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    Enzootic calcinosis in Toggenburg goats in New Zealand.
    (Taylor and Francis Group, 2024-01-01) Brown SE; Collett MG; Matthews ZM; Marshall JC; Dittmer KE
    CASE HISTORY: Necropsies on Toggenburg goats culled from a small farm in the Manawatū district of New Zealand, performed at Massey University (Palmerston North, NZ) over a period of 29 years (1991-2019), revealed soft tissue mineralisation, particularly of cardiovascular tissues. The farm spans 10 acres and runs between 15 and 30 Toggenburg goats. The goats are predominantly on pasture comprising a variety of types. PATHOLOGICAL FINDINGS: Necropsies were performed on all adult goats (n = 45) that died or were euthanised. Histopathology was performed on 42 goats (93%), of which 33 (73%) included sufficient tissues diagnostically relevant to soft tissue mineralisation. The most significant gross findings were in various arteries, with the aorta most commonly affected, followed by the heart and lungs. The aortic intima showed prominent, multifocal to coalescing, raised, wrinkled, white plaques. Microscopically there were multiphasic lesions of mineralisation, chondroid, and osseous metaplasia in the elastic arteries, aorta, heart and lungs. A lumbar vertebra from one goat had prominent, basophilic, fibrillar, tangled matrix lining Haversian canals and lamellae. LABORATORY FINDINGS: Blood samples were collected from 15 adult goats in the affected herd and from 10 adult Toggenburg goats from an unaffected herd. Samples were collected by jugular venipuncture at 2-month intervals for 12 months (April 2018-March 2019). Concentrations of calcium, phosphorus, 25-hydroxyvitamin D2 and D3 (25OHD2, 25OHD3) in serum were analysed. The concentration of total 25OHD in serum was 34.2 (95% CI = 18.9-49.4) nmol/L (p < 0.001) higher in goats from the affected herd than in goats from the unaffected herd. Serum 25OHD2 concentration was 46.2 (95% CI = 39.2-53.2) nmol/L higher (p < 0.001) in goats from the affected herd compared to the unaffected herd. Serum Ca concentrations in affected goats were 0.101 (95% CI = 0.005-0.196) mmol/L higher (p = 0.039) than unaffected goats, but remained within the reference range. There was no evidence of a difference in serum 25OHD3 and P concentration between the herds. VEGETATION SURVEY: All paddocks on the property were surveyed every 2 months along evenly spaced line transects, and then further traversed perpendicularly to form a grid. No known calcinogenic species were identified. Known plant sources of vitamin D identified on the farm included mushrooms (species not defined), Dactylis glomerata, lichen, pine pollen, and algae. DIAGNOSIS: Soft tissue mineralisation and enzootic calcinosis. CLINICAL RELEVANCE: Veterinarians are alerted to the possibility of either enzootic calcinosis in goats and the potential occurrence of calcinogenic plants in New Zealand; or chronic vitamin D toxicosis of non-plant origin.
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    A nutritional supplement during preconception and pregnancy increases human milk vitamin D but not B-vitamin concentrations.
    (Elsevier B.V., 2023-10-29) Han SM; Huang F; Derraik JGB; Vickers MH; Devaraj S; Redeuil K; Campos-Giménez E; Pang WW; Godfrey KM; Chan S-Y; Thakkar SK; Cutfield WS; NiPPeR Study Group
    BACKGROUND & AIMS: Optimal maternal vitamin status during pregnancy and lactation is essential to support maternal and infant health. For instance, vitamin D3 is involved in infant bone development, and B-vitamins are involved in various metabolic processes, including energy production. Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on human milk (HM) concentrations of vitamin D3 and B-vitamins. In addition, we aimed to characterise longitudinal changes in milk concentrations of these vitamins. METHODS: Both control and intervention supplements contained calcium, iodine, iron, β-carotene, and folic acid, while the intervention also contained zinc, vitamins B2, B6, B12, and D3, probiotics, and myo-inositol. HM samples were collected across 4 time points from 1 week to 3 months post-delivery from 158 mothers in Singapore, and 7 time points from 1 week to 12 months from 180 mothers in New Zealand. HM vitamin D was quantified using supercritical fluid chromatography and B-vitamins with mass spectrometry. Potential intervention effects on HM vitamins D3, B2, B6, and B9, as well as other B-vitamin (B1 and B3) concentrations were assessed using linear mixed models with a repeated measures design. RESULTS: Over the first 3 months of lactation, HM 25-hydroxyvitamin D3 concentrations were 20% (95% CI 8%, 33%, P = 0.001) higher in the intervention group, with more marked effects in New Zealand. There were no observed intervention effects on HM concentrations of vitamins B1, B2, B3, B6, and B9. In New Zealand mothers, longitudinally, vitamin D3 concentrations gradually increased from early lactation up to 12 months, while vitamins B1 and B2 peaked at 6 weeks, B3 at 3 weeks, and B6 and B9 at 3 months. CONCLUSIONS: Maternal supplementation during preconception and pregnancy increased HM vitamin D, but not B-vitamin concentrations in lactation. Further studies are required to examine the discrete benefits of vitamin D supplementation starting preconception vs during pregnancy, and to further characterise the effects of supplementation on later offspring health outcomes. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov on the 16 July 2015 (identifier NCT02509988); Universal Trial Number U1111-1171-8056. This study was academic-led by the EpiGen Global Research Consortium.
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    Relationship between vitamin D, iron, and hepcidin in premenopausal females, potentially confounded by ethnicity.
    (Springer Nature, 2023-08-29) Greenwood A; Von Hurst PR; Beck KL; Mazahery H; Lim K; Badenhorst CE
    PURPOSE: To investigate the associations between vitamin D, hepcidin, and iron status in premenopausal females of different ethnic cohorts residing in Auckland, New Zealand (NZ). METHODS: A total of 160 females aged 18-45 years participated in a cross-sectional study. Demographics, body composition, serum 25(OH)D, inflammatory markers (C-reactive protein and interleukin-6, IL-6), and iron biomarkers (serum ferritin, haemoglobin, soluble transferrin receptor, and hepcidin) were measured. Comparisons between parametric, non-parametric, and categorical variables were completed by using one-way ANOVA, Kruskal-Wallis, and Chi-squared tests, respectively. ANCOVA was used to compare serum 25(OH)D across iron parameter categories. RESULTS: Of the 160 participants, 60 were NZ European, 67 were South Asian, and 33 were from the 'other' ethnic groups. South Asians had significantly higher body fat percentage (BF%) and IL-6 concentration (38.34% and 1.66 pg·mL-1, respectively), compared to NZ Europeans (27.49% and 0.63 pg·mL-1, respectively, p < 0.001). South Asians had significantly lower 25(OH)D concentrations compared to NZ Europeans (33.59 nmol·L-1 vs 74.84 nmol·L-1, p < 0.001). In NZ Europeans, higher 25(OH)D concentration was seen in those with lower (≤ 3.5 nM) hepcidin concentration, p = 0.0046. In South Asians, higher 25(OH)D concentration was seen in those with higher (> 3.5 nM) hepcidin concentrations, p = 0.038. There were no associations between serum 25(OH)D and serum ferritin. CONCLUSION: Within South Asian women, an unexpected positive relationship between 25(OH)D and hepcidin concentration was observed which may be due to significantly higher IL-6 concentrations, BF%, and lower 25(OH)D concentrations. Future research is required to confirm these observations in this ethnic cohort.
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    Knowledge, attitudes and behaviours towards vitamin D and sun exposure of parents of infants and young children and health professionals in New Zealand.
    (SAGE Publications, 2023-07-02) Von Hurst P; Mazahery H; Reynolds E; Thomson A; Franklin M; Conlon C
    BACKGROUND: Vitamin D deficiency may result in adverse long-term health consequences in adulthood if it occurs during fetal development, infancy and childhood. To effectively improve vitamin D status of infants/toddlers, there needs to be knowledge and awareness of vitamin D among parents and health professionals. AIMS: The aim of this study was to investigate parents' and health professionals' knowledge, attitudes and behaviours towards vitamin D and sun exposure over two timepoints. METHODS: The study was an ecological study over two timepoints (Parents 2009 and 2021; Health professionals 2010 and 2019) and used an online questionnaire. RESULTS: The analysis included 9834 parents (2009 n = 8032; 2021 n = 1802) and 283 health professionals (2010 n = 193; 2019 n = 90). Parents and health professionals had good knowledge of vitamin D sources, roles and risk factors for deficiency over two timepoints. There were however some confusions regarding the vitamin D content of breast milk, exclusive breastfeeding as a risk factor for deficiency, and ineffectiveness of sun exposure through glass windows in relation to vitamin D synthesis. In 2019, only 37% of health professionals indicated giving advice on supplements for infants/toddlers. Most parents and health professionals believed there was not enough information available to parents regarding vitamin D (>90%) and that skin cancer prevention messages make it difficult to get information about vitamin D across (>70%). CONCLUSION: Although parents and health professionals had good knowledge in most areas, knowledge of some specific sources and risk factors for vitamin D deficiency was poor.
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    Inflammation and the Association of Vitamin D and Depressive Symptomatology.
    (MDPI (Basel, Switzerland), 2021-06) Dogan-Sander E; Mergl R; Willenberg A; Baber R; Wirkner K; Riedel-Heller SG; Röhr S; Schmidt FM; Schomerus G; Sander C
    Depression and vitamin D deficiency are major public health problems. The existing literature indicates the complex relationship between depression and vitamin D. The purpose of this study was to examine whether this relationship is moderated or mediated by inflammation. A community sample (n = 7162) from the LIFE-Adult-Study was investigated, for whom depressive symptoms were assessed via the German version of CES-D scale and serum 25-hydroxyvitamin D (25(OH)D) levels and inflammatory markers (IL-6 and CRP levels, WBC count) were quantified. Mediation analyses were performed using Hayes’ PROCESS macro and regression analyses were conducted to test moderation effects. There was a significant negative correlation between CES-D and 25(OH)D, and positive associations between inflammatory markers and CES-D scores. Only WBC partially mediated the association between 25(OH)D levels and depressive symptoms both in a simple mediation model (ab: −0.0042) and a model including covariates (ab: −0.0011). None of the inflammatory markers showed a moderation effect on the association between 25(OH)D levels and depressive symptoms. This present work highlighted the complex relationship between vitamin D, depressive symptoms and inflammation. Future studies are needed to examine the effect of vitamin D supplementation on inflammation and depressive symptomatology for causality assessment.
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    Factors Associated with Bone Mineral Density and Bone Resorption Markers in Postmenopausal HIV-Infected Women on Antiretroviral Therapy: A Prospective Cohort Study
    (MDPI (Basel, Switzerland), 2021-06-18) Ellis C; Kruger HS; Viljoen M; Dave JA; Kruger MC; Weaver C
    The study aimed to determine factors associated with changes in bone mineral density (BMD) and bone resorption markers over two years in black postmenopausal women living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART). Women (n = 120) aged > 45 years were recruited from Potchefstroom, South Africa. Total lumbar spine and left femoral neck (LFN) BMD were measured with dual energy X-ray absorptiometry. Fasting serum C-Telopeptide of Type I collagen (CTx), vitamin D and parathyroid hormone were measured. Vitamin D insufficiency levels increased from 23% at baseline to 39% at follow up. In mixed linear models serum CTx showed no change from baseline to end (p = 0.363, effect size = 0.09). Total and LFN BMD increased significantly over two years, but effect sizes were small. No significant change in spine BMD over time was detected (p = 0.19, effect size = 0.02). Age was significantly positively associated with CTx over time, and negatively with total and LFN BMD. Physical activity (PA) was positively associated with LFN BMD (p = 0.008). Despite a decrease in serum vitamin D, BMD and CTx showed small or no changes over 2 years. Future studies should investigate PA interventions to maintain BMD in women living with HIV.
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    Study protocol - metabolic syndrome, vitamin D and bone status in South Asian women living in Auckland, New Zealand: A randomised, placebo-controlled, double-blind vitamin D intervention
    (BioMed Central Ltd part of Springer Science+Business Media, 2008) von Hurst PR; Stonehouse W; Matthys C; Conlon C; Kruger MC; Coad J
    Background The identification of the vitamin D receptor in the endocrine pancreas suggests a role for vitamin D in insulin secretion. There is also some limited evidence that vitamin D influences insulin resistance, and thus the early stages of the development of type 2 diabetes. Methods Eighty-four women of South Asian origin, living in Auckland, New Zealand, were randomised to receive either a supplement (4000IU 25(OH)D3 per day) or a placebo for 6 months. At baseline, all participants were vitamin D deficient (serum 25(OH)D3 <50 nmol/L), insulin resistant (HOMA-IR > 1.93) and/or hyperinsulinaemic, hyperglycemic or had clinical signs of dislipidaemia. Changes in HOMA-IR, lipids, parathyroid hormone, calcium and bone markers were monitored at 3 months and 6 months. Discussion This randomised, controlled trial will be the first to investigate the effect of vitamin D supplementation on insulin resistance in non-diabetic subjects. It will subsequently contribute to the growing body of evidence about the role of vitamin D in metabolic syndrome.Registered clinical. Trial registration Registered clinical trial – Registration No. ACTRN12607000642482
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    Vitamin D and omega-3 fatty acid supplements in children with autism spectrum disorder: a study protocol for a factorial randomised, double-blind, placebo-controlled trial.
    (23/06/2016) Mazahery H; Conlon C; Beck KL; Kruger MC; Stonehouse W; Camargo CA; Meyer BJ; Tsang B; Mugridge O; von Hurst PR
    BACKGROUND: There is strong mechanistic evidence to suggest that vitamin D and omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs), specifically docosahexaenoic acid (DHA), have the potential to significantly improve the symptoms of autism spectrum disorder (ASD). However, there are no trials that have measured the effect of both vitamin D and n-3 LCPUFA supplementation on autism severity symptoms. The objective of this 2 × 2 factorial trial is to investigate the effect of vitamin D, n-3 LCPUFAs or a combination of both on core symptoms of ASD. METHODS/DESIGN: Children with ASD living in New Zealand (n = 168 children) will be randomised to one of four treatments daily: vitamin D (2000 IU), n-3 LCPUFAs (722 mg DHA), vitamin D (2000 IU) + n-3 LCPUFAs (722 mg DHA) or placebo for 12 months. All researchers, participants and their caregivers will be blinded until the data analysis is completed, and randomisation of the active/placebo capsules and allocation will be fully concealed from all mentioned parties. The primary outcome measures are the change in social-communicative functioning, sensory processing issues and problem behaviours between baseline and 12 months. A secondary outcome measure is the effect on gastrointestinal symptoms. Baseline data will be used to assess and correct basic nutritional deficiencies prior to treatment allocation. For safety measures, serum 25-hydroxyvitamin D 25(OH)D and calcium will be monitored at baseline, 6 and 12 months, and weekly compliance and gastrointestinal symptom diaries will be completed by caregivers throughout the study period. DISCUSSION: To our knowledge there are no randomised controlled trials assessing the effects of both vitamin D and DHA supplementation on core symptoms of ASD. If it is shown that either vitamin D, DHA or both are effective, the trial would reveal a non-invasive approach to managing ASD symptoms. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN12615000144516 . Registered on 16 February 2015.
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    Vitamin D and Autism Spectrum Disorder: A Literature Review.
    (21/04/2016) Mazahery H; Camargo CA; Conlon C; Beck KL; Kruger MC; von Hurst PR
    Low vitamin D status in early development has been hypothesised as an environmental risk factor for Autism Spectrum Disorder (ASD), given the concurrent increase in the prevalence of these two conditions, and the association of vitamin D with many ASD-associated medical conditions. Identification of vitamin D-ASD factors may provide indications for primary and secondary prevention interventions. We systematically reviewed the literature for studies on vitamin D-ASD relationship, including potential mechanistic pathways. We identified seven specific areas, including: latitude, season of conception/birth, maternal migration/ethnicity, vitamin D status of mothers and ASD patients, and vitamin D intervention to prevent and treat ASD. Due to differences in the methodological procedures and inconsistent results, drawing conclusions from the first three areas is difficult. Using a more direct measure of vitamin D status--that is, serum 25(OH)D level during pregnancy or childhood--we found growing evidence for a relationship between vitamin D and ASD. These findings are supported by convincing evidence from experimental studies investigating the mechanistic pathways. However, with few primary and secondary prevention intervention trials, this relationship cannot be determined, unless randomised placebo-controlled trials of vitamin D as a preventive or disease-modifying measure in ASD patients are available.