Low plasma levels of vitamin B(6) are independently associated with a heightened risk of deep-vein thrombosis.
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BACKGROUND: Elevated plasma levels of total homocysteine (tHcy) before and after an oral methionine load (PML) are associated with an elevated risk of deep-vein thrombosis (DVT). We investigated whether plasma levels of B vitamins that are involved in Hcy metabolism are associated with an elevated risk of DVT. METHODS AND RESULTS: We compared 397 cases with previous DVT with 585 matched healthy controls. The plasma levels of folate, vitamin B(12), vitamin B(6,), and fasting and PML tHcy were measured. The ORs for DVT associated with high (>95th percentile) fasting levels and PML increases of tHcy were 2.1 (95% CI, 1.2 to 3.4) and 2.4 (95% CI, 1.5 to 3.9) after adjustment for established risk factors for DVT. Fasting plasma levels and PML increases in tHcy correlated negatively with vitamin levels. The crude OR for folate levels in the lowest quartile compared with the highest was 1.5 (95% CI, 1.1 to 2.1), and that for B(6) levels in the lowest and second quartiles compared with the highest was 1.5 (95% CI, 1.0 to 2.1). However, after adjustment for established risk factors and fasting and PML tHcy, the ORs for B(6) levels in the lowest and second quartiles only remained statistically significant (lowest quartile: OR, 1.8; 95% CI, 1.2 to 2.8; second quartile, OR, 1.9; 95% CI, 1.3 to 2.9). CONCLUSIONS: High fasting and PML tHcy and low vitamin B(6) plasma levels are associated with an elevated risk for DVT independently of established risk factors for DVT. The association of low vitamin B(6) levels with the risk for DVT is independent of fasting and PML tHcy levels. (+info)
Plasma homocysteine level in relation to folate and vitamin B6 status in apparently normal men.
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The prevalence of subclinical deficiencies of folate and vitamin B6 in India is high and preliminary investigation showed higher mean plasma total homocysteine level in Indians compared with the values reported for western populations. The present study was carried out in 40 apparently normal men to examine the relationship between plasma total homocysteine level and folate and vitamin B6 status. The mean plasma homocysteine level was high and was inversely related to folate status as judged by red blood cells or plasma folate concentrations. There was no significant relationship between fasting homocysteine level and vitamin B6 status. (+info)
Cardiovascular risk in the Asia-Pacific region from a nutrition and metabolic point of view: vitamin deficiencies.
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In the past, recommended vitamin or micronutrient intakes have often been based on levels that were adequate to prevent clinical deficiencies from developing. Once these levels were reached, clinicians and nutrition scientists generally attributed little value to higher vitamin intake from supplements or food sources. Evidence has continued to mount showing that the intake and serum concentration of certain vitamins above those necessary to prevent clinical deficiencies, might importantly influence health status. This paper discusses the association of anti-oxidant vitamins and cardiovascular disease, and the association of low intake or serum concentrations of folate, vitamin B6 and vitamin B12, and elevated serum homocysteine, resulting in an increase in vascular disease risk. (+info)
Elevated plasma 4-pyridoxic acid in renal insufficiency.
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BACKGROUND: Renal insufficiency is associated with altered vitamin B-6 metabolism. We have observed high concentrations of 4-pyridoxic acid, the major catabolite of vitamin B-6 metabolism, in plasma during renal insufficiency. OBJECTIVE: The objective was to evaluate the renal handling of 4-pyridoxic acid and the effects of renal dysfunction on vitamin B-6 metabolism. DESIGN: We measured the renal clearance of 4-pyridoxic acid and creatinine in 17 nonpregnant, 17 pregnant, and 16 lactating women. We then examined the influence of vitamin B-6 or alkaline phosphatase activity on the ratio of 4-pyridoxic acid to pyridoxal (PA:PL) in plasma in 10 men receiving a low (0.4 mg pyridoxine.HCl/d) or high (200 mg pyridoxine.HCl/d) vitamin B-6 intake for 6 wk, in 10 healthy subjects during a 21-d fast, in 1235 plasma samples from 799 people screened for hypophosphatasia, and in 67 subjects with a range of serum creatinine concentrations. RESULTS: Renal clearance of 4-pyridoxic acid was 232 +/- 94 mL/min in nonpregnant women, 337 +/- 140 mL/min in pregnant women, and 215 +/- 103 mL/min in lactating healthy women. These values were approximately twice the creatinine clearance, indicating that 4-pyridoxic acid is at least partially eliminated by tubular secretion. Elevated plasma creatinine concentrations were associated with marked elevations in 4-pyridoxic acid and PA:PL. PA:PL was not affected by wide variations in vitamin B-6 intake or by the wide range of pyridoxal-P concentrations encountered while screening for hypophosphatasia. CONCLUSIONS: Plasma 4-pyridoxic acid concentrations are markedly elevated in renal insufficiency. Plasma PA:PL can distinguish between increases in 4-pyridoxic acid concentrations due to increased dietary intake and those due to renal insufficiency. (+info)
Plasma homocysteine levels in Taiwanese vegetarians are higher than those of omnivores.
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Mild hyperhomocysteinemia is an independent risk factor for cardiovascular disease and may result from a deficiency of folate, vitamin B-6 or vitamin B-12. Because vitamin B-12 deficiency is often associated with vegetarianism, this study was designed to examine the effect of Taiwanese vegetarian diets on B-vitamin status and plasma homocysteine levels. Female Buddhist lacto-vegetarians (n = 45; 31-45 y) and matched omnivores (n = 45) recruited in Hualien, Taiwan, were investigated. Taiwanese vegetarians consumed normal amount of folate, but only 21% of Taiwan Recommended Daily Nutrient Allowances (RDNA) values of vitamin B-12. Compared with the omnivores, the vegetarians had significantly higher levels of plasma folate (14.79 +/- 7.70 vs. 11.98 +/- 8.29 nmol/L), but lower levels of vitamin B-12 (207.7 +/- 127.1 vs. 403.5 +/- 138.9 pmol/L). Fasting plasma homocysteine levels were significantly higher in vegetarians than in omnivores (mean: 11.20 +/- 4.27 vs. 8.64 +/- 2.06 micromol/L; median: 10.5 vs. 8.5 micromol/L). Fasting plasma homocysteine was inversely correlated with plasma folate and vitamin B-12 in the vegetarian group. Multiple regression analysis revealed that plasma folate, vitamin B-12 and creatinine were independent determinants of homocysteine variation and contributed to 38.6% of homocysteine variation in the vegetarians. Compared with the omnivores, vegetarians also had significantly lower serum levels of valine, isoleucine, leucine, lysine, alanine and arginine, but higher levels of glycine. In the vegetarian group, fasting plasma homocysteine correlated negatively with serum threonine, lysine, histidine, arginine and cystine, and these amino acids contributed to 38.7% of homocysteine variation. In conclusion, the Buddhist nuns who consumed a lacto-vegetarian diet had mildly elevated fasting plasma homocysteine levels presumably due to lower levels of plasma vitamin B-12. (+info)
Total homocysteine lowering treatment among coronary artery disease patients in the era of folic acid-fortified cereal grain flour.
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The prevalence of deficient plasma folate status and elevated total plasma levels of homocysteine (tHcy), have been dramatically reduced after fortification of all enriched cereal grain flour products with folic acid at 140 microg/100 g flour. Against this new background fortification, we evaluated the tHcy-lowering efficacy of pharmacological dose, folic acid-based vitamin B supplementation among stable coronary artery disease (CAD) patients. Using a 2x2 factorial design, 131 stable CAD patients (mean age 60.1 years; 29.8% women) were randomly assigned to receive a combination of folic acid 2.5 mg/d, riboflavin 5 mg/d, + B12 0.4 mg/d, or placebo, with or without vitamin B6 50 mg/d, for 12 weeks of treatment. ANCOVA adjusted for baseline fasting tHcy levels revealed only very modest (ie, approximately 1.0 micromol/L), albeit statistically significant (P<0.05), reductions in mean fasting tHcy levels afforded by the folic acid-containing treatments. Additional analyses indicated that none of the treatments provided a statistically significant reduction in the 2-hour post-methionine increase in tHcy levels, relative to placebo treatment. CAD patients exposed to cereal grain flour products fortified with folic acid who receive high-dose, folic acid-containing vitamin B regimens, experience only very modest reductions in their mean fasting plasma tHcy levels. These findings have important implications for the statistical power of clinical trials testing the hypothesis that tHcy-lowering treatment may reduce recurrent atherothrombotic event rates. (+info)
The Arabidopsis salt overly sensitive 4 mutants uncover a critical role for vitamin B6 in plant salt tolerance.
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Salt stress is a major environmental factor influencing plant growth and development. To identify salt tolerance determinants, a genetic screen for salt overly sensitive (sos) mutants was performed in Arabidopsis. We present here the characterization of sos4 mutants and the positional cloning of the SOS4 gene. sos4 mutant plants are hypersensitive to Na(+), K(+), and Li(+) ions. Under NaCl stress, sos4 plants accumulate more Na(+) and retain less K(+) compared with wild-type plants. SOS4 encodes a pyridoxal kinase that is involved in the biosynthesis of pyridoxal-5-phosphate, an active form of vitamin B6. The expression of SOS4 cDNAs complements an Escherichia coli mutant defective in pyridoxal kinase. Supplementation of pyridoxine but not pyridoxal in the growth medium can partially rescue the sos4 defect in salt tolerance. SOS4 is expressed ubiquitously in all plant tissues. As a result of alternative splicing, two transcripts are derived from the SOS4 gene, the relative abundance of which is modulated by development and environmental stresses. Besides being essential cofactors for numerous enzymes, as shown by pharmacological studies in animal cells, pyridoxal-5-phosphate and its derivatives are also ligands for P2X receptor ion channels. Our results demonstrate that pyridoxal kinase is a novel salt tolerance determinant important for the regulation of Na(+) and K(+) homeostasis in plants. We propose that pyridoxal-5-phosphate regulates Na(+) and K(+) homeostasis by modulating the activities of ion transporters. (+info)
Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12.
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BACKGROUND: In a recent uncontrolled retrospective report we suggested that the long-term supplementation of high-dose, i.v. folinic acid combined with high-dose i.v. pyridoxine was highly effective in correcting plasma total homocysteine (tHcy) concentrations in haemodialysis patients. To confirm these findings, we conducted a randomized, controlled trial aimed at evaluating whether i.v. or oral folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients compared with oral folic acid. METHODS: In a 6-month prospective, randomized, controlled trial, 60 chronic haemodialysis patients, matched for age, gender, dialysis duration, and average screening pre-treatment-fasting tHcy levels, were given either 50 mg/week of i.v. calcium folinate (group 1), 50 mg/week of oral calcium folinate (group 2), or 45 mg/week oral folic acid (group 3). All 60 patients also received 750 mg/week of i.v. vitamin B6 and 3 mg/week of oral vitamin B12. RESULTS: Fasting tHcy decreased significantly and to a similar extent in the three groups after 2 months of treatment and remained stable at 4 and 6 months (16.6+/-3.5, 18.3+/-4, and 19.1+/-3.1, in groups 1, 2, and 3, respectively, P=NS). Mean percentage reduction at 6 months was also similar in the three treatment groups (46, 43, and 42% in groups 1, 2, and 3, respectively, P=NS). CONCLUSIONS: These findings show that the tHcy-lowering effects of high-dose i.v. folinic acid, oral folinic acid, or oral folic acid were comparable, suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is not due to abnormal folate metabolism. Furthermore, they are compatible with the view that other abnormalities are also involved in the impaired clearance of homocysteine in uraemic patients. (+info)