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Prevalence and determinants of profound vitamin D deficiency (25-hydroxyvitamin D <10 nmol/L) in the UK Biobank and potential implications for disease association studies.

BACKGROUND: 25-hydroxyvitamin D (25OHD) is the principal biomarker of vitamin D status. Values below the assay detection limit (<10 nmol/L) are often reported as missing. Thus the most severely deficient participants are excluded from research which can lead to inaccurate findings such as underestimated prevalence of deficiency, overlooked risk factors, and biased evaluation of disease associations. METHODS: In total 369,626 individuals from the UK Biobank cohort were included in this study. Data on 25OHD concentration and relevant demographic and lifestyle factors such as age, supplement intake, diet, and time spent outdoors were used in the analyses. Ambient UVB radiation was approximated for each participant. 25OHD was evaluated as a categorical outcome and we reintroduced participants with 25OHD values <&#x202f;10 nmol/L (conventionally reported as missing values) back to the dataset. Adjusted regression models were used to investigate the determinants of profound (25OHD <10 nmol/L) and severe (10-25 nmol/L) vitamin D deficiency and to assess disease associations (with 25-50 nmol/L as the reference category). RESULTS: 1,784 (0.48&#x202f;%) individuals were profoundly deficient and a further 47,226 (12.78 %) individuals were severely vitamin D deficient. The proportions of profoundly and severely deficient were highest among Asians, 9&#x202f;% and 47&#x202f;%, respectively. Ambient UVB radiation was the second strongest predictor: comparing the lowest vs. highest quartile, the risk of profound deficiency was 17-fold increased and that of severe deficiency 7.5-fold increased. Use of vitamin D supplements substantially reduced risk of profound (4.4-fold) and severe (2.5-fold) deficiency, as did fish intake (5- and 1.9-fold, respectively). Profound deficiency was more strongly associated with chronic illness, diabetes, and emphysema compared to severe deficiency. CONCLUSION: The prevalence of profound and severe vitamin D deficiency among Asian and Black ethnicities in the UK is high and requires targeted action. Solar radiation is potent in protecting against profound and severe vitamin D deficiency. Studies evaluating the relationship between vitamin D status and other health outcomes may be biased if profoundly deficient participants are excluded.

Humans

Vitamin D Deficiency During Pregnancy Is Associated With Greater LDL-C Increase, Elevated &#x3b2;-Hydroxybutyrate and Altered Neonatal Metabolic Markers-A Secondary, Pooled Analysis of the Randomized, Controlled Vitamin D and Lifestyle for Gestational Diabetes Prevention Trial (DALI).

INTRODUCTION: Vitamin D (vitD) plays a role in metabolic regulation, including lipid metabolism and insulin sensitivity. During pregnancy, profound physiological changes in lipid handling and ketogenesis occur to support fetal development. However, the extent to which maternal vitamin D status influences these metabolic adaptations and fetal metabolic markers remains unclear. METHODS: In this secondary analysis, we examined lipid distribution throughout pregnancy-from before 20&#x2009;weeks' gestation to delivery-in women with overweight or obesity, stratified by vitamin D status (deficiency, insufficiency, or sufficiency), assessing both maternal and cord blood. Main inclusion criteria were: age&#x2009;>&#x2009;=18&#x2009;years, singleton pregnancy, <&#x2009;20&#x2009;weeks' gestation, BMI &#x2265;&#x2009;29&#x2009;kg/m2. Women with GDM <&#x2009;20&#x2009;weeks' gestation were excluded. In total, 962 pregnant women were divided into vitD deficient (<&#x2009;30&#x2009;nmol/L, n&#x2009;=&#x2009;102), insufficient (30-50&#x2009;nmol/L, n&#x2009;=&#x2009;222) and sufficient (>&#x2009;50&#x2009;nmol/L, n&#x2009;=&#x2009;638) groups. VitD levels and lipid concentrations were assessed at <&#x2009;20, 24-28 and 35-37&#x2009;weeks' gestation and in cord blood. RESULTS: Compared with vitD sufficient women, women with vitD deficiency had significantly larger increases in LDL-C throughout pregnancy and &#xdf;-OH-butyrate at 24-28&#x2009;weeks' gestation, in adjusted analysis. VitD in cord blood was highest in offspring of mothers with vitD sufficiency. In cord blood, significantly higher &#xdf;-OH-butyrate was observed with vitD deficiency; lipid concentrations were similar between groups. CONCLUSIONS: Early vitamin D deficiency before 20&#x2009;weeks of gestation was associated with altered metabolic trajectories during pregnancy, including greater increases in LDL cholesterol and ketone body concentrations in women with overweight or obesity, as well as higher cord blood ketone levels in their offspring. These findings suggest that early maternal vitamin D status may influence maternal and fetal metabolic adaptations, although causal relationships and clinical implications require further investigation. TRIAL REGISTRATION: Trial registered at ISRCTN registry (https://doi.org/10.1186/ISRCTN70595832) trial number ISRCTN70595832. Registration date 02/12/2011.

Humans

The ionic control of 1,25-dihydroxyvitamin D3 synthesis in isolated chick renal mitochondria. The role of calcium as influenced by inorganic phosphate and hydrogen-ion.

Isolated kidney mitochondria prepared from Vitamin D-deficient chicks catalyze the conversion of 25-hydroxyvitamin D3 to 1,25 dihydroxyvitamin D3. It wasfound that changes in the concentrations of Ca-2plus, HPO4-2minus, and Hplus altered synthesis in an interrelated fashion. Increasing the Ca-2plus concentration from 10-6 to 10-5 M caused a four- to fivefold increase in 1 alpha-hydroxylase activity when the medium pH was between 6.5 and 7.0. increasing the [Ca2+] to 10-4 M caused to furhter stimulation. At higher pH values, Ca-2plus had little effect upon 1 alpha-hydroxylase activity. In the absence of calcium [Ca2+] less than or equal to 10-7 M), a change in pH from 6.5 to 7.1 had no effect upon 1 alpha-hydroxylase activity in the presence of 10-5 M calcium, increasing the medium pH had a biphasic effect. An increase in pH from 6.5 to 6.9 caused a 1.5-fold increase in 1 alpha-hydroxylase activity, but a further increase of the pH to 7.1 caused a profound decrease in rate of hydroxylation to approximately 20% of the peak value. Neither 10-5 M LaC13 nor 10 mug/ml of oligomycin altered the effects of Ca2+ upon hydroxylate activity. However, the effect of calcium was blocked by 2.5 times 10-5 M ruthenium red, 0.83 mug/ml of antimycin A, and 500 muM dinitrophenol. The clcium ionophore, A23187, decreased but did not prevent the stimulatory effect of calcium. These data are consistent with the concept that the [Ca2+ in the mitochondrial matrix space is of importance in regulating the 1 alpha-hydroxylase. Phosphate exerted a biphasic effect on 1,25(OH)2D3 production with maximal stimulation (approximately twofold) at 1-3 mM. Calcium enhanced the stimulation by phosphate at all concentrations studied. The presence of potassium modified the interrelated effects of calcium and phosphate in two ways: 10-3 M calcium blocked the stimulation by phosphate; and in the presence of phosphate, 10-3 M calcium resulted in less 1,25(OH)2D3 production by production by isolated mitochondria are qualitatively similar to the effects of these ions on 1,25(OH)2D3 production yb isolated renal tubules.

Animals

Guidelines for maintaining adequate nutrition in old age.

Nutrient requirements do not change markedly with advancing age, but life style, socioeconomic status, psychologic changes, and the presence of chronic disease alter nutrient intake in the elderly. It is important to recognize and deal with these factors in attempting to correct malnutrition and in prescribing dietary treatment. Malnutrition includes a variety of disorders: undernutrition, nutrient deficiencies and imbalances, and obesity. Frequent small feedings, with nutritional supplements for patients with profound weight loss, are the initial treatment for undernutrition. Iron supplements and a diet of foods rich in iron and in promoting iron absorption are required in treating iron deficiency anemia. Management of macrocytic anemia should include specific nutrient therapy plus improvement of diet to include leafy vegetables and animal foodstuffs. Diet is an important adjunct in treating chronic diseases. Maturity-onset diabetes mellitus often can be managed by diet alone, with attention to correct proportions of fat, carbohydrate, and protein and to the decreased caloric requirements of elderly patients. The importance of continuing dietary modifications in hyperlipidemia and hypertension is well known. Although dietary manipulation in osteoporosis is not curative, a diet high in calcium and containing adequate floride and vitamin D affords maximum dietary protection against progress of the disease.

Adult