We tested the hypothesis that vascular endothelial function, assessed by endothelium-dependent dilation, is related to serum vitamin D status among middle-aged and older adults without clinical disease, and that this is linked to inflammation. Brachial artery flow-mediated dilation, a measure of endothelium-dependent dilation, was lower (P<0.01) in vitamin D–insufficient (3.7±0.2%; serum 25-hydroxyvitamin D [25(OH)D]: 20 to 29 ng/mL; 62±1 years of age; n=31; mean± SE) and vitamin D–deficient (3.2±0.3%; 25(OH)D: <20 ng/mL; 63±2 years of age; n=22) versus vitamin D–sufficient (4.6±0.4%; 25(OH)D: >29 ng/mL; 61±1 years of age; n=22) subjects, whereas endothelium-independent dilation (brachial dilation to sublingual nitroglycerine) did not differ (P=0.45). Among all subjects, brachial flow-mediated dilation was positively related to serum 25(OH)D (%&Dgr;: r=0.35; P<0.01) but not 1,25-dihydroxyvitamin D (r=−0.06; P=0.61), the active form of vitamin D. Vascular endothelial cell expression of the proinflammatory transcription factor nuclear factor &kgr;B was greater in deficient versus sufficient subjects (0.59±0.07 versus 0.44±0.05; P<0.05), and inhibition of nuclear factor &kgr;B (4 days oral salsalate) improved flow-mediated dilation to a greater extent in subjects with lower versus higher 25(OH)D (+3.7±0.6 versus +2.0±0.2%; P<0.05). Endothelial cell expression of the downstream proinflammatory cytokine interleukin-6 also was higher in deficient versus sufficient subjects (0.67±0.08 versus 0.47±0.05; P<0.01) and inversely related to serum 25(OH)D level (r=−0.62; P<0.01), whereas vitamin D receptor and 1-&agr; hydroxylase, the 25(OH)D to 1,25-dihydroxyvitamin D converting enzyme, were lower (P<0.05). Inadequate serum 25(OH)D is associated with vascular endothelial dysfunction among healthy middle-aged/older adults, and this is mediated in part by nuclear factor &kgr;B–related inflammation. Reduced vitamin D receptor and 1-&agr; hydroxylase may be molecular mechanisms linking vitamin D insufficiency to endothelial dysfunction.

We evaluated associations between serum 25-hydroxyvitamin D [25(OH)D] level and severity of new coronavirus infection (COVID-19) in hospitalized patients. We assessed serum 25(OH)D level in 133 patients aged 21–93 years. Twenty-five (19%) patients had severe disease, 108 patients (81%) had moderate disease, and 18 (14%) patients died. 25(OH)D level ranged from 3.0 to 97.0 ng/mL (median, 13.5 [25%; 75%, 9.6; 23.3] ng/mL). Vitamin D deficiency was diagnosed in 90 patients, including 37 with severe deficiency. In patients with severe course of disease, 25(OH)D level was lower (median, 9.7 [25%; 75%, 6.0; 14.9] ng/mL), and vitamin D deficiency was more common than in patients with moderate course (median, 14.6 [25%; 75%, 10.6; 24.4] ng/mL, p = 0.003). In patients who died, 25(OH)D was 9.6 [25%; 75%, 6.0; 11.5] ng/mL, compared with 14.8 [25%; 75%, 10.1; 24.3] ng/mL in discharged patients (p = 0.001). Severe vitamin D deficiency was associated with increased risk of COVID-19 severity and fatal outcome. The threshold for 25(OH)D level associated with increased risk of severe course was 11.7 ng/mL. Approximately the same 25(OH)D level, 10.9 ng/mL, was associated with increased risk of mortality. Thus, most COVID-19 patients have vitamin D deficiency; severe vitamin D deficiency is associated with increased risk of COVID-19 severity and fatal outcome.

Vitamin D was discovered as a result of its ability to cure rickets, but recently many other important functions for it in the human body have been discoverred, and it counteracts several other diseases, such as diabetes and some forms of cancer. The nuclear vitamin D receptor has been found throughout the vertebrate phylum down to jawless fishes, but not in invertebrates. Its role in those organisms that are repsonsible for the main input to the aquatic food web and to human nutrition, i.e., phytoplankton and zooplankton, is not understood.This chapter summarizes the discovery of vitamin D and the chemistry and photochemistry of its precursors, transformations, and metabolites. The physiological roles of 1,25-dihydroxyvitamin D are briefly described, as well as evolutionary aspects of the signaling in animals based on this compound. The chapter is concluded with an overview of what is known about the occurrence and role of vitamin D in the plant kingdom, biogeographical aspects of vitamin D, and the relatively recent discovery of nonphotochemical production of vitamin D.

Vitamin D is one of the essential nutrients to sustain the human health. As a member of the steroid hormone family, it has a classic role in regulating metabolism of calcium and a non-classic role in affecting cell proliferation and differentiation. Epidemiological studies have shown that 25OHD deficiency is closely associated with common chronic diseases such as bone metabolic disorders, tumors, cardiovascular diseases, and diabetes. 25OHD deficiency is also a risk factor for neuropsychiatric disorders and autoimmune diseases. 25OHD deficiency is highly prevalent in the world. It is therefore necessary to know the adverse health effects of 25OHD deficiency, and to design interventions and early treatments for those who are likely to have low levels of 25OHD.

Vitamin D is obtained through food consumption and synthesis in the skin after ultraviolet (UV) B exposure (1). Researchers have reported associations between low 25-hydroxyvitamin D [25-(OH)D] levels and risk for fractures (26), falls (7, 8), cardiovascular disease (914), colorectal cancer (1320), diabetes (13, 14, 2129), depressed mood (13, 14, 30, 31), cognitive decline (13, 14), and death (13, 32). Vitamin D deficiency is determined by measuring total serum 25-(OH)D concentrations (33). Measuring 25-(OH)D levels is complicated by the presence of multiple assays (34); evidence of intermethod and interlaboratory variability in measurement (3543); and the lack of an internationally recognized, commutable vitamin D reference standard (44). Efforts to increase standardization are in progress (34, 44). There is no consensus on optimal 25-(OH)D concentrations. Although experts generally agree that levels lower than 50 nmol/L (20 ng/mL) are associated with bone health (36, 45), disagreement exists about whether optimal 25-(OH)D levels are higher than this threshold (Table 1). According to NHANES (National Health and Nutrition Examination Survey) data from 2001 to 2006, 33% of the U.S. population was at risk for 25-(OH)D levels below 50 nmol/L (20 ng/mL) (47) and 77% had 25-(OH)D levels below 75 nmol/L (30 ng/mL) (48). Risk factors for low vitamin D levels include darker skin pigmentation (33), low vitamin D intake (4951), little or no UVB exposure (49, 50, 5254), and obesity (4951, 55). Older age (4953), female sex (49, 51, 52), low physical activity (49, 50, 53), low education attainment (48), and low health status (51, 54) were factors also associated with vitamin D deficiency in some studies. Table 1. Summary of Current Opinions About Appropriate 25-(OH)D Level Cutoffs for Defining Vitamin D Deficiency and Associations Between These Cutoffs and Health Outcomes* Vitamin D deficiency is treated by increasing dietary intake of food fortified with vitamin D or oral vitamin D treatment. Two commonly available vitamin D treatments (vitamin D3 [cholecalciferol] and vitamin D2 [ergocalciferol]) are available in several forms (for example, tablet and gel capsule), dosages (for example, 200 to 500000 IU), and dosing regimens (for example, daily, weekly, monthly, or yearly) and can be given in combination with oral calcium (56, 57). Potential harms of vitamin D treatment include hypercalcemia, hyperphosphatemia, suppressed parathyroid hormone levels, and hypercalciuria (46, 58, 59). Although very high levels of vitamin D are associated with other potential harms, these events are rare with typical replacement doses (Table 1). Screening for vitamin D deficiency can identify persons with low levels who might benefit from treatment. This report reviews the current evidence on vitamin D screening in asymptomatic adults to help the U.S. Preventive Services Task Force (USPSTF) develop a recommendation statement. Although the USPSTF has not previously issued recommendations on screening for vitamin D deficiency, it has made recommendations on vitamin D supplementation to prevent adverse health outcomes (for example, falls, fractures, cancer, and cardiovascular disease) in populations not necessarily vitamin Ddeficient (that is, general populations who may or may not have been deficient) (6063). Methods Scope of the Review We developed a review protocol and analytic framework (Appendix Figure 1) that included the following key questions: Appendix Figure 1. Analytic framework. Numbers on figures indicate key questions. For a list of key questions, see the Methods section or Table 2. 1. Is there direct evidence that screening for vitamin D deficiency results in improved health outcomes? 1a. Are there differences in screening efficacy between patient subgroups? 2. What are the harms of screening (for example, risk for procedure, false positives, or false negatives)? 3. Does treatment of vitamin D deficiency using vitamin D lead to improved health outcomes? 3a. Are there differences in efficacy between patient subgroups? 4. What are the adverse effects of treatment of vitamin D deficiency using vitamin D? 4a. Are there differences in adverse effects between patient subgroups? Detailed methods and data for this review are contained in the full report, including search strategies, inclusion criteria, abstraction and quality rating tables, and contextual questions (46). We developed our protocol using a standardized process after gathering input from experts and the public. The analytic framework focuses on direct evidence that screening for vitamin D deficiency improves important health outcomes (for example, death, falls, fractures, functional status, or risk for cancer) versus not screening. Further, the framework details evidence that treatment in persons found to have vitamin D deficiency is associated with improved health outcomes, harms resulting from screening or subsequent treatment, and how effects of screening and treatment vary in subgroups defined by demographic and other factors (for example, body mass index, UV exposure, and institutionalized status). We did not review the accuracy of vitamin D testing because of the lack of an accepted reference standard and studies reporting diagnostic accuracy. For the purposes of this report, the term vitamin Ddeficient refers to populations in which at least 90% of persons have 25-(OH)D levels of 75 nmol/L (30 ng/mL) or less. For studies that did not restrict enrollment to persons with 25-(OH)D levels of 75 nmol/L (30 ng/mL), we used the mean 25-(OH)D level plus the SD multiplied by 1.282 to approximate the 90th percentile to determine whether this level was at or below the 75-nmol/L (30-ng/mL) threshold. Because of uncertainty about what 25-(OH)D level constitutes deficiency, we stratified studies according to whether at least 90% of persons had levels less than 50 nmol/L (<20 ng/mL in this report) or at least 90% had levels less than 75 nmol/L (30 ng/mL) with at least 10% greater than 50 nmol/L (20 ng/mL) (75 nmol/L [30 ng/mL] in this report). Data Sources and Searches A research librarian searched Ovid MEDLINE (1946 through the third week of August 2014), Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (through August 2014). We supplemented our electronic searches by reviewing reference lists of retrieved articles. Study Selection At least 2 reviewers independently evaluated each study to determine inclusion eligibility. For screening studies, we included randomized, controlled trials (RCTs) of screening for vitamin D deficiency versus no screening in healthy, asymptomatic adults (aged 18 years). For studies of the effectiveness of vitamin D treatment, we included RCTs of vitamin D treatment with or without calcium versus placebo or no treatment in vitamin Ddeficient persons that reported health outcomes after at least 8 weeks of treatment. Because the Women's Health Initiative (WHI) is the largest RCT about vitamin D (64), we included data from nested casecontrol studies of WHI participants with known 25-(OH)D status. We included English-language articles only and excluded studies published only as abstracts. We included studies conducted in the United States, Canada, United Kingdom, and other geographic settings generalizable to the United States. We excluded studies that specifically targeted populations with symptoms or conditions associated with vitamin D deficiency (for example, osteoporosis, history of nontraumatic fractures, or history of falls) or with medical conditions that increase a person's risk for deficiency (such as liver, kidney, or malabsorptive disease) because screening and treatment of vitamin D deficiency could be a component of medical management in these conditions. The summary of evidence search and selection is shown in Appendix Figure 2. Appendix Figure 2. Summary of evidence search and selection. 25-(OH)D = 25-hydroxyvitamin D. * Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Identified from reference lists or by hand-searching or suggested by experts. Studies that provided data and contributed to the body of evidence were considered included. Studies may have provided data for more than 1 key question or published article; 27 unique studies were included, and a total of 35 articles were included. Data Abstraction and Quality Rating One investigator abstracted details about the study design, patient population, setting, screening method, interventions, analysis, follow-up, and results. A second investigator reviewed data for accuracy. Two investigators independently applied USPSTF criteria (65) to rate the quality of each study as good, fair, or poor. We resolved discrepancies through a consensus process. We excluded from data synthesis studies rated as poor quality. Those studies had 1 or more fatal flaws, including inadequate randomization or lack of intervention fidelity combined with postrandomization exclusions, high rates of withdrawals, and unclear randomization. Data Synthesis and Analysis We assessed the aggregate internal validity (quality) of the body of evidence for each key question (good, fair, or poor) using methods developed by the USPSTF on the basis of the number, quality, and size of studies; consistency of results; and directness of evidence (65). We conducted meta-analyses to calculate risk ratios (RRs) using the DerSimonianLaird random-effects model (Review Manager, version 5.2; Cochrane Collaboration). Analyses were based on total follow-up (including time after discontinuation of vitamin D treatment). For falls per person, we calculated incidence rate ratios and assumed equal mean length of follow-up across treatment groups if these data were not reported. For analyses with between-study heterogeneity, we conducted sensitivity analyses using profile likelihood random-effects models (66). Rate ratio analysis and analyses using the profil

Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25‐hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population‐based cohort. This is the first longitudinal population‐based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10‐year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (−0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow‐up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels. © 2012 American Society for Bone and Mineral Research.

Vitamin D is best known for its influence on skeletal health. There is growing recognition, however, that vitamin D has nonskeletal actions, which could have important implications for understanding the consequences of vitamin D deficiency. In epidemiologic studies, vitamin D deficiency has been consistently associated with an increased risk for cardiovascular disease and hypertension. Disruption of vitamin D signaling in animal models promotes hypertension, cardiac hypertrophy, and atherosclerosis. This evidence has led to the initiation of prospective randomized trials of vitamin D supplementation in individuals at risk for cardiovascular disease. The results of these trials should help to guide strategies for screening and management of vitamin D deficiency in the clinic and at the population level.

Vitamin D has long been known to be vital to bone health. More recently, vitamin D has been shown to play a role in the risk of malignancy, infection, autoimmune disease, renal disease, and cardiovascular disease (CVD) including its associated risk factors of diabetes and hypertension. Within the umbrella of cardiovascular disorders, low vitamin D levels have been specifically linked to increased risk of congestive heart failure, left ventricular hypertrophy, peripheral arterial disease, subclinical vascular disease, myocardial infarction, stroke, and mortality - associations that remain even after traditional risk factors and lifestyle factors are taken into account. However, a direct causal relationship between 25(OH)D deficiency and the risk of CVD has not been completely established. A thorough review of the scientific evidence linking vitamin D deficiency with CVD as well as an explanation of the po- tential biologic mechanisms that may support these associations will be the focus of this review.

Vitamin D has important immunomodulatory effects on psoriasis in the Mediterranean region. To measure vitamin D intake in subjects with and without psoriasis, and to find an association with relevant clinical features, a case-control study was performed using cases (n = 50, 50% participation rate) clinically diagnosed with psoriasis and 200 healthy subjects (39.5% participation rate), leaving a final sample of 104 people. A survey was conducted using a food frequency questionnaire and clinical histories. Cases and controls were compared using univariate and multivariate analyses. We observed insufficient intake of cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) for both cases and controls. Patients with psoriasis were at greater risk of associated pathologies: dyslipidaemia (OR: 3.6, 95% CI: 0.8–15.2); metabolic syndrome (OR: 3.3, 95% CI: 0.2–53.9); hypertension (OR: 1.7, 95% CI: 0.4–7.2). Insufficient vitamin D intake in both psoriasis patients and controls in the Mediterranean population, and cardiovascular comorbility is more frequent in patients with psoriasis.

Vitamin D deficiency is common and has been proposed as a risk factor for cardiovascular disease (CVD), but much of this evidence is inconsistent. The aim of the thesis was to explore the associations between vitamin D status (25(OH)D) and selected risk biomarkers of CVD, in participants of the British 1958 birth cohort free from CVD. Different methodologies were used in an attempt to avoid confounded associations. Mediation analysis was used to infer an association between 25(OH)D and biomarkers from seasonal variations. A genome-wide association study (GWAS) was done to find single nucleotide polymorphisms (SNPs) associated with 25(OH)D. SNPs found by the GWAS and SNPs in candidate genes were evaluated as proxy markers for 25(OH)D, and used in Mendelian randomisation (MR) analysis with the biomarkers. Higher 25(OH)D concentrations were associated with lower levels of tissue plasminogen activator (tPA), after adjusting for lifestyle, socio-economic and adiposity covariates. An association between 25(OH)D and tPA was inferred using mediation analysis. In the GWAS, SNPs from genes involved in the synthesis, hydroxylation and transportation of vitamin D were associated with 25(OH)D. SNPs passing evaluation as proxy markers for 25(OH)D were classified as “synthesis” and “metabolism” based on gene function, with the former considered to be a more robust proxy than the latter. Statistical power to detect an association was limited in MR analysis. However, there was some evidence that 25(OH)D had a protective association with tPA, when metabolism SNPs were used as proxy for 25(OH)D in MR analysis. Findings from the different analyses were inconsistent for CRP, D-dimer and fibrinogen. In conclusion, the findings tentatively suggest that vitamin D has a beneficial influence on CVD through the mechanism of fibrinolysis. However, more evidence is required from large MR studies and randomised controlled trials before the role of vitamin D in CVD is conclusively understood.

Vitamin D deficiency is associated with osteoporosis and is thought to increase the risk of cancer and CVD. Despite these numerous potential health effects, data on vitamin D status at the population level and within key subgroups are limited. The aims of the present study were to examine patterns of 25-hydroxyvitamin D (25(OH)D) levels worldwide and to assess differences by age, sex and region. In a systematic literature review using the Medline and EMBASE databases, we identified 195 studies conducted in forty-four countries involving more than 168 000 participants. Mean population-level 25(OH)D values varied considerably across the studies (range 4·9–136·2 nmol/l), with 37·3 % of the studies reporting mean values below 50 nmol/l. The highest 25(OH)D values were observed in North America. Although age-related differences were observed in the Asia/Pacific and Middle East/Africa regions, they were not observed elsewhere and sex-related differences were not observed in any region. Substantial heterogeneity between the studies precluded drawing conclusions on overall vitamin D status at the population level. Exploratory analyses, however, suggested that newborns and institutionalised elderly from several regions worldwide appeared to be at a generally higher risk of exhibiting lower 25(OH)D values. Substantial details on worldwide patterns of vitamin D status at the population level and within key subgroups are needed to inform public health policy development to reduce risk for potential health consequences of an inadequate vitamin D status.

Vitamin D deficiency and asthma are common conditions that share risk factors such as African American ethnicity, inner-city residence, and obesity. This review provides a critical examination of current experimental and epidemiologic evidence of a causal association between vitamin D status and asthma or asthma morbidity, including potential protective mechanisms such as antiviral effects and enhanced steroid responsiveness. Because most published epidemiologic studies of vitamin D and asthma or asthma morbidity are observational, a recommendation for or against vitamin D supplementation as preventive or secondary treatment for asthma is not advisable and must await results of ongoing clinical trials. Should these trials confirm a beneficial effect of vitamin D, others will be needed to assess the role of vitamin D supplementation to prevent or treat asthma in different groups such as infants, children of school age, and ethnic minorities.

UNLABELLED Even in developed countries the prevalence of subjects with suboptimal vitamin D levels is high. The aim of this retrospective data analysis was to evaluate the prevalence of severe and moderate vitamin D deficiencies (defined as vitamin D levels<15 ng/ml and 15-30 ng/ml, respectively) among patients evaluated at Semmelweis University during a period between April, 2009 and March, 2010. METHODS AND RESULTS The average vitamin D level of 5808 subjects (3936 women and 1872 men) was 25.5 ± 10.9 ng/ml. The prevalence of moderate and severe vitamin D deficiency in whole population was 72% and 12%, respectively. Higher than normal vitamin D levels were measured in 0.8% of subjects. Female gender, older age and winter season were independent risk factors for vitamin D deficiency. Vitamin D levels were measured repeatedly in 1307 subjects. Interestingly, vitamin D levels measured later were lower compared to those measured at the first time (27.07±13.2 vs. 25.9±9.11 ng/ml, p<0.001). The prevalence of severe and moderate vitamin D deficiency was 8.1 and 71.5 per cent when vitamin D levels were measured at the second time. Of the 110 patients with severe vitamin D deficiency measured repeatedly only 11 patients (10%) presented with normal vitamin D levels at the second time. CONCLUSIONS These data indicate that severe and moderate vitamin D deficiencies are common in patients evaluated at Semmelweis University. Repeated measurements of vitamin D levels raise the notion that the efficacy of supplementation used for correction of vitamin D levels is not optimal.

To cite this article: Bozzetto S, Carraro S, Giordano G, Boner A, Baraldi E. Asthma, allergy, and respiratory infections: the vitamin D hypothesis. Allergy 2012; 67: 10–17.

This study investigated a potential independent association between hypovitaminosis D and suspected nonalcoholic fatty liver disease (NAFLD) in a nationally representative sample of the US adolescents. Data from 1630 subjects 12–19 years of age were examined using the National Health and Nutrition Examination Survey, 2001–2004. The vitamin D status of subjects was categorized into quartiles of serum 25-hydroxyvitamin D. Subjects with serum ALT > 30 U/L were classified as having suspected NAFLD. Data regarding age, sex, race, BMI, and poverty level were also analyzed in bivariate and multivariate analyses using SAS and SUDAAN software. Suspected NAFLD was identified in 12.1% of adolescents in the lowest quartile compared to 6.9% of adolescents in the second quartile, 8.0% in the third quartile, and 13.17% in the highest quartile of serum 25(OH)D concentrations (P = .05). In analyses utilizing vitamin D as a continuous variable, no independent association was found between Vitamin D levels and rates of elevated ALT levels. In multivariate analyses, higher risks for suspected NAFLD were observed in males and overweight adolescents; however, vitamin D status was not found to be independently associated with suspected NAFLD after adjusting for obesity.

This review provides an update on asthma in Hispanics, a diverse group tracing their ancestry to countries previously under Spanish rule. A marked variability in the prevalence and morbidity from asthma remains among Hispanic subgroups in the United States and Hispanic America. In the United States, Puerto Ricans and Mexican Americans have high and low burdens of asthma, respectively (the “Hispanic Paradox”). This wide divergence in asthma morbidity among Hispanic subgroups is multifactorial, likely reflecting the effects of known (secondhand tobacco smoke, air pollution, psychosocial stress, obesity, inadequate treatment) and potential (genetic variants, urbanization, vitamin D insufficiency, and eradication of parasitic infections) risk factors. Barriers to adequate asthma management in Hispanics include economic and educational disadvantages, lack of health insurance, and no access to or poor adherence with controller medications such as inhaled corticosteroids. Although considerable progress has been made in our understanding of asthma in Hispanic subgroups, many questions remain. Studies of asthma in Hispanic America should focus on environmental or lifestyle factors that are more relevant to asthma in this region (e.g., urbanization, air pollution, parasitism, and stress). In the United States, research studies should focus on risk factors that are known to or may diverge among Hispanic subgroups, including but not limited to epigenetic variation, prematurity, vitamin D level, diet, and stress. Clinical trials of culturally appropriate interventions that address multiple aspects of asthma management in Hispanic subgroups should be prioritized for funding. Ensuring high-quality healthcare for all remains a pillar of eliminating asthma disparities.

There is mounting evidence that periodontal disease (PD) is linked to low serum 25-hydroxyvitamin D [25(OH)D] concentrations in addition to recognized risk factors like diet and smoking. This paper reviews this evidence using Hill's criteria for causality in a biological system. Evidence for strength of association, consistency, cohesion and 'dose-effects' [biological 'gradients'] include strong inverse correlations between serum 25(OH) and both PD cross-sectionally and that PD is consistently more prevalent in darker vs. lighter skinned people and increases at higher latitudes with analogy for gingivitis and for disorders associated with PD whose risks increase with hypovitaminosis D. Evidence for plausibility includes that vitamin D increases calcium absorption and protects bone strength; induces formation of cathelicidin and other defensins that combat bacterial infection; reduces tissue production of destructive matrix metalloproteinases actively associated with PD and that prevalence of PD varies with common vitamin D receptor polymorphisms. Experimental evidence from limited supplementation studies [using calcium and vitamin D] shows that supplementation reduces tooth loss. Thus, existing evidence for hypovitaminosis D as a risk factor for PD to date meets Hill's criteria for causality in a biological system. Further experimental evidence for effectiveness and temporality, preferably from randomized controlled trials of vitamin D supplementation [adjusting for other PD risk factors including diet and smoking to reduce confounding] are necessary to confirm causality. If confirmed, dentists and periodontists could perform a valuable service to their patients by discussing the importance of adequate vitamin D status and on how to avoid deficiency.

The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

The vitamin D related pathway has been evaluated in carcinogenesis but its genetic contribution remains poorly understood. We examined single‐nucleotide polymorphisms (SNPs) in the vitamin D related pathway genes using data from a genome‐wide association study (GWAS) of breast cancer in the African Diaspora that included 3,686 participants (1,657 cases). Pathway‐ and gene‐level analyses were conducted using the adaptive rank truncated product test. Odds ratios (OR) and 95% confidence intervals (CI) were estimated at SNP‐level. After stringent Bonferroni corrections, we observed no significant association between variants in the vitamin D pathway and breast cancer risk at the pathway‐, gene‐, or SNP‐level. In addition, no association was found for either the reported signals from GWASs of vitamin D related traits, or the SNPs within vitamin D receptor (VDR) binding regions. Furthermore, a decrease in genetically predicted 25(OH)D levels by Mendelian randomization was not associated with breast cancer (p = 0.23). However, an association for breast cancer with the pigment synthesis/metabolism pathway almost approached significance (pathway‐level p = 0.08), driven primarily by a nonsense SNP rs41302073 in TYRP1, with an OR of 1.54 (95% CI = 1.24–1.91, padj = 0.007). In conclusion, we found no evidence to support an association between vitamin D status and breast cancer risk in women of African ancestry, suggesting that vitamin D is unlikely to have significant effect on breast carcinogenesis. Interestingly, TYRP1 might be related to breast cancer through a non‐vitamin D relevant mechanism but further studies are needed.

The recent review reported that African Americans had greater risk of complications including sepsis/ septicemia, urinary tract infections, renal failure, and all-cause mortality rate Caucasian burn victims.1 Lower vitamin D status for African Americans than Caucasians appears to play an important role in explaining the observed disparity.2 There are many health outcomes for which higher 25-hydroxyvitamin D [25(OH)D] concentrations are associated with better outcomes.3 During the period 2001 to 2004, 20 to 39–year– old U.S. blacks had mean 25(OH)D concentrations of 14 to 16 ng/mL, while whites had 26 to 28 ng/mL.4 Lower 25(OHO)D concentration is a significant risk factor for sepsis,5 risk of recurrent urinary tract infection in premenopausal women,6 mortality rates for those with chronic kidney disease,7 and all-cause mortality rate.8 While these studies were mostly related to whites, the role of vitamin D for blacks and whites are similar.2 Perhaps more importantly for burn patients, vitamin D also plays an important role in recovery from wounds. Treatment of fibroblasts with both vitamin D and low concentration of transforming growth factor, beta 1 (TGFβ1) increased gene expression of TGFβ1, connective tissue growth factor, and fibronectin 1, and enhanced fibroblast migration, myofibroblast formation, and collagen production.9 A mouse model study found that vitamin D and calcium signaling are necessary components of the epidermal response to wounding, likely by regulating stem cell activation through increased β-catenin transcriptional activity.10 An in vitro experiment demonstrated that vitamin D receptor and the calcium sensing receptor are required for β-catenin regulated cell proliferation and adherens junction formation essential for reepithelialization following wounding.11 A clinical trial of vitamin D supplementation in critically ill pediatric burn patients found during the following year nonsignificant but clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formation.12 Burn patients should be given vitamin D3 supplements, although the proper dosing does not appear to have been worked out.13