Cardiovascular disease-risk factors in middle-aged osteopaenic women treated with calcium alone or combined to three nutrients essential to artery and bone collagen.

BACKGROUND: Recent research suggests that cardiovascular disease (CVD) and bone loss are functionally interwoven. This study examined the concomitant effects of a nutritional treatment of osteopaenia on CVD-risk factors. METHODS: A 1-year placebo-controlled trial was conducted on middle-aged women with normal (group A) or low (groups B and C) bone mineral density. Subjects (n = 20 per group) took daily either a placebo, calcium carbonate alone or combined to a vitamin (C and B(6))-proline capsule, respectively. Urinary pyridoxic acid (used to assess treatment compliance), plasma homocysteine, serum lipids and lipoproteins were measured before and after nutritional intervention. RESULTS: Groups were comparable at baseline in most parameters of interest. No changes occurred in groups A and B. The 4%, 7% and 25% reductions of total cholesterol, LDL and triglycerides, and 14% elevation of HDL were all significant in group C. A trend toward reduction was observed for homocysteine in this group. CONCLUSIONS: Vitamins C (500 mg) and B(6) (75 mg) combined with proline had consistent beneficial effects on CVD-risk factors, whereas calcium alone did not. This study also underlined the importance of considering vitamin B(6) status as a potential CVD risk factor.

Vitamin B6 supplementation increases immune responses in critically ill patients.

OBJECTIVE: To investigate whether vitamin B6 supplementation has a beneficial effect on immune responses in critically ill patients. DESIGN: A single-blind intervention study. SETTING: The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan. SUBJECTS: Fifty-one subjects who stayed over 14 days in the intensive care unit completed the study. Subjects were not treated with any vitamin supplement before the intervention. INTERVENTIONS: Patients were randomly assigned to one of three groups, control (n = 20), a daily injection of 50 mg vitamin B-6 (B6 -50, n=15), or 100 mg vitamin B-6 (B6 -100, n = 16) for 14 days. MAIN OUTCOME MEASURES: Plasma pyridoxal 5'-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (4-PA), erythrocyte alanine (EALT-AC) and aspartate (EAST-AC) aminotransaminase activity coefficient, and urinary 4-PA were measured. The levels of serum albumin, hemoglobin, hematocrit, high-sensitivity C-reactive protein (hs-CRP) and immune responses (white blood cell, neutrophils, total lymphocytes count (TLC), T- (CD3) and B-(CD19) lymphocytes, T-helper (CD4) and suppressor (CD8) cells) were determined. RESULTS: Plasma PLP, PL, 4-PA and urinary 4-PA concentrations significantly increased in two treated groups. T-lymphocyte and T-helper cell numbers and the percentage of T-suppressor cell significantly increased on day 14 in the B6 -50 group. Total lymphocyte count, T-helper and T-suppressor cell numbers, the percentage of T-lymphocyte cells and T-suppressors significantly increased in the B6 -100 group at the 14th day. There were no significant changes with respect to immune responses in the control group over 14 days. CONCLUSIONS: A large dose of vitamin B6 supplementation (50 or 100 mg/day) could compensate for the lack of responsiveness of plasma PLP to vitamin B6 intake, and further increase immune response of critically ill patients. SPONSORSHIP: This study was supported by the National Science Council, Taiwan, Republic of China (NSC-92-2320-B-040-026).

Urinary total flavonoid excretion but not 4-pyridoxic acid or potassium can be used as a biomarker for the intake of fruits and vegetables.

To gain better insight into the potential health effects of fruits and vegetables, reliable biomarkers of intake are needed. The main purpose of this study was to investigate the ability of flavonoid excretion in both 24-h and morning urine samples to reflect a low intake and moderate changes in fruit and vegetable consumption. Furthermore, the urinary excretions of 4-pyridoxic acid (4-PA) and potassium were investigated as other potential biomarkers of fruit and vegetable intake. The study was designed as a 5-d randomized, controlled crossover study. On d 1-3, the men (n = 12) consumed a self-restricted flavonoid-free diet. On d 4, they were provided a strictly controlled diet containing no fruits or vegetables (basic diet). On d 5, they consumed the basic diet supplemented with 300 or 600 g of fruits and vegetables. The total excretion of flavonoids in 24-h urine samples increased linearly with increasing fruit and vegetable intakes (r(s) = 0.86, P < 1 x 10(-6)). The total excretion of flavonoids in morning urine also increased, but the association was weaker (r(s) = 0.59, P < 0.0001). Urinary 4-PA in 24-h and morning urine samples increased significantly only with the 600-g increase in fruit and vegetable intake, whereas the excretion of potassium in urine did not reflect the changes in fruit and vegetable intake. We conclude that the total excretion of flavonoids in 24-h urine may be used as a new biomarker for fruit and vegetable intake.

Vitamin B6 intakes and status of mechanically ventilated critically ill patients in Taiwan.

OBJECTIVE: To assess vitamin B6 intake and status of critically ill patients. The relationship between vitamin B6 status indicators and the severity of illness and outcome in these patients was also examined. DESIGN: Prospective clinical study. SETTING: The study was performed at the Taichung Veteran General Hospital, in the central part of Taiwan. SUBJECTS: Ninety-four patients in the intensive care unit (ICU) entered the study and 46 patients successfully completed this study. INTERVENTIONS: No intervention. MAIN OUTCOME MEASURES: Vitamin B6 intake was recorded for 14 days. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and urinary 4-pyridoxic acid (4-PA)) and indirect measures (erythrocyte alanine (EALT-AC) and aspartate (EAST-AC) aminotransaminase activity coefficient). The severity of illness (APACHE II score), the length of ventilation dependency, and the length of ICU and hospital stay were recorded. RESULTS: Patients had an adequate mean vitamin B6 intake (16.26+/-19.39 mg) during the 14 day study. Mean vitamin B6 intake was significantly higher on day 14 than on day 1 (P<0.001). However, plasma PLP and PL concentrations significantly decreased at the 14th day after admission (P<0.05). Erythrocyte alanine aminotransaminase activity coefficient and EAST-AC did not change significantly. Urinary 4-PA significantly increased at the 14th day (P<0.001). No significant relationships were found between APACHE II scores and clinical outcomes (the length of ICU and hospital stay, the length of ventilation dependency) of patients, vitamin B6 intake or status indicators. CONCLUSIONS: Critically ill patients received nutritional support in the ICU, and had sufficient mean vitamin B6 intake and adequate vitamin B6 status. Therefore, the severity of illness and the results should not be affected by vitamin B6 status. However, we have noted that plasma PLP and PL concentrations significantly decreased while vitamin B6 intake significantly increased on day 14. Critical clinical conditions and complex metabolism in the critically ill may account for the reduction of plasma PLP and PL. Since vitamin B6 deficiency causes profound effects on immune system function, dietary or supplemented vitamin B6 intake is suggested for hospitalized patients.

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.

A simple liquid-chromatographic method for measuring vitamin B6 compounds in plasma.

This relatively simple high-performance liquid chromatographic (HPLC) method for measuring all seven known forms of vitamin B6 in plasma from individuals supplemented with pyridoxine hydrochloride shows good analytical recovery (85-98%) and precision. Within-run and between-run CVs for plasmas supplemented with standards were 4% and 7%, respectively. The major forms of B6 found in unsupplemented plasma from normal subjects were pyridoxal phosphate and 4-pyridoxic acid, with pyridoxal just detectable. The HPLC procedure correlated well (r = 0.94) with a modification of an enzymatic method involving apotryptophanase (Anal Biochem 1972;45:567-76) for measuring plasma pyridoxal phosphate, and also (r = 0.94) with a routine method for determining 4-pyridoxic acid in urine (Clin Chem 1964;10:479-89). Elimination of pyridoxine from the plasma of both normal and hyperoxaluric individuals was shown to be very rapid, with half-lives (t1/2) of 45 and 40 min, respectively. Finally, we present evidence for the existence of two other forms of B6 and discuss the possibility of a new metabolic pathway in vitamin B6 metabolism.

Decreased vitamin B-6 status of submariners during prolonged patrol.

We investigated the effects of a 3-mo submarine patrol upon several vitamin B-6 indices in 23 male submariners. While on patrol, 12 subjects received a multivitamin-mineral supplement that provided 0.5 mg/d vitamin B-6 and 11 subjects received a placebo. The concentrations of plasma pyridoxal 5'-phosphate, total vitamin B-6, and urine 4-pyridoxic acid were significantly reduced during the patrol in both the placebo and the supplemented groups. The hematocrit of both groups also decreased by approximately 10% during the patrol and was not restored to prepatrol concentrations until several weeks postpatrol. Mood depressions, as measured by the Beck inventory and the depression adjective check list, were most pronounced during the 30 d before and at the beginning of the patrol. These depression measures did not correlate with the vitamin B-6 status indices, indicating that the mood depressions during a patrol do not appear to be related to the vitamin B-6 status of the submariners.

Vitamin B6 nutritional status in asthma: the effect of theophylline therapy on plasma pyridoxal-5'-phosphate and pyridoxal levels.

Plasma pyridoxal-5'-phosphate concentrations were significantly lower (p less than 0.001) in a group of 28 asthmatic women when compared to 33 controls. Plasma pyridoxal levels in the two groups were not different. Theophylline was administered to a group of 17 volunteers and resulted in large reductions in plasma pyridoxal-5'-phosphate levels, while plasma pyridoxal levels and urinary 4-pyridoxic acid excretion were unaffected by theophylline therapy. An in vitro study showed that theophylline did not interfere with the high performance liquid chromatography assay for pyridoxal-5'-phosphate, indicating that theophylline could affect liver metabolism of vitamin B6.

Vitamin B-6 metabolism in the pregnant rat: effect of progesterone on the (re)distribution in maternal vitamin B-6 stores.

Parameters of vitamin B-6 metabolism were studied in pregnant rats, nonpregnant control rats and progesterone-supplemented ovariectomized rats. Plasma pyridoxal 5'-phosphate (PLP) and pyridoxal concentrations in pregnant rats were 20 and 40% of those of nonpregnant rats, respectively. Excretion of 4-pyridoxic acid in the urine in pregnant rats was about 40% of that of nonpregnant rats. Liver PLP content was also lower during pregnancy, but liver pyridoxamine 5'-phosphate (PMP), kidney PLP and PMP and muscle PLP contents did not change significantly. Progesterone administration to ovariectomized rats resulted in slightly lower plasma, liver and kidney PLP levels than in intact untreated control rats. Liver and kidney pyridoxal kinase (PK) and pyridoxamine 5'-phosphate oxidase activities were similar in pregnant and nonpregnant rats. Progesterone treatment resulted in a significantly lower PK activity in the kidney of the treated rats than in untreated controls. It is concluded that the pregnancy-induced changes in vitamin B-6 metabolism were unlikely to be related directly to progesterone. However, progesterone may secondarily affect maternal vitamin B-6 stores during pregnancy, by temporary deposition and increased retention of vitamin B-6.

[Comparative study of the vitamin activity of pyridoxal phosphate and pyridoxine used cutaneously]. / Sravnitel'noe izuchenie vitaminnoi aktivnosti piridoksal'-fosfata i piridoksina pri ikh nakozhnom primenenii.

In white rats with B6-avitaminosis, the B6-vitamin activity of pyridoxal-phosphate and of pyridoxine was studied in their epicutaneous and peroral application. It is revealed that pyridoxal-phosphate in epicutaneous application displays more activity than pyridoxine and pyridoxal-phosphate applied perorally. Pyridoxine in epicutaneous application does not reveal the B6-vitamin activity.

Relationship between body store of vitamin B6 and plasma pyridoxal-P clearance: metabolic balance studies in humans.

Factors that regulate the clearance of plasma pyridoxal-P (PLP) are unknown. Four volunteers were given a diet supplying approximately 12 mumol pyridoxine (PN) per day. The pharmacokinetics of plasma PLP clearance were measured in these subjects before and after 4 weeks of intravenous PN supplementation (122 mumol/day). Urinary B6 excretion, mainly as 4-pyridoxic acid (4-PA), increased progressively after initiation of PN supplementation until a new steady state was reached on day 10 of supplementation, whereupon greater than 93% of the daily injected PN could be recovered in the urine. Hence, urinary excretion is almost the sole route for vitamin B6 elimination. Fasting plasma PLP concentration increased with supplementation and also reached a new steady state at this time. When supplementation was terminated, urinary B6 excretion decreased in 5 days to an amount only slightly higher than that before supplementation. This amount was maintained for 2 months. By comparison, plasma PLP decreased more slowly and remained considerably higher than the presupplementation level for the rest of the study. These data confirm that urinary 4-PA excretion is a better indicator of B6 intake than is plasma PLP content, whereas plasma PLP content is a better indicator of the body store of the vitamin. Plasma clearance and volume of distribution of PLP decreased significantly after supplementation, but half-life t 1/2 did not change. Plasma clearance of PLP, therefore, is dependent on the vitamin B6 status of an individual.

Differences in vitamin B6 status indicator responses between young and middle-aged women fed constant diets with two levels of vitamin B6.

The responses of adult women to two levels of vitamin B6, was conducted with five young and eight middle-aged subjects. A constant diet (2.3-2.4 mg vitamin B6 per day) was fed for four weeks followed by three weeks of the same diet supplemented with 8.0 mg pyridoxine. Plasma pyridoxal 5'-phosphate (PLP), plasma and urinary vitamin B6, and urinary 4-pyridoxic acid (4-PA) were determined. The older women had significantly lower plasma PLP, plasma and urinary vitamin B6 and slightly higher urinary 4-PA values on normal vitamin B6 intakes. With supplementation, only the difference in urinary total vitamin B6 remained significant. Tryptophan load tests revealed no significant between-group differences in xanthurenic acid or kynurenic acid excretion. These results demonstrate an age-related difference in vitamin B6 status indicators in women under controlled dietary intake of vitamin B6.

Effect of high dose ascorbic acid on vitamin B6 metabolism.

The influence of ascorbic acid intake on vitamin B6 metabolism in humans was determined in three separate studies. Five subjects in study I and two subjects in study II received 0.5 ( 2 days) and 1 g (7 days) doses of L-ascorbic acid (AA), respectively, before supplementation with 2 mg of pyridoxine hydrochloride (PN-HCl). From daily diet records the percentage of the intake of vitamin B6 excreted as urinary 4-pyridoxic acid (4PA) was calculated. Because of the variability in vitamin B6 intake, study III was conducted with four male and four female subjects, who received identical meals on days 2, 3, 9, and 10 and 1 g of AA on days 4 to 10. Two milligrams of PN.HCl were given the day before and the last day of AA administration. In contrast to studies I and II, where excretion of 4PA appeared to increase on the day of PN.HCl supplementation plus AA compared to pre-AA, urinary 4PA excretion in the eight subjects of study III was not significantly different when the same PN.HCl supplemented pre-AA and post-AA days were compared. Also, the fasting plasma pyridoxal 5'-phosphate level was not significantly altered when AA was administered. It is concluded that short-term AA supplementation did not alter vitamin B6 metabolism.

Vitamin B-6 metabolism and turnover in the ethanol-fed rat.

The effect of long-term ethanol supplementation on vitamin B-6 metabolism and storage was studied in McCollum rats receiving approximately 30% of their caloric intake as ethanol. Hepatic pyridoxal 5'-phosphate levels were significantly depressed in the ethanol-fed animals. However, total hepatic vitamin B-6 levels were slightly higher than in control animals because of a marked increase in pyridoxamine 5'-phosphate levels. The metabolism of a labeled pyridoxine dose appeared unaffected by ethanol administration, with the final distribution of labeled metabolites, almost entirely pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate, mirroring that observed with unlabeled endogenous vitamin B-6. The daily turnover of total-body vitamin B-6 stores in ethanol-fed animals (2.7%) was lower than in control animals (3.8%). Whether this resulted from ethanol administration or a reduced vitamin B-6 intake was not ascertained. However, it was apparent that ethanol did not increase the turnover of total-body vitamin B-6 or decrease total-body stores of the vitamin, which were similar in both groups of animals on a body store per kilogram weight basis. Pyridoxic acid excretion reflected vitamin B-6 intake in both groups of animals and accounted for approximately 30% of the total excreted vitamin.

[Effect of the combined use of flavin coenzyme preparations and pyridoxine on the body vitamin balance in animals]. / Vliianie sochetannogo primeneniia preparatov flavinovykh kofermentov i piridoksina na vitaminnyi balans organizma zhivotnykh.

The effect of combined administration of flavin coenzymes and pyridoxine on B2-avitaminosis rats' supply with these vitamins has been studied. It has been disclosed that pyridoxine promotes more effective normalization of riboflavin and pyridoxine balance in the body, this balance being measured from the excretion of riboflavin and 4-pyridoxin acid with urine as well as from the content of total flavins in blood and tissues. In vitamin B2 lack, it is recommended that pyridoxin be combined with flavin mononucleotide and in particular with flavin adenine dinucleotide.

The vitamin B6 requirement in oral contraceptive users. II. Assessment by tryptophan metabolites, vitamin B6, and pyridoxic acid levels in urine.

PIP: The requirement for vitamin B6 in oral contraceptive users was studied in 8 college-age women who used combined (7) or sequential (1) oral contraceptives. The subjects and 8 controls consumed a basal diet supplemented to result in daily intake of 2.06 mg pyridoxine hydrochloride for 10 days (predepletion) and then containing only .36 mg of vitamin B6 for 32 days. After the depletion period, the diet was supplemented with pyridoxine hydrochloride to increase the intake of B6 to .96, 1.56, and 5.06 mg for 8, 9, and 7 days respectively. Complete 14-hour urine collections were analyzed for xanthurenic acid, kynurenic acids, kynurenine, and 3-hydroxykynurenine after administration of a l load-dose of 2 gm L-trytophan on days 2, 11, 18, 25, 32, 39, 43, 50 , 59, and 66 for the subjects and days 2 and 10 for the controls. Pretryptophan urine was analyzed for vitamin B6. Posttryptophan urine was analyzed for 4-pyridoxic acid. It was found that during the depletion phase the excretion of tryptophan metabolites increased significantly. Excretion dropped significantly upon supplementation with 1.56 or 5.06 mg of vitamin B6, returning values to normal. Levels of vitamin B6 and 4-pyridoxic acid in the urine decreased during depletion to be restored to normal upon supplementation with 1.56 mg/day. Since an intake of 5.0 mg vitamin B6 caused a loss of the vitamin in the urine and all levels were returned to normal with an intake of 1.56 mg, it is suggested that 1.5 mg of vitamin B6 is sufficient to meet the needs of most oral contraceptive users and that there is no significant difference in the vitamin B6 requirement of oral contraceptive users and nonusers.^ieng

Excretion of 4-pyridoxic acid and oxalic acid in patients with urinary calculi.

Urinary excretion of 4-pyridoxic acid and oxalic acid was investigated in 75 patients with urinary calculi and in 50 normal subjects on regular diet. Mean excretion of 4-pyridoxic acid was 0.85 and 0.90 mg per day, respectively, and mean excretion of oxalic acid was 27.5 and 28.0 mg per day, respectively. Statistically there was no difference between the two groups in 4-pyridoxic acid excretion or in oxalic acid excretion. There was a weak positive correlation between the urinary excretion of 4-pyridoxic acid and oxalic acid. Patients who were on ascorbic acid supplementation during the urine collection period excreted increased amounts of oxalic acid. It was concluded from this investigation that most patients with urinary calculi had 4-pyridoxic acid excretion and oxalic acid excretion within normal limits. Low 4-pyridoxic acid values were not combined with high excretion values of oxalic acid, and the nutritional state of vitamin B6 in patients with urinary calculi was assumed to be satisfactory in order to control the endogenous oxalic acid production. The significance of high excretion values of 4-pyridoxic acid and oxalic acid is discussed.

Plasma pyridoxal phosphate levels in fulminant hepatic failure and the effects of parenteral supplementation.

Plasma concentrations of pyridoxal-5'-phosphate (PLP), the active coenzyme form of vitamin B6, were found to be markedly raised in patients with fulminant hepatic failure, when estimated within one week of the onset of symptoms. In parallel with the rise in plasma PLP, there was an increase in serum aminotransferase activity, suggesting that as a result of the severe hepatocyte injury, vitamin is released from theliver in the form of transaminase holoenzymes. There was no correlation between plasma levels of PLP and the urinary excretion of 4-pyridoxic acid, its main metabolite, either in the patients or normal control subjects. There was a progressive decline in plasma PLP levels after the initial period, which was not prevented by administration of high doses of pyridoxine hydrochloride (100 mg intravenously daily), suggesting that thseepatients are either unable to convert pyridoxine to PLP, or that degradation of PLP occurs at a pathologically incrased rate in this condition.

Vitamin B6 deficiency in chronic liver disease--evidence for increased degradation of pyridoxal-5'-phosphate.

Plasma levels of pyridoxal-5'-phosphate (PLP), the active coenzyme form of vitamin B6, were found to be significantly lower than normal in 22 out of 31 patients with decompensated cirrhosis or subacute hepatic necrosis. There was no significant difference in plasma PLP levels between those with liver disease due to alcohol and those with other varieties. When intravenous supplements with pyridoxine hydrochloride were given only 33% responded with an increase in plasma PLP. In contrast, all patients given PLP responded, although peak plasma levels were variable, the response being significantly less than that found in normal control subjects. After supplementation with pyridoxine hydrochloride, and with PLP, the urinary excretion of 4-pyridoxic acid, which is derived from the degradation of PLP, was higher in patients who showed the least increase in plasma PLP levels. Although impaired phosphorylation of pyridoxine hydrochloride may be one factor, the most likely explanation for these findings is an increased rate of PLP degradation which may be important in the pathogenesis of vitamin B6 deficiency in patients with severe liver disease.