Gender Differences in the Associations of Plasma Pyridoxal 5'-Phosphate with Plasma Polyunsaturated Fatty Acids among US Young and Middle-Aged Adults: NHANES 2003-2004.

Vitamin B6-restricted diets and low plasma pyridoxal 5'-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20-59 years; 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires; plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (ß) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (ß = 0.138, b = 0.104, p = 0.0004), DHA (ß = 0.101, b = 0.058, p = 0.036), EPA + DHA (ß = 0.125, b = 0.073, p = 0.005), EPA/AA (ß = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (ß = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.

Systemic bioavailability and pharmacokinetics of the doxylamine-pyridoxine delayed-release combination (Diclectin).

BACKGROUND: Diclectin, composed of 10 mg doxylamine succinate (DOX) and 10 mg pyridoxine hydrochloride, is the drug combination of choice for the management of nausea and vomiting during pregnancy in Canada. However, there is large variability in its onset and duration of action among women. To understand and improve its effectiveness, the variability in the pharmacokinetics of the ingredients in this doxylamine succinate/pyridoxine hydrochloride combination must be studied. OBJECTIVES: To determine the pharmacokinetics of DOX and pyridoxine after oral administration of two tablets of this drug combination in the form of Diclectin and to calculate their respective relative bioavailability by comparison with intravenous administration in another population. METHODS: Eighteen nonpregnant, nonlactating, healthy females between 18 and 45 years of age were administered two tablets of Diclectin with 240 mL of water under empty stomach conditions. Blood samples were analyzed for DOX and pyridoxine along with its four active metabolites: pyridoxal, pyridoxal-5'-phosphate (PLP), pyridoxamine, and pyridoxamine-5'-phosphate using tandem mass spectrometry. For the purpose of this study, pharmacokinetic values for DOX and PLP were adjusted for body weight. RESULTS: The mean DOX-AUC0→∞ was calculated to be 3137.22 ± 633.57 ng·hr/mL (range, 2056.59-4376.06 ng·hr/mL). The mean PLP-AUC0→∞ was calculated to be 5513.10 ± 2362.35 ng·hr/mL (range, 1572.56-10,153.77 ng·hr/mL). Based on literature values of the PLP-AUC0→∞ after intravenous administration and data from the current study, the relative bioavailability of pyridoxine in Diclectin was calculated at 100%. CONCLUSION: There was a 2.1-fold variability in the DOX-AUC0→∞ and 6.5-fold variability in the PLP-AUC0→∞ after oral administration of 20 mg Diclectin. Using literature values and data from the current study, we estimated the oral bioavailability of pyridoxine to be 100%. Therefore, interindividual differences in metabolism, and not in bioavailability, may be important sources of variability that need to be addressed in dosing guidelines.

Dietary intake of vitamin B-6, plasma pyridoxal 5'-phosphate, and homocysteine in Puerto Rican adults.

BACKGROUND: Vitamin B-6 is an important cofactor in many metabolic processes. However, vitamin B-6 intake and plasma status have not been well studied in the Puerto Rican population, a group with documented health disparities. OBJECTIVE: To assess dietary intake of vitamin B-6, food sources, and plasma status of pyridoxal 5'-phosphate (PLP), and their associations with plasma homocysteine in 1,236 Puerto Rican adults, aged 45 to 75 years, living in the greater Boston area. DESIGN: Baseline data were analyzed cross-sectionally. METHOD: Questionnaire data were collected by home interview. Dietary intake was assessed with a semiquantitative food frequency questionnaire. Plasma PLP and homocysteine were assayed from blood samples collected in the home. RESULTS: The mean daily intake of vitamin B-6 was 2.90 ± 1.28 mg for men and 2.61 ± 1.29 mg for women (P<0.001). Approximately 11% were deficient (PLP <4.94 ng/mL [PLP <20 nmol/L]) and another 17% insufficient (PLP ≥ 4.94 but <7.41 ng/mL [PLP ≥ 20 but <30 nmol/L]). Household income below the poverty threshold, physical inactivity, and current smoking were significantly associated with lower plasma PLP (P<0.05). Food groups contributing most to vitamin B-6 intake included ready-to-eat cereals, poultry, rice, potatoes, and dried beans. However, only intake of ready-to-eat cereals and use of supplements with vitamin B-6 were significantly associated with plasma PLP sufficiency (≥ 7.41 vs <7.41 ng/mL [PLP ≥ 30 vs <30 nmol/L], P<0.01). Both vitamin B-6 intake and PLP were significantly associated with plasma total homocysteine (P<0.001). The association between PLP and homocysteine remained statistically significant after further adjustment for plasma vitamin B-12 and folate (P=0.028). CONCLUSIONS: Given the known importance of vitamin B-6 to health, the high prevalence of low vitamin B-6 status in this Puerto Rican population is of concern. Further work is needed to clarify the potential role that insufficient vitamin B-6 may have in relation to the observed health disparities in this population.

Comparison of blood aminotransferase methods for assessment of myopathy and hepatopathy in Florida manatees (Trichechus manatus latirostris).

Muscle injury is common in Florida manatees (Trichechus manatus latirostris). Plasma aspartate aminotransferase (AST) is frequently used to assess muscular damage in capture myopathy and traumatic injury. Therefore, accurate measurement of AST and alanine aminotransferase (ALT) is important in managed, free-ranging animals, as well as in those rehabilitating from injury. Activities of these enzymes, however, are usually not increased in manatees with either acute or chronic muscle damage, despite marked increases in plasma creatine kinase activity. It is hypothesized that this absence of response is due to apoenzymes in the blood not detected by commonly used veterinary assays. Addition of coenzyme pyridoxal-5-phosphate (P5P or vitamin B6) should, therefore, result in higher measured enzyme activities. The objective of this study was to determine the most accurate, precise, and diagnostically useful method for aminotransferase measurement in manatees that can be used in veterinary practices and diagnostic laboratories. Additionally, appropriate collection and storage techniques were assessed. The use of an optimized commercial wet chemical assay with 100 micromol P5P resulted in a positive bias of measured enzyme activities in a healthy population of animals. However, AST and ALT were still much lower than that typically observed in domestic animals and should not be used alone in the assessment of capture myopathy and muscular trauma. Additionally, the dry chemistry analyzer, typically used in clinics, reported significantly higher and less precise AST and ALT activities with poor correlation to those measured with wet chemical methods found in diagnostic laboratories. Therefore, these results cannot be clinically compared. Overall, the optimized wet chemical method was the most precise and diagnostically useful measurement of aminotransferase in samples. Additionally, there was a statistically significant difference between paired serum and plasma measurement, indicating that separate reference intervals should be established for serum and plasma. Finally, storage of these enzymes at -70 degrees C for 1 mo resulted in up to a 25% decrease in enzymatic activity in manatee plasma.

Assessment of vitamin B-6 estimated average requirement and recommended dietary allowance for adolescents aged 13-15 years using vitamin B-6 intake, nutritional status and anthropometry.

Because of limited available information, the Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) of vitamin B-6 for adolescents were recently estimated by extrapolation from adult values. To determine vitamin B-6 requirements and to provide recommendations for intakes, vitamin B-6 intake, nutritional status and anthropometry were studied in 134 healthy adolescents (63 boys and 71 girls) aged 13-15 y in Tainan, Taiwan. Direct and indirect vitamin B-6 indicators were measured in plasma, erythrocytes and urine. The anthropometric data of the adolescents in this study were similar to those of the first Nutrition and Health Survey in Taiwan (NAHSIT), conducted from 1993 to 1996, showing the normal growth and development of this adolescent group. All subjects had plasma pyridoxal-5'-phosphate (PLP) concentrations > or = 20 nmol/L, indicating an adequate vitamin B-6 status. The mean dietary vitamin B-6 intakes of boys and girls were 1.04 +/- 0.24 and 0.83 +/- 0.26 mg/d, respectively. Vitamin B-6 status indicators, including plasma PLP, erythrocyte alanine activity coefficient (EALT-AC), aspartate aminotransferase activity coefficient (EAST-AC) and urinary 4-pyridoxic acid (4-PA), were correlated with vitamin B-6 intake (r = 0.84, -0.84, -0.77 and 0.86, respectively, P < 0.01). Adequate values of plasma PLP (> or = 20 nmol/L), EALT-AC (<1.25), EAST-AC (<1.8) and urinary 4-PA (>3.0 micromol/d) were used to determine the EAR according to the Dietary Reference Intake committee methodology. The present study suggests that vitamin B-6 EAR (RDA) for adolescent boys and girls aged 13-15 y are 1.07 (1.28) and 0.90 (1.08) mg/d, respectively.

Selenium status and its correlates in a British national diet and nutrition survey: people aged 65 years and over.

Plasma selenium (Se) concentrations were measured in 1134 British people aged 65 years and over, living in mainland Britain during 1994-1995. Eight hundred and eighty-three lived in the community ("free-living"), while the remainder lived in institutions (residential and nursing homes). The overall mean plasma Se concentrations was 0.90 micromol/l (inner 95% range 0.50-1.36 micromol/l). Free-living people had significantly higher values than counterparts living in institutions, and there was an overall inverse correlation with age. Plasma Se varied with season (lower from October to December than at other times of the year), while values were higher in southern Britain than in the North. Socio-economic associations also existed (lower plasma Se in people receiving state benefits or with poorer educational attainment), while smokers had lower values than non-smokers. Several indices of poor health status or of medicine use were correlated with lower plasma Se, which was also predicted by several biochemical or haematological indices of infection or inflammation. Plasma Se was strongly and directly correlated with plasma albumin, zinc, cholesterol, vitamin C, several carotenoids, alpha-tocopherol, pyridoxal phosphate, and with blood haemoglobin and several anthropometric indices. All relationships were independent of age and gender, and are consistent with the view that plasma Se levels are higher in fit and well-nourished elderly people and lower in those who are frail, poorly-nourished and unwell. Whole-blood glutathione peroxidase generally did not share these relationships, was only very weakly correlated with plasma Se, and appeared to be less useful as a status indicator in this population group.

Assessment of vitamin B-6 status in young women consuming a controlled diet containing four levels of vitamin B-6 provides an estimated average requirement and recommended dietary allowance.

The Recommended Dietary Allowance (RDA) of vitamin B-6 for young women was recently reduced from 1.6 to 1.3 mg/d based on an adequate plasma pyridoxal phosphate (PLP) concentration of 20 nmol/L. To assess vitamin B-6 requirements and suggest recommendations for intake, seven healthy young women consumed a controlled diet providing 1.2 g protein/kg body weight for a 7-d adjustment period (1.0 mg vitamin B-6/d) and three successive 14-d experimental periods (1.5, 2.1 and 2.7 mg/d, respectively). Direct and indirect vitamin B-6 status indicators were measured in plasma, erythrocytes and urine. Indicators most strongly correlated with vitamin B-6 intake [i.e., plasma and erythrocyte PLP, urinary 4-pyridoxic acid (4-PA) and total vitamin B-6] were regressed on vitamin B-6 intake and the dietary vitamin B-6 to protein ratio. Inverse prediction using adequate and baseline values estimated vitamin B-6 requirement. Adequate values were determined for plasma PLP and urinary 4-PA from baseline values of 60 previous subjects, using the statistical method suggested by Sauberlich. The current study suggests a vitamin B-6 Estimated Average Requirement (EAR) for young women of 1.1 mg/d or 0.016 mg/g protein, and a RDA of 1.5 mg/d or 0.020 mg/g protein. When results from this study are combined with data from four other recent studies, the combined data predict an EAR of 1.2 mg/d or 0.015 mg/g protein, and a RDA of 1.7 mg/d or 0.018 mg/g protein. This study suggests that the current vitamin B-6 RDA may not be adequate.

Vitamin B-6 requirement and status assessment: young women fed a depletion diet followed by a plant- or animal-protein diet with graded amounts of vitamin B-6.

The vitamin B-6 requirement of young women consuming a high-protein diet (1.55 g/kg body wt) and the effect of protein quality on this requirement was studied. In addition, the response of clinical, functional, and biochemical measures of vitamin B-6 nutriture to short-term depletion and step-wise repletion of vitamin B-6 were evaluated. Eight healthy young women resided in a metabolic unit and were fed a formula depletion diet (< 0.05 mg vitamin B-6/d) for 11-28 d followed by either an animal-protein (AP) or plant-protein (PP) diet with successively increasing vitamin B-6 intakes (0.5, 1.0, 1.5, and 2.0 mg/d) for periods of 14-21 d. Animal proteins were primarily from dairy and poultry sources and plant proteins were primarily from legumes. Vitamin B-6 status measures were assessed at weekly intervals. Results showed that a PP diet does not elevate the vitamin B-6 requirement over that required for an AP diet given the high amount of dietary protein used in this study. It was also found that 0.015 mg vitamin B-6/g protein intake normalized most biochemical indexes of vitamin B-6 status (including those indicative of functional status), and that 0.020 mg/g protein normalized all biochemical measures except total urinary vitamin B-6. Adding a margin of safety to either the 0.015 or 0.020 mg/g protein intake would raise the vitamin B-6 requirement for young women above the currently recommended dietary allowance of 0.016 mg/g protein.

A new perspective in the assessment of vitamin B-6 nutritional status during pregnancy in humans.

Plasma pyridoxal-5'-phosphate (PLP) concentration has been suggested as a valid indicator to assess vitamin B-6 nutritional status. Animal and human studies have shown that plasma PLP concentrations decrease progressively during pregnancy and large doses of vitamin B-6 supplementation are required to maintain plasma PLP at early or prepregnant levels. PLP is known to be hydrolyzed to pyridoxal (PL) by alkaline phosphatase (ALP), resulting in an inverse relationship between PLP and ALP. The object of this study was to compare the PLP-PL equilibrium in a group of healthy pregnant females with that of an age-matched nonpregnant control group from a similar socioeconomic background. The mean plasma PLP level was 37% lower, (P less than 0.0001), whereas the mean PL level was almost 90% higher (P less than 0.001) in the pregnant group than in the nonpregnant control group. The total amount of plasma PLP and PL levels, however, did not differ significantly (P greater than 0.24) between the two groups. Because the PL vitamer is regarded as the ultimate transport form of vitamin B-6, it may serve as a readily available source of vitamin B-6 to meet possible increased metabolic demands. Therefore, the estimation of plasma PLP alone does not permit an accurate assessment or understanding of the nutritional status and the physiology of vitamin B-6 in conditions associated with altered vitamin B-6 homeostases.

A micromethod for determination of plasma pyridoxal phosphate and its use in assessment of storage stability of the vitamer.

A widely used macromethod employing tyrosine apodecarboxylase for measurement of pyridoxal phosphate (PLP) concentration in 0.5-1.0-ml plasma was modified to a microscale utilizing 0.1-ml plasma. Mean PLP levels in 12 plasma samples were 160.6 +/- 32.8 pmol/ml (mean +/- SD) when analyzed by the macromethod, and were not significantly different compared to those obtained by the micromethod (158.4 +/- 28.2 pmol/ml). Results of the two methods were significantly correlated (r = +0.97, p less than 0.001). Plasma PLP concentrations of 11 samples determined by the micromethod (means = 151.8 +/- 30.0 pmol/ml) were similar and significantly correlated (r = +0.95, p less than 0.001) to levels measured in the same samples 1-2 years earlier (means = 145.1 +/- 26.2 pmol/ml). This suggests that plasma PLP content of the samples was stable for up to 2 years of storage when the micromethod was utilized for analysis. The strong significant correlation between macro- and micromethods attests that the micromethod is a reliable alternative to the macromethod. The micromethod is useful in instances where only small samples of plasma are available for measurement of PLP.

Clinical chemical methods for the routine assessment of the vitamin status in human populations. Part II: The water-soluble vitamins B1, B2 and B6.

Simple and proven techniques for the assay of the coenzyme stimulation of the erythrocyte enzymes transketolase, glutathione reductase and glutamate oxaloacetate aminotransferase are described. The results found in a cohort of 150 blood donors and their comparison with the values for total thiamine in whole blood and pyridoxal phosphate in erythrocytes are presented.

Effect of oral contraceptives on nutrients. III. Vitamins B6, B12, and folic acid.

The interactions of oral contraceptive agents (OCA's) with vitamins were studied in a large population of women. In the upper socioeconomic groups, higher incidences of abnormal clinical signs related to vitamin deficiencies were seen in OCA users than in the control subjects. Plasma pyridoxal phosphate and red cell and serum folate were lower in subjects using OCA's in the upper socioeconomic group as compared to levels in the control subjects. Reduction in erythrocyte glutamic oxalacetic transaminase (EGOT) activity and elevation in the EGOT-stimulation test were observed in subjects using OCA's in both upper and lower socioeconomic groups. These observations suggest a relatively deficient state with respect to vitamins B6 and folic acid in OCA users. No significant effect on serum vitamin B12 was observed as a result of OCA administration.

PIP: The effect of oral contraceptives (OCs) on Vitamins-B6, -B12, and folic acid metabolism was studied in a large population of women. The OCs Norinyl (1 mg norethindrone plus 50 mcg mestranol) and Ovral (.5 mg norgestrel and 50 mcg ethinyl estradiol) were administered for 3 or more months. Higher incidences of abnormal clinical signs related to vitamin deficiency were seen in the upper socioeconomic OC users then in the control subjects. Plasma pyridoxal phosphate and red cell and serum folate were lower in OC users in the upper socioeconomic group as compared with levels in control subjects. A reduction in erythrocyte gl utamic oxalacetic transaminase (EGOT) activity and an elevation in the EGOT-stimulation test were observed in OC users in both upper and lower socioeconomic groups. These results suggest a relatively deficient state with respect to Vitamin-B6 and folic acid in OC users. No marked effects were seen with respect to Vitamin-B12 levels. These data are consistent with the hypothesis that the subjects in lower socioeconomic groups were already marginally deficient in Vitamin-B6 and folic acid and further reduction due to OCs could not be detected.

Assessment of vitamin B 6 status. Studies on pregnant women and oral contraceptive users.

The vitamin B6 status of 10 pregnant women (third trimester), 9 oral contraceptive agent users, and 12 notnpregnant women (controls) was investigated over a 10-week period by means of the erythrocyte glutamate-oxaloacetate transaminase (E-GOT) activation test and by measurements of whole blood pyridoxal phosphate levels. Blood pyridoxal phosphate levels in oral contraceptive agent users (7.6 plus or minus 1.1 ng/ml) were significantly lower than in the control group (9.6 plus or minus 1.7 mg/ml)indicating a relative vitamin B6 deficiency. Pyridoxal phosphate levels in pregnant women(5.1 plus or minus 1.3ng/ml) were even lower; in fact, no overlap was found in individual mean values between the pregnant and control groups. The E-GOT activation test did not indicate a vitamin deficiency in the pregnant women or in oral contraceptive agent users and the E-GOT activation factor did not correlate with blood pyridoxal phosphate levels unless results obtained after pyridoxine hydrochloride (20 mg/day) administration were included. The E-GOT activation test appears to be a poor indicator of vitamin B6 status, except in pronounced deficiency as it is less responsive to vitamin depletion than blood pyridoxal phosphate levels, and suffers from relatively large variations in individual control values. This may be a result of factors unrelated to vitamin B6 as blood pyridoxal phosphate levels remained fairly constant in the individuals investigated.