Intestines folate absorption

D., Folate-losing gastropathy and intestinal folate absorption in patients with Men-etrier s disease (giant hypertrophic gastritis). Dig. Dis. Sci. 23, 143-147 (1978). 

Side ejfects of sulfasalazine occur in 10 5% of patients with ulcerative colitis and are related primarily to the sulfa moiety. Some are dose-related, including headache, nausea, and fatigue. These reactions can be minimized by giving the medication with meals or by decreasing the dose. Allergic reactions include rash, fever, Stevens-Johnson syndrome, hepatitis, pneumonitis, hemolytic anemia, and bone marrow suppression. Sulfasalazine reversibly decreases the number and motility of sperm but does not impair female fertility. It also inhibits intestinal folate absorption therefore, folate usually is given with sulfasalazine. 

These authors previously found (S12) that in all of 16 women who initially had subnormal serum folate concentrations, serum folate concentrations rose within 3 months after OCAs were stopped. Subsequently they reported (SIO) 3 women with low serum folate levels while taking OCAs and low folate polyglutamate absorption that persisted after medication was discontinued. It was of interest that one of these subjects developed gluten-sensitive enteropathy a year later and a second had a family history of that disease. Other case reports of folate deficiency and mild intestinal malabsorption in users of OCAs have appeared (J3, T2, W12). It should be emphasized, therefore, that evidence of impaired folate absorption in women taking these agents may suggest the presence of inapparent small bowel disease. 

About 80% of dietary folate is in the form of polyglutamates a variable amount may be replaced by various one-carbon fragments or be present as dihydrofolate derivatives. Folate conjugates are hydrolysed in the small intestine by conjugase (pteroyl-polyglutamate hydrolase), a zinc-dependent enzyme of the pancreatic juice, bile and mucosal brush border zinc deficiency can impair folate absorption. Free folate, released by conjugase action, is absorbed by active transport in the jejunum. 

Folate and anemia Inadequate serum levels of folate can be caused by increased demand (for example, pregnancy and lactation), poor absorption caused by pathology of the small intestine,... 

Unaltered folic acid is readily and completely absorbed in the proximal jejunum. Dietary folates, however, consist primarily of polyglutamate forms of N 5-methyltetrahydrofolate. Before absorption, all but one of the glutamyl residues of the polyglutamates must be hydrolyzed by the enzyme -1-glutamyl transferase ("conjugase") within the brush border of the intestinal mucosa. 

Bovine milk also contains binding proteins for vitamins B12, folic acid and riboflavin. It has been suggested that the folate-binding protein contributes to the absorption of folate in the intestines (Parodi, 1998). 

Deficiencies of vitamin B12 can result from either low dietary levels or, more commonly, from poor absorption of the vitamin due to the failure of gastric parietal cells to produce intrinsic factor (as in pernicious anemia) or to a loss of activity of the receptor needed for intestinal uptake of the vitamin.5 Nonspecific malabsorption syndromes or gastric resection can also cause vitamin B12 deficiency. The vitamin may be administered orally (for dietary deficiencies), or intramuscularly or deep subcutaneously (for pernicious anemia). [Note Folic acid administration alone reverses the hematologic abnormality and thus masks the B12 deficiency, which can then proceed to severe neurologic dysfunction and disease. Therefore, megaloblastic anemia should not be treated with folic acid alone, but rather with a combination of folate and vitamin B12.] Therapy must be continued for the remainder of the life of a patient suffering from pernicious anemia. There are no known adverse effects of this vitamin. 

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. 

DiphenyUiydantoin and other anticonvulsants impair the intestinal absorption of folates. This may be by inhibition of intestinal conjugase however, the evidence from various studies is conflicting. 

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