Dissertationen zum Thema „Vitamin D in the body“

Inaugural address delivered on 2 November 2011
Marietjie Herselman was born in the Langkloof, where she matriculated at the McLachlan High School. She obtained a BSc (Physiology and Dietetics) degree at Stellenbosch University and for the next 18 years worked as a dietitian at Tygerberg Hospital, where she specialised in renal nutrition. She obtained a master’s degree in nutrition in 1985 and in 1991 was appointed as a lecturer in the Department of Human Nutrition, Faculty of Health Sciences, at Stellenbosch University. In the same year she obtained her PhD in nutritional sciences at this university, where she was later promoted to senior lecturer (1995), associate professor (2001) and full professor (2010). From 2008 to 2010 she was appointed first as acting head and later as head of the Division of Human Nutrition. She served on the Professional Board of Dietetics from 1998 to 2003 and also on various sub-committees of the Board. She regularly reviews papers and research applications for scientific councils/associations as well as five national and four international scientific journals. Currently, she serves on the editorial boards of four international scientific journals and in 2008 she was elected as the co-editor (Africa region) of the international journal Nutrition. She successfully delivered 17 master’s students and published 29 scientific papers in national and international journals and three chapters in textbooks. Marietjie also presented papers at 19 international and 37 national conferences. Three international and four national awards were bestowed on her for her research in renal nutrition. She played a leading role in the initiation of the Community Nutrition Security Project (CNSP) in the Breede Valley, as part of Stellenbosch University’s HOPE Project, as well as the NOMA master’s programme in Nutrition, Human Rights and Governance in collaboration with the universities of Oslo and Akershus (Norway) as well as Makerere and Kyambogo (Uganda).

60 % of Canadians have suboptimal vitamin D (<75 nmol/L) and 25% are obese. Obesity has been reported to be a risk factor for low vitamin D, but there is uncertainty about the magnitude of the association. Linear regression was performed using data from the nationally representative cross-sectional Canadian Health Measures Survey (2007-2009). Height, weight, waist circumference (WC), and vitamin D levels were directly measured. There were 5298 participants aged 6 to 79 years. Using a conservative p value of 0.001, body mass index (BMI) category obese / obese I was positively associated and WC was inversely associated with vitamin D level in crude analysis. WC was inversely associated with vitamin D level in multivariate analysis. The pattern of relationship is not the same as other studies, yet this was a large study with direct measurements. There may be issues with linearity of relationships or subgroups disturbing the relationship.

Cross sectional and observational data suggest that HIV-positive individuals and those receiving antiretroviral (ARV) therapy are prone to higher rates of osteoporosis and osteopaenia than HIV-negative individuals. Likewise, HIV-positive individuals often have low vitamin D status. Evidence is emerging more generally of a strong association between HIV infection and poor bone health. There is also evidence that treatment with ARV therapy (ART) and suboptimal vitamin D status may exacerbate this problem (Brown et al, 2006a, 2010). But, to date, causal relationships have not been fully established. This thesis explores the interactions between these separate factors and provides novel data about the effects of HIV infection and its treatment, on bone health in a particular group of black, South African women. Bone loss and poor vitamin D status in the context of HIV infection are important global health issues because these conditions may affect millions of individuals. If HIVassociated bone loss is causally associated with an increased risk of bone fracture then it is possible that there will be an epidemic of HIV-associated fractures in coming decades, particularly in the developing world, including Africa. Study data have so far often been limited by several factors, including cross-sectional design, absence of control groups, a preponderance of attention to bone outcomes in males and in Caucasians, and a lack of good quality data in Africans living in Africa. Th is study aimed to -assess the magnitude of HIV- and ART-associated changes in areal bone mineral density (aBMD), size-adjusted bone mineral content (SA-BMC) and vitamin D status in adult, premenopausal women living in Johannesburg, South Africa. Ninetyeight HIV-negative (Negative reference: Nref) and 149 HIV-positive women were enrolled to allow for comparison between groups. The HIV-positive women were recruited into those eligible to start ART (Positive low CD4 : Plow, n=75) and those unlikely to require ART (Positive preserved CD4 : Ppres, n=74) during a 12-month followup period. The design was longitudinal with visits at 0, 6 and 12 months for measurement of body composition, bone measures and dietary assessment. Blood and urine samples were collected for the evaluation of relevant musculoskeletal analytes, including 25(0H)D at each time point. Most women ( > 80%) who received ART during the course of the study received South African standard first-line therapy consisting of lamivudine, tenofovir and efavirenz. A post hoe analysis of possible effects of ART was performed by retrospectively dividing HIV-positive women into ART-unexposed (n=66) and ART-exposed (n=74). At baseline there was a high prevalence of overweight with 65%, 65% and 44% with BMI > 25 kg/m2 in Nref, Ppres and Plow respectively. Plow had lower weight, BMI, fat mass, lean mass, waist and hip circumferences than the other groups. Nref and Ppres were not different from each other. There were no differences in aBMD or SA-BMC 1 between groups at baseline and no significant differences in vitamin D status between the groups. The mean ±SD serum 25(0H)D concentrations were 59.7 ±16.5, 59.2 ±16.5 and 61.6 ±22.3 nmol/1 in Nref, Ppres and Plow respectively. Plow had significantly lower serum albumin concentration (p < 0.0001) and higher serum phosphate concentration (p < 0.0001). The magnitude of differences in serum phosphate was: Ppres-Nref = 12. 7 ±2.9%; Plow-Nref = 20.3 ±2.9% and Plow-Ppres = 7.6 ±3.1% (p < 0.001). Tubular maximum Reabsorption of Phosphate/Glomerular Filtration Rate (TmP/GFR) was 11.2 ±3.2% and 27.4 ±3.2% respectively greater in Ppres and Plow than Nref (p < 0.0001), and higher in the Plow compared to Ppres 16.2 ±3.4%, (p=0.0002). Serum alkaline phosphatase and urine phosphate to creatinine ratio were not significantly different (p > 0.05). At the 12-month follow-up, Plow subjects remained lighter than their Nref and Ppres counterparts. However, there was a 3.9 ±0.9% increase in mean weight in the Plow group over 12 months (p < 0.001), which represented 10.2 ±0.8% (p < 0.001) increase in fat, rather than lean, mass accumulation. There were significant mean decreases in aBMD and SA-BMC in Plow subjects, and those exposed to ART of the order of 2-3% at total hip, femoral neck and lumbar spine. There were no significant differences in mean vitamin D status between the groups and no significant changes, the mean 25(0H)D concentrations were 63.3 ±17.7, 66.0 ±18.4 and 61.1 ±20.1 nmol/1 in Nref, Ppres and Plow respectively. Serum albumin concentrations had risen by a mean of 9.1 ±1.1% in the Plow group to reach comparable concentrations with the other groups. Alkaline phosphatase activity had significantly risen in the Plow group compared with the other groups (p < 0.001). Serum phosphate concentration remained higher in Plow than the other groups, though the mean value had not increased. Serum phosphate had significantly increased in Nref from baseline to 12 months 7.0 ±2.3% (p=0.05) and non-significantly in Ppres 5.2 ±2.4%. TmP/GFR had declined from baseline by 11.2 ±3.6% in Plow and non-significantly increased in Nref and Ppres (6.4 ±3.3% and 3.8 ±3.5% respectively). These data suggest that HIV infection in South African women is associated with differences in body composition but not with differences in bone measures or vitamin D status. However, being in the Plow group, and ART exposure, was associated with a significant decrease in mean aBMD and SA-BMC, of the order of 2-3%, over 12 months of observation at the hip, femoral neck and lumbar spine. These decreases, in young women, exceed those seen in early menopause, which is of the order of 1-2% annual decrease. The decreases were evident despite the fact that HIV-positive women exposed to ART had increases in fat mass, weight and serum albumin and alkaline phosphatase over time. In this group serum phosphate concentration and TmP/GFR decreased after the introduction of ART, suggesting an effect of ART on renal phosphate handling. ART exposure was not associated with change in vitamin D status. In the post hoe analysis the biochemical results in ART-unexposed compared to ARTexposed was very similar to that in Ppres compared with Plow. Further studies to assess skeletal effects over a longer time in HIV-positive, ARTexposed and na"ive women are warranted. Studies are also required in post-menopausal women, children and men. Given the high prevalence of overweight and obesity recorded in the study population, there may also be a need for interventions to reduce cardiometabolic disease risk in this population.

Introdução - A vitamina D desempenha funções na regulação da homeostase do cálcio e fósforo, diferenciação celular, metabolismo de hormônios e regulação do sistema imune. Sua deficiência em crianças pode ocasionar raquitismo, convulsões e insuficiência respiratória. Objetivo - Determinar a relação entre adiposidade materna e do recém-nascido com as concentrações de vitamina D materna e do cordão umbilical. Metodologia - Foram envolvidas 101 mães e seus respectivos recém-nascidos selecionados no Hospital Maternidade Vila Nova Cachoeirinha, São Paulo. A concentração de vitamina D foi determinada por cromatografia líquida. A composição corporal materna foi determinada por bioimpedância segmentada (InBody®, Coréia do Sul) e a dos recém-nascidos obtida por pletismografia por deslocamento de ar (PEA POD®, USA). Para análise estatística, utilizou-se análise de regressão linear múltipla e coeficiente de correlação de Spearman. Valores de p <0,05 foram considerados significantes. Resultados - As médias das concentrações de vitamina D da mãe e do cordão umbilical foram de 30,16 (DP=21,16) ng/mL e 9,56 (DP=7,25) ng/mL, respectivamente. As médias das porcentagens de massa gorda das mães e dos recém-nascidos foram de 32,32 (DP=7,74) por cento e 8,55 (DP=4,37) por cento , respectivamente. Foi observada relação positiva entre concentração de vitamina D materna e do cordão umbilical (r=0,210; p<0,04). Não foi observada associação entre adiposidade do recém-nascido e concentração de vitamina D do cordão umbilical, nem entre adiposidade materna e concentrações de vitamina D materna e do cordão umbilical. Conclusão Neste estudo, original na literatura internacional, foi utilizado método de referência, validado, de alta precisão e imparcial na estimativa do percentual de gordura neonatal, nem sempre utilizado em outros estudos. Foi observada relação positiva entre concentração de vitamina D materna e do cordão umbilical. A ausência de associação entre as variáveis analisadas pode ser devido à alta prevalência de sobrepeso e obesidade entre as gestantes, baixas concentrações de vitamina D nas gestantes e recém-nascidos, alteração do metabolismo da vitamina D e da composição corporal no período da gestação e imaturidade do processo de sequestro da vitamina D pelo tecido adiposo 1 neonatal. Torna-se relevante o desenvolvimento de estudos prospectivos do tipo coorte para avaliar desde o início da gestação a influência da adiposidaidade materna nas concentrações de vitamina D materna e do cordão umbilical.
Introduction - Vitamin D plays a role in the regulation of mineral homeostasis, cell differentiation, hormone metabolism, and regulation of the immune system. Its deficiency can cause rickets in children, convulsions and difficulty breathing. Objective - To determine the relationship between maternal adiposity and the newborn with concentrations of vitamin D maternal and umbilical cord. Methodology- 101 mothers and their newborns were involved. The prevalence of insufficiency (21-29 ng/ml) and deficiency (<20 ng/ml) of vitamin D were determined. The 25(OH)D concentration was analyzed by liquid chromatography, and the umbilical cord blood was collected for up to 10 minutes after childbirth. The maternal nutritional status was assessed by body mass index before pregnancy. Maternal body composition was determined by bioimpedance segmented. Body composition of newborns was obtained by technology plethysmography air displacement. For statistical analysis, multiple linear regression analysis and Pearsons correlation coefficient were used. P values <0.05 were considered significant. Results - The mean concentration of vitamin D from the mother and the umbilical cord were 30.16 (SD = 21.16) ng/mL and 9.56 (SD = 7.25) ng/mL, respectively. The observed prevalence of maternal vitamin D insufficiency and deficiency were 56.44 per cent and 41.58 per cent . Ninety-five percent (95.92 per cent ) and 89.80 per cent of the newborns had vitamin D insufficiency and deficiency, respectively. The mean maternal prepregnancy BMI was 27.79 (SD = 5.61) kg/m2. The mean percentages of fat mass of mothers and newborns were 32.32 (SD= 7.74) and 8.55 per cent (SD= 4.37) per cent , respectively. Positive relationship between concentration of vitamin D maternal and cord blood (r=0,248; p<0,013) was observed. No relationship between adiposity newborn and concentration of vitamin D in the umbilical cord, or relationship between maternal adiposity and concentrations of vitamin D maternal and umbilical cord was observed. Conclusion - Despite it is an original study, no relationship between maternal adiposity and concentrations of vitamin D maternal and umbilical cord was observed. It is significant further research to investigate the influence of maternal fat in neonatal body composition and vitamin D concentrations in maternal and cord blood.

Includes bibliographical references (leaves 226-273.) Investigates the regulation of the expression of CYP27B1, CYP24 and vitamin D receptor (VDR) mRNA, both in the bone and in the kidney, with the aim to determine whether the regulation of the vitamin D metabolism in the bone is independent from that in the kidney. The effects of age, dietary calcium and vitamin D status on the expression of these genes in both the kidney and the bone, as well as on a number of biochemical factors known to regulate the renal metabolism of 1,25D, such as PTH, calcium and 1,25D itself, were examined. CYP27B1 mRNA expression was also studied in histological sections of rat femoral bone.

The in utero environment to which a fetus is exposed might influence body composition and muscle strength in later life. Modulation of this environment could therefore represent an approach to addressing the increasing burden of obesity and sarcopenia. One potential modifiable exposure is vitamin D. The aim of this work was to explore the determinants of maternal serum 25-hydroxyvitamin D [25(OH)D] status in pregnancy and the use of antenatal vitamin D supplementation to improve offspring growth, body composition and muscle strength. The Southampton Women’s Survey (SWS) is a prospective birth cohort study that included assessment of maternal serum 25(OH)D at 11 (n=2019) and 34 weeks (n=2328) of gestation. Marked seasonal variation in serum 25(OH)D was observed at both gestations (p < 0.001 for both). After adjustment for season, 25(OH)D tracked moderately from early to late pregnancy (r=0.53), but supplementation use and pregnancy weight gain were significantly associated with changes in 25(OH)D status. The offspring of 678 women who had a late pregnancy 25(OH)D measurement were reviewed at 4 years of age. There were no significant associations between maternal 25(OH)D and offspring lean mass (LM) measured by dual-energy x-ray absorptiometry (DXA), but a positive association with grip strength was found (β=0.10 SD/SD, p=0.01). These findings were translated to an intervention study using the MAVIDOS trial, a randomised placebo-controlled trial of antenatal vitamin D supplementation (1000 IU/day cholecalciferol from 14 weeks of gestation until delivery) in women with a baseline 25(OH)D of 25-100 nmol/l. Offspring anthropometry was assessed at birth (n=768), 1 year (n=594) and 2 years (n=577) of age. At 4 years (n=378), body composition was assessed by DXA and grip strength by hand dynamometry. Weight, length/height and measures of adiposity (skinfold thicknesses at birth, 1 and 2 years of age; fat mass measured by DXA at 4 years) did not differ between the randomisation groups at any age (p > 0.05 for all) despite a significantly greater maternal 25(OH)D in the cholecalciferol supplementation group at 34 weeks of gestation (mean difference 24.7 nmol/l, p < 0.001). LM and grip strength at 4 years were also similar, but in women with baseline 25(OH)D < 30 nmol/l, offspring grip strength was greater in those randomised to cholecalciferol (0.70 SD [95% CI 0.02, 1.38], p=0.04). LM did not differ in this subgroup. These findings suggest that 1000 IU/day cholecalciferol supplementation during mid and late pregnancy in women with baseline 25(OH)D 25-100 nmol/l does not improve offspring body composition or muscle strength despite an increase in maternal 25(OH)D status. Supplementation increased muscle strength in offspring of women with the lowest 25(OH)D levels, highlighting the need for further trials of vitamin D supplementation in deficient women.

O termo vitamina D compreende um grupo de hormônios esteróides com ações biológicas semelhantes. O método mais acurado para determinar o estado de vitamina D é através dos níveis plasmáticos de 25 hidroxivitamina D [25(OH)D]. A deficiência de 25(OH)D é considerada um problema de saúde pública, tendo como principal causa à baixa exposição solar, idade avançada e doenças crônicas. A deficiência de 25(OH)D é frequente em pacientes com doença renal crônica (DRC) na fase não dialítica. Estudos têm evidenciado que os níveis séricos de 25(OH)D apresentam associação inversa com adiposidade corporal e resistência à insulina (RI) na população em geral e na DRC. O excesso de gordura corporal e o risco de Doença Cardiovascular (DVC) vêm sendo estudados em pacientes com DRC e dentre as complicações metabólicas associadas à adiposidade corporal elevada observa-se valores aumentados de HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) um marcador para RI. Estudos avaliando o perfil da 25(OH)D na DRC na fase não dialítica, especialmente relacionados com a adiposidade corporal e RI são escassos. O presente estudo tem como objetivo avaliar a relação entre os níveis séricos de 25(OH)D, RI, e adiposidade corporal em pacientes com DRC na fase não dialítica. Trata-se de um estudo transversal observacional, incluindo pacientes adultos, clinicamente estáveis e com filtração glomerular estimada (FGe) ≤ 60 ml/min., em acompanhamento regular no Núcleo Interdisciplinar de Tratamento da DRC. Os participantes foram submetidos à avaliação do estado nutricional por antropometria (peso, altura, índice de massa corporal (IMC), circunferências e dobras cutâneas) e absorciometria de duplo feixe de raios X (DXA); foram avaliados no sangue: creatinina, uréia, glicose, albumina, colesterol total e frações e triglicérides, além de leptina, insulina e 25(OH)D. Níveis séricos < 20ng/dL de 25(OH)D foram considerados como deficiência. As análises estatísticas foram realizadas utilizando-se o software STATA versão 10.0, StataCorp, College Satation, TX, USA. Foram avaliados 244 pacientes (homens n=135; 55,3%) com média de idade de 66,3 13,4 anos e de FGe= 29,4 12,7 ml/min. O IMC médio foi de 26,1 kg/m (23,0-30,1) com elevada prevalência de sobrepeso/obesidade (58%). A adiposidade corporal total foi elevada em homens (gordura total-DXA= 30,2 7,6%) e mulheres (gordura total-DXA= 39,9 6,6%). O valor mediano de 25(OH) D foi de 28,55 ng/dL (35,30-50,70) e de HOMA-IR foi 1,6 (1,0-2,7). Os pacientes com deficiência de 25(OH)D (n= 51; 20,5%) apresentaram maior adiposidade corporal total (DXA% e BAI %) e central (DXA%) e valores mais elevados de leptina. A 25(OH)D apresentou correlação significante com adiposidade corporal total e central e com a leptina, mas não se associou com valores de HOMA-IR. Estes resultados permitem concluir que nos pacientes DRC fase não dialítica a deficiência de 25(OH)D e a elevada adiposidade corporal são frequentes. Estas duas condições estão fortemente associadas independente da RI; a alta adiposidade corporal total e central estão positivamente relacionadas com RI; 25(OH)H e RI não estão associados nessa população com sobrepeso/obesidade.
The term vitamin D comprises a group of steroid hormones with similar biological actions. The status of vitamin D is most accurately determined by measuring the plasma levels of 25-hydroxyvitamin D [25(OH) D]. The deficiency of 25(OH)D is considered a public health problem and the main cause is the low sun exposure, advanced age and chronic diseases. Patients with chronic kidney disease (CKD) non dialysis dependent show high prevalence of 25(OH)D deficiency. The 25(OH)D serum levels have been described, in many studies, as being inversely associated with total and abdominal adiposity and insulin resistance. The higher risk for CVD related with excess of body fat have been studied in patients with CKD and the high values of HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), a marker for insulin resistance (RI), are described as metabolic complication strongly associated with excessive body fat. Nevertheless, studies evaluating the 25(OH)D status in patients with CKD non dialysis dependent, and its association with body adiposity and IR are scarce. The present study aims to evaluate the relationship between the levels of 25(OH)D, IR and body fat in patients with CKD non dialysis dependent. This is an observational cross-sectional study including adult patients, clinically stable and with estimated glomerular filtration rate (FGE)≤ 60 mL/min. The studied population receives regular care at the Interdisciplinary Center for treatment of CKD. Participants underwent assessment of nutritional status by anthropometry (weight, height, body mass index (BMI), circumferences and skinfolds) and by DXA (Dual-energy X-ray absorptiometry); blood samples were also analysed for creatinine, urea, glucose, albumin, total cholesterol and triglycerides, 25(OH)D, leptin and insulin. Levels of 25(OH)D <20ng/dL were considered deficient. Statistical analyzes were performed using STATA version 10.0 software, StataCorp, CollegeSatation, TX, USA. We evaluated 244 patients (men n= 135; 55.3%) with a mean age of 66.3 13.4 years and eGFR= 29.4 12.7 mL/min. The mean BMI was 26.1 kg/m (23.0 to 30.1) with a high prevalence of overweight/obesity (58%). Total body fat was high in men (total body fat by DXA= 30.2 7.6%) and women (total body fat by DXA= 39.9 6.6%). The median value of 25(OH)D was 28.55 (35.30 to 50.70) ng/dL and HOMA-IR was 1.6 (1.0 to 2.7) and patients with deficiency of 25(OH D n= 51 - 20.5%) had higher total (DXA% and BAI%) and central adiposity (DXA%) and higher levels of leptin. The 25(OH)D showed an inverse correlation with the total and central body fat and leptin, but was not associated with HOMA-IR values. These results allow to conclude that patients with CKD, non dialysis dependent, show deficiency of 25(OH)D and high body adiposity. These two conditions are strongly associated independent of the IR; the high total and central body adiposity is positively related with IR; the 25(OH)H and IR are not associated in this overweight/obese population.

Background: Studies have not examined the relationships between serum vitamin D (SVitD), serum cortisol (SCort), bone mineral density (BMD), and body fat percent (BF%) in elite figure skaters. However, studies of non-athletes have found that BMD is inversely related to SCort and directly related to SVitD, and BF% is inversely related to SVitD and directly related to SCort. It was, therefore, the purpose of this study to assess the relationships between SCort, SVitD, BMD, and BF% in elite figure skaters. Methods: U.S. national team figure skaters were assessed at a national training camp during the summer, 2012. BMD and body composition were measured by dual energy x-ray absorptiometry (DEXA). Blood chemistry values for SVitD and SCort were obtained via venous puncture after an overnight fast, the same morning as the DEXA measurement. Georgia State University Institutional Review Board approval was obtained for the assessment of data collected at this training camp. Results: 24 out of 39 training camp attendees (61.5%) volunteered to be assessed as part of this study. Subjects ranged from 17 to 34 years and included males (n=11) and females (n=12). In all skaters statistically significant negative correlations (2-tailed Spearman) were found between SCort and BMD of the spine (r=-0.458, p=0.032), pelvis (r=-0.532, p=0.011), ribs (r=-0.517, p=0.014), and trunk (r=-0.538, p=0.010). In females, SCort was negatively correlated with BMD of the pelvis (r=-0.664, p=0.026) and trunk (r=-0.609, p=0.047), and was positively correlated with total BF% (r=0.657, p=0.020) and trunk fat % (r=0.708, p=0.010). In males, SCort was significantly correlated with BMD of the ribs (r=-0.627, p=0.039). The 3 skaters (all female) with SCort > 28 mcg/dL had significantly lower mean BMD of the total body, left femoral neck, legs, trunk, and pelvis, and significantly greater BF% of the total body and trunk when compared to the 20 skaters with SCort 7-28 mcg/dL. No significant correlations between SVitD and BMD or BF% were found. A Mann-Whitney U test found no significant differences in BMD and BF% between the 8 skaters with SVitD ≥ 30 ng/mL compared to the 15 skaters with SVitD < 30 ng/mL (p>0.05). Females with SVitD ≥ 30 ng/mL had significantly higher BMD (p=0.041) of the right femoral neck when compared to those with lower SVitD. Conclusions: Correlations consistently found negative associations between SCort cortisol and BMD in multiple assessment areas, particularly those composed of trabecular bone. Higher SCort was also associated with higher BF% in female skaters. Despite spending a great deal of time in indoor facilities, limiting vitamin D creation through sunlight exposure, no significant correlation between SVitD and BMD was found. Female athletes in ‘appearance’ sports, may be predisposed to restrained eating behaviors, which may be associated with elevated SCort. These findings suggest a need for further study of the interaction between SCort, BMD, and BF% in these athletes. The lack of a statistically significant relationship between SVitD and BMD suggests the need to investigate additional factors associated with bone injury risk in athletes.

The human vitamin D receptor (hVDR) is a member of the nuclear receptor superfamily, involved in calcium and phosphate homeostasis; hence implicated in a number of diseases, such as Rickets and Osteoporosis. This receptor binds 1α,25-dihydroxyvitamin D3 (also referred to as 1,25(OH)2D3) and other known ligands, such as lithocholic acid. Specific interactions between the receptor and ligand are crucial for the function and activation of this receptor, as implied by the single point mutation, H305Q, causing symptoms of Type II Rickets. In this work, further understanding of the significant and essential interactions between the ligand and the receptor were deciphered, through a combination of rational and random mutagenesis. A hVDR mutant, H305F, was engineered with increased sensitivity towards lithocholic acid, with an EC50 value of 10 µM and 40 + 14 fold activation in mammalian cell assays, while maintaining wild-type activity with 1,25(OH)2D3. Furthermore, via random mutagenesis, a hVDR mutant, H305F/H397Y, was discovered to bind a novel small molecule, cholecalciferol, a precursor in the 1α,25-dihydroxyvitamin D3 biosynthetic pathway, which does not activate wild-type hVDR. This variant, H305F/H397Y, binds and activates in response to cholecalciferol concentrations as low as 100 nM, with an EC50 value of 300 nM and 70 + 11 fold activation in mammalian cell assays.

Introdução a redução da massa muscular esquelética relacionada à idade, denominada sarcopenia, está associada com maior incidência de quedas, fraturas e dependência funcional em idosos. Muitos são os fatores que podem contribuir para o surgimento da sarcopenia, dentre eles a deficiência de vitamina D e a inadequação do consumo alimentar, principalmente a ingestão de proteína. Objetivos investigar a relação da sarcopenia com o consumo alimentar e concentração sérica de 25(OH)D. Métodos Foram avaliadas 200 mulheres acima de 65 anos, sendo 35 com sarcopenia e 165 sem sarcopenia. Avaliou-se a densidade mineral óssea (DMO) da coluna lombar, fêmur proximal e a composição corporal (massa muscular total, massa muscular esquelética, massa adiposa, conteúdo mineral ósseo do corpo total) por meio do densitômetro de dupla emissão com fonte de raios-X (DXA), avaliação radiográfica das colunas dorsal e lombar (T4 a L4). Foi realizada também avaliação da ingestão alimentar (diário de três dias), bioquímica do metabolismo mineral e ósseo (cálcio total, fósforo, creatinina, albumina, paratormônio intacto, calcidiol) e a história clínica das pacientes. Resultados O presente estudo observou que as pacientes que apresentavam um consumo de proteína acima de 1,2g/kg/dia apresentaram massa muscular total [33,94 (4,72) vs 31,87 (3,52) kg, p=0,020], massa muscular esquelética [14,54 (2,38) vs 13,38 (1,95) kg, p=0,013], CMO do corpo total [1,945 (0,325) vs 1784 (0,265) g, p=0,005], DMO de corpo total [1,039 (0,109) vs 0,988 (0,090) g/cm2, p=0,011], DMO coluna lombar [0,983 (0,192) vs 0,903 (0,131) g/cm2, p=0,014], DMO colo de fêmur [0,813 (0,117) vs 0,760 (0,944) g/cm2, p=0,017] e DMO fêmur total [0,868 (0,135) vs 0,807 (0,116) g/cm2, p=0,026] significativamente maior quando comparado com pacientes que apresentavam consumo de proteína abaixo de 0,8g/kg/dia. Além disso, a ingestão de aminoácidos essenciais, principalmente os de cadeia ramificada como a valina [3,10 (0,89) vs 3,40 (1,04) g/dia, p=0,044] foi significantemente menor em mulheres com sarcopenia. O consumo de proteína se correlacionou positivamente com o índice de massa muscular esquelética (r=0,157; p=0,028) e a DMO do trocânter (r=0,185; p=0,010). Adicionalmente, a deficiência de vitamina D associados ao PTH elevado (> 65pg/dL), hiperparatiroidismo secundário, a prevalência de sarcopenia aumentada (77,1 vs 22,9%, p=0,032), além disso mulheres com hiperparatiroidismo secundário apresentaram massa muscular total [29,70 ( 2,99) vs 31,84 (3,65), p=0,043], índice de massa muscular esquelética [5,51 (0,55) vs 5,92 (0,78), p=0,043] significativamente menor. Alta prevalência de deficiência de vitamina D em mulheres com sarcopenia (71,4%). As mulheres com deficiência de vitamina D apresentaram massa muscular total [30,30 (2,92) vs 32,14 (3,84) kg, p=0,007], massa muscular esquelética apendicular [12,71 (1,59) vs 13,55 (0,82) kg, p=0,031]; índice de massa muscular esquelética [5,67 ( 0,60) vs 5,98 (0,82) kg/m2, p=0,030] e fêmur total BMD [0,791 (0,107) vs 0,838 (0,116) g/cm2, p=0,035] significativamente menor. Conclusões - A ingestão de proteínas acima 1,2g/kg/d, especialmente aminoácidos essenciais e suplementação de vitamina D deve ser considerada como terapia preventiva na redução da massa muscular e óssea em mulheres idosas
Introduction - Reduction of skeletal muscle mass, called sarcopenia, is associated with increased incidence of falls, fractures and functional dependence in the elderly. There are many factors that can contribute to the development of sarcopenia, among them the vitamin D deficiency and inadequate food intake, especially protein intake. Objectives - to investigate the relationship among sarcopenia, dietary intake and serum concentration of 25(OH)D. Methods - We evaluated 200 women over 65 years, 35 with sarcopenia and 165 without sarcopenia. Bone mineral density of lumbar spine, proximal femur and body composition (total muscle mass, skeletal muscle mass, fat mass, bone mineral content of the whole body) were assessed by Dual energy X-ray absorptiometry (DXA), radiological evaluation of the dorsal columns and lumbar (T4 to L4). Three-day dietary records were undertaken to estimate dietary intake and serum total albumin, calcium, phosphorus, creatinin, intact parathyroid hormone, 25(OH)D were measured. Results - Patients who presented protein intake above 1.2g/kg/day showed total muscle mass [33.94 (4.72) vs 31.87 (3.52) kg, p=0.020], muscle mass skeletal [14.54 (2.38) vs 13.38 (1.95) kg, p=0.013], total body BMC [1.945 (0.325) vs 1784 (0.265) g, p=0.005], total body BMD [1.039 (0.109) vs 0.988 (0.090) g/cm2, p=0.011], lumbar spine BMD [0.983 (0.192) vs 0.903 (0.131) g/cm2, p=0.014], femoral neck BMD [0.813 (0.117) vs 0.760 (0.944) g/cm2, p=0.017] and total femur BMD [0.868 (0.135) vs 0.807 (0.116) g/cm2, p=0.026] significantly higher when compared with patients who presented protein intake below 0.8g/kg/day. Essential amino acids intake, especially branched chain such as valine [3.10 (0.89) vs 3.40 (1.04) g/day, p=0.044] was significantly lower in women with sarcopenia. Protein intake positively correlated to skeletal muscle mass index (r=0.157, p=0.028) and trochanter BMD (r=0.185, p=0.010). Additionaly, presence of sarcopenia increases more than 20% when vitamin D deficiency is associated to PTH levels higher than 65pg/dL (77.1 vs 22.9%; p=0.032). Women with secondary hyperparathyroidism presented significantly lower total muscle mass [29.70 (2.99) vs 31.84 (3.65); p=0.043], SMMI [5.51 (0.55) vs 5.92 (0.78); p=0.043]. it was also observed high prevalence of vitamin D deficiency in women with sarcopenia (71.4%). Women with deficiency of vitamin D presented significantly lower TSMM [30.30 (2.92) vs 32.14 (3.84) kg; p=0.007], ASMM [12.71 (1.59) vs 13.55 (0.82) kg; p=0.031]; SMMI [5.67 (0.60) vs 5.98 (0.82) kg/m2; p=0.030] and total femur BMD [0.791 (0.107) vs 0.838 (0.116) g/cm2; p=0.035]. Conclusions Protein intake above 1.2g/kg/d, particularly essencial amino acids and vitamin D supplementation should be considered as preventive therapy in reducing muscle and bone mass in elderly women

Adequate vitamin D status plays an important role in bone health and may also protect against Type 1 Diabetes (T1D), multiple sclerosis and certain cancers. Vitamin D is obtained from two sources; diet and through skin synthesis through the action of ultraviolet (UV) light. Dietary intakes of vitamin D are low in New Zealand (NZ) and the majority of our vitamin D comes from UV exposure. The NZ population may be at risk of low vitamin D status because of low dietary intakes, the country�s latitude (35-46 �S), and high proportion of darker skinned Maori and Pacific People. While case reports have described the occurrence of rickets, predominantly in immigrant groups, there are currently no national data on the vitamin D status of the NZ population. Reports of low vitamin D status in countries of similar latitude to NZ justify an examination of New Zealanders� vitamin D status. The best method to assess of vitamin D status is to measure circulating 25-hydroxyvitamin D concentrations. This thesis comprises three main studies. The first two had the following aims: to measure 25-hydroxyvitamin D concentrations and their determinants in a national sample (n=1585) of NZ children aged 5-14 y and to measure serum 25-hydroxyvitamin D concentrations and their determinants in a national sample (n=2948) of New Zealanders aged 15 y and over. The 2002 Children�s Nutrition Survey CNS02 was a year long (December, March-November) cross-sectional survey of a nationally representative sample of NZ school children 5-14 y. Over-sampling of Maori and Pacific children allowed ethnic specific analyses. The 1997 National Nutrition Survey (NNS97) participants were recruited over one year according to an area-based sampling frame with a 3 stage stratified design consisting of primary sampling units, households within each unit, and one randomly selected respondent from each household. Mean (99% CI) serum 25-hydroxyvitamin D concentrations were similar in children and adults (both 50 nmol/L). Among Maori, Pacific and NZEO children respectively, prevalence (%, 99% CI) of serum 25-hydroxyvitamin D deficiency (< 17.5 nmol/L) was 5% (2, 12), 8% (5, 14), and 3% (1,7). Based on a cutoff of < 37.5 nmol/L, prevalence of insufficiency was 41% (29, 53), 59% (42, 75) and 25% (15, 35), respectively. Based on a cutoff of 50 nmol/L, 56% of children were insufficient. Three percent of adult New Zealanders had serum 25-hydroxyvitamin D concentrations indicative of deficiency ([less than or equal to] 17.5 nmol/L); 48% and 84% were insufficient based on cutoffs of [less than or equal to] 50 and [less than or equal to] 80 nmol/L The main determinants of vitamin D status in NZ children were season, ethnicity and sex. After adjustment for other factors and covariates, boys had an adjusted mean (99% CI) 25-hydroxyvitamin D concentration 5 (1, 9) nmol/L higher than girls, Maori children were 7 (2, 11) and Pacific children 15 (11, 20) nmol/L lower than NZ European and Other (NZEO) children. Obese children were 7 (2, 11) nmol/L lower than overweight or �normal� weight. Children�s mean 25-hydroxyvitamin D concentrations (adjusted for other variables) peaked in March (69 nmol/L) and was at its lowest in August (36 nmol/L). In adults, there were effects of a similar magnitude of ethnicity and season on serum 25-hydroxyvitamin D concentrations. Obesity, latitude and age were determinants of vitamin D status in women but not men. Obese (BMI > 30) women had an adjusted mean vitamin concentration 6 (3, 10) nmol/L lower than women with BMI < 25. Women living in the South Island were 6 (3, 9) nmol/L lower than women living in the North Island. Additionally, adjusted mean serum 25-hydroxyvitamin D was 13 (8, 18) higher in women 15 -18 y than women 65 y or older. The third and final study aimed to determine whether the higher rates of vitamin D inadequacy reported in the winter than summer months in NZ also result in higher PTH concentrations, which would provide evidence for functional effect of inadequate vitamin D status. We also aimed to objectively explore the effect of natural skin colour on vitamin D status, given the higher prevalence of vitamin D insufficiency in dark-skinned groups living far from the equator. Skin colour measurements were taken with a hand-held light reflectometer (Datacolor Mercury[TM] 1000 colorimeter, Lawrenceville, NJ). In the 342 residents of Invercargill and Dunedin, mean serum 25-hydroxyvitamin D concentrations were lower in the late summer versus early spring (79 vs 51 nmol/L; P< 0.001). The lower serum 25-hydroxyvitamin D in early spring versus summer was associatedwith a 2 pg/mL (P< 0.001) higher parathyroid hormone (PTH) concentration. Interestingly, no significant effect of natural skin colour, based on light reflectance at the inside of the upper arm, was discovered, though there was a positive effect of tanning, based on light reflectance at the upper forearm, on serum 25-hydroxyvitamin D concentrations. Ethnicity and season are major determinants of serum 25-hydroxyvitamin D in New Zealanders. There is a high prevalence of vitamin D insufficiency in NZ children and adults, which may contribute to increased risk of osteoporosis and other chronic disease. While there is a pressing need for more convincing evidence with regards to the health risks associated with the low vitamin D status in children, evidence from the study of adults, where higher PTH concentrations were found during spring versus summer, suggests that the low 25-hydroxyvitamin D concentrations are having an adverse effect on bone health of adults. The high prevalence of vitamin D insufficiency in New Zealanders, warrants serious consideration of strategies such as fortification, to improve the vitamin D status of the population.

Primarily synthesised via cutaneous exposure to solar ultraviolet B (UVB) radiation, serum vitamin D concentrations, measured as 25-hydroxyvitamin D (25(OH)D), fluctuate according to solar availability. Seasonal variations in vitamin D are common in areas of high or low latitude determined by the distance from the sun. Seasonal variations in blood pressure, immune markers and some diseases including influenza, have also been reported. However, the contributions of UVB light or vitamin D on the immune markers have not been fully determined. Against this background, the purpose of this research was to investigate the effects of UVB light therapy and dietary vitamin D supplementation on markers of immune function. The D SIRe1 study aimed to assess whether dietary-derived 25(OH)D could have similar effects on immune function as light-derived 25(OH)D. The study was an 8-week comparative intervention trial in healthy adults randomised to receive either 3 times weekly UVB radiation (equivalent to doses received during a Grampian-summer) for 4 weeks; or oral vitamin D3 (1000 IU a day for 8 weeks). Total 25(OH)D was measured by dual tandem mass spectrometry of serum samples following removal of protein and de-lipidation, whilst regulatory T cells (Tregs), known for maintaining immune system homeostasis, by flow cytometry. The study showed similar short-term effects between oral vitamin D and UVB exposure on measured outcomes. However, study interpretation was limited by the lack of a placebo group, yet, to our knowledge, this was the first study to directly compare dose-matched UVB therapy and vitamin D supplementation in healthy participants. Using similar laboratory techniques, the D-SIRe2 study, a placebo-controlled trial, assessed short-term (12 weeks) and long-term (43 weeks) effects of vitamin D supplementation on immune markers. Commencing in spring (March) and finishing in winter (January) 2015/2016, the study showed seasonal fluctuations in most immune markers. The fluctuations did not change according to variations in 25(OH)D concentrations nor were they correlated with solar UVB doses, with the exception of T cell proliferative responses, which were positively correlated with daily solar UVB doses. An interesting finding from this study was the prevention of increases in pro-inflammatory IFN-γ cytokine concentrations in the spring and summer time in the vitamin D3 supplemental group versus placebo. IFN-γ concentrations were raised from 7940 pg/mL at baseline in March, to roughly 12400 pg/mL at week 4 and to 13909 pg/mL at week 12 in the placebo group. The concentrations were roughly 1.3 times the mean concentrations measured in the vitamin D group at the timepoints following baseline concentrations of 10678 pg/mL, and 10013 pg/mL and 10233 pg/mL at weeks 4 and 12, respectively. The interactions between solar light or seasonal effects and oral vitamin D supplementation, as well as their individual and combined effects on immune function, are yet to be fully determined. Moreover, the metabolic and physiological implications of seasonal variation in serum 25(OH)D concentration and markers of immune function are currently unknown, requiring further investigation.

Introduction: Bone health development and maintenance is important in children to reduce the risk for osteoporosis later in life. Knowledge on the vitamin D and bone health status of preadolescent children in South Africa is limited. Vitamin D and body composition both play important roles in bone health, but the relationship between adiposity and bone mass in children has been debated. The objective of this study was firstly, to describe the bone health status, body composition and vitamin D status of preadolescent children in Pretoria, South Africa. Secondly, the study examined bone health in relation to body composition and vitamin D status. Methods: A cross-sectional study, using conveniently sampled preadolescent black children aged 5-10, was conducted. Body weight was measured with the Seca medical body composition analyser and height using the Seca 274 stadiometer. Dual x-ray absorptiometry (DXA) was used for bone health (bone mineral content (BMC), areal bone mineral density (BMD) and bone area at the total body less the head (TBLH) and lumbar spine (LS) sites) and body composition (body fat percentage, fat mass and lean mass) assessments (n = 84). Vitamin D status (25(OH)D2 and 25(OH)D3) was determined from blood spot analysis (n = 59). To compare bone health means between vitamin D status groups, children were grouped as sufficient (25(OH)D ? 30 ng/ml), insufficient (25(OH)D = 21-29 ng/ml) or deficient (25(OH)D ? 20 ng/ml) accordingly. To compare bone health means between body composition groups, children were grouped as normal (BMIfor- age Z-score ? 1) or over-nourished (BMI-for-age Z-score > 1). Simple linear regression models were used in defining the relationship between bone health parameters and body composition components. Adjustments of bone health parameters for height-for-age, gender, age and body composition components was done using multiple linear regression. Comparison between adjusted bone health parameters of normal and over-nourished were made using the student’s two sample t-test. Results: The 59 children in the vitamin D study groups had a 24% prevalence of low BMD for chronological age and 7% presented with a low BMC for chronological age. A peculiar finding was that LS-BMAD differed significantly between the vitamin D insufficient and deficient groups. There was no relationship between any bone health parameters at all sites measured and serum levels of 25(OH)D (p > 0.05). Fat mass (FM) and body fat percentage least explained the observed variation in bone health parameters, whereas lean mass (LM) was the most important body composition component in explaining the variations observed in bone health parameters. The relationship between LS bone health parameters and body composition components was weaker than the relationship between TBLH bone health parameters and body composition components. Summary and / or Conclusion: In this population, 66% of preadolescents were vitamin D insufficient or deficient, but with a healthy bone health status and 40% of the preadolescents were over-nourished with greater crude BMD than those with healthy BMI Z-scores. Vitamin D status does not appear to be associated with parameters of bone health. Lean mass was the greatest body compositional determinant for variations observed in bone health parameters. Bone health parameters of healthy and over-nourished children did not differ after adjusting for body composition.
Dissertation (MSc)--University of Pretoria, 2017.
Food Science
MSc
Unrestricted

As the prevalence of vitamin D deficiency continues to grow, mounting evidence supporting its link with chronic disease strengthens suggesting vitamin D’s candidacy in the prevention and treatment of multiple disease states and their complications. Dietary guidelines, however, do not take sun exposure into account. The present study sought to explore the impact of sun exposure on vitamin D status (serum 25(OH)D), and identify other significant determinants of serum levels which may have the greatest effects on overall health. Participants (n = 34) were pre-menopausal women aged 18 to 50 years (mean age 39 ± 6 years), who had their blood drawn at a local pathology lab and a follow-up appointment at a health assessment lab for the collection of other measurements. Mean serum 25(OH)D level was 64 ± 18 nmol/L, and mean dietary vitamin D intake was approximately 327 ± 229 IU/day. Although 82% of participants were below the RDA guidelines (600 IU/day for females ages 9-50 years) for dietary vitamin D intake, only 32% had serum 25(OH)D levels < 50 nmol/L (the recommended level of sufficiency for bone health) reflecting deficiency. While serum 25(OH)D levels were significantly correlated to dietary vitamin D intake (r = 0.42, p = 0.0139), it is reasonable to assume that participants obtained adequate vitamin D from sun exposure. Fasting serum insulin levels were significantly, positively correlated with BMI (r = 0.83, p < 0.0001), and sun exposure index (Body Surface Area x Minutes of Direct Sunlight) was significantly, positively correlated with serum 25(OH)D levels (fall weekend SEI: r = 0.47, p = 0.0059; spring weekend SEI: r = 0.43, p = 0.0135; average weekend SEI: r = 0.43, p = 0.013; and average overall SEI: r = 0.39, p = 0.0247). Reported sun exposure appeared to be least during winter weekdays and the most during summer weekends. Regression analysis was used to determine the strongest predictors of serum 25(OH)D levels, which were found to be sun exposure, dietary vitamin D intake, skin reflectance, age, BMI, and ethnicity (R2 = 0.58 , p = 0.0031), demonstrating that simple questionnaires, such as those employed in this study, can help to predict serum 25(OH)D status and thus be considered in the future treatment of vitamin D deficiency.

Background: Body fat distribution, in particular visceral adipose tissue (VAT), contributes to risk of cardiovascular disease (CVD). The Multicultural-Community Health Assessment Trial (M-CHAT) reported that South Asians have greater VAT than Europeans despite similar BMIs, putting them at greater risk of CVD. However, the molecular mechanisms underlying ethnic-specific differences in body fat distribution are unclear. Low circulating 25-hydroxyvitamin D (25OHD) and adiponectin concentrations are prevalent in individuals with obesity (BMI ≥ 30kg/m²), and are associated with increased risk of CVD. Furthermore, 25OHD is inversely associated with blood pressure. Adiponectin is an adipokine that has insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties. Adiponectin circulates as isoforms low (LMW), medium (MMW), and the reported most biologically active isoform, high (HMW) molecular weight. This thesis aims to investigate ethnic-specific differences in the relationship between plasma 25OHD and adiponectin concentrations with body fat distribution and CVD risk factors. Methods/Results: Europeans (n=171) and South Asians (n=176) from the M-CHAT cohort were assessed for demographics, plasma 25OHD, total and HMW adiponectin concentrations, and CVD risk factors. A computed tomography (CT) scan was used to quantify VAT and subcutaneous adipose tissue (SAT) deposition. South Asians had lower (p < 0.001) 25OHD in comparison to the Europeans (63.0 nmol/L vs. 39 nmol/L, respectively). VAT was inversely associated (p < 0.05) with 25OHD even after adjustment for age, sex, BMI, season of blood collection, SAT and total body fat (%). This suggests that VAT mediates the relationship between plasma 25OHD and CVD risk. Furthermore, the inverse association between systolic and diastolic blood pressure and 25OHD was no longer significant after adjustment for VAT. However, circulating plasma adiponectin concentrations remained strongly associated with fasting plasma HDL-cholesterol, triglycerides, insulin, and HOMA-insulin resistance (HOMA-IR), even after adjustment for VAT. Interestingly, South Asians also had lower (p<0.001) total and HMW adiponectin concentrations compared to Europeans. Conclusion: These findings demonstrate that plasma 25OHD and total and HMW adiponectin concentrations are associated with VAT deposition in Europeans and South Asians. Furthermore, plasma 25OHD and total and HMW adiponectin concentrations are lower in South Asians than the Europeans, which may contribute to elevated CVD risk in South Asians.

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In addition to the importance of vitamin D for bone health, is of great interest to elucidate its relationship with obesity. The objective of this study was to examine the relationship between habitual dietary intake of vitamin D and body weight in all age groups of the same population. A cross-sectional population-based study, involving 866 individuals from a city in northeastern Brazil. Demographic data were collected and 24-hour recalls, and held anthropometric assessment. The adequacy of nutrients was estimated by adjusting the person variance of nutrient intake. Applied to multiple regression between variables. In the total sample, 45.27% of the participants were overweight or obese. The average habitual intake of vitamin D is approximately 2mg. There was a relationship between habitual dietary intake of vitamin D and body weight in the total sample (t = -2.34, p = 0.019), in adolescents (t = -2.51, p = 0.012) and adults (t = -2.75, p = 0.006). For children and the elderly these relationships were observed. The existence of a relationship between habitual dietary intake of vitamin D and body weight in adolescents and adults but not in children and the elderly, suggests that those most vulnerable age groups the metabolic pathways of vitamin D, which may favor weight loss, are not being stimulated or active, although the intake of children was higher and the elderly similar to the other groups.
Além da importância da vitamina D para a saúde óssea, é de grande interesse elucidar sua relação com a obesidade. O objetivo deste estudo foi examinar a relação entre o consumo alimentar habitual de vitamina D e o peso corporal em todos os grupos etários de uma mesma população. Estudo epidemiológico transversal de base populacional, envolvendo 866 indivíduos de um município do nordeste do Brasil. Foram coletados dados demográficos e recordatórios de 24 horas, e realizou-se a avaliação antropométrica. A adequação de nutrientes foi estimada ajustando a variância intrapessoal da ingestão de nutrientes. Aplicou-se a regressão múltipla entre as variáveis estudadas. Na amostra total, 45,27% dos participantes apresentavam sobrepeso ou obesidade. A média de ingestão habitual de vitamina D foi aproximadamente 2μg. Houve relação entre consumo alimentar habitual de vitamina D e peso corporal na amostra total (t=-2,34; p=0,019), no grupo de adolescentes (t=-2,51; p=0,012) e de adultos (t=-2,75; p=0,006). Para as crianças e idosos estas relações não foram observadas. A existência de relação entre consumo alimentar habitual de vitamina D e peso corporal em adolescentes e adultos, mas não em crianças e idosos, sugere que nesses grupos etários mais vulneráveis as vias metabólicas da vitamina D, que provavelmente favorecem a perda de peso, não estão sendo estimuladas ou atuantes, embora o consumo das crianças foi superior e o dos idosos semelhante aos demais grupos.

OBJECTIVE: To examine the relationships between socioeconomic status (SES), body mass index (BMI), and vitamin D levels in African American (AA) women living in areas with abundant sunshine; and to explore if diabetes moderates these relationships. SIGNIFICANCE: More AA's live in poverty, and experience obesity, diabetes, and chronic disease compared to other groups. Eighty percent of AA women are overweight or obese, and rates of type 2 diabetes is highest in this group. Minority race, obesity, and diabetes increase risks for low vitamin D, and are associated with p DESIGN AND METHOD: A cross-sectional descriptive research design was used to examine the specified relationships. Data from 611 non-pregnant AA women ≥ age 20 from the National Health and Nutrition Examination Survey (NHANES) cycles 2003 - 2006 were studied. SES was measured as poverty to income ratio (PIR), education level, and annual household income. Mean ± SD for BMI was 31 ± 8, and 14ng/ml ± 7ng/ml for vitamin D level. Only 8% of the sample had diabetes (n = 49). One hundred-eighty lived in areas with abundant sunshine. RESULTS: BMI independently predicted the vitamin D level without regard for SES, or geographical locale. Vitamin D supplement use emerged as an independent predictor of vitamin D on covariate analysis. SES did not explain significant variation in the vitamin D level. A moderating influence of diabetes could not be determined. CONCLUSIONS: BMI inversely predicts vitamin D level independent of geographic locale in AA women. Ethno/cultural measures to reduce BMI should be standard in caring for AA women which may affect vitamin D level and/or reduce morbidity and mortality in this group. Persons with low vitamin D suffer with more adverse health outcomes, and future research should examine if vitamin D deficiency accelerates risks for poor health outcomes where BMI is high.

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate the expression of genes involved in all physiological activities. Disruption in NR function (e.g. mutations) can lead to a variety of diseases; making these receptors important targets for drug discovery. The ability to bind a broad range of 'drug-like' molecules also make these receptors attractive candidates for protein engineering, such that they can be engineered to bind novel small molecule ligands, for several applications. One application is the creation of potential molecular switches, tools that can be used for controlling gene expression. Gaining knowledge of specific molecular interactions that occur between a receptor and its ligand is of interest, as they contribute towards the activation or repression of target genes. The focus of this work has been to investigate the structural and functional relationships between the human vitamin D receptor (hVDR) and its ligands. To date, mutational assessments of the hVDR have focused on alanine scanning and residues typically lining the ligand binding pocket (LBP)that are involved in direct interactions with the ligand. A comprehensive analysis of the tolerance of these residues in the binding and activation of the receptor by its ligands has not been performed. Furthermore, residues not in contact with the ligand or that do not line the LBP may also play an important role in determining the activation profiles observed for NRs, and therefore need to be explored further. In order to engineer and use the hVDR in chemical complementation, a genetic selection system in which the survival of yeast is linked to the activation of a NR by an agonist, the hVDR gene was isolated from cDNA. To gain insight into how chemical and physical changes within the ligand binding domain (LBD) affect receptor-ligand interactions, libraries of hVDR variants exploring the role and tolerance of hVDR residues were created. To develop a comprehensive mutational analysis while also engineering the hVDR to bind a novel small molecule ligand, a rational and a random mutagenic approach were used to create the libraries. A variant, hVDRC410Y, that displayed enhanced activity with lithocholic acid (LCA), a known hVDR ligand, and novel activation with cholecalciferol (chole), a precursor of the hVDR's natural ligand known not to activate the wild-type hVDR, was discovered. The presence of a tyrosine at the C410 position resulting in novel activation profiles with both LCA and chole, and the fact that this residue does not line the hVDR's LBP led to interest in determining whether a physical or chemical property of the residue was responsible for the observed activity. When residue C410 was further assessed for its tolerance to varying amino acids, the results indicated that bulkiness at this end of the pocket is important for activation with these ligands. Both LCA and chole have reduced molecular volumes compared to the natural ligand, 1alpha, 25(OH)2D3. As a result, increased bulkiness at the C410 position may contribute additional molecular interactions between the receptor and ligands. Results obtained throughout this work suggest that the end of the hVDR's LBP consisting of two ligand anchoring residues, H305 and H397, and residue C410 tolerates structural variations, as numerous variants with mutations at these positions displayed enhanced activity. The receptor contains two tyrosines, Y143 and Y147, which were targeted for mutagenesis in one of the rationally designed libraries, located at the exact opposite end of the pocket. In an effort to gain further insight into the role of these residues at the other end of the LBP, mutagenesis assessing the tolerance of tyrosines 143 and 147 was performed. Overall, most changes at these positions proved to be detrimental to the function of the receptor supporting the hypothesis that this end of the LBP is less tolerant of structural changes, compared to the opposite end consisting of residues H305, H397 and C410. Overall, a better understanding of the structural and functional relationships between the human vitamin D receptor (hVDR) and its ligands was achieved. The effects of residue C410 on specificity and activation with the different ligands studied were unforeseen, as this residue does not line the receptor's ligand binding pocket (LBP). However, they serve as an example of the significant impact distant residues can have on receptor activation and also emphasize the important role physical properties of residues, such as volume, can play for specific ends of the LBP compared to chemical properties.

Menopause is an important period for bone health in women. Objective: To assess the determinants of bone mineral density (BMD) changes in women transitioning to menopause. Method: A secondary data analysis of the MONET (Montreal-Ottawa New Emerging Team) study. Outcome measures included yearly assessment of menopause status, body composition, BMD, physical activity energy expenditure (PAEE) and dietary calcium and vitamin D intakes. Results: 84 of the original 102 women had complete data for the purpose of the present study. Repeated measures analysis revealed significant decreases in lumbar spine and femoral neck BMD (P< 0.01). Regression analysis revealed that baseline femoral neck BMD, changes in PAEE and trunk fat explained 31% of the variation of BMD changes at the femoral neck, while changes in both PAEE and trunk fat account for 27% of BMD change at lumbar spine. Conclusion: Baseline femoral neck and changes in physical activity energy expenditure and trunk fat are determinants of the reduction of bone mineral density in women transitioning to menopause.

Objective: This study was conducted to investigate the relationship between hip bone mineral density (BMD), fat free mass (FFM), fat mass (FM), and total body mass (TBM) and the extent to which these relationships were modified by various confounding factors. The cross-sectional analysis included 262 healthy females (mean age 41.6±3.0 years). Methods: BMD of the hip and body composition were assessed by the Hologic 4500W dual energy x-ray absorptiometry (DXA) system. Total and intensity of physical activity (PA) were objectively measured using an Actigraph accelerometer. Dietary calcium and vitamin D from food and beverages, as well as from supplements, were measured separately using the Block food frequency questionnaire. Menopause status and prescription bone drug use were measured by a questionnaire. Results: The relationship between FFM and hip BMD was strong and robust (F=24.5, P<0.0001). Using the pooled standard deviation revealed a large effect size of 1.2 when comparing hip BMD of women with low FFM and high FFM. Potentially confounding variables, considered individually and collectively, did not change this relationship. The association between FM and hip BMD was also substantial (F=9.9, P<0.0001) and remained significant when controlling for all potentially confounding variables, except differences in FFM. The relationship between TBM and hip BMD was also strong and dose-response (F=21.5, P<0.0001) and remained significant, except when differences in FFM were controlled. Conclusion: The relationships between body mass (total, fat, and fat free) and BMD of the hip in middle-age women are strong and significant. The associations are not influenced by differences in age, height, menopause status, calcium or vitamin D intake, volume or intensity of PA, or the use of bone enhancing prescription drugs. The findings suggest that women with low body mass, particularly low FFM, tend to have low hip BMD and there is little that can be done to change this association.

Pastarąjį dešimtmetį nustatyta, kad vitaminas D dalyvauja ne tik skeleto sistemos metaboliniuose procesuose, bet jo trūkumas siejamas ir su įvairiomis kitomis patologinėmis būsenomis, nes daugumoje organizmo ląstelių yra išsidėstę vitamino D receptoriai. Įvertinę šią vitamino D svarbą, epideminio pobūdžio jo trūkumą įvairiose šalyse bei tai, kad iki šiol panašaus pobūdžio mokslinių tyrimų mūsų šalyje neatlikta, nuspendėme įvertinti jaunų vyrų – Lietuvos kariuomenės šauktinių – vitamino D koncentracijos, kūno sandaros, endokrininės, psichologinės būklės ir gyvenimo kokybės rodiklių tarpusavio sąsajas. Daugumai tirtųjų nustatytas ženklus vitamino D trūkumas (95 proc. tyrimo pradžioje ir 96,7 proc. tyrimo pabaigoje). Tyrimo pabaigoje buvo nustatytas didesnis vitamino D trūkumas, kuris sąlygojo reikšmingą prieskydinių liaukų hormono koncentracijos padidėjimą, tačiau osteokalcino koncentracija reikšmingai nesikeitė. Taip pat nustatyta, kad didesnė vitamino D koncentracija teigiamai koreliuoja su didesne raumenų ir liesąja kūno mase, o tiems, kuriems nustatytas ryškus vitamino D trūkumas (≤10 ng/ml), būdinga mažesnė testosterono koncentracija. Be to, nustatyta, kad mažesnė vitamino D koncentracija sąlygoja depresiškumą–liūdesį ir įtampą–nerimą bei blogesnę psichologinę ir fizinę gyvenimo kokybę. Reikšmingų vitamino D koncentracijos ir pažintinių funkcijų tarpusavio ryšių bei sąsajų su tirtais stresiniais hormonais (kortizoliu, prolaktinu, tireotropiniu hormonu) nenustatyta.
Over the last decade it has been established that vitamin D is involved not only in the skeletal system metabolic processes, but its deficiency is associated with a variety of other pathological conditions, because vitamin D receptors are located in most of the body cells. Taking into consideration the importance of vitamin D, epidemic deficiency in different countries worlwide and the fact that similar studies in our country have not been performed yet, we evaluated vitamin D levels, body composition, endocrine, psychological status and quality of life in young men - Lithuanian army conscripts. Vitamin D deficiency was determined in the majority of the studied young men (95% at the beginning and 96.7% at the end of the study). There was a greater vitamin D deficiency determined at the end of the study, which conditioned a significant increase in parathyroid hormone concentration; however, there were no significant changes in the osteocalcin concentration observed. Vitamin D deficiency correlated with a smaller amount of lean body and muscle mass. A significantly smaller testosterone concentration was determined in the group of a lower vitamin D concentration (≤10 ng/mL). It was determined that a lower vitamin D concentration conditioned depression-sadness and tension-anxiety as well as psychological and physical life quality. No significant correlations between vitamin D concentration and cognitive functions, concentrations of cortisol, prolactin and thyreotropic hormone... [to full text]

O tecido ósseo é extremamente complexo que, juntamente com a cartilagem, constitui o sistema esquelético. Tanto os ossos quanto a cartilagem são compostos por tecido metabolicamente ativo com duas funções básicas para o organismo, uma mecânica e outra bioquímica. O impacto do déficit calórico e da perda de peso pode reduzir a massa óssea e mudar a composição corpórea. Na pancreatite crônica alcoólica o paciente relata ingestão alcoólica por longo período, além da referência do alto consumo de cigarros e de uma alimentação deficiente. Os objetivos do presente estudo foram avaliar a frequência da doença osteometabólica, os hábitos alimentares, a frequência de deficiência de vitamina D assim como, se os achados de massa corpórea por densitometria de corpo total se relacionam à deficiência de massa óssea, em indivíduos portadores de pancreatite crônica de etiologia alcoólica. Foram avaliados três grupos de pacientes do sexo masculino com pancreatite crônica alcoólica. Foram divididos de acordo com o resultado da densitometria óssea: 5 pacientes no grupo da osteoporose, 26 no grupo da osteopenia e 8 no grupo normal. Todos os pacientes foram submetidos ao registro alimentar de três dias, mensuração de peso, altura, cintura e quadril, Índice de Massa Corpórea (IMC) e exames laboratoriais. A composição corpórea foi avaliada pela densitometria óssea por raios X de dupla energia (DXA) e por bioimpedância elétrica. 79% dos pacientes do sexo masculino com pancreatite crônica alcoólica tiveram densidade mineral óssea comprometida. Os pacientes que tinham vitamina D prescrita foram excluídos porém nos nossos resultados a maioria dos pacientes apresentavam níveis normais da vitamina. Em relação ao tabagismos, dos pacientes fumavam. Os pacientes com maior comprometimento ósseo eram mais magros,contudo, não houve diferença entre os pacientes de acordo com o IMC. Os pacientes classificados pelo DXA como normais eram mais jovens do que os pacientes com osteopenia e osteoporose. Em síntese, a osteoporose e osteopenia são fontes subvalorizadas de morbidade em pacientes com pancreatites crônicas sendo necessárias diretrizes de gestão de saúde óssea neste grupo de pacientes
The bone tissue is extremely complex, along with cartilage constitutes the skeletal system. Both bones as cartilage are composed of metabolically active tissue with two basic functions for the body, mechanical and biochemistry. The impact of the caloric deficit and weight loss can reduce bone mass and change body composition. In chronic alcoholic pancreatitis patients alcohol intake over a long period, in addition to reference the high consumption of cigarettes and poor nutrition. The objectives were to evaluate the frequency of osteometabolic disease, eating habits, the frequency of vitamin D deficiency and how the body mass found by total body densitometry relate to bone deficiency in individuals with chronic pancreatitis of alcoholic etiology . We evaluated three groups of male patients with chronic pancreatitis alcoholic. They were according to the results of bone densitometry. 5 in osteoporosis group, 26 in the osteopenia group and 8 in the normal group. All patients underwent three-day food record, measurements of weight, height, waist and hip, body mass index (BMI) and laboratory tests. The body composition was evaluated by densitometry by dual energy X-ray absorptiometry (DXA) and electrical bioimpedance. 79% of male patients with alcoholic chronic pancreatitis had compromised bone mineral density. Patients were prescribed vitamin D were excluded however results in the majority of patients had normal levels of the vitamin. Half of all patients smoking. Patients with higher bone involvement were thinner, there was no difference between patients according to BMI. Patients classified as normal by DXA were younger than patients with osteopenia and osteoporosis. In summary, osteoporosis and osteopenia are undervalued sources of morbidity in patients with chronic pancreatitis and necessary health management guidelines bone in this group of patients

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Objetivos: Avaliar os efeitos de 6 meses de suplementação com colecalciferol e cálcio sobre o metabolismo mineral e sobre os parâmetros de força muscular de membros inferiores, oscilação postural e mobilidade funcional. Desenho do Estudo: Ensaio clínico prospectivo, randomizado, duplo-cego, placebocontrolado. Local de realização: Duas instituições de longa permanência para idosos, em São Paulo - SP, Brasil. Participantes: 56 idosos de ambos os sexos (12 homens e 44 mulheres), com 60 anos de idade ou mais (mediana=77,6; limites=62-94 anos). Métodos: Os pacientes foram randomizados em Grupo-Ca (n=28) para placebo, ou Grupo-Ca+D (n=28) para colecalciferol. Todos os participantes receberam 1000 mg/dia de cálcio. O Grupo-Ca+D recebeu colecalciferol oral nas doses de 150.000 UI/ mês durante os 2 primeiros meses de estudo e 90.000 UI/mês nos 4 meses subseqüentes, correspondendo a uma dose mensal de 3670 UI/dia em média, de Dezembro-2004 a Maio-2005. Níveis séricos de 25-Hidroxivitamina D (25OHD), paratormônio intacto (PTH) e cálcio foram mensurados no início do estudo (M1), 2 meses (M2) e 6 meses (M3) após tratamento. Os testes neuromusculares foram realizados antes do início da intervenção e repetidos após o fim do tratamento. A força muscular dos membros inferiores foi avaliada através de um índice de força muscular (IFM), incluindo a força dos músculos flexores do quadril e extensores do joelho, mensurada por dinamômetro mecânico portátil. Para avaliar a oscilação postural foi criado um índice (IOP) a partir da mensuração da oscilação do corpo nos diâmetros sagital e frontal ao nível da cintura. A mobilidade funcional foi mensurada através dos testes “Timed Up&Go” (TUG) e alcance funcional (TAF). Resultados: A 25OHD sérica aumentou em ambos os grupos no M2, porém mais no Grupo-Ca+D do que no Grupo-Ca (OR=2,2; 95%IC=1,98-2,4 vs. OR=1,76; 95%IC=1.55-1.99, respectivamente). No M3, os níveis de 25OHD declinaram apenas no Grupo-Ca, contudo, o PTH sérico diminuiu no M2 (p<0.0001) e retornou aos valores basais no M3 (p<0.0001) igualmente nos dois grupos. Antes do tratamento, deficiência/insuficiência de 25OHD (<50 nmol/L) afetava 67,9% do total de participantes. No M3, nenhum paciente do Grupo-Ca+D, mas 40% dos pacientes do Grupo-Ca tinham deficiência/insuficiência de 25OHD. Hipercalcemia não foi detectada em nenhum paciente. Apenas no Grupo-Ca+D, o IFM teve um aumento de 20% no M3 (OR=1,20; 95%IC=1,12-1,29), enquanto que IOP e TAF aumentaram igualmente nos dois grupos, provavelmente porque os pacientes de ambos os grupos aumentaram sua exposição solar durante o verão. Conclusões: A suplementação com colecalciferol e cálcio foi segura e efetiva em aumentar os níveis séricos de 25OHD, reduzir a prevalência de deficiência/insuficiência de 25OHD e aumentar a força muscular de membros inferiores nos idosos do grupo tratado. Palavras-chave: 25-Hidroxivitamina D, colecalciferol, idosos, força muscular, oscilação postural, mobilidade funcional.
Objectives: To assess the effects of a 6-month supplementation with vitamin D and calcium on mineral metabolism and parameters of lower-extremity muscle-strength, body sway (BS) and functional mobility, measured by the Functional Reach Test (FRT) and Timed Up&Go test (TUG). Design: Prospective, double-blind, placebo-controlled trial. Setting: Institutionalized elderly of two long-stay geriatric care units of São Paulo-SP, Brazil. Participants: 56 elderly volunteers of both genders (12 men and 44 women) of ages 60 and older (median=77.6; range=62-94 years). Methods: Subjects were randomized into a Ca-group (n=28) to receive placebo or a Ca+D-group (n=28) to receive cholecalciferol. All participants received 1,000 mg/day of calcium. Laboratory measurements were performed at baseline (M1), 2 moths (M2) and 6 months (M3) after intervention. The Ca+D-group received oral cholecalciferol on a monthly basis (3670 IU/day on average, from December-2004 to May-2005). Neuromuscular measurements were performed at baseline and 6 months. Results: Serum 25(OH)D increased in both groups at M2, but more so in the Ca+Dgroup than in the Ca-group (OR=2.2, 95%CI=1.98-2.4 vs. OR=1.76, 95%CI=1.55- 1.99, respectively). At M3, 25(OH)D levels declined only in the Ca-group. Nevertheless, serum PTH diminished at M2 (p<0.0001) and went back to baseline levels at M3 (p<0.0001) equally in both groups. Before treatment, 25(OH)D deficiency/insufficiency (<50 nmol/liter) affected 67.9% of the entire group. At M3, no patient in the Ca+D-group, but 40% of the Ca-group patients had 25(OH)D deficiency/insufficiency. Hypercalcemia was not detected at any time. The odds of improving lower-extremity muscle strength increased by 20% (OR=1.20, 95%CI=1.12-1.29) only in the Ca+D-group, whereas BS and FRT increased equally in both groups, probably because the study was conducted during the summer. Conclusions: The supplementation with calcium and supra-physiological doses of cholecalciferol was safe and effective in enhancing 25(OH)D levels, reducing the prevalence of 25(OH)D insufficiency, and increasing lower-extremity muscle strength in institutionalized elderly.
FAPESP: 03/13194-6
BV UNIFESP: Teses e dissertações

Orientador: Jacqueline Costa Teixeira Caramori
Resumo: Background: function and muscle mass depletion is frequent in hemodialysis patients, as well as vitamin D deficiency. Vitamin D supplementation exerts positive effects on muscles, and clinical trials combining vitamin D supplementation and physical training have promoted improvements on functional capacity and muscle quality in elderly. Objective: to assess the effects of vitamin D supplementation and intradialytic aerobic training (IDAT) on biochemical parameters, body composition, and muscle function in patients on maintenance hemodialysis. Methods: clinical trial with two arms: randomized, controlled, and double-blind for vitamin D, and randomized, controlled and open-label for IDAT. Patients were randomized in one of the four groups: vitamin D supplementation and IDAT, placebo and IDAT, vitamin D supplementation, and placebo. Muscle mass was assessed by dual-energy X-ray absorptiometry and muscle function was assessed by handgrip strength. Intervention lasted 16 weeks. IDAT program was performed using cycle ergometer, three times a week during hemodialysis session. Vitamin D supplementation was cholecalciferol 50,000 IU per week and vitamin D status was evaluated by serum 25-hydroxyvitamin D (25(OH)D) levels. Results: twenty-nine patients were enrolled in this trial. Nine were excluded during the intervention. Serum vitamin D significantly rose in both groups supplemented with cholecalciferol (baseline: 30.1 ± 6.26 ng/ml; post-intervention: 41.3 ± 9.85 ng/ml; p<0.001). Th... (Resumo completo, clicar acesso eletrônico abaixo)
Doutor

Ormarsdóttir, S. 2001. Osteoporosis in Chronic Liver Disease. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1037. 60 pp. Uppsala. ISBN 91-554-5021-0.

Osteoporosis is a well-known and frequently reported complication of chronic liver disease (CLD) with a high fracture rate contributing to significant morbidity after liver transplantation. The pathogenesis is unknown and controversy exists about many risk factors for osteoporosis in CLD.

In the present thesis, bone mineral density (BMD) was found to be significantly lower at the lumbar spine (p<0.01) in a cohort of patients with CLD compared with age- and gender -matched individuals. Osteoporosis was found in 30% of the patients and 15% of the controls, respectively. Low body mass index (BMI), corticosteroid treatment, prothrombin time, age and female gender were independent risk factors for osteoporosis in the patients.

In a follow-up study, 43 of 72 patients were available for a second BMD measurement 25 months (median) after the first. Bone loss at the femoral neck was 1.5 ± 2.4% in females and 2.9 ± 2.0% in males with a significant decrease in BMD Z-score over time (p=0.005 and p=0.02 for females and males, respectively), indicating increased bone loss at this site. Hyperbilirubinaemia and low circulating levels of 25-hydroxy vitamin D₃ predicted increased bone loss at the femoral neck. These findings suggest that cortical bone, in addition to trabecular bone, may be affected in CLD and bilirubin and vitamin D₃ may be involved in the pathophysiology of osteoporosis in CLD.

In order to elucidate the suggested role of insulin-like growth factors (IGFs) and leptin in the pathophysiology of osteoporosis in CLD, we studied the relationship between these factors and BMD. Levels of IGFs were extremely low (p<0.0001 compared with the controls) and related to liver function but no correlation was found between the IGFs and BMD. Serum leptin adjusted for BMI correlated negatively with BMD in female patients (p=0.003 and p=0.04 at the lumbar spine and the femoral neck, respectively) and in male patients at the femoral neck (p=0.04). Thus, the IGFs appear not to be involved in the pathophysiology of osteoporosis in CLD but a role of circulating leptin is possible.

A 700bp portion of the promoter of CYP2D25, the porcine microsomal vitamin D 25-hydroxylase was isolated and sequenced. The computer analysis of the sequence revealed the existence of a putative VDRE at 220 bp upstream of the transcription start site. A CYP2D25 promoter-luciferase reporter plasmid was constructed in order to study the transcriptional regulation of the gene. Treatment with the vitamin D metabolites calcidiol and calcitriol suppressed the promoter, provided that the nuclear receptors VDR and RXR were overexpressed. Phenobarbital was also capable of suppressing the promoter if the nuclear receptors PXR or CAR were overexpressed. The 25-hydroxylases are not expressed solely in liver but in a wide array of other organs as well. It is therefore possible at least in theory to study the vitamin D 25-hydroxylation in human subjects using cells from extrahepatic organs, from which biopsy retrieval is easier than from the liver. Dermal fibroblasts are frequently used to study different pathological conditions in human subjects and they are easy to come by. Dermal fibroblasts were shown to express two vitamin D 25-hydroxylases: CYP27A1 and CYP2R1. The expression pattern of CYP2R1 displayed considerable interindividual variation. The fibroblasts were also capable of measurable vitamin D 25-hydroxylation, which makes dermal fibroblasts a possible tool in studying vitamin D 25-hydroxylation in human subjects. Little is known about the regulation of expression and activity of the human vitamin D 25-hydroxylases. Therefore dermal fibroblasts – expressing CYP2R1 and CYP27A1 – and human prostate cancer LNCaP cells, that express CYP2R1 and CYP2J2, were treated with calcitriol and phenobarbital and efavirenz, two drugs that give rise to vitamin D deficiency. Treatment decreased the mRNA levels of CYP2R1 and CYP2J2 provided that the treated cells also expressed the necessary nuclear receptors. CYP27A1 did not respond to any of the treatments. The treatments also managed to decrease the 25-hydroxylating activity of the cells. The results show that vitamin D 25-hydroxylases can be regulated by both endogenous and xenobiotic compounds.

Background Vitamin supplements are commonly used in women of reproductive age. There is a range of vitamin supplements such as iron, folate, vitamin B and vitamin D that are used. Deficiencies in vitamin D can result in adverse health outcomes, such as exacerbation of asthma and fractures. Some studies suggest that vitamin D deficiency may be associated with increases in depressive symptoms and severity. These associations need further exploration to ascertain confirmation, with more vigorous research. Furthermore, there has been limited research on the reasons behind vitamin supplement use in women of reproductive age who originate from culturally and linguistically diverse (CALD) populations. These need further exploration to examine the beliefs, attitudes and practices of women regarding vitamin supplement use. Aims and Objectives Aims: To explore vitamin supplements use in women of reproductive age in terms of their beliefs, attitudes and practices particularly in CALD communities, with a focus on vitamin D and its potential role in depression in women of reproductive age. Objectives: 1) To investigate any association of vitamin D deficiency with depression in women of reproductive age. 2) To examine whether vitamin D supplementation results in a decrease depressive symptoms and severity. 3) To explore the beliefs, attitudes and practices of women of reproductive age, including those from CALD backgrounds, in relation to vitamin supplement use. 4) To explore the beliefs, attitudes and practices of CALD women regarding the Hijab and vitamin D. Content of this thesis This thesis is made up of four chapters. Chapter 1 contains the background. The challenges identified in Chapter 1 led to the exploration of the effect of vitamin D on depression in women of reproductive age via a systematic review in Chapter 2. The qualitative study in Chapter 3 describes the factors behind the beliefs, attitudes and practices of women of reproductive age in terms of vitamin supplement use. Lastly Chapter 4 presents general discussion and conclusions from the work described in this thesis. Methods A systematic review was conducted to investigate the effect of vitamin D on depression in women of reproductive age based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement checklist (Chapter 2). A systematic search strategy was deployed in ten databases including Medline, EMBASE, PsycINFO, CINAHL, AMED, International pharmaceutical abstracts, Maternal and infant care, EBM ALL, Global health, and PubMed to identify primary studies that met eligibility criteria. A qualitative study using semi-structured interviews was undertaken to explore the use of vitamin supplements in women of reproductive age. A semi-structured interview guide was developed and applied to facilitate the interview. Participants were recruited through advertisements in pharmacies, medical centres and community centres as well as via the distribution of flyers across a large university campus in Sydney, through social media, word of mouth and snowball sampling. Interviews were audio-recorded and transcribed. Interviews were conducted until thematic saturation was achieved and data was analysed. NVivo12 Plus Qualitative Data Analysis software (QSR International Pty Ltd. Version 12, 2019) was used to analyse the emerging themes. Initial codes were highlighted and organised into general themes and sub-themes, which were reviewed and refined. Results Chapter 2 Systematic review identified a total of 2377 studies through comprehensive search and search of cited references. After removing duplicates and based on title and abstract screening, 128 studies remained. Full text review yielded 21 observational studies (11 cohort studies and 10 cross-sectional studies) that assessed the association between vitamin D deficiency and depression and two intervention studies (two RCTs) that investigated women of reproductive age of 15-49 years in US, Australia, New Zealand, Asia, Europe, Middle East and South America. Two cohort studies that showed no difference in depression scores in relation to vitamin D, while 9 other cohort studies reported that after measuring participants’ depression scores and vitamin D level over time, lower vitamin D levels were associated with higher depression scores. Similarly, there were two cross sectional studies that did not find an association between vitamin D level and depression scores. However, eight other cross-sectional studies showed that low vitamin D levels were linked with higher depression scores. One RCT did not find any improvement in depression symptoms and severity based on the supplementation of vitamin D used. Another RCT showed a reduction in depression scores compared to controls. Chapter 3 Semi-structured interviews were conducted with 25 women aged 19-49 years old, all from CALD backgrounds. The beliefs, attitudes and practices regarding the use of vitamin supplements of women from CALD backgrounds were explored. Thematic analysis generated four main themes: 1) health literary 2) cultural factors that influence vitamin supplement use 3) life circumstances and 4) women’s perception of health outcomes. Health literacy and information sources were key factors that affected women’s decision-making about taking vitamin supplements; and sources such as Google were heavily relied upon. Moreover, cultural factors greatly influenced women’s initiation of vitamin supplement therapy. There were discrepancies regarding the impact of wearing the Hijab on vitamin D status and more research in this area is needed. Conclusion Prior to this research, there has been limited data on CALD women of reproductive age and their beliefs, attitudes and practices in terms of vitamin supplement usage. This body of research was the first to explore the use of vitamin supplements in women of reproductive age particularly from CALD backgrounds. Furthermore, it was also one of the few studies around the world that examined the effect of vitamin D on depression in women of reproductive age. Findings from this body of work demonstrated the reoccurring themes that shaped women’s beliefs, attitudes and practices towards vitamin supplement use specifically include health literacy, cultural factors, life circumstances and women’s perception of health outcomes. This study also ascertained that CALD women of reproductive age had differing levels of health literacy and use of a range of information sources. This study also highlighted differing views regarding the practice of Hijab and rate of vitamin D supplementation. In addition, this study provides a basis for further studies to explore whether the practice of Hijab affects vitamin D levels, which has consequences for recommendations around vitamin D supplementation in countries where the Hijab is commonly worn. There was an indication of an association between vitamin D deficiency and depression symptoms and severity from this research. However, the exact clinical association in terms of vitamin D being a causal factor in developing depression remains unclear. Supplementation with vitamin D that results in changing status from vitamin D deficient to vitamin D sufficient warrants further investigation, specifically to ascertain whether an optimal level is needed to achieve a reduction in depressive symptoms and severity. Thesis overview This thesis presents an analysis of previous research on the role of vitamin D deficiency in depression in women of reproductive age. It explores the role of supplementation with vitamin D on depression symptoms and severity. It also investigates the beliefs, attitudes and practices of women of reproductive age regarding their vitamin supplements usage. It examines the motivations behind usage in women particularly those from CALD backgrounds. Rationale for this study Vitamin D deficiency is common throughout the world, including Australia which has ample sunlight all year round. Low vitamin D status has been associated with multiple adverse health outcomes, one of which is depression (1). Consensus around the optimal level of vitamin D for women of reproductive age remains to be reached. It is critical to establish if a relationship between vitamin D levels and depression exists and what that relationship is in women of reproductive age. In order to evaluate this association, a systematic review of past studies was undertaken to examine the effect of vitamin D on depression in women of reproductive age. This is further discussed in Chapter 2 of this thesis. Similarly, vitamin supplementation use has grown in the last decade worldwide and in Australia (2). This may be due to increased advertising and availability, cultural influences, affordability and increase in the use of social media platforms. It is important to understand the beliefs, attitudes and cultural practices especially in women of reproductive age, around their use of vitamin supplements. In order to explore this research question, a qualitative study was undertaken to explore the use of vitamin supplements in women of reproductive age from CALD backgrounds. This is further discussed in Chapter 3 of this thesis. Research aim, objectives and research questions The overall aim of this project was to explore the use of vitamin supplements in women of reproductive age, with a focus on CALD communities as well as investigating vitamin D and its possible association with depression in women of reproductive age. The specific objectives of this research were to: • Evaluate the effect of vitamin D status on depression and depressive symptoms. • Explore the use of vitamin supplements in women of reproductive age, particularly in women of CALD backgrounds, with a particular focus on vitamin D • Describe the beliefs, attitudes, and practices of women of reproductive age, particularly women from CALD backgrounds, regarding vitamin supplement use. The research questions were: • Does vitamin D deficiency affect depression and depressive symptoms? • What level of vitamin D is needed to decrease depression severity and symptoms? • What level of vitamin D supplementation is required to increase level of vitamin D in order to decrease depression severity and symptoms? • What factors are involved when women of reproductive age initiate vitamin supplement use? • What are the beliefs, attitudes and practices of women of reproductive age around vitamin supplement use? • What are the beliefs and attitudes and practices of women from CALD backgrounds regarding vitamin supplement use? • What are the beliefs and practices of women from CALD backgrounds regarding the Hijab and its possible connection with vitamin D deficiency? Significance This research will contribute to the expanding body of knowledge related to vitamin D deficiency and depression as well as exploring vitamin supplement use in women of reproductive age particularly those from CALD backgrounds. It is the first study to systematically evaluate the effect of vitamin D on depression in women of reproductive age and explore the use of vitamin supplements in CALD women of reproductive age in Australia. This study complements current understanding of the links between vitamin D and depression as well as the differences in the beliefs, attitudes and practices of women from CALD backgrounds regarding vitamin supplement use. Considering existing evidence, public health interventions to decrease the prevalence of vitamin D deficiency in women of reproductive age in Australia are required, in addition to increasing awareness regarding the optimal vitamin D status in order to decrease the risk of depression and depressive symptoms. The identification of several motivating factors associated with vitamin supplement use in women of reproductive age and in particular those from CALD backgrounds is an important first step in future programs of public health research aimed at identifying and targeting culturally appropriate health related information that aides decision making when it comes to vitamin supplement use. This thesis investigates women’s use of vitamin supplements, vitamin D and its possible association with depression in women of reproductive age. The first chapter provides background information on vitamin supplements, vitamin D, depression and population characteristics. The second chapter examines the effect of vitamin D on depression in women of reproductive age in the form of a systematic review. The third chapter explores the use of vitamin supplements in women of reproductive age and in particular, women from CALD backgrounds through a qualitative study. The fourth chapter discusses the significance of all the findings, future research directions and conclusions.

The aim of this research was to apply analytical epidemiology to examine associations between hypertension and vitamin D status (serum 25-hydroxyvitamin D (25OHD)). The first objective was to appraise and synthesize the research evidence on the relationship between hypertension and 25OHD. The follow-up objective was to complete a sequence of studies exploring the association between hypertension and 25OHD in two populations with high hypertension and vitamin D deficiency rates, Finland and China. The results of the meta-analysis were that higher vitamin D levels were associated with lower hypertension rates. In a prospective study from Finland higher 25OHD levels at baseline were found to associate with less hypertension and a lower pulse rate. On follow-up only low pulse rate remained associated with higher 25OHD. A hypertension prevalence rate of 34% was reported from a cross-sectional survey in Macau 2012. Potentially modifiable predictors of hypertension were found to be smoking, obesity and lack of exercise, sunlight exposure and low intake of fish. Only 45% of this population on whom blood was collected were found to have sufficient vitamin D status (≥50 nmol/L). Young highly educated women were at greatest risk of not being sufficient. Higher sun exposure, fish intake and more physical activity and less sitting were associated with higher 25OHD levels. In the older population (≥55 years) higher 25OHD levels significantly predicted having either lower hypertension or lower pulse rates. The evidence from these series of studies indicates a small consistent association between vitamin D sufficiency and reduction in hypertension risk. These results are consistent with recent meta-analyses of observational studies. The unique finding from this study is that there is an age cohort differential with younger Chinese having lower vitamin D status and in a population with increasing hypertension this fact may have public health consequences in the future.

Little is known regarding the vitamin D status of Canadian youth. Our objectives were: (i) to describe the vitamin D status of Québec youth using a representative sample; (ii) examine the relative contributions of diet, physical activity and fat mass to the variance in plasma 25-hydroxyvitamin D{25(OH)D}, the best biomarker of vitamin D status; and (iii) examine the influence of household income and food insecurity on the intakes of dietary vitamin D, calcium and dairy foods.
To describe vitamin D status, we used data from a cross-sectional survey representative of Québec youth aged 9, 13 and 16, the Québec Child and Adolescent Health and Social Survey (QCAHS). For the second objective, 159 youth, aged 8-11 whose parents (at least one) were obese or had the metabolic syndrome were used for cross-sectional analysis in the Québec Adipose and Lifestyle InvesTigation in Youth (QUALITY). Fat mass was measured using Dual X-ray Absorptiometry (DXA) and physical activity was assessed by accelerometer. Finally, we analyzed data from the Canadian Community Health Survey (CCHS), a sample of 8960, 9-18-year-olds representative of Canadian youth for whom a single 24 hour dietary recall, measured height and weight, sociodemographic and information on food insecurity were available.
Greater than 90% of youth had sub-optimal vitamin D levels {plasma 25(OH)D < 75 nmol} at the end of winter and beginning of spring in both the QUALITY and QCAHS study. In the QCAHS study, older youth had a higher prevalence of vitamin D deficiency {25(OH)D < 27.5 nmol} (> 10%) than younger youth and girls from low income households had lower plasma 25(OH)D concentrations. In the QUALITY study, milk consumption and physical activity had modest associations with plasma 25(OH)D corresponding to 2.9 nmol/L and 2.1 nmol/L higher plasma 25(OH)D per standard deviation increase in these exposures, respectively. In the CCHS study, we found evidence that milk intake was being displaced by sweetened beverages amongst low income boys and food insecure girls.
Population wide measures to increase dietary vitamin D intake should be examined in Canadian youth.
Il y a peu de connaisances concernant le statut vitamin D des jeunes Canadiens. Nos objectifs étaient de: (i) décrire le statut vitamin D des jeunes Québécois en utilisant un échantillon représentatif; (ii) examiner la contribution de la diète, l'activité physique et l'adiposité a expliquer la variance du 25-hydroxyvitamin D, {25(OH)D.}, le meilleur biomarqueur du statut vitamine D; et (iii) examiner l'influence du statut socio-économique et l'insécurité alimentaire sur le consommation des produits laitiers, du calcium et de la vitamine D alimentaire.
Pour décrire le statut vitamine D on a utilisé les données transversales d'un échantillon représentatif des jeunes Québecois agés de 9, 13 et 16 ans. Pour le deuxième objectif, 159 jeunes, âgés 8-11 ans avec des parents (au moins un) qui étaient obèses ou avaient le syndrome métabolique etaient utilisés pour une analyse transversale dans l'étude Québec Adipose and Lifestyle InvesTigation in Youth (QUALITY). Le tissu adipeux a été mesuré avec le dual X-ray absorptiometry (DXA) et l'activité physique était mésurer par accéléromètre. Finalement, on a utilisé des données du Canadian Community Health Survey (CCHS), un échantillon de 8960 jeunes, agés de 9-18 ans qui avaient un rappel alimentaire de 24 heures, le poids et la taille mesuré, l'information sociodémograhique et le statut de sécurité alimentaire.
Dans l'étude QUALITY et le QCAHS plus de 90% des jeunes avaient un statut de vitamine D sub-optimal {plasma 25(OH)D < 75 nmol} à la fin de l'hiver et au début du printemps. Dans l'étude QCAHS, les adolescents avaient une prévalence de déficience de vitamine D élevé {25(OH)D < 27.5 nmol} (> 10%) et les filles venant des foyers défavorisés avait des niveaux de vitamine D plus bas. Dans l'étude QUALITY, un augmentation d'un écart-type de la consommation du lait et l'activité physique était associée avec une augmentation du niveau de vitamin D de 2.9 nmol/L and 2.1 nmol/L respectivement. Dans l'étude CCHS nous avons remarqué que les garçons de milieux défavorisés et les filles avec une insécurité alimentaire consommaient moins de lait et le lait étaitremplacé par les breuvages sucrés.
Des mesures pour augmenter la consommation de vitamine D parmi les jeunes Canadiens devraient être examinées.

Background: Older people presenting with hip fractures requiring surgery have a high prevalence of hypovitaminosis D, which is an important modifiable risk factor for falls and fractures. Inadequate sun exposure is the main reason for vitamin D deficiency in older people. Vitamin D supplements, with or without calcium have been shown to reduce falls and fracture risk in this population. Undertreated pain is a risk factor for delirium and a barrier to rehabilitation interventions following a hip fracture. A small number of randomised controlled trials (RCTs) have shown increased 25-OHD levels with a loading dose of vitamin D may improve falls and fractures. Low vitamin D levels have also been implicated in pain generally, as well as static and dynamic pain responses to mobility. It is not known whether oral vitamin D replenishment using a loading dose is effective, and if it is, what is the interplay this is with patient characteristics, in particular self-reported pain rating levels, lower limb mobility and 25-OHD levels. Aims: The aims of this research were (1) to characterise the predictive factors of 25-OHD levels; (2) to characterise the predictive factors of self-reported pain after hip fracture; (3) to determine the benefit of early loading-dose oral vitamin D replenishment and determine the 25-OHD response; (4) to evaluate safety profile of an initial high-dose (250,000IU) vitamin D followed by daily maintenance for 6 months; (5) to monitor its effects on functional mobility, falls, fractures, grip strength, health related quality of life and mortality. Methods: Participants of the REVITAHIP RCT cohort (mean age of 220 participants was 83.9 (SD 7.2) years and 77.1% were women): Active (111) and Placebo (107) participants were randomised to loading dose (250000IU vitamin D3) vs placebo followed by 6 months maintenance oral therapy (vitamin D3/calcium: 800IU/600mg) daily. Primary outcome measures are 2.4m gait-velocity, with secondary outcome measures of falls, fractures (Week-4), 25-OHD levels, quality-of-life measure (EQ-5D), mortality at weeks-2, 4 and 26 with additional measures of pain (via the numerical rating scale [NRS]) were correlated with patient characteristics in this cohort. Results: Hypovitaminosis D (25-OHD <50nmol/L) was present in 46.8% of participants and 15.4% had 25-OHD levels lower than 30nmol/L. Multivariate regression models demonstrated higher baseline vitamin D levels were significantly associated with higher premorbid Barthel Index scores and lower post-operative NRS pain levels. Further, the mean (SD) NRS pain score was 3.5 (2.3). More than half (61.9%, n=113) had NRS>3 and 18.1% (n=52) had NRS>5. Using the EQ-5D pain sub-score, 78.1% had moderate pain or discomfort and 7.9% had extreme pain or discomfort. Using a multivariate regression model, postoperative NRS was significantly higher in persons with a higher comorbidity count, those previously living independently alone, and surgical fixation with hemiarthroplasty. After loading dosing administration, 25-OHD levels were significantly higher for the Active group when compared to the Placebo group at 2 weeks (73 vs 66 nmol/L; p=.019) and at 4 weeks (83 vs 75nmol/L; p=.030). At week 4, the Active group had a significantly lower percentage of people with suboptimal 25-OHD levels (3.2% vs 15.4%, p=.019). At week 4, participants in the Active group had a gait velocity over 2.4m of 0.42m/s compared with 0.39m/s in the placebo group (p=.490). To week 4, seven (6.3%) participants in the Active group reported 1 or more falls compared to twenty-three (21.1%) in the Placebo group (χ2 = 4.327; p=.024) but there were no differences in fractures (2.7% vs 2.8%, p=.964) or grip strength. The number of deaths was non-significantly lower in the Active group compared with the Placebo group at 4 weeks (1 vs 3, p = .295). There was a trend for Active participants to have a higher total EQ-5D scores at Week 26 (88.1+/-13.2 vs 84.3+/-15.8, F=2.87, p=.092). Active participants were significantly more likely to present with ‘no pain or discomfort’ at Week 26 (96.4% vs 88.8%, p=.037). One case of hypercalcemia at 2 weeks was noted in the Active group which normalised after 4 and 26 weeks. Discussion and Conclusions: This study cohort shared similar demographic characteristics and comorbidities with other cohorts of people with hip fracture. Hypovitaminosis D was not as prevalent as previously documented. Patients taking vitamin D supplements and with higher premorbid Barthel Index, reflecting greater independence and activity, tended to have higher 25-OHD levels at baseline. Further, lower NRS pain ratings following surgery were associated with higher vitamin D levels. Overall, the levels of pain reported by this cohort are acceptable although approximately 10% to 15% had higher than reasonable levels of pain. Despite a higher than expected baseline 25-OHD level and moderate increases in 25-OHD levels, participants in the Active REVITAHIP group resulted in a greater percentage with target 25-OHD levels (>50nmol/L) compared with the placebo group with no significant differences in gait velocity at 4 weeks. Lower numbers of falls and improved pain control were noted in the Active group over the study period. In this cohort, there was a higher than expected baseline 25OH level which could have underestimated the effect of the intervention in a group with lower baseline 25-OHD levels.

Abstract The aim of the present study was to examine associations between serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D[(1,25(OH)2D]—the circulating and active forms of vitamin D—and periodontal infection. The data were gathered from a case-control study (63 periodontitis patients and 30 periodontally healthy controls) and an intervention study among individuals with type 1 diabetes mellitus (T1DM, 80 patients at the baseline and 65 after periodontal treatment). The periodontal data and the levels of serum 25(OH)D, 1,25(OH)2D and parathyroid hormone (PTH) were available. A third data set included periodontal data and the serum level of 25(OH)D of 1262 non-smoking and non-diabetic 30–49-year-old individuals (Health 2000 Survey). Serum 25(OH)D analyses were done using enzyme-linked immunoassay and radioimmunoassay, 1,25(O)2D analyses using enzyme-immunoassay after purification of 1,25(OH)2D by immunoextraction and PTH analyses using electrochemiluminescence immunoassay. In the case-control study individuals with a low serum 1,25(O)2D level were more likely to belong to the periodontitis group than to the periodontally healthy group and an inverse association was observed between serum 1,25(OH)2D and severity of periodontitis at the baseline of the intervention study. Serum 1,25(OH)2D increased significantly after periodontal treatment in the T1DM patients; a finding that was considered suggestive of a causal relationship between serum 1,25(OH)2D and periodontal infection. Also, serum PTH increased after periodontal treatment; this increase, which was statistically significant (p = 0.016) in patients with moderate or severe periodontitis, may partly account for the earlier observed post-treatment increase in serum 1,25(OH)2D level. Possible explanations for low serum 1,25(OH)2D in periodontal infection may be increased degradation of 1,25(OH)2D, increased use of 1,25(OH)2D, or decreased hydroxylation of 25(OH)D The association between serum 25(OH)D level and periodontal infection was weak, if existent. An inverse association between serum 25(OH)D and the severity of periodontal infection was observed only in the T1DM patients. Among individuals with low plaque level, those in higher 25(OH)D quintiles tended to have fewer teeth with deepened periodontal pockets than those in lower quintiles; a finding which was interpreted to mean a slight protective role of 25(OH)D against periodontal infection
Tiivistelmä Tutkimuksen tarkoituksena oli selvittää seerumin 25-hydroksivitamiini D:n [25(OH)D, D-vitamiinin varastomuoto] ja 1,25-dihydroksivitamiini D:n [1,25(OH)2D, D-vitamiinin aktiivinen muoto] tasojen yhteyttä parodontiumin alueen infektiosairauksiin. Tulokset perustuvat kolmeen tutkimusasetelmaan: tapaus-verrokki-tutkimus (63 parodontiitti-potilasta, 30 verrokkia), interventio-tutkimus [80 tyypin 1 diabetes mellitus (T1DM) potilasta, joista 65 osallistui seurantaan parodontologisen hoidon jälkeen] ja poikittaistutkimus Terveys 2000 tutkimuksen osa-aineistossa (1262 30-49 vuotiasta tupakoimatonta ei-diabeetikkoa). Tapaus-verrokki- ja interventiotutkimuksissa tutkittiin myös seerumin parathormoonin (PTH) yhteyttä parodontaali-infektioon sekä PTH:n vaikutusta seerumin 1,25(OH)2D tasoon infektion hoidon jälkeen. D-vitamiinin ja PTH:n tasot määritettiin immunologisin menetelmin. Yhteyksiä tutkittiin käyttäen vakioituja monimuuttujamalleja. Tapaus-verrokki-tutkimuksessa yksilöt, joilla seerumin 1,25(OH)2D taso oli alhainen, kuuluivat todennäköisemmin parodontiitti- kuin verrokkiryhmään. Interventiotutkimuksen alkutilanteessa seerumin 1,25(OH)2D:n ja parodontaali-infektion vaikeusasteen välillä vallitsi tilastollisesti merkittävä käänteinen yhteys ja taso nousi merkittävästi infektion hoidon jälkeen. Myös seerumin PTH taso nousi parodontaali-infektion hoidon jälkeen; nousu oli tilastollisesti merkittävä (p = 0.016) pitkälle edennyttä parodontiittia sairastavilla. Interventiotutkimuksen tulokset viittaavat kausaaliseen yhteyteen 1,25(OH)2D:n ja parodontaali-infektion välillä. Alhainen seerumin 1,25(OH)2D pitoisuus infektion vallitessa voi selittyä sen suurella käytöllä immuunipuolustukseen infektion aikana tai lisääntyneellä hajoamisella. Tason nousu hoidon jälkeen tukee edellä mainittua. PTH on 25(OH)D:n hydroksylaation pääsäätelijä ja 1,25(OH)2D:n nousua hoidon jälkeen voi osittain selittää myös seerumin PTH tason kohoaminen. Seerumin 25(OH)D:n ja parodontaali-infektion välillä havaittu yhteys oli heikko, mutta ei täysin sulje pois 25(OH)D:n suojaavaa vaikutusta. Käänteinen yhteys löytyi vain interventiotutkimuksen alkutilanteessa T1DM potilailla. Infektion hoito ei vaikuttanut 25(OH)D tasoon. Terveys 2000 tutkimuksen osa-aineistossa havaittiin hyvän suuhygienian omaavilla jonkin verran alhaisempi määrä syventyneitä ientaskuja ylemmissä kuin alemmissa 25(OH)D kvintiileissä