Folic acid vitamin B12 and

Elevated homocysteine concentrations have been associated with an increased risk for cardiovascular disease in both epidemiologic and clinical studies.43 Several studies have evaluated the benefit of lowering homocysteine levels with folic acid supplementation. One study reported a reduction in major cardiac events with the combination of folic acid, vitamin B12, and vitamin B6 following PCI.44 However, a more recent study found an increased risk of instent restenosis and the need for target-vessel revascularization with folate supplementation following coronary stent placement.45 The role of folate in the management of IHD is currently unclear. 

Effect of homocysteine-lowering therapy with folic acid, vitamin B12. and vitamin B6 on clinical outcome after coronary angioplasty. 

Schnyder G, Rofifi M, Flammer Y, Pin R, Hess OM. Effect of Homocysteine-Lowering Therapy With Folic Acid, Vitamin B12, and Vitamin B6 on Clinical Outcome After Percutaneous Coronary Intervention The Swiss Heart Study A Randomized Controlled Trial. JAMA 2002 288 973-979. 

The Inhibition and Promotion of Cancers by Folic Acid, Vitamin B12, and Their Antagonists... 

Folic acid, vitamin B12 and Bg are involved in homocysteine metabolism. 

Schnyder, G., Roffi, M., Flammer, Y., Pin, R., and Hess, O.M., 2002. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention the Swiss Heart study a randomized controlled trial. The Journal of the American Medical Association. 288 973-979. 

Clarke, R., Smith, A.D, Jobst, K.A, Refsum, H., Sutton, L., and Ueland P.M., 1998. Folic acid, vitamin B12, and serum homocysteine levels in confirmed Alzheimer s disease. Archives of Neurology. 55 1449-1455. 

VITATOPS study follows up 8000 patients between 2000 and 2009 provided a reliable estimate of the safety and effeetiveness of dietary supplementation with folic acid, vitamin B12 and vitamin Bg in reducing recurrent serious vaseular events and transient ischemie attacks stroke. 

Orotic acid in the diet (usually at a concentration of 1 per cent) can induce a deficiency of adenine and pyridine nucleotides in rat liver (but not in mouse or chick liver). The consequence is to inhibit secretion of lipoprotein into the blood, followed by the depression of plasma lipids, then in the accumulation of triglycerides and cholesterol in the liver (fatty liver) [141 — 161], This effect is not prevented by folic acid, vitamin B12, choline, methionine or inositol [141, 144], but can be prevented or rapidly reversed by the addition of a small amount of adenine to the diets [146, 147, 149, 152, 162]. The action of orotic acid can also be inhibited by calcium lactate in combination with lactose [163]. It was originally believed that the adenine deficiency produced by orotic acid was caused by an inhibition of the reaction of PRPP with glutamine in the de novo purine synthesis, since large amounts of PRPP are utilized for the conversion of orotic acid to uridine-5 -phosphate. However, incorporation studies of glycine-1- C in livers of orotic acid-fed rats revealed that the inhibition is caused rather by a depletion of the PRPP available for reaction with glutamine than by an effect on the condensation itself [160]. 

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

Little information is available concerning alterations in vitamin requirements in ARF. Reduced plasma concentrations of vitamin A, ascorbate, vitamin D, and vitamin E have been reported in patients with ARF, whereas vitamin K concentrations are relatively increased. Losses of vitamins via dialysis also must be considered. Traditional HD clears several water-soluble vitamins such as folic acid, vitamins C and B12, and pyridoxine, but not the highly protein-bound vitamins A and D. The clinical significance of these findings in ARF is unknown. Currently, it seems prudent to administer vitamins at least daily in doses recommended by the Nutrition Advisory Group of the American Medical Association for patients receiving PN (see Chap. 137)." Administration of ascorbic acid should be restricted to under 200 mg/day to avoid secondary oxalosis which may worsen renal function." If the enteral route is used for nutritional support, vitamin administration should at least meet the recommended daily allowances (RDAs). 

Table 3.1 Folic acid, Bg, B12 and cardiovascular outcomes. This table summarizes all the important double-blind randomized clinical trials with the use of folie acid, Bg and B12 vitamins for cardiovascular disease prevention. 5-MTHF 5-methyl tetrahydrofolate CKD chronic kidney disease CVD cardiovascular disease DVT deep vein thrombosis ESRD end stage renal disease FA folic acid f/u follow-up MI myocardial infarction RR relative risk UA unstable angina.

A recent study evaluated whether a combination of folic acid, vitamin Bg and vitamin B12 lowers risk of CVD among high-risk women with and without CVD. A total of 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or three or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive... 

Some findings of this clinical trial are that daily administration of folic acid, vitamin Bg and vitamin B12 to patients with recent stroke or transient ischemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins (VITATOPS Trial Study Group 2010). 

Folic acid, vitamin Bg and vitamin B12 are all cofactors in homocysteine metabolism. 

Zhang, S.M., Cook, N.R., Albert, C.M., Gaziano, J.M., Buring, J.E., and Manson, J.E., 2008. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women a randomized trial. The Journal of the American Medical Association. 300 2012-2021. 

The homocysteine hypothesis of vascular disease has attracted considerable interest since homocysteine levels are readily lowered by daily dietary supplementation with folic acid, vitamin Bg and vitamin B12 (Homocysteine Lowering Trialists Collaboration 2005), raising the prospect that dietary supplementation with these B vitamins could prevent vascular disease. Indeed, dietary supplementation with B vitamins to lower homocysteine levels of affected individuals is remarkably effective for the prevention of cardiovascular disease and other complications of homocystinuria (Yap et al. 2001). This review examines the evidence from the observational studies of homocysteine and vascular disease and from the randomized trials of B vitamin supplementation for the prevention of vascular disease. 

Noronha, J, M. and Silverman, M. (1962) On folic acid, vitamin B12, methionine and formiminoglutamic acid metabolism, in ... 

Generally, AA is determined individually, and only about a 10% of the published methods determine AA simultaneously with other analytes such as uric acid, glucose, fructose, dopamine, iodate, bromate, hypochlorite, thiourea, glutathione, hydrogen peroxide, acetylsalicylic acid, kojic acid, ascorbyl glucoside, paracetamol, cysteine, and other water soluble vitamins (thiamine [vitamin Bj], folic acid [vitamin B12], niacin [vitamin B3], riboflavin [vitamin B2], and pyridoxine [vitamin B ]). 

Methyl-tetrahydro folic acid is furthermore, together with vitamin B12 and B6, required to regenerate homocysteine (see Vitamin B12, Fig. 1). Homocysteine results when methionine is used as a substrate for methyl group transfer. During the last few years, homocysteine has been acknowledged as an independent risk factor in atherosclerosis etiology. Folic acid supplementation can help reduce elevated homocysteine plasma levels and is therefore supposed to reduce the risk of atherosclerosis as well [2]. 

A decrease in erythrocyte production can be multifactorial. A deficiency in nutrients (such as iron, vitamin B12, and folic acid) is a common cause that often is easily treatable. In addition, patients with cancer and CKD are at risk for developing a hypoproductive anemia. Furthermore, patients with chronic immune-related diseases (such as rheumatoid arthritis and systemic lupus erythematosus) can develop anemia as a complication of their disease. Anemia related to these chronic inflammatory conditions is typically termed anemia of chronic disease. 

B37. Brown, D. D., Silva, O. L., Gardiner, R. C., and Silverman, M., Metabolism of formiminoglutamic acid by vitamin B12 and folic acid deficient rats fed excess methionine. J. Biol. Chem. 235, 2058-2062 (1960). 

G12. Girdwood, R. H., Microbiological methods of assay in clinical medicine with particular reference to the investigation of deficiency of vitamin B12 and folic acid. Scot. Med. J. 5, 10-22 (1960). 

Group-transfer reactions often involve vitamins3, which humans need to have in then-diet, since we are incapable of realizing their synthesis. These include nicotinamide (derived from the vitamin nicotinic acid) and riboflavin (vitamin B2) derivatives, required for electron transfer reactions, biotin for the transfer of C02, pantothenate for acyl group transfer, thiamine (vitamin as thiamine pyrophosphate) for transfer of aldehyde groups and folic acid (as tetrahydrofolate) for exchange of one-carbon fragments. Lipoic acid (not a vitamin) is both an acyl and an electron carrier. In addition, vitamins such as pyridoxine (vitamin B6, as pyridoxal phosphate), vitamin B12 and vitamin C (ascorbic acid) participate as cofactors in an important number of metabolic reactions. 

The importance of this reaction is suggested from the observation that, if the level of the methylating agent is low (which can be caused by deficiency of vitamin B12 and/or folic acid), this can restrict formation of phosphatidyl... 

There is a possibility that a partial deficiency of some vitamins (especially vitamin B12 and folic acid) impairs the activity of key enzymes in the brain which might be one factor in the development of senile dementia and even Alzheimer s disease (see above for discussion of homocysteine in this context). 

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