Evidence for potential underestimation of clinical folate deficiency in resource-limited countries using blood tests

Although a low serum folate concentration is a useful biomarker of pure folate deficiency, the presence of vitamin B12 deficiency or hemolysis or both in individuals with low folate status predictably raises serum folate levels. Therefore, in resource-limited settings where dietary folate deficiency can coexist with vitamin B12 deficiency or malaria or both, the serum folate concentration can range from normal to high, leading to serious underestimation of tissue folate status. This review traces the genesis of an inappropriate overreliance on the serum folate concentration to rule out folate deficiency in vulnerable populations of women and children. Of significance, without due consideration of a chronically inadequate dietary folate intake, authors of influential studies have likely wrongly judged these populations to have an adequate folate status. Through repetition, this error has led to a dangerous entry into the contemporary medical literature that folate deficiency is rare in women and children. As a consequence, many millions of under-resourced women and children with mild to moderate tissue folate deficiency may have been deprived of folate replacement. This review uses historical documents to challenge earlier conclusions and re-emphasizes the need for contextual integration of clinical information in resource-limited settings.