The purpose of this study was to determine the relationship between the overall changes in concentration of plasma pyridoxal 5'-phosphate (PLP), red blood cell PLP (rbc PLP) and plasma glucose during an oral glucose tolerance test (OGTT) in persons with diabetes mellitus (DM), and to test the hypothesis that the decrease in plasma PLP concentration that occurs with increasing plasma glucose would be explained by a subsequent increase in rbc PLP concentration. A second objective was to compare the distribution of PLP between the red blood cell and the plasma (as measured by the rbc PLP/ plasma PLP ratio) in persons with diabetes to the distribution in non-diabetic controls. The third objective was to measure fasting plasma alkaline phosphatase (AP) activity, and to compare it to fasting plasma PLP concentrations, fasting rbc PLP concentrations, and the rbc PLP/plasma PLP ratio. The purpose of this third objective was to test the hypothesis that an increased plasma AP activity in persons with DM would be associated with decreased plasma PLP and increased rbc PLP concentrations. The study included 8 persons (3F; 5M) with insulin dependent diabetes mellitus (IDDM), 9 persons (5F; 4M) with non-insulin dependent diabetes mellitus (NIDDM) and 18 healthy control individuals (9F; 9M). All subjects were given a 75 gm oral D-glucose dose, and blood was drawn at 0 (fasting), 30, 60 and 120 minutes after the glucose load. Plasma glucose, PLP, insulin, and rbc PLP concentrations were measured at all time points during the OGTT. Fasting plasma alkaline phosphatase (AP) activity, percent glycosylated hemoglobin (%GlyHb), and the ratio between fasting rbc PLP and fasting plasma PLP were also determined. In general, females with DM were in poorer diabetic control as compared to males with DM. Mean fasting glucose levels, %GlyHb and body mass index (BMI) were highest in females with DM as compared to all other groups, and fasting insulin was nearly 2x higher in females with NIDDM as compared to males with NIDDM. There was an overall decrease in plasma PLP during the OGTT with increasing plasma glucose, which agrees with results from other studies. The overall decrease in plasma PLP (as measured by the negative, cumulative area under the curve: -AUC plp) was significantly correlated with the overall increase in plasma glucose (as measured by the positive, cumulative area under the curve: +AUC glu) for all study groups. The relationship was stronger in all males, and control females as compared to females with diabetes (p< 0.001 vs. p< 0.01, respectively). This difference was in part explained by lower mean fasting PLP levels in females with DM (19.3 nmol/L), as compared to males with DM (47.2nmol/L) and male and female controls (35.4 nmol/L and 34.0 nmol/L, respectively). The changes in rbc PLP during the OGTT were minimal, and did not significantly correlate with the increase in plasma glucose or the decrease in plasma PLP. Thus, the acute drop in plasma PLP concentration that occurred during the OGTT was not explained by a subsequent increase in rbc PLP concentration, as had been hypothesized. However, the higher than normal % glycosylated hemoglobin levels along with elevated rbc PLP concentrations in persons with diabetes as compared to controls suggests that chronically elevated blood glucose can contribute to increased rbc PLP concentrations. This was the first study to date that has measured rbc PLP in persons with diabetes mellitus. Rbc PLP values for persons with DM were 20-40% greater than respective control values at all time points during the OGTT. These differences between mean rbc PLP in persons with DM as compared to control groups were all statistically significant (p< 0.05) with the exception of the difference in the mean fasting rbc PLP value for females with NIDDM as compared to controls. The mean values ± standard deviations (SD) for fasting rbc PLP (nmol/L) were as follows: Females-IDDM, 49.5 ± 6.5; NIDDM, 39.3 ± 4.9; controls, 31.4 ± 9.0; Males-IDDM, 37.8 ± 10.9; NIDDM, 45.6 ± 12.3; controls, 28.3 ± 4.4. The ratio of fasting rbc PLP concentration to fasting plasma PLP concentration was 2-3x higher in females with DM as compared to control females and all male groups. Females with IDDM had a ratio of 3.2, and the ratio for females with NIDDM was 2.2. The ratios for all male groups, and control females were approximately 1:1, with a range of 0.8-1.2. The mean fasting plasma AP activity was within the normal range for all study groups. However, females with DM had higher AP activity (0.543 μkat/L) as compared to female controls and males with DM (0.408 μkat/L, .425 μkat/L, respectively p<0.05). There were no significant differences in mean fasting plasma AP activity between any male group (range 0.390-0.465 μkat/L). These results suggest that increased plasma glucose levels, increased AP activity, and overall poor glycemic control contribute to decreased plasma PLP concentrations, increased rbc PLP concentrations, and possibly to changes in the PLP distribution within the body. / Graduation date: 1994

Previous studies suggest that vitamin B-6 supplementation can alter fuel metabolism during exercise and plasma amino acid levels at rest. To examine the effect of vitamin B-6 supplementation on plasma fuel substrates and amino acid levels during exercise, five trained males (age: 29±7; V0₂ max: 54.7±6.2 ml/kg/min) performed two separate submaximal, endurance, exercise tests on a cycle ergometer. Subjects were exercised to exhaustion at 74.5±7.8% V0₂ max in a fasted condition on the seventh morning of two separate nine day controlled diet periods. The first exercise test (T1) occurred following a control or non-supplemented (NS) diet (i.e. 1.9 mg B-6/day), and the second exercise test (T2) occurred following a vitamin B-6 supplemented (S) diet (i.e. 1.9 mg B-6/day + 20 mg PN/day). Blood was drawn pre, during (i.e. 60 minutes into exercise), post, and post-60 minutes of exercise, and plasma was analyzed for glucose, lactic acid, glycerol, free fatty acids (FFA), and amino acids. Expired air was collected for three minutes at 10 minute intervals during both tests. Although not statistically different, there were observed trends for higher mean lactate levels and lower mean glycerol and FFA levels in T2 (S) compared to T1 (NS). Mean lactate, glycerol, and FFA concentrations all changed statistically significantly over time in both exercise tests. Mean plasma tyrosine levels were significantly lower (p = 0.007) at post-60 minutes of exercise and mean plasma methionine levels were significantly lower (p = 0.03) at post-exercise in T2 relative to T1. Of the 13 amino acids quantitated, only alanine and histidine concentrations changed significantly over time. Although not statistically significant, mean respiratory exchange (R) values tended to be higher in T2 compared to T1. Mean oxygen consumption values were significantly higher (p = 0.02) during the first 10 minutes of exercise and at multiple later time points showed a trend for being higher in T2 compared to T1. No statistically significant differences were observed in subjects' performance times to exhaustion between T1 (1:35:49; hr:min:sec) and T2 (1:31:56). These results indicate that vitamin B-6 supplementation can potentially alter fuel metabolism and plasma amino acid levels during exhaustive endurance exercise; however, not to such a degree that one's endurance capacity is affected. / Graduation date: 1995

Four young trained men were studied during 50 min of continuous bicycle ergometer exercise [30 min at 60%, 15 min at 80%, and 5 min at 90% maximal heart rate (MHR)] to elucidate changes in fuel metabolism resulting from a glycogen depletion-repletion regimen, and to determine the effect of supplemental vitamin B-6 (B6). The diets were: Week 1, 40% CHO normal diet (NC); Week 2, days 1-3 CHO 11% (LC), days 4-7 CHO 71% (HC); Week 3, same as week 2 but with an 8 mg B6 supplement each day (LC+B6, HC+B6). The men exercised after an overnight fast on days 4 and 7, upon completing the depletion or repletion phase. Blood was collected before exercise (PRE), during the 80% MHR work (DURING), immediately after completion of the 90% MHR work (POST), and 30 min and 60 min after exercise (30 MIN POST, 60 MIN POST). Plasma FFA concentrations were from 30% to 75% higher (p<0.05) after the LC and LC+B6 diets than after the NC-1, NC-2, HC, or HC+B6 diets, and B6 did not appear to affect plasma FFA levels. Plasma glucose values were from 3% to 4% lower (p<0.01) for DURING HC and HC+B6 than DURING NC-1. Since plasma HC and HC+B6 lactate values were 57% higher (p<0.05) than DURING control values, the simultaneously low glucose and high lactate levels indicate that glucose was primarily derived from muscle glycogen in the HC and HC+B6 conditions. Addition of B6 to the HC diet resulted in elevated POST lactate levels, but this difference was not significant. LC glucose and lactate values did not differ significantly from control values. However, PRE LC+B6 glucose values were 12% lower than PRE control values (p<0.02) and continued to be lower during exercise. POST and 30 MIN POST LC+B6 values were 47% lower than the LC values (p<0.005 and p<0.01, respectively). The glucose and lactate data indicate that B6 supplementation does alter CHO metabolism when added to a glycogen depletion-repletion regimen. Due to the possible role of glycogen phosphorylase as an expanding depot for B6 storage, supplementation with B6 may cause a more rapid emptying of muscle glycogen stores and a reduction of athletic endurance. / Graduation date: 1983

There were two main purposes to this study. The first was to determine the vitamin B-6 and pyridoxine β-glucoside content of selected foods commonly consumed in Malawi. The second was to examine the effect of preparation procedures of foods in Malawi on the content of vitamin B-6 and pyridoxine β- glucoside in foods. Seventeen plant foods commonly eaten in Malawi were determined for vitamin B-6 and pyridoxine β-glucoside using a microbiological assay. In addition, two commercial weaning foods, roasted maize-soy bean blend and extruded maize-soy bean blend, were also determined for vitamin B-6 and pyridoxine β-glucoside contents. Among all the foods analyzed, whole maize flour contained the highest amount of vitamin B-6 (0.66 mg/100 g), therefore, an excellent source of vitamin B-6 content in foods. Cooking decreased vitamin B-6 in pinto beans, kidney beans, sugar beans and cow peas by 34%, 45%, 14% and 48%, respectively. Roasting decreased vitamin B-6 in chick peas and soy beans by 59% and 38%, respectively. Soaking and fermentation reduced vitamin B-6 in soaked maize flour and cassava flour by 86% and 89 %, respectively. Therefore, these data suggest that some of the preparation procedures practiced in Malawi have a negative impact on the vitamin B-6 content of the processed foods. Cooked and roasted foods contained lower total amount of pyridoxine-glucoside than that of the raw food. The high pyridoxine β-glucoside content have adverse impact on the bioavailability of vitamin B-6 content. Based on typical diets for the urban and rural populations in Malawi, the rural diet contained less vitamin B-6 compared to that of urban diet. Therefore, the rural population may be at risk of inadequate vitamin B-6 intake compared to the urban population. / Graduation date: 2002

The status of vitamin B-6 (B6) nutriture of nine persons (4F;5M) with insulin dependent diabetes mellitus (IDDM), nine persons (5F;4M) with non-insulin dependent diabetes mellitus (NIDDM), and 18 control individuals (9F;9M) was evaluated, using biochemical and dietary indicators of B6 status. The biochemical indices employed were plasma concentration of pyridoxal 5'-phosphate (PLP), urinary 4-pyridoxic acid (4PA) excretion, and urinary kynurenic acid (KA) and xanthurenic, acid (XA) excretion following a tryptophan load test (2 g L-tryptophan oral load). Dietary B6 intake and the ratio of B6 (mg) to dietary protein (g) (B6:protein) were determined. Fasting blood, two consecutive 24 h urine collections and three consecutive daily weighed diet records were obtained on each of two occasions, separated by 30-70 d. Diet records were analyzed for vitamin B-6 and protein intake using nutrient data bases. Samples of 70 foods, for which the data bases lacked B6 values, were obtained and analyzed for total B6 content by a microbiological method. The plasma concentration of PLP was determined by an enzymatic method, and plasma alkaline phosphatase activity by a colorimetric method. Urinary 4PA was separated by HPLC, urinary KA and XA by ion exchange, and each metabolite was determined fluorometrically. The mean daily vitamin B-6 intake of each group exceeded the recommended dietary allowance (RDA). The mean B6:protein ratios ± standard deviations (SD) for the groups of females were 0.0200±0.0027, 0.0304±0.0101, and 0.0254±0.0099 for IDDM, NIDDM and control (C), respectively. The respective B6:protein ratios for the males were 0.0280±0.0040, 0.0242±0.0038 and 0.0241±0.0078. The mean±SD plasma PLP concentrations for females were 22.4±6.8, 21.8±9.6 and 37.4126.8 nmol/L for IDDM, NIDDM and C, respectively. The mean plasma PLP concentrations of the two groups of females with diabetes were at the low end of a range (22.4-25.3 nmol/L) suggested to indicate marginal status, and 56% of the females with diabetes had PLP concentrations below the lower boundary of the marginal range. For the three groups of males the PLP concentrations were in the same rank order as dietary B6 intake; 53.9±18.2, 43.6±7.2 and 37.5±17.7 nmol/L for IDDM, NIDDM and C, respectively. Plasma PLP concentration was strongly and significantly correlated with B6 intake in both diabetes (n=18, r=.744, p<.001) and C (n=18, r=.695, p<.001) groups, but was also negatively associated with plasma AP activity only for the diabetes group (n=18, r=- .454, a=.058). The mean plasma AP activity of females with NIDDM was significantly higher than that of the female C group (p<.01). Greater than normal AP hydrolysis of PLP is thought to have contributed to the low plasma PLP concentrations observed in the females with NIDDM. Levels of urinary 4PA excretion by females were 8.76±2.10, 7.61±12.57 and 8.15±14.43 μmol/d for IDDM, NIDDM and C, respectively, or 87, 63 and 72% of B6 intake. For males the urinary 4PA levels were 12.76±14.53, 10.32±11.77 and 9.81+3.34 μmol/d, respectively, or 76, 68 and 78% of B6 intake. All subjects excreted 4-PA in amounts indicative of adequate B6 status. All means for tryptophan metabolites were within ranges seen for normal subjects, both pre and post-tryptophan load. None of the subjects with diabetes and only one female C subject excreted more than 65 μmol XA in 24 h after the tryptophan load (upper boundary of normal response to 2 g tryptophan load). Mean post-load excretion of XA and KA of diabetes groups was numerically lower than that of same sex controls in all comparisons, although in only one instance was the difference significant (NIDDM females post-load KA, p<.05). The results of the tryptophan load test suggest adequate B6 function in the kynurenine pathway those with diabetes and controls. Individuals with diabetes were found to consume adequate or above amounts of B6 by the standard of the RDA. Low plasma PLP levels were observed in females with IDDM who had the lowest B6 intake, and in females with NIDDM who had the highest plasma AP activity. The present research indicates that low PLP may be present in diabetes, as observed by other investigators, despite seemingly adequate B6 nutriture. However, normal to above normal amounts of urinary 4-PA excretion indicated adequate body stores of B6, and normal response to the tryptophan load test suggested adequate function of B6 in the liver of persons with diabetes. Plasma PLP concentration alone may not be an adequate B6 status indicator in persons with diabetes. Based upon the levels of multiple indicators, the vitamin B-6 status of those persons with diabetes studied was judged to be adequate. / Graduation date: 1991

Graduation date: 1985

Thesis (Ph. D. in Chemistry)--Vanderbilt University, May 2008. / Title from title screen. Includes bibliographical references.

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