Clinical Pearls Feature - Week of August 12, 2003

DEMENTIA - Homocysteine, Vitamin - In a study of 149 patients at high risk for dementia, subjects were randomized to receive either low-dose aspirin at 81 mg or placebo; and folic acid at 2 mg plus vitamin B12 at 1 mg or placebo; and vitamin E at 500 mg plus vitamin C at 200 mg or placebo for a 12-week trial. Prior to treatment, cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane, which were independent of age. Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73%. Vitamins B12 at 1 mg and folic acid at 2 mg lowered plasma homocysteine levels by 30%, and antioxidant vitamins lowered isoprostane excretion by 26%. There was no effect of any treatment on cognitive function. “Effect of Vitamins and Aspirin on Markers of Platelet Activation, Oxidative Stress and Homocysteine in People at High Risk of Dementia,” Clarke R, et al, J Intern Med, 2003;254:67-75. (Address: Dr. Robert Clarke, (FAX) +44 (0) 1865 558817, E-mail: [email protected]) 40722

RHEUMATOID ARTHRITIS - Fish Oil - Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are homologues of the omega-6 fatty acid, arachidonic acid, and therefore the omega-3 fatty acids provide an antagonism to arachidonic acid metabolism, which can lead to proinflammatory and prothrombotic omega-6 eicosanoids, as well as the production of less active omega-3 eicosanoids. Fish oils have shown protective benefits in occlusive cardiovascular disease, for which patients with rheumatoid arthritis are at risk. Fish oils are not promoted industrywide due to lack of ability to patent, and therefore the profit motive is not present. Many practitioners are not aware of their pharmacodynamics, since they are not promoted by pharmaceutical companies. EPA can inhibit the cyclooxygenase enzymes which lead to proinflammatory prostaglandins and thromboxanes. In 13 randomized controlled trials of fish oil in rheumatoid arthritis with a mean disease duration of more than 10 years, the most consistent finding was a reduction in morning stiffness and a decrease in tender joint count. Antiinflammatory effects have been shown with doses between 2.6 g/day and 7.1 g/day, but not with doses at 1.0 g/day. Ninety mg/kg/day of EPA/DHA in a 3:2 ratio has been associated with a quicker response than 45 mg/kg/day, which has had little additional benefit. Omega-6 fats are present as linoleic acid in sunflower oil, corn oil, soybean oil and cottonseed oil and eventually are converted to arachidonic acid. Omega-3 fats are found in flaxseed oil, canola oil and soybean oil as alpha-linolenic acid and are converted to EPA, which is converted to DHA. Fish and fish oil are also a source of EPA and DHA. Preliminary data state that omega-3 long-chain polyunsaturated fatty acids have a favorable effect on bone density. Fish oils can inhibit tumor necrosis factor á and interleukin 1â, which makes it also an inexpensive associate therapy for highly expensive biological agents that have been designed to block these cytokines. “The Role of Fish Oils in the Treatment of Rheumatoid Arthritis,” Cleland LG, James MJ, Proudman SM, Drugs, 2003;63(9):845-853. (Address: Dr. Leslie G. Cleland, E-mail: [email protected] ) 40712

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