The regulatory effects of pyridoxine deficiency on the grass carp (Ctenopharyngodon idella) gill barriers immunity, apoptosis, antioxidant, and tight junction challenged with Flavobacterium columnar.

The effects of dietary pyridoxine (PN) on the gill immunity, apoptosis, antioxidant and tight junction of grass cap (Ctenopharyngodon idella) were investigated in this study. Fish were fed semi-purified diets containing graded levels of PN for 10 weeks, and then challenged with Flavobacterium columnare by bath immersion exposure for 3 days. The results indicated that compared with the optimal PN level, PN deficiency resulted in a decline in the antimicrobial compound production of gill. In addition, PN deficiency up-regulated the pro-inflammatory cytokines and down-regulated the anti-inflammatory cytokines gene expression, which might be associated with the enhanced nuclear factor κB p65 and the inhibited target of rapamycin signalling pathways, respectively, suggesting that PN deficiency could impair gill immune barrier function. Furthermore, PN deficiency (1) induced cell apoptosis, which may be partly associated with the (apoptotic protease activating factor-1, Bcl-2 associated X protein)/caspase-9 and c-Rel/tumor necrosis factor α (rather than FasL)/caspase-8 mediated apoptosis pathway. (2) Inhibited Kelch-like ECH-associating protein 1a/NF-E2-related factor 2 mRNA expression, decreased the mRNA expression and activities of antioxidant enzymes, increased the levels of reactive oxygen species, protein carbonyl and malondialdehyde. (3) Increased the mRNA expression level of myosin light chain kinase, which may be result in the down-regulation of tight junction complexes such as zonula occludens 1, occludin and claudins (expect claudin-12 and claudin-15). These results suggest that PN deficiency could impair gill physical barrier function. In summary, dietary PN deficiency could cause the impairment of gill barrier function associated with immunity, apoptosis, antioxidant and tight junction, which may result in the increased the susceptibility of fish to pathogenic bacteria. Moreover, based on the gill rot morbidity, LZ activity and MDA content, the dietary PN requirements for grass cap were estimated to be 4.85, 4.78 and 4.77 mg kg-1 diet, respectively.

Insight into vitamin B6 -dependent epilepsy due to PLPBP (previously PROSC) missense mutations.

Vitamin B6 -dependent genetic epilepsy was recently associated to mutations in PLPBP (previously PROSC), the human version of the widespread COG0325 gene that encodes TIM-barrel-like pyridoxal phosphate (PLP)-containing proteins of unclear function. We produced recombinantly, purified and characterized human PROSC (called now PLPHP) and its six missense mutants reported in epileptic patients. Normal PLPHP is largely a monomer with PLP bound through a Schiff-base linkage. The PLP-targeting antibiotic d-cycloserine decreased the PLP-bound peak as expected for pseudo-first-order reaction. The p.Leu175Pro mutation grossly misfolded PLPHP. Mutations p.Arg241Gln and p.Pro87Leu decreased protein solubility and yield of pure PLPHP, but their pure forms were well folded, similarly to pure p.Pro40Leu, p.Tyr69Cys, and p.Arg205Gln mutants (judged from CD spectra). PLPHP stability was decreased in p.Arg241Gln, p.Pro40Leu, and p.Arg205Gln mutants (thermofluor assays). The p.Arg241Gln and p.Tyr69Cys mutants respectively lacked PLP or had a decreased amount of this cofactor. With p.Tyr69Cys there was extensive protein dimerization due to disulfide bridge formation, and PLP accessibility was decreased (judged from d-cycloserine reaction). A 3-D model of human PLPHP allowed rationalizing the effects of most mutations. Overall, the six missense mutations caused ill effects and five of them impaired folding or decreased stability, suggesting the potential of pharmacochaperone-based therapeutic approaches.

Vitamin B-6 restriction reduces the production of hydrogen sulfide and its biomarkers by the transsulfuration pathway in cultured human hepatoma cells.

BACKGROUND: Pyridoxal 5'-phosphate (PLP) functions as a coenzyme in many cellular processes including one-carbon metabolism and the interconversion and catabolism of amino acids. PLP-dependent enzymes, cystathionine ß-synthase and cystathionine γ-lyase, function in transsulfuration but also have been implicated in the production of the endogenous gaseous signaling molecule hydrogen sulfide (H2S) concurrent with the formation of the biomarkers lanthionine and homolanthionine. OBJECTIVE: Our objective was to determine if H2S production and concurrent biomarker production is affected by vitamin B-6 restriction in a cell culture model. METHODS: We used cultured human hepatoma cells and evaluated static intracellular profiles of amino acids and in vivo kinetics of H2S biomarker formation. Cells were cultured for 6 wk in media containing concentrations of pyridoxal that represented severe vitamin B-6 deficiency (15 nmol/L pyridoxal), marginal deficiency (56 nmol/L pyridoxal), adequacy (210 nmol/L pyridoxal), and standard medium formulation providing a supraphysiologic pyridoxal concentration (1800 nmol/L pyridoxal). RESULTS: Intracellular concentrations of lanthionine and homolanthionine in cells cultured at 15 nmol/L pyridoxal were 50% lower (P < 0.002) and 47% lower (P < 0.0255), respectively, than observed in cells cultured at 1800 nmol/L pyridoxal. Extracellular homocysteine and cysteine were 58% and 46% higher, respectively, in severely deficient cells than in adequate cells (P < 0.002). Fractional synthesis rates of lanthionine (P < 0.01) and homolanthionine (P < 0.006) were lower at 15 and 56 nmol/L pyridoxal than at both higher pyridoxal concentrations. The rate of homocysteine remethylation and the fractional rate of homocysteine production from methionine were not affected by vitamin B-6 restriction. In vitro studies of cell lysates using direct measurement of H2S also had a reduced extent of H2S production in the 2 lower vitamin B-6 conditions. CONCLUSION: In view of the physiologic roles of H2S, these results suggest a mechanism that may be involved in the association between human vitamin B-6 inadequacy and its effects on human health.

Pyridoxine supply in human development.

Vitamin B(6) has an important role in the function of the human nervous system. Experimental data are not generally available on the role in human development, but significant conclusions may be made from studies of the effect of disorders of B(6) vitamer metabolism. Vitamin B(6) comprises seven compounds - pyridoxal, pyridoxine, pyridoxamine and their respective 5' phosphates. The common active form in human tissue is the 5'-phosphate form of pyridoxal (PLP) most of which is found in muscle bound to phosphorylase. Like many vitamins, B(6) can function both as a co-enzyme and as a chaperone. Pyridoxal-5'-phosphate is the metabolically active form and is involved in 100 enzymatic reactions including carbohydrate, amino acid, and fatty acid metabolism. There is evidence that in some situations B(6) vitamers can function as antioxidants. The fetus is dependent on the placenta for supply of vitamin B(6) and the demand correlates with amino acid metabolism. Few reports are available on the role of B(6) in embryogenesis. Studies of human disorders where B(6) metabolism is blocked show a major role in neurotransmitter function with secondary cerebral and cerebellar hypoplasia. Pyridoxine potentiates vitamin A teratogenicity and an excess leads to peripheral nerve cell degeneration. The key role of vitamin B(6) in the developing human is in metabolism, especially of the neurotransmitters.

Marginal vitamin B-6 deficiency decreases plasma (n-3) and (n-6) PUFA concentrations in healthy men and women.

Previous animal studies showed that severe vitamin B-6 deficiency altered fatty acid profiles of tissue lipids, often with an increase of linoleic acid and a decrease of arachidonic acid. However, little is known about the extent to which vitamin B-6 deficiency affects human fatty acid profiles. The aim of this study was to determine the effects of marginal vitamin B-6 deficiency on fatty acid profiles in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC) of healthy adults fed a 28-d, low-vitamin B-6 diet. Healthy participants (n = 23) received a 2-d, controlled, vitamin B-6-adequate diet followed by a 28-d, vitamin B-6-restricted diet to induce a marginal deficiency. Plasma HDL and LDL cholesterol concentrations, FFA concentrations, and erythrocyte and PBMC membrane fatty acid compositions did not significantly change from baseline after the 28-d restriction. Plasma total arachidonic acid, EPA, and DHA concentrations decreased from (mean ± SD) 548 ± 96 to 490 ± 94 µmol/L, 37 ± 13 to 32 ± 13 µmol/L, and 121 ± 28 to 109 ± 28 µmol/L [positive false discovery rate (pFDR) adjusted P < 0.05], respectively. The total (n-6):(n-3) PUFA ratio in plasma exhibited a minor increase from 15.4 ± 2.8 to 16.6 ± 3.1 (pFDR adjusted P < 0.05). These data indicate that short-term vitamin B-6 restriction decreases plasma (n-3) and (n-6) PUFA concentrations and tends to increase the plasma (n-6):(n-3) PUFA ratio. Such changes in blood lipids may be associated with the elevated risk of cardiovascular disease in vitamin B-6 insufficiency.

A history of the isolation and identification of vitamin B(6).

In the 1930s, Rudolf Peters showed that young rats kept on a semi-synthetic diet with added thiamin and riboflavin but no other supplement developed 'rat acrodynia', a condition characterized by severe cutaneous lesions. In 1934, Paul György showed that the factor which cured 'rat acrodynia' was vitamin B(6). Other studies soon showed that vitamin B(6) deficiency produced convulsions in rats, pigs, and dogs, and a microcytic anemia in certain animals. Samuel Lepkovsky isolated and crystallized vitamin B(6) in 1938. The following year, Leslie Harris and Karl Folkers, and Richard Kuhn and his associates independently showed that vitamin B(6) was a pyridine derivative, 3-hydroxy-4,5-dihydroxy-methyl-2-methyl-pyridine. György proposed the term pyridoxine for this derivative. Esmond Snell developed a microbiological growth assay in 1942 that led to the characterization of pyridoxamine, the animated product of pyridoxine, and pyridoxal, the formyl derivative of pyridoxine. Further studies showed that pyridoxal, pyridoxamine, and pyridoxine have largely equal activity in animals and owe their vitamin activity to the ability of the organism to convert them into the enzymatically active form pyridoxal-5-phosphate. Pyridoxal-5-phosphate plays a role in a wide variety of enzyme systems, especially in the metabolic utilization and transformation of amino acids.

Vitamin B6 deficiency disrupts serotonin signaling in pancreatic islets and induces gestational diabetes in mice.

In pancreatic islets, catabolism of tryptophan into serotonin and serotonin receptor 2B (HTR2B) activation is crucial for ß-cell proliferation and maternal glucose regulation during pregnancy. Factors that reduce serotonin synthesis and perturb HTR2B signaling are associated with decreased ß-cell number, impaired insulin secretion, and gestational glucose intolerance in mice. Albeit the tryptophan-serotonin pathway is dependent on vitamin B6 bioavailability, how vitamin B6 deficiency impacts ß-cell proliferation during pregnancy has not been investigated. In this study, we created a vitamin B6 deficient mouse model and investigated how gestational deficiency influences maternal glucose tolerance. Our studies show that gestational vitamin B6 deficiency decreases serotonin levels in maternal pancreatic islets and reduces ß-cell proliferation in an HTR2B-dependent manner. These changes were associated with glucose intolerance and insulin resistance, however insulin secretion remained intact. Our findings suggest that vitamin B6 deficiency-induced gestational glucose intolerance involves additional mechanisms that are complex and insulin independent.

New treatment paradigms in neonatal metabolic epilepsies.

Neonatal seizures represent a major challenge among the epilepsies vis-à-vis seizure classification, electroclinical correlation, inherent excitability of neocortex, ontogenic characteristics of neurotransmitter receptors, and responsiveness to standard antiepileptic drugs. Each of these factors renders neonatal seizures more difficult to treat, and therapy has been a vexing area for recent advances in this seizure category. Conversely, specific metabolic disorders have very special therapeutic considerations in the clinical setting of neonatal seizures which require a high index of clinical suspicion and rapid intervention for a successful outcome. The prototype is pyridoxine dependency, although pyridoxal 5'-phosphate dependency is a recently recognized but treatable neonatal epilepsy that deserves earmarked distinction. Clinicians must remain vigilant for these possibilities, including atypical cases where apparent seizure-free intervals may occur. Folinic acid-dependent seizures are allelic with pyridoxine dependency. Serine-dependent seizures and glucose transporter deficiency may present with neonatal seizures and have specific therapy. A vital potassium channel regulated by serum ATP/ADP ratios in the pancreas and brain may be mutated with a resultant neuroendocrinopathy characterized by development delay, epilepsy, and neonatal diabetes (DEND). This requires oral hypoglycaemic therapy, and not insulin, for neurological responsiveness. The startle syndrome of hyperekplexia, which mimics neonatal epilepsy, has been associated with laryngospasm and sudden death but is treated with benzodiazepines.

Vitamin B6 status, deficiency and its consequences--an overview.

BACKGROUND: Vitamin B6 is thought to be a most versatile coenzyme that participates in more than 100 biochemical reactions. It is involved in amino acid and homocysteine metabolism, glucose and lipid metabolism, neurotransmitter production and DNA/RNA synthesis. Vitamin B6 can also be a modulator of gene expression. Nowadays, clinically evident vitamin B6 deficiency is not a common disorder, at least in the general population. Nevertheless, a subclinical, undiagnosed deficiency may be present in some subjects, particularly in the elderly. OBJECTIVE: This review gives a complete overview over the metabolism and interactions of vitamin B6. Further, we show which complications and deficiency symptoms can occur due to a lack of vitamin B6 and possibilities for public health and supplemental interventions. METHODS: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "vitamin B6", "pyridoxal", "cancer", "homocysteine", etc. For a complete understanding, we included studies with early findings from the forties as well as recent results from 2006. These studies were summarised and compared in different chapters. RESULTS AND CONCLUSION: In fact, it has been proposed that suboptimal vitamin B6 status is associated with certain diseases that particularly afflict the elderly population: impaired cognitive function, Alzheimer's disease, cardiovascular disease, and different types of cancer. Some of these problems may be related to the elevated homocysteine concentrations associated to vitamin B6 deficiency, but there is also evidence for other mechanisms independent of homocysteine by which a suboptimal vitamin B6 status could increase the risk for these chronic diseases.

Vitamin B-6, Independent of Homocysteine, Is a Significant Factor in Relation to Inflammatory Responses for Chronic Kidney Disease and Hemodialysis Patients.

The purpose of this study was to investigate whether plasma pyridoxal 5'-phosphate (PLP) and homocysteine were dependent on or independent of each other in order to be associated with inflammatory markers in patients with chronic kidney disease (CKD) or those receiving hemodialysis treatment. This was a cross-sectional study. Sixty-eight stage 2-5 CKD patients and 68 hemodialysis patients had one time fasting blood drawn for measurements of plasma PLP, pyridoxal (PL), homocysteine, and several inflammatory markers. Early CKD stage (stages 2-3) patients showed significantly lower plasma PLP levels and homocysteine concentrations than patients in an advanced CKD stage (stages 4-5) and those undergoing hemodialysis. Plasma PLP significantly correlated with CRP levels (partial rs = -0.21, p < 0.05) and plasma PL significantly correlated with IL-10 levels (partial rs = -0.24, p < 0.01), while plasma PLP plus PL significantly correlated with both CRP levels (partial rs = -0.20, p < 0.05) and interleukin-1ß (partial rs = 0.22, p < 0.05) levels after adjusting for plasma homocysteine and other potential confounders. Plasma homocysteine displayed no significant correlations with any inflammatory markers. Vitamin B-6 status, rather than homocysteine, appeared to be a significant factor in relation to inflammatory responses for CKD and hemodialysis patients.

Plasma folate, vitamin B-6, and vitamin B-12 and breast cancer risk in BRCA1- and BRCA2-mutation carriers: a prospective study.

BACKGROUND: B vitamins [vitamins B-6, B-9 (folate), and B-12] play important roles in nucleotide biosynthesis and biological methylation reactions, aberrancies of which have all been implicated in carcinogenesis. In the general population, evidence has suggested that high circulating folate and folic acid (synthetic form of folate) supplement use may increase breast cancer risk, but the role of folate in BRCA-associated breast cancer is not clear. OBJECTIVE: We prospectively evaluated the relation between plasma folate, pyridoxal 5'-phosphate (PLP; the biologically active form of vitamin B-6), and vitamin B-12 and breast cancer risk in women with a BRCA1/2 mutation. DESIGN: Baseline blood samples and biennial follow-up questionnaires were available for 164 BRCA1/2-mutation carriers with no previous history of cancer other than nonmelanoma skin cancer. Plasma folate, PLP, and vitamin B-12 concentrations were categorized dichotomously as high compared with low based on the upper 25% and the lower 75% of distribution, respectively. Cox proportional hazards were used to estimate the HR and 95% CI for the association between plasma biomarkers of each B vitamin and incident breast cancer. RESULTS: Over a mean follow-up of 6.3 y, 20 incident primary invasive breast cancers were observed. Women with high plasma folate concentrations (>24.4 ng/mL) were associated with significantly increased breast cancer risk (HR: 3.20; 95% CI: 1.03, 9.92; P = 0.04, P-trend across quintiles = 0.07) compared with that of women with low plasma folate concentrations (≤24.4 ng/mL). Plasma PLP and vitamin B-12 concentrations were not associated with breast cancer risk. CONCLUSIONS: Our data suggest that elevated plasma folate concentrations may be associated with increased risk of breast cancer in women with a BRCA1/2 mutation. Additional studies with a larger sample size and longer follow-up periods are warranted to clarify the relation between folate status and breast cancer risk in high-risk women.

Electrocardiographic changes in vitamin B6 deficient rats.

Serial electrocardiograms of vitamin B6 deficient rats show significant changes from those of rats on a complete diet. Animals fed a totally deficient diet from weaning grow slowly and die after about 12 weeks, often with a terminal weight loss. R and T amplitudes increase, then terminally decrease and are significantly greater than those of control animals. The PR interval is significantly shorter at times. Individuals have shown transient AV block, irregular sinus rhythm, wandering pacemaker, and inverted T waves. Autopsy findings include hypertrophy (89%), dilatation (61%) and atrial thrombi (44%). ECG's of adult animals remained normal for about three months after being fed the deficient diet. The two males developed premature ventricular contractions of several ectopic foci. Finally, split QRS complexes were observed. The female had a normal ECG until the final record at 234 days when some minor changes were seen. Extensive cardiomyopathic changes were found in two out of the three adults at autopsy.

Oral exposure to the anti-pyridoxine compound 1-amino D-proline further perturbs homocysteine metabolism through the transsulfuration pathway in moderately vitamin B6 deficient rats.

Pyridoxal 5'-phosphate (PLP; a B6 vitamer) serves as an important cofactor in a myriad of metabolic reactions, including the transsulfuration (TS) pathway, which converts homocysteine (Hcy) to cysteine. While overt vitamin B6 deficiency is rare, moderate deficiency is common and may be exacerbated by anti-pyridoxine factors in the food supply. To this end, we developed a model of moderate B6 deficiency and a study was conducted to examine the in vivo effect of 1-amino D-proline (1ADP), an anti-pyridoxine factor found in flaxseed, on indices of Hcy metabolism through the TS pathway in moderately B6 deficient rats. Male weaning rats received a semi-purified diet containing either 7 mg/kg (control; CD) or 0.7 mg/kg (moderately deficient; MD) diet of pyridoxine·hydrochloride (PN∙HCl), each with 1 of 4 levels of 1ADP, viz. 0, 0.1, 1 and 10 mg/kg diet for 5 weeks. Perturbations in vitamin B6 biomarkers were more pronounced in the MD group. Plasma PLP was significantly reduced, while plasma Hcy (8-fold) and cystathionine (11-fold) were increased in rats consuming the highest amount of 1ADP in the MD group. The activities of hepatic cystathionine ß-synthase and cystathionine γ-lyase enzymes were significantly reduced in rats consuming the highest 1ADP compared to the lowest, for both levels of PN∙HCl. Dilation of hepatic central veins and sinusoids, mild steatosis and increased liver triglycerides were present in MD rats consuming the highest 1ADP level. The current data provide evidence that the consumption of an anti-pyridoxine factor linked to flaxseed may pose a risk for subjects who are moderate/severe vitamin B6 deficient.

Neuroendocrinology of pyridoxine deficiency.

Dihydroxyphenylalanine decarboxylase and 5-hydroxytryptophan decarboxylase respectively have high and low affinities for pyridoxal phosphate. In the pyridoxine-deficient animal, hypothalamic serotonin content is significantly reduced without any change in catecholamine levels. Hypothalamic neurotransmitters affect the hypothalamo-pituitary-end organ axes. Specifically, the decrease in hypothalamic serotonin in the pyridoxine-deficient rat results in tertiary hypothyroidism. In addition, pineal function is affected in deficient animals due to decreased synthesis of melatonin.

Sympathetic stimulation and hypertension in the pyridoxine-deficient adult rat.

Pyridoxal phosphate is the coenzyme of various decarboxylases involved in the formation of monoamine neurotransmitters such as gamma-aminobutyric acid, serotonin, dopamine, and norepinephrine. Adult male Sprague-Dawley rats placed on a pyridoxine-deficient diet for 8 weeks showed significant hypertension compared with pyridoxine-supplemented controls. Hypothalamic contents of pyridoxal phosphate, gamma-aminobutyric acid, and serotonin in the pyridoxine-deficient rats were significantly lower than those in pyridoxine-supplemented controls. Hypertension was associated with sympathetic stimulation. Treatment of pyridoxine-deficient rats with a single dose of pyridoxine (10 mg/kg body weight) reversed the blood pressure to normal levels within 24 hours, with concomitant restorations of hypothalamic serotonin and gamma-aminobutyric acid as well as the return of plasma norepinephrine and epinephrine to normal levels. Also, pyridoxine treatment reversed the hypothalamic hypothyroidism observed in pyridoxine-deficient rats. These results indicate an association between pyridoxine deficiency and sympathetic stimulation leading to hypertension.

Effects of exhaustive exercise and vitamin B6 deficiency on free radical oxidative process in male trained rats.

There is growing evidence that oxygen free radical production and subsequent lipid peroxidation are normal sequelae to the rise in oxygen consumption concomitant with exercise. In addition, increased lipid peroxidation has also been shown in vitamin B6-deficient rat plasma, liver, and kidney. To investigate the potential for a role of vitamin B6 in exercise-induced oxidative stress, 36 male Sprague-Dawley rats received 0 (n = 12), 2 (n = 12), and 8 mg pyridoxine (PN)-HCl/kg diet (n = 12) and were trained by a 9-week swimming program. After 9-weeks of training, six rats (exhausted: E rats) of each vitamin group were exercised to exhaustion by swimming while the other six rats rested (nonexhausted: NE rats). Ascorbate, ascorbate free radical and antilipoperoxidant capability (AC) were evaluated in plasma. These parameters were higher in E rats than in NE rats. Free radical-mediated lipid peroxidation was measured in tissue and plasma by evaluation of thiobarbituric acid reactive substances (TBARS) content. This index of peroxidation was significantly increased in liver of E rats but not in plasma, heart, and gastrocnemius muscle. Concentration of TBARS in liver was the highest in vitamin B6-deficient rats (consuming 0 mg PN-HCl/kg diet) and the lowest in vitamin B6-sufficient rats (consuming 8 mg PN-HCl/kg diet). Vitamin E (alpha-tocopherol) levels in liver and heart were negatively related to vitamin B6 levels in the diet. Independently of vitamin B6, liver and muscle alpha-tocopherol levels were significantly higher in E animals than in NE animals. There is good evidence according to our results that exercise induced an oxidative stress, as indicated by a significant increase of ascorbyl radical levels in the plasma. The effects of vitamin B6 deficiency on the free radical metabolism are low in trained rats. On the contrary, exhaustive exercise induced modifications in the metabolism pathways of vitamin C and E objectivated by variations of levels of vitamin C in the plasma and vitamin E in liver.

Thiamin, riboflavin, and vitamins B-6 and C: impact of combined restricted intake on functional performance in man.

A double-blind study of combined restriction of thiamin, riboflavin, and vitamins B-6 and C was carried out with 23 healthy males. During 8 wk of low vitamin intake, 12 deficient subjects consumed daily a diet of normal food products, providing maximally 32.5% of the Dutch Recommended Dietary Allowances (RDA) for thiamin, riboflavin, vitamins B-6 and C. Other vitamins were supplemented at twice the RDA. Eleven control subjects consumed the same diet but with a supplementation of twice the RDA of all vitamins. In deficient subjects blood vitamin levels, urinary vitamin excretion, and erythrocytic enzyme activities decreased; in vitro enzyme stimulation increased. Vitamin depletion had no ill effects on health, physical activity, and mental performance. A significant decrease was observed in aerobic power (VO2max) and onset of blood lactate accumulation (p less than 0.001) of 9.8 and 19.6%, respectively. A combined restricted intake of thiamin, riboflavin, and vitamins B-6 and C causes a decrease in physical performance within a few weeks.

Vitamin B-6 status of Egyptian mothers: relation to infant behavior and maternal-infant interactions.

Functional consequences of marginal maternal vitamin B-6 status for behavior of the neonate and for mother-infant interactions at age 3-6 mo were assessed by a double-blind procedure. In 27 of 70 Egyptian village women studied, vitamin B-6 concentration of their milk was considered indicative of poor maternal vitamin B-6 nutriture. Neonatal behavior, quantified by the Brazelton Neonatal Behavioral Assessment Scale, showed that consolability, appropriate build-up to a crying state, and response to aversive stimuli were significantly correlated with maternal vitamin B-6 nutriture. Naturalistic observational procedures, used twice monthly with infants aged 3-6 mo, indicated that mothers assessed as having marginal vitamin B-6 status were less responsive to their infants' vocalizations, showed less effective intervention to infant distress, and were more likely to use older siblings as care-givers than were mothers of better vitamin status. We conclude that vitamin B-6 was a factor influencing both the behavior of the mother and her infant.

Electroencephalographic changes and periodontal status during short-term vitamin B-6 depletion of young, nonpregnant women.

As part of a larger investigation to determine the effect of animal vs. plant proteins on the vitamin B-6 requirement of young women, clinical changes during vitamin B-6 depletion were documented. Eight healthy young women were confined to a metabolic unit and fed a defined formula diet nearly devoid of vitamin B-6 (less than 0.05 mg/d). Serial electroencephalographic (EEG) tracings, peripheral nervous system tests, periodontal evaluations, and biochemical measures of vitamin B-6 status were conducted. Within 12 d on the depletion diet, two of the eight women exhibited abnormal EEG tracings. These changes were readily reversed by repletion of vitamin B-6 at the 0.5-mg/d level. Biochemical measures reflected lowered vitamin B-6 status but were not predictive of the onset of EEG changes. No detectable alterations in oral or periodontal status were found, nor did plaque flora change markedly. This study is the first report of EEG changes occurring in women undergoing vitamin B-6 depletion and the first report to document EEG changes in adults within 12 d on a vitamin B-6-depletion regimen.

Physical and neuromotor development of progeny of pyridoxine-restricted rats cross-fostered with control or isonutritional dams.

Female rats were fed diets containing graded levels of pyridoxine throughout gestation. At parturition, the pups were cross-fostered with a dam which had been fed the same diet as the biological mother throughout gestation (an isonutritional foster mother), or with one which had received a control diet containing 400% of the National Research Council recommendations for B6 throughout gestation (a control foster mother), or were left to suckle the biological mother. Physical, neuromotor, and reflexological development of the pups was assessed throughout the 3 week lactation period. There were no significant differences between pups nursed by their biological mothers and by isonutritional foster mothers. Growth, reflex acquisition, and neuromotor activities were impaired in pups subjected to pyridoxine restriction during gestation. Acquisition of a number of reflexes and time spent in neuromotor activities were responsive to cross-fostering with a control foster mother but the deficits were not completely eliminated. Growth was only slightly affected by cross-fostering and acquisition of audicular startle and negative geotaxis was not affected by the nature of the foster mother. The latter reflexes are apparently determined directly by the gestational nutrition of the fetus whereas other reflexes and neuromotor activities are influenced by long-term effects of pyridoxine restriction on the postnatal performance of the dam as a mother, in addition to being directly influenced by maternal diet during gestation.