Cause Of Folate Deficiency Research Articles

Folic acid and birth defects

Folic acid deficiency is associated with birth defects such as fetal spina bifida and congenital heart disease.Folic acid supplementation during pregnancy can prevent various birth defects, but excessive folic acid may increase the risk of certain diseases.This article reviews the causes of folate deficiency, single nucleotide polymorphisms of folate metabolism-related enzyme genes, the mechanism of birth defects caused by folic acid deficiency, and the correct supplementation of folic acid to prevent birth defects. Key words: Folic acid deficiency; Birth defect; Single nucleotide polymorphism; Homocysteine

Folate Deficiency Induces Dysfunctional Long and Short Telomeres; Both States Are Associated with Hypomethylation and DNA Damage in Human WIL2-NS Cells

The essential role of dietary micronutrients for genome stability is well documented, yet the effect of folate deficiency or excess on telomeres is not known. Accordingly, human WIL2-NS cells were maintained in medium containing 30, 300, or 3,000 nmol/L folic acid (FA) for 42 days to test the hypothesis that chronic folate deficiency would cause telomere shortening and dysfunction. After 14 days, telomere length (TL) in FA-deficient (30 nmol/L) cultures was 26% longer than that of 3,000 nmol/L FA cultures; however, this was followed by rapid telomere attrition over the subsequent 28 days (P trend, P < 0.0001); both long and short telomere status was positively correlated with biomarkers of chromosome instability (P ≤ 0.003) and mitotic dysfunction (P = 0.01), measured by the cytokinesis-block micronucleus cytome (CBMN-cyt) assay. The early increase in TL was associated with FA-deficiency-induced global DNA hypomethylation (P = 0.05), with an effect size similar to that induced by the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine. Quantitative PCR analysis indicated a negative association between FA concentration and uracil incorporation into telomeric DNA (r = -0.47, P = 0.1), suggesting a possible plausible mechanism for uracil as a cause of folate deficiency-induced telomere dysfunction or deletion. Peptide nucleic acid-FISH (PNA-FISH) analysis showed that FA deficiency resulted in 60% of micronuclei containing acentric terminal fragments, an observation consistent with the 3-fold increase in terminal deletions (P = 0.0001). Together, these results demonstrate the impact of folate deficiency on biomarkers of telomere maintenance and integrity, and provide evidence that dysfunctional long telomeres may be as important as critically short telomeres as a cause of chromosomal instability.

Causes of Vitamin B12 and Folate Deficiency

This review describes current knowledge of the main causes of vitamin B12 and folate deficiency. The most common explanations for poor vitamin B12 status are a low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and malabsorption. Although it has long been known that strict vegetarians (vegans) are at risk for vitamin B12 deficiency, evidence now indicates that low intakes of animal-source foods, such as occur in some lacto-ovo vegetarians and many less-industrialized countries, cause vitamin B12 depletion. Malabsorption of the vitamin is most commonly observed as food-bound cobalamin malabsorption due to gastric atrophy in the elderly, and probably as a result of Helicobacter pylori infection. There is growing evidence that gene polymorphisms in transcobalamins affect plasma vitamin B12 concentrations. The primary cause of folate deficiency is low intake of sources rich in the vitamin, such as legumes and green leafy vegetables, and the consumption of these foods may explain why folate status can be adequate in relatively poor populations. Other situations in which the risk of folate deficiency increases include lactation and alcoholism.

Cough mixture abuse as a novel cause of folate deficiency: a prospective, community-based, controlled study

Cough mixture abuse has been reported to cause severe folate deficiency and neurological defects. We carried out a prospective case-controlled survey to confirm this association and define the incidence and severity of the problem. A total of 57 cough mixture abusers and 47 other substance abusers (controls) were studied. When compared with controls, cough mixture abusers had a high incidence of low folate levels that could only be detected by screening.

Sulfasalazine and Folate Deficiency-Reply

In Reply.— Folate deficiency is a common occurrence in patients with inflammatory bowel disease, and different causes of folate deficiency have been described in the past. However, only recently, Dr Halsted and colleagues' demonstrated, using the jejunal perfusion technique, a clear relation between the use of sulfasalazine and the incidence of folate deficiency in patients with ulcerative colitis. Minor hemolysis has been shown in patients taking sulfasalazine. As I previously pointed out, anemia in the patient I described was in part caused by a hemolytic process, but clearly, folate deficiency was present and played an important role. The anemia was corrected with folic acid supplementation without discontinuation of sulfasalazine therapy. The current evidence suggests that folate deficiency in patients with ulcerative colitis receiving long-term sulfasalazine therapy, with or without anemia, may be prevented by folic acid supplementation or increased dietary intake of folate.

Elevated serum levels of unsaturated folate binding protein: clinical correlates in a general hospital population ,

We measured the capacity of unsaturated folate binding protein to bind 3H-pteroylglutamic acid (UFBC) in scrums from 489 general hospital patients. Of the patients 20% had mild-to-moderate elevations in UFBC (250 to 500 pg/ml), but only 6% had marked elevations (>650 pg/ml), which correlated with metastatic cancer, active granulomatous disease, and especially with liver disease. The poor correlation of serum UFBC with folate status of the patient suggests that in many instances the elevated serum UFBC is neither the consequence nor the cause of folate deficiency. Although the role of folate binding protein remains unknown, it may be primarily an intracellular protein that is released into the serum as an index of activity of liver cells, granulocytes, and perhaps certain cancer cells.

Inhibition of Intestinal Absorption of Folic Acid by Phenytoin

Folate deficiency in four patients could be ascribed to anticonvulsant therapy with phenytoin. Their intestinal absorption of folic acid was depressed only when phenytoin was given simultaneously. Otherwise the absorption of folic acid was normal. This malabsorption of folic acid is probably due to a rise in the jejunal pH produced by phenytoin. It is assumed, however, that this effect of phenytoin is rather the result than the cause of folate deficiency occurring during anticonvulsant drug therapy.

Iron and folate metabolism in tuberculosis.

Hypochromic anaemia associated with the accumulation of excessive numbers of iron granules in the perinuclear zone of erythroblasts ( sideroblastic anaemia ) has been described in patients being treated with isoniazid (Redleaf, 1962 ; Kohn et al., 1962 ; McCurdy, 1963 ; MacGibbon and Mollin, 1965). The condition is apparently very rare in patients receiving isoniazid alone, and it may be that this drug affects only the haemopoietic tissue of certain susceptible individuals. However, sideroblastic anaemia does not appear to be infrequent in patients given isoniazid in conjunction with other antituberculous drugs such as cycloserine or pyrazinamide (Verwilghen et al., 1963, 1965). The combination of these drugs is also more effective in pro ducing sideroblastic anaemia in experimental animals than the administration of isoniazid alone (Harriss et al., 1965). It therefore seems possible that the incidence and severity of siHeroblastic anaemia in patients receiving antituberculous treat ment is partly related to the dose and the type of drug given. If this is g?, minor degrees of sideroblastic change might be more common in patients receiving antituberculous therapy than has previously been suspected. To investigate this point haematological studies were carried out on a group of tuber culous patients receiving chemotherapy. Early m this survey it became apparent that many of the patients showed haematological evidence of folate deficiency. The investigation was therefore extended to determine the incidence and cause of folate deficiency in these tuberculous patients. This paper reports the results of both studies.

Folate Deficiency in Chronic Liver Disease

Abstract Fifty-five patients with liver disease of varied etiology and severity have been studied. Serum folate concentrations were subnormal and folic acid clearances rapid, when studied, in 19 actively imbibing alcoholic cirrhotics who had a megaloblastic anemia. Eleven patients, from both the nonalcoholic and alcoholic groups, had rapid folic acid clearances, with subnormal serum folate levels in seven, in the absence of morphologic evidence of folate deficiency. Serum B12 concentrations were uniformly normal or elevated. Dietary deficiency appeared to be the major cause of folate deficiency; all 19 patients who had megaloblastic changes were considered to have an inadequate dietary intake. Increased requirement for folate due to hyperactivity of the bone marrow secondary to gastrointestinal bleeding. hypersplenism, or hemolysis appeared to contribute to the development of abnormal folic acid determinations in many patients in both the alcoholic and nonalcoholic groups. Two of 10 patients studied had malabsorption of folic acid. Such factors as the presence of ascites, an expanded plasma volume, a Patent portacaval shunting procedure, the type of alcoholic beverage imbibed, and the severity of impairment of liver function did not appear to be of significance in the development of folate deficiency.