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Glycine is a precursor of purines, protein, glutathione, and 1-carbon units as 5,10-methylenetetrahydrofolate. Glycine decarboxylation through the glycine cleavage system (GCS) and glycine-serine transformation by serine hydroxymethyl- transferase (SHMT) require pyridoxal 5'-phosphate (PLP; active form of vitamin B-6) as a coenzyme. The intake of vitamin B-6 is frequently low in humans. Therefore, we determined the effects of vitamin B-6 restriction on whole-body glycine flux, the rate of glycine decarboxylation, glycine-to-serine conversion, use of glycine carbons in nucleoside synthesis, and other aspects of 1-carbon metabolism We used a primed, constant infusion of [1,2-[sup.13][C.sub.2]glycine and [5,5,5- [sup.2][H.sub.3]leucine to quantify in vivo kinetics in healthy adults (7 males, 6 females; 20-39 y) of normal vitamin B-6 status of marginal vitamin B-6 deficiency. Vitamin B-6 restriction lowered the plasma PLP concentration from 55 [+ or -] 4 nmol/L (mean [+ or -] SEM) to 23 [+ or -] 1 nmol/L (P < 0.0001), which is consistent with marginal deficiency, whereas the plasma glycine concentration increased (P< 0.01 ). SHMT-mediated conversion of glycine to serine increased from 182 [+ or -] 7 to 205 [+ or -] 9 [micro]mol x [kg.sup.-1] x [h.sup.-1] (P < 0.05), but serine production using a GCS-derived 1-carbon unit (93 [+ or -] 9 vs. 91 [+ or -] 6 [micro]mol x [kg.sup.-1] x [h.sup.-1]) and glycine cleavage (163 [+ or -] 11 vs. 151 [+ or -] 8 [micro]mol x [kg.sup.-1] x [h.sup.-1]) were not changed by vitamin B-6 restriction. The GCS produced 1- carbon units at a rate (~140-170 [micro]mol x [kg.sup.-1] x [h.sup.-1]) that greatly exceeds the demand for remethylation and transmethylation processes (~4-7 [micro]mol x [kg.sup.-1] x [h.sup.-1]). We conclude that the in vivo GCS and SHMT reactions are quite resilient to the effects of marginal vitamin B-6 deficiency, presumably through a compensatory effect of increasing substrate concentration.

We investigated the association of dietary intakes of folate, vitamin B-6, vitamin B-12, and methionine with the risk of colorectal cancer in a large prospective cohort study of middle-aged Japanese men and women. A total of 81,184 subjects (38,107 men and 43,077 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995-1998 to the end of 2002, during which 526 cases of colorectal cancer (335 men, 191 women) were newly identified. Dietary intake of nutrients was calculated using a 138-item self-administered FFQ. We observed a significant inverse association between vitamin B-6 intake and colorectal cancer in men. Compared with the lowest quartile, the multivariate hazard ratio (95% [Cl]) in the highest quartile of intake was 0.69 (0.48-0.98) ([P.sub.trend] = 0.03). Men who consumed 150 g/wk alcohol or more had twice the risk of colorectal cancer of those who drank less in the lowest quartile of vitamin B-6 intake, but risk due to alcohol intake was not higher in the highest quartile of vitamin B-6 intake. Vitamin B-6 intake and colorectal cancer were not associated in women. Folate and methionine intakes were not associated with colorectal cancer risk in men or women, but colorectal cancer risk tended to increase ([P.sub.trend] = 0.05) with increasing intake of vitamin B-12 in men. Our results support previous evidence that low vitamin B-6 intake is associated with an increased risk of colorectal cancer. In particular, a higher intake of vitamin B-6 appears beneficial in men with higher alcohol intake.

The transsulfuration pathway, which aids in regulating homocysteine concentration and mediates cysteine synthesis, may be sensitive to vitamin B-6 status because cystathionine [beta]-synthase (CBS) and cystathionine [gamma]-lyase (CGL) require pyridoxal 5'-phosphate (PLP). To assess relations between vitamin B-6 and transsulfuration, we evaluated the effects of dietary pyridoxine (PN) on the hepatic concentration of relevant metabolites and in vitro activity of CBS and CGL. Growing rats were fed AIN-93G- or AIN-76A-based diets that ranged from adequate to deficient in vitamin B-6 (2, 1, 0.5, 0.1, or 0 mg of PN/kg diet, n = 5). This design allowed assessment of the effects of supplemental methionine (AIN-76A) vs. cysteine (AIN-93G) in common research diets over a range of vitamin B-6 levels. CBS activity, assayed in the presence or absence of added S-adenosylmethionine, was independent of diet type and PN level. CGL activity was independent of diet type but proportional to dietary PN. Rats fed deficient (0 and 0.1 mg PN/kg) diets exhibited only ~30% of the CGL activity of those fed the 2 mg PN/kg diets. Hepatic cystathionine increased from 20 to 30 nmol/g for the 1-2 mg PN/kg diets to ~85 nmol/g for the 0 mg PN/kg diet; however, cysteine was reduced only in B-6--deficient rats consuming the AIN-93G diet (means of 30-40 nmol/g for adequate to 11.6 nmol/g for 0 mg PN/kg AIN-76A diet). In spite of these effects, hepatic glutathione concentration increased in vitamin B-6 deficiency. These results suggest that vitamin B-6-dependent changes in transsulfuration do not limit hepatic glutathione production.

This research was conducted to investigate 1) the bioavailability of pyridoxine-5[prime]-[Beta]-D-glucoside (PN-glucoside) relative to that of pyridoxine (PN) in human subjects, and 2) the competitive effect of PN-glucoside on the metabolism of co-ingested PN. To evaluate PN-glucoside bioavailability, the subjects were administered a single oral dose of either deuterium-labeled ([2[H.sub.2]]) PN (Trial 1) or [2[H.sub.2]]PN-glucoside (Trial 2), and the urinary excretion rates of labeled 4-pyridoxic acid (4PA) were measured. The [2[H.sub.2]]4PA derived from [2[H.sub.2]]PN or [2[H.sub.2]]PN-glucoside was excreted mainly in the first 8 h after the dose. Excretion of [2[H.sub.2]]4PA during the 48-h postdose period indicated that the bioavailability of PN-glucoside was [approximately]50% relative to PN, which is consistent with our previous report of 58% bioavailability determined using a different protocol and fewer subjects. To assess the effects of PN-glucoside on PN utilization, the subjects were administered different ratios of nonlabeled PN-glucoside with [2[H.sub.2]]PN in Trials 3 and 4. Comparing Trial 1 with Trials 3 and 4, the quantity of nonlabeled PN-glucoside, as a fraction of total vitamin B-6 administered, ranged from 0 to 40% (on the basis of pyridoxine equivalents), with a constant dose of [2[H.sub.2]]PN in each. In these trials, the rate but not the total extent of the excretion of [2[H.sub.2]]4PA derived from [2[H.sub.2]]PN was inversely related to the proportion of co-ingested nonlabeled PN-glucoside. Thus, antagonistic effects of PN-glucoside on PN metabolism do occur in humans, although the effect is less pronounced than that seen previously in rats. Such interactive effects must be considered in evaluating the net bioavailability of dietary forms of vitamin B-6. KEY WORDS: vitamin B-6; pyridoxine-5[prime]-[Beta]-D-glucoside; bioavailability; stable isotope; humans

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[prime]-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. INDEXING KEY WORDS: vitamin B-6; protein intake; status; requirements; women

Pyridoxine glucoside is a partially available form of vitamin B-6 present in plant-derived foods. in this set of three studies, rats were fed diets containing different concentrations of either pyridoxine or pyridoxine glucoside in the presence or absence of a fixed concentration of pyridoxine for 2 wk. The distribution of B-6 vitamers and [Beta]-glucosidase activity in tissues was examined to determine the metabolic effects of chronic consumption of pyridoxine glucoside. Rats fed pyridoxine glucoside either with or without pyridoxine exhibited a significant increase in the amount of hepatic pyridoxine 5[prime]-phosphate (not detected in rats fed pyridoxine alone), whereas hepatic pyridoxal 5[prime]-phosphate was decreased with increasing dietary pyridoxine glucoside. The activity of cytosolic [Beta]-glucosidases in small intestine and kidney was affected by the dietary concentration of both pyridoxine and pyridoxine glucoside. Enzymatic activity capable of hydrolyzing pyridoxine glucoside was found in mucosal and intraluminal fractions of small intestine and in the kidney. Other tissues examined, including liver, spleen and stomach, did not hydrolyze pyridoxine glucoside in detectable quantities. These findings indicate that microbial and mucosal enzymes can participate in the intestinal hydrolysis of pyridoxine glucoside and that the kidney may contribute to postabsorptive hydrolysis. These findings further support the observations that dietary pyridoxine glucoside influences vitamin B-6 metabolism. INDEXING KEY WORDS: * vitamin B-6 * pyridoxine-5[prime]-[Beta]-D-glucoside * [Beta]-glucosidase * rats

Weanling male rats were fed diets that varied in protein quality (casein or wheat gluten) and vitamin B-6 (0.0, 0.5, 1.0 and 1.5 mg pyridoxine HCl/kg diet) to test the hypotheses that low protein quality would depress vitamin B-6 nutritional status and that activity of ornithine decarboxylase (ODC) would be a sensitive functional indicator of vitamin B-6 nutritional status. The wheat gluten diet depressed body weight gain [approximately]17% at higher vitamin B-6 levels, as expected. However, vitamin B-6 nutritional status was not worse in gluten-fed compared with casein-fed groups, as evidenced by static measures (B-6 vitamer concentrations in plasma and tissues) and a functional indicator (tryptophan load test). The activity of ODC (holo- and total) in liver, kidney and small intestine did not vary significantly at the three higher levels of vitamin B-6 intake. in groups fed casein, total ODC activity in these tissues was two- to fivefold higher in rats fed diets containing 0.0 mg vitamin B-6/kg compared with higher B-6 levels, without corresponding differences in ODC mRNA abundance in liver and kidney. Concentrations of B-6 vitamers (except pyridoxal phosphate in plasma) increased linearly with dietary vitamin B-6 in plasma, liver, kidney and intestine. These data suggest that low quality protein fed as wheat gluten suppresses growth but not vitamin B-6 nutritional status, and that ODC activity is not a sensitive functional indicator of marginal vitamin B-6 status. INDEXING KEY WORDS: vitamin B-6; ornithine decarboxylase; nutritional status; protein quality; rats

The cause of reduced plasma pyridoxal-5 prime-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.

The cause for reduced plasma pyridoxal phosphate PLP) concentration during pregnancy is not well understood. in this study, nonplegnant (control) and pregnant rats were gavaged with [[H.sup.3]]pyridoxine for assessment of the intestinal absorption, tissue distribution, metabolic utilization and urinary excretion of the vitamin. In addition, plasma PLP and pyridoxal levels and erythrocyte aspartate aminotransferase (EAST) activity were measured. There was 50% lower plasma PLP concentration and 50% greater EAST activity in the pregnant rats and no difference in the stimulation of EAST with exogenous PLP. There was no difference in the intestinal absorption, hepatic uptake and retention or urinary excretion of the radioisotope. Less than 3% of the oral dose was detected in fetal/uterine tissue of the pregnant rats. Results of this study indicate that reduced plasma PLP concentration during pregnancy is not a result of diminished total vitamin B-6 body pools or fetal sequestration of vitamin B-6. Low plasma PLP during pregnancy may be a result of altered distribution of PLP between the plasma and erythrocytes. J. Nutr. 122: 1892-1897, 1992. INDEXIMG KEY WORDS: * pregnancy * vitamin B-6 * rats * bioavailability, The influence of pregnancy on the bioavailability of vitamin B-6 was analyzed by oral administration of pyridoxine to pregnant and non-pregnant rats. Plasma pyridoxal 5 phosphate levels (PLP) were found to be less in pregnant than in non-pregnant rats despite increased intake. Oral pyridoxine was almost totally absorbed in the gut and hepatic uptake was constant. Alkaline phosphatase activity does not affect PLP levels. PLP levels are decreased in pregnancy because of associated increase in erythrocyte levels available for binding and fetal consumption.

Male ICR mice were examined for the effect of vitamin B-6 [pyridoxine (PN) HCl] on azoxymethane-induced colon tumorigenesis. Mice were fed the diets containing 1, 7, 14 or 35 mg PN HCl/kg for 22 wk, and given a weekly injection of azoxymethane (5 mg/kg body) for the initial 10 wk. Compared with the 1 mg PN HCl/kg diet, 7, 14 and 35 mg PN HCl/kg diets significantly suppressed the incidence and number of colon tumors, colon cell proliferation and expressions of c-myc and c-fos proteins. For some variables, 14 and 35 mg PN HCl/kg diets were more effective than the 7 mg/kg diet. Supplemental vitamin B-6 had no influence on the number of colon apoptotic cells. The results suggest that elevating dietary vitamin B-6 suppresses colon tumorigenesis by reducing cell proliferation. J. Nutr. 131: 2204-2207, 2001. KEY WORDS: * vitamin B-6 * pyridoxine * colon tumorigenesis * cell proliferation * mice

Little is known about the micronutrient status of Chinese women of childbearing age. We assessed nonfasting plasma concentrations of folic acid, vitamin B-12, vitamin B-6 (as pyridoxal-5'-phosphate), hemoglobin (Hb), ferritin and transferrin receptor (TfR) in 563 nonpregnant textile workers aged 21-34 y from Anqing, China. All women had obtained permission to become pregnant and were participating in a prospective study of pregnancy outcomes. Mean (SD) plasma concentrations were 9.7 (4.1) nmol/L folic acid, 367 (128) pmol/L vitamin B-12, 40.2 (15.8) nmol/L vitamin B-6, 108 (12.9) g/L Hb, 42.6 (34.2) [micro]g/L ferritin and 5.2 (2.7) mg/L TfR. Twenty-three percent of women had biochemical evidence of folic acid deficiency, 26% were deficient in vitamin B-6 and 10% had low vitamin B-12. Overall, 44% of women were deficient in at least one B vitamin. Although anemia (Hb [is less than] 120 g/L) was detected in 80% of women, only 17% had depleted iron stores (ferritin [is less than] 12 [micro]g/L); 11% had elevated TfR concentrations. Distinct seasonal trends were observed in the prevalence of moderate anemia (Hb [is less than] 100 g/L) and deficiencies of folic acid and vitamin B-6, with significantly lower concentrations of folate and Hb occurring in summer and lower concentrations of vitamin B-6 occurring in winter and spring than in other seasons. We conclude that deficiencies of folic acid, vitamin B-6 and iron were relatively common in this sample of Chinese women of childbearing age and were contributing to the high prevalence of anemia. Without appropriate supplementation, these deficiencies could jeopardize the women's health and increase their risk of adverse pregnancy outcomes. J. Nutr. 130: 2703-2710, 2000. KEY WORDS: * China * women * folic acid * vitamin B-12 * vitamin B-6 * iron