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Plasma B vitamins and their relation to the severity of chronic heart failure.

BACKGROUND: Total homocysteine (tHcy) has been linked to the severity of chronic heart failure (CHF). Elevated tHcy concentrations are mainly caused by folate and vitamin B-12 deficiencies. OBJECTIVE: We hypothesized that folate and vitamin B-12 deficiencies can explain the relation between tHcy and the severity of CHF. DESIGN: We investigated 987 CHF patients. All subjects underwent a physical examination and blood sampling. Cardiac catheterization was performed in 929 patients and echocardiography in 460 patients. Serum tHcy, folate, vitamin B-12, and N-terminal pro-B-type natriuretic-peptide (NT-proBNP) were measured and renal and hepatic function were studied. RESULTS: tHcy increased with increasing New York Heart Association (NYHA) classes of heart failure (P < 0.001) and correlated with the left ventricular ejection fraction (EF; r = -0.150, P < 0.001). Contrary to the hypothesis, vitamin B-12 (P < 0.001) increased with NYHA class (P < 0.001) and was negatively correlated with EF (r = -0.080, P = 0.015). Folate showed no relation with NYHA class or EF. Comparable results were obtained for NT-proBNP (tHcy: r = 0.27, P < 0.001; vitamin B-12: r = 0.091, P = 0.004; folate: r = -0.045, P = 0.169). The correlations between tHcy, EF, and NT-proBNP were significantly stronger in patients without coronary artery disease (CAD) than in those with CAD. Regression analysis showed that tHcy, but not B vitamins, is a strong predictor of EF and NT-proBNP. CONCLUSIONS: This study showed that tHcy, but not folate and vitamin B-12, is related to clinical, echocardiographic, and laboratory variables of CHF, which indicates a relation between tHcy and the severity of CHF. This relation is stronger in patients without CAD. The lack of association of folate and the paradoxical relation of vitamin B-12 with CHF can possibly be explained by a disturbance in hepatic homeostasis.

Aged↗

Preconception folate and vitamin B(6) status and clinical spontaneous abortion in Chinese women.

OBJECTIVE: To assess the association between preconception homocysteine and B vitamin status and risk of clinical spontaneous abortion in women from Anqing, China. METHODS: All women were aged 21-34 years, had never smoked, and were primigravid. Patients (n = 49) were women with a clinically recognized pregnancy who experienced a fetal death before 100 days' gestation. Controls (n = 409) were women who maintained a pregnancy that ended in a live birth. Homocysteine, folate, and vitamins B(6) and B(12) concentrations were measured in plasma obtained before conception. RESULTS: Mean vitamin B(6) concentration was lower in patients than in controls (34.0 versus 37.9 nmol/L, P =.04). In addition, the risk of spontaneous abortion tended to increase with decreasing plasma vitamin B(6) and folate concentration (P for trend =.06 and.07, respectively), although the significance of these trends was further reduced in logistic models that included age, body mass index, and both vitamins. The risk of spontaneous abortion was four-fold higher among women with suboptimal plasma concentrations of both folate and vitamin B(6) (folate less than or equal to 8.4 nmol/L and vitamin B(6) less than or equal to 49 nmol/L) than in those with higher plasma concentrations of both vitamins (odds ratio 4.1, 95% confidence interval 1.2, 14.4). Homocysteine and vitamin B(12) status were not associated with spontaneous abortion risk. CONCLUSION: Suboptimal preconception folate and vitamin B(6) status, especially when they occur together, may increase the risk of clinical spontaneous abortion. Additional prospective studies are needed to confirm these findings and to determine whether antenatal B vitamin supplementation reduces spontaneous abortion risk.

Abortion, Spontaneous↗

Low plasma levels of vitamin B(6) are independently associated with a heightened risk of deep-vein thrombosis.

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.

Adolescent↗

Effect of smoking on serum concentrations of total homocysteine and B vitamins in mid-pregnancy.

There are conflicting findings in the literature on the effect of smoking on total homocysteine (tHcy) concentrations in non-pregnant subjects. We evaluated the effect of smoking on serum concentrations of tHcy, folate, vitamin B-12 pyridoxal 5'-phosphate (PLP, a coenzyme form of vitamin B-6) in 196 women at 18 and 30 weeks' gestation. The smokers were defined as those who self-reported cigarette smoking and had serum concentrations of thiocyanate, a biomaker of smoking, in the highest quartiles of the population. Mid-pregnancy serum tHcy concentrations were not significantly different between smokers and non-smokers. Folate, vitamin B-12 and PLP concentrations were generally lower in smokers than non-smokers. In smokers, tHcy concentrations had significant negative correlations with folate at both time points. The multiple regression analyses indicated that serum folate concentration was the most significant factor associated with tHcy concentrations among smokers, whereas thiocyanate concentrations showed no such effect. We conclude that serum tHcy concentrations were most strongly associated with the nutritional status of folate among the B vitamins tested during mid-pregnancy in our subjects. We suggest that it is essential to consider the nutritional status of folate, vitamin B-12 and vitamin B-6 in evaluating the effect of smoking on homocysteine metabolism.

Female↗

Biochemical indexes of the B vitamins in cord serum are predicted by maternal B vitamin status.

BACKGROUND: The concentration of total homocysteine (tHcy) is higher in newborns than in older children. Vitamin B-12 is the major determinant of tHcy in newborns. Maternal status of folate, vitamin B-12, and vitamin B-6 during pregnancy may affect the biochemical markers of these micronutrients in newborns. OBJECTIVE: Our objective was to study the relation between concentrations of the metabolites and B vitamins in maternal sera and concentrations in the umbilical venous blood of the corresponding newborns. DESIGN: We studied healthy pregnant women at the time of labor who were expecting healthy, full-term, appropriate-birth-weight babies. Samples were available from 82 mother-infant pairs. RESULTS: Concentrations of B vitamins were higher in cord samples than in maternal blood (folate, 2-fold; vitamin B-12, 1.5-fold; and vitamin B-6, 6-fold). Concentrations of cystathionine and methylmalonic acid (MMA) were also higher in the infants than in the mothers (x +/- SD: cystathionine, 462 +/- 189 and 343 +/- 143 nmol/L; MMA, 353 +/- 144 and 233 +/- 110 nmol/L). No significant differences in tHcy concentrations were observed between fetal and maternal samples. Concentrations of vitamin B-12 did not differ significantly between mothers of infants from different quartiles of cord MMA. Higher fetal MMA concentrations were related to higher maternal MMA and vitamin B-12 concentrations and lower fetal concentrations of vitamin B-12. Fetal concentrations of cystathionine were predicted by maternal cystathionine, gestational age, fetal vitamin B-6, and fetal tHcy. CONCLUSIONS: Maternal concentrations of the metabolic markers of B vitamins predict values in fetal blood at delivery. Fetal tHcy concentrations were low but were predicted by the vitamin status of the mother. The effect of increasing maternal intake of vitamins B-12 and B-6 during pregnancy on the fetal concentrations of the metabolites should be investigated.

Adult↗

Dietary intake of total and glycosylated vitamin B-6 and the vitamin B-6 nutritional status of unsupplemented lactating women and their infants.

The mean dietary intakes of total and glycosylated vitamin B-6, determined from analysis of 3-d diet composites collected from 30 lactating women, were 8.63 +/- 4.04 and 1.33 +/- 0.85 mumol/d (mean +/- SD), respectively. A comparison of linear regression models that either included or excluded dietary glycosylated vitamin B-6 content indicates that the intake of glycosylated vitamin B-6 had little, if any, effect upon maternal plasma pyridoxal 5'-phosphate concentration and maternal urinary excretion of total vitamin B-6 and 4-pyridoxic acid. On the basis of guidelines from the literature for evaluating biochemical indices of vitamin B-6 nutriture, the women appeared to be consuming adequate amounts of the vitamin. The mean breast-milk concentrations of total and glycosylated vitamin B-6 were 733 and 18 nmol/L, respectively. Infant plasma pyridoxal 5'-phosphate concentration was 54 +/- 44 nmol/L (mean +/- SD) and all infants had lengths and weights appropriate for age.

Adult↗

Homocysteine, B vitamin status, and cognitive function in the elderly.

BACKGROUND: Old age is associated with reduced cognitive performance. Nutritional factors may contribute to this association. OBJECTIVE: We tested associations between cognitive performance and plasma vitamin B-12, folate, and homocysteine concentrations in the elderly. DESIGN: We studied survivors of the Scottish Mental Surveys of 1932 (Aberdeen 1921 Birth Cohort, or ABC21) and 1947 (Aberdeen 1936 Birth Cohort, or ABC36), which surveyed childhood intelligence quotient. We measured folate, vitamin B-12, and homocysteine concentrations in fasting blood samples and cognitive performance by the Mini Mental State Examination (MMSE), National Adult Reading Test (NART), Raven's Progressive Matrices (RPM), Auditory Verbal Learning Test (AVLT), digit symbol (DS) subtest, and block design (BD) subtest. RESULTS: Homocysteine was higher in the ABC21 than in the ABC36 (P < 0.0001). There were positive correlations between folate and vitamin B-12 and negative correlations between homocysteine and both folate and vitamin B-12. MMSE, RPM, AVLT, DS, and BD scores were higher in the ABC36. In the ABC21, folate, vitamin B-12, and MMSE score were positively correlated and homocysteine was negatively correlated with RPM, DS, and BD scores. Folic acid was positively correlated with AVLT and DS scores. In the ABC36, folate was positively correlated with BD score. After adjustment for childhood intelligence quotient, partial correlations were strengthened between vitamin B-12 and NART score and between homocysteine and RPM score but weakened between red blood cell folate and DS score. CONCLUSIONS: B vitamins and homocysteine are associated with cognitive variation in old age. In the ABC21 but not the ABC36, homocysteine accounted for approximately 7-8% of the variance in cognitive performance. This may prove relevant to the design of neuroprotective studies in late life.

Aged↗

Low erythrocyte folate, but not plasma vitamin B-12 or homocysteine,is associated with dementia in elderly Latinos.

The relationship between B vitamin status and cognitive function has been of interest for many years. There is evidence of relationships between intake and status of folate and vitamin B-12 with neurological, cognitive, and memory impairment, but results have been inconsistent. Plasma B-12, erythrocyte folate, methylmalonic acid,and homocysteine were evaluated as predictors of cognitive function in a large population based sample of Latino elderly living in the Sacramento, California region. The hypothesis tested was that low folate and/or B-12 status predicts cognitive function impairment and dementia. Logistic regression was used to examine the differences in B-vitamin status by cognitive function category. Erythrocyte folate was related to dementia after controlling for age, gender, education, income, diabetes diagnosis, serum creatinine, and depressive symptoms. The highest prevalence of low erythrocyte folate occurred in the Dementia group and was significantly higher than in the Normal group. Plasma B-12, MMA, Hcy, and prevalence of a normal values for these variables, were not significantly different among the cognitive function classes. We conclude that folate status is associated with dementia but that more research is needed on the relationship between vitaminB-12 status, Hcy and cognitive function to explore possible associations with these parameters.

Aged↗

Methylmalonic acid and coenzyme A concentrations in the livers of pair-fed vitamin B 12-deficient and vitamin B 12-treated sheep.

The concentrations of CoA in the livers of severely vitamin B(12)-deficient ewes were about 2.6 times those in pair-fed animals treated with vitamin B(12). When the feeding rates of the pair-fed animals were closely similar, the concentrations of methylmalonic acid in deficient livers were about twice those in vitamin B(12)-sufficient livers. The molar concentrations of CoA present were more than three times those of methylmalonic acid in both deficient and treated animals, and it is concluded that the elevated concentrations of CoA in the deficient livers were not primarily due to accumulation of methylmalonyl-CoA.

Animals↗

Effects of B vitamin injections on plasma B vitamin concentrations of feed-restricted beef calves infected with bovine herpesvirus-1.

For nonruminants, stress and disease greatly increase requirements for vitamin B6, folic acid, pantothenic acid, and ascorbate. The effects of feed restriction, virus infection, and vitamin injections on plasma concentrations of B vitamins critical to the immune response were evaluated. Twelve beef steer calves, 6 to 8 mo of age, were fed below maintenance for 17 d and deprived of food for 3 d during a 20-d period after weaning. They then were inoculated intranasally with live attenuated bovine herpesvirus-1 (BHV-1). Six calves received saline injections and six received injections of a B vitamin mixture and ascorbate every 48 h for 14 d before and 14 d after inoculation. A mild respiratory infection developed in all calves 4 to 5 d after inoculation. In control calves, restricted intake and food deprivation decreased plasma vitamin B6 and pantothenate and increased vitamin B12 but did not affect folic acid and ascorbate concentrations. Vitamin injections increased plasma concentrations of vitamin B6, folic acid, vitamin B12, pantothenic acid, and ascorbate (P < .002). Plasma concentrations of vitamin B6, vitamin B12, pantothenic acid, and ascorbate, but not folic acid, were markedly reduced in all calves during the BHV-1 infection (P = .001). The vitamin B6, pantothenic acid, vitamin B12, and ascorbate status of stressed calves may affect their immune response to vaccination or infection.

Administration, Intranasal↗

The role of the pancreas in vitamin B 12 absorption: studies of vitamin B 12 absorption in partially pancreatectomized rats.

The effect of partial pancreatectomy (80-90%) on vitamin B(12) absorption was studied in the rat. The absorption of 5 ng of (57)Co-labeled vitamin B(12) was significantly reduced from 70 +/-2.5% (mean +/-SE) in control and sham-operated rats to 32 +/-2.6% in partially pancreatectomized rats. Hog pancreatic extract (0.17 g/kg) improved vitamin B(12) absorption from 30.0 to 61.0% in partially pancreatectomized rats but did not alter vitamin B(12) absorption in control rats. Chloramphenicol did not enhance vitamin B(12) absorption in partially pancreatectomized rats with pancreatic extract-improved vitamin B(12) malabsorption. The partially pancreatectomized rats with pancreatic extract-improved vitamin B(12) malabsorption were sacrificed and the stomach and small bowel studied in vitro to further define the pathogenesis of the vitamin B(12) malabsorption. Rat gastric intrinsic factor stimulated vitamin B(12) uptake by intestinal sacs prepared from partially pancreatectomized rats 3.1-fold. Gastric intrinsic factor prepared from partially pancreatectomized rats was as effective in promoting vitamin B(12) uptake by rat intestinal sacs as intrinsic factor prepared from control rats. These data indicate that partially pancreatectomized rats develop an abnormality in the absorption of labeled vitamin B(12) which can be corrected by pancreatic extract. The vitamin B(12) malabsorption is due to neither an alteration in gastric intrinsic factor activity nor an impairment of the intrinsic factor-vitamin B(12) receptor in the intestine. It is suggested that in the partially pancreatectomized rats the intrinsic factor-vitamin B(12) complex exists in a form which is not available for absorption.

Animals↗

Is there any relationship between lipids and vitamin B levels in persons with elevated risk of atherosclerosis?

BACKGROUND: There is increasing evidence that plasma homocysteine level is an independent risk factor for atherosclerosis. Low levels of serum folates, cobalamin and pyridoxine are associated with increased risk of cardiovascular disease. Most dietary products contain cholesterol as well as methionine, so hyperlipidemia could be associated with a higher level of homocysteine and inversely with lower levels of B vitamins. The aim of this study was to investigate the differences in levels of lipids and vitamins affecting homocysteine metabolism in different groups of patients. MATERIAL/METHODS: We examined 38 healthy persons, 55 patients hospitalised for cardiac surgery, and 62 patients without clinical evidence of atherosclerosis but with one of the atherosclerosis risk factors (hypercholesterolemia, NIDDM or chronic renal insufficiency). The levels of total cholesterol, triglycerides, vitamin B12, folic acid and vitamin B6 index in serum were determined using routine laboratory methods. RESULTS: We found no association between lipids and B vitamins in any examined group. There were significant differences between concentrations of analysed parameters in all groups of patients as compared to controls. CONCLUSIONS: The lack of correlation between the levels of lipid parameters and B vitamins in serum indicates that these may be independent, additional risk factors for atherosclerosis. Higher vitamin B6 deficiency in dialysis patients is probably caused by low intake combined with the increased requirements of uremic patients. Permanent monitoring of B vitamins in serum is necessary in patients with elevated risk of atherosclerosis, as well as long-term education, careful diet planning and supplementation.

Adult↗

Thyroid function during B-vitamin supplementation of patients on antiepileptic drugs.

OBJECTIVES: Patients on antiepileptic drugs (AEDs) may have low serum concentrations of thyroxine, with or without a compensatory increment in thyroid-stimulating hormone (TSH). Furthermore, patients on AEDs often have hyperhomocysteinemia and low concentrations of vitamins B(6), B(2) and folate. Previously, an inverse relationship between thyroxine and homocysteine concentrations has been observed. In animals, deficiency of vitamin B(6) has been found to impair the hypophyseal release of TRH. We have studied the effect of B-vitamin supplements on thyroid function in patients on AEDs. DESIGN AND METHODS: Thirty-two patients on AEDs were identified with hyperhomocysteinemia and low folate, B(6) and B(2). They were supplemented with pyridoxine, riboflavin and folic acid for 30 days. RESULTS: At baseline, the patients had low serum concentrations of free thyroxin and slightly elevated TSH. On day 30 of the B-vitamin supplements, homocysteine had decreased, however, the thyroid parameters remained unchanged. CONCLUSIONS: Hyperhomocysteinemic patients on AEDs have indications of hypothyroidism, however, supplementation with B-vitamins does not improve their thyroid function.

Adult↗

Role of third serum vitamin B 12 binding protein in vitamin B 12 transport.

A third vitamin B(12) binding protein present in normal serum has been shown to participate in transport of labelled vitamin B(12) absorbed from the gut. All three vitamin B(12) binding proteins in serum were labelled at the same time after oral administration of vitamin B(12), implying that "free" vitamin B(12) reached the portal blood from the gut mucosa.

Biological Transport↗