Neural tube defects tan be prevented by adequate intake of periconcept
ional folate, and inverse associations between folate status and cardi
ovascular disease and various cancers have been noted. Thus, there is
renewed interest in the analysis of red cell folate (RCF) as an indica
tor of folate deficiency risk. Assessment of the assumptions that unde
rpin RCF assays indicates that many are false. Published literature su
ggests that increased deoxy-hemaglobin (which can bind RCF electrostat
ically) yields more assayable folate, and increased oxy-hemoglobin (wh
ich cannot bind RCF) yields less assayable folate. It is argued that a
s deoxy-hemoglobin picks up oxygen and switches quaternary structure,
any bound folate must, on purely theoretical grounds, become physicall
y ''trapped''. Venous blood taken for analysis is 65% to 75% saturated
with oxygen, and pro-rata ''trapping'' will lead to serious underesti
mation of RCF. Hence, doubt is cast over the validity of all previous
RCF values. Some strategies for accurately assessing RCF are suggested
.