Vitamin D insufficiency remains a costly pandemic in veterans. Treatment requires achievement of desired 25-hydroxyvitamin D [25(OH)D] concentrations. The frequency with which 25(OH)D should be measured following treatment remains speculative. A retrospective analysis of veterans with vitamin D insufficiency was conducted. The group was stratified on the basis of initial 25(OH)D and assessed for frequency of follow-up 25(OH)D concentrations. Over 3 years, 278 patients with insufficient 25(OH)D concentrations were identified. Of these, 87 (31%) patients had subsequent levels assessed in the year following initial documentation of vitamin D insufficiency. The likelihood of follow-up testing was unrelated to the initial vitamin D level. In the patients with follow-up 25(OH)D levels, 90% eventually achieved a serum level of 30 ng/mL or greater. Veterans with vitamin D insufficiency have inadequate serial monitoring of 25(OH)D concentrations.

The increased number of international immigrants and associated global problems of health deterioration and vitamin D (vitD) deficiency/insufficiency may lead to significant burdens for host countries. This thesis investigated immigrants’ health deterioration and vitD status through a comprehensive analysis of Canadian national vitD data, systematic evaluation of the quality/content of clinical practice guidelines, and global systematic review of vitD status and determinants among first-generation immigrants. Immigrants had lower serum 25-hydroxyvitamin D (S-25(OH)D) and higher melanin levels than non-immigrants. S-25(OH)D levels improved over time, with ethnicity the main factor explaining variations. The longer immigrants lived in Canada, the higher the prevalence of chronic diseases (CDs), potentially reflecting health deterioration. Low levels of accumulated S-25(OH)D may impact CD-related biomarkers, partially explaining immigrants’ health deterioration over time. Local and international guidance regarding immigrants’ vitD deficiency/insufficiency was lacking. Improving immigrants’ vitD status requires prevention and intervention programs (e.g., vitD supplementation/screening), relevant national/international guidelines, and longitudinal research clarifying the complex bidirectional association between S-25(OH)D and CDs.

Background: Vitamin D deficiency is a concern in the US. Association between vitamin D status and metabolic syndrome (MetS), insulin resistance (IR), and inflammation is unclear in children. Objective: The relationship between serum vitamin D and MetS, C-reactive protein (CRP), and Homeostatic Model Assessment-IR (HOMA-IR) was investigated. Design: Data from 3 cycles of National Health and Nutrition Examination Survey, 2001-2006 for 3700 (1820, boys; 1880, girls) children and adolescents, aged 12-17 y were used to assess prevalence of vitamin D deficiency (<20 ng>/mL) and association between serum vitamin D and prevalence of MetS, various components of MetS, CRP, and HOMA-IR using multivariate regression models. Results: Overall, prevalences of MetS and vitamin D deficiency were 6.1% and 30.5%, respectively. Prevalence of vitamin D deficiency was higher in girls (52%), blacks (74%), non-supplement users (50%), persons who were examined in winter (56%), and persons in the low poverty income ratio group (57%) compared to their counterparts. Serum vitamin D was inversely associated with waist circumference (P<0.001), systolic blood pressure (P=0.009), and HOMA-IR (P=0.003) and positively associated with HDL-cholesterol (P<0.001). Children with lowest serum vitamin D are at increased risk for MetS (P=0.04; OR 2.26; 95% CI: 1.11, 4.61). Serum vitamin D was not related to CRP (P<0.10). Conclusions: Children with poor vitamin D status are at increased risk for MetS and IR. Because of negative health outcomes associated with MetS and poor vitamin D status when existed individually or in combination, early detection and intervention of these conditions are paramount, especially in children.

Abstract Vitamin D deficiency, obesity and short telomere length are reported to be associated with increased risk of metabolic diseases and all-cause mortality, through modulation of inflammatory pathways. The season of blood sampling, obesity and physical activity have been identified as determinants of 25-hydroxyvitamin D [25(OH)D], but their association with 25(OH)D2 (D2) and 25(OH)D3 (D3) is still poorly understood. In addition, relationships between 25(OH)D, body mass index (BMI), inflammation, and leukocyte telomere length (LTL) has not been previously established. A better understanding of the determinants, risk factors of vitamin D deficiency, and their relationship with BMI, inflammation, and LTL is needed. The study was based on the 31-year follow-up study of the Northern Finland Birth Cohort 1966 (N=4,758). Statistical analyses were used to 1) examine potential determinants of D2 and D3, and identify risk factors associated with hypovitaminosis D, 2) investigate the relationship of 25(OH)D and BMI with LTL and test whether it is independent of inflammatory pathways and, 3) assess how the association of BMI with inflammatory biomarkers might be mediated through 25(OH)D. Our results showed that D2 contributed 5% and D3 95% of the total 25(OH)D concentrations. When examined, the determinants for each isoform, periods of low sunlight exposure associated with increased D2, but with decreased D3. Oral contraceptives associated with increased concentrations of both. We confirmed the known risk factors of low vitamin D: low sunlight periods, residing in northern latitudes, and physical inactivity. Serum 25(OH)D was not an important determinant of LTL, and inflammation may partly mediate the BMI-LTL association. Higher serum 25(OH)D was inversely associated with inflammatory biomarkers, and the association between BMI and biomarkers was modestly mediated through lowered 25(OH)D. In conclusion, our results support the role of known risk factors in vitamin D deficiency and add information on specific determinants of D2 and D3. 25(OH)D did not associate with LTL in young adulthood. We have also provided new insights into a plausible role of vitamin D in BMI associated inflammation. An improved understanding of the role of vitamin D benefits public health in many ways (it can help prevent vitamin D deficiency by implementing lifestyle modification and supplementation). / Tiivistelmä D-vitamiinin puutos, lihavuus ja lyhyt telomeerien pituus liittyvät mahdollisesti lisääntyneeseen riskiin sairastua metabolisiin sairauksiin sekä yleisemmin kuolleisuuteen. Eräs selitys tälle voi löytyä tulehdustekijöistä. Lihavuuden, liikunnan puutteen ja verinäytteenoton ajankohdan tiedetään vaikuttavan 25-hydroksi-D-vitamiinin [25(OH)D]-pitoisuuteen, mutta niiden yhteys D-vitamiinin isomuotoihin (D2, D3) on vielä huonosti tunnettu. Aiemmin ei ole selvitetty 25(OH)D:n, painoindeksin (BMI), tulehduksen ja leukosyyttien telomeerien pituuden (LTL) välisiä yhteyksiä, ja siksi näistä tarvitaan lisätutkimusta. Tutkimusaineistona oli Pohjois-Suomen 1966 syntymäkohortin, 31-vuoden seurantaan osallistuneet henkilöt (N=4,758). Tutkimuksessa keskityttiin 1) selvittämään D2- ja D3-vitamiinipitoisuuksien määrittäviä tekijöitä ja tunnistamaan D-vitamiinin puutteeseen liittyviä riskitekijöitä, 2) tutkimaan 25(OH)D-pitoisuuden ja BMI:n suhdetta LTL:n kanssa sekä testaamaan, onko suhde riippumaton tulehduksellisista tekijöistä ja 3) arvioimaan ilmeneekö BMI:n ja tulehdussytokiinien välinen yhteys 25(OH)D-pitoisuuden kautta. Tutkimus osoitti, että D2-isomuodon osuus oli 5 % ja D3:n osuus 95 % koko 25(OH)D-pitoisuudesta. Näitä isomuotoja määrittäviä tekijöitä tutkittaessa havaittiin, että vähäisellä auringonvalolle altistumisella on todennäköisesti yhteys lisääntyneeseen D2-pitoisuuteen, mutta alhaisempaan D3-pitoisuuteen. Suun kautta otettavien ehkäisypillereiden käytöllä oli yhteys molempien muotojen lisääntyneisiin pitoisuuksiin. Tutkimus vahvisti alhaisten D-vitamiinipitoisuuksien tunnetut riskitekijät: lyhyt altistus auringon valolle sekä fyysinen passiivisuus. 25(OH)D-pitoisuus ei ollut yhteydessä LTL:ään mutta tulehdus näytti osittain vaikuttavan BMI-LTL-assosiaatioon. Korkeampi 25(OH)D-pitoisuus yhdistyi matalampiin tulehdussytokiinipitoisuuksiin, kun taas matala 25(OH)D-pitoisuus muokkasi BMI:n ja biomarkkereiden välisisiä yhteyksiä, tosin heikosti. Yhteenvetona voidaan todeta, että tulokset tukevat tunnettujen riskitekijöiden merkitystä D-vitamiinin puutoksessa ja tuovat lisää tietoa eri isomuotoihin vaikuttavista tekijöistä. Tutkimus antaa myös uusia näkemyksiä D-vitamiinin roolista lihavuuteen liittyvässä matala-asteisessa tulehduksessa. D-vitamiinin vaikutuksien tarkempi tunteminen on merkityksellistä myös kansanterveyden kannalta.

Changes in bone and mineral metabolism and the role of vitamin D in very low birth weight infants. Firstly, the aim of dissertation work was to estimate physiological parathyroid hormone (PTH) levels and their relationship with bone metabolism parameters in otherwise healthy preterm newborns with birth weight 1000-1500 g. Secondly, to evaluate vitamin D status in mothers and their very low birth weight infants (VLBW) at birth and at discharge with currently recommended supplementation of vitamin D. Thirdly, to compare clinical outcomes of VLBW infants with 25-hydroxy vitamin D [25(OH)D] levels ≤ and > 25 nmol/l in umbilical cord blood and finally to evaluate umbilical cord vitamin D as a risk factor for respiratory distress syndrome in preterm infants. It is a set of prospective observational studies involving immature newborns with birth weight below 1500 g. The parameters of mineral and bone metabolism were analysed in umbilical cord blood and newborn serum and urine during hospitalisation (PTH, 25-hydroxy vitamin D, S-Ca, S-P, ALP, U-Ca, U-P) and in pregnant women before delivery (25-hydroxy vitamin D). Bone mineralization was evaluated by bone densitometry. In a pilot study, from the total 134 examined serum samples for PTH levels the estimated reference range was 1.6 - 9.3 pmol/l. From the...