Hyperhomocysteinemia in hemodialysis patients: effects of 12-month supplementation with hydrosoluble vitamins.
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BACKGROUND: High-efficiency hemodialysis may induce a deficiency in hydrosoluble vitamins. Supplementation with B-complex vitamins has been shown to lower serum homocysteine concentrations in several groups, but relatively few studies have concerned hemodialysis patients. Our objectives were to determine the status in B-complex vitamins in a large cohort of unsupplemented hemodialysis patients and to assess the effects of supplementation with hydrosoluble vitamins on serum homocysteine over one year. METHODS: Serum total homocysteine (tHcy), vitamin B12, folate, pyridoxal-5'-phosphate (P-5'-P; the active moiety of vitamin B6), as well as red blood cell folate concentrations, were measured in 168 chronic dialysis patients on three times weekly high-efficiency hemodialysis and not supplemented with hydrosoluble vitamins. Their methylenetetrahydrofolate reductase C677T (MTHFR) genotypes were also determined (homozygotes TT, heterozygotes CT, without mutation CC). All involved patients were then supplemented with hydrosoluble vitamins (once daily by mouth, DiaVite; R&D Laboratories, Minneapolis, MN, USA), and half of them were randomized to receive in addition 10 mg intravenously of folic acid posthemodialysis (30 mg intravenously per week). Serum tHcy was monitored after 6 and 12 months of supplementation in the 140 and 128 patients available for follow-up. RESULTS: At baseline, serum and red blood cell folate concentrations were within normal limits in all patients except for two with borderline serum folate (mean values of 21 +/- 8 and 1195 +/- 454 nmol/L), whereas serum vitamin B12 and P-5'-P were below normal in 11 and 65 patients, respectively (mean values of 327 +/- 215 pmol/L and 19 +/- 16 nmol/L for the 168 patients). Initial tHcy levels were increased in all patients (mean 33.3 +/- 16.6 for a normal below 11.8 +/- 1.5 micromol/L); tHcy significantly decreased to 23.5 +/- 7.6 micromol/L after six months (P < 0.0001 vs. baseline) and to 21.7 +/- 6.1 micromol/L after 12 months (P < 0.0001 vs. baseline) for the entire group, but was normalized in only four patients at 12 months. After six months, the mean reduction in tHcy was slightly but significantly greater for patients receiving intravenous folic acid (12.2 +/- 18.5 micromol/L) compared with patients not receiving it (8.3 +/- 9.8 micromol/L, P < 0.05). However, at 12 months, no difference between both subgroups persisted. When considering the different genotypes, tHcy at baseline tended to be higher for TT than CT and CC (39.8 +/- 30.9 vs. 31.4 +/- 10.5 vs. 31.6 +/- 11.8 micromol/L) and decreased to respective values of 21.1 +/- 6.9 versus 21.4 +/- 6.1 versus 22.2 +/- 5.9 micromol/L at 12 months. The impact of the addition of folic acid to DiaVite appeared particularly significant in TT patients at six months. CONCLUSIONS: (1) Hyperhomocysteinemia was present in 100% of our hemodialysis patients. (2) Nearly 40% of our unsupplemented hemodialysis patients were deficient in vitamin B6. (3) Supplementation with DiaVite(R) has resulted in significant tHcy reductions for all three genotypes. (4) The impact of the proposed supplementation protocol was found after six months and was maintained, but did not increase further after 12 months of the same regimen. (5) The addition of intravenous folic acid has been associated with a more pronounced decrease in tHcy in TT patients. (+info)
The controversy over homocysteine and cardiovascular risk.
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Elevated plasma total homocysteine (tHcy) is a risk factor for occlusive cardiovascular disease (CVD). This concept is based on the observations of premature vascular disease in patients with homocystinuria, the relation between tHcy and both clinical CVD as well as preclinical atherosclerotic disease, the relation between tHcy in children and CVD in their parents or relatives, and reduction in CVD or surrogate endpoints after tHcy-lowering intervention with B vitamins. Plausible mechanisms include the in vivo interference with nitric oxide-dependent reactive vasodilatation. Some observations have raised questions about tHcy as a risk factor. 1) Some prospective studies showed a weak relation or no relation between tHcy and CVD. 2) Several traditional risk factors are associated with tHcy and may confound the relation between tHcy and CVD. 3) tHcy is related to renal function, and hyperhomocysteinemia may reflect early nephrosclerosis. 4) The C677T transition of the methylenetetrahydrofolate reductase gene causes a moderate increase in tHcy but no or only minor increased CVD risk. However, the strength of some of these arguments can be questioned because there is increasing evidence that tHcy is a proximate risk factor provoking the acute event, it strongly interacts with traditional risk factors, and it may predict CVD or death in patients with chronic renal failure. Furthermore, the studies of the C677T polymorphism lack statistical power, and the TT genotype may even modulate CVD risk independently of homocysteine. Thus, only placebo-controlled intervention studies with tHcy-lowering B vitamins and clinical endpoints can provide additional valid arguments for the debate over whether tHcy is a causal CVD risk factor. (+info)
Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet.
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Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease. Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies, no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine. We determined whether a multivitamin/mineral supplement formulated at about 100% Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid. In this randomized, double-blind, placebo-controlled trial, 80 free-living men and women aged 50-87 y with total plasma homocysteine concentrations of > or =8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet. After the 8-wk treatment, subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls (P: < 0.01). Plasma folate, pyridoxal phosphate (PLP) and vitamin B-12 concentrations were increased 41.6, 36.5 and 13.8%, respectively, in the supplemented group, whereas no changes were observed in the placebo group. The mean homocysteine concentration decreased 9.6% in the supplemented group (P: < 0.001) and was unaffected in the placebo group. There were no significant changes in dietary intake during the intervention. Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet. (+info)
Vitamin profile of 174 mothers and newborns at parturition.
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Thiamin, biotin, B12, folate, pantothenate, riboflavin, nicotinate, B6, vitamins A, E, C, and beta-cartene was estimated in the blood of 174 mothers and in the cord blood of their neonates at parturition. A vitamin profile of normal preganancy was established for mother and neonate. This was based on values obtained from 95 percent confidence limits in 74 mothers not taking oral vitamins and 133 mothers ingesting various vitamin supllements. Circulating vitamin levels in 38 neonates born to mothers with no laboratory evidence of hypovitaminemia was persented. The higher incidence of hypobitaminemia in gravidas not taking vitamins was folate, thiamin, vitamins A, C, B12, BL and nicotinate in descending order. Ingestion of vitamins supplements reduced the incidence of hypovitaminemia. A similar relationship held for neonates from these mothers. However, despite vitamin ingestion thiamin, folate, vitamins C, A, B6, B12 and nicotinate hypovitaminemia was evident. There was an approximate 1:2-5 ratio between mother and neonate blood vitamins; vitamins A, B6, E, and beta-carotene were exceptions. Vitamin B6 ran parallel, while vitamins A, B6, E, and beta-carotene ratios reversed in favor of the mother at an approximate ratio of 2:1, 4:1 and 7:1, respectively. It is concluded that vitamin profile for mother and neonate, taking into account values established from a lorge gravid population, should now permit an evaluation of the effects of hypoviteminemia on the outcome of pregnancy and infant health. (+info)
Nutrient-dense foods and exercise in frail elderly: effects on B vitamins, homocysteine, methylmalonic acid, and neuropsychological functioning.
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BACKGROUND: Frail elders are at risk of suboptimal micronutrient status, functional decline, and neurologic disorders. The influence of oral multimicronutrients in physiologic doses and of moderately intense physical exercise on homocysteine (Hcy), methylmalonic acid (MMA), and neurologic functioning have not yet been investigated. OBJECTIVE: Our goal was to determine the effects of enriched foods and exercise on blood vitamins, Hcy, MMA, and neuropsychological functioning in the frail. DESIGN: A 17-wk randomized controlled intervention trial was used to study 1) enriched foods plus a social program, 2) regular foods plus exercise, 3) enriched foods plus exercise, and 4) regular foods plus a social program. Enriched foods contained multiple micronutrients (25-100% of the Dutch recommended dietary allowances); exercises focused on strength, coordination, flexibility, and endurance. Vitamin (cobalamin, red blood cell folate, and pyridoxal 5'-phosphate), Hcy, and MMA concentrations were measured and 2 neuropsychological tests were conducted. RESULTS: Vitamin concentrations were higher in the supplemented groups than in the unsupplemented groups (P < 0.001; total n = 130). Compared with baseline, cobalamin in the supplemented groups was increased by 22%, plasma folate by 101%, red blood cell folate by 87%, and pyridoxal 5'-phosphate by 68%. Concentrations in the unsupplemented groups changed by -2%, -6%, 1%, and -13%, respectively. Hcy decreased by 25% and MMA by 30% in the supplemented groups, compared with a small increase in Hcy (2%) and decrease in MMA (9%) in the unsupplemented groups. Exercise did not significantly affect vitamin, Hcy, or MMA concentrations. No significant effect of either intervention was observed on the neuropsychological tests. CONCLUSIONS: The decrease in Hcy and MMA in frail elders confirms a subclinical metabolic deficiency state. Enriched foods containing physiologic amounts of micronutrients have a beneficial effect on these metabolites. No effects of B vitamins on mental health were identified. (+info)
Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y.
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BACKGROUND: An elevated plasma total homocysteine (tHcy) concentration is associated with an increased risk of cardiovascular diseases. Folate, riboflavin, vitamin B-6, and vitamin B-12 are essential in homocysteine metabolism. OBJECTIVE: The objective was to describe the association between dietary intakes of folate, riboflavin, vitamin B-6, and vitamin B-12 and the nonfasting plasma tHcy concentration. DESIGN: A random sample of 2435 men and women aged 20-65 y from a population-based Dutch cohort examined in 1993-1996 was analyzed cross-sectionally. RESULTS: Univariately, intakes of all B vitamins were inversely related to the plasma tHcy concentration. In multivariate models, only folate intake remained inversely associated with the plasma tHcy concentration. Mean plasma tHcy concentrations (adjusted for intakes of riboflavin, vitamin B-6, vitamin B-12, and methionine and for age, smoking, and alcohol consumption) in men with low (first quintile: 161 microg/d) and high (fifth quintile: 254 microg/d) folate intakes were 15.4 and 13.2 micromol/L, respectively; in women, plasma tHcy concentrations were 13.7 and 12.4 micromol/L at folate intakes of 160 and 262 microg/d, respectively. In men, the difference in the mean plasma tHcy concentration between men with low and high folate intakes was greater in smokers than in nonsmokers (2.8 compared with 1.6 micromol/L) and greater in nondrinkers than in drinkers of >2 alcoholic drinks/d (3.5 compared with 1.4 micromol/L). In women, the association between folate intake and plasma tHcy was not modified by smoking or alcohol consumption. CONCLUSIONS: In this Dutch population, folate was the only B vitamin independently inversely associated with the plasma tHcy concentration. Changing dietary habits may substantially influence the plasma tHcy concentration in the general population. (+info)
Lifestyle factors and plasma homocysteine concentrations in a general population sample.
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The authors cross-sectionally investigated the extent to which coffee, tea, and alcohol consumption, physical activity, and smoking were associated with nonfasting total plasma homocysteine concentrations in a random sample of 3,025 Dutch adults aged 20--65 years from a population-based cohort examined in 1993--1996 (n = 19,066). The lifestyle factors most strongly associated with plasma total homocysteine level were smoking (positive), alcohol drinking (negative), and coffee consumption (positive). The smoking effect was most prominent in women, and the alcohol effect was most pronounced in men. Data indicated that independently of other lifestyle factors, age, and intake of folate and B vitamin supplements, a change in lifestyle could result in a 0.1- to 1.7-micromol/liter change in plasma total homocysteine level. The authors conclude that lifestyle changes could result in a public-health-relevant change in plasma total homocysteine concentrations. (+info)
Plasma homocysteine is not subject to seasonal variation.
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BACKGROUND: Studies investigating the relationship between plasma total homocysteine (tHcy) and vascular disease usually rely on a single measurement. Little information is available, however, on the seasonal variability of plasma tHcy. The aim of this study was to investigate the seasonal variation in fasting plasma tHcy and related B-vitamin intake and status in a group of people who did not consume fortified foods or take B-vitamin supplements. METHODS: In this longitudinal study, a group of 22 healthy people were followed for 1 year. A fasting blood sample and dietary information were collected from each individual every 3 months, i.e., at the end of each season. RESULTS: There was no significant seasonal variation in plasma tHcy or in B-vitamin intake or status with the exception of red cell folate (significantly lower in spring compared with autumn or winter) and serum folate (significantly lower in spring compared with the other seasons). Although the between-person variation in plasma tHcy was high (47%), the within-person variation was low (11%). This low variation, combined with the low methodologic imprecision of 3.8%, yielded a high reliability coefficient for plasma tHcy (0.97). CONCLUSIONS: Although there was a small seasonal variation in folate status, there was no corresponding seasonal variation in plasma tHcy. The high reliability coefficient for plasma tHcy suggests that a single measurement is reflective of an individual's average plasma tHcy concentration, thus indicating its usefulness as a potential predictor of disease. This, however, needs to be confirmed in different subgroups of the population. (+info)