Folate erythrocytes

Some antiepileptic drugs have been associated with low serum and erythrocyte folate concentrations and high total plasma homocysteine concentrations in some patients. The concentrations of folate and homocysteine have been measured in 42 patients taking carbamazepine and 42 matched healthy controls (241). Patients taking carbamazepine had significantly lower serum and erythrocyte folate concentrations. There was hyperhomocystinemia (over 15 gmol/l) in 24% of the patients and 5% of the controls. 

A cross-sectional study showed a 20% lower serum vitamin B12 concentration in patients taking lithium (n = 81) than in controls (n = 14) (serum and erythrocyte folate concentrations were normal) (346). 

Serum folate below 7 nmol per L or erythrocyte folate below 320 nmol per L indicates negative folate balance and early depletion of body reserves. At this stage, the first bone marrow changes are detectable. 

Wright AJ, Finglas PM, and Southon S (1998) Erythrocyte folate analysis a cause for concern Ciinicai Chemistry 44, 1886-91. 

Concentrations of plasma homocysteine, plasma pyridoxal 5 -phosphate (active vitamin B6), serum folate, erythrocyte folate, and serum vitamin B12 have been measured both during fasting and after methionine in 60 epileptic patients (aged 14-18 years) and 63 sex- and age-matched controls before therapy and after 1 year of therapy with valproate or carbamazepine (33). After 1 year the patients who took valproate and carbamazepine had significantly increased plasma homocysteine concentrations compared with both baseline and control values and there was a significant fall in serum folate and plasma pyridoxal 5 -phosphate. Serum vitamin B12 and erythrocyte folate were unchanged. 

Folate status may be reliably assessed by direct measurement of serum and erythrocyte or whole blood concentrations, and its metabolic function as coen2yme assessed by metabolite concentrations, such as plasma homocysteine (see Chapters 20 and 26). Serum folate concentrations are considered indicative of recent intake and not of tissue stores, but serial measurements have been used to confirm adequate intake. Whole blood or erythrocyte folate concentrations are more indicative of tissue stores and have been shown to have a moderate correlation with liver folate concentrations taken through a biopsy. Because folate is taken up only by the developing erythrocyte in the bone marrow and not by the mature cell, erythrocyte concentrations reflect folate status over the 120-day lifespan of the ceU. Urine folate excretion is not considered to be a sensitive indicator of folate status. ... 

Plasma homocysteine Urinary excretion Blood levels Urinary excretion Erythrocyte folate... 

It is of paramount importance to rule out vitamin B12 deficiency when folate deficiency is detected, as symptoms are similar. Laboratory changes associated with folate deficiency are similar to those seen in vitamin Bn deficiency, except vitamin Bn levels are normal. Decreases occur in the serum folate level (<3 ng/mL) within a few days of dietary folate limitations. The RBC folate level (<150 ng/mL) also declines and may be a better indicator of deficiency, as levels remain constant throughout the life span of the erythrocyte. Serum folate levels are sensitive to short-term changes such as dietary restrictions or alcohol intake, which may result in a short-term decline in serum levels with adequate tissue stores. It should be noted that an estimated 60% of patients with pernicious anemia have falsely low RBC folate levels, in all probability due to the requirement of cobal-amin for the normal transfer of methyltetrahydrofolate from plasma to cells. Additionally, if serum or erythrocyte folate levels are borderline, serum homocysteine is usually increased with a folic acid deficiency. If serum MMA levels are also elevated, vitamin B12 deficiency needs to be ruled out. 

Davis et al. found that folate was not the only B group vitamin which was reduced in patients receiving treatment with anticonvulsant drugs (D4). In a study of 68 patients suffering from severe epileptic seizures they found that 18 patients had a low folate, 10 a low serum pyridoxal, and in 15 both the folate and pyridoxal were reduced. Only two patients in this series had a reduced erythrocyte folate, and this is in accord with the infrequency with which a macrocytic anemia is seen in these patients. All the patients in this series had a normal hemoglobin concentration and a normal mean corpuscular volume. However, in a study of 75 epileptic children Maxwell (M3) found both the serum and erythrocyte folate levels to be reduced in 60% and similar observations have been made by other workers (M4, N2). 

With the introduction of automated and semiautomated microbiological methods, the measurement of erythrocyte folate was simplified and only required predilution with 1% aqueous ascorbate after which the procedure was the same as for serum (M5). 

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