Folate absorption

After absorption, folate is reduced to THF by dihydrofolate reductase. The majority of circulating folate is in the form of N -methyl THF. Cells use specific transporters for THF uptake, and cellular machinery polyglutamates the folate to aid in cellular retention. 

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... 

Milk is an excellent source of calcium, phosphorus, riboflavin (vitamin B2), thiamine (vitamin Bl) and vitamin B12, and a valuable source of folate, niacin, magnesium and zinc (Food Standards Agency, 2002). In particular, dairy products are an important source of calcium, which is vital for maintaining optimal bone health in humans (Prentice, 2004). The vitamins and minerals it provides are all bioavailable (i.e. available for absorption and use by the body) and thus milk consumption in humans increases the chances of achieving nutritional recommendations for daily vitamins and mineral intake (Bellew et al., 2000). 

Figure 1 is the infrared spectrum taken from a mineral oil suspension of a representative sample of calcium leucovorin. A common feature of folate derivative ir spectra obtained in this laboratory is the absence of sharp absorption bands, which is usually attributed to lack of crystallinity. Below are listed the major absorption assignments ... 

Answer E. The genetic defect would result in malabsorption of the 3 fatty acids listed, but only linoleate is strictly essential in the diet. Absorption of water-soluble ascorbate and folate would not be significantly affected. 

Vitamin Bn deficiency Deficiency, although rare, results in two serious problems megaloblastic anaemia (which is identical to that caused by folate deficiency) and a specific neuropathy called Bi2-associated neuropathy or cobalamin-deficiency-associated neuropathy (previously called, subacute combined degeneration of the cord). A normal healthy adult can survive more than a decade without dietary vitamin B12 without any signs of deficiency since it is synthesised by microorganisms in the colon and then absorbed. However, pernicious anaemia develops fairly rapidly in patients who have a defective vitamin B12 absorption system due to a lack of intrinsic factor. It results in death in 3 days. Minot and Murphy discovered that giving patients liver, which contains the intrinsic factor, and which is lightly cooked to avoid denaturation, cured the anaemia. For this discovery they were awarded the Nobel Prize in Medicine in 1934. 

Following oral administration leucovorin is rapidly absorbed and expands the serum pool of reduced folates. Oral absorption of leucovorin is saturable at doses greater than 25 mg. The apparent bioavailability of leucovorin was 97% for 25 mg, 75% for 50 mg, and 37% for 100 mg. 

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. 

Severe cyanocobalamin (vitamin B12) deficiency results in pernicious anemia that is characterized by megaloblastic anemia and neuropathies. The symptoms of this deficiency can be masked by high intake of folate. Vitamin B12 is recycled by an effective enterohep-atic circulation and thus has a very long half-hfe. Absorption of vitamin B12 from the gastrointestinal tract requires the presence of gastric intrinsic factor. This factor binds to the vitamin, forming a complex that... 

Many drugs interact with folate to affect its absorption, antagonize its biochemical activity, or increase its loss from the body. These drugs include ethanol, phenytoin, and oral contraceptives. Salicylates can compete with foUc acid for plasma protein binding. Methotrexate, a cytotoxic agent, is a folate antagonist that inhibits the biosynthesis of this coenzyme. 

Sulfasalazine has a high incidence of adverse effects, most of which are attributable to systemic effects of the sulfapyridine molecule. Slow acetylators of sulfapyridine have more frequent and more severe adverse effects than fast acetylators. Up to 40% of patients cannot tolerate therapeutic doses of sulfasalazine. The most common problems are dose-related and include nausea, gastrointestinal upset, headaches, arthralgias, myalgias, bone marrow suppression, and malaise. Hypersensitivity to sulfapyridine (or, rarely, 5-ASA) can result in fever, exfoliative dermatitis, pancreatitis, pneumonitis, hemolytic anemia, pericarditis, or hepatitis. Sulfasalazine has also been associated with oligospermia, which reverses upon discontinuation of the drug. Sulfasalazine impairs folate absorption and processing hence, dietary supplementation with 1 mg/d folic acid is recommended. 

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,... 

Anon. 1982A. Folate binder in milk may facilitate folate absorption. Nutr. Rev. 40, 90-92. 

Vi Lamm B12 is one of the most potent nutrients known the minimal daily requirement for absorption by the normal adult is probably in the range of 0,1 microgram. This equals, for example, l/500th of the minimal daily adult folate requirement, which is in the range of 50 micrograins. 

Folacin bioavailability varies among the vitamers (120,125). Folic acid is more readily available than the naturally occurring food folates but may be less available from fortified foods than in aqueous solution or tablet form. Food folates have been reported to be 30-80% as available as folic acid. Folacin availability, absorption, and metabolism were recently reviewed (20,120,122). 

Both sequential and non-sequential types of oral contraceptives impair the absorption of polyglutamic folate but not that of monoglutamic folate the change can result in megaloblastic anemia in predisposed subjects, for example those with celiac disease or having a deficient diet (182). 

Metformin can cause reduced vitamin Bi2 absorption, reducing serum Bi2 concentrations and causing megaloblastic anemia (87), the prevalence of which was 9% in 600 patients with type 2 diabetes taking biguanides (phen-formin or metformin) for a mean of 12 years (88). In 353 patients with type 2 diabetes, treated with insulin, who took metformin for 16 weeks in a placebo-controlled study, metformin increased serum homocysteine concentrations by 4% and reduced serum folate by 7% and vitamin Bi2 by 14% (89). 

Its natural occurrence is unique in citrus fruits (4-6J. Furthermore, by employing triple lumen perfusion techniques, it was shown that diphenylhydantoin does not influence the absorption of citrus folate in human volunteers. This may be clinically significant, since diphenylhydantoin in dosages sufficient to control epileptic seizures influences absorption of forms of folate present in other food sources. 

Rosenburg, I. 1990. Herman award lecture. Folate absorption clinical questions and metabolic answers. Am J Clin Nutr 51 531. 

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. 

Folic acid deficiency, unlike vitamin B12 deficiency, is often caused by inadequate dietary intake of folates. Alcoholics and patients with liver disease develop folic acid deficiency because of poor diet and diminished hepatic storage of folates. There is also evidence that alcohol and liver disease interfere with absorption and metabolism of folates. Pregnant women and patients with hemolytic anemia have increased folate requirements and may become folic acid-deficient, especially if their diets are marginal. Evidence implicates maternal folic acid deficiency in the occurrence of fetal neural tube defects, eg, spina bifida. (See Folic Acid Supplementation A Public Health Dilemma.) Patients with malabsorption syndromes also frequently develop folic acid deficiency. Folic acid deficiency is occasionally associated with cancer, leukemia, myeloproliferative disorders, certain chronic skin disorders, and other chronic debilitating diseases. Patients who require renal dialysis also develop folic acid deficiency, because folates are removed from the plasma each time the patient is dialyzed. 

Folic acid deficiency can be caused by drugs that interfere with folate absorption or metabolism. Phenytoin, some other anticonvulsants, oral contraceptives, and isoniazid can cause folic acid deficiency by interfering with folic acid absorption. Other drugs such as methotrexate and, to a lesser extent, trimethoprim and pyrimethamine, inhibit dihydrofolate reductase and may result in a deficiency of folate cofactors and ultimately in megaloblastic anemia. 

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