Plasma PLP Research Articles

Role of vitamins B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani population of patients with acute myocardial infarction

Pakistani people belong to an ethnic group which has the highest rate of coronary artery disease (CAD). We investigated the possible correlation between deficiency of vitamins B6, B12 or folic acid and hyperhomocysteinemia in Pakistani patients with acute myocardial infarction (AMI). A case-control study was carried out involving 224 AMI patients (age 30-70 years; 55 females and 169 males) and 126 normal healthy subjects (age 31-70 years; 35 females and 91 males). Fasting venous blood was obtained from cases and controls. Serum was analyzed for folic acid and B12 using radioassays. Plasma was analyzed for pyridoxal phosphate (PLP; coenzymic form of B6) using a radioenzymatic assay and for total homocysteine using a fluorescence polarization immunoassay. Mean serum B12 concentration in AMI patients was found to be significantly lower than the mean for controls (241+/-185 pg/ml vs 608+/-341 pg/ml; p < 0.001). Mean serum folate level in patients was also found to be lower than controls (3.35+/-3.78 ng/ml vs 4.93+/-2.93 ng/ml), however, the differences were not statistically significant. Similarly, mean PLP concentration in plasma of cases (19.4+/-24.4 nmol/l) was lower than the concentration in controls (23.2+/-17.6 nmol/l), but the difference was not statistically significant. Mean plasma homocysteine level in AMI cases (18+/-8.36 micromol/l) was higher than the mean level in controls (16.4+/-4.9 micromol/l), but not to a significant extent. However, this mean homocysteine concentration in normal healthy subjects was among the highest reported in the literature and was significantly more than mean values reported in most Eastern and Western studies. Compared to controls, there was significantly greater deficiency of folate (32.5% vs 67.1%), B12 (3.2% vs 63.4%) and PLP (49.2% vs 74.1%) in AMI patients. Deficiencies of folate, B12 and PLP were defined as serum folate levels less than 3.5 ng/ml, serum levels of B12 less than 200 pg/ml and plasma PLP levels less than 20 nmol/l. Mean plasma homocysteine levels in smokers were found to be significantly higher in both cases and controls. Similarly, mean serum folate levels in smokers (compared to nonsmokers) were significantly lower in both cases and controls. Substantial nutritional deficiencies of these three vitamins along with mild hyperhomocysteinemia, perhaps through an interplay with the classical cardiovascular risk factors (highly prevalent in this population), could be further aggravating the risk of CAD in the Pakistani population.

Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study

The results of prospective studies on the relations between the plasma concentration of total homocysteine (tHcy) and B-vitamins, on the one hand, and coronary heart disease (CHD) mortality, on the other hand, are inconclusive and scarce considering the relation with B-vitamins. We prospectively determined these relations in a case-cohort study. The full-cohort existed in ∼36,000 Dutch adults aged 20–59 years at baseline. The statistical analyses were done with a random sample from the cohort ( n=630) complemented with all subjects who died of CHD ( n=102) during a mean follow-up of 10.3 years. All subjects reported the absence of cardiovascular diseases (CVDs) at baseline. The plasma concentrations of tHcy, folate, PLP, and vitamin B12 were determined in samples obtained at baseline. Men with a tHcy concentration in the highest tertile (T3) compared with men in the lowest tertile (T1) had a relative risk (RR) of 1.14 for CHD (95% confidence interval (CI): 0.50, 2.61) after adjusting for age, study center, hypertension, HDL and total cholesterol, smoking, and creatinine. For women, this RR was 2.04 (95% CI: 0.48, 8.62). For each 5 μmol/l increase in tHcy, the RR of CHD was 1.03 (95% CI: 0.83–1.29) for men and women combined. In women only, high folate levels were associated with a statistically significant protection of fatal CHD (T3 versus T1; RR: 0.22, 95% CI: 0.06, 0.87). Plasma PLP (B6) and vitamin B12 concentrations were not associated with CHD risk. We conclude that elevated tHcy concentrations do not seem to be a risk factor for CHD mortality in these relatively young healthy Dutch subjects free of baseline CVD. Higher folate concentrations may be protective of CHD, but this needs confirmation.

Dietary Effects of Punicic Acid on the Composition and Peroxidation of Rat Plasma Lipid.

The purpose of the present study is to examine the oxidative behavior of punicic acid (9 cis, 11 trans, 13 cis-18:3 octadecatrienoic fatty acid) under in vivo condition using male albino rats after blending with dietary soybean oil. Male weanling Charles Foster rats (n = four to eight), weighing 65-68 grams, were allocated for fourteen weeks to diets containing 0.6, 1.2 and 2.4% (by weight) punicic acid obtained from snake gourd seed oil (Trichosanthes anguina) after mixing with soybean oil, vis-à-vis control group consisting of 100% soybean oil, containing 50.3% C18:2, 6.2% 9 cis, 12 cis, 15 cis-18:3 (linolenic acid) and does not contain punicic acid. Increase in weight remained higher than control in rats fed with 0.6 and 1.2% punicic acid throughout the experimental period. There was significant lowering in plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the groups fed with 2.4% punicic acid. Lipoprotein oxidation susceptibility or LOS expressed as nmoles of malondialdehyde (MDA) per mg of non-high density lipoprotein cholesterol (non-HDL-C) and plasma lipid peroxidation or PLP expressed as nmoles of MDA per ml of plasma exhibited maximum antioxidant efficiency at 1.2% punicic acid, being equivalent to that of control (100% soybean oil). While LOS expressed as nmoles of MDA decreased significantly (except at 2.4% punicic acid level) with the least oxidation at 0.6% punicic acid, with respect to control. Accordingly, punicic acid seemed to be acting both as pro-oxidant (at 1.2% punicic acid level) and antioxidant (at 0.6% punicic acid level), with significant decrease in TC and LDL-C at 2.4% punicic acid level when compared to control.

Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine

Objective: To evaluate plasma homocysteine (Hcy) concentrations in children receiving sodium valproate (VPA) and carbamazepine (CBZ), monotherapy, in comparison with healthy control subjects and to determine the possible relationship between Hcy levels and dosage and plasma concentrations of the antiepileptic drugs. Methods: We measured levels of fasting and post-methionine Hcy, plasma pyridoxal 5′-phosphate (PLP, active vitamin B6), serum folate, erythrocyte folate and serum vitamin B12 in 60 epileptic patients (29 females, 31 males), aged from 14.2 to 17.9 years, subdivided into two groups according to their therapy. Sixty-three healthy sex- and age-matched children served as controls. These measurements have been performed before the beginning of therapy and after 1 year of therapy with VPA or CBZ. Results: Before the beginning of therapy, there were no significant differences in fasting and post-methionine Hcy, plasma PLP, serum folate, erythrocyte folate and serum vitamin B12 values between the control group and the two groups of epileptic children. After 1 year of therapy, patients treated with VPA and CBZ showed a significant increase of the plasma concentrations of Hcy when compared to baseline data and controls values. Moreover, was observed a significant decrease of serum folate and plasma PLP. On the contrary, serum vitamin B12 and erythrocyte folate levels remained in the normal range. Conclusions: Our study demonstrates that prolonged treatment with VPA and CBZ increases plasma concentrations of Hcy.

Homocysteine, B vitamins, and vascular-access thrombosis in patients treated with hemodialysis

To evaluate whether increased plasma homocysteine concentrations (hyperhomocysteinemia) are associated with thrombosis of arteriovenous (AV) grafts, we determined plasma homocysteine, plasma and erythrocyte folate, plasma vitamin B12, and vitamin B6 (pyridoxal-5'-phosphate [PLP]) in 48 patients (45 black patients and three white patients) with end-stage renal disease who received hemodialysis. 5,10- Methylenetetrahydrofolate reductase (MTHFR) genotypes were also analyzed. The patients were divided into two groups, including a thrombosis-prone group with frequent graft loss (n = 24) and a control group with prolonged graft survival who were matched by age and duration of dialysis (n = 24). Hyperhomocysteinemia (>15 micromol/L) was found in 42 patients. There were no significant differences in all values, including the concentrations of homocysteine and vitamins between the two groups. Based on plasma folate and PLP concentrations, over 70% of patients appeared to have inadequate folate and/or vitamin B6 nutriture. Plasma homocysteine concentrations showed significant negative correlations with plasma and erythrocyte folate, and plasma vitamin B12 in all patients combined, whereas no significant correlation was found between plasma PLP and homocysteine concentrations. Among 48 patients, the heterozygous mutation (Val/Ala) of MTHFR was found only in three patients, two of whom belonged to the thrombosis-prone group and one to the control group, and there were no individuals with homozygous thermolabile mutation (Val/Val). All three white patients had Ala/Ala genotype, and 3 in 45 black patients (6.7%) were heterozygotes (Val/Ala). (Am J Kidney Dis 1998 Sep;32(3):475-81)

Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people

Free-living elderly people aged >65 y were recruited to assess riboflavin and vitamin B-6 intakes and status and the effect of riboflavin supplementation on biochemical indicators of these 2 vitamins. The status of riboflavin (erythrocyte glutathione reductase activation coefficient; EGRAC) and vita-min B-6 (plasma pyridoxal-5'-phosphate; PLP) were determined in a total sample of 92 subjects, from whom dietary intake data were obtained by using the diet history method (n = 83). Although dietary intakes of both vitamins were considered to be adequate according to current reference values, abnormal EGRAC and plasma PLP values were identified in 49% and 38% of subjects, respectively, with 21% having suboptimal status for both nutrients. A subgroup of subjects from the initial sample (n = 45) was assigned in a double-blind manner to receive either 1.6 or 25 mg riboflavin or placebo daily for 12 wk. In those subjects with a baseline EGRAC or plasma PLP value falling outside the currently accepted threshold value for adequacy, low- dose riboflavin supplementation improved status of the limiting nutrient significantly (P <0.0001 and P = 0.020 for EGRAC and plasma PLP responses, respectively). We conclude that a high proportion of healthy elderly people may have suboptimal status for these nutrients despite apparently adequate dietary intakes. Furthermore, we showed that riboflavin supplementation at physiologic doses corrects biochemical abnormalities of not only EGRAC, but also plasma PLP, confirming the biochemical interdependency of these vitamins and suggesting that riboflavin is the limiting nutrient. Am J Clin Nutr 1998;68:389–95.

Vitamin B6, vitamin C, and carpal tunnel syndrome. A cross-sectional study of 441 adults.

As part of an ongoing study of carpal tunnel syndrome (CTS) in industry, we measured plasma concentrations of pyridoxal 5'-phosphate (PLP, a measure of vitamin B6 status) and total ascorbate (ASC, a measure of vitamin C status) in 441 adult volunteers from six industries and a university exercise study. In the entire study group and in non-vitamin users (n = 218), there were no significant differences in mean plasma PLP or ASC concentrations between controls (neither symptoms nor slowing), subjects with symptoms only, subjects with median nerve slowing only, or subjects with CTS (symptoms + slowing). In male non-vitamin users (n = 137), there were significant inverse univariate associations between plasma PLP concentration and the prevalence of pain, the frequency of tingling and nocturnal awakening, and the Phalen test result. In this same subgroup, the ASC/PLP ratio was directly associated with the prevalence of pain and nocturnal awakening, and with the frequency of pain, tingling, and nocturnal awakening. In multivariate analyses, plasma ASC concentration predicted more median nerve slowing and confirmed CTS, and vitamin or vitamin interaction variables were independent predictors of 20 CTS-related outcomes. These multivariate relationships often occurred only after adjustment for age, gender, body mass index, serum alkaline phosphatase activity, or tobacco use. We conclude that there are significant relationships between plasma vitamin levels and both components of CTS (specific symptoms and median nerve slowing). The interaction between plasma PLP and ASC appears to be particularly important with respect to symptoms.

Vitamin B-6 metabolism is altered in chronic renal failure rats

Effect of chronic renal failure on plasma pyridoxal phosphate and total vitamin B-6 concentrations and the activation coefficients of erythrocyte aminotransferases in rats were studied. The uremia was induced by two-stage five–sixths nephrectomy. Urine and blood samples were collected eight weeks after the surgery. Serum urea levels were significantly greater in uremic animals. Creatinine clearance of uremic group was 30% of the control value. Food intake of the control and uremic groups did not significantly differ. The levels of plasma pyridoxal phosphate of the uremic group were 43% lower than those of the control group, but the concentrations of plasma total vitamin B-6 were not significantly different between the control and uremic groups. No differences were observed in activation coefficients of erythrocyte aspartate aminotransferase and alanine aminotransferase between the control and uremic groups. Results of this study indicated that vitamin B-6 metabolism was altered in chronic renal failure animals. More than one biochemical index for assessing vitamin B-6 status should be employed in chronic renal failure. The serum alkaline phosphatase activity was comparable between the control and uremic groups, indicating that serum alkaline phosphatase was not involved in lowering plasma PLP of chronic renal failure animals.

Change in blood levels of vitamin B-6 derivatives in pregnant and lactating rats.

By using an HPLC method which we have developed, concentration changes of vitamin B-6 derivatives in blood of pregnant and lactating rats were studied. PLP and PL were the main derivatives in plasma and erythrocytes, and occasionally, PMP was found in the plasma of rats fed a normal solid diet which contained 8.3 mg PN.HCl/kg diet. Upon pregnancy, the plasma PLP concentration decreased significantly (p < 0.01), whereas plasma PL tended to increase (p < 0.05). PLP concentration in erythrocytes tended to increase upon pregnancy. These results suggest that metabolism or utilization of vitamin B-6 is altered upon pregnancy and that plasma PLP concentrations alone may not be a good indicator of nutritional status. Further confirmation was needed for so from erythrocyte samples under our analytical conditions was not so from erythrocyte samples under our analytical conditions was not converted to PIC-P via PLP, after the sample was treated with glyoxylic acid and then with KCN.

Separation and quantification of the B6 vitamers in plasma and 4-pyridoxic acid in urine of adolescent girls by reversed-phase high-performance liquid chromatography

The vitamin B6 status of seemingly healthy adolescent girls was determined using several accepted and proposed parameters in an effort to establish guidelines for status evaluation. High-performance liquid chromatography-derived plasma B6 vitamers (pyridoxal phosphate, PLP; pyridoxine phosphate. PNP; pyridoxamine phosphate, PMP; pyridoxal, PL; pyridoxine, PN; and pyridoxamine, PM) and 4-pyridoxic acid (4-PA) concentrations and urinary 4-PA levels of 28 white adolescent females, 12-15 years, having radiomonitored plasma PLP concentrations and coenzyme stimulation of erythrocyte alanine aminotransferase activities indicative of adequate status were determined. Mean vitamin B6 and protein intakes were 1.48 mg and 78.3 g. Ranges for plasma B6 vitamer and 4-PA concentrations (nmol/l) were: PLP, 40.9-122.2; PNP, non-detectable (ND)-16.1; PMP, ND-8.1; PL, ND-15; PN, ND-21.9; PM, ND-17.8; and 4-PA, ND-55.7. PLP was the only vitamer found in plasma of all subjects. Urinary 4-PA concentrations ranged from 0.11 to 2.50 mumol/mmol of creatinine. B6 vitamer values of these girls should be of use in the establishment of normal ranges for vitamin B6 status parameters.

Impaired collagen maturity in vitamins B 2 and B 6 deficiency—Probable molecular basis of skin lesions

Solubility of collagen was increased and the proportion of insoluble collagen was reduced in the skin of both riboflavin as well as pyridoxine-deficient rats. Collagen content of the skin, and aldehyde concentration of salt-soluble collagen were also lower in the deficient groups. The α:β subunit ratio of salt-soluble collagen was higher in riboflavin deficiency. In food-restricted weight-matched control groups, similar changes in collagen solubility, but of lesser magnitude were observed. Both food restriction and riboflavin deficiency decreased plasma PLP concentration. Increase in the solubility of collagen, decrease in the aldehyde content of soluble collagen and increase in the α:β subunit ratio of soluble collagen, suggest that the maturation of collagen may be affected in pyridoxine or riboflavin deficiency. These molecular events may be etiologically related to the pathogenesis of the skin lesions in vitamin B 2 or B 6 deficiency.

Vitamin B-6 and Plasma PLP in Pregnancy, Lactation

Vitamin B-6 and Plasma PLP in Pregnancy, Lactation