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Secondary Folate Deficiency Induced in the Rat by Dietary Iron Deficiency¹

Joseph J. Vitale, Alberto Restrepo, Herna Velez, Jeffrey B. Riker and Earl E. Hellerstein

Department of Nutrition, Harvard School of Public Health, the Department of Pathology, Harvard Medical School, Boston, Massachusetts, and the Department of Medicine, University de Antioquia, Medellin, Colombia

The effects of iron deficiency on folate metabolism in rats were studied. Dietary iron deficiency was induced in 18-day-old male rats, following which the animals developed the expected hypochromic, microcytic anemia. In addition, notwithstanding that the diet contained adequate folate, iron deficiency resulted in biochemical and morphological changes of folate deficiency such as increased urinary excretion of formiminoglutamic acid, decreased serum folate and megaloblastoid dysplasia of the bone marrow elements. In a second experiment, iron deficiency was shown to result in a decreased activity of the enzyme glutamate formimino-transferase isolated from livers. It was concluded that a secondary folate deficiency can be induced by a dietary deficiency of iron and that this defect in folate metabolism is related to the decreased activity of the enzyme formimino-transferase whose optimal activity is dependent on iron.

Manuscript received 1 November 1965.