Folate, absorption excretion

Freedman, D. S., Brown, J. P., Weir, D. G., and Scott, J. M., The reproducibiUty and use of the tritiated folic acid urinary excretion test as a measure of folate absorption in clinical practice Effect of methotrexate on absorption of folic acid. /. Clin. Pathol. 26, 261-267 (1973). 

As reviewed in detail by Rosenberg and Godwin (R18), folate absorption has been measured by three basically different methods (1) measurement of rises in blood folate after an oral dose, (2) measurement of folate compounds in urine after an oral dose, and (3) administration of isotopically labeled folate by mouth followed by measurement of isotope appearing in plasma and excreted in urine and feees. Folate in plasma and urine is assayed with bacteria, usually strains of Lactobacillus casei or Streptococcus faecalis, which require folate for growth. They differ somewhat in the forms of folate they can utilize, but in general these microbiological assays measure unconjugated folate in either their reduced or unreduced forms. 

There is considerable enterohepatic circulation of folate, equivalent to about one-third of the dietary intake. Methyl-tetrahydrofolate is secreted in the bUe, then reabsorbed in the jejunum together with food folates. In experimental animals, bUe drainage for 6 hours results in a reduction of serum folate to 30% to 40% of normal (Steinberg et al., 1979). There is very litde loss of folate jejunal absorption is very efficient, and the fecal excretion of 450 nmol (200 /xg) of folates per day largely represents synthesis by intestinal flora and does not reflect intake to any significant extent. 

A. Pernicious anemia occurs when the stomach does not produce adequate intrinsic factor for absorption of vitamin B12, which is required for the conversion of methylmalonyl CoA to succinyl CoA and homocysteine to methionine. A vitamin B12 deficiency results in the excretion of methylmalonic acid and an increased dietary requirement for methionine. The methyl group transferred from vitamin B12 to homocysteine to form methionine comes from 5 -methyl tetrahydrofolate, which accumulates in a vitamin B12 deficiency, causing a decrease in folate levels and symptoms of folate deficiency, including increased levels of FIGLU and decreased purine biosynthesis. 

Formic acid can be readily absorbed from the digestive tract and the respiratory system. Systemic absorption produces acidosis, neuropathy, and visual and mental disturbances. Acidosis can also be produced when formic acid is produced by liver aldehyde dehydrogenase from formaldehyde. Formaldehyde in turn can also be produced metabolically by alcohol dehydrogenase from methanol. Formic acid is oxidized to carbon dioxide by the folate-dependent pathway. Some formic acid is excreted unchanged in the urine. 

Shuster et al. (Sll) measured B12 levels in the sera of 20 patients with psoriasis and found normal levels in all but one. Folic acid levels were decreased below normal in 21 out of 28 patients, urinary FIGLU excretion was elevated in 19 of 30, and in 5 of 9 patients sternal marrow puncture revealed megaloblastic erythropoiesis, thereby implying a true folate deficiency. Neither serum iron deficiency nor lack of absorption of folate could be implicated as a cause of the folate deficiency, and presumably it is related to the skin lesions. 

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. 

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