Plasma pyridoxal 5'-phosphate concentration and dietary vitamin B-6 intake in free-living, low-income elderly people

Free-living, elderly persons (aged greater than or equal to 60 y, n = 198) were recruited to determine the effects of age, sex, health status, dietary vitamin B-6 intakes, and B-6 supplement use on plasma pyridoxal 5'-phosphate (PLP). Vitamin B-6 intakes were determined from 3-d diet records; supplementation was based on self-reported brand and frequency data. Fasting blood samples were analyzed for PLP. Subjects were primarily low-income Caucasians. There was no linear relationship between dietary vitamin B-6 intake, age, sex or health status, and PLP while accounting for supplemental vitamin B-6 use. PLP, however, was negatively correlated with age (p less than 0.001) in individuals with PLP values between 32 and 90 nmol/L. Vitamin B-6 status was low (PLP less than 32 nmol/L) in 32% of this elderly population (n = 198) and could be attributed to low dietary vitamin B-6 intakes and/or the presence of health problems reported to alter vitamin B-6 status. This research suggests that low vitamin B-6 status is prevalent in low-income, elderly persons, especially those with multiple health problems.     

Acute ingestion of glucose decreases plasma pyridoxal 5'-phosphate and total vitamin B-6 concentration

The effect of the acute ingestion of glucose on the concentration of pyridoxal 5'-phosphate (PLP) and total vitamin B-6 (TB6) in plasma was studied. Five males and four females were given 1 g D-glucose/kg body wt. A blood sample was collected at 0-10 min and 0, 0.5, 1, 2, 3, 4, and 5 h and the plasma was analyzed for PLP and TB6. There was a significant decrease in both plasma PLP and TB6 (p less than 0.05) at 2 h. All nine subjects exhibited a decrease, and by 5 h the mean change from fasting was 8-10 nmol/L for PLP and 8-12 nmol/L for TB6 (an 18-21% decrease from that when fasting). Ingestion of 300 mL water in four subjects resulted in a mean decrease of 3.4 nmol PLP/L plasma and indicated that some but not all of the decrease may have been due to fluid ingestion per se. Ingestion of glucose is associated with a decrease in both circulating plasma PLP and TB6; therefore, carbohydrate ingestion should be considered when plasma PLP and TB6 concentrations are used to evaluate vitamin B-6 status. In addition, fasting blood samples should be used when evaluating vitamin B-6 status.     

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.     

Pyridoxal-5'-phosphate and pyridoxal biokinetics in male Wistar rats fed graded levels of vitamin B-6

Biokinetic parameters of plasma pyridoxal-5'-phosphate (PLP) and pyridoxal (PL) disposition were studied in male Wistar rats (age 8 mo) fed a purified diet containing less than 0.5, approximately 3 or approximately 6 mg pyridoxine.HCl/kg diet from weaning, with animals fed the 6 mg/kg diet serving as the control group. Basal plasma PLP concentration was lower in both the less than 0.5 and 3 mg/kg diet groups than in control animals (98 +/- 12, 314 +/- 40 and 514 +/- 56 nmol/L, respectively). Basal plasma PL concentration was lower in the less than 0.5 mg/kg diet group only [60 nmol/L (measured in pooled samples), 190 +/- 73 and 235 +/- 63 nmol/L for less than 0.5, 3 and 6 mg/kg diet groups, respectively]. In both the less than 0.5 and 3 mg/kg diet groups, PLP clearance was lower than in control rats (0.158 +/- 0.025, 0.131 +/- 0.040 and 0.240 +/- 0.051 L.h-1.kg body weight-1, respectively). In the less than 0.5 mg/kg diet group, PLP synthesis was more efficient than in control animals (34.7 +/- 9.3, 12.1 +/- 2.5 and 16.7 +/- 11.4% for less than 0.5, 3 and 6 mg/kg diet groups, respectively). In both the less than 0.5 and 3 mg/kg diet groups, volume of distribution of PLP as well as of PL was larger than in controls. It is concluded that B-6 vitamer metabolism is influenced by vitamin B-6 status. The metabolic pathway involved (PLP synthesis and/or PLP degradation) was observed to depend on degree of vitamin B-6 deficiency.     

Effect of different levels of oral pyridoxine supplementation on plasma pyridoxal-5'-phosphate and pyridoxal levels and urinary vitamin B-6 excretion

Plasma pyridoxal-5'-phosphate and pyridoxal levels increased significantly (p less than 0.05) when single, oral bolus doses of pyridoxine were increased from 10 to 25 and from 25 to 50 mg in nine female volunteers. However, when the dose was increased to 100 mg, plasma pyridoxal-5'-phosphate levels did not differ significantly from those recorded after the 50 mg dose. Within 3 h plasma pyridoxal levels rose with a factor of 3.85 compared with the 50 mg dose but high pyridoxal levels were eliminated from the circulation. Renal clearance of pyridoxal remained a constant, low percentage (less than 2.0%) of each pyridoxine supplement in spite of the observed very high circulating pyridoxal levels. Pyridoxine supplementation is discussed in relation to circulating pyridoxal-5'-phosphate and pyridoxal availability for cellular metabolism.     

Increased plasma pyridoxal 5'-phosphate and vitamin B6 in male adolescents after 4500-meter run

To investigate the effect of running on vitamin B6 metabolism, plasma pyridoxal 5'-phosphate and total vitamin B6 levels were determined in male adolescent trained athletes before and immediately after a 4500-m run. Six to seven subjects were studied twice during the fall and once during the spring training seasons. A mean increase in pyridoxal 5'-phosphate of 0.77 +/- 0.31 to 1.83 +/- 0.77 nmol/100 ml of plasma was observed after the three runs (p less than 0.01). Similarly, significant increases (p less than 0.05) in plasma total vitamin B6 were seen in all three runs. These increases were not solely due to changes in plasma volume. From urine samples collected on two runs, urinary 4-pyridoxic acid excretion in this group of adolescents was found to be similar to that reported for male adults. While changes in plasma glucose were not significantly correlated with changes in vitamin B6 metabolites, it is hypothesized that the significant changes in vitamin B6 metabolites found in this study were related to an increased need for cofactor for gluconeogenesis. The changes found in this study do not provide evidence for or against an increased need for vitamin B6 in persons that exercise, but does show, for the first time, that exercise in the form of long distance running dramatically alters plasma levels of pyridoxal 5'-phosphate.     

Combined dietary folate, vitamin B-12, and vitamin B-6 intake influences plasma docosahexaenoic acid concentration in rats

Background

Folate, vitamin B-12, and vitamin B-6 are essential nutritional components in one-carbon metabolism and are required for methylation capacity. The availability of these vitamins may therefore modify methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) by PE-N-methyltransferase (PEMT) in the liver. It has been suggested that PC synthesis by PEMT plays an important role in the transport of polyunsaturated fatty acids (PUFAs) like docosahexaenoic acid (DHA) from the liver to plasma and possibly other tissues. We hypothesized that if B-vitamin supplementation enhances PEMT activity, then supplementation could also increase the concentration of plasma levels of PUFAs such as DHA. To test this hypothesis, we determined the effect of varying the combined dietary intake of these three B-vitamins on plasma DHA concentration in rats.

Methods

In a first experiment, plasma DHA and plasma homocysteine concentrations were measured in rats that had consumed a B-vitamin-poor diet for 4?weeks after which they were either continued on the B-vitamin-poor diet or switched to a B-vitamin-enriched diet for another 4?weeks. In a second experiment, plasma DHA and plasma homocysteine concentrations were measured in rats after feeding them one of four diets with varying levels of B-vitamins for 4?weeks. The diets provided 0% (poor), 100% (normal), 400% (enriched), and 1600% (high) of the laboratory rodent requirements for each of the three B-vitamins.

Results

Plasma DHA concentration was higher in rats fed the B-vitamin-enriched diet than in rats that were continued on the B-vitamin-poor diet (P?=?0.005; experiment A). Varying dietary B-vitamin intake from deficient to supra-physiologic resulted in a non-linear dose-dependent trend for increasing plasma DHA (P?=?0.027; experiment B). Plasma DHA was lowest in rats consuming the B-vitamin-poor diet (P?>?0.05 vs. normal, P?. enriched and high) and highest in rats consuming the B-vitamin-high diet (P?. poor and normal, P?>?0.05 vs. enriched). B-vitamin deficiency significantly increased plasma total homocysteine but increasing intake above normal did not significantly reduce it. Nevertheless, in both experiments plasma DHA was inversely correlated with plasma total homocysteine.

Conclusion

These data demonstrate that dietary folate, vitamin B-12, and vitamin B-6 intake can influence plasma concentration of DHA.     

Validation of the diagnostic value of plasma pyridoxal 5'-phosphate measurements in vitamin B6 nutrition of the rat

The relationship of plasma pyridoxal 5'-phosphate (PLP) to PLP content of tissues and activities of PLP-dependent enzymes was examined to establish its value in assessing vitamin B6 nutrition. Weanling rats were fed ad libitum for 9 weeks purified diets which supplied 0, 4, 12, 24, and 100 micrograms of pyridoxine daily. Growth increased with increasing pyridoxine intake, reaching a maximum at 24 micrograms/day. Liver and brain PLP also increased, attaining maximal values at 12 micrograms. By contrast, muscle and plasma PLP did not saturate when vitamin B6 intake was increased to 100 micrograms. Erythrocytic holoenzyme activity of aspartate (Asp) aminotransferase became maximal with 24 micrograms but that of alanine (Ala) aminotransferase did not. Hepatic holoenzyme activities of Ala, Asp and tyrosine aminotransferases reached maximal values with only 4 micrograms vitamin B6 but that of serine dehydratase became maximal with 12 micrograms. Measurement of coenzyme saturability suggested that apoenzyme degradation, coenzyme affinity and PLP transfer determine the activities of these enzymes. It is concluded that plasma and muscle PLP behave as mobilizable storage pools and that plasma PLP is a sensitive and reliable indicator of vitamin B6 nutrition.     

Effect of vitamin B-6 deficiency on fasting plasma homocysteine concentrations.

The catabolism of homocysteine through cystathionine synthesis requires pyridoxal-5'-phosphate, thus the effect of vitamin B-6 deficiency on plasma homocysteine concentrations was evaluated. Total fasting plasma homocysteine concentrations were measured in 11 elderly subjects aged 64.4 +/- 1.7 y (mean +/- SE) who consumed a vitamin B-6-deficient diet for less than or equal to 20 d. Only 1 of the 11 subjects was found to have elevated homocysteine concentrations even though all subjects exhibited high urinary xanthurenic acid concentrations after a tryptophan load, a measure indicative of vitamin B-6 deficiency. In a supporting study, fasting plasma homocysteine concentrations were measured in 3- and 23-mo-old rats fed vitamin B-6-deficient diets and were compared with those of vitamin B-6-replete, pair-fed controls. There was no difference in homocysteine concentrations between deficient and pair-fed animals after 6 wk of the dietary regimen for either age group; after 9 wk a modest elevation was observed in the 3-mo-old deficient rats whereas no difference was observed for the 23-mo-old rats. It is concluded that fasting plasma homocysteine concentrations are not initially elevated in vitamin B-6 deficiency and therefore fasting plasma homocysteine concentrations are not a good indicator of vitamin B-6 status.     

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.     

Aging and vitamin B-6 depletion: effects on plasma pyridoxal-5'-phosphate and erythrocyte aspartate aminotransferase activity coefficients in rats

Plasma pyridoxal-5'-phosphate (PLP) and erythrocyte aspartate aminotransferase activity coefficients were longitudinally determined in rats. Blood was obtained at weeks 0, 1, 2, 4, 6, 9, and 11 from rats initially aged 3 wk, 3 mo, 12 mo, and 23 mo (weeks 0, 1, 4, 6, and 9 only). The diet groups were ad libitum control (ALC), deficient (DEF), and pair-fed control (PF). Plasma PLP concentrations of controls were highest at 3 mo, intermediate at 3 wk and 12 mo, and lowest at 23 mo. When an additional group of 22-mo-old rats was fed a high-vitamin B-6 diet for 4 wk, their low baseline plasma PLP concentrations did not increase significantly. Plasma PLP decreased significantly within 1 wk and activity coefficients increased significantly by week 4 in all DEF rats. Depletion was most rapid and severe in the youngest DEF rats and least in 12-mo-old DEF rats. Mechanisms for the low plasma PLP control values and resistance to depletion in aged rats remain to be determined.     

Response of vitamin B-6 content of muscle to changes in vitamin B-6 intake in men

Previous reports indicated that in growing rats the vitamin B-6 pool in muscle was relatively stable during deficiency but increased in response to increased vitamin B-6 intake. To determine whether human muscle would show a similar response 10 college-aged males received a low vitamin B-6 diet (1.76 mumol/d) for 6 wk followed by 6 wk on a self-selected diet supplemented with 0.98 mmol pyridoxine HCl/d. During depletion, excretion of pyridoxic acid rapidly adjusted to approximate the intake. Plasma pyridoxal phosphate concentrations at the end of the baseline, depletion, and supplementation periods were 81 +/- 51, 9 +/- 3, and 455 +/- 129 nmol/L, respectively, whereas muscle concentrations were 21 +/- 9, 20 +/- 4, and 25 +/- 7 nmol/g, respectively and total vitamin B-6 in muscle was 28 +/- 10, 27 +/- 4, and 35 +/- 10 nmol/g, respectively. These data provide further confirmation that the vitamin B-6 pools in skeletal muscle are resistant to depletion. They also demonstrate that in humans with constant body weight, vitamin B-6 supplementation is not associated with marked increases in vitamin B-6 in muscle.     

Relationship of folate,vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers

It is hypothesized that diets deficient in folate, methionine, and vitamins B-6 and B-12 cause DNA hypomethylation and, as a result, increase risk of colorectal cancers. Furthermore, it is proposed that alcohol, a methyl group antagonist, increases risk of colorectal cancers among those with low intake of folate. Data from the Iowa Women's Health Study, a population-based cohort of incident cancer, were used to examine the relationship of folate, methionine, and vitamins B-6 and B-12 to occurrence of cancers of the colon (n = 598) and rectum (n = 123) over 13 yr of follow-up. There were no independent associations of folate, methionine, or vitamins B-6 and B-12 derived from a food frequency questionnaire with incidence of colon cancer. Adjusted relative risks (RRs) of rectal cancer were similar across categories of folate, vitamin B-12, and methionine intake, but RRs increased progressively with increasing intake of vitamin B-6 [P (for trend) = 0.03]. RRs suggested that incidence of cancer of the proximal colon was lower among those with 1) high folate and high vitamin B-12 intake [RR = 0.59, 95% confidence interval (CI) = 0.39-0.89] and 2) high folate and high vitamin B-6 intake (RR = 0.65, 95% CI = 0.50-0.84) than among those with the lowest intake of these nutrients. Incidence of cancer of the proximal colon was also somewhat lower among those with high folate and low alcohol intake (RR = 0.44, 95% CI = 0.22-0.89). Findings provide limited support for an association between dietary factors involved in DNA methylation and risk of cancers of the colon and rectum.     

Elevated plasma homocysteine and low vitamin B-6 status in nonsupplementing older women with rheumatoid arthritis

OBJECTIVE: The purpose of this study was to determine if nonsupplementing older women (aged >or=55 years) with rheumatoid arthritis had higher plasma homocysteine and lower B-vitamin status compared to healthy controls. Elevated plasma homocysteine, a risk factor for cardiovascular disease, may help explain why individuals with rheumatoid arthritis have an increased risk of cardiovascular disease. METHODS: Older, free-living women were classified as rheumatoid arthritis (n=18) or healthy control (n=33). Participants were not using B-vitamin supplements. Fasting blood samples were measured for pyridoxal 5'phosphate (PLP) (the metabolically active coenzyme form of vitamin B-6), folate, red blood cell folate, vitamin B-12, transcobalamin II, homocysteine, C-reactive protein, and lipid concentrations. Participants completed 7-day weighed food records, the Stanford Health Assessment Questionnaire (HAQ), and a visual analog pain scale. RESULTS: PLP concentrations were lower in the rheumatoid arthritis vs healthy control participants (4.93+/-3.85 vs 11.35+/-7.11 ng/mL [20+/-16 vs 46+/-29 nmol/L]; P<0.01) whereas plasma homocysteine was higher in the rheumatoid arthritis group (1.63+/-0.74 vs 1.15+/-0.38 mg/L [12.1+/-5.5 vs 8.5+/-2.8 micromol/L]; P=0.02). Red blood cell folate concentrations were lower in the rheumatoid arthritis vs healthy control participants [414+/-141 vs 525+/-172 ng/mL [938+/-320 vs 1,190+/-390 nmol/L]; P=0.02). No significant differences were found for plasma folate, vitamin B-12, and transcobalamin II. An inverse correlation was found between PLP concentrations and the HAQ disability index (r=-0.37; P<0.01). A positive correlation was found between homocysteine concentrations and the HAQ disability index (r=0.36; P=0.01). Total cholesterol and low-density lipoprotein cholesterol levels were lower in the rheumatoid arthritis group (cholesterol 191+/-43 vs 218+/-33 mg/dL [4.95+/-1.11 vs 5.65+/-0.85 mmol/L]; P=0.02; low-density lipoprotein cholesterol 110+/-36 vs 137+/-29 mg/dL [2.85+/-0.93 vs 3.55+/-0.75 mmol/L]; P<0.01). No significant differences were seen between groups for protein (g/day), fat (g/day), cholesterol (mg/day), folate (microg/day), vitamin B-12 (microg/day), and vitamin B-6 (mg/day) dietary intakes. CONCLUSIONS: Poor vitamin B-6 status and elevated plasma homocysteine concentrations were seen in older women with rheumatoid arthritis compared to healthy controls and may contribute to their increased risk of cardiovascular disease.     

Induction of pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats.

The effectiveness of dietary and hormonal treatments in inducing several pyridoxal phosphate-(PLP)-dependent enzymes has been examined in vitamin B-6 deficient rats. Holo- and apoenzymes of serine dehydratase and ornithine aminotransferase were inducible in both control and deficient rats by feeding them 80% casein diets or by injecting them with glucagon. Holo- and apotyrosine aminotransferase were induced in both control and deficient rats by injecting them with glucagon or with dexamethasone phosphate. Phosphoenolpyruvate carboxykinase, a non-PLP-dependent enzyme, was inducible in both control and deficient rats by glucagon treatment if the rats were fed, but not if they had been starved. The degree of induction of certain enzymes depended upon whether rats were fed ad libitum, starved overnight, or fed a protein-free diet prior to the induction period. Phosphoenolpyruvate carboxykinase activities were about the same in both control and deficient rats. In vitamin B-6 deficient rats, both uninduced and induced activities of serine dehydratase, ornithine aminotransferase, and tyrosine aminotransferase assayed in the prsence of PLP, but not in its absence, either equaled or exceeded control values under most experimental conditions. Synthesis of excess of apoenzyme of PLP-dependent enzymes generally accounted for the high total enzyme activity in deficient rats. Differences between values for control and deficient rats could not be accounted for by differences in liver cyclic AMP concentrations nor were they apparently related to reduced food intake of the deficient rats. High apoenzyme concentration during depletion of coenzyme would tend to prevent depletion of active enzyme.