Excretion Of 4-pyridoxic Acid Research Articles

Influence of the rat diet enrichment with oat β-gucans on the assimilation of B group vitamins, mineral elements and lipid metabolism

Despite the widespread use of oat β-glucans as ingredient of foods and dietary supplements, there is insufficient data on their effect on the metabolism of vitamins and minerals. The purpose of the study was to evaluate the effect of including oat bran with a high content of β-glucans (β-glucan) in the diet on the absorption of micronutrients and lipid metabolism in growing rats deficient in vitamins D, group B and trace elements (iron, copper, zinc). Material and methods. After the development of micronutrient deficiency (for 23 days), in order to assess the effect of oat bran (5%) with a high content of β-glucans on the correction of the micronutrient status of growing male Wistar rats (with initial body weight of 70.7±0.7 g), the missing micronutrients were introduced in the semi-synthetic diet deficient in vitamins D, group B, iron, copper and zinc within 7 days either along with β-glucan (1.47%) or without its addition. Indicators of micronutrient sufficiency (riboflavin serum concentration, daily urinary excretion of thiamine, riboflavin and 4-pyridoxic acid, measured by fluorometric methods; serum concentration and urinary excretion of calcium, magnesium, iron, zinc, copper, phosphorus, measured by the atomic absorption method or using standard methods on a biochemical analyzer) and the biochemical parameters of blood serum were compared with the parameters of rats adequately provided with all micronutrients throughout the experiment. Results. Replenishment of missing micronutrients in the diet of rats with deficiency in vitamins D and group B, iron, copper and zinc for 7 days led to the elimination of deficiency of vitamins B1, B2 and B6, regardless of the presence of β-glucans in the diet. At the same time, against the background of the presence of β-glucans in the feed, an increase in the absorption of iron was observed, as evidenced by an increase by 1.73 times in iron blood plasma level (р<0.05) and a tendency towards its urinary excretion decrease by 1.60 fold (р<0.10) compared to animals from the control group. Adding oat bran with β-glucans to the feed did not lead to a decrease in blood plasma level of total cholesterol and low-density lipoproteins cholesterol. The levels of high-density lipoprotein cholesterol and triglycerides in rats of all three groups did not have statistically significant differences. Conclusion. The presence of β-glucans in the diet had virtually no effect on the absorption of B vitamins and improved the absorption of iron.

Vitamin B-6 Status Indices Are Lower in Pregnant than in Nonpregnant Women but Urinary Excretion of 4-Pyridoxic Acid Does Not Differ1–4

The cause of reduced plasma pyridoxal-5'-phosphate (PLP) concentration and the validity of plasma PLP concentration as a vitamin B-6 status indicator during pregnancy are not well understood. In this study, pregnant and nonpregnant women consumed a controlled diet for 5 d to exclude dietary intake as a factor in altered vitamin B-6 metabolic utilization. Plasma PLP and pyridoxal (PL) concentrations were significantly lower and higher, respectively, and plasma PL+PLP concentration was significantly lower during pregnancy. When plasma PLP and PL concentrations were normalized based on plasma albumin concentration, the differences were less marked but were still significant. The erythrocyte aspartate aminotransferase activity coefficient was significantly greater in pregnant women which is a further indication of reduced vitamin B-6 concentrations in the blood. No difference was observed in the urinary excretion of 4-pyridoxic acid between the pregnant and nonpregnant women. Results of this study demonstrate that vitamin B-6 status indices are lower during pregnancy without differences in the urinary excretion of 4-pyridoxic acid.

Vitamin B-6 Status of Women with a Constant Intake of Vitamin B-6 Changes with Three Levels of Dietary Protein

To determine the effect of varying levels of dietary protein with a constant intake of vitamin B-6 (B-6) on B-6 status, nine women were fed diets providing daily intakes of 1.25 mg B-6 and 0.5, 1.0 and 2.0 g protein/kg body weight. After an 8-d adjustment period, the women consumed each level of dietary protein for 14 d in a Latin-square design. Several direct and indirect B-6 status indicators were measured in blood and urine. Significant differences among protein levels were found for urinary 4-pyridoxic acid (4-PA) excretion (P < 0.01), plasma pyridoxal 5′-phosphate (PLP) concentration (P < 0.05), and urinary excretion of volatile amines (VA, kynurenine plus acetylkynurenine) after a 2-g L-tryptophan load (P < 0.05). Nitrogen intake was significantly negatively correlated with urinary 4-PA excretion (r = -0.619, P < 0.001) and plasma PLP concentration (r = -0.549, P < 0.01), and positively correlated with erythrocyte alanine aminotransferase percentage stimulation (r = 0.418, P < 0.05) and urinary post-tryptophan load excretion of xanthurenic acid (r = 0.535, P < 0.05), kynurenic acid (r = 0.563, P < 0.05) and VA (r = 0.626, P < 0.01). Compared with men consuming diets with similar B-6 to protein ratios in a previous study, the women excreted a greater percentage of the B-6 intake as 4-PA, had lower plasma PLP concentrations and excreted greater amounts of postload urinary tryptophan metabolites at all three protein levels. If the Recommended Dietary Allowance (RDA) of vitamin B-6 is to be based on the dietary B-6 to protein ratio, gender differences in response to varying protein intakes should be considered. For the levels of protein intake used in this study and a B-6 intake of 1.25 mg/d, a B-6 to protein ratio of greater than 0.020 mg/g is required for adequate vitamin B-6 status in women.

Effect of B-vitamin deficiency on biochemical, immunologic markers and trace element status of rats and mice of various lines

Biochemical, vitamin, trace element and immunological changes were searched for the combined nutritional deficiency of vitamins B1, B2, B6 on in vivo models in rats and mice. Female rats of Wistar (W) strain and hybrids of the 1st generation of Dark Aguti and Wistar (DA x W) strains, female mice of BALB/c strain and DBCB tetrahybrids were used in experiment. Animals received for 35 days a balanced diet (control) according to AIN-93 or a similar diet with the exception of vitamins B1, B2, B6 (experimental groups). The content of vitamins B1, B2 in liver, riboflavin blood plasma level and urinary excretion of thiamine, riboflavin and 4-pyridoxic acid were determined, as well as in rats: blood and liver content of α-tocopherol and retinol, blood biochemical indices of lipid and nitrogen metabolism, activity of cytochrome P isoforms-450 (CYP) in liver; in mice: the circulating levels of pro- and anti-inflammatory cytokines of blood plasma, in animals of both species - the content of essential and toxic elements in the kidneys. DAxW rats compared to W and DBCB mice compared to BALB/c were more sensitive to the development of B-vitamin deficiency judging by the B-vitamin status indicators. In the rats of the experimental groups, there were signs of a deterioration in blood and liver levels of vitamin E, multidirectional shifts in vitamin A sufficiency, increased activity of the CYP3A isoform (6β-TG), a decrease in triglycerides, total protein and albumin fraction levels with an increase in urea level. Manifestation degree of these effects depended on the choice of the animal's line. In mice, the B-vitamin deficiency was characterized by an increase in the levels of proinflammatory cytokines TNF-α, IL-10, IL-Ιβ, IL-6 and a decrease in IFN-γ and IL-17A. The content of magnesium, copper, zinc, chromium and silver was lowered, of cesium - was increased in the kidneys of the rats of the experimental groups. In mice, B-vitamin deficiency resulted in diminishment of magnesium, copper, zinc, chromium, selenium, cadmium and lead content, excess accumulation of cobalt and cesium. Some of these biomarkers are supposed to be used in pre-clinical evaluation of the effectiveness of new vitamin complexes, specialized foods and dietary supplements, as well as studies of interactions of various vitamins.

Urinary excretion of B-group vitamins reflects the nutritional status of B-group vitamins in rats.

We have reported previously that the urinary excretion of B-group vitamins reflects recent dietary intakes of these vitamins. We also proposed reference values for the urinary levels of B-group vitamins for human subjects, and used these for evaluating human nutritional status. However, the question arises as to whether the urinary excretion of B-group vitamins in animals or human subjects decreases immediately before they become B-group vitamin insufficient or when fed a diet low in vitamins. In the present study, rats were fed a vitamin-free diet for 5d, and changes in the levels of B-group vitamins in urine and blood were monitored. Urinary excretion of vitamin B1, vitamin B2, 4-pyridoxic acid (a catabolite of vitamin B6), pantothenic acid, folate and biotin steeply decreased, and all of the values reached zero within 1-2d. With respect to blood, the concentrations of only three of the eight B-group vitamins (vitamin B1, pyridoxal phosphate and biotin) decreased to 15% (P<0·0001), 7% (P<0·0001) and 2% (P<0·0001) on day 5, respectively, compared with the values at the beginning of the experiment. The decrease was more rapid and the changes were greater in the urine samples than in the blood samples. The present data complement our previous proposal that the urinary excretion of B-group vitamins reflects the nutritional status of these vitamins.

Disturbance of B-vitamin status in people with type 2 diabetes in Indonesia—Link to renal status, glycemic control and vascular inflammation

BackgroundDiabetes is associated with mishandling of thiamine in the kidney and development of diabetic nephropathy. The aim of this study is to assess the disturbance of thiamine and other B-vitamin status of patients with type 2 diabetes in Indonesia. MethodsOne hundred and fifteen patients with type 2 diabetes with and without microalbuminuria or albuminuria and 39 healthy people were recruited. After a 2-month washout period for B-vitamin supplementation, markers of vitamins B1, B6, B9 and B12, were determined. ResultsFractional excretion of thiamine (22.8 versus 33.5%; P<0.05) and urinary excretion of the vitamin B6 degradation product 4-pyridoxic acid (0.081 versus 0.133μmol/g creatinine, P<0.001) was increased in patients with type 2 diabetes with respect to healthy controls. There was also increased total plasma cobalamin (398 versus 547pmol/l, P<0.001) and holotranscobalamin (74 versus 97pmol/l, P<0.001) in patients with type 2 diabetes. In multiple regression analysis these were linked to HbA1c, duration of diabetes and systolic blood pressure, and fasting plasma glucose, folate and C-reactive protein, respectively. ConclusionsThere was renal mishandling of thiamine, increased degradation of vitamin B6 and cytosolic metabolic resistance to vitamin B12 in patients with type 2 diabetes in Indonesia.

Vitamin B6Requirement: Indicators and Factors Affecting

The purpose of this study was to establish the selection of indicators for estimating and factors affecting the requirement of vitamin B6. There has been a need to establish the human requirements of vitamin since vitamin is thought to be involved in more than one hundred biochemical reactions as a coenzyme in the metabolism of amino acids, glucose, and lipid, and the synthesis of neurotransmitters. For the review of the literature, this study included from early findings of the sixties to studies of 2009. This study suggests that plasma pyridoxal 5' phosphate (PLP) is the best single indicator of vitamin status for the healthy but not for the non-healthy. Erythrocyte aspartate aminotransferase and alanine aminotransferase activation by PLP as an indirect measure and urinary 4-pyridoxic acid excretion as a direct measure are useful as supporting indicators. Bioavailability, nutrient interaction, physiological need, and chronic diseases may increase the requirement for vitamin . However, these effects can not be quantified due to insufficient evidences.

Evaluation of Vitamin B6 Status of Adult Saudis in Al-Qassim Region-Saudi Arabia

The aim of this study was to evaluate vitamin B status of adult Saudis in Al-Qassim region-Saudi 6 Arabia. A sample of 239 (127 males and 112 females) healthy Saudi adults was recruited. Vitamin B status 6 was evaluated by dietary intake and biochemical measurements. Results of dietary intake measurements showed that means of vitamin B intake and intake of vitamin B to protein ratio for males and females were 6 6 1.97±0.58 mg/day, 0.021±0.003 and 1.89±0.61 mg/day, 0.020±0.04, respectively. Results of biochemica l measurements showed that means of plasma pyridoxal phosphate (PLP) concentration and average urinary 4-Pyridoxic Acid (4-PA) excretion for males and females were 29.6±9.6 nmol L and 7.0±2.4 µmol day and -1 -1 31.7±10.4 nmol L and 6.8±2.5 µmol day , respectively. The study also investigated and discussed other -1 -1 health indicators that are related to vitamin B status including Body Mass Index (BMI), plasma albumin 6 concentration and alkaline phosphatase activity. Results of dietary intakes and biochemical measurements indicated an adequate status of vitamin B. There were no significant differences between males and 6 females in any of the previous measurements. This study indicated an adequate status of vitamin B among 6 healthy adult Saudis in Al-Qassim region, however due to the numerous functions and the importance of the vitamin, the study suggested a further evaluation in various groups of the Saudi population in other regions of the country.

Inflammation causes tissue-specific depletion of vitamin B6

Previously we observed strong and consistent associations between vitamin B6 status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B6 levels. Such strong associations imply that impaired vitamin B6 status in these patients results from inflammation. In the present study we examined whether inflammation directly alters vitamin B6 tissue contents and its excretion in vivo. A cross-sectional case-controlled human clinical trial was performed in parallel with experiments in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5'-phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity coefficient of erythrocyte aspartate aminotransferase were compared between patients and healthy subjects. Adjuvant arthritis was induced in rats for investigating hepatic and muscle contents as well as the urinary excretion of vitamin B6 during acute and chronic inflammation. Patients with rheumatoid arthritis had low plasma pyridoxal 5'-phosphate compared with healthy control subjects, but normal erythrocyte pyridoxal 5'-phosphate and urinary 4-pyridoxic acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid excretion or muscle storage of pyridoxal 5'-phosphate, but it resulted in significantly lower pyridoxal 5'-phosphate levels in circulation and in liver during inflammation. Inflammation induced a tissue-specific depletion of vitamin B6. The low plasma pyridoxal 5'-phosphate levels seen in inflammation are unlikely to be due to insufficient intake or excessive vitamin B6 excretion. Possible causes of decreased levels of vitamin B6 are discussed.

Vitamin B6 metabolites in idiopathic calcium stone formers: no evidence for a link to hyperoxaluria.

Vitamin B6 metabolites and their potential correlates to urinary oxalate excretion in idiopathic calcium stone formers (ICSF) compared with healthy subjects were investigated. This clinical study was performed in a population of male ICSF with (Hyperoxalurics, n=55) or without hyperoxaluria (Normooxalurics, n=57) as well as in 100 healthy male control subjects. Pyridoxal 5'-phosphate serum concentration (S-pyridoxal 5'P) and 24-h urinary excretion of 4-pyridoxic acid (U-4pyridoxic acid) were measured using HPLC; 24-h urinary excretion of oxalate (U-oxalate) was measured concurrently. A subgroup of subjects (40 Hyperoxalurics, 15 Normooxalurics and 50 controls) underwent the same measurements before and after 7-day pyridoxine loading per os (pyridoxine hydrochloride, 300 mg/d). Under usual conditions, U-4pyridoxic acid was similar in the three groups, whereas mean S-pyridoxal 5'P was significantly lower ( p<0.0001) in the Hyperoxalurics (59.6+/-21.2 nmol/L) and in the Normooxalurics (64.9+/-19.7 nmol/L) than in the controls (86.0+/-31.0 nmol/L). No correlation could be found between U-oxalate and U-4pyridoxic acid or S-pyridoxal 5'P. After B6 loading, S-pyridoxal 5'P was still significantly lower in the Hyperoxalurics (415+/-180 nmol/L, p<0.001) and in the Normooxalurics (429+/-115 nmol/L, p=0.036) than in the controls (546+/-180 nmol/L), although there was no difference between groups for U-4pyridoxic acid. No correlation in any group could be found between changes in U-oxalate and changes in U-4pyridoxic acid or S-pyridoxal 5'P. Although there is no vitamin B6 deficiency in ICSF with or without hyperoxaluria, these patients, on average, have lower levels of S-pyridoxal 5'P than healthy subjects. However, this slight decrease does not seem to account for idiopathic hyperoxaluria.

The Influence of Dietary Restriction on Vitamin B-6 Vitamer Distribution and on Vitamin B-6 Metabolizing Enzymes in Rats

Objective: The purpose of this study was to assess the effect of dietary restriction on tissue distribution of vitamin B-6 vitamers and activities of vitamin B-6 metabolizing enzymes in rats.Methods: Male rats were subjected to a 40% dietary restriction for 10, 20 or 40 weeks. The tissue vitamin B-6 vitamer concentrations and activities of the vitamin B-6 metabolizing enzymes of the animals were determined.Results: The plasma pyridoxal 5′-phosphate (PLP) concentrations of the diet-restricted (DR) rats were comparable to those of the control group at week ten but were significantly lower at weeks 20 and 40. These significantly lower levels of plasma PLP in DR rats might in part be related to lower hepatic pyridoxal kinase and pyridoxamine (pyridoxine) 5′-phosphate oxidase activities. The urinary 4-pyridoxic acid excretion of the DR groups responded to the reduced food intake and were lower at weeks 10 and 20. Tissue levels of PLP were not affected by dietary restriction. In contrast, greater levels of pyridoxamine 5′-phosphate were found in liver, kidney and heart of the DR animals.Conclusion: The duration of dietary restriction influenced the distribution of vitamin B-6 vitamers. When plasma PLP is used to evaluate vitamin B-6 status, the length of dietary restriction should be considered.

Konjac mannan improves the vitamin B-6 status of rats fed a vitamin B-6-deficient diet.

To investigate how dietary fiber in the diet affects vitamin B-6 nutriture of rats which have been deprived of vitamin B-6, rats were made vitamin B-6-deficient by feeding a vitamin B-6-deficient 70% casein diet. They were fed 2% cellulose powder-based vitamin B-6-deficient diets supplemented with 3% of additional dietary fiber sources (agar, konjac mannan, pectin and cellulose powder) for subsequent 18 days. Vitamin B-6 status was evaluated according to several biological criteria (weight gain, urinary excretion of xanthurenic acid after tryptophan loading, plasma pyridoxal 5'-phosphate, apparent pyridoxal 5'-phosphate-saturation of liver kynureninase, urinary excretion of 4-pyridoxic acid and fecal output of vitamin B-6). Vitamin B-6 status evaluated by these criteria was considerably improved in the konjac mannan-fed group, when compared with the respective data of the vitamin B-6 supplemented group. The relative mean effect of the konjac mannan diet was about 40% of the vitamin B-6 supplemented diet. In conclusion, konjac mannan was effective for improving the vitamin B-6 nutritional state in vitamin B-6-deprived rats.

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.

Chronic Exercise Affects Vitamin B-6 Metabolism but Not Requirement of Growing Rats , ,

The effect of chronic exercise (forced swimming) on vitamin B-6 status and metabolism was studied in growing male rats fed deficient (0 mg pyridoxine-HCl/kg), suboptimal (2 mg pyridoxine-HCl/kg) or control (7 mg pyridoxine-HCl/kg) diets for 9 wk. Sedentary rats were fed the same diets. Body weight gain was lower in deficient rats than in both other dietary groups. Sedentary rats were heavier than trained rats of all diet groups. Erythrocyte aspartate aminotransferase, urinary 4-pyridoxic acid excretion, blood (plasma and erythrocytes) and tissue B-6 vitamers were measured. Urinary 4-pyridoxic acid, plasma pyridoxal 5′-phosphate and erythrocyte aspartate aminotransferase values of exercised and sedentary rats responded to changes in dietary pyridoxine but were not different from one another. After 9 wk of vitamin B-6 depletion, tissue concentrations of pyridoxal 5′-phosphate and pyridoxamine 5; 5'-phosphate were 41–66% and 26–49% lower, respectively, in the deficient groups than in the control groups. Larger percentage differences occurred in plasma than in tissues (95 vs. 22–66%). In liver, pyridoxal 5′-phosphate concentrations were lower, whereas pyridoxal concentrations were higher in trained than in sedentary rats. In gastrocnemius muscle, pyridoxal 5′-phosphate, pyridoxamine 5′-phosphate and total vitamin B-6 concentrations were higher in trained than in sedentary rats. Concentrations of vitamin B-6 compounds in heart, kidneys, brain and adrenals were not affected by training. On the basis of the vitamin B-6–dependent variables measured in this study, we conclude that prolonged exercise affects the metabolism of vitamin B-6, but does not increase the vitamin B-6 requirement in growing rats.

Pyridoxic acid excretion during low vitamin B-6 intake, total fasting, and bed rest

Vitamin B-6 metabolism in 10 volunteers during 21 d of total fasting was compared with results from 10 men consuming a diet low only in vitamin B-6 (1.76 mumol/d) and with men consuming a normal diet during bed rest. At the end of the fast mean plasma concentrations of vitamin B-6 metabolites and urinary excretion of 4-pyridoxic acid tended to be higher in the fasting subjects than in the low-vitamin B-6 group. The fasting subjects lost approximately 10% of their total vitamin B-6 pool and approximately 13% of their body weight. The low-vitamin B-6 group lost only approximately 4% of their vitamin B-6 pool. Compared with baseline, urinary excretion of pyridoxic acid was significantly increased during 17 wk of bed rest. There was no increase in pyridoxic acid excretion during a second 15-d bed rest study. These data suggest the possibility of complex interactions between diet and muscle metabolism that may influence indexes that are frequently used to assess vitamin B-6 status.

Relative bioavailability of B-6 vitamers from cooked ground beef in humans

The relative bioavailability of vitamin B-6 from cooked beef, supplemented with pyridoxal (PL) or pyridoxamine (PM), was investigated in two groups of healthy young men (age 22–35 years). The subjects were fed a controlled diet (2100–2500 kcal/day) for four days during the two test periods. After two days of controlled dietary intake, subjects ingested equimolar amounts of PL (5.98 μmol) or PM (5.95 μmol) in apple juice or cooked beef (176 0 C, 75 mins). After vitamin B-6 dosage, 24 hr urine samples were collected. In vitro assays revealed an increase in the irreversible binding (15–20%) of the [ 3H]B-6 vitamers to proteins in cooked beef extrinsically labelled with [ 3H]PL or [ 3H]PM compared to their respective controls in apple juice. There was no difference in the urinary excretion of 4-pyridoxic acid (4-PA) when subjects consumed the vitamin in apple juice or in cooked beef. Furthermore, urinary 4-PA excretion was not significantly different between the groups supplemented with PL or PM in the cooked test samples. In conclusion, vitamin B-6 from cooked beef appears to be highly bioavailable despite the increased irreversible binding of B-6 vitamers to proteinaceous components in beef.

Metabolism of vitamin B 6 by human kidney

A continuous intravenous pyridoxine-infusion (dose = 100 mg PN·HCl τ = 6 h) was given to 10 healthy male volunteers (aged between 23 and 32). Concentration-time curves of B 6-metabolites in urine and blood plasma were observed over a period of 240 hours. From these curves biokinetic parameters were calculated. Renal clearances (ml/min/1.73 m 2) were 257.5 ± 92.1 (pyridoxine), 249.8 ± 48.2 (4-pyridoxic acid), and 20.1 ± 6.0 (pyridoxal). Rate constants of elimination (h −1) obtained by non-linear regression of the excretion curves were 1.231 ± 0.877 (pyridoxine), 0.314 ± 0.118 (k α) and 0.048 ± 0.070 (k β) (4-pyridoxic acid), and 0.653 ± 0.360 (pyridoxal). The main part of the infused pyridoxine was eliminated in the form of metabolites (63.7 ± 6.4% for 4-pyridoxic acid, 3.3 ± 0.9% for pyridoxal); only 6.7 ± 1.8% was excreted unchanged. The proportion of 4-pyridoxic acid within each miction increased from 53.0 to 100.0%. Our data indicate a very effective metabolism of the physiologically inactive pyridoxine. An enzyme induction suggested by the increasing proportion of 4-pyridoxic acid cannot be excluded. Large doses of vitamin B 6 are excreted rapidly via the kidney, with the excretion of pyridoxine and 4-pyridoxic acid being enhanced by tubular secretion.

Influence of Age and Sex on Vitamin B-6 Vitamer Distribution and on Vitamin B-6 Metabolizing Enzymes in Wistar Rats

Vitamin B-6 vitamer distribution and activities of vitamin B-6 metabolizing enzymes were evaluated in aging male and female Wistar rats fed a purified diet (containing 250 g of casein and 6 mg of pyridoxine hydrochloride per kg) from weaning until 31 mo of age. Plasma pyridoxal 5'-phosphate (PLP) concentration became lower with increasing age, with the largest decrease in the 1st yr of life. An age-related change in vitamin B-6 distribution between the various tissues examined was observed: B-6 vitamer content increased in heart and brain, whereas PLP content decreased in gastrocnemius muscle, kidney and liver. The decrease in muscle PLP content occurred in concert with a decrease in muscle glycogen phosphorylase activity. Urinary 4-pyridoxic acid (4-PA) excretion increased with age, especially in female rats, in parallel with an increase in liver pyridoxal oxidase and pyridoxal dehydrogenase activities. Age-related changes in vitamin B-6 distribution were probably not causally related to changes in activity of vitamin B-6 metabolizing enzymes; they were regarded as consequences of changes in protein metabolism. The higher urinary 4-PA excretion in older rats may reflect a lower vitamin B-6 requirement; however, the lower PLP content of gastrocnemius muscle may indicate an age-related decrease in vitamin B-6 body stores.

Effect of sulfasalazine on vitamin B-6 status and metabolism in vitamin B-6adequate and deficient rats

Diets adequate or deficient in vitamin B-6 were supplemented or not supplemented with sulfasalazine and fed to rats for 5 weeks. After that time period, 24 hour urine samples were collected, rats were sacrificed, and liver and blood samples were collected. During the 5 week feeding period, reduced weight gain was observed for rats fed the deficient diet supplemented with sulfasalazine compared to deficient controls. There was no difference in the plasma pyridoxal 5′-phosphate (PLP) concentrations, plasma or red blood cell aspartate aminotransferase activity, and urinary excretion of 4-pyridoxic acid between the deficient control rats and deficient rats fed sulfasalazine. Hepatic PLP concentrations were lower in deficient rats fed sulfasalazine compared to the deficient controls. Observations from this study would suggest that sulfasalazine intake may aggravate a vitamin B-6 deficiency.

Relationship Between Vitamin B-6 Status and Elevated Pyridoxal Kinase Levels Induced by Theophylline Therapy in Humans

Theophylline administration to seven healthy male volunteers resulted in a rapid and significant decline in both plasma and erythrocyte pyridoxal-5'-phosphate levels. Total erythrocyte pyridoxal kinase levels increased during 15 wk of theophylline treatment from a mean initial activity of 19.23 +/- 5.03 (mean +/- SD) to 62.64 +/- 11.59 nmol pyridoxal-5'-phosphate formed/(g hemoglobin.h). Although plasma pyridoxal levels remained normal, the threefold increase in total erythrocyte pyridoxal kinase activity levels did not normalize plasma and erythrocyte pyridoxal-5'-phosphate levels. Pyridoxal-5'-phosphate hydrolysis was not affected by theophylline therapy. Increased pyridoxal oxidation was confirmed by elevated urinary 4-pyridoxic acid excretion after 15 wk of theophylline treatment. Mean erythrocyte alanine aminotransferase activity declined by 70%, and aspartate aminotransferase activity declined by 50%, indicating that decreased availability of pyridoxal-5'-phosphate can have widespread metabolic consequences. We conclude that the effect of theophylline on vitamin B-6 metabolism is not transitory and cannot be overcome by elevated intracellular levels of pyridoxal kinase. However, pyridoxine supplementation (10 mg/d for 1 wk) normalized indices of vitamin B-6 status and reversed the downward trend in both alanine aminotransferase and aspartate aminotransferase activity levels.