Folates serum levels

Serum folate levels Serum folate levels may be depressed by therapy. 

Waxman, Schreiber, and Herbert first described a radioisotopic assay for the measurement of serum folate in 1971 (W14) which they claimed gave almost identical results to those obtained by with the L. casei microbiological assay and could separate low, borderline, and normal folate levels. Serum was mixed with PHjmethyltetrahydrofolic acid in a phosphate buffer and a folate binder was added which, in this case, was Carnation brand instant powdered milk. Following incubation, free vitamin was separated from that which was bound using hemoglobin-coated charcoal. The radioactivity of the supernatant was determined, and from this the folate concentration in the serum sample could be calculated using appropriate standards and blanks. 

Patients sustain convulsions and neurological deterioration. The urine contains low levels of the metabolites of serotonin, norepinephrine and dopamine. The reductase also plays a role in the maintenance of tetrahydrofolate levels in brain, and some patients have had low folate levels in the serum and CNS. Treatment has been attempted with tryptophan and carbidopa to improve serotonin homeostasis and with folinic acid to replete diminished stores of reduced folic acid. This therapy is sometimes effective. Diagnosis involves assay of DHPR in skin fibroblasts or amniotic cells. Phenylalanine hydroxylase activity is normal. 

Parenteral administration of folic acid is rarely necessary, since oral folic acid is well absorbed even in patients with malabsorption syndromes. A dose of 1 mg folic acid orally daily is sufficient to reverse megaloblastic anemia, restore normal serum folate levels, and replenish body stores of folates in almost all patients. Therapy should be continued until the underlying cause of the deficiency is removed or corrected. Therapy may be required indefinitely for patients with malabsorption or dietary inadequacy. Folic acid supplementation to prevent folic acid deficiency should be considered in high-risk patients, including pregnant women, patients with alcohol dependence, hemolytic anemia, liver disease, or certain skin diseases, and patients on renal dialysis. 

Folate deficiency results in a megaloblastic anemia that is microscopically indistinguishable from the anemia caused by vitamin B12 deficiency (see above). However, folate deficiency does not cause the characteristic neurologic syndrome seen in vitamin B12 deficiency. In patients with megaloblastic anemia, folate status is assessed with assays for serum folate or for red blood cell folate. Red blood cell folate levels are often of greater diagnostic value than serum levels, since serum folate levels tend to be quite labile and do not necessarily reflect tissue levels. 

Gambichler, T. etal., Serum folate levels after UVA exposure a two-group parallel randomized controlled trial, BMC Dermatol., 1, 8, 2001. 

Systemic evaluation of the patient includes a complete blood count, blood chemistry, thiamine level, urinalysis, serum vitamin B12 and folate levels, heavy metal screening (lead, mercury, arsenic), and tests for megaloblastic anemia. The hair may also be tested for indications of toxicity. 

DEFICIENCY Folate deficiency resembles B12 deficiency so far as the anemia goes, but without the neurologic abnormalities. Unlike B12, for which there are tremendous body stores, folate needs continued replacement, and poor diet is the most common cause of folate deficiency. Serum levels of folate may help establish the diagnosis. Pregnant women are encouraged to take folate in pregnancy to help prevent birth defects. 

Folate status can be assessed by the measurement of serum or red blood ceil folate levels, by the histidine load test, and by hematological methods. 

Scrum contains folate monoglutamates. The normal level of serum folate is 6-0 ng/ml or greater. A value of 3.0 ng/ml or less indicates a folate deficiency. Scrum folate levels are sensitive to recent dietary practices aitd hence may not accurately reflect the amount of folate in tissues. True folate status is closely related to the tissue or cellular level of folate, rather than the serum level. 

The effect of antimicrobial agents on serum folate level was studied using the standard autoclaving technique of Lactobacillus casei microbial assay. The blood for serum folate assay was obtained from adult human subjects before and 2 hours after a 24 hours test dose of the antibiotic (72). The results show that lincomycin produced a falsely low serum folate level. 

Lower than normal serum folate concentrations have been reported in patients with psychiatric disorders. In two studies, about one third of psychiatric patients had low RBC folate levels, with most of the low values being in depressed patients. Another study reported an inverse correlation between serum folate levels and the duration of depressive iUness. Limited evidence suggests that folate may have a role as a supplement to other treatments for depression. ... 

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). 

As the clinical usefulness of the microbiological assay for folate became more widely recognized so the number of variations and modifications to the method increased. As a consequence there was a wide range in the reported values found in normal subjects and a considerable variation in the level below which a patient was considered folate deficient. Some of these are shown in Table 1. Some workers have even suggested that folate levels in serum be graded as low, intermediate, or normal. In general it appears that serum folate levels below 3.0 xg/liter reflect a deficient state. 

In a follow-up experiment three volunteers were placed on this same very-low-folate diet and supplemented with 25, 50, and 100 p.g of folate daily (H17). After 1 month there was a fall in the serum folate level from 10.3 to... 

During pregnancy the serum folate level progressively foils. Davis (D15) measured the serum folate in blood samples collected from 100 consecutive... 

The effect of oral contraceptive agents on serum folate levels has been the subject of numerous studies (S23, S24, P7). Davis and Smith (D16) as part of... 

Formiminotransferase deBciency syndrome was first described in two patients by Arakawa (A7). It was characterized by mental retardation, a very high serum folate level, and excessive excretion of formiminoglutamic acid following a histidine load. A third patient with this syndrome was later... 

There have been other single reports of megaloblastic anemia associated with an apparent abnormality of folate metabolism. One child had a normal serum folate of 6 p,g/liter, an erythrocyte folate of 1480 p.g/liter, and a megaloblastic anemia which responded to treatment with folic acid (VI). Lampkin (Lll) described two sisters with a severe megaloblastic anemia and normal vitamin 6 2 folate levels. Absorption of vitamin 6, 2 normal and both patients excreted an increased amount of formiminoglutamic acid. It was thought that they required both vitamin B 2 and folate to restore normoblastic hemopoiesis. 

Many patients in intensive care units receive intravenous nutrition, which is a mixture of various amino acids, sorbitol, and ethanol. In a study of 30 patients with normal preoperative folate levels who were operated on for gastrointestinal disease, the serum folate fell within 48 hours by 60-95% in 20 patients receiving intravenous nutrition (W24). Seven patients had a megaloblastic bone marrow. Daily treatment with 0.5 mg of folic acid given intravenously prevented any clinical signs of folate deficiency. These patients received between 100 and 150 g of ethanol daily as part of their parenteral nutrition, and this may have played a significant role in the development of folate deficiency. However, Tennant (T12) examined this possibility and found that acute depression of the serum folate concentration occurred with both alcohol-firee and alcohol-containing preparations used for parenteral nutrition. It was also noted that only one particular brand of... 

Serum folate levels have been found to be significantly reduced in patients with rheumatoid arthritis. In a study of 77 patients, 42 with rheumatoid arthritis and 35 with osteoarthritis, Sanderson (S36) found the serum folate to be lower in the group with rheumatoid arthritis to a significant degree... 

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