Low circulating 25-hydroxyvitamin D 25(OH)D is prevalent in African Americans, but predictors of vitamin D status are understudied compared to Caucasian populations.
We investigated whether certain ...environmental and genetic factors are predictors of circulating 25(OH)D in 989 elderly African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study.
Regression analysis estimated the cross-sectional association of nongenetic (environmental) factors with 25(OH)D. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D in Caucasian genome-wide association studies (GWASs) were analyzed for association with serum 25(OH)D, including analyses of all imputed SNPs in identified genomic regions. Genome-wide complex trait analysis (GCTA) evaluated the association of all (genome-wide) genotyped SNPs with serum 25(OH)D in the Health ABC Study with replication in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.
Gender, study site, season of blood draw, body mass index, dietary supplement use, dairy and cereal consumption, Healthy Eating Index score, and walking >180 min/wk were associated with 25(OH)D (P < 0.05), jointly explaining 25% of the variation in circulating 25(OH)D. Multivitamin supplement use was the strongest predictor of circulating 25(OH)D, and supplement users had a 6.3-μg/L higher serum 25(OH)D concentration compared with nonusers. Previous GWAS-identified gene regions were not replicated in African Americans, but the nonsynonymous rs7041 SNP in group-specific component (vitamin D binding protein) was close to significance thresholds (P = 0.08), and there was evidence for an interaction between this SNP and use of multivitamin supplements in relation to serum 25(OH)D concentration (P = 0.04). Twenty-three percent (95% CI: 0%, 52%) of the variation in serum 25(OH)D was explained by total genetic variation in a pooled GCTA of 2087 Health ABC Study and MESA African-American participants, but population substructure effects could not be separated from other genetic influences.
Modifiable dietary and lifestyle predictors of serum 25(OH)D were identified in African Americans. GCTA confirms that a proportion of 25(OH)D variability is attributable to genetic variation, but genomic regions associated with the 25(OH)D phenotype identified in prior GWASs of European Americans were not replicated in the Health ABC Study in African Americans.
The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D) enhances innate immunity by inducing the cathelicidin antimicrobial peptide (hCAP). In monocytes/macrophages, this occurs ...primarily in response to activation of TLR, that induce expression of the vitamin D receptor and localized synthesis of 1,25(OH)(2)D from precursor 25-hydroxyvitamin D(3) (25OHD). To clarify the relationship between vitamin D and innate immunity, we assessed changes in hCAP expression in vivo and ex vivo in human subjects attending a bone clinic (n = 50). Of these, 38% were vitamin D-insufficient (<75 nM 25OHD) and received supplementation with vitamin D (50,000 IU vitamin D(2) twice weekly for 5 wk). Baseline 25OHD status or vitamin D supplementation had no effect on circulating levels of hCAP. Therefore, ex vivo changes in hCAP for each subject were assessed using peripheral blood monocytes cultured with 10% autologous serum (n = 28). Under these vitamin D "insufficient" conditions the TLR2/1 ligand 19 kDa lipopeptide or the TLR4 ligand LPS, monocytes showed increased expression of the vitamin D-activating enzyme CYP27b1 (5- and 5.5-fold, respectively, both p < 0.01) but decreased expression of hCAP mRNA (10-fold and 30-fold, both p < 0.001). Following treatment with 19 kDa, expression of hCAP: 1) correlated with 25OHD levels in serum culture supplements (R = 0.649, p < 0.001); 2) was significantly enhanced by exogenous 25OHD (5 nM); and 3) was significantly enhanced with serum from vivo vitamin D-supplemented patients. These data suggest that a key role of vitamin D in innate immunity is to maintain localized production of antibacterial hCAP following TLR activation of monocytes.
Increased awareness of the importance of vitamin D to health has led to concerns about the prevalence of hypovitaminosis D in many parts of the world.
We aimed to determine the prevalence of ...hypovitaminosis D in the white British population and to evaluate the influence of key dietary and lifestyle risk factors.
We measured 25-hydroxyvitamin D 25(OH)D in 7437 whites from the 1958 British birth cohort when they were 45 y old.
The prevalence of hypovitaminosis D was highest during the winter and spring, when 25(OH)D concentrations <25, <40, and <75 nmol/L were found in 15.5%, 46.6%, and 87.1% of participants, respectively; the proportions were 3.2%, 15.4%, and 60.9%, respectively, during the summer and fall. Men had higher 25(OH)D concentrations, on average, than did women during the summer and fall but not during the winter and spring (P = 0.006, likelihood ratio test for interaction). 25(OH)D concentrations were significantly higher in participants who used vitamin D supplements or oily fish than in those who did not (P < 0.0001 for both) but were not significantly higher in participants who consumed vitamin D-fortified margarine than in those who did not (P = 0.10). 25(OH)D concentrations <40 nmol/L were twice as likely in the obese as in the nonobese and in Scottish participants as in those from other parts of Great Britain (ie, England and Wales) (P < 0.0001 for both).
Prevalence of hypovitaminosis D in the general population was alarmingly high during the winter and spring, which warrants action at a population level rather than at a risk group level.
Despite an increasing interest in vitamin D status, a reference range of the nutrient has not been fully established. This is partly due to a paucity of standardized measuring systems with high ...throughput. In addition, the range may vary by populations and may change with modernization of lifestyles.
This study aims to calculate the current reference concentration of 25-hydroxyvitamin D (25(OH)D) among healthy people living in an urban area in Japan.
A newly developed fully automated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) system was used to measure serum 25(OH)D concentrations. Reproducibility was assessed by measuring standardized samples. Accuracy was validated by comparing with commercially available immunoassays. Then, mass screening was conducted targeting participants who received medical checkups in Tokyo from April 2019 to March 2020, and the reference ranges were calculated.
The coefficients of variations of interoperator and interday reproducibility were 4.1%–8.5% and 3.7%–8.0% for 25-hydroxyvitamin D2 (25(OH)D2) and 4.7%–7.0% and 4.0%–6.9% for 25-hydroxyvitamine D3, respectively. The measured total 25(OH)D concentrations correlated well with those measured by immunoassays. In total, 5518 participants were measured for 25(OH)D concentrations, among whom 98% showed inadequate concentrations (<30 ng/mL). The reference ranges of total 25(OH)D for female, male, and total participants were 7–30 ng/mL, 5–27 ng/mL, and 6–29 ng/mL, respectively. After excluding those with abnormal renal and liver function, the range was 6–30 ng/mL.
The high prevalence of vitamin D insufficiency among seemingly healthy population may be attributed to lifestyle characteristics of people living in urban areas of Japan, including spending less time outdoors and lower intake of traditional foods. Longitudinal follow-up and mass screenings targeting different population will help elucidate reasons for discrepancies between official guidelines and the observed concentrations, to which the well-validated measurement system is essential.
Vitamin D deficiency has been linked to an increased risk of hypertension, diabetes, congestive heart failure, peripheral arterial disease, myocardial infarction, stroke, and related mortality, even ...after adjustment for traditional cardiovascular risk factors. Accumulating evidence from experimental, clinical, and epidemiological studies suggests that vitamin D may also be associated with several indices of vascular function, including the development and progression of atherosclerotic cardiovascular disease. These findings may provide at least a partial explanation for several recent epidemiologic studies implicating low vitamin D status in the pathogenesis of cardiovascular disease. However, many questions still remain. Only a handful of studies are currently available, and the results of these studies have generally been mixed. Additionally, it is unknown whether findings differ across varied subpopulations, including minority subgroups in the United States, younger adults, and those residing in areas with varying amounts of regular sunlight. Furthermore, the exact mechanism by which vitamin D may influence the atherosclerotic disease process has not yet been completely elucidated. In addition, if vitamin D is important in the etiology of atherosclerosis, it is unclear at what stage(s) in the atherosclerotic disease process vitamin D may exert its effects. Large-scale, well-conducted, placebo controlled clinical trials testing the efficacy of vitamin D supplementation in delaying, slowing, or reverting the atherosclerotic disease process have not yet been conducted. Until the results of these studies are available, we believe it is premature to recommend vitamin D as a therapeutic option in atherosclerosis.
Patients with asthma exhibit variable response to inhaled corticosteroids (ICS). Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid (GC) response in asthma.
To determine the ...effect of vitamin D levels on phenotype and GC response in asthma.
Nonsmoking adults with asthma were enrolled in a study assessing the relationship between serum 25(OH)D (vitamin D) concentrations and lung function, airway hyperresponsiveness (AHR), and GC response, as measured by dexamethasone-induced expression of mitogen-activated protein kinase phosphatase (MKP)-1 by peripheral blood mononuclear cells.
A total of 54 adults with asthma (FEV(1), 82.9 +/- 15.7% predicted mean +/- SD, serum vitamin D levels of 28.1 +/- 10.2 ng/ml) were enrolled. Higher vitamin D levels were associated with greater lung function, with a 22.7 (+/-9.3) ml (mean +/- SE) increase in FEV(1) for each nanogram per milliliter increase in vitamin D (P = 0.02). Participants with vitamin D insufficiency (<30 ng/ml) demonstrated increased AHR, with a provocative concentration of methacholine inducing a 20% fall in FEV(1) of 1.03 (+/-0.2) mg/ml versus 1.92 (+/-0.2) mg/ml in those with vitamin D of 30 ng/ml or higher (P = 0.01). In ICS-untreated participants, dexamethasone-induced MKP-1 expression increased with higher vitamin D levels, with a 0.05 (+/-0.02)-fold increase (P = 0.02) in MKP-1 expression observed for each nanogram per milliliter increase in vitamin D, a finding that occurred in the absence of a significant increase in IL-10 expression.
In asthma, reduced vitamin D levels are associated with impaired lung function, increased AHR, and reduced GC response, suggesting that supplementation of vitamin D levels in patients with asthma may improve multiple parameters of asthma severity and treatment response. Clinical trials registered with www.clinicaltrials.gov (NCT00495157, NCT00565266, and NCT00557180).
Studies conducted among populations of tropical countries have reported high prevalences of vitamin D deficiency and insufficiency. Information resulting from meta-analyses on the spatial ...distribution of vitamin D deficiency and insufficiency in tropical countries is still rare. The aim of this review was investigated the prevalence of vitamin D deficiency and insufficiency among the Brazilian population. Observational studies were searched in eight electronically databases. Additionally, theses and dissertations and abstracts were screened. Details on study design, methods, population, mean and data on serum concentrations of vitamin D in different age groups in Brazil were extracted. Data were pooled using a random-effects model and choropleth maps were created based on the geopolitical regions of the country. 72 published paper met the inclusion criteria. The mean vitamin D concentration among the Brazilian population between 2000 and 2017 of 67.65 nmol/L (95% CI: 65.91, 69.38 nmol/L).The prevalences of vitamin D deficiency and insufficiency were 28.16% (95% CI: 23.90, 32.40) and 45.26% (95% CI: 35.82, 54.71), respectively, for the Brazilian population. The highest prevalence of deficiency were observed in the southern and southeastern regions and the highest occurrence of vitamin D insufficiency was among the populations of the southeastern and northeastern regions. Finally, there are high prevalence of inadequate vitamin D concentrations among the population, regardless of age group in Brazil. The development of vitamin D food fortification policies in needs to be cautious and carefully planned.
Vitamin D, the sunshine vitamin, has been recognized for almost 100 years as being essential for bone health. Vitamin D provides an adequate amount of calcium and phosphorus for the normal ...development and mineralization of a healthy skeleton. Vitamin D made in the skin or ingested in the diet, however, is biologically inactive and requires obligate hydroxylations first in the liver to 25-hydroxyvitamin D, and then in the kidney to 1,25-dihydroxyvitamin D. 25-Hydroxyvitamin D is the major circulating form of vitamin D that is the best indicator of vitamin D status. 1,25-dihydroxyvitamin D is the biologically active form of vitamin D. This lipid-soluble hormone interacts with its specific nuclear receptor in the intestine and bone to regulate calcium metabolism. It is now recognized that the vitamin D receptor is also present in most tissues and cells in the body. 1,25-dihydroxyvitamin D, by interacting with its receptor in non-calcemic tissues, is able to elicit a wide variety of biologic responses. 1,25-dihydroxyvitamin D regulates cellular growth and influences the modulation of the immune system. There is compelling epidemiologic observations that suggest that living at higher latitudes is associated with increased risk of many common deadly cancers. Both prospective and retrospective studies help support the concept that it is vitamin D deficiency that is the driving force for increased risk of common cancers in people living at higher latitudes. Most tissues and cells not only have a vitamin D receptor, but also have the ability to make 1,25-dihydroxyvitamin D. It has been suggested that increasing vitamin D intake or sun exposure increases circulating concentrations of 25-hydroxyvitamin D, which in turn, is metabolized to 1,25-dihydroxyvitamin D
3 in prostate, colon, breast, etc. The local cellular production of 1,25-dihydroxyvitamin D acts in an autocrine fashion to regulate cell growth and decrease the risk of the cells becoming malignant. Therefore, measurement of 25-hydroxyvitamin D is important not only to monitor vitamin D status for bone health, but also for cancer prevention.
Vitamin D deficiency occurs in the United States in exclusively breastfed infants who have high levels of skin pigmentation, inadequate vitamin D supplementation, and insufficient sunlight exposure. ...I review serum 25-hydroxyvitamin D 25(OH)D concentrations and functional outcomes of vitamin deficiency in young children and breastfed and nonbreastfed infants. These outcomes include the presence or absence of vitamin D deficiency rickets, bone mineral content, and serum parathyroid hormone concentration. Daily vitamin D supplements of 400 IU/L keep serum 25(OH)D concentrations higher than 50 nmol/L and prevent rickets in infants and young children. The available evidence is not sufficient to support the use of bone mineral content or parathyroid hormone concentrations in infants and young children as functional outcomes to define deficient or sufficient levels of 25(OH)D. I therefore propose a research agenda to establish the functional definitions of vitamin D sufficiency or deficiency in infants and young children.
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