William Fraser | University of East Anglia (original) (raw)

Papers by William Fraser

Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the developme... more Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D 2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety volunteers (aged 40-65 years) were randomly assigned to one of two 4-week studies: mushroom study (15 µg vitamin D 2 or placebo mushroom powder) and capsule study (15 µg vitamin D 3 or placebo capsules). Consumption of vitamin D 2-enhanced mushrooms increased serum 25-hydroxyvitamin D 2 (25(OH)D 2) by 128 % from baseline (3•9 (SD 1•9) nmol/l; P < 0•05). Serum 25(OH)D 3 increased significantly in the vitamin D 3 capsule group (a 55 % increase from a baseline of 44.0 (SD 17•1) nmol/l; P < 0•05). Vitamin D status (25(OH)D) was affected only in the vitamin D 3 group. Plasminogen activator inhibitor-1 was lowered by vitamin D 2 intake. Vitamin D 2 from enhanced mushrooms was bioavailable and increased serum 25(OH)D 2 concentration with no significant effect on 25(OH)D 3 or total 25(OH)D.

American Journal of Physiology-Endocrinology and Metabolism, 2015

Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D ... more Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (45 ± 25 nmol/l). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors, with peak torque measured over the following 7 days of recovery. Parallel experimentation using isolated human skeletal muscle-derived myoblast cells from biopsies of 14 males with low serum 25(OH)D (37 ± 11 nmol/l) were subjected to mechanical wound injury, which enabled corresponding in vitro studies of muscle repair, regenerat...

Thorax, 2014

pressure (MAP), heart rate and 6 min walk distance (6MWT). Based on the change in PWV in hyperten... more pressure (MAP), heart rate and 6 min walk distance (6MWT). Based on the change in PWV in hypertensive patients, progressors were defined as individuals with >0.5 m/s PWV increase, over 2 years. 2 Results Thus far 200 patients with COPD have completed the 2 year follow-up assessment. At baseline the progressor and nonprogressor were similar in age, gender, BMI, heart rate and 6 MWT. However the progressors had greater airways obstruction, and lower mean arterial pressure and aPWV (Table 1). After 2 years the mean [95% CI] PWV change in progressors was +1.7 [2.0-1.5]m/s while FEV 1 declined by 140 [76-206]ml (p < 0.05). In contrast the non-progressors had no change in lung function, while there was a decrease in aPWV 0.7 [0.5-0.9] m/s and MAP 5 [3-7] mmHg (p < 0.05). Conclusions Almost half of the ARCADE subjects with COPD had a significant increase of PWV, the clinical relevance requires investigation using longer-term outcome data. The identification of CV risk phenotypes in COPD and the underlying pathophysiology may help identify novel therapeutic targets and improve CV outcomes for patients. Thank you to all our volunteers and GlaxoSmithKline who funded ARCADE NCT01656421 REFERENCES

Endocrine-related cancer, May 1, 2017

paediatric osteosarcoma to evaluate similarities and/or differences between the two age-related i... more paediatric osteosarcoma to evaluate similarities and/or differences between the two age-related incidence peaks of osteosarcoma.

The lancet. Diabetes & endocrinology, 2013

Hypoparathyroidism results in impaired mineral homoeostasis, including hypocalcaemia and hyperpho... more Hypoparathyroidism results in impaired mineral homoeostasis, including hypocalcaemia and hyperphosphataemia. Treatment with high-dose oral calcium and active vitamin D does not provide adequate or consistent control of biochemical indices and can lead to serious long-term complications. We aimed to test the efficacy, safety, and tolerability of once-daily recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) in adults with hypoparathyroidism. In this double-blind, placebo-controlled, randomised phase 3 study (REPLACE), we recruited patients with hypoparathyroidism (≥ 18 months duration) aged 18-85 years from 33 sites in eight countries. After an optimisation period, during which calcium and active vitamin D doses were adjusted to achieve consistent albumin-corrected serum calcium, patients were randomly assigned (2:1) via an interactive voice response system to 50 μg per day of rhPTH(1-84) or placebo for 24 weeks. Active vitamin D and calcium were progressively reduced, while rhP...

Endocrinology, Jan 8, 2015

Autosomal dominant hypocalcemia type 1 (ADH1) is caused by germline gain-of-function mutations of... more Autosomal dominant hypocalcemia type 1 (ADH1) is caused by germline gain-of-function mutations of the calcium-sensing receptor (CaSR) and may lead to symptomatic hypocalcemia, inappropriately low serum parathyroid hormone (PTH) concentrations and hypercalciuria. Negative allosteric CaSR modulators, known as calcilytics, have been shown to normalise the gain-of-function associated with ADH-causing CaSR mutations in vitro and represent a potential targeted therapy for ADH1. However, the effectiveness of calcilytic drugs for the treatment of ADH1-associated hypocalcemia remains to be established. We have investigated NPS 2143, a calcilytic compound, for the treatment of ADH1 by in vitro and in vivo studies involving a mouse model, known as Nuf, which harbors a gain-of-function CaSR mutation, Leu723Gln. Wild-type (Leu723) and Nuf mutant (Gln723) CaSRs were expressed in HEK293 cells and the effect of NPS 2143 on their intracellular calcium responses determined by flow cytometry. NPS 2143...

Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 2021

To date, no research has explored the effects of low energy availability (EA) on cognitive perfor... more To date, no research has explored the effects of low energy availability (EA) on cognitive performance using dietary and exercise regimens relevant to athletes. Twenty female participants (10 eumenorrheic, 10 oral contraceptive [OC] users) completed three, 3-day conditions: 1) controlled-balanced EA without exercise (BAL; 45 kcal·kg·LBM-1·day-1), 2) diet-induced low EA without exercise (DIET; 15 kcal·kg·LBM-1·day-1) and 3) exercise-induced low EA (EX; 15 kcal·kg·LBM-1·day-1, including 30 kcal·kg·LBM-1·day-1 treadmill running at 70% V̇O2max). A cognitive test battery was completed before and after each 3-day condition. Mental rotation test accuracy improved in the BAL condition, but there was a decline in accuracy in the EX condition (BAL, +2.5%; EX, -1.4%; P = 0.042, d = 0.85). DIET (+1.3%) was not different to BAL or EX (P > 0.05). All other measures of cognitive performance were not affected by condition (P > 0.05) and OC use did not affect cognitive responses (P > 0.05)....

Calcified Tissue International, 2019

The demand for measurement of vitamin D metabolites for clinical diagnosis and to advance our und... more The demand for measurement of vitamin D metabolites for clinical diagnosis and to advance our understanding of the role of vitamin D in human health has significantly increased in the last decade. New developments in technologies employed have enabled the separation and quantification of additional metabolites and interferences. Also, developments of immunoassays have changed the landscape. Programmes and materials for assay standardisation, harmonisation and the expansion of the vitamin D external quality assurance scheme (DEQAS) with the provision of target values as measured by a reference measurement procedure have improved standardisation, quality assurance and comparability of measurements. In this article, we describe developments in the measurement of the commonly analysed vitamin D metabolites in clinical and research practice. We describe current analytical approaches, discuss differences between assays, their origin, and how these may be influenced by physiological and ex...

Bone, 2019

Author contributions: JG designed the study. RMI and TJO collected, and TJO analysed, the imaging... more Author contributions: JG designed the study. RMI and TJO collected, and TJO analysed, the imaging data. Biochemical samples were collected by NPW and analysed by JCYT and WDF.

PLOS ONE, 2018

Objective Neonatal morbidity and mortality can be influenced by maternal health status. Informati... more Objective Neonatal morbidity and mortality can be influenced by maternal health status. Information on maternal and fetal biomarkers of adverse health outcomes is limited. This work aims at identifying maternal biomarkers associated with low and high birth weight for gestational age groups. Design and settings Population-based prospective cohort study of the potential adverse health effects of exposure to environmental contaminants on pregnancy and infant health. Methods Third trimester maternal plasma samples (n = 1588) from a pregnancy cohort (Maternal-Infant Research on Environmental Chemicals Study, MIREC) were analyzed for changes in a target spectrum of biomarkers of vascular health (e.g., matrix metalloproteinases MMPs, vascular endothelial cell growth factor VEGF), inflammation (e.g. cellular adhesion molecules CAMs, cytokines, chemokines) by affinity-based multiplex protein array analyses. Multivariate logistic regression analyses were done to examine associations between target plasma biomarkers, maternal-infant characteristics, and birth weight outcomes assessed as small for gestational age (SGA) �10 th percentile and large for gestational age (LGA) �90 th percentile groups.

BMJ (Clinical research ed.), Jan 12, 2018

To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia... more To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35. Randomised, phase III, double blinded international, multicentre clinical trial. 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). 2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses. Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation. The primary outcome was...

The American journal of clinical nutrition, Jan 11, 2018

The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evid... more The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking. The aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans. An RCT was undertaken across 5 European centers. Subjects in the intervention group consumed the NU-AGE diet for 1 y by receiving individually tailored dietary advice, coupled with supplies of foods including whole-grain pasta, olive oil, and a vitamin D3 supplement (10 µg/d). Participants in the control group were provided with leaflets on healthy eating available in their country. A total of 1294 p...

Frontiers in endocrinology, 2018

Small for gestational age (SGA) infants are at increased risk of type 2 diabetes in adulthood. It... more Small for gestational age (SGA) infants are at increased risk of type 2 diabetes in adulthood. It is unknown whether any prenatal biomarkers are helpful for identifying SGA infants with altered metabolic health profile at birth or later life. In a nested study of 162 SGA (birth weight < 10th percentile) and 161 optimal birth weight (25th-75th percentiles) control infants in the 3D (design, develop and discover) birth cohort in Canada, we assessed whether maternal circulating placental growth factor (PlGF), a biomarker of placental function, is associated with metabolic health biomarkers in SGA infants. Main outcomes were cord plasma insulin, proinsulin, insulin-like growth factor-I (IGF-I), leptin, and high-molecular weight (HMW) adiponectin concentrations. Maternal PlGF concentrations at 32-35 weeks of gestation were substantially lower in SGA versus control infants ( < 0.001), so as were cord plasma proinsulin ( = 0.005), IGF-I ( < 0.001), leptin ( < 0.001), and HMW ad...

Bone, Jan 19, 2018

We aimed to explore the effects of low energy availability (EA)[15 kcal·kg lean body mass (LBM)·d... more We aimed to explore the effects of low energy availability (EA)[15 kcal·kg lean body mass (LBM)·d] achieved by diet or exercise on bone turnover markers in active, eumenorrheic women. By using a crossover design, ten eumenorrheic women (VO: 48.1 ± 3.3 ml·kg·min) completed all three, 3-day conditions in a randomised order: controlled EA (CON; 45 kcal·kgLBM·d), low EA through dietary energy restriction (D-RES; 15 kcal·kgLBM·d) and low EA through increasing exercise energy expenditure (E-RES; 15 kcal·kgLBM·d), during the follicular phase of three menstrual cycles. In CON, D-RES and E-RES, participants consumed diets providing 45, 15 and 45 kcal·kgLBM·d. In E-RES only, participants completed supervised running sessions (129 ± 10 min·d) at 70% of their VO that resulted in an exercise energy expenditure of 30 kcal·kg LBM·d. Blood samples were collected at baseline (BASE) and at the end of the 3-day period (D6) and analysed for bone turnover markers (β-CTX and P1NP), markers of calcium met...

Bone, Mar 1, 2018

Genotype plays an important role in influencing bone phenotypes, such as bone mineral density, bu... more Genotype plays an important role in influencing bone phenotypes, such as bone mineral density, but the role of genotype in determining responses of bone to exercise has yet to be elucidated. To determine whether 10 SNPs associated with genes in the vicinity of P2X7R, RANK/RANKL/OPG and Wnt Signalling Pathways are associated with bone phenotypes in elite academy footballers (Soccer players) and to determine whether these genotypes are associated with training induced changes in bone. Design, participants, and methods: 99 elite academy footballers volunteered to participate. Peripheral computed tomography of the tibia (4%, 14%, 38% and 66% sites) was performed immediately before and 12 weeks after an increase in football training volume. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays. No significant genotype by time interactions were shown for any of the SNPs analysed (P > .05). A main effect of genotype was shown. SOST SNP rs1...

Bone, Jan 25, 2017

The short-term effects of low energy availability (EA) on bone metabolism in physically active wo... more The short-term effects of low energy availability (EA) on bone metabolism in physically active women and men are currently unknown. We evaluated the effects of low EA on bone turnover markers (BTMs) in a cohort of women and a cohort of men, and compared effects between sexes. These studies were performed using a randomised, counterbalanced, crossover design. Eleven eumenorrheic women and eleven men completed two 5-day protocols of controlled (CON; 45kcal·kgLBM(-1)·d(-1)) and restricted (RES; 15kcal·kgLBM(-1)·d(-1)) EAs. Participants ran daily on a treadmill at 70% of their peak aerobic capacity (VO2 peak) resulting in an exercise energy expenditure of 15kcal·kgLBM(-1)·d(-1) and consumed diets providing 60 and 30kcal·kgLBM(-1)·d(-1). Blood was analysed for BTMs [β-carboxyl-terminal cross-linked telopeptide of type I collagen (β-CTX) and amino-terminal propeptide of type 1 procollagen (P1NP)], markers of calcium metabolism [parathyroid hormone (PTH), albumin-adjusted calcium (ACa), ma...

The American journal of clinical nutrition, Jan 14, 2017

Background: Assessments of the dietary intakes in various populations suggest that pregnant women... more Background: Assessments of the dietary intakes in various populations suggest that pregnant women have difficulty meeting all their nutritional requirements through diet alone. Few large-scale studies have considered both food sources and supplements in assessing the adequacy of nutritional intakes during pregnancy.Objectives: Our study aimed to assess nutritional intakes during pregnancy by examining dietary sources and supplements. It then compared these findings with Dietary Reference Intakes.Design: We conducted a nutrition study in a large pregnancy cohort using a 3-d food record during the second trimester of pregnancy. Detailed information about supplement consumption was obtained by interview at each prenatal visit. We estimated the distribution of total usual intakes for energy, macronutrients, and micronutrients for 1533 pregnant women.Results: A third of the participants had total fat intakes that exceeded the Acceptable Micronutrient Distribution Range. A majority of wom...

The American journal of clinical nutrition, Jan 15, 2017

Background: Folate requirements increase during pregnancy and lactation. It is recommended that w... more Background: Folate requirements increase during pregnancy and lactation. It is recommended that women who could become pregnant, are pregnant, or are lactating consume a folic acid (FA)-containing supplement.Objectives: We sought to determine breast-milk total folate and unmetabolized folic acid (UMFA) contents and their relation with FA-supplement use and doses in a cohort of Canadian mothers who were enrolled in the MIREC (Maternal-Infant Research on Environmental Chemicals) study.Design: Breast-milk tetrahydrofolate (THF), 5-methyl-THF, 5-formyl-THF, 5,10-methenyl-THF, and UMFA were measured with the use of liquid chromatography-tandem mass spectrometry (n = 561). Total daily supplemental FA intake was based on self-reported FA-supplement use.Results: UMFA was detectable in the milk of 96.1% of the women. Total daily FA intake from supplements was associated with breast folate concentration and species. Breast-milk total folate was 18% higher (P < 0.001) in supplement users (n...

Chemosphere, Jan 16, 2016

Given the susceptibility of the fetus to toxicants, it is important to estimate their exposure. A... more Given the susceptibility of the fetus to toxicants, it is important to estimate their exposure. Approximately 2000 pregnant women were recruited in 2008-2011 from 10 cities across Canada. Cd, Pb, Mn and total Hg were measured in maternal blood from the 1st and 3rd trimesters, umbilical cord blood, and infant meconium. Nutrient intakes of vitamin D, iron, and calcium (Ca) were assessed using a food frequency questionnaire and a dietary supplement questionnaire. Median concentrations in 1st trimester maternal blood (n = 1938) were 0.20, 8.79 and 0.70 μg/L for Cd, Mn and Hg, respectively, and 0.60 μg/dL for Pb. While the median difference between the paired 1st and 3rd trimester concentrations of Cd was 0, there was a significant decrease in Pb (0.04 μg/dL) and Hg (0.12 μg/L) and an increase in Mn (3.30 μg/L) concentrations over the course of the pregnancy. While Cd was rarely detected in cord blood (19%) or meconium (3%), median Pb (0.77 μg/dL), Mn (31.87 μg/L) and Hg (0.80 μg/L) conc...