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Current Status of Knowledge A biochemical paradox Reference to the relation between high folate and low vitamin B-12 as a biochemical paradox was first made by the late Rene Malinow, who expressed concern at the time of the planning for the Vitamin Intervention for Stroke Prevention (VISP) Study, a randomized controlled trial that was designed to assess the effects of high-dose folic acid, vitamin B-12, and vitamin B-6 supplementation on recurrent stroke (36, 37)