Background: South Africa is in the midst of a health transition that is characterized by a high burden of both infectious diseases and non-communicable diseases. One of the drivers of non-communicable diseases in South Africa is the current epidemic of obesity. Vitamin D deficiency, which is defined by 25(OH)D levels in blood, has been reported to be a risk factor for cardiovascular disease and shares a number of risk factors with those traditionally linked to non-communicable diseases. Osteoporosis is another non-communicable disease that is reportedly increasing in prevalence worldwide and may be linked to vitamin D levels and to body fat. There is limited data on 25(OH)D levels in South Africa and its association with cardiovascular risk factors. There is also limited data on body composition including bone mineral density. Aims: The aims of this thesis were to describe 25(OH)D levels in healthy Black African and Indian subjects recruited from the greater Johannesburg metropolis and to determine if differences in 25(OH)D levels contributed to differences in cardiovascular risk. A further aim was to describe body composition in both ethnic groups and to see if differences in body composition contribute to differences in 25(OH)D levels or to differences in bone mineral density and to determine if differences in bone mineral density are mediated by differences in 25(OH)D. Methods: This was a cross sectional study carried out from July 2011 to March 2012 on 714 male and female subjects (male: female=340:374) of whom 371 were Black African and 343 were Indian. Subjects were recruited via the caregivers of the Birth to Twenty cohort. The first step was a descriptive analysis of 25(OH)D as well as its predictors including whole body fat, visceral and subcutaneous adiposity. This was followed by examining the associations of 25(OH)D and parathyroid hormone with cardiovascular risk factors that comprise the metabolic syndrome. Final analysis was description of bone mineral density according to ethnicity and gender and the contribution of lean mass, sub-total fat mass, visceral and subcutaneous adiposity to bone mineral density in each ethnic group. Results: Vitamin D deficiency was very prevalent in Indians, 28.6% in comparison to 5.1% in the Black African group (p<0.0001). In both groups season of collection was a positive predictor and PTH was negatively associated with 25(OH)D. Neither whole body fat nor visceral or subcutaneous adiposity was predictive of 25(OH)D in either group. Using the harmonized definition of the metabolic syndrome (Met S), was diagnosed in 29% of the Black African and 46% of the Indian subjects (p<0.0001). Subjects with Met S had higher PTH than those without (p<0.0001), whilst 25(OH)D levels were not significantly different (p=0.50). Logistic regression analysis showed that Indian ethnicity (OR 2.24; 95% CIs 1.57, 3.18; p<0.0001) and raised PTH (OR 2.48; 95% CIs 1.01, 6.08; p=0.04) adjusted for 25(OH)D) produced an increased risk of Met S but 25(OH)D did not (OR 1.25; 95% CIs 0.67, 2.24; p=0.48). Whole body, hip, femoral neck and lumbar spine bone mineral density were significantly higher in Black African than Indian subjects (p<0.001 for all). Whole body lean mass positively associated with bone mineral density at all sites in both ethnic groups (p<0.001 for all), and partially explained the higher bone mineral density in Black African females compared to Indian females. Whole body fat mass correlated positively with lumbar bone mineral density in Black African (p=0.001) and inversely with sub-total bone mineral density in Indian subjects (p<0.0001). Visceral adiposity correlated inversely with sub-total bone mineral density in the Black African subjects (p=0.037) and with lumbar bone mineral density in the Indian group (p=0.005). No association was found between serum 25(OH)D and bone mineral density. PTH was inversely associated with hip bone mineral density in the Black African group (p=0.01) and with sub-total (p=0.002), hip (p=0.001) and femoral bone mineral density (p<0.0001) in the Indian group. Conclusions: This study highlighted the high prevalence of vitamin D deficiency in the Indian population and the fact that local conditions such as sunshine exposure and season of collection of blood are important determinants of 25(OH)D levels. It also showed that Indian ethnicity and PTH are risk factors for the Met S, but differences in risk between both ethnic groups are not due to differences in 25(OH)D levels. The thesis also showed that there are significant differences in bone mineral density across ethnicity, with lean mass an important contributor to bone mineral density across race and gender.

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Acute respiratory infections (ARI) are a major global cause of morbidity and mortality. Vitamin D deficiency has been reported to associate with susceptibility to ARI and with greater severity and poorer control of asthma and chronic obstructive pulmonary disease (COPD). Clinical trials of vitamin D for the prevention of ARI have yielded heterogeneous results, with some showing protection and others not. This may reflect variation in the frequency of genetic variants influencing response to vitamin D supplementation in different populations. The impact that genetic variation in the vitamin D pathway has on vitamin D status, disease phenotype and response to vitamin D supplementation in prevention of ARI has not been comprehensively investigated. Methods: I conducted: 1. A systematic review and meta-analysis of clinical studies which have investigated vitamin D as a potential therapy for ARI; 2. Three cross-sectional studies (in n=297 adult asthma patients, n=278 COPD patients, and n=272 older adults) to investigate potential environmental determinants (lifestyle and anthropometric) and genetic determinants (35 single nucleotide polymorphisms [SNP] in 11 vitamin D related genes) of serum 25-hydroxyvitamin D concentration (25[OH]D) and clinical phenotype; 3. Three prospective studies investigating the influence of genetic variation in the vitamin D pathway on a) susceptibility to ARI (main effects analysis) and b) efficacy of vitamin D supplementation for the prevention of ARI (interaction analysis). Results: My systematic review identified consistent reports of an inverse association between vitamin D status and risk of ARI in observational studies, and heterogeneous reports from clinical trials. My cross-sectional studies identified a range of classical environmental factors which predict vitamin D status in the three study populations, but did not identify any genetic variants in the vitamin D pathway that associate with vitamin D status. I identified an association between vitamin D deficiency and decreased lung function in COPD patients, but no associations between vitamin D deficiency and asthma phenotype. Finally, my analysis identified a haplotype of 5 single nucleotide polymorphisms in the vitamin D receptor (VDR) gene which significantly modify the effect of vitamin D supplementation on risk of upper respiratory infection in COPD patients. Conclusions: I identified environmental determinants that predict 25(OH)D concentrations in all three study populations, but only found an association between vitamin D deficiency and disease severity in COPD patients. Furthermore, I identified a haplotype in VDR which modifies the effect of vitamin D supplementation in COPD patients to result in a significantly reduced risk of ARI.

Thesis (Ph. D.)--University of Hong Kong, 1984.

Objective：Low vitamin D has been implicated in the development of type 2 diabetes. However, whether vitamin D continues to have a clinically significant effect in existing diabetes is unclear. The objective of this study was to examine the association of serum vitamin D with glycemic control in established type 2 diabetes. Methods: This was a retrospective analysis of medical records. Characteristics of 487 patients with type 2 diabetes were stratified by vitamin D status and serum glycosylated hemoglobin (HbA1c). Vitamin D deficiency among the subjects was studied. The relationship between vitamin D and glycemic control was explored by multiple linear regression, multivariate analysis of variance (MANOVA) and chi-square test. Patients were stratified into overweight and non-overweight group based on body mass index (BMI), and the association of serum vitamin D concentration with glycemic control was evaluated in each group. Insulin resistance and C-peptide as mediators between vitamin D and HbA1c was tested. The impact of vitamin D on cholesterol metabolism was also assessed. Results: (1) Vitamin D deficiency was highly prevalent, accounting for 88.3% of the study sample. (2) Serum vitamin D levels were significantly inversely associated with serum HbA1c. This correlation was stronger in overweight group than in non-overweight group. There was no significant relationship between serum vitamin D levels and fasting plasma glucose (FPG). HbA1c was significantly lower in vitamin D insufficiency group than in vitamin D severe deficiency group. (3) Insulin resistance partially mediated the association between vitamin D and HbA1c. (4) No significant association of Vitamin D with low density lipoprotein (LDL) or high density lipoprotein (HDL) was found in this study. Conclusions: There was an inverse association between serum vitamin D levels and HbA1c. The inverse correlation of serum vitamin D level and HbA1c was stronger in overweight group than in non-overweight group, which indicates patients with obesity might benefit more from vitamin D supplementation. / published_or_final_version / Public Health / Master / Master of Public Health

Access to abstract restricted until 05/2017. / Access to thesis restricted until 05/2017. / Department of Family and Consumer Sciences

Thesis (M.S.) in Food Science and Human Nutrition--University of Maine, 2003. / Includes vita. Includes bibliographical references (leaves 45-47).

Vitamin D is a fat-soluble vitamin that has proven to be extremely important for human health. Vitamin D has important functions that regulate calcium and phosphate absorption from the gastrointestinal tract. The regulation of calcium and phosphorus metabolism is extremely important for the maintenance of the structural integrity of the human skeleton, neuromuscular function and a wide variety of metabolic processes. A major source of vitamin D for most children and adults if exposure to sunlight. During sun exposure 7-dehydrocholesterol in the epidermis and dermis absorb solar ultraviolet B radiation with wavelengths of 290-315nm. This results in it being converted to previtamin D. Once formed, the thermodynamically unstable previtamin D is isomerized to vitamin D. Vitamin D is then hydroxylated in the liver and the kidneys to its active form before it can act as a homeostatic regulator of calcium and phosphorus metabolism. There are certain patients who do not respond well to vitamin D supplements because they suffer from fat malabsorption syndromes such as cystic fibrosis, Crohn’s disease and ulcerative colitis. In addition, gastric bypass patients have difficulty in absorbing dietary and supplemental vitamin D. One approach for treating vitamin D deficiency in these patients is to recommend that they be exposed to artificial UVB radiation either from a tanning bed or from a Sperti vitamin D producing lamp. Novel ultraviolet emitting light emitting diodes (LED) have emerged as a promising solution because of their size, efficiency, and ability to use narrow band UV radiation. A LED has been developed to emit narrowband UVB radiation with a peak wavelength of that 295nm. This thesis provides evidence that this novel UVB-LED is able to cause the photo-conversion of 7-deyhdrocholesterol to previtamin D3 in vitro, using 7-dehydrocholesterol containing borosilicate ampoules as positive controls, as well as produce vitamin D3 in surgically obtained type II human skin. Results from this study suggest that vitamin D producing LEDs can be developed for the treatment of vitamin D deficiency, especially in patients with fat malabsorption syndromes.

Since vitamin D deficiency is common at birth, the objective of this study was to test if postnatal vitamin D supplementation would normalize bone mineralization. Forty guinea pigs were randomized to receive a diet with or without vitamin D3 during pregnancy. Newborn pups were randomized to receive 10 IU of vitamin D3 or a placebo daily until d28. Measurements at birth and d28 included whole body and regional bone mass, osteocalcin and deoxypyridinoline, plus biomechanical testing of excised tibias and femurs. Offspring from deficient sows had lower body weight, whole body and tibia bone mineral content (BMC) and lower osteocalcin and biomechanical integrity. By d28 this group had lower whole body bone density and femur BMC, unless supplemented. Interactions with gender showed males continued to have low 25(OH)D despite supplementation. Therefore, neonates born to sows with dietary vitamin D deficiency require supplemental vitamin D to support normal bone mineral accretion.

No description available.