Where there are chronic, incurable medical problems, alternative therapies will usually be found, and arthritis is certainly fertile ground. Some arthritis alternatives have been in use long enough to verge on mainstream medicine, including acupunctur e and glycosaminoglycans. Others are virtually unknown to all but a few practitioners, and veterinarians have no way of evaluating their efficacy. How do we know which ones to recommend and investigate?
When disruption and inflammation that affect compo nents of the joint (articular cartilage, subchondral bone, synovium and joint capsule) have their origin in abnormal forces traumatizing the joint, nutritional supplements can only slow the degenerative process. This slowing of joint changes, however, i s not a benefit currently offered by most nonsteroidal or steroid anti-inflammatory drugs. Nutritional supplements, then, have a unique and important function in treatment of arthritis.
Cartilage is composed of chondrocytes which produce extracellular matrix. The matrix is composed of collagen which is primarily supportive, water, and proteoglycans, which make up 22-38% of the cartilage by dry weight. These proteoglycans include chondroitin sulfate, keratan sulfate and dermatan sulfate. They can occupy up to 50 times their dry weight volume when hydrated, and they are negatively charged. These proteoglycans are, then, ‘fluffy', but are constrained and supported by the collagen framework.
Osteoarthritis is accompanied by a number of functional changes. Synoviocytes appear to release metalloproteinases that degrade proteoglycans and collagen fragments, as well as cytokines that mediate ongoing inflammation, all leading to proteoglycan depletion. In time, the joint capsule thickens and vascularity in creases, there is subchondral bone stiffening and osteophytes form.
The aims of nutritional and herbal therapies include supporting proteoglycan synthesis and decreasing inflammation. Quite a few supplements have been proposed.
Comp lex sugars used for treatment of osteoarthritis include polysulfated glycosaminoglycan (Adequan), pentosan polysulfate (Elmiron), glucosamine, chondroitin sulfate, or combinations of the two (Cosequin, Chonflex, Osteocare and many others) or Perna canalic ulus mussel (a source of chondroitin plus other components of the mussel). Clinical impression tends to support use of these supplements as early in the disease as possible.
There is good evidence that PSGAG (Adequan) is absorbed and incorporated into cartilage following intramuscular, intraarticular and subcutaneous injection. PSGAG appears to concentrate in sufficient quantity to decrease cartilage catabolism, inhibit proteinase activity and is accompanied by an increase in hyaluronan, a major const ituent of synovial fluid. PSGAG is recommended for treatment of osteoarthritis as well as for immediate post operative support following some joint surgeries. The currently recommended dose is 5mg/kg twice weekly for 4 weeks, then as needed.
Pentosan p olysulfate is isolated from beechwood hemicellulose, and the preparation may be administered orally (as Elmiron, in the U.S. where it is not approved for dogs) or intramuscularly in other countries where it is approved for use in dogs. It is used under the same circumstances as PSGAG, and the dose for osteoarthritis treatment is 2-3 mg/kg weekly as needed.
Glucosamine is probably the most popular of alternative treatments administered orally for arthritis. Demand for proteoglycan precurso rs exceeds supply due to increased destruction in osteoarthritis, and oral administration of glucosamine may support greater synthesis of glycosaminoglycans, proteoglycans and collagen. In addition, glucosamine may act as a cyclooxygenase-independant ant i -inflammatory agent. Concerns have been raised regarding gastrointestinal absorption of glucosamine; in one study, 87% of orally administered glucosamine was absorbed in the GI tract (Setnikar, 1991). Glucosamine has been shown as effective as ibuprof e n in well designed human clinical trials, and is safer than NSAIDs (Qiu 1998). Although much is made in sales publications about differing efficacy of the HCL vs. sulfate forms, we dont' know if there is a difference in dogs. This author recommends 20-50 mg/kg divided daily.
Chondroitin sulfate is a related compound that often combined with glucosamine. It is also well absorbed (62% of orally administered chondroitin, in one study) (Conte, 1995). Chondroitin sulfate probably has similar anti-inflammatory and stimulatory properties that result in decreased cartilage destruction. Clinically, chondroitin sulfate is much more expensive than plain glucosamine. Since glucosamine is a precursor molecule for chondroitin, glucosamine alone may provide cli nical effects and cost less to use.
Vitamin C (ascorbate) functions in collagen synthesis by reducing prolyl hydroxylase and lysyl hydroxylase, catalysts in the formaton of hydroxyproline an d hydroxylysine. In one study (Berge, 1990), 100 dogs were given polyascorbate (calcium ascorbate plus ascorbate metabolites, a pH neutral form said to have better absorption than other forms of ascorbate). The dose was 30mg TID po for 6 months. Diagno s is was based on lameness, decrease in mobility, pain, physical exams, and in some cases, radiography. There were no controls in this study. Outcomes were based on owner reports and physical exam results at 7 days, 6 weeks and 6 months. Only dogs with s i gns lasting longer than 6 weeks were included. After 1 week, 71% of dogs with hip dysplasia were judged to have good improvement or were symptom free. Another 28% were judged to have shown small improvements. Of dogs with spondylosis and disk disease, 7 6% were judged to have shown good improvement and 24% small improvement. No side effects were reported. These authors additionally conducted a very small crossover trial, where 6 of the dogs with chronic arhtritis examined. 3 were given the polyascorba te product and 3 given placebo. After a washout of 4 weeks, the groups were crossed over with similar results – those on the polyascorbate improved while those given placebo did not.
In one study in dogs, Vitamin E appeared to show bene fit (Impellizeri, 1998). Other antioxidant micronutrients have proved helpful in people (McAlindon, 1996, Sowers, 1999). In practice, many find that antioxidant combinations are more beneficial than choosing selected antioxidant vitamins, and veterinary products can be supplied at label doses. Antioxidant enzymes, particularly superoxide dismutase, have also been used in the treatment of osteoarthritis and may be found in veterinary products designed for osteoarthritis treatment. Studies are suggestive , but not conclusive that superoxide dismutase is of therapeutic aid.
Methysulfonylmethane is an oxidation product of DMSO (dimethyl sulfoxide), and is sometimes considered a nutraceutical. It is found in plants such as horsetail (Equisetum arvense), fruits, vegetables and grains and provides a sulfur source for methionine. MSM is said to reduce inflammation by acting as an antioxidant. Although toxicity has not been reported, the anti-inflammatory effects have not been substantiated. Clinical rep orts of efficacy against osteoarthritic pain continue to be encouraging. Practitioners dose MSM at 100-1000mg daily.
SAMe has been used in human medicine for depression, liver disease and arthritis. Laboratory animal studies su ggest that SAMe has some chondroprotective function, and human clinical trials indicate that it may be as effective as NSAIDs with fewer side effects. SAMe is not in popular use in veterinary medicine at this time. A veterinary product is available from Nutramax.
Proteolytic enzymes have been used as anti-inflammatory pain agents by virtue of their inhibition of proinflammatory compounds and fibrinolytic activity. In a recent randomised double blind study comparing a combination enzyme product (bromelain, trypsin and rutin) to diclofenac, the enzyme produced equivalent improvements in pain indices (Klein, 2000). Although that product is not available in the U.S., a similar product (Wobenzym â) is used in the authorÕs practice at doses proportional to the human label dose.
Cetyl myristoleate (CMO)
CMO has apparently anti-inflammatory actions (Diehl, 1994) , although it is not well studied. It is being used by some practitioners at a dose of 250mg SID t o 1155mg BID. One potential advantage to using CMO is that it can be used for 2-4 weeks then stopped indefinitely, as opposed to the constant use required by most other nutritional supplements for osteoarthritis.
N-6 fatty acids (Ernst, 2000)
Evening Prim ose oil and Borage oil, sources of gamma-linoleic acid, have been recommended for treatment of osteoarthritis in humans. Black currant oil, which supplies gamma-linoleic acid as well as alpha-linoleic acid, has also been recommended. In an excellent co n trolled study in people by Belch (1988) , evening primrose oil did not reduce morning stiffness, grip strength, joint tenderness or debility scores, but did reduce the use of NSAIDs. Leventhal (1994) examined black currant oil, and found that 15 capsule s daily reduced some symptoms but did not produce an overall better response than in control groups. The large dose may be a deterrant to clinical use even if it does show better efficacy in future trials. Leventhal (1993) and Zurier (1993) conducted c o ntrolled trials comparing borage seed oil to cottonseed or safflower oil controls in clinical trials of 37 and 56 people, respectively. Borage oil appeared to lead to significant improvement in clinical signs with negligible side effects. The dose in Zu rier's trial was 4 capsules BID for a human.
N-3 fatty acids
Although omega-3 fatty acids are potentially useful for their anti-inflammatory effects, work to date only suggests that fish oil is effective for induced and immune-mediated arthritides.
Herbal Arthritis Treatments
Harpagophytum procumbens is a plant used in traditional African medicine for arthritis. In 2 large trials totalling 315 patients by Chrubasik (described in Ernst, 2000) , Devil's claw treatment resulted in more p ain-free patients at the end of the trial. Chrubasik used doses of 600 to 1600 mg per day.
2 studies reviewed in Ernst, 2000 suggest that willow bark significantly decreases pain. Willow bark is a source of salicin, and might be expected to exert its effects through salicylate mechanims.
Tanacetum parthenium is an herb with potential use in migraine headaches. In one trial detailed in Ernst, 2000, feverfew was not effective in reducing pain in arthritis patients.
Ernst, in his review, describes unpublished data from a randomized controlled trial where a stew of aerial parts, but not a concentrated juice containing 10 times more of the presumed active ingredient (lipoxygenase inhibitor caffeoyl malic acid) of Urtica dioica is effective for pain.
Ginger has been recommended for anti-inflammatory effects through eicosanoid modulation. Studies are few, but may suggest some activity (Bliddall, 2000).
Corydalis turtschaninovii, C. decumbens, and C. incisa are part of traditional Chinese herbal combinations for pain. Although a specific mechanism of action has not been well described, authorities state that continued use will lead to tolerance and to cross tolerance with opioids.
Boswellia probably reduces pain and inflammation through its activity as a lipoxygenase inhbitor. It is commonly combined with curcumin (turmeric) in Ayurvedic arthritis remedies.
Yucca is popular but not well studied. One proposed mechanism of action involves saponins suppressing gut bacterial endotoxin production, removing a supposed suppressor of proteoglycan synthesis.
Several proprietary herbal combinations have been shown effective in people and are briefly described in Ernst, 2000.
One Chinese herbal combination tested in dogs appeared effective (Bonnett)
In a study on 143 clinical canine patients, a Chinese herbal combination was compared to DevilÕs claw combination, aspirin and placebo. The Chinese herbal prescriptio n contained white peony, licorice, epimedium, oyster shell, reish mushroom, isatidis and corydalis. The Chinese herbal combination and aspirin produced significant improvement in owner and veterinary evaluation, while the response to devils claw combinati on was equivalent to the placebo response (Bonnett, 1996). This combination is not commercially available to this authorÕs knowledge, but can be formulated on request by reputable Chinese pharmacies (like Mayway) or naturopathic pharmacies.
Ancillary Nutritional Strategies
Leaky Gut is a theoretical situation where mucosal inflammation (due to food allergy, intolerance to other dietary factors or toxins, or nonsteroidal or other drugs which induce inflammation in the gut) leads to systemic absorption of su bstances normally sequestered in the gut. This increased permeability allows abnormally large (and potentially immunogenic) food proteins and microbial elements systemic access, potentially exacerbating inflammation elsewhere in the body. Elimination die ts, glutamine, fiber and probiotics are often recommended for this diagnosis.
Whether or not leaky gut is a real diagnosis, many dogs experience less inflammation and pain when switched to a diet of fresh foods. Some believe that preparation and cooking of commercial diets changes proteins sufficiently that switching to whole food versions of the same ingredients essentially changes the food antigens presented at the gut. It is also possible that fresh foods provide sources of phyto-antioxidants, MSM a nd other nutrients useful for arthritis. Homemade diet recipes may be found in these books: Home Prepared Dog and Cat Diets (Donald Strombeck) and Natural Health for Dogs and Cats (Richard Pitcairn).
Berge GE 1990
. Polyascorbate (C-Flex R) an interesting alternative by problems (sic) in the support and movement apparatus in dogs. The Norwegian Veterinary Journal 102:
Bliddal H; Rosetzsky A; Schlichting P et al, 2000. A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis: Osteoarthritis Cartilage 8(1):9-12
Bonnett B, Poland C, 1996. Preliminary results of a randomized, double blind, multicenter, controlled clinical tria of two herbal therapies, acetylsalicylic acid and placebo for osteoarthritic dogs. Proceedings of the American Holistic Veterinary Medical Association, Burlington, VT, p 143-147.
Budsberg SC, Todhunter RJ, and PS McNamara, 2000. Use of Chondromodulating Drugs and Substances in the Prevention and Treatment of Osteoarthritis in Dogs. Kirk's Current Veterinary Therapy XIII: Small Animal Practice , John Bonagura, Ed. W.B. Saunders, Philadelphia.
Conte A, 1995, Arzneimittelforschung 45:918
Diehl HW, May EL, 1994 Cetyl myristoleate isolated from Swiss albino mice: an apparent protective agent against adjuvant arthritis in rats. J Pharm Sci. 1994 83(3):296-9
Ernst E, Chrubasik S, 2000. Phyto-anti-inflammatories: a systematic review of randomized placebo controlled double blind trials. Rheumatic Disease Clinics of North America 26(1):13-27.
Impellizeri JA; Lau RE; Azzara FA , 1998. Fourteen week clinical evaluation of an oral antioxidant as a treatment for osteoarthritis secondary to canine hip dysplasia. Vet Q 1998;20 Suppl 1:S107-8
Johnston S, Ed, 1997. Osteoarthritis. Veterinary Clinics of North America 27:4 (July). W.B. Saunders, Philadelphia.
McAlindon TE, Jacques P, Zhang Y et al, 1996. Do antioxidant micronutrients protect against the development and progression of knee osteoarthrits? Arthritis Rheum 39:648
Monograph a, 1998. Boswellia serrata. Altern Med Rev 3(4):306-7
Morrison L, ed, 1974 Coronary Heart Disease and Mucopolysaccharides, p 109
Qiu GX, Gao SN, Giacovelli G et al, 1998. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung 48:469-474.
Setnikar I 1991 Arzneimittelforschung 36:729
Sowers M; Lachance L , 1999. Vitamins and arthritis. The roles of vitamins A, C, D, and E. Rheum Dis Clin North Am 25(2):315-32