Red cell or serum folate: what to do in clinical practice?

Abstract

Folate deficiency has been linked to diverse clinical manifestations and despite the importance of accurate assessment of folate status, the best test for routine use is uncertain. Both serum and red cell folate assays are widely available in clinical laboratories; however, red cell folate is the more time-consuming and costly test. This review sought to evaluate whether the red cell assay demonstrated superior performance characteristics to justify these disadvantages. Red cell folate, but not serum folate, measurements demonstrated analytical variation due to sample pre-treatment parameters, oxygen saturation of haemoglobin and haematocrit. Neither marker was clearly superior in characterising deficiency but serum folate more frequently showed the higher correlation with homocysteine, a sensitive marker of deficiency. Similarly, both serum and red cell folate were shown to increase in response to folic acid supplementation. However, serum folate generally gave the greater response and was able to distinguish different supplementation doses. The C677T polymorphism of methylenetetrahydrofolate reductase alters the distribution of folate forms in red cells and may thereby cause further analytical variability in routine red cell folate assays. Overall, serum folate is cheaper and faster to perform than red cell folate, is influenced by fewer analytical variables and provides an assessment of folate status that may be superior to red cell folate.

Laboratory assessment of folate (vitamin B9) status

“…tHcy is a sensitive marker of folate status that correlates well with serum folate and RCF 38. However, its specificity is compromised in patients with deficiencies in vitamins B 2 , B 6 or B 12 , as well as in the cases of inborn errors/polymorphisms in genes related to homocysteine metabolism that is, MTHFR, MS and cystathionine-β-synthase (CBS).…”

Genetic polymorphisms and folate status

“…The effect size of tHcy reduction in the TT genotype was estimated to be 2.4‐fold compared with that in the CC genotype. The inconsistent response of serum and RBC folate or tHcy could be explained by the observation that the baseline folate status appeared to influence changes in these markers (Farrell et al 2013). These metabolic data regarding folate in individuals with SNPs should be useful for the development of personalized nutrition programs to prevent cardiovascular diseases and dementia.…”

Folic Acid; Is Simple Folic Acid Effective to Replenish RBC Folate Stores Among Pakistani Femal Epatients? Small Case.

“…Folic acid is stable while the natural forms of folate are unstable. [21][22][23] The folate that is most commonly found in foods cannot be absorbed at the brush border of the intestine until it is converted to simpler form of monoglutamate from naturally occurring polyglutamates. Synthetic folic acid is already in the monoglutamate form so absorption is easy and quick.…”

“…Folic acid must be converted first into tetrahydrofolate (THF) by an enzyme named dihydrofolate reductase and then finally converted into the active form of 5-MTHF by the enzyme MTHFR through a series of steps .5-MTHF is the most common form found in the bloodstream. [21][22][23] It is still unclear whether supplementation of folic acid or 5-MTHF is preferred and the best form of supplemental folate is unresolved; as both seems to be good choices. 24 Various studies are in progress to understand any differences …”