Bare Bones of Arthritis

References

Arthritis impairs joint mobility and interferes with quality of life for millions of people. Non-steroidal anti-inflammatory drugs (NSAIDs) are the conventional treatment for most forms of arthritis; however, due to dangerous side effects, not to mention expense, these drugs aren’t right for everyone. A gentler regime involving supplementation with micronutrients and herbs that lower inflammation and counter oxidative damage can often replace or complement therapy with NSAIDs, expanding treatment options for those who live with joint issues.

The word “arthritis” is derived from arthron, the Greek term for joint, and the suffix itis, meaning disease or inflammation. True to its name, arthritis, comprising more than 100 diseases and conditions affecting joints and tangent tissues, as well as other connective tissues,¹ causes pain and inflammation, and limits mobility. More than 43 million (or approximately one in five) Americans have arthritis or other rheumatic conditions, and another 23 million individuals suffer from chronic joint symptoms but have not been diagnosed with arthritis.² From an economic standpoint, arthritis is the leading cause of disability in the United States, costing $51.1 billion in direct medical-related costs and $35.1 billion in indirect costs or lost wages.³

The two main forms of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). OA is characterized by degeneration of joint cartilage and related bone (most commonly in the hips, hands, spine and knees), which eventually culminates in pain and stiffness. Disease onset is gradual and usually begins after the age of 40. A cure for OA still eludes scientists.

The specific causes of OA are unknown, but are believed to stem from mechanical and molecular events within the affected joint, according to Jason Theodosakis, M.D., M.S., M.P.H., author of The Arthritis Cure (St. Martin’s Griffin). “Several things can cause disease and distress in the cartilage, creating painful movement and possibly leading to OA,” he said. “It may be sudden and severe trauma such as a blow to the knee while playing sports. Or perhaps the trauma is slow and gradual, the built-up effects of hundreds or thousands of tiny injuries. When trauma occurs, the surface of damaged cartilage may become ragged and pockmarked. Without healthy and whole cartilage to cushion them, the bones may begin to rub against each other, causing severe pain. Or small fractures may develop in the cartilage. The body usually responds to this by producing more but inferior cartilage to ‘plug the cracks’. As the joint degenerates, looseness in the joint causes the tendons and ligaments to be abnormally strained. In addition, the joint lining or synovium often becomes inflamed, sending pain messages to the brain. The synovium tries to solve the problem by producing more and more synovial fluid: the slick, watery substance that lubricates and nourishes the cartilage. This sounds like a good idea but the resulting fluid ends up flooding the joint space, causing swelling and perhaps even more pain.”

OA’s sister ailment, RA, is a systemic inflammatory disease primarily affecting the lining of the joints. As with OA, inflammation of the synovium causes pain, swelling, erosions of cartilage and bone, and possibly joint deformity. The affliction is believed to be autoimmune in nature. RA can begin at any age and is associated with fatigue and prolonged stiffness after rest. As with OA, currently there is no cure for RA.

NSAIDs are prescribed to arthritis patients for their potent analgesic and anti-inflammatory effects. However, the Food and Drug Administration (FDA) has issued a public health advisory pertaining to health risks associated with use of these drugs. Specifically, data from recent controlled clinical trials indicates COX-2 selective agents including Vioxx®, Celebrex® and Bextra® may be associated with an increased risk of serious cardiovascular events such as heart attack and stroke, especially when used for long periods of time or in very high risk settings such as immediately after heart surgery.

Fortunately, arthritis patients looking to avoid or reduce use of NSAIDs may find a viable solution in dietary supplements, which provide an effective, safer alternative to prescription drugs, according to Theodosakis. “There are several safe, natural alternatives to find relief, [and] for pain, I’d much rather recommend a supplement or topical than a drug that may lead to other problems such as kidney disease, ulcers, heart attacks and strokes,” he said.

Diet may play a role in the management of OA and RA by providing raw materials necessary for support of joint health, combating symptoms, counteracting side-effects of therapy and reducing the risk of complications.^4,5 The foundation of a nutritional support program for arthritis patients involves supplementation with vitamins and minerals, some of which fight oxidative damage, which exacerbates inflammation. Vitamin A, vitamin C and selenium may defend against increased oxidative stress associated with arthritis, and supplementation with calcium and vitamin D in patients treated with corticosteroids reduces bone loss.⁶B vitamins for arthritis patients help reduce excessive serum homocysteine levels elevated by inflammation and conventional medical treatment,⁷ and there appears to be an inverse association between serum vitamin B6 and arthritis disability scores, duration of morning stiffness, degree of pain and inflammatory markers.⁸

Supplying important mineral support is also important for both structural integrity and antioxidant impact. SierraSil™, from Sierra Mountain Minerals, is a 65 macro- and trace mineral complex marketed for preventive and therapeutic effects on joint symptoms. “This ingredient works at the level of gene suppression, stopping inflammation and the degradation of cartilage,” said Britney Obstar, spokes-person for Sierra Mountain Minerals. [And], unlike [other arthritis] formulas, which can take months to work, SierraSil has proven benefits for most people in two weeks or less, sometimes even in three to five days.”

A recent mechanism of action study found SierraSil suppresses cartilage degradation and inflammation when used alone or in conjunction with Vincaria®, a cat’s claw extract.¹¹ A human pilot study showed SierraSil alone and in combination with Vincaria safely provided significant improvements in pain, stiffness and inflammation in 100 percent of test subjects with previously diagnosed OA of the knee.

And a double blind, randomized, placebo-controlled study of more than 100 OA patients published in the Journal of Inflammation showed SierraSil at three different doses significantly reduced pain, stiffness and inflammation, and improved joint functionality one month of therapy, with symptom improvements evident within one to two weeks from baseline.¹²

Another fatty compound derived from n-3s and of benefit to arthritis patients is comprised of esterified fatty acid carbons (EFACs). “Esterifying these fatty acids makes them stable and prevents them from reacting with oxygen, making them particularly effective in treating the pain and inflammation of arthritis,” said Theodosakis. “Esterified fatty acid carbons are believed to work by beneficially altering the body’s production of chemical mediators that lead to inflammation and pain. The result is improved function and less pain for those who suffer with arthritis.”

In one study, administration of EFACs (as Celadrin®, a complex of EFACs and other active synergists, from Proprietary Nutritionals) produced a significant increase in knee flexibility and overall function.¹⁵ The ingredient appears to work both orally and topically, producing activity in the blood and showing significant localization of absorption in topical application.¹⁶ In fact, topical application of Celadrin has improved range of motion of knee OA patients in a series of physical tests, whereas no difference was observed in the placebo group.¹⁷

Since excessive intake of n-6s can increase formation of the pro-inflammatory cytokines TNF-alpha and interleukin-6, and of reactive oxygen species (ROS), a marker of oxidative stress,²¹ it is important for arthritis patients to consume a balance of n-3s and n- 6s, according to Ian Lucas, executive vice president of global marketing with Ocean Nutrition Canada. “In the North American diet, the ratio of n-3 to n-6 is about 16-to-1,” he said. “Excessive n-6 causes a build-up of arachadonic acid, a precursor of inflammation. This can be combated by intake of EPA, which is the most powerful natural anti-inflammatory agent.”

Among the joint health powerhouses are glucosamine, an endogenous amino sugar, and chondroitin sulfate, a constituent of proteoglycans, hydrophilic protein molecules in cartilage, both which are natural substances found in and around the cells of cartilage. Glucosamine may halt or reverse joint degeneration by acting as an essential substrate for, and stimulating the biosynthesis of, structural molecules known as glycosaminoglycans as well as the hyaluronic acid framework needed for support of the structural matrix of joints.²² And, chondroitin sulfate provides other substrates for the formation of proteoglycans, protein molecules comprising a healthy joint matrix.²³

The combination of glucosamine and chondroitin sulfate has been shown to help arthritis patients in a number of clinical trials. A double blind, placebo-controlled clinical trial conducted in Zurich investigated the efficacy and tolerability of a twice yearly, three-month, intermittent treatment with oral chondroitin sulfate (800 mg/d, as CSb™ Bio- Active, from Bioiberica) in 120 symptomatic knee OA patients, and found supplementation significantly improved functionality and disease parameters.²⁴ In addition, after one year, the placebo group showed significantly decreased joint space whereas patients on the CS had no change. Perhaps the most definitive—and most controversial—research on the combination, however, is the National Institutes of Health (NIH)-funded, multicenter, double blind, placebo- and NSAID-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT), which evaluated the efficacy and safety of glucosamine and chondroitin versus celecoxib (Celebrex) and placebo as a treatment for knee pain from OA. (For more on GAIT, see story, page 22.) Another organic compound thought to support cartilage growth and repair is MSM (methylsulfonylmethane), a readily-available source of sulfur, an essential component of cartilage. Administration of 3 g MSM (as OptiMSM®, from Cardinal Nutrition) twice daily to 50 men and women with knee OA pain for 12 weeks produced statistically significant decreases in pain and significantly improved patients’ ability to perform daily activities.²⁵ “In low-dose (less than 1,000 mg per day), MSM can help offset some of the loss of sulfur that occurs in OA and in people who take pain medications such as acetaminophen or aspirin,” said Theodosakis. “In higher doses—1,500 mg and above— MSM also has a beneficial effect on pain.”

Another cartilage support ingredient shown to combat arthritis symptoms is chicken collagen. An independent proprietary study from BioCell Technology, hydrolyzed type II collagen from chicken sternum (as BioCell Collagen II™) was pronounced a safe and effective dietary supplement for the adjunctive treatment of OA. In the randomized, double blind, placebo-controlled trial, 16 age-, race- and gender-balanced subjects with OA of the knee or hand and who were taking COX-2 inhibitors or NSAIDs were randomized to receive the active treatment or placebo for 2 months. The group receiving hydrolyzed type II collagen experienced a significant improvement in all WOMAC subscales and in total WOMAC score when compared to placebo.

InterHealth’s UC-II® is an undenatured or intact form of type II collagen found in the cartilage of joints that has been shown clinically to improve joint flexibility and arthritis symptoms. According to a review, several studies have shown significant improvement in symptoms when patients were supplemented with undenatured type II collagen, including improved joint mobility and flexibility, reduced joint pain, and in some patients, complete remission of symptoms.²⁶ The researchers noted undenatured type II collagen’s ability to enhance immune function could be useful in reducing inflammation associated with OA. According to a study from Harvard Medical School, six of 10 RA patients taking undenatured type II collagen for three months showed substantial improvement; of these, one patient recovered completely.²⁷

According to the CDC, arthritis education has been shown to help reduce pain, yet only one in 10 arthritis patients have taken such courses, and health-care providers and persons with arthritis are missing opportunities to improve health through recommending or participating in arthritis education.³⁰ Retailers are another group that could benefit from arthritis education, first by educating themselves, then educating their customers.

“The success of the natural product retailer, demonstrated by percentage gain in market share against the mass market, I believe is firmly grounded in education,” said Eric Anderson, brands manager with P.L. Thomas. “Understanding the product offerings in the category and especially the benefits and attributes are important to help a consumer make a product choice that is satisfying.”

Carole Ruhnke, senior marketing manager with InterHealth Nutraceuticals Inc., agreed with the assessment: “The most effective way retailers can market any nutraceutical product is to keep abreast of consumer concerns and ongoing scientific developments, and to become an information resource for their customers. Providing thorough explanations and information, such as differentiating premium ingredients from lower-quality knock-offs, and OTC and prescription products from natural products, is of great help to consumers. This added value instills confidence in consumers and leads to increased and repeat sales.”

David Lakey, president of Cardinal Nutrition, stressed the importance of shelf presentation. “Joint health is a unique health condition where there are few substitute nutritional products,” he said. “Therefore, it’s important to create a ‘joint health’ section on the shelf so products are easy to find and the customer can more easily evaluate dosage forms, daily doses, cost per day, etc., in one place. Joint health is also one of the few segments (other than multivitamins) with strong brands and brand loyalty. Enough space should be allocated to the fastest moving ingredients and brands in order to avoid costly out-of-stocks that can also destroy store loyalty. Look for opportunities to educate consumers about clinical studies and also that they need to take these products religiously for weeks or months to reach the desired effect. Because joint health gets lots of traffic from your most profitable customers, look for ways to ‘upsell’ customers into higher counts; put floor displays or bins near the area.”

Overall, the future of the joint health industry looks bright for retailers, according to Anderson. “The joint health category continues to be quite vigorous, and widespread complex phenomena such as joint pain, deterioration of joint tissues and limited flexibility will continue to present quality of life challenges, particularly for the aging baby boomer population,” he said. “This dynamic market attracts therapeutic approaches from many different nutritional technologies, targeting differing mechanisms of action.”

Ruhnke agreed, citing an abundance of potential customers. It is helpful for retailers to understand the [significant] extent to which consumers—even relatively young consumers—are concerned about bone and joint health and are willing to use supplements to treat related problems,” she said.

Armed with an arsenal of researchbacked compounds, retailers possess the unique opportunity to help their customers control joint pain, possibly without using potentially harmful NSAIDs or perhaps with more judicious use of these compounds, and spread awareness about arthritis.

References

1. Centers for Disease Control. "Arthritis." [Online] Available April 1, 2006. http://www.cdc.gov/arthritis/arthritis/index.htm 

2. Ibid.

3. Ibid.

4. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. "Public Health Advisory
Non-Steroidal Anti-Inflammatory Drug Products , NSAIDS." [Online] Available April 1, 2006. http://www.fda.gov/cder/drug/advisory/nsaids.htm 

5. Miggiano GA. "[Diet, nutrition and rheumatoid arthritis]." Clin Ter. 156, 3:115-23, 2005.

6. Goggs R et al. "Nutraceutical therapies for degenerative joint diseases: a critical review." Crit Rev Food Sci Nutr. 5, 3:145-64, 2005 .http://taylorandfrancis.metapress.com/ 

7. Yxfeldt A et al. "Homocysteine in patients with rheumatoid arthritis in relation to inflammation and B-vitamin treatment." Scand J Rheumatol. 32, 4:205-10, 2003.. http://taylorandfrancis.metapress.com/

8. Chiang EP et al. "Inflammation causes tissue-specific depletion of vitamin B6." Arthritis Res Ther. 7, 6:R1254-62, 2005. http://arthritis-research.com 

9. Bae SC et al. "Inadequate antioxidant nutrient intake and altered plasma antioxidant status of rheumatoid arthritis patients." J Am Coll Nutr. 22, 4:311-5, 2003. www.jacn.org

10. Jaswal S et al. "Antioxidant status in rheumatoid arthritis and role of antioxidant therapy." Clin Chim Acta. 338, 1-2:123-9, 2003. www.elsevier.com

11. Proprietary study, property of Sierra Mountain Minerals, 2005.

12. Miller MJ et al. "Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: a randomized controlled trial [ISRCTN38432711]." J Inflamm, Lond. 2:11. 2005. www.journal-inflammation.com

13. Darlington LG et al. "Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders." Br J Nutr. 85, 3:251-69, 2001. www.ingentaconnect.com

14. Adam O. "Dietary fatty acids and immune reactions in synovial tissue." Eur J Med Res. 8, 8:381-7, 2003.

15. Hesslink R Jr et al. "Cetylated fatty acids improve knee function in patients with osteoarthritis." J Rheumatol. 29, 8:1708-12, 2002. www.jrheum.com

16. Kraemer WJ et al. "Effect of a cetylated fatty acid topical cream on functional mobility and quality of life of patients with osteoarthritis." J Rheumatol. 31, 4:767-74, 2004. www.jrheum.com

17. Darlington LG et al. "Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders." Br J Nutr. 85, 3:251-69, 2001. www.ingentaconnect.com

18. Leventhal LJ et al. "Treatment of rheumatoid arthritis with blackcurrant seed oil." Br J Rheumatol. 33, 9:847-52, 1994.

19. Ibid.

20. Darlington LG et al. "Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders." Br J Nutr. 85, 3:251-69, 2001. www.ingentaconnect.com

21. Kelly GS. "The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease." Altern Med Rev. 3, 1:27-39, 1998. www.thorne.com/altmedrev

22. Ibid

23. Ibid.

24. Uebelhart D et al. "Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo." Osteoarthritis Cartilage.12, 4:269-76, 2004. www.elsevier.com

25. Kim LS et al. "Efficacy of methylsulfonylmethane [MSM] in osteoarthritis pain of the knee: a pilot clinical trial." Osteoarthritis Cartilage. 14, 3:286-94, 2006. www.elsevier.com

26. Trentham DE et al. "Use of Undenatured Type II Collagen in the Treatment of Rheumatoid Arthritis." Clin Practice Altern Med., 2:254-259, 2001.

27.Trentham DE et al."Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis." Science, 261:1727-30, 1993.

28. Zenk JL et al. "The effects of milk protein concentrate on the symptoms of osteoarthritis in adults: an exploratory, randomized, double-blind, placebo-controlled trial." Current Therapeutic Res. 63, 7:430-42, 2002. www.sciencedirect.com

29. Colker CM et al. "Effects of Milk-Based Bioactive Micronutrient Beverage on Pain Symptoms and Activity of Adults with Osteoarthritis: A Double-blind, Placebo-controlled Trial." Nutrition. 18:388-392, 2002. www.sciencedirect.com

Centers for Disease Control. "Arthritis." [Online] Available April 1, 2006. http://www.cdc.gov/arthritis/ 

Inflammation Control

References

Frequently, arthritis is categorized as an inflammation-driven disorder, characterized by a worsening cycle of swelling and pain. Although taking nonsteroidal anti-inflammatory drugs (NSAIDs) is a popular approach to controlling inflammation in arthritis patients, use of these compounds has been linked with cardiovascular problems. One alternative to NSAIDs is supplementation with various botanicals and other natural treatments backed by clinical evidence supporting their efficaciousness and safety.

“My top five natural remedies for inflammation are boswellia, ginger, scullateria, turmeric and acacia,” said Shawn Talbott, Ph.D., author of Natural Solutions for Pain-Free Living (Currant Books). “Boswellia sap has a long history of safe and effective use as a mild anti-inflammatory to reduce pain and stiffness; ginger has been used throughout history to relieve inflamed joints, scutellaria (skullcap) is used in traditional Chinese medicine (TCM) as an anti-inflammatory agent; turmeric has a very long and revered history of use as a spice and a medicinal agent by traditional healers in Asia, India, China, and Central and South America; and acacia has likewise enjoyed a long history of traditional use for treating inflammation and pain.”

The efficacy of boswellia (Boswellia serrata) in reducing inflammation, believed to be due to the herb’s content of boswellic acids,¹ is backed by numerous clinical trials supporting its ability to decrease pain and swelling in the joints.^2,3 “The boswellia plant produces a sap that has been used in traditional Indian medicine as a treatment for arthritis and inflammatory conditions,” Talbott said. “The primary compounds thought to be responsible for the anti-inflammatory activity of boswellia are known as boswellic acids. These compounds are known to interfere with enzymes that contribute to inflammation and pain: cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LO) and 12-lipoxygenase (12-LO).”

One concentrated source of boswellic acids is 5-LOXIN,® from P.L. Thomas. “5- LOXIN provides the highest concentration of the most potent boswellic acid called 3-OAcetyl- 11-keto-beta-boswellic acid (AKBA),” said Eric Anderson, brands manager with P.L. Thomas. “5-LOXIN complements products like glucosamine and chondrotin by working though a different mechanism to help combat pain and inflammation, and helping to protect against the breakdown of connective tissues. 5-LOXIN, manufactured through a patent pending process, has been subject to rigorous study, with published research demonstrating its mechanism of action.

In a study headed at Ohio State University, researchers tested the genetic basis for the anti-inflammatory effects of boswellia extract (as 5-LOXIN) in a system of TNFa-induced gene expression in human microvascular endothelial cells, and found 113 of the 522 genes induced by TNFa treatment were sensitive to 5-LOXIN.⁴ Further, the researchers found 5-LOXIN inhibited carrageenan-induced rat paw edema, consistent with their in vitro findings.

Another tuberous botanical with efficacy against inflammation is ginger. Ginger suppresses prostaglandin synthesis through inhibition of COX-1 and COX-2 as well as 5-LO, which may give ginger a better therapeutic profile and have fewer side effects than nonsteroidal anti-inflammatory drugs.⁷ Japanese and Korean research has shown ginger constituents, aframodial, and galanal B, [6]- gingerol and galanolactone, suppress free radical generation and inducible proinflammatory gene expressions.^8,9,10

According to Talbott, supplementation with proteolytic enzymes is another strategy arthritis patients can follow to lower inflammation. “Proteolytic is a catch-all term for enzymes that digest protein,” he said. “Supplemental forms can incorporate any of a wide variety of enzymes including trypsin, chymotrypsin, pancreatin, bromelain, papain and a range of fungal proteases.”

One multi-enzyme complex of benefit to arthritis patients is Wobenzym, from Naturally Vitamins. Wobenzym contains the proteolytic enzymes trypsin, chymotrypsin, pancreatin, bromelain and papain, and a powerful antioxidant known as rustosid.

According to the company, the enzymes are absorbed into the bloodstream in the small intestine, and travel throughout the body capturing excess cytokines and breaking up potentially harmful proteins, which cleans debris from the bloodstream and helps normalize inflammation and support the immune system to promote overall health.

Another compound thought to alleviate inflammation is astaxanthin. In a proprietary study from Cyanotech, researchers randomly assigned 21 RA test subjects to receive a supplement containing 4 mg astaxanthin (as BioAstin), 40 mcg lutein, 65 IU vitamin A as beta-carotene, and 50 IU of vitamin E (n=14) or placebo (n=7) three times daily for eight weeks. The results showed a significant difference in pain and satisfaction scores between the treatment and control groups.

“The differences between blockbuster pharmaceuticals such as Vioxx and Celebrex, and BioAstin Natural Astaxanthin are that BioAstin has no side effects or contraindications, whereas Vioxx and Celebrex have been shown to have serious potential side effects, and BioAstin will take a few weeks to show its effects in most cases,” said Bob Capelli, vice president of sales with Cyanotech. “This is because BioAstin works through several different pathways to combat inflammation in the body in a much gentler manner.”

Beyond botanicals and enzymes, an anti-inflammatory ingredient from the avian realm often recommended to arthritics is emu oil, which can be applied topically or taken internally. Research from the University of Adelaide in Australia showed emu oil delivered in a transdermal vehicle produced anti-inflammatory, anti-rheumatic activity in a variety of rat models.¹¹

“Emu oil is rich in naturally occurring omega-6 fatty acids, which lower inflammation,” said Anne Geller, chief executive officer (CEO) of Thunder Ridge Emu Products. “In addition, the oil increases circulation, which promotes healing in stiff joints.”

Lowering inflammation contributes to a reduction in pain, according to Robert Hunt, president of RZN Nutraceuticals, producers of Arthri-Zen, which contains juniper, goldenrod, dandelion, meadowsweet and willow bark. “The reduction of pain, swelling and inflammation are closely tied together,” he said. “Virtually every one of the chemicals produced by the body as part of the acute reaction to injury or disease is water soluble and travels around via the blood plasma and gets through the tissues via cellular fluid. Reduction of pain is accomplished by reducing the number and intensity of pain signals traveling to the brain through nerves and reducing the concentration of substances which promote and/or increase those signals.”

References

1. Ammon HP. "[Boswellic acids (components of frankincense) as the active principle in treatment of chronic inflammatory diseases]."Wien Med Wochenschr. 152, (15-16):373-8, 2002. www.blackwell-synergy.com

2. Fan AY et al. "Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on adjuvant-induced arthritis in lewis rats." J Ethnopharmacol. 101, (1-3):104-9, 2005. www.elsevier.com

3. Kimmatkar N et al. "Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial." Phytomedicine. 10, 1:3-7, 2003.

4. Human genome screen to identify the genetic basis of the anti-inflammatory effects of boswellia in microvascular endothelial cells." Dna and cell biology. 24, 4:244-255, 2005.

5. Chainani-Wu N. "Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa)." J Altern Complement Med. 9, 1:161-8, 2003. www.liebertonline.com

6. Aggarwal BB et al. "Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning." Ann N Y Acad Sci. 1030:434-41, 2004. www.annalsnyas.com

7, Grzanna R et al. "Ginger--an herbal medicinal product with broad anti-inflammatory actions." J Med Food. 8, 2:125-32, 2005.

8. Aggarwal BB et al. "Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning." Ann N Y Acad Sci. 1030:434-41, 2004. www.annalsnyas.com

9. Funk JL et al. "Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis." J Nat Prod. 69, 3:351-5, 2006.

10. Joe B et al. "Presence of an acidic glycoprotein in the serum of arthritic rats: modulation by capsaicin and curcumin." Mol Cell Biochem. 169, (1-2):125-34, 1997. www.springerlink.com

Addressing Canine Arthritis

References

Many of the same compounds with efficacy against arthritis in humans also bring relief to man’s best friend. Likely due to their safety and cost-effectiveness, nutraceuticals have become attractive adjunctive or alternative treatments for cats and dogs suffering from osteoarthritis (OA), one of the most common chronic musculoskeletal diseases and causes of lameness in dogs.¹

One ingredient boasting both testimonials and research studies about its impact on canine OA is type II chicken collagen. Ahmad Alkayali, consultant to Collagen Nutraceuticals, related a story of how daily supplementation with type II collagen reversed hip dysplasia that could have potentially resulted in arthritis in an Airedale Terrier. “It was determined the dog would face significant osteophyte formation relatively soon, and surgery was recommended,” he said. “Six years following daily supplementation with type II collagen— as ArthroPet™, from Neocell Corp.; marketed to humans as Kolla2®—the same examiners were surprised to find there was a ‘definite filling in of bilateral femoral necks’ with the dog having clinically normal mobile activity.”

He added another dog with osteoarthritis and a missing leg was placed on ArthroPet by his veterinarian and was found to have his comfort and mobility level “improved at least 75 percent over his previous condition after supplementing with ArthroPet for about six months,” he said. “Based on these preliminary findings, additional canines are being recruited to be subjects of a larger clinical trial.”

There has been some study on the usefulness of other compounds for their ability to treat animal arthritis.

• Administration of green lipped mussel extract significantly improved pain and swelling in dogs with clinical signs of arthritis after a six week intervention.⁴
• Elk velvet antler
significantly improved gait, daily life activities and vitality in dogs with OA.⁵
• In a study involving 50 large-breed 7- to 12-year-old dogs with OA, those given milk protein concentrate (as MicroLactin®, from Humanetics) for eight weeks found 68 percent of animals showed improvements in orthopedic conditions.⁶
• Boswellia
has been found to improve clinical signs of arthritis in dogs in a dose of 400 mg/10 kg/d.⁷
• The botanical extract turmeric has been shown to significantly impact joint pain and lameness, as assessed by pet owners.⁸

Given the frequency of occurrence of arthritis in veterinary patients, retailers should remain aware of the mechanisms of the disease, related literature and different treatment options. Although there still much to be learned in regard to management of canine arthritis, currently, the best recommendation is to use products that have well-designed experimental and clinical research evaluating efficacy and safety, and products that are manufactured under high quality standards.

References

1. Henrotin Y et al. "Pharmaceutical and nutraceutical management of canine osteoarthritis: present and future perspectives." Vet J. 170, 1:113-23, 2005. www.elsevier.com

2. Deparle LA et al. "Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs." J Vet Pharmacol Ther. 28, 4:385-90, 2005. www.blackwell-synergy.com

3. D’Altilio M et al. "Safety and Therapeutic Efficacy of Denatured Type II Collagen Alone, and in Combination with Glucosamine and Chondroitin in Arthritic Dogs." 45th Annual Meeting of the Society of Toxicology, San Diego, CA, Volume 90:1, Abs 1682, Pg 344, March 2006.

4. Bui LM et al. "Influence of green lipped mussels (Perna canaliculus) in alleviating signs of arthritis in dogs." Vet Ther. 4, 4:397-407, 2003.

5. Moreau M et al. "Clinical evaluation of a powder of quality elk velvet antler for the treatment of osteoarthrosis in dogs." Can Vet J. 45, 2:133-9, 2004.

6. Gingerich DA et al. "Use of client-specific outcome measures to assess treatment effects in geriatric, arthritic dogs: controlled clinical evaluation of a nutraceutical." Vet Ther. 4, 1:56-6, 6, 2003.

7. Reichling J et al. "Dietary support with Boswellia resin in canine inflammatory joint and spinal disease." Schweiz Arch Tierheilkd. 146, 2:71-9, 2004.

8. Innes JF et al. "Randomised, double-blind, placebo-controlled parallel group study of P54FP for the treatment of dogs with osteoarthritis." Vet Rec. 152, 15:457-60, 2003.

Clinicaltrials.gov, National Institutes of Health. "Glucosamine Unum In Die [Once A Day] Efficacy , GUIDE Trial: Glucosamine Sulfate in Patients With Knee Osteoarthritis." [Online] Available Jan. 1, 2006. http://www.clinicaltrials.gov/ct/show/NCT00110474 

GAIT Ignites Controversy

Throughout the health care community, debate surrounds results of the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT), the first largescale, multicenter clinical trial in the United States to test the effects of glucosamine hydrochloride (glucosamine) and sodium chondroitin sulfate (chondroitin sulfate) for treatment of knee osteoarthritis (OA),¹ funded by the National Institutes of Health (NIH). According to a range of health care practitioners and qualified experts, the study’s abstract and portrayal to the media do not accurately reflect the data collected during the trial, which was published in The New England Journal of Medicine (354, 8:795-808, 2006).

In the 24-week study, researchers from more than a dozen health care facilities across the United States compared the effects of 1,500 mg/d glucosamine hydrochloride, 1,200 mg/d sodium chondroitin sulfate, both of these treatments administered simultaneously, 200 mg/d celecoxib (marketed under the name Celebrex) and placebo, on patients with knee pain. All study participants were allowed up to 4,000 mg/d acetaminophen as a “rescue” analgesia, except within 24 hours of patient evaluations. Of 1,583 participants, 1,258 individuals (64 percent women) with a mean age of 58.6 years, a body mass index of 31.7 kg/m2, and a 10-year history of OA symptoms completed the study. In the abstract, the researchers noted the rate of response was significantly higher in the glucosamine plus chondroitin group than in the placebo group (79.2 percent vs. 54.3 percent). They also noted exploratory analyses suggest the combination of glucosamine and chondroitin sulfate may be effective in patients with moderate-to-severe knee pain. However, the authors of the study did not mention the data showed the combination of glucosamine and chondroitin reduced pain more effectively than Celebrex; further, they concluded glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients.

“Although the data in the study showed the natural remedies more effective for pain relief than Celebrex—and they’re much cheaper and don’t cause literally tens of thousands of unnecessary deaths every year—the conclusion of the study was ‘use the drugs’,” said Jacob Teitelbaum, author of Pain Free 1-2-3 (McGraw-Hill). “Eleven of the authors of the study were employees of the company that manufactures Celebrex.”

Teitelbaum explained many important data were overlooked in the abstract:

• 79 percent of those who took the natural remedies achieved the primary outcome—a 20-percent reduction in WOMAC scores— whereas only 69 percent of individuals taking the prescription medication achieved this.
• Statistically, if the P value is greater than .05, the treatment didn’t work. The P value for the glucosamine plus chondroitin combination was 0.02, whereas the P value for Celebrex was 0.06.
• 60.1 percent of the placebo group, 66.6 percent of the glucosamine plus chondroitin group and 70.1 percent of the Celebrex group responded to treatment; Teitelbaum explained these percentages aren’t a big difference, clinically.
• The placebo group had an 86.1-point reduction in WOMAC score, the glucosamine plus chondroitin group had a 100.5-point reduction, and the Celebrex group had a 100.0-point reduction; the greater the drop, the greater the overall pain relief, Teitelbaum said.
• The placebo group had a 16.6-point reduction in HAQ scores, the natural remedies group had a 20.8-point reduction, and the Celebrex group had a 20.2-point reduction, which is less than the reduction achieved in the glucosamine plus chondroitin group; again, the greater the drop, the greater the overall pain relief, according to Teitelbaum.

Jason Theodosakis, M.D., who was one of the six members on the steering oversight committee for GAIT, agreed the abstract may have missed key data and added the study design may have promoted misrepresentation of the data.

“It’s sometimes difficult to get the results of a large and complicated study into the small confines of an abstract; this is certainly the case with GAIT,” he said. “The original abstract of the study, presented and published before the full write-up of the article in NEJM in February 2006, was very concise and revealed the most important finding: the combination of glucosamine and chondroitin was the most effective intervention for those subjects who really needed the most help (those with moderate to severe pain). The abstract, as it appeared in the full article in the journal, deemphasized what many of us thought was the most clinically significant finding. The biggest flaw the study design allowed for an unusually high placebo response. Since each of the treatments were compared to placebo, a high placebo rate would essentially dilute the data. This is exactly what happened as evidenced by the failure of the positive control drug (Celebrex), in 48 out of 52 of the outcome measures across the three groups of subjects. Some have argued that when the positive control fails in so many cases, that the whole study is really understating the true effects and should be deemed inconclusive or void. Since this study was performed using taxpayer money, I’m sure there was a concern to list the study as inconclusive since many would have felt the $14 million was wasted.”

Theodosakis agreed the oversight of key data in the abstract may have contributed to confusion, particularly in the press. “The primary outcome measure was a 20 percent or more decrease in WOMAC scores; 13 other outcome measures were part of the study, however, and the results from these were barely noted in the press,” he said. “For instance, chondroitin was found to be the most effective agent for reducing joint swelling or ‘fluid in the knee.’ This is a very sensitive indicator of a treatment’s anti-inflammatory properties. The dietary supplement actually beat out the prescription anti-inflammatory drug.”

Todd Henderson, DVM, vice president of Nutramax Laboratories, agreed the trial was irresponsibly reported to the media. “If you look at some of the authors’ quotes regarding the results of the trial, they waffle,” said Henderson, whose company supplied the chondroitin sulfate used in the study (CSb™ Bio-Active, from Bioiberica). “One minute it’s a positive study, the next minute it’s a negative study. They spent $14 million of taxpayers’ money. What exactly were they supposed to find?”

In spite of the controversy over GAIT, however, Theodosakis believes the confusion within the media should not affect retailers. “Since glucosamine and chondroitin often provide symptomatic benefit in those who are smart enough to stay on them for a period of several months, it’s unlikely that the results of GAIT would result in a decreased use of these supplements,” he said. “For those who were patient enough to read the results and conclusion of the entire study, they were able to see that nearly 80 percent of the study subjects had significant pain relief if they started out with moderate to severe symptoms. This should actually benefit the sales of glucosamine and chondroitin. Unfortunately, people tend to base decisions just on the most previously reported study. One should keep in mind that GAIT was one of almost 40 human clinical trials utilizing these supplements. Recommendations should be based on the entirety of the data.”

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