inflammatory compounds like cytokines, interleukin 1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha).

“Between an excess of omega-6 fatty acids, a lack of omega-3 fatty acids, and inadequate intake of antioxidants,” Holtby concludes, “the body’s pro-inflammatory reaction goes out of control, leading to chronic inflammation and pain. As humans grow older, systemic inflammation can inflict devastating degenerative effects throughout the body.”


Intervention Time

So what’s an achy, inflamed body to do? It can start with eating a balanced diet, exercising, losing weight, and-to target joints specifically-engaging in physical therapy and the use of orthotic braces. Beyond that, nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen, and indomethacin “decrease pain and improve function,” says Spell. But they’re no cure. And they’re not without drawbacks.

For example, NSAIDs reduce inflammation and relieve pain, but their side effects range from stomach ulcers and diarrhea to kidney and liver damage and even heart failure. Further, Torkos says, “They don’t prevent joint damage, and there is evidence that they can actually accelerate cartilage breakdown.”

For those with more severe pain, cortisone injections at the joint or orally administered prednisone are short-term interventions at best, as “they can damage cartilage and remove minerals from the bone, further weakening the joint,” Torkos says. A newer treatment known as viscosupplementation involves injecting the joint with a solution of hyaluronic acid (HA), a natural lubricant and shock absorber found in synovial fluid. Though an alternative for those with low tolerance for NSAIDs, it, too, provides only temporary relief and can also induce immune reactions.

Then again, you could always get a new joint. But as Dockery notes, “Joint replacement involves a major surgical procedure that carries with it the normal risks of anesthesia reactions and blood clots.” There’s also evidence that surgery can lead to arthritis itself. And given that the life expectancy of an artificial joint is only about 20 years-assuming a snazzy new model doesn’t tempt you to upgrade sooner-Dockery points out that such interventions are “not recommended for younger individuals.”


Sensible Supplements

Maybe it’s just as well, as younger folks may not have the nest egg to pay for them. At about $15,000 a pop, according to the Kaiser Family Foundation, knee replacements alone cost Americans some $9 billion annually. Not surprisingly, a consensus is emerging that we need to address joint health more affordably, and effectively.

Chuck Ray, acidulants/glucosamine technical services manager, Cargill (Minneapolis), notes that some researchers and clinicians believe that waiting until symptoms are present-pain, restricted mobility-is too late because the joint is no longer “healthy.” This reinforces the need to focus on ways to help keep joints healthy from the start.

That sounds like a job for supplementation, the goal of which focuses more on maintaining health than treating disorder. Moreover, by targeting supplement action toward stemming the inflammation that characterizes joint pain-rather than just soothing the pain itself-we “can help slow down the degeneration of the joints and provide relief, as well as reduce the loss of cartilage due to inflammation,” Pande says.


Support from the Sea

In the pantheon of joint-health supplements, omega-3 fatty acids enjoy positive attention for their anti-inflammatory benefits. Fortunately, they also enjoy wide scientific support and a fairly well elucidated mechanism of action.

Notes Becky Wright, communications and marketing manager, Aker Biomarine Antarctic US (Issaquah, WA), “The presence of omega-3s in cell membrane phospholipids shifts the production of hormone-like substances called prostaglandins away from the undesirable series 2 prostaglandins and toward the beneficial series 1 prostaglandins.” In addition, omega-3s may help support the integrity of articular cartilage, and, hence, joint comfort.

Processors have a number of sources from which to extract omega-3s. Wright points out that results from a mouse-model study using newer comer krill oil-rich in the omega-3 fatty acids EPA and DHA-revealed improvements in inflammation and suppressed development of collagen-induced arthritis (Ierna M et al.).

Her company extracts its branded Superba krill oil from an Antarctic species, Euphausia superba, with what she says are especially high levels of EPA and DHA. And by being attached to phospholipids, the oil’s omega-3s assimilate into cells more rapidly and efficiently. Wright says that the ingredient delivers 60% more omega-3s to needy tissues like joints, while also allowing manufacturers to pack effective doses into smaller pills-a plus for consumers already taking all the big pills they can swallow.


The Esterification Effect

Dean Mosca, president of Proprietary Nutritionals Inc., claims that his company’s Celadrin product “works similarly to, but much more dramatically than, the essential fatty acids EPA and DHA from fish oils.” The reason, he says, is that the fatty acids in the ingredient are esterified and thus more stable against oxidation.

The ingredient’s benefits are largely anti-inflammatory. Mosca says it reduces the production of interleukin 6 (IL-6) and helps control other pro-inflammatory immune factors. “This alone could explain some effects of Celadrin,” he says, “such as reduction of pain in joints affected by osteoarthritis. And certainly, these functions are very important in preventing further tissue and joint damage while promoting healing.”

But the supplement also inhibits the enzyme 5-lipoxygenase that turns the fatty acid arachidonate into pro-inflammatory leukotrienes. “It may also alter cellular membranes,” Mosca adds, “protecting them from the action of inflammatory cytokines, or by reducing the secretion of inflammatory cytokines and C-reactive protein.” Compounds in the supplement appear to lubricate joints, too, which, combined with its anti-inflammatory effects, “explains some of the significant improvements in mobility and function,” says Mosca.

In a 2004 study of the supplement published in The Journal of Rheumatology (Kraemer WJ et al.), 42 patients with osteoarthritis of the knee received either twice-daily topical application of the supplement or a placebo. After 30 days of treatment, researchers evaluated the subjects’ physical function, postural sway, pain, and range of motion and found that the treatment group had reduced pain and stiffness, better balance and strength, and more mobility.

“What was most exciting,” Mosca notes, was that within 30 minutes of application, “patients experienced a dramatic improvement in all aspects tested.” The suggested dose of the supplement-natural, available in both animal- and vegetarian-source forms, and suitable for use only in supplements-is 1,500 mg/day.


Botanicals to the Rescue

Moving beyond fatty acids, Sabinsa’s Pande notes that Boswellia and the botanical compound curcumin have shown a great deal of success in countering joint pain by reducing inflammation. The name Boswellia actually refers to a genus of plants known for their anti-inflammatory resin-think frankincense of the legend of Christmas, specifically the Three Wise Men’s gifts of gold, frankincense, and myrrh. While therapeutic use of this resin dates back to those bygone times, contemporary research both supports and explains its efficacy.

Boswellic acid, the active compound in Boswellia, is also a lipoxygenase inhibitor and, as such, impedes the conversion of arachidonic acid into undesirable leukotrienes. When Boswellin, Sabinsa’s branded extract of Boswellia serrata gum, underwent clinical study as part of a joint-care formulation, it produced improvements in WOMAC and VAS scores, Pande notes. (The WOMAC, or Western Ontario and McMaster University Osteoarthritis Index, is a marker test used in joint-health studies; a VAS, or visual analogue scale, is a research tool that lets study participants measurably rate their pain.)

Pande says that the company uses HPLC to standardize its Boswellia product for boswellic acid content, with grades ranging from 20% to above 50%. Effective doses are manageable in supplements, with the standard concentration of the supplement demonstrating efficacy at 300 mg/day to 600 mg/day, and more highly concentrated forms dosing at only 75 mg/day to 215 mg/day.

And while boswellic acid is effective on its own, it synergizes with curcumin. Sabinsa’s Curcumin C3 Complex, a supplemental extract of curcuminoinds from the turmeric rhizome Curcuma longa, contains “all three curcuminoids,” Pande says, which “have shown strong potential as anti-inflammatory products.” Studies indicate that curcumin can protect chondrocytes-the primary cells in healthy cartilage-from breakdown.

The curcumin complex is natural and self-affirmed GRAS and has served as the curcumin supplement used in many of the published clinical trials establishing curcumin’s efficacy. Pande says doses range from 250 mg/day to 500 mg/day, and, like Boswellin, the ingredient is heat and processing stable.


Hops to It

Another botanically derived ingredient with solid scientific backing is a supercritical extract of the hops plant, Humulus lupulus L. Called Perluxan, the product is standardized to contain high amounts of naturally occurring alpha acids and provides “natural, fast-acting anti-inflammatory–related temporary relief for minor aches and pains without the side effects commonly associated with prescription anti-inflammatory products,” says Holtby, whose Soft Gel Technologies is an exclusive supplier.

How does it work? Holtby says it “positively affects several enzymatic and non-enzymatic pro-inflammatory biomarkers,” including prostaglandin E2, cyclooxygenase 1 and 2 (COX-1 and COX-2), IL-1, isoprostanes, the nitric oxide synthases iNOS and nNOS, TNF-alpha, and nuclear factor kappa B (NF-kappB).

In a double-blind, randomized, parallel-design trial (Lemay M et al.), 19 healthy subjects received either a single 400-mg dose of ibuprofen, a 450-mg standardized hops resin soft gel, or the resin in powdered form delivered in four 300-mg doses daily. After nine hours of monitoring, the researchers found that the hops preparations were as effective at inhibiting COX-2 as ibuprofen, “but had significant COX-1–sparing activity,” Holtby says. The recommended dose is one soft gel, standardized to 150 mg alpha acids, taken twice daily with food.


All Hail Hyaluronate

While ingredients like hops extract, curcumoinds, boswellic acid, and healthful fatty acids attack the inflammation aspect of joint pain, other supplements work by restoring some of the very substances that inflammation destroys when it hits healthy joints in the first place. As Dockery says, “Supplements containing collagen, glucosamine, or glycosaminoglycans function in this way to replenish these nutrients for which the body’s own production has diminished.”

Consider the glycosaminoglycan HA, which, as mentioned before, is the natural shock absorber injected into joints during viscosupplementation. Among the most important roles HA plays, says Sam Kwon, Vesta Pharmaceuticals Inc. (Indianapolis), “is to increase viscosity and reduce friction between articular surfaces. Fibroblastic synoviocytes synthesize sodium hyaluronate, which then releases into the synovial fluid.” The compound also helps lubricate joints by polymerizing with other glycosaminoglycans and retaining water; further, supplements appear to boost our bodies’ endogenous synthesis of it.

Kwon points to a year-long, double-blind clinical study that was published last year in Scientific World Journal (Tashiro T et al.) in which the authors stated that “improvement tended to be more obvious” with the HA group compared to the placebo group. Kwon says that his company’s Hyal-Flex product delivers HA benefits at doses of 135 mg/day to 150 mg/day and is all natural, non-GMO, and allergen free.


Glucosamine: Stay Tuned

“One can understand how keeping the cells in the cartilage healthy could benefit overall joint health,” says Cargill’s Ray, “and emerging preclinical research in cell culture and animal models shows that supplemental glucosamine activates autophagy in cartilage and other tissues.” This process helps keep cells healthy, he says, especially in low-turnover tissue like cartilage.

True, some studies on glucosamine have been equivocal. But, Ray notes, “If the purpose of the supplement is to maintain healthy joints, many studies on glucosamine supplementation are not applicable because they were conducted in a study population with osteoarthritis.” Dosing, individual variation in glucosamine metabolism or use, and other factors may also explain the results’ inconsistency.

While we still have more to learn, Ray maintains that he and his colleagues are “supporting research that examines a glucosamine mechanism of action in healthy joints, beginning with foundational preclinical research in cell culture and animal models, in an effort to help address a gap in glucosamine research.”

For the time being, fans of the supplement can turn to his company’s Regenasure, the first vegetarian glucosamine HCl on the market. Produced via a patented fermentation process “using a naturally occurring organism,” the product is effective at 1,500 mg/day, dosed in 500-, 750-, and 1,500-mg servings, says Ray. And as a GRAS ingredient, it “can be a drop-in to beverages, gels, and dairy products as long as the pH is less than 4 to 4.5.”


The Essential Element

Rod Benjamin, director of technical development at Bergstrom Nutrition, notes that some research hints at the possibility of achieving better results from glucosamine supplementation when the ingredient is paired with methylsulfonylmethane, or MSM (Usha PR et al.). MSM is a naturally occurring compound that supplies sulfur, an essential element in bone and connective tissues, including collagen and the glucosamine and chondroitin in cartilage.

In addition, MSM performs as an antioxidant. “Although MSM’s exact mechanism of action is not fully understood,” Benjamin says, “studies have suggested that it impacts the trans-location of NF-kappa B, and down-regulates the expression of inflammatory cytokines like IL-1beta–induced IL-6 and IL-8, TNF-alpha, and IL-1. With these compounds being destructive to cartilage, helping to minimize them could aid in protecting and preserving the cartilage.”

Bergstrom produces OptiMSM, a nature-identical-or biomimetic-MSM supplement for use in capsules, tablets, powders, and sachets, as well as in functional foods and beverages. “We recently collaborated with Glanbia Nutritionals [Fitchburg, WI] to formulate a prototype of an exercise-recovery and joint-support protein powder called PepForm BCAA 2:1:1 Peptides,” Hammond notes. “It featured 3 g of OptiMSM and Glanbia’s PepForm BCAA 2:1:1,” the latter a source of the branched-chain amino acids important for post-workout muscle recovery.


The Stuff of Joints Itself

What about supplementing with collagen itself? According to Dockery, “Collagen ingredients are also still popular, as they provide one of the essential components of healthy joint tissue.”

One such ingredient is BioCell collagen, from BioCell Technology LLC (Newport Beach, CA). Joosang Park, PhD, MBA, the company’s vice president of scientific affairs, says its effectiveness is a result of its unique matrix of three major naturally occurring cartilage constituents: hydrolyzed collagen type II, chondroitin sulfate, and HA, “all of which are essential for the structure and function of cartilage,” he says.

By reducing the ingredient’s constituent macromolecules to a very low molecular weight, Park adds, its production ensures that it more rapidly and effectively enters the bloodstream. “More importantly,” he says, “this patented process creates a novel set of biological properties, including stimulation not only of the chondrocytes but of the synovial cells to synthesize collagen and HA. This regenerative activity appears specific to hydrolyzed collagen because undenatured or unhydrolyzed collagen fails to stimulate these cells.”

The ingredient is natural and derived from young chicken sternal cartilage, and received GRAS affirmation in 2010, allowing for its use in foods and beverages in addition to supplements. Doses depend on application, with 2 g/day clinically proven to aid joint health. This is a more practical supplemental dose than the 10-plus g/day that aren’t unheard of in supplements made from bovine-, porcine-, or fish-source collagen, Park notes.


Joint Relief, In an Eggshell

Eggshell membrane is another source of collagen, as well as the glucosamine, chondroitin sulfate, and HA found in healthy joints. ESM Technologies (Carthage, MO) developed a process, since patented, to steam-separate the delicate membrane from the egg’s outer shell. And while the shell itself contains “a very desirable form of elemental calcium,” Dockery says, “it wasn’t until they developed the separation technique and began analyzing the membrane that they uncovered this nutrient-rich material.”

Known by the product name NEM, the natural supplement has been the subject of research, and a study published in early 2012 in the Journal of Medicinal Food (Benson KF et al.) concluded that it contains compounds that directly modulate immune T-cell activation and diminish production of pro-inflammatory TNF-alpha. In the pharmaceutical industry, TNF-alpha inhibitors are drugs that help manage the symptoms of joint disorders, including rheumatoid arthritis, Dockery says, “though these drugs carry the risk of serious side effects. Moderation of the immune response involving TNF-alpha might offer the advantage of decreased inflammation without the risk posed by complete inhibition.”

The clinically proven dose of NEM for ameliorating discomfort and stiffness is 500 mg/day-easily deliverable in a medium-sized capsule or small tablet, Dockery says. And because the ingredient is neutral in flavor and self-affirmed GRAS, it “lends itself well to application in conventional foods and beverages or in chewable tablets.”

The promise of relief inherent in supplements like these should give joint-pain sufferers hope; the fact that science stands behind their role in healthy joint maintenance and damage prevention should give them confidence. But, as Wright says, “Where the science remains thin or nonexistent is in the area of treating severe joint issues, which is reserved for drugs. Supplements are really reserved for someone who wants to address their joint issues before they become too serious.”

Indeed, the most satisfied consumers tend to congregate on the milder end of the pain spectrum. Even so, in many cases, these products “offer a new lease on life,” Wright says. “Obviously, the category is alive and well if consumers continue to use these products.” 

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