Absorption of folic acid

When treating folic acid deficiency, an initial daily dose of 1 mg/day by mouth typically is effective. Absorption of folic acid generally is rapid and complete. However, patients with malabsorption syndromes may require larger doses (up to 5 mg/day). Similar to vitamin B12 deficiency, resolution of symptoms and reticulocytosis is prompt, occurring within days of commencing therapy. Hgb will start to rise after 2 weeks of therapy and may take from 2 to 4 months to resolve the deficiency completely. Afterwards, if the underlying deficiency is corrected, folic acid replacement can be discontinued. However, in cases where folic acid is consumed rapidly or absorbed poorly, chronic replacement may be required. 

The L. casei method described here can also be used to determine absorption of folic acid. Five milligrams of folic acid is given by mouth samples are obtained at 0, 2, 4, 6, and 8 hours. In cases of deficient folic acid absorption, normal peak levels are not obtained in the malabsorption syndrome, a flat curve indicates no absorption. Normal peak levels are maintained during 2-4 hour intervals (B3). 

Since sulfasalazine inhibits the absorption of folic acid, patients may become folate deficient during longterm therapy. Sulfasalazine decreases the bioavailabiUty of digoxin. Cholestyramine reduces the metabolism of sulfasalazine. Sulfasalazine causes a reversible decrease in sperm counts. Sulfasalazine is safe in pregnancy. 

Antibiotics. Long-term administration of antibiotics could lead to vitamin B6 deficiency, If symptoms of peripheral neuropathy develop (numbness and tingling of the extremities), administer vitamin B6. Sulfasalazine can decrease the absorption of folic acid, and trimethoprim can cause folate deficiency, hence the need to administer folic acid if there is evidence of deficiency. Rifampicin can cause disturbances in vitamin D metabolism and lead to osteomalacia. The absorption of tetracyclines can be reduced by calcium, magnesium, iron and zinc, while this antibiotic could also decrease the absorption of these minerals. This effect is probably least with minocycline and is not confirmed with doxycycline. Doses of minerals and antibiotic should be separated by at least 2 hours. The absorption of quinolones is reduced by cationic and anionic supplements. 

Malabsorption syndromes. Particularly in gluten-sensitive enteropathy and tropical sprue, poor absorption of folic acid from the small intestine often leads to a megaloblastic anaemia. 

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). 

L9. Luhby, A. L., Eagle, F. J., Roth, E., and Cooperman,. M., Relapsing megaloblastic anemia in an infant due to a specific defect in gastrointestinal absorption of folic acid. Am. 

R8. Russell, R. M., Ismail-Beigi, F., and Reinhold, J. G., Folate content of Iranian breads and the effect of their fibre content on the intestinal absorption of folic acid. Am. /. Clin. Nutr. 29, 799-802 (1976). 

Folic acid deficiency can occur due to pregnancy, malabsorption syndromes or inadequate diet. Some drugs, for example phenytoin (used in epilepsy), oral contraceptives and isoniazid (used in treating tuberculosis), can cause reduced absorption of folic acid. Oral replacement therapy with folic acid is effective. 

The absorption of folic acid was reduced by about one-third (from 65 to 44.5%) in patients with ulcerative and granulomatous colitis, when compared with healthy subjects, and even further reduced (down to 32%) when sulfasalazine was taken. Another study confirmed that serum folate levels are lower in patients with ulcerative colitis taking sulfasalazine, and that the impairment of the absorption of folates by sulfasalazine was a mechanism in this. Sulfasalazine is also known to interfere with folate metabolism. 

Pernicious anemia arises when vitamin B,2 deficiency blocks the metabohsm of folic acid, leading to functional folate deficiency. This impairs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The commonest cause of pernicious anemia is failure of the absorption of vitamin B,2 rather than dietary deficiency. This can be due to failure of intrinsic factor secretion caused by autoimmune disease of parietal cells or to generation of anti-intrinsic factor antibodies. 

Deficiency of folic acid Decreased intake, defective absorption, or increased demand (eg, in pregnancy) for folate... 

Phenytoin decreases folic add absorption, but folic acid replacement enhances phenytoin clearance and can result in loss of efficacy. Phenytoin tablets and suspension contain phenytoin acid, while the capsules and parenteral solution are phenytoin sodium, which is 92% phenytoin. Clinicians should remember that there are two different strengths of phenytoin suspension and capsules. 

R6. Rodriguez-Molina, R., Cancio, M., and Asenjo, C. F., The effect of folic acid on the steatorrhea of tropical sprue and other tests for intestinal absorption. Am. J. Trop. Med. Hyg. 9, 308-314 (1960). 

Blood levels of folic acid may become inadequate due to dietary insufficiency or poor absorption due to Intestinal problems or alcoholism. 

Ascorbic acid or vitamin C is found in fruits, especially citrus fruits, and in fresh vegetables. Man is one of the few mammals unable to manufacture vitamin C in the liver. It is essential for the formation of collagen as it is a cofactor for the conversion of proline and lysine residues to hydroxyproline and hydroxylysine. It is also a cofactor for carnitine synthesis, for the conversion of folic acid to folinic acid and for the hydroxylation of dopamine to form norepinephrine. Being a lactone with two hydroxyl groups which can be oxidized to two keto groups forming dehydroascorbic acid, ascorbic acid is also an anti-oxidant. By reducing ferric iron to the ferrous state in the stomach, ascorbic acid promotes iron absorption. 

The anemia of hyperthyroidism is usually normochromic and caused by increased red blood cell turnover. The anemia of hypothyroidism may be normochromic, hyperchromic, or hypochromic and may be due to decreased production rate, decreased iron absorption, decreased folic acid absorption, or to autoimmune pernicious anemia. LDH, lactic dehydrogenase AST, aspartate aminotransferase. 

The higher RDA is specified to allow for absorption of only 25% of folic acid activity in a manner comparable to the crystalline folic acid and to allow for a wide range of availability of the polyglutamate form (13). 

Oxidized folate is not only metabolically dead buyt may even be neurotoxic. For example, a patient with epilepsy who has not had a convulsion in years because dilantin has produced complete control, can be thrown into an immediate convulsion with a megadose of folic acid, because folic acid and dilantin compete for absorption at the brain cell surface, and too much oxidized folic acid will block the ability of the brain cell to take up dilantin, similar to the competition between dilantin and folic acid for uptake by the gutcell (22). 

Examination of the bone marrow, although important, will only confirm that the hemopoiesis is megaloblastic. A deficiency of folic acid will also cause a megaloblastic anemia and it is not possible to identify the cause on the basis of morphology. A serum assay of both vitamins will usually indicate which is responsible. If the patient is vitamin B12 deficient, the next step is to carry out a vitamin B12 absorption test to confirm that the deficiency is due to a lack of intrinsic factor. Preferably this should not be done until the patient s vitamin B12 and hemoglobin levels have returned to normal, since the gastric and intestinal cells are also affected by a lack of vitamin B12 aborption may be less than optimal if it is attempted too early. Patients with pernicious anemia also have a histamine-fast achlorhydria and gastric atrophy. The disease appears to have an autoimmune basis and antibodies to intrinsic factor can be demonstrated in the serum of more than half of affected patients. 

Drugs. Antiepilepsy drugs, particularly phenytoin, primidone and phenobarbital, occasionally cause a macrocytic anaemia that responds to folic acid. This may be due to enzyme induction by the antiepileptics increasing the need for folic acid to perform hydroxylation reactions (see Epilepsy) but other factors such as reduced absorption may be involved. Administration of folic acid causes a recurrence of seizures in some patients. Some anti-malarials, e.g. pyrimethamine, may interfere with conversion of folates to the active tetrahydrofolic acid, causing macrocytic anaemia. Methotrexate, another folate antagonist, may cause a megaloblastic anaemia especially when used long-term for leukaemia, rheumatoid arthritis or psoriasis. 

The authors of the Dietary Reference Intakes (15) have concluded that reports of the effect of folic acid supplementation on the intestinal absorption of zinc are controversial, but that the recent literature shows that folic acid supplementation has either no effect or an extremely weak effect on zinc supply. 

A complex interaction of phenytoin with folic acid also has been described, making vitamin ingestion an important part of the drug history. Phenytoin reportedly decreases fohc acid absorption, but folic acid enhances the clearance of phenytoin. Replacement of folic acid can reduce phenytoin concentrations and result in loss of efficacy. ... 

Folic acid deficiency, a macrocytic anemia, results from in- adequate intake, decreased absorption, hyperutilization, or inadequate utilization. Treatment consists of the oral administration of folic acid, even in patients with absorption problems. Adequate folic acid intake is essential in women of childbearing years to decrease the risk of neural tube defects in their children. 

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