Dissertations / Theses on the topic 'Vitamin B6 – Physiological aspects'

Background: Inverse associations have been reported between homocysteine concentrations and poor cognitive performance in several cross-sectional studies of healthy elderly subjects. Folate supplementation with or without vitamins B-12 and B-6 is an effective means of lowering homocysteine concentrations. Mood disturbances, from mild mood changes to clinical depression, are common in older populations. Several studies have shown that depressed people have lower levels of folate and vitamin B-12 and higher levels of homocysteine than non-depressed people. Improvement of mood has been reported in depressed people following supplementation with folic acid. Clinical trials are required to determine if lowering homocysteine concentration with vitamins improves cognitive function and/or mood in healthy elderly participants. Objective: The primary aim of this research project was to carry-out a 2 year randomised, double-blind, placebo-controlled trial to determine if a supplement containing folate (1mg L-Mefolinic acid), vitamin B-12 (500(mu)g) and vitamin B-6 (10mg) improves scores or prevents decline on tests of cognition in a group of healthy older people ([greater than or equal to]̲ 65 years) with a plasma homocysteine concentration [greater than or equal to]̲13 (mu)mol/L. A second aim of this study was to determine if homocysteine lowering vitamins improved scores on tests of mood in this group. Methods: Four hundred and sixty-five individuals, aged 65 and over, were recruited from Dunedin and surrounds, and asked to attend a screening clinic and provide a fasting blood sample. Two-hundred and seventy-six volunteers with a plasma homocysteine concentration [greater than or equal to]13(mu)mol/L were randomised to take either a combination of 1mg L-Mefolinic acid, 500(mu)g vitamin B-12 and 10mg vitamin B-6 or placebo for 2 years. A battery of cognitive tests and indices of mood was administered at baseline, one year, and two years. A fasting blood sample was collected at baseline and every six months thereafter. Results: From baseline to 6 months of the intervention, homocysteine concentrations decreased by 37.5%, from 16.7 to 10.5 (mu)mol/L in the vitamin supplemented group and then plateaued. In the vitamin supplemented group there was a 181% increase in red blood cell folate concentration from a mean of 977 to 2752 nmol/L, and a 90.1% increase in plasma vitamin B-12 (from a mean 283 to 538 (mu)mol/L) over the study period of two years. In the vitamin supplemented group there was a trend to poorer performance on almost all tests of cognition compared to placebo group. The vitamin group was 8% slower on Part B of the Reitan Trail Making Test, a test of speeded attention, mental tracking, visual search and mental flexibility (p=0.009). The vitamin group scored significantly lower on tests of short-term recall, Weschler Paragraphs (p=0.03) after 2 years, and the Rey Auditory Verbal Learning Test ((p=0.04) after one year, than the placebo group. There was no difference in mood score by treatment in this largely non-depressed group. Conclusion: These results suggest a detrimental effect of high dose homocysteine lowering vitamin supplements on cognitive function in healthy older people. These results need to be confirmed in other randomised controlled trials.

The problem of this study is to determine the vitamin B-6 status of patients who have chronic obstructive pulmonary disease (COPD). Erythrocyte aspartate transaminase assay was the method for measuring vitamin B-6 status. The vitamin B-6 status was examined in thirty subjects (ten COPD subjects and twenty control subjects). An unpaired t-test was used to compare the vitamin B-6 status of the COPD group versus the control group. Four determinants (percentage stimulation, ratio of basal to stimulated activity, basal activity, and stimulated activity) were used to determine vitamin B-6 status in both groups of subjects. Percentage stimulation and ratio of basal to stimulated activity were not significantly different (control group versus COPD group) at the .05 level. However, two of ten COPD subjects had values for percentage stimulation that were two standard deviations above the mean, indicating a poor B-6 status. In contrast, basal activity and stimulated activity of erythrocyte aspartate transaminase were found to be significantly lower at the .05 level in the COPD group than the control group. Therefore, the COPD subjects as a group had some biochemical characteristics of a lower level of vitamin B-6 than the controls.

The purpose of this study was to separate acute and chronic effects of moderate exercise on the immune system by analyzing three sets of experimental and control groups; (1) 72 hours, (2) 1 week, (3) 2 weeks post exercise. Mice swam 5 days per week for 3 weeks accumulating a total of 125, 225, and 225 minutes of exercise in weeks 1, 2, and 3, respectively. Moderate swimming exercise did not result in a significant increase in SDH levels (p > 0.05). There was no change in tissue cell responses as measured by mitogen responsiveness, nor in splenic and thymic cell counts in response to the training regimen at any time point (p ≥ 0.05). Total, CD4, CD8, and T cell counts in the lymph nodes were significantly suppressed at 72 hours and 2 weeks post exercise (p ≤ 0.05). It appears that chronic exercise resulted in an increased trafficking of lymphatic cells, which could be interpreted as a sign of heightened immune reactivity.

The aim of this study was to examine whether vitamins E (200 IU) and C (1 g) in combination would influence exercise-induced lipid peroxidation to a greater extent than vitamin E (400 IU) alone. A placebo-controlled study was carried out on 7 collegiate cyclists who were supplemented with 1) vitamin C (1 g); 2) vitamins E (200 IU) and C (1 g); and vitamin E (400 IU) during 3 treatments, each 3 weeks in duration. The serum concentrations of hematocrit and MDA, one marker of lipid peroxidation, were measured immediately before, immediately after, and 24 hours after each exercise bout. After the vitamin C treatment, MDA serum concentration of the athletes (n=7) increased 85% above the baseline values of the placebo values, the vitamin E/C treatment showed a 29% increase, and the vitamin E treatment showed a 39% decrease. Pre- to post-exercise serum MDA levels increased 64% in the placebo group, a 29% increase in the vitamin C treatment group, a 23.2% increase in the vitamins E/C treatment group, and a 46.9% increase in the vitamin E treatment group. It is concluded that exercise-induced lipid peroxidation is more greatly influenced post-exercise by a combination of vitamins E (200 IU) and C (1 g), than by either vitamin C (1 g) alone, or vitamin E (400 IU) alone.
Department of Family and Consumer Sciences

The purpose of this study was to examine collegiate female swimmers' attitudes toward gender and coaching. The study also examined the coaching styles of male and females coaches and determined whether a difference between styles existed. A purposeful sample of 250 female swimmers from the Mid-American Conference (MAC) during the 2001-2002 swimming season participated in the study. Swimmers were required to have been coached by both female and male coaches in order to be eligible to participate. Addressing the purpose of this study, participants were asked to complete a 30-item questionnaire developed by the researcher. Frequency counts revealed that 23 of the 57 participants preferred a male coach to a female coach. Only two individuals reported their preference for a female with 32 participants citing no gender preference. Two sections, including 14 questions for each gender on the Gender Preference Instrument, assessed coaching style. Independent t -tests were calculated on each question (p < .05). Eight significant gender differences were observed on coaching styles, with the participating athletes scoring the male coach higher on all of the eight categories.
School of Physical Education

Falls in the older population have devastating consequences on the psychological and physiological health of the individual. Due to the complexity of interacting factors associated with ageing, pathology and falling episodes, determination of a primary cause or set of causes has been difficult to establish. Deficits in components of neuromuscular control have been widely studied with the coordinated interaction of sensory and motor system components being presented as a fundamental factor in the reduction of falling episodes. A causal relationship between deficits in vitamin D status and falling episodes has also been suggested. Furthermore, a relationship between poor vitamin D status, falling episodes and poor neuromuscular performance has been reported. The aims of the current study were designed to advance understanding in three aspects of the problem of falls prevention. Firstly an examination of the reliability of testing procedures commonly used in assessment of falls risk was undertaken. The Physiological Profile Assessment (PPA) testing procedure was selected as a commonly used tool and the reliability of its various components (sensory, motor and balance) was undertaken as an independent assessment of this approach to assessing falls propensity. Secondly, a case control study of fallers and non fallers was undertaken in which the neuromuscular tests evaluated in the reliability study were used to assess differences in neuromuscular control. The influence of vitamin D status on these measures was also considered. Thirdly, a 12-month randomised controlled trial of vitamin D/calcium supplementation or placebo/calcium was undertaken to identify the effect on falls outcome and individual measures of neuromuscular control.

Findings were that caregivers considered all items on the Information Needs and Patient Care Needs subscales to be important but most of the unmet needs were from the Patient Care subscale. The needs less satisfied in relation to importance were (a) ways to improve patient appearance, (b) activities that will make patient feel purposeful, (c) information on how to give medications, (d) ways to reassure patient, (e) ways of coping with patient's diagnosis, (f) ways to dress patient comfortably, (g) ways to deal with patient's decreased energy, and (h) importance of not leaving patient alone.The implications for nursing are to assess and anticipate the needs of the caregiver of the stroke survivor so that his or her needs can be met. Preparing caregivers for their new role by meeting their needs will help the nurse met the primary goal of helping the patient.
School of Physical Education

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

Research suggests that, in individuals with carpal tunnel syndrome (CTS), low plasma pyridoxal 5'-phosphate (PLP) concentrations are related to an increased incidence and severity of symptoms associated with CTS. This study was designed to determine the relationship between plasma and red blood cell PLP concentrations and the severity and incidence of CTS symptoms. Thirty people with CTS were selected for a 9 month exercise study. Subjects were divided into either vitamin users or non-vitamin users based on supplement use data gathered at the beginning of the study. Blood was drawn at 1, 6 and 9 months. CTS symptoms questionnaires and health questionnaires were also administered at these intervals. The symptoms questionnaires were used to gather data on the frequency and nature of hand and wrist symptoms. Health questionnaires focused on vitamin supplement usage including frequency, amount and length of use. Mean plasma PLP, total plasma vitamin B6 and erythrocyte PLP concentrations were significantly higher in the sixteen vitamin users when compared to the fourteen non-vitamin users (p<0.001). While there was variation in plasma PLP and total plasma vitamin B6 over time, within each group, there were no significant changes in any of the status measures over the nine month period. Mean erythrocyte PLP concentration, in particular, was stable over time. In vitamin users, the intensity of pain, numbness and tingling was significantly higher when compared to non-vitamin users. In both groups, plasma PLP was negatively correlated with pain. This correlation reached statistical significance in vitamin users at month one and nine (p<0.01), but not at month six; a statistically significant correlation between these two variables was not found in non-vitamin users at any time point. Pain was also negatively and significantly correlated with plasma total vitamin B6 and erythrocyte PLP in vitamin users. No other symptoms were significantly correlated with the status measures. These results indicate that a higher vitamin B6 status may be related to a decrease in the severity of pain experienced by some individuals with CTS.
Graduation date: 1998

This study examined the effect of vitamin B-6 supplementation and exhaustive submaximal exercise on plasma catecholamine concentrations, and the relationship between plasma catecholamines and fuel use, heart rate and oxygen consumption. Five trained men (age= 18-35 years; V0₂max=53 ml 0₂/kg/min.) participated in two controlled dietary periods that were identical except for the addition of 20 mg/d pyridoxine (PN) supplementation during the second period. On the seventh morning of each period, fasted subjects exercised to exhaustion on a cycle ergometer at 74.5% ± 7.8 V0₂max. Blood was drawn pre-exercise (twice), 60 minutes into exercise, immediately post-exercise and 60 minutes post-exercise. Plasma was analyzed for norepinephrine, epinephrine, glucose, pyridoxal 5'-phosphate (PLP), lactic acid, glycerol and free fatty acids (FFA). Heart rate and oxygen consumption were measured pre-exercise and at 10-minute intervals during exercise. Mean plasma PLP concentration was significantly higher during the supplemented versus the nonsupplemented trial at all time points. There were no statistically significant differences in mean plasma catecholamine concentrations or mean plasma fuel concentrations between the nonsupplemented and supplemented trials at any of the time points examined. There were significant changes in the mean plasma concentrations of norepinephrine, lactic acid, glycerol and FFA over time in both trials. Respiratory exchange ratios (R) were higher during the supplemented trial compared to the nonsupplemented trial, but the differences did not attain statistical significance. There were no significant differences in mean exercise times to exhaustion or mean heart rates between the trials. The overall mean oxygen consumption during exercise was consistently higher during the supplemented versus the nonsupplemented trial and the difference attained significance (p=0.016) at one time point (10 min.). The mean oxygen consumption during rest was lower during supplementation versus nonsupplementation, but the difference was not statistically significant. The percent plasma volume change (PVC) was significantly greater at post-exercise, relative to pre-exercise, during the supplemented versus the nonsupplemented trial. The percent PVC also increased significantly over time during the supplemented but not the nonsupplemented trial. These results suggest that 20 mg/d of vitamin B-6 supplementation does not effect plasma catecholamine concentrations, fuel utilization or heart rate at rest or during submaximal exercise to exhaustion. The results may suggest a higher oxygen consumption during exhaustive exercise after PN supplementation.
Graduation date: 1996

The objectives of this study were a) to determine if pyridoxine (PN) supplementation increases the rate at which plasma urea and ammonia return to basal levels, following exercise, b) to determine, by open circuit calorimetry, the utilization of carbohydrates, and c) to further understand vitamin B-6 metabolism during and following strenuous exercise. Six male athletes (age 26 ± 5 years and VO₂ max 66.4 ± 6.9 ml/kg/min) exercised for 1 hour on a cycle ergometer at 72% VO₂ max at two points during a 17 day study. For the first 8 days subjects received daily a placebo solution, while during the next half they received a PN dose (20 mg). Subjects consumed a constant diet the day before, day of, and day after the exercise test. Blood samples were taken the day of the exercise test at fasting (Fl), pre-exercise (PE), during exercise (DE), 1 min post exercise (I'P), 6 hour post exercise (6hP), and the day after the exercise test at fasting (F2). Plasma was analyzed for ammonia, urea, and pyridoxal 5'-phosphate (PLP). ANOVA showed no significant difference between treatments for either plasma ammonia or urea. While there was a significant increase (p<0.001) in plasma ammonia levels over time with the placebo, with supplementation the increase over time was not significant. With PN supplementation, plasma PLP levels were significantly correlated (p<0.05) with plasma ammonia levels at I'P. A slight decrease in plasma urea concentration was observed with the PN treatment at PE, DE, I'P, and 6hP. It was concluded that PN may reduce adverse consequences of plasma ammonia and urea seen with exercise. On the other hand, pyridoxine supplementation may produced a shift in the utilization of substrates of the subjects. Metabolic rate results showed that the contribution of carbohydrates as a energy source increased from 43.5 ± 13.7% with the placebo, to 52.0 ± 6.7% with the PN treatment (not significantly different). This observation lead to the conclusion that PN supplementation decreases glycogen stores compared to the glycogen stores without supplementation. Since the findings from this study suggest slightly more rapid plasma ammonia and urea restoration but decreased glycogen stores, they do not provide evidence for or against an increased need for vitamin B-6 in persons that are involved in strenuous exercises of medium duration.
Graduation date: 1988

The purpose of this study was to examine the effect of extreme exercise on vitamin B-6 metabolism and urea nitrogen. Nine men and five women completed two 5-day trials; Trial 1 (T1) included a 50-km ultramarathon on day 4 and during Trial 2 (T2) subjects were "inactive" on day 4. During both trials, subjects consumed a diet providing men 2.0 and women 1.5 mg of vitamin B-6. With the exception of the ultramarathon, T1 activity was replicated during T2. Twenty four-hour urine collections were completed and blood was drawn pre-race (pre), mid-race (mid), post-race (post) and 60 minutes post race (P-60). On the inactive, day blood was drawn at the same intervals. Plasma was analyzed for pyridoxal 5'-phosphate (PLP), pyridoxal, 4-pyridoxic acid (4-PA), urea nitrogen (PUN), creatinine, albumin, glucose, and lactate concentration and alkaline phosphatase activity. Urine was analyzed for 4PA, creatinine, and total urinary nitrogen (TUN). During T1, compared to pre, plasma PLP concentration increased 17% at mid, decreased 5% by post, and 19% by P-60. During T2, plasma PLP concentration decreased 13% pre to P-60. During T1, plasma 4-PA concentration increased 135% and the percent dietary vitamin B-6 that was excreted as urinary 4-PA the day of the ultramarathon was higher than that excreted the day before and the day after. During T1, from pre to post mean PUN concentration increased 36.9%, and the average rate ofincrease from pre to mid, mid to post, and post to P60 was 0.5, 1.75, and 2 mg/dL/hour, respectively. During T1 on days 3, 4, and 5,88%, 100%, and 95% of nitrogen intake was excreted in the urine compared to 86%, 83%, and 84% for the same days during T2. The day of the ultramarathon, 24-hour TUN excretion was 2 g higher than the previous day. Extreme exercise of greater than six hours initially increases the plasma concentration of PLP but ultimately results in a significant decrease in plasma PLP, an increase in plasma 4-PA, and an increase in percent of dietary vitamin B-6 (as 4-PA) excreted in the urine. Additionally, the rate of change in PUN inoeases as duration increases.
Graduation date: 2001

Previous studies have found that smoking may have a negative effect on vitamin B-6 indices and have demonstrated a possible association between smoking and depressed plasma pyridoxal-5'-phosphate (PLP) concentration. Individuals with plasma PLP values below the adequate level of 30 nmoles/L might benefit from consumption of vitamin B-6 supplements, but no data are available on vitamin B-6 status in smokers consuming a controlled vitamin B-6 intake and receiving a vitamin B-6 supplement. The objectives of this research were to assess vitamin B-6 status in smokers as compared to non-smokers receiving a controlled diet and to evaluate the effect of an oral vitamin B-6 supplementation in these subjects. The vitamin B-6 (B-6) status of 5 (four males / one female) smokers (S) and 4 (three males / one female) non-smokers (NS) was assessed. A constant diet was fed for 20 days and provided 1.95 mg of B-6 or 1.65 mg of B-6 for males and females, respectively. For the last 10 days, an additional 2-mg of pyridoxine (PN) was given daily. Blood samples were collected on days 1.7, 11.14 and 21; and 24 hour urine samples were collected daily. Urinary 4-pyridoxic acid (4-PA) and total B-6 (UB6) excretion, plasma B-6 vitamers (PLP, PN, pyridoxal and 4-PA) and red blood cell PLP (RBC PLP) concentrations, as well as plasma alkaline phosphatase activity (APA) were determined. Mean plasma PLP, 4-PA, and RBC PLP concentrations were significantly lower (P [less than or equal to] 0.05) at all time points in S compared to NS. With a daily supplement of 2-mg vitamin B-6, the mean plasma PLP concentration of S increased 85.8% but was 48.5% lower than that of NS consuming 1.65-1.95 mg/d of B-6. Mean plasma pyridoxal concentrations were not different between S and NS before and after supplementation. Excretion of 4-PA was not significantly different between S and NS, but the mean values of 4-PA excretion were consistently greater in NS compared to that of S throughout the 20-day study. The percent of ingested B-6 excreted as 4-PA for the S and NS was 38 and 49 in the non-supplemented period, and 47 and 53 in the supplemented period, respectively, indicating that non-smokers excreted more 4-PA than smokers. However, the difference in 4-PA excretion between S and NS was not significantly different both before and after supplementation (P>0.05). In addition, there was no significant difference between S and NS for plasma PN concentration, AP, and UB6 excretion for both periods. Results suggested an adverse effect of smoking on B-6 metabolism, thus an increased requirement of vitamin B-6 in smokers. A 2-mg PN supplement was sufficient to bring the concentration of plasma PLP in smokers to the level suggested as adequate, but it didn't bring it to the level of non-smokers.
Graduation date: 1999

This study was designed to evaluate the effect of glucose on plasma pyridoxal 5'- phosphate (PLP) concentration. The objective was to determine whether there was a negative relationship between glucose ingestion and plasma PLP concentration and to evaluate the possible mechanism of decreased PLP after acute glucose ingestion. Seven healthy subjects (three males and four females) completed the oral glucose tolerance test (OGTT) on three separate occasions over a period of three weeks. Each week, subjects ingested the assigned solutions (a water solution with artificial sweetener equivalent to 25g glucose, a 25g glucose or a 75g glucose load) in a randomized order. Plasma PLP, pyridoxal (PL), 4-pyridoxic acid (4-PA), pyridoxine (PN), glucose, insulin, alkaline phosphatase (AP) activity and red blood cell PLP concentrations were measured at 0 (fasting) (TO), 1 (T1), 2 (T2) and 3 (T3) hours. The mean vitamin B-6 intake based on two 3-day dietary records was 1.57 ± 0.34 mg/day. All subjects had normal glucose tolerance. There were gender differences among the three solutions. Both the water solution and the 75g glucose load showed a significant decrease in the mean plasma PLP concentration was observed at T3 for males and at T2 for females (p<0.05). An overall mean decrease of 20% (9nmol/L) and 15% (7 nmol/L) was observed for males and females, respectively, after the 75g glucose load. The 25g glucose load resulted in a lower decrease in the mean plasma PLP concentration at each time point compared with the 75g glucose load, but no significant difference was found in the level of decrease between the two glucose loads. Both genders had a non-significant increase in the mean plasma PL and PN concentrations for the three solutions. Mean plasma 4-PA concentration was decreased at T1 with the three solutions. There was no significant change in the plasma AP activity at any time points after the three solutions. In addition, no significant increase in mean red blood cell PLP concentration was observed at all time points after the three solutions. This study found a negative relationship between glucose ingestion and plasma PLP concentration. However, it did not provide clear evidence for the hypothesized mechanism of the decreased plasma PLP concentration after acute glucose load. Further studies are required to determine the mechanism by which glucose decreases plasma PLP concentration.
Graduation date: 2000

Two studies were conducted to determine the effect of varying vitamin B-6 (B- 6) status on lymphocyte mitogenic response and pyridoxal 5'-phosphate (PLP) concentration in peripheral blood mononuclear cells (PBMC) in young women. In the first study, women were fed 1 mg/d for the first week and 1.5, 2.1 and 2.7 mg/d during 2 weeks of each of the subsequent 3 experimental periods. Plasma PLP and urinary 4: pyridoxic acid (4-PA) were increased with increasing B-6 intake. B-6 intake > 2.1 mg significantly enhanced lymphocyte proliferation, and non-significantly increased plasma interleukin-2 concentration. Lymphocyte proliferation was significantly correlated with B-6 intake, erythrocyte aminotransferase activity coefficients and plasma PLP. PBMC PLP tended to increase after 2 weeks of 2.7 mg B-6 intake, and was significantly correlated with plasma PLP. In the second study, women consumed their normal diets whose estimated mean dietary B-6 intake was 0.9 mg for 27 d. For the last 20 d, all subjects were given a multivitamin supplement containing 1.8 mg B- 6, and half of the subjects were given an additional 50 mg of B-6 supplement. Plasma PLP and urinary 4-PA were significantly higher in the group with 50 mg B-6, but lymphocyte proliferation did not significantly differ between the groups. After 10 d of supplementation, lymphocyte proliferation was significantly higher than the other time points. A significant increase in PBMC PLP was observed after 3 days and 20 days following 50 mg and multivitamin supplementation only, respectively. After 20 days of supplementation, there was no significant difference of mean PBMC PLP between the groups. PBMC PLP was significantly correlated with plasma PLP, PL and 4-PA. In both studies, no strong relationship was found between PBMC PLP and lymphocyte proliferation. The findings from these studies demonstrate no further benefit of a higher B-6 intake than 2.1 mg on lymphocyte mitogenic response, once the response was significantly enhanced with B-6 intake 0.8 mg higher than the current recommendation. Finally, results from two studies suggest that the current recommendation of vitamin B-6 for young women may not be adequate to maximize lymphocyte mitogenic response and PLP concentration in PBMC.
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

Trained male cyclists (6 in study 1, 5 in study 2) cycled to exhaustion (EXH) at 75% of VO₂ max twice; once in the non-supplemented (NS) state and once in the vitamin B-6 (B-6)(20 mg PN) supplemented (S) state. The diet contained 2.3 mg B-6 in study 1 and 1.9 mg B-6 in study 2. Urine was collected during each dietary period. During each exercise (EX) test, blood was drawn prior to (PRE), one hour during (DX), immediately after (POST) and one hour after (POST 60) EX and sweat was collected. Compared to baseline (PRE) levels, plasma pyridoxal 5'-phosphate (PLP) and vitamin B-6 (PB-6) concentrations increased at DX, decreased at POST, and decreased below PRE at POST 60 in the NS and S states. EX to EXH in the S state resulted in a greater increase in PLP DX in study 1 (31% increase vs. 16%) and PB-6 in study 2 (25% increase vs. 11%) as compared to the NS state. Red blood cell (RBC) PLP significantly increased from POST to POST 60 in the S state in study 2. The excretion of urinary 4-pyridoxic acid (4-PA) and urinary B-6 (UB-6) was not significantly altered by EX to EXH. The mean excretion of 4-PA was significantly greater in the NS state in study 2 (7.98 ±1.83 mmol/d) as compared to the excretion in study 1 (6.20 ±0.93 mmol/d), whereas the excretion was significantly greater in the S state in study 1 (92.2 ±8.69 mmol/d) compared to the excretion in study 2 (82.7 ±6.16 mmol/d). The percent of B-6 intake excreted as UB-6 (6% in study 1 and 10% in study 2) was significantly different between the studies in the NS state. Vitamin B-6 supplementation did not significantly alter the rise in growth hormone (hGH) concentration seen with EX to EXH. The loss of B-6 in sweat with EX to EXH was not altered by B-6 supplementation. The loss of B-6 in sweat ranged from 0.0011 mmol to 0.0039 mmol. Therefore, EX to EXH in the B-6 S state resulted in a greater increase in plasma PLP and PB-6 DX as compared to the NS state. The decrease in PB-6 and PLP at POST 60 in the S state coincided with a significant increase in RBC PLP, suggesting the movement of B-6 from the plasma into the RBC at POST 60. EX to EXH and B-6 supplementation did not alter the excretion of 4-PA or UB-6 suggesting that B-6 metabolism was unchanged. The loss of B-6 in sweat was comparable to previously reported values and was not altered by B-6 supplementation. B-6 supplementation did not alter the changes in hGH resulting from EX to EXH alone.
Graduation date: 1995

Oxidative stress is the major driving force behind the aging process and many age-related diseases. However, direct experimental evidence of whether antioxidants, such as ascorbate (AA) and lipoic acid (LA) can slow the progression of aging process and/or reduce risks of developing degenerative disease is largely absent. This suggests a better understanding of the precise mechanism of how dietary micronutrient affect parameters of involved in cellular redox balance and aging are warranted. In this dissertation, young and old rats were used as our model to understand potential pro-oxidant events that contribute to increases in oxidative stress in various tissues and how antioxidants such as ascorbate and lipoic acid influence these events. Our major findings are that the age-related impairment of mitochondria and increased deposition of iron contribute significantly to heighten levels of oxidative stress, as evidenced by the resultant increases in the rates of oxidant appearance and in the levels of oxidative damage to DNA, lipids and proteins. We find that AA and LA strongly protected against transition metal-ion dependent increases in oxidative stress. AA effectively inhibited transition metal-mediated lipide peroxidation in human plasma. LA in its reduced form effectively binds iron and copper in a redox inactive manner and reversed chronically elevated levels of iron in the brain without removing enzyme bound transition metal ions. LA also significantly attenuated the age-related increase in oxidative stress associated with mitochondrial decay in the heart, as evidenced by the improvements in AA levels and glutathione redox status. The declines in tissue GSH levels in aged rats were strongly associated with the diminished γ-GCL activity (in parallel with decreased expression of the catalytic and modulatory subunits), and lowered Nrf2 expression and binding to ARE sequence in rat liver. Remarkably, all these events were effectively reversed by the administration of LA, modulating the parameters to return to the observed in young animals. The implications of this work open new avenues not only for further understanding of the aging process but also for possible strategies in its modulation by the micronutrients.
Graduation date: 2004

該前瞻性研究對香港中國裔孕婦的25羥基維生素D（25（OH）D）的水平及其影響因素進行調查，并對25（OH）D與甲狀旁腺激素（PTH）、孕期肌肉酸痛、不良妊娠結局、孕期及産後骨質流失，以及嬰兒的骨骼發育等關係進行探索，力求建立適用于香港的中國孕婦的25（OH）D正常值。
共有237名單胎妊娠婦女以及62名多胎妊娠的婦女在2010年8月至2011年11月間參加本研究中的隊列研究，分別在參加研究時（<20 孕周）、24-28孕周、31-36孕周以及産後6-11周進行抽血測量血清25（OH）D以及PTH水平，同時填寫一份包括對每月攝取含維生素D的食物以及營養補充劑頻度、接受日照情況及喜好、以及肌肉不適等情況的問卷，并在24-28孕周進行75克口服葡萄糖耐量試驗。參與隊列研究的單胎孕婦在20周前、31-36孕周以及産後隨訪時接受用定量超聲測量非優勢手的橈骨遠端以及中指近掌指骨的骨質超聲速率（SoS）。在産後複查時，對其嬰兒左側腓骨中部的骨質SoS進行測量。記錄婦女各次檢查時的體重、抽血月份紫外線輻射強度的歷史記錄、以及妊娠結局。另外募集一批孕婦參加病例對照研究，比較患早產（PTB）、子癇前期（PET）、妊娠糖尿病 （GDM）以及胎兒生長受限（FGR）併發癥的婦女與對照組 （體重指數以及抽血時紫外線強度配對）的血清25（OH）D水平。
孕婦在孕期的平均25（OH）D水平在44.7 ± 12.6 至48.9 ± 17.1 nmol/l範圍，25（OH）D水平與體重指數、維生素D營養補充劑、抽血時紫外線強度以及個人對陽光的喜好情況有關，而與胎兒數量、孕次、孕周以及終止妊娠無關。
單胎妊娠的孕婦三個孕期的血清25（OH）D與PTH水平均負相關，但在多胎妊娠中，二者無明顯相關性。PTH在孕期以及産後的變化相對不受25（OH）D影響。孕婦25（OH）D的水平與孕婦肌肉酸痛癥狀、産後恢復、孕期及產褥期骨質流失以及嬰兒骨質無關。患早期PTB（< 34孕周）、PET或FGR的孕婦的血清25（OH）D比對照組低，但GDM患者的25（OH）D水平與對照組無差別。血清25（OH）D低於34.3 nmol/l者的早期早產以及子癇前期的風險增高，低於50 nmol/l者發生胎兒生長受限的風險增高。服用維生素D補充劑情況可能影響25（OH）D與FGR的關係。
總而言之，血清25（OH）D水平不足以全面完全反映孕期維生素D的情況，對預測不良妊娠結局的作用有限。
This prospective study explored the maternal serum level of 25(OH)D in Chinese pregnant women in Hong Kong and the factors affecting 25(OH)D level. It also explored the correlation between maternal 25(OH)D with PTH level, maternal musculoskeletal complaints, adverse pregnancy outcome, maternal bone turnover during pregnancy and postpartum, and the bone development of the offspring, aiming to explore and establish a normal range of 25(OH)D level in pregnancy for the Hong Kong Chinese women.
A total of 237 women with singleton pregnancy and 62 women with multiple pregnancies were recruited for the cohort study from August, 2010 to November, 2011. Maternal blood samplings for 25(OH)D and PTH measurements were performed at recruitment, 24-28 weeks, 31-36 weeks of gestation, and 6-11 weeks postpartum respectively. A questionnaire which included the monthly dietary and supplement intake of vitamin D, questions about sunlight exposure, and musculoskeletal complaints was administered on each visit. A 75g oral glucose tolerance test (OGTT) was performed on cohort cases at 24-28 weeks of gestation. Measurements of the speed of sound (SoS) at the distal one third of the maternal radius and the proximal phalanx of the third finger of the non-dominant side were performed with quantitative ultrasonography (QUS) measurement during the visits at the first and third trimesters, and postnatal period. The SoS at the left mid-shaft tibia of the offspring was determined during the postnatal visit. Maternal characteristics, ultraviolet radiation (UVR) intensity at blood sampling, and pregnancy outcome, were also recorded. Cases with pregnancy complications were recruited for case-control studies, and maternal 25(OH)D level was examined with respect to preterm birth (PTB), preeclampsia (PET), gestational diabetes (GDM), and fetal growth restriction (FGR, birthweight below the 10th percentile of the customized estimated birthweight). The controls were matched for booking body mass index (BMI) and UVR intensity at blood sampling.
The mean 25(OH)D level in ranged from 44.7 ± 12.6 to 48.9 ± 17.1 nmol/l in the three trimesters, and was related to BMI, vitamin D supplementation, UVR intensity at blood sampling, and the acceptance of sunlight exposure, but not the number of fetus, parity, gestational age, or the completion of pregnancy.
Inverse correlation between PTH and 25(OH)D were observed in singleton, but not in multiple, pregnancy. The change in maternal PTH level is found to be relatively independent from that of 25(OH)D. There was no correlation between maternal 25(OH)D level with musculoskeletal complaints, postnatal recovery, bone turnover during and after pregnancy, or the bone density of the offspring. Maternal 25(OH)D level was lower in women with early PTB ( < 34 weeks), PET, and FGR, but not for GDM. A maternal 25(OH)D level of lower than 34.3nmol/l and 50 nmol/l was associated with increased risk of early PTB, PET, and FGR respectively. But the correlation between maternal 25(OH)D level with FGR might be affected by supplementation.
In conclusion, serum level of 25(OH)D is insufficient in reflecting maternal vitamin D status and metabolism in pregnancy, and is of limited use in predicting adverse pregnancy outcome.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Hu, Zhiyang.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references (leaves 201-223).
Abstracts and appendixes also in Chinese.
Thesis dedication --- p.i
Acknowledgments --- p.ii
Abstract --- p.v
Abstract (Chinese) --- p.viii
List of Abbreviation --- p.x
Table of contents --- p.xiii
List of Figures --- p.xxii
List of Tables --- p.xxiv
Chapter Chapter 1: --- Literature Review --- p.1
Chapter 1.1 --- The synthesis and metabolism of vitamin D --- p.3
Chapter 1.1.1 --- The synthesis of vitamin D --- p.3
Chapter 1.1.2 --- The metabolism of vitamin D --- p.4
Chapter 1.1.3 --- Vitamin D binding protein --- p.10
Chapter 1.1.4 --- Factors related to 25(OH)D level --- p.11
Chapter 1.2 --- Function of vitamin D --- p.13
Chapter 1.2.1 --- Mechanism of vitamin D function --- p.13
Chapter 1.2.2 --- Classic function --- p.14
Chapter 1.2.3 --- Non-classic function --- p.16
Chapter 1.2.3.1 --- Immune system --- p.17
Chapter 1.2.3.2 --- Cardiovascular system --- p.18
Chapter 1.2.3.3 --- Cell proliferation and differentiation --- p.18
Chapter 1.2.3.4 --- Neurological system --- p.19
Chapter 1.2.3.5 --- Reproductive system --- p.20
Chapter 1.2.3.6 --- Fetal development --- p.21
Chapter 1.3 --- The definition of vitamin D deficiency --- p.21
Chapter 1.4 --- Vitamin D status and pregnancy --- p.24
Chapter 1.4.1 --- Alteration in vitamin D metabolism during pregnancy --- p.24
Chapter 1.4.2 --- Factors affecting maternal serum level of 25(OH)D --- p.25
Chapter 1.4.3 --- Vitamin D and bone resorption during pregnancy and lactation --- p.27
Chapter 1.4.3.1 --- Alteration of calcium metabolism, bone absorption and the role of vitamin D --- p.27
Chapter 1.4.3.2 --- Measurement of bone density in pregnant women and babies --- p.33
Chapter 1.4.4 --- Current studies on maternal vitamin D status and pregnancy outcome --- p.35
Chapter 1.4.4.1 --- Birthweight --- p.35
Chapter 1.4.4.2 --- Infection --- p.37
Chapter 1.4.4.3 --- Preterm delivery --- p.39
Chapter 1.4.4.4 --- Diabetes (DM) and gestational diabetes (GDM) --- p.39
Chapter 1.4.4.5 --- Hypertension and preeclampsia --- p.41
Chapter 1.4.4.6 --- Multiple pregnancy, muscular symptoms --- p.42
Chapter 1.4.4.7 --- Vitamin D supplementation and pregnancy outcome --- p.44
Chapter 1.5 --- Defining vitamin D deficiency in pregnancy --- p.45
Chapter 1.6 --- Objective of the study --- p.46
Chapter Chapter 2: --- Study design and methods --- p.48
Chapter 2.1 --- Case recruitment and study design --- p.48
Chapter 2.1.1 --- Longitudinal singleton study --- p.49
Chapter 2.1.2 --- Cross-sectional study --- p.50
Chapter 2.1.2.1 --- Preterm birth (PTB) --- p.51
Chapter 2.1.2.2 --- Preeclampsia (PET) --- p.51
Chapter 2.1.2.3 --- Gestational diabetes (GDM) --- p.52
Chapter 2.1.3 --- Multiple pregnancy study --- p.52
Chapter 2.2 --- Measurements --- p.53
Chapter 2.2.1 --- Hormonal analysis of serum levels of 25(OH)D and PTH --- p.53
Chapter 2.2.2 --- Calculation of monthly intake of vitamin D from diet --- p.55
Chapter 2.2.3 --- SoS measurements --- p.56
Chapter 2.2.4 --- Ultraviolet radiation strength assessment --- p.59
Chapter 2.3 --- Statistical analysis --- p.60
Chapter Chapter 3 --- Longitudinal Study on the Level of and Factors Affecting Vitamin D in Singleton Pregnancy --- p.62
Chapter 3.1 --- Introduction --- p.62
Chapter 3.2 --- Material and method --- p.63
Chapter 3.3 --- Statistics --- p.64
Chapter 3.4 --- Results --- p.65
Chapter 3.4.1 --- Demographic data of the subjects --- p.65
Chapter 3.4.2 --- Maternal levels of 25(OH)D and PTH, and the factors affecting their levels --- p.66
Chapter 3.4.2.1 --- Distribution of 25(OH)D level and PTH level in the four visits --- p.66
Chapter 3.4.2.2 --- Dietary intake of vitamin D and supplementation --- p.69
Chapter 3.4.2.3 --- Seasonality and sunlight exposure --- p.73
Chapter 3.4.2.4 --- Parity --- p.76
Chapter 3.4.3 --- Changes of maternal levels of 25(OH)D and PTH in pregnancy --- p.78
Chapter 3.4.4 --- Independent factors related to maternal 25(OH)D level in pregnancy --- p.79
Chapter 3.4.5 --- Maternal and fetal 25(OH)D level at delivery --- p.80
Chapter 3.4.6 --- Muscular symptoms and other complaints in pregnancy, pregnancy outcome, and their relationships with maternal 25(OH)D level --- p.81
Chapter 3.4.7 --- Postnatal recovery and factors related to postnatal level of 25(OH)D and PTH --- p.86
Chapter 3.4.7.1 --- Postnatal symptoms and relationship with 25(OH)D and PTH --- p.86
Chapter 3.4.7.2 --- The postnatal level of 25(OH)D and PTH in women with different feeding mode --- p.88
Chapter 3.4.7.3 --- Independent factors related to postnatal 25(OH)D and PTH level --- p.89
Chapter 3.4.7.4 --- Factors related to the change of 25(OH)D and PTH after delivery --- p.90
Chapter 3.4.8 --- Correlation between 25(OH)D with PTH in pregnancy and postnatal period --- p.91
Chapter 3.5 --- Discussion --- p.92
Chapter 3.5.1 --- 25(OH)D level in Chinese pregnant women --- p.92
Chapter 3.5.2 --- Factors related to maternal 25(OH)D level --- p.93
Chapter 3.5.2.1 --- Dietary and supplementation --- p.93
Chapter 3.5.2.2 --- Seasonality and outdoor activity --- p.96
Chapter 3.5.2.3 --- Gestational age --- p.98
Chapter 3.5.2.4 --- Age and parity --- p.98
Chapter 3.5.3 --- Relationship of 25(OH)D level in the cord blood with maternal 25(OH)D level --- p.99
Chapter 3.5.4 --- 25(OH)D level and muscular complains in pregnancy --- p.100
Chapter 3.5.5. --- Postnatal recovery and 25(OH)D level --- p.101
Chapter 3.5.6 --- PTH level in pregnancy and postnatal period --- p.101
Chapter 3.6 --- Conclusion --- p.102
Chapter Chapter 4 --- Longitudinal Study on the Relationship between Maternal 25(OH)D level with Changes of Maternal Bone Density in Pregnancy and Lactation, and Factors Affecting Bone Density of newborn Infants --- p.105
Chapter 4.1 --- Introduction --- p.105
Chapter 4.2 --- Material and method --- p.106
Chapter 4.3 --- Statistics --- p.108
Chapter 4.4 --- Results --- p.108
Chapter 4.4.1 --- Demographic data --- p.108
Chapter 4.4.2 --- Maternal bone density and the changes in pregnancy and postnatal recovery --- p.109
Chapter 4.4.2.1 --- Maternal bone density in the first trimester and related factors --- p.109
Chapter 4.4.2.2 --- Maternal bone density in the three visits --- p.109
Chapter 4.4.2.3 --- The change in maternal bone density in the three visits --- p.110
Chapter 4.4.2.4 --- Diversity in the change of bone density in pregnant women --- p.112
Chapter 4.4.3 --- Factors related to the changes in bone density --- p.114
Chapter 4.4.3.1 --- Changes between the first and the third trimesters --- p.114
Chapter 4.4.3.2 --- Change between the third trimester and postnatal visits --- p.116
Chapter 4.4.4 --- The bone density in infants and related factors --- p.120
Chapter 4.5 --- Discussion --- p.122
Chapter 4.5.1 --- Maternal bone density changes in pregnancy and postnatal period --- p.122
Chapter 4.5.2 --- Factors related to the maternal bone density changes in pregnancy and postnatal period --- p.124
Chapter 4.5.2.1 --- Initial bone density, parity, and BMI --- p.125
Chapter 4.5.2.2 --- 25(OH)D and PTH level --- p.126
Chapter 4.5.2.3 --- Supplement --- p.127
Chapter 4.5.2.4 --- Lactation --- p.128
Chapter 4.5.2.5 --- Height --- p.129
Chapter 4.5.3 --- Factors related to bone density of the infant. --- p.130
Chapter 4.5.3.1 --- Maternal 25(OH)D level --- p.130
Chapter 4.5.3.2 --- Gestational age and birthweight --- p.131
Chapter 4.5.3.3 --- Maternal bone density change --- p.131
Chapter 4.5.3.4 --- The gender of the offspring and feeding method --- p.132
Chapter 4.6 --- Conclusion --- p.133
Chapter Chapter 5 --- Maternal 25(OH)D Level in Multiple Pregnancy --- p.134
Chapter 5.1 --- Introduction --- p.134
Chapter 5.2 --- Material and method --- p.135
Chapter 5.3 --- Statistics --- p.136
Chapter 5.4 --- Results --- p.137
Chapter 5.4.1 --- Demographic data of the subjects --- p.137
Chapter 5.4.2 --- The level of 25(OH)D in multiple pregnancy and singleton pregnancy --- p.137
Chapter 5.4.3 --- Supplementation in multiple pregnancy --- p.140
Chapter 5.4.4 --- The change of maternal 25(OH)D and PTH levels in the three trimesters --- p.141
Chapter 5.4.5 --- 25(OH)D level in cord blood and its correlation with 25(OH)D level of the sibling --- p.143
Chapter 5.4.6 --- Correlation between 25(OH) with PTH in pregnancy --- p.143
Chapter 5.5 --- Discussion --- p.144
Chapter 5.5.1 --- 25(OH)D level in multiple pregnancy and singleton pregnancy --- p.144
Chapter 5.5.2 --- Supplementation in multiple pregnancy --- p.146
Chapter 5.5.3 --- Changes of maternal levels of 25(OH)D and PTH in the three trimesters in multiple pregnancy --- p.146
Chapter 5.5.4 --- The PTH/25(OH) correlation --- p.147
Chapter 5.6 --- Conclusion --- p.148
Chapter Chapter 6 --- Maternal level of 25(OH)D in complicated pregnancy --- p.150
Chapter 6.1 --- Introduction --- p.150
Chapter 6.2 --- Method --- p.153
Chapter 6.2.1 --- Preterm birth --- p.155
Chapter 6.2.2 --- Preeclampsia --- p.155
Chapter 6.2.3 --- Gestational diabetes --- p.156
Chapter 6.2.4 --- Fetal growth restriction --- p.157
Chapter 6.2.5 --- The association between 25(OH)D level with pregnancy complication --- p.158
Chapter 6.3 --- Statistics --- p.159
Chapter 6.4 --- Results --- p.160
Chapter 6.4.1 --- Setting of the cutoff values of hypovitaminosis D --- p.160
Chapter 6.4.2 --- Preterm birth --- p.160
Chapter 6.4.3 --- Preeclampsia --- p.164
Chapter 6.4.4 --- Gestational diabetes --- p.168
Chapter 6.4.4.1 --- Case-control study --- p.168
Chapter 6.4.4.2 --- Factors affecting OGTT results --- p.170
Chapter 6.4.5 --- Fetal growth restriction --- p.173
Chapter 6.5 --- Discussion --- p.179
Chapter 6.5.1 --- Adjustment for confounders for case-control study --- p.179
Chapter 6.5.2 --- PTB and 25(OH)D level --- p.181
Chapter 6.5.3 --- PET and 25(OH)D level --- p.182
Chapter 6.5.4 --- GDM and 25(OH)D level --- p.186
Chapter 6.5.5 --- FGR and 25(OH)D level --- p.189
Chapter 6.5.6 --- Defining vitamin D deficiency in pregnancy --- p.192
Chapter 6.6 --- Conclusion --- p.195
Chapter Chapter 7 --- Summary --- p.196
References --- p.201
Chapter Appendix 1 --- Antenatal questionnaire (English/Chinese) --- p.224
Chapter Appendix 2 --- Postnatal questionnaire (English/Chinese) --- p.238

Indiana University-Purdue University Indianapolis (IUPUI)
Multiple sclerosis (MS) is a disabling disease that afflicts an estimated two million people worldwide. The disease is characterized by degradation of the myelin sheath that insulates neurons of the central nervous system manifesting as a heterogeneous collection of symptoms. Two enzymes, protein arginine deaminases type 2 and 4 (PAD2 and PAD4) have been implicated to play an etiologic role in demyelination and neurodegeneration by catalyzing a post-translational modification of arginine peptide residues to citrulline. The pathogenesis of MS is poorly understood, though vitamin D deficiency is a well-associated risk factor for developing the disorder. Using the experimental autoimmune encephalomyelitis (EAE) model of MS we demonstrate vitamin D treatment to attenuate over-expression of PAD 2 and 4 in the brain and spine during EAE. In addition, we identify two molecules produced by peripheral immune cells, IFNɣ and IL-6, as candidate signaling molecules that induce PAD expression in the brain. We demonstrate vitamin D treatment to inhibit IFNɣ mediated up regulation of PAD2 and PAD4 both directly within the brain and by modulating PAD-inducing cytokine production by infiltrating immune cells. These results provide neuroprotective rational for the supplementation of vitamin D in MS patients. More importantly, these results imply an epigenetic link between vitamin D deficiency and the pathogenesis of MS that merits further investigation.