top Clinical Studies References
Folic Acid is a B vitamin necessary for the production of red blood cells and for normal metabolism. A deficiency may cause anemia. Drinking alcohol and taking oral contraceptives can cause lower levels of this vitamin in your body. It is especially important during pregnancy to prevent birth defects.
Folic Acid may be beneficial for depression, schizophrenia, atherosclerosis, heart disease, diarrhoea, epilepsy, gingivitis (periodontal disease), gout, cancer (reduces risk), osteoporosis, peripheral vascular disease, psoriasis, restless legs syndrome, seborrheic dermatitis and high homocysteine levels (plays an important role in heart disease and myocardial infarction).
Published Clinical Studiesclin
1 DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations.
Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J, Dierkes J, Weger M; DACH-LIGA Homocystein e.V.
Landesklinik fur Herzchirurgie, Landeskliniken Salzburg, Salzburg, Austria.
About half of all deaths are due to cardiovascular disease and its complications. The economic burden on society and the healthcare system from cardiovascular disability, complications, and treatments is huge and getting larger in the rapidly aging populations of developed countries. As conventional risk factors fail to account for part of the cases, homocysteine, a "new" risk factor, is being viewed with mounting interest. Homocysteine is a sulfur-containing intermediate product in the normal metabolism of methionine, an essential amino acid. Folic acid, vitamin B12, and vitamin B6 deficiencies and reduced enzyme activities inhibit the breakdown of homocysteine, thus increasing the intracellular homocysteine concentration. Numerous retrospective and prospective studies have consistently found an independent relationship between mild hyperhomocysteinemia and cardiovascular disease or all-cause mortality. Starting at a plasma homocysteine concentration of approximately 10 micromol/l, the risk increase follows a linear dose-response relationship with no specific threshold level. Hyperhomocysteinemia as an independent risk factor for cardiovascular disease is thought to be responsible for about 10% of total risk. Elevated plasma homocysteine levels (>12 micromol/l; moderate hyperhomocysteinemia) are considered cytotoxic and are found in 5 to 10% of the general population and in up to 40% of patients with vascular disease. Additional risk factors (smoking, arterial hypertension, diabetes, and hyperlipidemia) may additively or, by interacting with homocysteine, synergistically (and hence over-proportionally) increase overall risk. Hyperhomocysteinemia is associated with alterations in vascular morphology, loss of endothelial anti-thrombotic function, and induction of a procoagulant environment. Most known forms of damage or injury are due to homocysteine-mediated oxidative stress. Especially when acting as direct or indirect antagonists of cofactors and enzyme activities, numerous agents, drugs, diseases, and lifestyle factors have an impact on homocysteine metabolism. Folic acid deficiency is considered the most common cause of hyperhomocysteinemia. An adequate intake of at least 400 microg of folate per day is difficult to maintain even with a balanced diet, and high-risk groups often find it impossible to meet these folate requirements. Based on the available evidence, there is an increasing call for the diagnosis and treatment of elevated homocysteine levels in high-risk individuals in general and patients with manifest vascular disease in particular. Subjects of both populations should first have a baseline homocysteine assay. Except where manifestations are already present, intervention, if any, should be guided by the severity of hyperhomocysteinemia. Consistent with other working parties and consensus groups, we recommend a target plasma homocysteine level of <10 micromol/l. Based on various calculation models, reduction of elevated plasma homocysteine concentrations may theoretically prevent up to 25% of cardiovascular events. Supplementation is inexpensive, potentially effective, and devoid of adverse effects and, therefore, has an exceptionally favorable benefit/risk ratio. The results of ongoing randomized controlled intervention trials must be available before screening for, and treatment of, hyperhomocysteinemia can be recommended for the apparently healthy general population.
PMID: 14656016 [PubMed - in process]
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[Hyperhomocysteinemia related cerebral venous thrombosis]2
Fernandez Moreno MC, Castilla Guerra L, Castella Murillo A, Cueli Rincon B, Fernandez Bolanos R, Gutierrez Tous R, Jimenez Hernandez MD.
Hospital Universitario Virgen de Valme, Sevilla, Espana.
INTRODUCTION. Moderate hyperhomocystinemia is a causal risk factor for atherosclerosis and venous thromboembolism. Recent researches have tried to find out a causal relationship. However, only a small number of cases have been reported on hyperhomocysteinemia and cerebral venous thrombosis in the world medical literature. CASE REPORT. We present the case of a 21 years old woman, and oral contraceptives taker, who consulted for a one week clinical picture of biparietal headache, nausea and vomiting. Examination revealed bilateral papilledema, and subsequent CT scan, MRI and MR angiography showed thrombosis of the left lateral sinus. Immunologic tests (antinuclear antibodies, antiphospholipid antibodies) were negative. Hypercoagulability studies showed persistent homocysteine high levels. The patient improved and was discharged after treatment with anticoagulants and therapeutic measures against brain edema. DISCUSSION. The 70 percent of the patients with thrombosis of the cerebral venous sinuses present hypercoagulable states, including moderate hyperhomocysteinemia. Several mechanisms are proposed for venous thrombosis in hyperhomocysteinemia, homocysteine induced endothelial dysfunction between others. Otherwise, oral contraceptives can increase the risk of venous thrombosis in other prothrombotic conditions. Folic acid and vitamins supplementation therapy are commented.
PMID: 14669145 [PubMed - in process]
Folic acid and neural tube defects in pregnancy: a review.3
Geisel J.
State University of New York at Buffalo, School of Nursing, Buffalo, NY 14214, USA. jgeisel@buffalo.edu
Neural tube defects (NTDs) are common fetal malformations. They are multifactorial in origin, with folic acid as the primary known environmental factor. It is recommended that all women consume 0.4 mg of synthetic folic acid daily if there is any possibility of becoming pregnant. Women who have had a previous pregnancy affected by NTD should increase their folic acid intake to 4.0 mg daily periconceptually. The purpose of this article is to review the relationship between folic acid and NTDs. It also discusses how the knowledge and use of folic acid has affected the incidence of NTDs, and ways in which the knowledge and use of folic acid before pregnancy can be increased.
Publication Types:
PMID: 14655787 [PubMed - indexed for MEDLINE]
Folate improves endothelial function in patients with coronary heart disease.4
Doshi S, McDowell I, Moat S, Lewis M, Goodfellow J.
Cardiovascular Sciences Research Group, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff, UK.
Elevated plasma homocysteine is associated with increased cardiovascular risk but it remains unproven that the effect is directly causal. Folate and homocysteine metabolism are closely linked such that administration of folic acid in doses ranging from 0.2-10 mg/day lowers plasma total homocysteine (tHcy) by up to 25%. Folic acid has been widely advocated as a therapy which may reduce cardiovascular risk, but the clinical benefit remains as yet unproven and the choice of dose remains unclear. The effect of folic acid on endothelial function has been investigated in patients with proven coronary heart disease (CHD) by measuring flow-mediated dilatation (FMD) in the brachial artery. Oral folic acid (5 mg/day) markedly enhances endothelial function (FMD) and lowers homocysteine. Studies of the acute effects of folic acid have shown that this improvement occurs within the first 2-4 hours following the first dose, at which times there was no significant reduction in plasma tHcy. Administration of 5-methyltetrahydrofolate directly into the brachial artery markedly enhances FMD, an effect that is blocked by monomethyl arginine (LNMMA), suggesting that the effects of folate are mediated by nitric oxide. This Review summarises studies which show that pharmacological doses of folate markedly enhance endothelial function in patients with CHD. The discordance with changes in plasma homocysteine suggests that these effects may occur by mechanisms distinct from homocysteine lowering.
PMID: 14656033 [PubMed - in process]
The role of genetic factors in the development of hyperhomocysteinemia.5
Geisel J, Hubner U, Bodis M, Schorr H, Knapp JP, Obeid R, Herrmann W.
Department of Clinical Chemistry, Saarland Medical School, Homburg, Germany. kchjgei@uniklinik-saarland.de
Moderate hyperhomocysteinemia has been identified as a new independent risk factor for cardiovascular and neurodegenerative diseases. This fact has produced interest in the study of genetic variants involved in homocysteine metabolism and its relationship to pathogenesis. Recently, more than 15 different genes were studied for their relationship to plasma homocysteine levels. We determined the influence of genetic variants in five genes (5,10-methylenetetrahydrofolate reductase (MTHFR) 677C --> T, serine hydroxymethyltransferase (SHMT) 1420C --> T, thymidylate synthase (TS) 2R --> 3R, catechol-O-methyltransferase (COMT) 1947G --> A and transcobalamin (TC) 776C --> G) on plasma homocysteine, folic acid and parameters of vitamin B12 metabolism in 111 vegetarians (mean age: 46 +/- 15 years) and 118 healthy seniors (mean age: 82 +/- 6.5 years). Median homocysteine concentration in plasma was significantly influenced by the MTHFR genotypes in both populations. In the vegetarians the median homocysteine level was increased by 8 micromol/l in individuals homozygous for the mutation as compared to wild-type or heterozygous genotypes (20.4 micromol/l vs. 12.9 and 12.7 micromol/l, respectively). This unexpected increase was observed although the folate levels were in medium to elevated ranges. Our results suggest that vegetarians have a higher demand for folate to neutralize the genotype effect. Preclinical vitamin B12 deficiency in vegetarians may be the cause for disturbed remethylation and folate trap. Plasma homocysteine was not significantly influenced by the SHMT, TS, COMT and TC mutations. In addition, for the TC mutation a trend toward cellular vitamin B12 deficiency was observed. The methylmalonic acid (MMA) levels were slightly elevated and the holotranscobalamin-II (holoTC-II) levels decreased. In the vegetarian group a significant relationship between the COMT genotype and holoTC-II concentration in plasma was determined, whereas the high activity COMT genotype (G/G) resulted in increased levels (35 micromol/l vs. 21 micromol/l for heterozygous and low activity genotypes). The MMA levels were inversely correlated to holoTC-II concentrations. In conclusion, the study on vegetarians and seniors documents interesting lifestyle-genotype interactions. Although the TC and COMT mutations influence cellular vitamin B12 metabolism, this effect did not result in overt homocysteine elevation.
PMID: 14656021 [PubMed - in process]
The role of food supplements in the treatment of the infertile man.7
Comhaire FH, Mahmoud A.
Centre for Medical and Urological Andrology, Ghent University Hospital, De Pintelaan, 185, B 9000 Gent, Belgium.
Recently, concerns have been raised about the presumptive increased risk of serious undesirable side effects in children born after IVF and intracytoplasmic sperm injection (ICSI). These treatments must, therefore, be reserved as the ultimate option after evidence-based and cause-directed treatment of the male patient with deficient semen has been exhausted. The present authors found that sperm quality and function improved with the intake of complementary food supplementation using a combination of zinc and folic acid, or the antioxidant astaxanthin (Astacarox(R)), or an energy-providing combination containing (actyl)-carnitine (Proxeed(R)). Also, double blind trials showed that the latter two substances increase spontaneous or intrauterine insemination- (IUI-) assisted conception rates. Extracts of Pinus maritima bark (Pycnogenol(R)), which inhibits the cyclo-oxygenase enzyme, reducing prostaglandin production and inflammatory reaction, and extracts of the Peruvian plant Lepidium meyenii were shown to improve sperm morphology and concentration, respectively, in uncontrolled trials. Linseed (flaxseed) oil contains alfa-linolenic acid and lignans. The former corrects the deficient intake of omega-3 essential fatty acids, which is correlated with impaired sperm motility among subfertile men. Lignans are precursors of enterolacton, which inhibits aromatase and reduces the ratio of 16-OH over 2-OH oestrogen metabolites. The resulting reduction in oestrogen load may favourably influence Sertoli cell function.
PMID: 14656398 [PubMed - in process]
Micronutrient deficiencies Hohenheim Consensus Conference.8
Biesalski HK, Brummer RJ, Konig J, O'Connell MA, Ovesen L, Rechkemmer G, Stos K, Thurnham DI.
Dept. of Biological Chemistry and Nutrition, University of Hohenheim, Fruwirthstr. 12, 70593, Stuttgart, Germany.
OBJECTIVE: The aim of this study was to consider the risk of micronutrient deficiencies and approaches for intervention, and to summarize existing knowledge and identify areas of ignorance. DESIGN: Experts from a range of relevant disciplines received and considered a series of questions related to aspects of the topic. INTERVENTION: The experts met and discussed the questions and arrived at a consensus. CONCLUSION: Though healthy balanced diet is available for the general European population, a few defined groups are at risk of micronutrient deficiencies. In addition, the intake of specific micronutrients such as iron, folic acid, vitamin D and vitamin B12 are often marginal. To overcome these deficiencies, either selected micronutrients or a mixture of different micronutrients might be recommended. However, to define and detect micronutrient deficiencies, specific biomarkers are only available for a few micronutrients (e. g. vitamin D, folic acid, vitamin C, iron). The definition of a risk group, based on scientific data, might be an appropriate way to justify intervention with supplements.
PMID: 14673609 [PubMed - in process]
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