Zinc has been shown to inhibit the inflammatory response (Simkin PA. Treatment of rheumatoid arthritis with oral zinc sulfate. Agents Actions 1981;8:587-595).

As a result, it has been investigated as a possible treatment for RA. In one double-blind study, 24 patients with moderately severe RA, refractory to conventional therapy, were randomly assigned to receive zinc (50 mg elemental zinc three times daily in the form of zinc sulfate) or placebo for 12 weeks. Compared with the placebo group, the zinc treated group had significantly reduced joint swelling, morning stiffness, and improved patient subjective assessment of disease activity (Simkin PA. Oral zinc sulfate in rheumatoid arthritis. Lancet 1976;2:539-542).

However, in two other controlled studies, zinc was not significantly more effective than a placebo (Rasker JJ, Kardaun SH. Lack of beneficial effect of zinc sulphate in rheumatoid arthritis. Scand J Rheumatol 1982;11:168-170. Mattingly PC, Mowat AG. Zinc sulphate in rheumatoid arthritis. Ann Rheum Dis 1982;41:456-457).

Studies drawing different results and conclusions are not uncommon in rheumatoid arthritis. In one of the negative studies, the disease was more severe than in the study that produced positive results. It is highly likely that a trace metal like zinc is helpful only for mild or moderately severe RA. In addition, administration of large doses of zinc can result in a deficiency of copper, a mineral that may be even more important for arthritis than zinc (Abdulla M. Copper levels after oral zinc. Lancet 1979;1:616).

While the evidence does not indicate supplementation of zinc alone will produce great benefit, it is possible that combining zinc with copper and perhaps other nutritional treatments might be more effective.

Copper also has mild anti-inflammatory effects. Rats fed a copper-deficient diet had an exaggerated inflammatory response in two models of acute inflammation (Milanino R, Conforti A, Fracasso ME, et al. Concerning the role of endogenous copper in the acute inflammatory process. Agents Actions 1979;9:581-588).

The role of copper complexes as anti-arthritic agents has been reviewed (Sorenson JRJ. Copper chelates as possible active forms of the antiarthritic agents. J Medicinal Chem 1976;19:135-148). Some studies have surmised that copper complexes of NSAIDs have greater anti-inflammatory effect and are less toxic than the parent compounds. For example, in animal models of inflammation, the copper chelate of aspirin was active at one-eighth the effective dose of aspirin. Another interesting phenomenon is that while NSAIDs lead to peptic ulcer, copper chelates of these same drugs have anti-ulcer activity in animal studies. It has been postulated that NSAIDs become active in vivo by forming copper complexes. If true, then the ulcer causing effect of NSAIDs may be due to their tendency to extract copper from certain tissues.

NSAID copper complexes have not been approved by the U.S. Food and Drug Administration. The long-term safety of administering copper complexes to humans has not been studied. An interesting theory is that perhaps supplementation with "nutritional" doses of copper (e.g., 2-4 mg per day) could increase the efficacy and reduce the toxicity of NSAIDs.

Copper bracelets have been claimed by some to be beneficial for arthritis. Most conventional doctors do not agree.

With that as background, a pilot study using copper bracelets was performed. A total of 160 individuals with arthritis, half of whom had previously worn a copper bracelet, were randomly assigned to one of two groups. Group 1 wore a copper bracelet for one month, and then a placebo bracelet (anodized aluminum resembling copper) for a second month. Group 2 wore the same bracelets in reverse order. Of those patients who noticed a difference between the two bracelets, significantly more preferred copper (p < 0.01) than placebo (Walker WR, Keats DM. An investigation of the therapeutic value of the "copper bracelet:" dermal assimilation of copper in arthritic/rheumatoid conditions. Agents Actions 1976;6:454-459).

Previous users of copper bracelets had their symptoms worsen during the time they were wearing the placebo bracelet. Interestingly, the weight of the copper bracelets fell by an average of 13 mg during the month they were being worn, suggesting that some copper from the bracelet may have been absorbed through the skin. One disturbing cosmetic side effect of some copper bracelets is greenish discoloration of the skin underneath the bracelet.

Obviously, further research is needed.

Some naturopathic practitioners prescribe 30-90 mg zinc and 2-4 mg copper daily as part of an overall nutritional program for RA. These supplements can cause nausea, particularly if taken on an empty stomach. Since taking large amounts of zinc alone may lead to copper deficiency, these minerals probably should be used in combination. There is no evidence that taking zinc and copper at separate times of the day improves their efficacy. Although studies on zinc as a treatment for RA typically used 150 mg of elemental zinc per day (as zinc sulfate), some doctors recommend lower doses of better-absorbed forms of zinc such as zinc picolinate or zinc citrate.

Selenium is also known to have anti-inflammatory effects (Roberts ME. Antiinflammation studies. II. Anti-inflammatory properties of selenium. Toxicol Appl Pharmacol 1963;5:500-506).

Serum selenium levels were significantly lower in a group of 87 patients with RA than in healthy individuals. The reduction in serum selenium was greatest among patients with the most severe disease (Tarp U, Overvad K, Hansen JC, Thorling EB. Low selenium level in severe rheumatoid arthritis. Scand J Rheumatol 1985;14:97-101).

In one double-blind trial, 15 women with RA received either 200 mcg selenium daily (from selenium-rich yeast) or a placebo for three months. Pain and joint inflammation were reduced in six of eight women treated with selenium, but there was no significant change in the placebo group (Peretz A, Neve J, Duchateau J, Famaey JP. Adjuvant treatment of recent onset rheumatoid arthritis by selenium supplementation: preliminary observations. Br J Rheumatol 1992;31:281-286).

On the other hand, selenium did not improve RA symptoms in another study (Tarp U, Overvad K, Thorling EB, et al. Selenium treatment in rheumatoid arthritis. Scand J Rheumatol 1985;14:364-368). The reasons for this dichotomy of findings are not entirely clear.

So. What's the bottom line? Trace metals have shown some interesting properties when used to treat patients with RA. Like all alternative therapies, they should be used with caution.