Osteoarthritis - Nutritional and Herbal support ratings
Rating	Nutritional Supplements	Herbs
	Chondroitin sulfate Glucosamine sulfate SAMe Vitamin B3 (niacinamide)	Boswellia (also in combination with ashwagandha, turmeric, and zinc) Cat’s claw Cayenne (topical, for pain only) Ginger
	Cartilage Cetyl myristoleate Collagen DMSO (topical) Green-lipped mussel Vitamin E	Devil’s claw Guggul Nettle Willow
	Boron Bovine cartilage D-phenylalanine (DPA) Fish oil (EPDHA) Glucosamine hydrochloride Methylsulfonylmethane (MSM)	Colchicine Horsetail Meadowsweet Yucca
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. Herb supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

What are the symptoms of osteoarthritis?

The onset of OA is gradual and most often affects the hips, knees, fingers, and spine, although other joints also may be involved. Pain is the main symptom, which usually worsens with exercise and is relieved by rest. Morning stiffness is also common and diminishes with movement. As OA progresses, joint motion is lost, and tenderness and grating sensations may develop. OA of the spine may lead to shooting pains down the arms or legs.

Medical treatments

Over the counter nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin (Bayer®, Ecotrin®, Bufferin®), ibuprofen (Motrin®, Advil®), and naproxen (Aleve®), as well as acetaminophen (Tylenol®), may help provide pain relief in mild cases. Topical creams containing capsaicin (Zostrix®) may also be used for local pain relief. Prescription medications for pain relief include NSAIDs, such as diclofenac (Voltaren®), etodolac (Lodine®), ibuprofen (Motrin®), and indomethacin (Indocin®). Treatment designed to relieve OA symptoms includes the use of hot soaks, warm paraffin applications, heating pads, and joint support devices.

Dietary changes that may be helpful

In the 1950s through the 1970s, Dr. Max Warmbrand used a diet free of meat, poultry, dairy, chemicals, sugar, eggs, and processed foods for people with rheumatoid arthritis and OA, anecdotally claiming significant success. He reported that clinical results took at least six months to develop. The Warmbrand diet has never been properly tested in clinical research. Moreover, although the diet is healthful and might reduce the risk of being diagnosed with many other diseases, it is difficult for most people to follow. This difficulty, plus the lack of published research, leads many doctors who are aware of the Warmbrand diet to use it only if other approaches have failed.

Solanine is a substance found in nightshade plants, including tomatoes, white potatoes, all peppers (except black pepper), and eggplant. In theory, if not destroyed in the intestine, solanine may be toxic. One horticulturist hypothesized that some people might not be able to destroy solanine in the gut, leading to solanine absorption and resulting in OA. This theory has not been proven. However, eliminating solanine from the diet has been reported to bring relief to some arthritis sufferers in preliminary research. In a survey of people avoiding nightshade plants, 28% claimed to have a “marked positive response” and another 44% a “positive response.” Researchers have never put this diet to a strict clinical test; however, the treatment continues to be used by some doctors with patients who have OA. As with the Warmbrand diet, proponents claim exclusion of solanine requires up to six months before potential effects may be seen. Totally eliminating tomatoes and peppers requires complex dietary changes for most people. In addition, even proponents of the diet acknowledge that many arthritis sufferers are not helped by using this approach. Therefore, long-term trial avoidance of solanine-containing foods may be appropriate only for people with OA who have not responded to other natural treatments.

Most of the studies linking allergies to joint disease have focused on rheumatoid arthritis, although mention of what was called “rheumatism” in older reports (some of which may have been OA) suggests a possible link between food reactions and aggravations of OA symptoms.⁴ If other therapies are unsuccessful in relieving symptoms, people with OA might choose to discuss food allergy identification and elimination with a physician.

Lifestyle changes that may be helpful

Obesity increases the risk of OA developing in weight-bearing joints, and weight loss in women is associated with reduced risk for developing OA.^{5 6} Weight loss is also thought to reduce the pain of existing OA.⁷

Nutritional supplements that may be helpful

Glucosamine sulfate (GS) is a natural compound that is found in healthy cartilage. Glucosamine sulfate is a normal constituent of glycoaminoglycans in cartilage matrix and synovial fluid. Available evidence from randomized controlled trials supports the use of glucosamine sulfate in the treatment of osteoarthritis, particularly of the knee. It is believed that the sulfate moiety provides clinical benefit in the synovial fluid by strengthening cartilage and aiding glycosaminoglycan synthesis

Glucosamine sulfate , a nutrient also derived from seashells and from Commiphora mukul (Gugul), is a building block needed for the synthesis and repair of joint cartilage. GS supplementation has significantly reduced symptoms of OA in uncontrolled and single-blind trials. Many double-blind trials have also reported efficacy. Only one published trial¹⁷ has reported no effect of GS on OA symptoms. While most research trials use 500 mg GS taken three times per day, results of a three-year, double-blind trial indicate that 1,500 mg taken once per day produces significant reduction of symptoms and halts degenerative changes seen by X-ray examination. GS does not cure people with osteoarthritis, and they may need to take the supplement for the rest of their lives in order to maintain benefits. Fortunately, GS appears to be virtually free of side effects, even after three or more years of supplementation. Benefits from GS generally become evident after three to eight weeks of treatment.

Only one trial has evaluated another form of glucosamine as a single remedy for OA. This trial found only minor benefits from 1,500 mg per day of glucosamine hydrochloride (GH) for eight weeks in people with osteoarthritis of the knee; these people were also taking up to 4,000 mg per day of acetaminophen for pain relief. To more fairly evaluate the effects of GH, future research should exclude people taking pain-relieving medication. Another form of glucosamine sometimes found in combination formulas, N-acetyl-glucosamine (NAG), has not been studied in people with osteoarthritis.

Chondroitin sulfate (CS) The major source of Chondroiten is from the traches of cows. Chondroitin was first extracted and purified in the 1960s. It is currently manufactured from natural sources (shark/beef cartilage or bovine trachea) or by synthetic means. The consensus of expert and industry opinions support the use of chondroitin and its common partner agent, glucosamine, for improving symptoms and arresting (or possibly reversing) the degenerative process of osteoarthritis. Chondroitin is a major component of the lining of joints. The structure of CS includes molecules related to glucosamine sulfate. CS levels have been reported to be reduced in joint cartilage affected by OA. Possibly as a result, CS supplementation may help restore joint function in people with OA. On the basis of preliminary evidence, researchers had believed that oral CS was not absorbed in humans; as a result, early double-blind CS research was done mostly by giving injections. This research documented clinical benefits from CS injections. It now appears, however, that a significant amount of CS is absorbable in humans, though dissolving CS in water leads to better absorption than swallowing whole pills.

Strong clinical evidence now supports the use of oral CS supplements for OA. Many double-blind trials have shown that CS supplementation consistently reduces pain, increases joint mobility, and/or shows evidence (including X-ray changes) of healing within joints of people with OA. Most trials have used 400 mg of CS taken two to three times per day. One trial found that taking the full daily amount (1,200 mg) at one time was as effective as taking 400 mg three times per day. Reduction in symptoms typically occurs within several months.

S-adenosyl methionine (SAMe) found in Flaxseed, possesses anti-inflammatory, pain-relieving, and tissue-healing properties that may help protect the health of joints, though the primary way in which SAMe reduces OA symptoms is not known. A very large, though uncontrolled, trial (meaning that there was no comparison with placebo) demonstrated “very good” or “good” clinical effect of SAMe in 71% of over 20,000 OA sufferers. In addition to this preliminary research, many double-blind trials have shown that SAMe reduces pain, stiffness, and swelling better than placebo and equal to drugs such as ibuprofen and naproxen in people with OA. These double-blind trials all used 1,200 mg of SAMe per day.

Lower amounts of oral SAMe have also produced reductions in the severity of OA symptoms in preliminary clinical trials. A two-year, uncontrolled trial showed significant improvement of symptoms after two weeks at 600 mg SAMe daily, followed by 400 mg daily thereafter. This amount was also used in a double-blind trial, but participants first received five days of intravenous SAMe. A review of the clinical trials on SAMe concluded that its efficacy against OA was similar to that of conventional drugs but that patients tolerated it better.⁵⁰

People who have OA and eat large amounts of antioxidants in food have been reported to exhibit a much slower rate of joint deterioration, particularly in the knees, compared with people eating foods containing lower amounts of antioxidants. Of the individual antioxidants, only vitamin E has been studied as a supplement in controlled trials. Vitamin E supplementation has reduced symptoms of OA in both single-blind and double-blind research. In these trials, 400 to 1,600 IU of vitamin E per day was used. Clinical effects were obtained within several weeks. However, in a six-month double-blind study of patients with osteoarthritis of the knee, 500 IU per day of vitamin E was no more effective than a placebo.

In the 1940s and 1950s, one doctor reported that supplemental niacinamide (a form of vitamin B3) increased joint mobility, improved muscle strength, and decreased fatigue in people with OA. In the 1990s, a double-blind trial confirmed a reduction in symptoms from niacinamide within 12 weeks of beginning supplementation. Although amounts used have varied from trial to trial, many doctors recommend 250 to 500 mg of niacinamide four or more times per day (with the higher amounts reserved for people with more advanced arthritis). The mechanism by which niacinamide reduces symptoms is not known.

The effects of New Zealand green-lipped mussel supplements have been studied in people with OA. In a preliminary trial, either a lipid extract (210 mg per day) or a freeze-dried powder (1,150 mg per day) of green-lipped mussel reduced joint tenderness and morning stiffness, as well as improving overall function in most participants. In a double-blind trial, 45% of people with OA who took a green-lipped mussel extract (350 mg three times per day for three months) reportedly had improvements in pain and stiffness. Another double-blind trial reported excellent results from green-lipped mussel extract (2,100 mg per day for six months) for pain associated with arthritis of the knee. Side effects, such as stomach upset, gout, skin rashes, and one case of hepatitis have been reported in people taking certain New Zealand green-lipped mussel extracts.

The therapeutic use of DMSO (dimethyl sulfoxide) is controversial because of safety concerns, but some preliminary research shows that diluted preparations of DMSO, applied directly to the skin, are anti-inflammatory and alleviate pain, including pain associated with OA. A recent double-blind trial found that a 25% concentration of DMSO in gel form relieved osteoarthritis pain significantly better than a placebo after three weeks. DMSO appears to reduce pain by inhibiting the transmission of pain messages by nerves rather than through a process of healing damaged joints. DMSO comes in different strengths and different degrees of purity; in addition, certain precautions must be taken when applying DMSO. For these reasons, DMSO should be used only with the supervision of a doctor.

According to a small double-blind trial, 2,250 mg per day of oral methylsulfonylmethane (MSM), a variant of DMSO, reduced OA pain after six weeks.⁶⁸

Cetyl myristoleate (CMO) has been proposed to act as a joint “lubricant” and anti-inflammatory agent. In a double-blind trial, people with various types of arthritis who had failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs) received CMO (540 mg per day orally for 30 days), while others received a placebo.⁶⁹ These people also applied CMO or placebo topically, according to their perceived need. A statistically significant 63.5% of those using CMO improved, compared with only 14.5% of those using placebo.

Boron affects calcium metabolism, and a link between boron deficiency and arthritis has been suggested. Although people with OA have been reported to have lower stores of boron in their bones than people without the disease, other minerals also are deficient in the bones of people with OA. One double-blind trial found that 6 mg of boron per day, taken for two months, relieved symptoms of OA in five of ten people, compared with improvement in only one of the ten people assigned to placebo. This promising finding needs confirmation from larger trials.

The omega-3 fatty acids present in fish oil, EPA and DHA, have anti-inflammatory effects and have been studied primarily for rheumatoid arthritis, which involves significant inflammation. However, OA also includes some inflammation.⁷³ In a 24-week controlled but preliminary trial studying people with OA, people taking EPA had “strikingly lower” pain scores than people who took placebo.⁷⁴ However, in a double-blind trial by the same research group, supplementation with 10 ml of cod liver oil per day was no more effective than a placebo.⁷⁵

Supplementation with D-phenylalanine (DPA), a synthetic variation of the amino acid, L-phenylalanine (LPA), has reduced chronic pain due to OA in a preliminary trial. In that study, participants took 250 mg three to four times per day, with pain relief beginning in four to five weeks. Other preliminary trials have confirmed the effect of DPA in chronic pain control, but a double-blind trial found no benefit. DPA inhibits the enzyme that breaks down some of the body’s natural painkillers, substances called enkephalins, which are similar to endorphins. An increase in the amount of enkephalins may explain the reported pain-relieving effect of DPA. If DPA is not available, a related product, D,L-phenylalanine (DLPA), may be substituted (1,500 to 2,000 mg per day). Phenylalanine should be taken between meals, because protein found in food may compete for uptake of phenylalanine into the brain, potentially reducing its effect.⁷⁹

Several trials have suggested that people with OA may benefit from supplementation with bovine cartilage, which contains a mixture of protein and molecules related to chondroitin sulfate. In one preliminary trial, use of injected and topical bovine cartilage led to symptom relief in most people studied. A ten-year study confirmed improvement with long-term use of bovine cartilage. Optimal intake of bovine cartilage is not known.

Are there any side effects or interactions?
Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful

Several double-blind trials have shown that topical use of cayenne extract creams containing 0.025 to 0.075% capsaicin reduces pain and tenderness caused by OA. These creams are typically applied four times daily for two to four weeks, after which twice daily application may be sufficient.⁸⁶ Products containing capsicum oleoresin rather than purified capsaicin may not be as effective.

Willow has anti-inflammatory and pain-relieving properties. Although pain relief from willow supplementation may be slow in coming, it may last longer than pain relief from aspirin. One double-blind trial found that a product containing willow along with black cohosh, guaiac (Guaiacum officinale, G. sanctum), sarsaparilla, and aspen (Populus spp.) bark effectively reduced OA pain compared to placebo. Another trial found that 1,360 mg of willow bark extract per day (delivering 240 mg of salicin) was somewhat effective in treating pain associated with knee and/or hip OA.

Stinging nettle has historically been used for joint pain. Topical application with the intent of causing stings to relieve joint pain has been assessed in preliminary⁹⁰ and double-blind trials. The results found intentional nettle stings to be safe and effective for relieving the pain of OA. The only reported adverse effect is a sometimes painful or numbing rash that lasts 6 to 24 hours.

Ginger has historically been used for arthritis and rheumatism. A preliminary trial reported relief in pain and swelling among people with arthritis who used powdered ginger supplements More recently, a double-blind trial found ginger extract (170 mg three times a day for three weeks) to be slightly more effective than placebo at relieving pain in people with OA of the hip or knee. In another double-blind study, a concentrated extract of ginger, taken in the amount of 255 mg twice daily for six weeks, was significantly more effective than a placebo, as determined by the degree of pain relief and overall improvement.

In a preliminary trial, supplementation with 500 mg of a concentrated extract (3.5% guggulsterones) of Commiphora mukul (guggul) three times per day for one month resulted in a significant improvement in symptoms in people with osteoarthritis of the knee. Double-blind trials are needed to rule out the possibility of a placebo effect.

More recently, purified extracts of bovine cartilage containing chondroitin sulfate have been found to benefit people with osteoarthritis.

In a double-blind study, collagen hydrolysate was compared with gelatin and egg protein as a treatment for osteoarthritis of the hip and/or knee. When subjects took 10 grams per day either of gelatin or collagen hydrolysate for two months, they reported significantly more pain relief than when they took a similar amount of egg protein. More research is needed to confirm the benefits of gelatin or collagen hydrolysate in osteoarthritis.

Devil’s claw extract was found in one clinical trial to reduce pain associated with OA as effectively as the slow-acting analgesic/cartilage-protective drug diacerhein. The amount of devil’s claw used in the trial was 2,610 mg per day. The results of this trial are somewhat suspect, however, as both devil’s claw and diacerhein are slow-acting and there was no placebo group included for comparison.

Boswellia has anti-inflammatory properties that have been compared to those of the NSAIDs used by many for inflammatory conditions. Clinical trials in humans using boswellia alone are lacking. However, one clinical trial found that a combination of boswellia, ashwagandha, turmeric, and zinc effectively treated pain and stiffness associated with OA but did not improve joint health, according to X-rays of the affected joint. Unlike NSAIDs, however, long-term use of boswellia does not lead to irritation or ulceration of the stomach.

Horsetail is rich in silicon, a trace mineral that plays a role in making and maintaining connective tissue. Practitioners of traditional herbal medicine believe that the anti-arthritis action of horsetail is due largely to its silicon content. The efficacy of this herb for OA has not yet been evaluated in controlled clinical trials.

According to arthritis research, saponins found in the herb yucca appear to block the release of toxins from the intestines that inhibit normal formation of cartilage. A preliminary, double-blind trial found that yucca might reduce symptoms of OA. Only limited evidence currently supports the use of yucca for people with OA.

Cat’s claw has been used traditionally for OA. In a double-blind trial, 100 mg per day of a freeze-dried preparation of cat's claw taken for four weeks was significantly more effective than a placebo at relieving pain and improving the overall condition.

Meadowsweet was historically used for a wide variety of conditions, including treating complaints of the joints and muscles. The herb contains salicylates, chemicals related to aspirin, that may account for its reputed ability to relieve the pain of OA.

Colchicine is a remedy derived from autumn crocus (Colchicum autumnale) that may be helpful for chronic back pain caused by herniated discs. A review of research reports that colchicine can relieve pain, muscle spasm, and weakness associated with disc disease. The author of this study suggests that colchicine produces dramatic improvement in about 40% of cases of disc disease. In most studies, colchicine has been given intravenously. However, oral colchicine may also be moderately effective for OA. A physician expert in the use of herbal medicine should be consulted for the administration of colchicine.

Are there any side effects or interactions? Refer to the individual herb for information about any side effects or interactions.

Holistic approaches that may be helpful

Several clinical trials have examined the efficacy of acupuncture for OA, with mixed results. Some trials found acupuncture treatment to be no more effective than either placebo or sham acupuncture at relieving OA pain. Other trials have demonstrated a significant effect of acupuncture on the relief of OA pain compared to placebo. A well-designed trial found that acupuncture treatments (twice weekly for eight weeks) significantly improved pain and disability in people with OA of the knee compared to no treatment. When the group receiving no treatment was switched to acupuncture treatments, they experienced similar improvements.

In a controlled trial, a combination of manual physical therapy (by a qualified physical therapist) and supervised exercise significantly improved walking distance and pain in a group of people with OA of the knee. The therapeutic regimen consisted of manual therapy to the knee, low back, hip, and ankle as necessary, as well as a standardized knee-exercise program performed at home and in the clinic. The treatments were given twice weekly at the clinic for four weeks.

References

1. Warmbrand M. How Thousands of My Arthritis Patients Regained Their Health. New York: Arco Publishing, 1974.
2. Childers NF. A relationship of arthritis to the solanaceae (nightshades). J Internat Acad Pre Med 1982;Nov:31–7.
3. Childers NF, Margoles MS. An apparent relation of nightshades (Solanaceae) to arthritis. J Neurol Orthop Med Surg 1993;14:227–31.
4. Taylor MR. Food allergy as an etiological factor in arthropathies: a survey. J Internat Acad Prev Med 1983;8:28–38 [review].
5. Felson DT, Zhang Y, Anthony JM, et al. Weight loss reduces the risk for symptomatic knee osteoarthritis in women. The Framingham Study. Ann Intern Med 1992;116:535–9.
6. Felson DT, Zhang Y, HanNan MT, et al. Risk factors for incident radiographic knee osteoarthritis in the elderly: the Framingham Study. Arthritis Rheum 1997;40:728–33.
7. Altman RD, Lozada CJ. Practice guidelines in the management of osteoarthritis. Osteoarthritis Cartilage 1998;6(Suppl A):22–4 [review].
8. Tapadinhas MJ, Rivera IC, Bignamini AA. Oral glucosamine sulphate in the management of arthrosis: report on a multi-centre open investigation in Portugal. Pharmtherapeutica 1982;3:157–68.
9. Giordano N, Nardi P, Senesi M, et al. The efficacy and safety of glucosamine sulfate in the treatment of gonarthritis. Clin Ter 1996;147:99–105.
10. D’Ambrosio E, Casa B, Bompani G, et al. Glucosamine sulphate: a controlled clinical investigation in arthrosis. Pharmatherapeutica 1981;2(8):504­8.
11. Crolle G, DiEste E. Glucosamine sulfate for the management of arthrosis. Curr Ther Res 1980;7:104–9.
12. Qiu GX, Gao SN, Giacovelli G, et al. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung 1998;48:469–74.
13. Reichelt A, Förster KK, Fischer M, et al. Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. Arzneimittelforschung 1994;44:75–80.
14. Drovanti A, Bignamini AA, Rovati AL. Therapeutic activity of oral glucosamine sulfate in osteoarthritis: a placebo­controlled double­blind investigation. Clin Ther 1980;3(4):260–72.
15. Vaz AL. Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthritis of the knee in out­patients. Curr Med Res Opin 1982;8(3):145–9.
16. Pujalte JM, Llavore EP, Ylescupidez FR. Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis. Curr Med Res Opin 1980;7(2):110–4.
17. Rindone RP. Randomized controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med 2000;172:91–4.
18. Reginster JY, Deroisy R, Rovati L, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001;357:251–6.
19. Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999;26:2423–30.
20. Kerzberg EM, Roldan EJA, Castelli G, Huberman ED. Combination of glycosaminoglycans and acetylsalicylic acid in knee osteoarthritis. Scand J Rheum 1987;16:377.
21. Baici A, Hörler D, Moser B, et al. Analysis of glycosaminoglycans in human serum after oral administration of chondroitin sulfate. Rheumatol Int 1992;12:81–8.
22. Kerzberg EM, Roldán EJA, Castelli G, Huberman ED. Combination of glycosaminoglycans and acetylsalicylic acid in knee osteoarthrosis. Scand J Rheumatol 1987;16:377–80.
23. Rovetta G. Galactosaminoglycuronoglycan sulfate (Matrix) in therapy of tibiofibular osteoarhtirits of the knee. Drugs Exptl Clin Res 1991;17:53–7.
24. Conte A, Volpi N, Palmieri L, et al. Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate. Arzneimittelforschung 1995;45:918–25.
25. Ronca F, Palmieri L, Panicucci P, Ronca G. Anti-inflammatory active of chondroitin sulfate. Osteoarthritis Cartilage 1998;6(Suppl A):14–21.
26. Uebelhart D, Thonar EJ, Delmas PD, et al. Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthritis Cartilage 1998;6(Suppl A):39–46.
27. Verbruggen G, Goemaere S, Veys EM. Chondroitin sulfate: S/DMOAD (structure/disease modifying anti-osteoarthritis drug) in the treatment of finger joint OA. Osteoarthritis Cartilage 1998;6(Suppl A):37–8.
28. Bucsi L, Poór G. Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Osteoarthritis Cartilage 1998;6(Suppl A):31–6.
29. Bourgeois P, Chales G, Dehais J, et al. Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3X400 mg/day vs placebo. Osteoarthritis Cartilage 1998;6(Suppl A):25–30.
30. Pipitone V, Ambanelli U, Cervini C, et al. A multicenter, triple-blind study to evaluate galactosaminoglucuronoglycan sulfate versus placebo in patients with femorotibial gonarthritis. Curr Ther Res 1992;52:608–38.
31. Bazières B, Loyau G, Menkès CJ, et al. Le chondroïtine sulfate dans le traitement de la gonarthrose et de la coxarthrose. Rev Rhum Mal Ostéoartic 1992;59:466–72 [in French].
32. Conrozier T, Vignon E. Die Wirkung von Chondroitinsulfat bei der Behandlung der Hüft Gelenksarthrose. Eine Doppelblindstudie gegen Placebo. Litera Rheumatologica 1992;14:69–75 [in German].
33. L’Hirondel JL. Klinische Doppelblind-Studie mit oral verabreichtem Chondroitinsulfat gegen Placebo bei der tibiofermoralen Gonarthrose (125 Patienten). Litera Rheumatologica 1992;14:77–82 [in German].
34. Morreale P, Manopulo R, Galati M, et al. Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol 1996;23:1385–91.
35. Leeb BF, Petera P, Neumann K. Results of a multicenter study of chondroitin sulfate (Condrosulf) use in arthroses of the finger, knee and hip joints. Wien Med Wochenschr 1996;146:609–14.
36. Bourgeois P, Chales G, Dehais J, et al. Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3X400 mg/day vs placebo. Osteoarthritis Cartilage 1998;6(Suppl A):25–30.
37. Schumacher HR. Osteoarthritis: the clinical picture, pathogenesis, and management with studies on a new therapeutic agent, S-adenosylmethionine. Am J Med 1987;83(Suppl 5A):1–4 [review].
38. Harmand MF, Vilamitjana J, Maloche E, et al. Effects of S-adenosylmethionine on human articular chondrocyte differentiation: an in vitro study. Am J Med 1987;83(Suppl 5A):48–54.
39. Berger R, Nowak H. A new medical approach to the treatment of osteoarthritis. Report of an open phase IV study with ademetionine (Gumbaral). Am J Med 1987;83:84–8.
40. Domljan Z, Vrhovac B, Durrigl T, Pucar I. A double-blind trial of ademetionine vs naproxen in activated gonarthrosis. Int J Clin Pharmacol Ther Toxicol 1989;27:329–33.
41. Müller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine in versus ibuprofen in the treatment of osteoarthritis. Am J Med 1987;83(Suppl 5A):81–3.
42. Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 1987;83(Suppl 5A):78–80.
43. Maccagno A. Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis. Am J Med 1987;83(Suppl 5A):72–7.
44. Caruso I, Pietrogrande V. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987;83(Suppl 5A):66–71.
45. Marcolongo R, Giordano N, Colombo B, et al. Double-blind multicentre study of the activity of s-adenosyl-methionine in hip and knee osteoarthritis. Curr Ther Res 1985;37:82–94.
46. Glorioso S, Todesco S, Mazzi A, et al. Double-blind multicentre study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 1985;5:39–49.
47. Montrone F, Fumagalli M, Sarzi-Puttini P, et al. Double-blind study of S-adenosyl-methionine versus placebo in hip and knee arthrosis. Clin Rheumatol 1985;4:484–5.
48. Konig B. A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis. Am J Med 1987;83:89–94.
49. Bradley JD, Flusser D, Katz BP, et al. A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by or SAM therapy in patients with knee osteoarthritis. J Rheumatol 1994;21:905–11.
50. Di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med 1987;83:60–5 [review].
51. McAlindon TE, Jacques P, Zhang Y. Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis? Arthrit Rheum 1996;39:648–56.
52. Machtey I, Ouaknine L. Tocopherol in osteoarthritis: a controlled pilot study. J Am Geriatr Soc 1978;25(7):328–30.
53. Blankenhorn G. Klinische Wirtsamkeit von Spondyvit (vitamin E) bei aktiverten arthronsen. Z Orthop 1986;124:340–3 [in German].
54. Scherak O, Kolarz G, Schödl Ch, Blankenhorn G. Hochdosierte Vitamin-E-Therapie bei Patienten mit aktivierter Arthrose. Z Rheumatol 1990;49:369–73 [in German].
55. Brand C, Snaddon J, Bailey M, Cicuttini F. Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study. Ann Rheum Dis 2001;60:946–9.
56. Kaufman W. The use of vitamin therapy for joint mobility. Therapeutic reversal of a common clinical manifestation of the ‘normal’ aging process. Conn State Med J 1953;17(7):584–9.
57. Kaufman W. The use of vitamin therapy to reverse certain concomitants of aging. J Am Geriatr Soc 1955;11:927.
58. Hoffer A. Treatment of arthritis by nicotinic acid and nicotinamide. Can Med Assoc J 1959;81:235–8.
59. Jonas WB, Rapoza CP, Blair WF. The effect of niacinamide on osteoarthritis: a pilot study. Inflamm Res 1996;45:330–4.
60. Gibson SL, Gibson RG. The treatment of arthritis with a lipid extract of Perna canaliculus: a randomized trial. Comp Ther Med 1998;6:122–6.
61. Gibson RG, Gibson SL, Conway V, et al. Perna canaliculus in the treatment of arthritis. Practitioner 1980;224L:955–9.
62. Audeval B, Bouchacourt P. Double-blind, placebo-controlled study of the mussel perna canaliculus (New Zealand green-lipped mussel) in gonarthrosis (arthritis of the knee). Gazette Med 1986;93:111–5.
63. Brooks PM. Side effects from Seatone. Med J Aust 1980;2:158 [letter].
64. American Medical Association. Dimethyl sulfoxide. Controversy and Current Status—1981. JAMA 1982;248:1369–71.
65. Jimenez RA, Willkens RF. Dimethyl sulfoxide: a perspective of its use in rheumatic diseases. J Lab Clin Med 1982;100:489–500.
66. Eberhardt R, Zwingers T, Hofmann R. DMSO in patients with active gonarthrosis. A double-blind placebo controlled phase III study. Fortschr Med 1995;113:446–50 [in German].
67. Jacob SW, Wood DC. Dimethyl sulfoxide (DMSO). Toxicology, pharmacology, and clinical experience. Am J Surg 114:414–26.
68. Lawrence RM. Methylsulfonylmethane (MSM): a double-blind study of its use in degenerative arthritis. Int J of Anti-Aging Med 1998;1:50.
69. Siemandi H. The effect of cis-9-cetyl myristoleate (CMO) and adjunctive therapy on arthritis and auto-immune disease: a randomized trial. Townsend Letter for Doctors and Patients 1997;Aug/Sept:58–63.
70. Newnham RE. The role of boron in human nutrition. J Applied Nutr 1994;46:81–5.
71. Helliwell TR, Kelly SA, Walsh HP, et al. Elemental analysis of femoral bone from patients with fractured neck of femur or osteoarthrosis. Bone 1996;18:151–7.
72. Travers RL, Rennie GC, Newnham RE. Boron and arthritis: the results of a double-blind pilot study. J Nutr Med 1990;1:127–32.
73. Altman R, Gray R. Inflammation in osteoarthritis. Clin Rheum Dis 1985;11:353.
74. Stammers T, Sibbald B, Freeling P. Fish oil in osteoarthritis. Lancet 1989;ii:503 [letter].
75. Stammers T, Sibbald B, Freeling P. Efficacy of cod liver oil as an adjunct to non-steroidal anti-inflammatory drug treatment in the management of osteoarthritis in general practice. Ann Rheum Dis 1992;51:128–9.
76. Balagot RC, Ehrenpreis S, Kubota K, Greenberg J. Analgesia in mice and humans by D-phenylalanine: Relation to inhibition of enkephalin degradation and enkephalin levels. In: Bonica JJ, Liebeskind JC, Albe-Fessard DG, eds., Advances in Pain Research and Therapy, Vol 5. New York: Raven Press, 1983, 289–93.
77. Budd K. Use of D-phenylalanine, an enkephalinase inhibitor, in the treatment of intractable pain. In: Bonica JJ, Liebeskind JC, Albe-Fessard DG, eds., Advances in Pain Research and Therapy, Vol 5. New York: Raven Press, 1983, 305–8.
78. Walsh NE, Ramamurthy S, Schoenfeld LS, Hoffman J. Analgesic effectiveness of D-phenylalanine in chronic pain patients. Arch Phys Med Rehabil 1986;67:436–9.
79. Seltzer S, Marcus R, Stoch R. Perspectives in the control of chronic pain by nutritional manipulation. Pain 1981;11:141–8 [review].
80. Prudden JF, Balassa LL. The biological activity of bovine cartilage preparations. Semin Arthritis Rheum 1974;3:287–320.
81. Reijholec V. Long term studies of antiosteoarthritic drugs: an assessment. Semin Arthritis Rheum 1987;17(2 Suppl 1):35–53.
82. McCarthy GM, McCarty DJ. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands J Rheumatol 1992;19:604–7.
83. Altman RD, Aven A, Holmburg CE, et al. Capsaicin cream 0.025% as monotherapy for osteoarthritis: a double-blind study. Sem Arth Rheum 1994;23(Suppl 3):25–33.
84. Deal CL, Schnitzer TJ, Lipstein E, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther 1991;13:383–95.
85. Schnitzer T, Morton C, Coker S. Topical capsaicin therapy for osteoarthritis pain: achieving a maintenance regimen. Sem Arth Rheum 1994;23(Suppl 3):34–40.
86. Schnitzer T, Morton C, Coker S. Topical capsaicin therapy for osteoarthritis pain: achieving a maintenance regimen. Sem Arth Rheum 1994;23(Suppl 3):34–40.
87. Deal CL. The use of topical capsaicin in managing arthritis pain: a clinician’s perspective. Sem Arth Rheum 1994;23(Suppl 3):48–52.
88. Mills SY, Jacoby RK, Chacksfield M, Willoughby M. Effect of a proprietary herbal medicine on the relief of chronic arthritic pain: a double-blind study. Br J Rheum 1996;35:874–88.
89. Schmid B, Tschirdewahn B, Kàtter I, et al. Analgesic effects of willow bark extract in osteoarthritis: results of a clinical double-blind trial. Fact 1998;3:186.
90. Randall C, Meethan K, Randall H, Dobbs F. Nettle sting of Urtica dioica for joint pain—an exploratory study of this complementary therapy. Compl Ther Med 1999;7:126–31.
91. Randall C, Randall H, Dobbs F, et al. Randomized controlled trial of nettle sting for treatment of base-of-thumb pain. J R Soc Med 2000;93:305–9.
92. Srivastava KC, Mustafa T. Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. Med Hypotheses 1992;39:342–8.
93. Bliddal H, Rosetzsky A, Schlichting P, et al. A randomized, placebo-controlled crossover study of ginger extracts and ibuprofen in osteoarthritis. Osteoarthritis Cartilage 2000;8:9–12.
94. Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum 2001;44:2531–8.
95. Singh BB, Mishra LC, Vinjamury SP, et al. The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcomes study. Altern Ther Health Med 2003;9:74–9.
96. Leeb BF, Schweitzer H, Montag K, Smolen JS. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol 2000;27:205-11 [review].
97. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469-75 review].
98. Adam M. Osteoarthritis therapy with gelatin preparations: Results of a clinical study. Therapiewoche 1991;38:2456–61 [in German].
99. Chantre P, Cappelaere A, Leblan D, et al. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine 2000;7:177–83.
100. Safayhi H, Mack T, Saieraj J, et al. Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther 1992;261:1143–6.
101. Kulkarni RR, Patki PS, Jog VP, et al. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 1991;33:91–5.
102. Bingham R, Bellow BA, Bellow JG. Yucca plant saponin in the management of arthritis. J Appl Nutr 1975;27:45–51.
103. Piscoya J, Rodriguez Z, Bustamante SA, et al. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res 2001;50:442–8.
104. Zeylstra H. Filipendila ulmaria. Br J Phytotherapy 1998;5:8–12.
105. Rask MR. Colchicine use in five hundred patients with disk disease. J Neurol Orth Surg 1980;1:1–19.
106. Simmons JW, Harris WP, Koulisis CW, et al. Intravenous colchicine for low back pain: A double blind study. Spine 1990;15:716–7.
107. Gaw AC, Chang LW, Shaw L-C. Efficacy of acupuncture on osteoarthritic pain. A controlled, double-blind study. N Engl J Med 1975;293:375–8.
108. Takeda W, Wessel J. Acupuncture for the treatment of pain of osteoarthritic knees. Arthritis Care Res 1994;7:118–22.
109. Thomas M, Eriksson SV, Lundeberg T. A comparative study of diazepam and acupuncture in patients with osteoarthritis pain: a placebo controlled study. Am J Chin Med 1991;19:95–100.
110. Christensen BV, Iuhl IU, Vilbek H, et al. Acupuncture treatment of severe knee osteoarthrosis. A long-term study. Acta Anaesthesiol Scand 1992;36:519–25.
111. Berman BM, Singh BB, Lao L, et al. A randomized trial of acupuncture as an adjunctive therapy in osteoarthritis of the knee. Rheumatology (Oxford) 1999;38:346–54.
112. Deyle GD, Henderson NE, Matekel RL, et al. Effectiveness of manual physical therapy and exercise in osteoarthritis of the knee. A randomized, controlled trial. Ann Intern Med 2000;132:173–81.

 


 Idaho Web Design Tools