The mild fasting hyperhomocysteinemia commonly observed in chronic (ie, >/=6 months posttransplantation) renal transplant recipients (RTRs) can be effectively treated with combined B-vitamin supplementation featuring supraphysiological doses of folic acid. There are no controlled data evaluating the comparative efficacy of supraphysiological versus standard multivitamin dose folic acid supplementation in reducing fasting total homocysteine (tHcy) levels among RTRs. We block-randomized 60 chronic, stable RTRs on the basis of their screening fasting tHcy level to 3 groups of 20 subjects treated for 12 weeks with folic acid at either 2.
View Article and Find Full Text PDFCancer Epidemiol Biomarkers Prev
September 1999
We previously reported (J. Chen et al., Cancer Res.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
September 1999
Serum creatinine, a surrogate for both renal function and homocysteine generation, is a determinant of fasting plasma total homocysteine levels in coronary artery disease (CAD) patients. We hypothesized that among stable-CAD patients with normal creatinine levels (ie, =1.4 mg/dL), serum cystatin C, a more sensitive indicator of glomerular filtration rate, would better predict fasting total homocysteine levels in comparison with serum creatinine.
View Article and Find Full Text PDFBackground: Total homocysteine levels are associated with arteriosclerotic outcomes.
Objective: To determine whether total homocysteine levels predict incident stroke in elderly persons.
Design: Prospective population-based cohort study with 9.
Background: The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. Elevated homocysteine concentrations are associated with an increased risk for vascular disease.
Objective: To identify reference ranges for serum total homocysteine concentration in U.
Background: Elevated plasma total homocysteine level has been associated with cardiovascular disease in many studies, mostly in Europe and North America. Data on persons from other areas and on associations with overall mortality are sparse.
Objective: To determine the relation of plasma homocysteine level to all-cause and cause-specific mortality.
Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation to methionine, which requires folate and vitamin B12 (or betaine in an alternative reaction); and transsulfuration to cystathionine, which requires pyridoxal-5'-phosphate. The two pathways are coordinated by S-adenosylmethionine, which acts as an allosteric inhibitor of the methylenetetrahydrofolate reductase reaction and as an activator of cystathionine beta-synthase. Hyperhomocysteinemia, a condition that recent epidemiological studies have shown to be associated with increased risk of vascular disease, arises from disrupted homocysteine metabolism.
View Article and Find Full Text PDFBackground: Although several studies have demonstrated an unadjusted association between folate status and fasting plasma total homocysteine (tHcy) levels among renal transplant recipients, no data confirming the strength or independence of this association have been reported.
Methods: We determined fasting plasma folate, B12, and pyridoxal 5'-phosphate (active vitamin B6) levels, along with other potential determinants of plasma tHcy levels (i.e.
Cereal grain flour products fortified with 140 microg folic acid per 100 g flour became widely available in southeast New England by July 1997. We hypothesized that improved folate status secondary to this fortification policy would have a much more limited impact on the prevalence of mild fasting hyperhomocysteinemia in renal transplant versus coronary artery disease patients. Between October 1997 and October 1998, fasting plasma total homocysteine (tHcy), folate and vitamin B12 levels were determined in a total of 86 renal transplant patients with stable allograft function, and 175 coronary artery disease patients whose serum creatinine was (1.
View Article and Find Full Text PDFBackground: Elevated fasting total homocysteine (tHcy) levels were recently shown to confer an independent risk for all-cause and cardiovascular disease (CVD) mortality among selected Norwegian patients with confirmed coronary heart disease. We examined whether elevated fasting plasma tHcy levels were predictive of all-cause and CVD mortality in a large, population-based sample of elderly US women and men.
Methods: Nonfasting plasma tHcy levels were determined in 1933 elderly participants (mean age, 70 +/- 7 years; 58.
Background: In 1996, the Food and Drug Administration issued a regulation requiring all enriched grain products to be fortified with folic acid to reduce the risk of neural-tube defects in newborns. Fortification (140 microg per 100 g) began in 1996, and the process was essentially complete by mid-1997.
Methods: To assess the effect of folic acid fortification on folate status, we measured plasma folate and total homocysteine concentrations (a sensitive marker of folate status) using blood samples from the fifth examination (January 1991 to December 1994) of the Framingham Offspring Study cohort for baseline values and the sixth examination (January 1995 to August 1998) for follow-up values.
Cancer Epidemiol Biomarkers Prev
March 1999
To investigate the incidence of breast cancer and prediagnostic serum levels of folate, B12, and pyridoxal 5'-phosphate (B6), we conducted a nested case-control study using resources from the Washington County (Maryland) serum bank. In 1974, 12,450 serum specimens were donated, and in 1989, 14,625 plasma specimens were donated by female residents of Washington County. One hundred ninety-five incident breast cancer cases and 195 controls were matched by age, race, menopausal status at donation, and cohort participation as well as by date of blood donation.
View Article and Find Full Text PDFBackground: The elevation of circulating total homocysteine concentrations in a fasting state is associated with an increased risk of occlusive vascular disease.
Objective: The primary goals of this study were to describe the distribution of serum total homocysteine concentrations in the United States and to test for differences in homocysteine concentrations among sex, age, and race-ethnicity categories.
Design: Using surplus sera from phase 2 of the third National Health and Nutrition Examination Survey, we measured serum total homocysteine concentrations for a nationally representative sample of 3766 males and 4819 females aged > or = 12 y.
Background: Elevated blood concentrations of total homocysteine (tHcy) have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. Previous studies identified suboptimal nutritional status and dietary intake of folate, vitamin B-6, and vitamin B-12 as determinants of elevated tHcy.
Objective: We identified other nutritional factors associated with tHcy in 260 retired schoolteachers in the Baltimore metropolitan area.
Serum creatinine, a surrogate for both renal function and homocysteine generation, is an important determinant of fasting plasma total homocysteine levels in stable renal transplant recipients. In this study, it is hypothesized that among stable renal transplant recipients with normal creatinine levels (i.e.
View Article and Find Full Text PDFThe intestinal absorption of folate occurs at the monoglutamyl level, and an important measure of food folate bioavailability is how much folate from the food reaches the intestinal sites in forms that can readily be absorbed. In the absence of protecting agents, e.g.
View Article and Find Full Text PDFA common mutation (C677T) in the gene encoding for methylenetetrahydrofolate reductase (MTHFR) (5-methyltetrahydrofolate:(acceptor) oxidoreductase, EC 1.7.99.
View Article and Find Full Text PDFHyperhomocysteinemia is a condition which, in the absence of kidney disease, indicates a disrupted sulfur amino acid metabolism, either because of vitamin deficiency (folate, B12 and B6) or a genetic defect. Epidemiologic evidence suggests that mild hyperhomocysteinemia is associated with increased risk of arteriosclerotic disease and stroke. The relationship between hyperhomocysteinemia and thrombosis has been investigated in 10 studies involving a total of 1200 patients and 1200 controls.
View Article and Find Full Text PDFBackground: Stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia, which is a risk factor for arteriosclerosis.
Objective: To determine the effect of treatment with 1) vitamin B6 or 2) folic acid plus vitamin B12 on fasting and post-methionine-loading plasma total homocysteine levels in renal transplant recipients.
Design: Block-randomized, placebo-controlled, 2 x 2 factorial study.
Arterioscler Thromb Vasc Biol
November 1997
There is an excess prevalence of hyperhomocysteinemia in dialysis-dependent end-stage renal disease (ESRD) patients. Cross-sectional studies of the relationship between elevated total homocysteine (tHcy) levels and prevalent cardiovascular disease (CVD) in this patient population suffer from severe methodologic limitations. No prospective investigations examining the association between tHcy levels and the subsequent development of arteriosclerotic CVD outcomes among maintenance dialysis patients have been reported.
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