Homocysteine plasma concentration

Koyama, K., Usami, T., Takeuchi, O., Morozumi, K., and Kimura, G., 2002. Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high-dose folic acid supplementation. Nephrology Dialysis Transplantation. 17 916-922. 

Brevick A, Vollset S, Tell G, Refsum H, Ueland P, Locken E, Drevon C and Andersen L. 2005. Plasma concentration of folate as a biomarker for the intake of fruit and vegetables the Hordaland Homocysteine Study. Am J Clin Nutr 81 434 139. 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

Compared with healthy controls, 51 patients with epilepsy taking a variety of antiepileptic drugs (mostly carbamaze-pine) had higher mean plasma concentrations of homocysteine (130). This effect, which could be related to reductions in the concentrations of folate and vitamin B6, was likely to be drug-induced, but a causative role of the underlying disease could not be excluded. Although homocysteine is an experimental convulsant and a risk factor for atherosclerosis, the clinical relevance of these findings is uncertain. 

Cilastatin prevents the metabolism of imipenem by renal tubular dipeptidase, which also hydrolyses the glutathione metabolite cysteinylglycine. In patients taking imipenem + cilastatin, plasma concentrations of cysteinylglycine were significantly increased, while cysteine concentrations fell and homocysteine concentrations were unchanged (483). The clinical significance of this is not clear. 

Schwaninger M, Ringleb P, Winter R, Kohl B, Fiehn W, Rieser PA, Waiter-Sack I. Elevated plasma concentrations of homocysteine antiepileptic drug treatment. Epilepsia 1999 40(3) 345-50. 

As shown in the review of the homocysteine metabolism, vitamin B 2, vitamin B6, and folate are important cofactors in the metabolic pathways for homocysteine elimination, and consequently, deficiencies of these vitamins are characterized by elevated plasma concentrations of tHcy. Hyperhomocysteinemia is also frequently found in diseases such as renal failure, rheumatic and auto-immune diseases, hypothyroidism, and malignancies. Several drugs are also known to increase plasma tHcy concentrations (16-24). 

Amino acids (AA) have also been studied on microdevices for development of microclinical analysis devices. In urine, normal ranges for standard amino acids and their metabolites range from 0 to 24 mM, with abnormal concentrations indicative of a number of disease states. Plasma concentrations of certain amino acids can also be used for disease detection. Elevated homocysteine levels in plasma is an independent risk factor for cardiovascular disease. Microdevices employing end-column amperometric detection were used for the determination... 

Epidemiological smdies suggest that hyperhomocysteineima is most significantly correlated with low folate status, but there is also a significant association with low vitamin Bg status (SeUiub et al., 1993). Trials of supplementation have shown that whereas folate supplements lower fasting homocysteine in moderately hyperhomocysteinemic subjects, supplements of 10 mg per day of vitamin Bg have no effect, although supplements do reduce the peak plasma concentration of homocysteine after a test dose of methionine (Ubbink et al., 1994 Ubbink, 1997 Dierkes et al., 1998). This can probably be explained on the basis of the kinetics of the enzymes involved the of cystathionine... 

It thus seems unlikely that intakes of vitamin Bg above amounts that are adequate to prevent metabolic signs of deficiency will be beneficial in lowering plasma concentrations of homocysteine (ffomocysteine Lowering Trialists Collaboration, 1998). 

Although folate is widely distributed in foods, dietary deficiency is not uncommon, and a number of commonly used drugs can cause folate depletion. Marginal folate status is a factor in the development of neural tube defects and supplements of 400 fj,g per day periconceptually reduce the incidence of neural tube defects significantly. High intakes of folate lower the plasma concentration of homocysteine in people genetically at risk of hyperhomo-cysteinemia and may reduce the risk of cardiovascular disease, although as yet there is no evidence from intervention studies. There is also evidence that low folate status is associated with increased risk of colorectal and other cancers and that folate may be protective. Mandatory enrichment of cereal products with folic acid has been introduced in the United States and other countries, and considered in others. 

Deficiency of vitamins Bg, B12, or folate are aU associated with elevated plasma homocysteine, with vitamin Bg deficiency as a result of impaired activity of cystathionine synthetase (Section 9.5.5) and folate and vitamin B12 as a result of impaired activity of methionine synthetase (Section 10.3.4). In subjects with apparently adequate intakes of vitamins Bg and B12, supplements of these two vitamins have little or no effect on fasting plasma homocysteine, although additional vitamin Bg reduces the plasma concentration of homocysteine after a test dose of methionine. By contrast, supplements of... 

At tbe time that the U. K. and European Union reference intakes of folate shown in Table 10.3 were being discussed, the results of intervention trials for the prevention of neural tube defects (Section 10.9.4) were only just becoming available. At that time, there was no information concerning the effects of folate status onhyperhomocysteinemia (Section 10.3.4.2). TheU.S./Canadianreport (Institute of Medicine, 1998) notes specifically that protective effects with respect to neural tube defects were not considered relevant to the determination of the Dietary Reference Intake of folate, and there was insufficient evidence to associate higher intakes of folate (and lower plasma concentrations of homocysteine) with reduced risk of cardiovascular disease. 

Supplements of400 /xg per day of folic acid, begun before conception, halve the risk of neural tube defect (Section 10.9.4), and similar supplements reduce the plasma concentration of homocysteine in people homozygous for the ther-molabile variant of methylene-tetrahydrofolate reductase (Section 10.3.4.2), although it is not known whether or not this will reduce their risk of cardiovascular disease. A number of manufacturers voluntarily enrich foods with folic acid. In the United States and other countries, there is mandatory enrichment of cereal products with folic acid. 

High plasma concentrations of homocysteine are associated with increased risk of thrombotic vascular... 

Concentrations of plasma homocysteine, plasma pyridoxal 5 -phosphate (active vitamin B6), serum folate, erythrocyte folate, and serum vitamin B12 have been measured both during fasting and after methionine in 60 epileptic patients (aged 14-18 years) and 63 sex- and age-matched controls before therapy and after 1 year of therapy with valproate or carbamazepine (33). After 1 year the patients who took valproate and carbamazepine had significantly increased plasma homocysteine concentrations compared with both baseline and control values and there was a significant fall in serum folate and plasma pyridoxal 5 -phosphate. Serum vitamin B12 and erythrocyte folate were unchanged. 

The biochemical phenotype of homocystinuria is characterized by increased plasma concentrations of methionine, free homocysteine and cysteine-homocysteine disulfide, together with low cystine (Figure 55-6, C). Determination of total homocysteine after treatment of the sample with... 

Epidemiological studies. Epidemiology is the study of the distribution and determinants of disease frequency in human populations and the application of this study to control health problems. Therefore, epidemiological studies harvest valid and precise information about the causes, prevention and treatments for disease. Types of epidemiological studies are experimental studies and observational studies (cohort and case-control studies). Homocysteine. Homocysteine is a sulfur-containing amino acid that occurs naturally in all humans. Elevated plasma homocysteine concentration is linked to an increased risk of ischemic stroke. Lowering homocysteine plasma levels is linked to increasing the intake of folic acid and vitamins Bg and Bi2-... 

Red cell folate is a more sensitive indicator of serum folate deficiency. Low red cell folate accompanied by high plasma concentration of homocysteine is a better guide to the degree of deficiency than serum folate (Reynolds 2006). 

Metabolism In a prospective controlled study in 74 patients taking isotretinoin for cystic acne, blood concentrations of homocysteine, vitamin B12, and folate were assessed before and after 45 days of isotretinoin therapy [39 ]. The control group consisted of 80 individuals. Homocysteine concentrations were significantly higher in those who took isotretinoin. The vitamins were unaffected, but serum lipids and liver enzymes increased significantly. These effects may have been due to inhibition of cystathionine-beta-synthase, an enzyme required for the metabolism of homocysteine by either the drug or liver dysfunction. Daily supplementation with vitamin B12 and folate can lower plasma concentrations of homocysteine, and the authors therefore recommended the use of these vitamins in patients taking isotretinoin. 

A number of studies have shown that while folate supplements lower fasting homocysteine in moderately hyperhomocysteinemic subjects, lOmg/day vitamin Bg has no effect, although they do reduce the peak plasma concentration of homocysteine following a test dose of methionine. 

Homocysteine arises from dietary methionine. High levels of homocysteiae (hyperhomocysteinemia) are a risk factor for occlusive vascular diseases including atherosclerosis and thrombosis (81—84). In a controlled study, semm folate concentrations of <9.2 nmol/L were linked with elevated levels of plasma homocysteiae. Elevated homocysteine levels have beea associated also with ischemic stroke (9). The mechanism by which high levels of homocysteine produce vascular damage are, as of yet, aot completely uaderstood. lateractioa of homocysteiae with platelets or eadothehal cells has beea proposed as a possible mechanism. Clinically, homocysteine levels can be lowered by administration of vitamin B, vitamin B 2> foHc acid. 

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