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Changes in vitamin B-6 status indicators of women fed a constant protein diet with varying levels of vitamin B-6.

Changes in vitamin B-6 status indicators were evaluated in vitamin B-6-replete subjects. Ten young women consumed diets providing 85 g protein/d and 1.03, 1.33, 1.73, and 2.39 mg vitamin B-6/d for 12 or 15 d during four successive diet periods; in a second study, six women were fed diets providing 85 g protein/d and 0.84, 1.14, and 2.34 mg vitamin B-6/d for 10 or 12 d during three successive diet periods. Vitamin B-6 status indicators showing significant differences among intakes included urinary excretion of 4-pyridoxic acid and total vitamin B-6, pyridoxal 5'-phosphate and total vitamin B-6 in plasma, and xanthurenic acid excretion after a 2-g L-tryptophan load. Significant correlations were found between vitamin B-6 intake and 4-pyridoxic acid, total vitamin B-6, plasma pyridoxal 5'-phosphate, plasma total vitamin B-6, erythrocyte alanine aminotransferase percentage stimulation and postload excretion of xanthurenic acid and volatile amines (kynurenine plus acetylkynurenine). Depending on the indicator, between 20% and 70% of the subjects had inadequate values for 4-pyridoxic acid, total vitamin B-6, plasma pyridoxal 5'-phosphate, and erythrocyte alanine aminotransferase percentage stimulation at a vitamin B-6 intake of 1.33 mg/d (0.016 mg vitamin B-6/g protein). A ratio of dietary vitamin B-6 to protein > 0.016 mg/g is required for adequate vitamin B-6 status in women.

Adult↗

Relationship among homocyst(e)ine, vitamin B-12 and cardiac disease in the elderly: association between vitamin B-12 deficiency and decreased left ventricular ejection fraction.

We evaluated the association of moderate hyperhomocyst(e)inemia and vitamin B-12 status with coronary artery disease (CAD) and left ventricular ejection fraction in 367 elderly patients undergoing coronary angiography. The extent of CAD was scored, left ventricular ejection fraction was assessed and vitamins B-12 and folate and the metabolites homocyst(e)ine, methylmalonic acid and 2-methylcitric acid were measured. There was no significant trend in change in homocyst(e)ine as the extent of CAD increased. There was an association between vitamin B-12 deficiency, i.e., vitamin B-12 < 221 pmol/l and homocyst(e)ine > 16 nmol/ml and low left ventricular ejection fraction (P = 0.014). Of 105 samples, selected for vitamin B-12 < 221 pmol/l or high normal vitamin B-12 and folate levels, metabolites including methylmalonic acid revealed a specific diagnosis of vitamin B-12 deficiency in 18 patients. The trend among these vitamin B-12-deficient patients and low left ventricular ejection fraction was significant (P = 0.028). In vitro studies on rat heart revealed that nitrous oxide in the presence of 200 microM/l methionine reduced contractility of the heart. In conclusion, vitamin B-12-deficient patients had significantly lower left ventricular ejection fractions than nonvitamin B-12-deficient patients. Whether low left ventricular ejection fraction results in malabsorption of vitamin B-12 and vitamin B-12 deficiency, or conversely, whether vitamin B-12 and its marker, elevated homocyst(e)ine, depress left ventricular function warrants further evaluation.

Aged↗

Effects of chelation with EDTA and vitamin B therapy on nitric oxide-related endothelial vasodilator function.

1. 'Chelation therapy' with EDTA is being frequently used in patients with cardiovascular disease, despite limited objective evidence of effectiveness. Depressed nitric oxide (.NO)-related endothelial function accompanies atherosclerosis, and even the vascular risk factors alone, and is improved by numerous interventions that also improve prognosis in vascular disease. 2. The aim of the present study was to determine the influence of chelation therapy with EDTA alone and EDTA in combination with B vitamins on endothelial function. 3. After a control series of saline infusions, we examined the effects of a series of EDTA infusions (1.5 g, 10 times over 6 weeks) in eight subjects with coronary artery disease. In addition, because EDTA is commonly supplemented by other components, particularly B group vitamins, we subsequently examined the effect of a similar series of vitamin-supplemented EDTA infusions. 4. Forearm blood flow (FBF) was assessed by plethysmography and graded intrabrachial infusions of the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent dilator sodium nitroprusside (SNP). 5. There was no difference in vasodilation to either drug after EDTA alone compared with the control periods, but the response to ACh was augmented after combined therapy (P < 0.03, ANOVA). The latter was accompanied by a small but consistent mean (+/- SEM) fall in plasma homocysteine of 1.6 +/- 0.5 mumol/L (P < 0.05). 6. The selective increase in the vasodilator response to ACh after therapy with EDTA and several B group vitamins indicates that NO-related endothelial function was improved. The absence of response to EDTA alone suggests that the supplementary vitamins were necessary for this benefit, which may have been related to the accompanying decrease in plasma homocysteine. These results, along with the current interest in the possible cardioprotective effects of vitamins and the increasing administration of 'chelation therapy', call for more definitive studies on these aspects of 'alternative medicine'.

Acetylcholine↗

Abnormal concentrations of B vitamins and amino acids in plasma and B vitamins in bile of rabbits with aflatoxicosis.

The dosages of aflatoxin B1 (AFB1) required to produce significant changes in concentrations of B vitamins in plasma and bile and of amino acids in plasma of rabbits were determined. Folate increased by 98% in plasma, whereas concentration of thiamine, vitamin B6, and biotin decreased by more than 50%. In bile, choline and biotin increased 14- and 18-fold, respectively, whereas folate and niacin decreased by more than 50%. All amino acids in plasma increased between 76 and 155%. The dosages of AFB1 required to induce these changes were usually between 12.5 and 37.5 microgram/kg of body weight per day. Except for changes in biliary concentrations of pantothenic acid, folic acid, and biotin, lower threshold dosages of aflatoxin were required to produce weight loss and anorexia (5.0 and 8.5 microgram of AFB1/kg per day, respectively) than for changes in vitamins and amino acids (approximately 25 to 50 microgram of AFB1/kg per day). The data indicated that AFB1 interfered with the metabolism of B vitamins and amino acids in rabbits.

Aflatoxin B1↗

Vitamin B-6 requirement and status assessment of young women fed a high-protein diet with various levels of vitamin B-6.

The vitamin B-6 requirement of young women consuming a constant high-protein diet (1.55 g/kg body wt) and the effect of various ratios of vitamin B-6 to protein on this requirement were studied. Eight women were fed a lactoovovegetarian basal diet containing 0.45 mg vitamin B-6 (2.66 micromol as pyridoxine) and 30 micromol carnitine for 92 d. The protocol consisted of successive baseline adjustment (9 d), depletion (27 d), and repletion (two 21-d and then one 14-d) periods. Vitamin B-6 intakes were 1.60, 0.45, 1.26, 1.66, and 2.06 mg, resulting in ratios of vitamin B-6 (in mg) to protein (in g) for the five periods of 0.016, 0.005, 0.013, 0.017, and 0.021, respectively. Direct and indirect as well as short- and long-term vitamin B-6 status measures were assessed weekly. Regression analysis revealed that the amount of dietary vitamin B-6 required to normalize urinary 4-pyridoxic acid, plasma pyridoxal-P, erythrocyte pyridoxal-P and pyridoxal, and erythrocyte alanine and aspartate aminotransferase activity coefficients to predepletion baseline values was 1.94 mg vitamin B-6/d (0.019 mg vitamin B-6/g protein). This study suggests that the current vitamin B-6 recommended dietary allowance of 1.6 mg/d based on 0.016 mg/g protein is not an adequate intake and may require reevaluation.

Adult↗

Biosynthesis of vitamin B-12. Part I. Role of the ribosomal proteins in vitamin B-12 biosynthesis.

1. 70 S ribosomes isolated from strains of Escherichia coli 113-3, K12 and B take part in vitamin B-12 biosynthesis from AdoCbi-GDP, NAD and dimethylbenzimidazole in the presence of enzymes of the cytosol fraction. 2. 70 S ribosomes from E.coli 113-3 bind Ado[58Co]Cbi-GDP. This reaction is independent of fusidic acid. 3. Proteins from 5 S RNA complex as well as l3 protein isolated from E.coli 113-3 ribosomes catalyze vitamin B-12 biosynthesis. The main catalytic function in this reaction is preformed by protein L18. 4. Vitamin B-12 biosynthesis proceeding in the presence of isolated ribosomal proteins is inhibited by fusidic acid, chloramphenicol and vernamycin but not by erythromycin. 5. Vitamin B-12 synthesized in the presence of isolated ribosomal proteins is biologically active.

Anti-Bacterial Agents↗

Plasma vitamin B-12 concentrations in an elderly latino population are predicted by serum gastrin concentrations and crystalline vitamin B-12 intake.

The prevalence of vitamin B-12 deficiency increases with age, probably resulting from malabsorption of food-bound B-12 secondary to gastric atrophy. On the basis of this assumption, the Institute of Medicine (IOM) recommends those aged >50 y consume crystalline vitamin B-12. There is limited information on the prevalence of gastric atrophy in the elderly and whether the IOM recommendation would be effective. The objective of this study was to assess predictors of vitamin B-12 status and their interactions in free-living elderly. Individuals (n = 57) with deficient plasma vitamin B-12 (p-B12 < 148 pmol/L) were compared with 68 individuals with marginal p-B12 (148-221 pmol/L) and 52 with normal p-B12 (>221 pmol/L) in a cross-sectional sample (n = 1546) of elderly (>60 y) Latinos in California. Associations were examined among p-B12 and serum gastrin, vitamin B-12 intake from food and crystalline sources, and medications that putatively affect vitamin B-12 absorption. Serum gastrin was elevated, indicating gastric atrophy, in 48% of participants with deficient p-B12, 23% with marginal p-B12 and 21% of normal p-B12 participants, and was a significant predictor of deficient p-B12 and high plasma homocysteine (p-tHcy). Median total vitamin B-12 intake exceeded recommendations and was similar among status groups. Crystalline vitamin B-12 intake in the normal p-B12 group was higher than in the deficient p-B12 group (P < 0.01), and tended to be higher than the marginal group (P = 0.07). When serum gastrin was elevated, p-B12 was predicted by crystalline vitamin B-12, but not by intake of vitamin B-12 from food. Elevated serum gastrin was highly prevalent and predicted vitamin B-12 depletion. Crystalline vitamin B-12 intake predicted p-B12 in individuals with elevated serum gastrin, supporting IOM recommendations to increase consumption of crystalline vitamin B-12.

Aged↗

Plasma folate but not vitamin B(12) or homocysteine concentrations are reduced after short-term vitamin B(6) supplementation.

Adverse effects of high vitamin B(6) intake include peripheral neuropathy. Recent studies focussing on the reduction of plasma homocysteine as a risk factor for vascular disease showed that vitamin B(6) reduces plasma folate levels. The significance of this finding is unclear. We therefore analyzed plasma folate and basal homocysteine levels as well as the response to an oral methionine loading test in 8 healthy individuals before and after a controlled supplementation with oral doses of 25 mg pyridoxine for 10 days. Plasma pyridoxal phosphate increased from 40.6 +/- 13.6 to 426.8 +/- 200.3 nmol/l (p < 0.001), whereas plasma folate decreased from 6.3 +/- 1.6 to 4.6 +/-1.5 ng/ml (p < 0.01), respectively. Plasma vitamin B(12) and basal homocysteine levels remained unchanged (234.0 +/- 27.8 vs. 217.1 +/- 50.4 pg/ml and 10.9 +/- 4.8 vs. 10.1 +/- 3.6 micromol/l). There was no significant effect of vitamin B(6) supplementation on the area under methionine and homocysteine concentration versus time curve. Significant correlations were found between pre- and post-supplement levels of folate as well as PLP levels (r = 0.73, p < 0.05; r = 0.75, p < 0.05). These data suggest that a dose of 25 mg vitamin B(6) supplemented for 10 days reduces plasma folate but did not affect basal and postprandial homocysteine levels suggesting (1) a normal cellular availability of folate or (2) a compensation of impaired homocysteine remethylation by increased transsulfuration.

Adult↗

Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial.

BACKGROUND: Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive. OBJECTIVE: The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency. DESIGN: In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function. RESULTS: Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains. CONCLUSION: Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function.

Administration, Oral↗

Role of vitamin B 6 biosynthetic rate in the study of vitamin B 6 synthesis in Escherichia coli.

Nutritional auxotrophs of Escherichia coli synthesize vitamin B(6) compounds at a rate of 1 x 10(-10) to 2 x 10(-10) moles per hr per mg (dry weight) of cells when they are suspended in minimal medium lacking their required nutrients. A few auxotrophs have been found to stop or reduce vitamin B(6) synthesis during such an experiment. These include thiamineless, citrate synthaseless, and pyridoxineless mutants as well as mutants which require four carbon compounds for growth. Glycolaldehyde was found to restore vitamin B(6) synthesis in the last named of these mutants without restoring normal growth. A class of pyridoxineless mutants which responded with normal growth to 0.4 mm glycolaldehyde or 0.15 x 10(-3) mm pyridoxol was also found. The results suggest that a thiamine pyrophosphate-requiring step as well as glycolaldehyde may be involved in pyridoxal phosphate biosynthesis.

Acetates↗

Plasma pyridoxal 5'-phosphate concentration is correlated with functional vitamin B-6 indices in patients with rheumatoid arthritis and marginal vitamin B-6 status.

Many patients with rheumatoid arthritis (RA) have low plasma pyridoxal-phosphate (PLP) but a normal erythrocyte aspartate aminotransferase activity coefficient (alpha EAST), a measure of vitamin B-6 status in the erythrocytes, compared with healthy subjects. The goal of the present study was to examine the correlations of PLP levels in these two compartments (plasma and erythrocytes) with other established indices of vitamin B-6 status, and to determine which indicator better reflects functional status of vitamin B-6 in patients with RA. Multiple indices of vitamin B-6 status were measured in 33 patients with RA. Plasma PLP, urinary 4-pyridoxic acid (4-PA), net increase in plasma total homocysteine after a methionine load (DeltatHcy) and net increase in urinary xanthurenic acid after a tryptophan load (DeltaXA) were log-transformed to reach normality for statistical analyses. We found that log-plasma PLP levels were inversely correlated with both log-DeltatHcy (r = -0.368, P = 0.035) and log-DeltaXA (r = -0.333, P = 0.05). Plasma PLP was not correlated with alpha EAST or urinary 4-PA excretion. In contrast, erythrocyte PLP was inversely correlated with alpha EAST (r = -0.431, P = 0.012) and positively correlated with log-4-PA (r = 0.475, P = 0.005), but erythrocyte PLP was not correlated with the outcomes of a methionine or tryptophan load test. Erythrocyte PLP and log-4-PA, but not plasma PLP, were correlated with dietary intake of vitamin B-6 after adjusting for protein intake (r = 0.420, P = 0.015 and r = 0.333, P = 0.05, respectively). We suggest that in patients with RA, plasma PLP levels are a better diagnostic indicator of functional vitamin B-6 status than erythrocyte PLP levels.

Adult↗

Vitamin B-6 adequacy in neonatal nutrition: associations with preterm delivery, type of feeding, and vitamin B-6 supplementation.

Concerns about vitamin B-6 adequacy in neonatal nutrition relate to critical functions of the vitamin in development. Vitamin B-6 status was assessed in six groups of neonates: two groups each of breast-fed term and preterm infants whose mothers were supplemented with 2 or 27 mg pyridoxine-hydrochloride (PN-HCl); a subgroup of term infants (2-mg maternal group) supplemented with 0.4 mg PN-HCl/d; and a formula-fed preterm group. During the 28-d experimental period, weekly assessments showed lower concentrations of total vitamin B-6 and percentages of pyridoxal in milk from mothers of preterm infants than in milk from mothers of term infants, even when maternal PN-HCl supplementation was 27 mg/d. The vitamin B-6 concentration of milk and estimated intakes of the vitamin by breast-fed infants paralleled maternal supplements (ie, 2 and 27 mg). Plasma and erythrocyte measurements of infants correlated with their vitamin B-6 intakes; values were highest for infants given vitamin B-6 supplements and those that wee formula-fed. Vitamin B-6 adequacy was questionable for unsupplemented breast-fed infants of mothers in the 2-mg supplemented groups.

Adolescent↗

Cutaneous metabolism of vitamin B-6.

Vitamin B-6 is important for skin development and maintenance. We examined vitamin B-6 metabolism in human and mouse skin collected at different phases of the hair cycle; in hamster melanomas; in normal and immortalized human keratinocytes (HaCaT) and several human melanoma cell lines. Pyridoxamine 5'-phosphate content was higher in mouse and hamster than in human skin. Activity of both pyridoxamine 5'-phosphate oxidase and pyridoxal 5'-phosphate hydrolase was significantly increased in rapidly growing melanomas compared to either normal skin or slower growing skin tumors. Reducing the pyridoxine content of the culture medium significantly increased the activity of pyridoxal kinase and pyridoxamine 5'-phosphate oxidase. Pyridoxal 5'-phosphate hydrolase has been proposed as a regulatory enzyme for vitamin B-6, but we found B-6 vitamer content to be significantly correlated only with kinase and oxidase activity and not with pyridoxal 5'-phosphate hydrolase activity. Although pyridoxal 5'-phosphate hydrolase activity is usually attributed to tissue-nonspecific alkaline phosphatase, tissue-nonspecific alkaline phosphatase knockout mice showed preservation of normal histology of the skin and adnexal structures. Furthermore, expression of tissue-nonspecific alkaline phosphatase mRNA was not detected in either HaCaT cells or human skin, both of which exhibited significant pyridoxal 5'-phosphate hydrolase activity. This suggests that an enzyme different from the classical tissue-nonspecific alkaline phosphatase may perform cutaneous pyridoxal 5'-phosphate hydrolase activity.

Aldehyde Oxidoreductases↗