American Journal of Clinical Nutrition, Vol 25, 152-165, Copyright © 1972 by The American Society for Clinical Nutrition, Inc.

Folate requirements of children. II. Response of children recovering from protein-calorie malnutrition to graded doses of parenterally administered folic acid

¹ From the United States Naval Medical Research Unit No. (NAMRU-3) % Spanish Embassy, Cairo, the Department of Pediatrics, Ain Shams Faculty of Medicine, Cairo, Egypt, and Division of Nutrition, Vanderbilt University, Nashville, Tennessee

Twenty-three cases of protein-calorie malnutrition exhibiting signs of iron and folate deficiency were given a diet nutritionally adequate in all nutrients except folic acid. This was provided by a low folate diet that supplied 5.8 µg free and 6.3 µg total folate/kg body wt per day. Iron dextran equivalent to 300 mg Fe was administered intramuscularly over 6 days to correct existing iron deficiency and to replenish iron stores. After 2 to 3 weeks on this diet alone, most clinical features of PCM and iron deficiency had disappeared, but other features suggestive of folate deficiency were variably intensified; for example, the average serum and RBC folate were reduced to 1.8 and 144 ng/ml, respectively, and the megaloblastic character of the bone marrow had mildly intensified and hypersegmentation of PMN had become more pronounced.

The patients were continued on the low folate diet and were given folic acid by intramuscularly graded doses of 20, 30, 40, and 50 µg/day for 2 to 5 weeks. The response of the patients was assessed hematologically and by measurement of serum and RBC folic acid levels. Hematologic evaluations included reticulocyte counts, hemoglobin concentration, hematocrit, MCHC, morphology of peripheral blood and of bone marrow. Key data are summarized in Tables 3, 4, and 7. After the evaluation of response to folic acid in doses of 20, 30, 40, or 50 µg/day, a second period of treatment was instituted during which an additional 50 µg folic acid daily was given intramuscularly. The same parameters were observed, thus allowing for assessment of adequacy by the double reticulocyte response technique (Table 5).

This subsequent daily administration of 50 µg in addition to the dose already being received resulted in a reticulocyte response in five patients, indicating that in these cases the lower dose was inadequate for maximal response. A further slight rise in hemoglobin levels was observed in most cases and 19 out of 23 bone marrows were normoblastic at the end of the treatment.

Considering all the data obtained in this investigation and taking into account the amount of free folate in the formula diet and its relative physiologic availability together with the doses of folic acid given intramuscularly, it is tentatively concluded that approximately 11.2 µg of total free dietary folate/kg body wt per day would have been sufficient to promote recovery from folate deficiency in most children recovering from PCM. Neither this amount, nor indeed the maximal level equivalent to 18.8 µg/kg per day of dietary folate sufficed for maximal therapeutic response. The influence of diverse factors such as infection, heightened requirement due to recovery from protein-calorie starvation, or excessive demands for hemopoiesis, cannot be assessed. Only a study of otherwise healthy children can give a valid estimate of the normal requirement.

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