Factors Affecting Postpartum Bone Mineral Density in a Clinical Trial of Vitamin D Supplementation.

Background: Few studies evaluate the effects of vitamin D status and supplementation on maternal bone mineral density (BMD) during lactation and further lack inclusion of diverse racial/ethnic groups, body mass index (BMI), or physical activity. Objective: Determine the effects of vitamin D treatment/status, feeding type, BMI, race/ethnicity, and physical activity on postpartum women's BMD to 7 months. Methods: Women with singleton pregnancies beginning 4-6 weeks' postpartum were randomized into two treatment groups (400 or 6400 IU vitamin D/day). Participant hip, spine, femoral neck, and whole-body BMD using Dual-energy X-ray absorptiometry (DXA Hologic), serum 25-hydroxyvitamin D [25(OH)D] (RIA; Diasorin), BMI, and physical activity were measured at 1, 4, and 7 months postpartum. A general linear mixed modeling approach was undertaken to assess the effects of vitamin D status [both serum 25(OH)D concentrations and treatment groups], feeding type, race/ethnicity, BMI, and physical activity on BMD in postpartum women. Results: During the 6-month study period, lactating women had 1-3% BMD loss in all regions compared with 1-3% gain in nonlactating women. Higher maternal BMI was associated with less bone loss in femoral neck and hip regions. Black American women had less BMD loss than White/Caucasian or Hispanic lactating women in spine and hip regions. Exclusively breastfeeding women in the 6400 IU vitamin D group had less femoral neck BMD loss than the 400 IU group at 4 months sustained to 7 months. Physical activity was associated with higher hip BMD. Conclusion: While there was BMD loss during lactation to 7 months, the loss rate was less than previously reported, with notable racial/ethnic variation. Breastfeeding was associated with loss in BMD compared with formula-feeding women who gained BMD. Higher BMI and physical activity independently appeared to protect hip BMD, whereas higher vitamin D supplementation appeared protective against femoral neck BMD loss.

Residential Greenness, Lifestyle, and Vitamin D: A Longitudinal Cohort of South Asian Origin and Caucasian Ethnicity Women Living in the South of the UK.

The global population is at risk of vitamin D deficiency due to low exposure to sunlight and low intake of the vitamin through diet. The aim of this study was to investigate in women the association between vitamin D status and parathyroid hormone (PTH), ultraviolet radiation, lifestyle, ethnicity, social conditions, and residential greenness. A 1-year longitudinal study assessed vitamin D status in 309 women living at latitude 51°14' N. Blood samples were taken four times throughout the year for analysis of 25(OH)D and serum PTH concentration. After each seasonal visit, the individuals completed 4-day diet diaries and used two dosimeter badges for 1 week to estimate weekly UVR exposure. A questionnaire was applied to provide information about lifestyle and their ethnicity. Residential greenness was measured by Normalized Difference Vegetation Index (NDVI), within a 1000 m radius around each participant's home address. Women living in greener spaces were more likely to have improved vitamin D status (RR: 1.51; 95%CI: 1.13-2.02), as well as those who were more exposed to UVR (RR: 2.05; 95%CI: 1.44-2.92). Our results provide an insight into the connection between residential greenness, lifestyle, and vitamin D status comparing two ethnicities in a country with a temperate climate and with a high degree of urbanization.

Vitamin D levels among adult psychiatric inpatients and the association with psychosis.

BACKGROUND: The association between low vitamin D levels and mental illness has been described in earlier research. The aim of our study was to examine the association between vitamin D levels with psychotic symptoms among hospitalized patients. METHODS: A total of 1,456 patient records from an academic psychiatric hospital were examined. Vitamin D levels were classified as normal (>30 ng/mL); insufficient (20 to 30 ng/mL); and deficient (<20 ng/mL). We then analyzed the association among vitamin D groups and symptoms of psychosis. RESULTS: The average vitamin D level in our sample was 23.59 ng/mL, with 76.2% of patients presenting with vitamin D levels <30 ng/mL. There was a significant association between vitamin D levels <20 ng/mL and symptoms of psychosis (P < .05). African American patients had lower mean vitamin D levels than White patients (15.6 ± 0.2 ng/mL vs 25.8 ± 0.4 ng/mL, P < .001). There was no sex difference in vitamin D levels (females: 23.3 ± 11.5 ng/mL; males: 23.9 ± 11.0 ng/mL). CONCLUSIONS: Patients with vitamin D levels <30 ng/mL were 1.5 times more likely to have symptoms of psychosis. Patients who were African American, Hispanic, Asian, or biracial had lower vitamin D levels than patients who were White. Multivariate analysis found that after adjusting for age, sex, and race, the association between vitamin D and psychosis was not statistically significant. Possible explanations could include the known tendency to overdiagnose psychosis among individuals who are African American, referral bias, subgroup effect, or an epiphenomenon.

Serum 25-hydroxyvitamin D concentrations are inversely associated with all-cause mortality among Koreans: a nationwide cohort study.

Evidence on the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and all-cause and cause-specific mortality in Asians, especially Koreans, is limited. We hypothesized that high concentrations of 25(OH)D are associated with lower all-cause and cause-specific mortality in the general Korean population. This study included 27,846 adults participating in the Fourth and Fifth Korean National Health and Nutrition Examination Survey 2008-2012, followed up through December 31, 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using multivariable-adjusted Cox proportional hazards regression. The weighted mean serum 25(OH)D of study participants was 17.77 ng/mL; 66.5% had vitamin D deficiency (<20 ng/mL) and 94.2% had insufficient vitamin D (<30 ng/mL). During a median follow-up of 9.4 years (interquartile range, 8.1-10.6 years), 1680 deaths were documented, including 362 CVD deaths and 570 cancer deaths. Serum 25(OH)D levels ≥30 ng/mL were inversely associated with all-cause mortality (HR, 0.57; 95% CI, 0.43-0.75) compared with serum 25(OH)D levels <10 ng/mL. Based on the quartile cutoffs of serum 25(OH)D concentration, the highest quartile of serum 25(OH)D concentration (≥21.8 ng/mL) was associated with the lowest all-cause mortality (HR, 0.72; 95% CI, 0.60-0.85; P trend < .001), and CVD mortality (HR, 0.60; 95% CI, 0.42-0.85; P trend = .006). No association with cancer mortality outcome was found. In conclusion, higher serum 25(OH)D levels were associated with lower all-cause mortality in the general Korean population. An additional association was found between higher quartile of serum 25(OH)D and lower CVD mortality.

Effect of Vitamin D Supplementation on Outcomes in People With Early Psychosis: The DFEND Randomized Clinical Trial.

Importance: People with psychotic disorders have an increased risk of vitamin D deficiency, which is evident during first-episode psychosis (FEP) and associated with unfavorable mental and physical health outcomes. Objective: To examine whether vitamin D supplementation contributes to improved clinical outcomes in FEP. Design, Setting, and Participants: This multisite, double-blind, placebo-controlled, parallel-group randomized clinical trial from the UK examined adults 18 to 65 years of age within 3 years of a first presentation with a functional psychotic disorder who had no contraindication to vitamin D supplementation. A total of 2136 patients were assessed for eligibility, 835 were approached, 686 declined participation or were excluded, 149 were randomized, and 104 were followed up at 6 months. The study recruited participants from January 19, 2016, to June 14, 2019, with the final follow-up (after the last dose) completed on December 20, 2019. Interventions: Monthly augmentation with 120 000 IU of cholecalciferol or placebo. Main Outcomes and Measures: The primary outcome measure was total Positive and Negative Syndrome Scale (PANSS) score at 6 months. Secondary outcomes included total PANSS score at 3 months; PANSS positive, negative, and general psychopathology subscale scores at 3 and 6 months; Global Assessment of Function scores (for symptoms and disability); Calgary Depression Scale score, waist circumference, body mass index, and glycated hemoglobin, total cholesterol, C-reactive protein, and vitamin D concentrations at 6 months; and a planned sensitivity analysis in those with insufficient vitamin D levels at baseline. Results: A total of 149 participants (mean [SD] age, 28.1 (8.5) years; 89 [59.7%] male; 65 [43.6%] Black or of other minoritized racial and ethnic group; 84 [56.4%] White [British, Irish, or of other White ethnicity]) were randomized. No differences were observed in the intention-to-treat analysis in the primary outcome, total PANSS score at 6 months (mean difference, 3.57; 95% CI, -1.11 to 8.25; P = .13), or the secondary outcomes at 3 and 6 months (PANSS positive subscore: mean difference, -0.98; 95% CI, -2.23 to 0.27 at 3 months; mean difference, 0.68; 95% CI, -0.69 to 1.99 at 6 months; PANSS negative subscore: mean difference, 0.68; 95% CI, -1.39 to 2.76 at 3 months; mean difference, 1.56; 95% CI, -0.31 to 3.44 at 6 months; and general psychopathology subscore: mean difference, -2.09; 95% CI, -4.36 to 0.18 at 3 months; mean difference, 1.31; 95% CI, -1.42 to 4.05 at 6 months). There also were no significant differences in the Global Assessment of Function symptom score (mean difference, 0.02; 95% CI, -4.60 to 4.94); Global Assessment of Function disability score (mean difference, -0.01; 95% CI, -5.25 to 5.23), or Calgary Depression Scale score (mean difference, -0.39; 95% CI, -2.05 to 1.26) at 6 months. Vitamin D levels were very low in the study group, especially in Black participants and those who identified as another minoritized racial and ethnic group, 57 of 61 (93.4%) of whom had insufficient vitamin D. The treatment was safe and led to a significant increase in 25-hydroxyvitamin D concentrations. Conclusions and Relevance: In this randomized clinical trial, no association was found between vitamin D supplementation and mental health or metabolic outcomes at 6 months. Because so few patients with FEP were vitamin D replete, the results of this study suggest that this group would benefit from active consideration in future population health strategies. Trial Registration: isrctn.org Identifier: ISRCTN12424842.

Vitamin D Status of the British African-Caribbean Residents: Analysis of the UK Biobank Cohort.

The vitamin D status of the United Kingdom (UK) African-Caribbean (AC) population remains under-researched, despite an increased risk of vitamin D deficiency due to darker skin phenotypes and living at a high latitude. This cross-sectional study explored the vitamin D status and intake of AC individuals (n = 4046 with a valid serum 25(OH)D measurement) from the UK Biobank Cohort, aged ≥40 years at baseline (2006-2010). Over one third of the population were deficient (<25 nmol/L), 41.1% were insufficient (25-50 nmol/L) and 15.9% were sufficient (>50 nmol/L). Median (IQR) 25(OH)D was 30.0 (20.9) nmol/L. Logistic regression showed that brown/black skin phenotype, winter blood draw, not consuming oily fish and not using vitamin D supplements predicted increased odds of vitamin D deficiency, whilst older age and a summer or autumn blood draw were significantly associated with reduced odds of vitamin D deficiency. Vitamin D deficiency and insufficiency were prevalent in this AC population and is of considerable concern given the individual and societal implications of increased morbidity. Public health messaging for this group should focus on year-round vitamin D supplementation and increasing intakes of culturally appropriate vitamin D-rich foods. These data also support the urgent requirement for a revised vitamin D RNI for ethnic groups.

Risk Allele Frequency Analysis of Single-Nucleotide Polymorphisms for Vitamin D Concentrations in Different Ethnic Group.

The prevalence of vitamin D deficiency varies from 20.8% to 61.6% among populations of different ethnicities, suggesting the existence of a genetic component. The purpose of this study was to provide insights into the genetic causes of vitamin D concentration differences among individuals of diverse ancestry. We collected 320 single-nucleotide polymorphisms (SNPs) associated with vitamin D concentrations from a genome-wide association studies catalog. Their population-level allele frequencies were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher's exact tests to assess the significance of the enrichment or depletion of the effect allele at a given SNP in the database. In addition, we calculated the SNP-based genetic risk score (GRS) and performed correlation analysis with vitamin D concentration that included latitude. European, American, and South Asian populations showed similar heatmap patterns, whereas African, East Asian, and Korean populations had distinct ones. The GRS calculated from allele frequencies of vitamin D concentration was highest among Europeans, followed by East Asians and Africans. In addition, the difference in vitamin D concentration was highly correlated with genetic factors rather than latitude effects.

Vitamin D Status among First-Generation Immigrants from Different Ethnic Groups and Origins: An Observational Study Using the Canadian Health Measures Survey.

One in five Canadians are first-generation immigrants. Evidence suggests the baseline risk for vitamin D (vitD) deficiency is increased among immigrants who move from equatorial to northern countries. We investigated the prevalence and determinants of vitD deficiency/insufficiency among first-generation immigrants compared with native-born Canadians and identified explanatory covariables. We used a cross-sectional design with data from the national Canadian Health Measures Survey (Cycles 3 and 4) (11,579 participants aged 3-79 years). We assessed serum 25-hydroxyvitamin D (S-25(OH)D) levels, sociodemographic and environmental factors, immigration status, length of time in Canada, vitD-rich food intake, ethnicity, and place of birth. Immigrants had lower mean S-25(OH)D than non-immigrants (51.23 vs. 62.72 nmol/L, p < 0.001). Those with younger age at the time of immigration (<18 years) had a high risk for low vitD, and S-25(OH)D levels increased with the length of time they had lived in Canada. The highest deficiency levels were in immigrants born in Morocco, India, and Lebanon compared with native-born Canadians. Ethnicity was the factor most strongly associated with S-25(OH)D. Compared with the white ethnic grouping, the Japanese had the highest level of vitD deficiency, followed by Arabs and Southeast Asians. Ethnic variations, dietary intake, and lifestyle factors are the main predictors of/explanatory factors for vitD status among Canadian immigrants.

The Relationship between Sarcopenia and Vitamin D Levels in Adults of Different Ethnicities: Findings from the West China Health and Aging Trend Study.

OBJECTIVES: Sarcopenia is a condition associated with progressive loss of skeletal muscle mass and function resulting in substantial negative health outcomes and disability in older adults. It is thus important that sarcopenia-related risk factors be explored. The present study was based upon the Asian Working Group on Sarcopenia 2019 (AWGS2019) criteria to assess whether vitamin D levels are a risk factor associated with sarcopenia in various ethnic groups in western China. DESIGN: Cross-sectional study. SETTING: Communities in Yunnan, Guizhou, Sichuan, and Xinjiang provinces. PARTICIPANTS: We included 4236 individuals that were 50 years of age or older from the West China Health and Aging Trend (WCHAT) study. MEASUREMENTS: An InBody 770 instrument was used for bioimpedance-based analyses of muscle mass, while a digital grip strength dynamometer was used for handgrip strength-based measurements of muscle strength. Physical performance was assessed based upon gait speed over 4 m. Other secondary variables were additionally analyzed as potentially relevant risk factors. RESULTS: Sarcopenia affected an estimated 22.45% of studied individuals who were 50 years of age or older, with respective prevalence rates in the < 60, 60-64, 65-79, and ≥80 age groups of 11.78%,19.44%, 32.65%, and 67.97%. Rates in males and females were 26.66% and 20.05%, respectively. In males, a significant difference in vitamin D levels was detected when comparing individuals with and without sarcopenia, although no such relationship was detected in females. Following adjustment for confounding variables, binary logistic regression analyses revealed that inadequate vitamin D was able to independently predict sarcopenia risk only in males (OR=1.875,95%CI: 1.109-3.169, P=0.019). CONCLUSIONS: Among middle-aged and older adults of multiple ethnicities in western China, we found that inadequate vitamin D was an independent predictor of sarcopenia risk specifically in males.

Cross-sectional observational study - Investigation of vitamin D concentration in Caucasian cancer patients. what is the adequate dose of vitamin D for these patients?

BACKGROUND & AIMS: Vitamin D impairs tumour-related transformation and supports the anticancer function of the immune system. Currently, there are no guidelines on vitamin D supplementation devoted solely to cancer patients. The primary objective of the study was to evaluate the frequency of vitamin D deficiency in Caucasian cancer patients and to characterize the clinical factors that predispose individuals to decreased vitamin D concentration. Secondly, the study aimed to estimate the dose of vitamin D supplementation that would prevent deficiencies in patients with cancer. METHODS: In the presented cross-sectional study the population consisted of 500 consecutive Caucasian patients with a diagnosis of neoplastic disease, some of which declared long-term vitamin D supplementation in various doses. Serum vitamin D concentration was measured once in all patients and clinical data were obtained from the hospital database. The frequencies of vitamin D deficiency were compared to certain clinical variables by appropriate statistical tests. The dose of vitamin D substitution in cancer patients was estimated using the receiver operating characteristic (ROC) curve. RESULTS: Vitamin D deficiency was diagnosed in 66.8% of patients with cancer and even in 31.6% who declared vitamin D supplementation. Older age, male gender, diagnosis of head and neck cancer or squamous cell carcinoma and body mass loss were identified as factors that predispose to vitamin D deficiency. The dose of vitamin D that would prevent deficiency in Caucasian patients with cancer was set at 2250 IU daily. CONCLUSIONS: Vitamin D deficiency was very common in Caucasian patients with cancer, even in terms of vitamin D supplementation. The greatest predisposition was related to elder age, male gender, diagnosis of head and neck or squamous cell carcinoma and body mass loss. The dose of vitamin D supplementation in cancer patients should probably be higher than in the general population.

Vitamin D Deficiency is Associated with Handgrip Strength, Nutritional Status and T2DM in Community-Dwelling Older Mexican Women: A Cross-Sectional Study.

The aim of this study was to evaluate the association between handgrip strength, nutritional status and vitamin D deficiency in Mexican community-dwelling older women. A cross sectional study in women ≥ 60 years-old was performed. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured by a quantitative immunoassay technique. Handgrip strength was assessed using a dynamometer, while nutritional status was assessed through the Full Mini Nutritional Assessment (Full-MNA). A total of 116 women participated in the study, their mean age was 70.3 ± 5.8 years; 49.1% of the study group had plasma 25(OH)D levels lower than 40 nmol/L [16 ng/mL]. Meanwhile, 28.45% of participants had low handgrip strength (<16 kg), and 23.1% were identified at risk of malnutrition/malnourished according with Full-MNA score. Women with 25(OH)D deficiency (<40 nmol/L [16 ng/mL]) were more likely to have low handgrip strength (OR = 2.64, p = 0.025) compared with those with higher 25(OH)D values. Additionally, being malnourished or at risk of malnutrition (OR = 2.53, p = 0.045) or having type 2 diabetes mellitus (T2DM) (OR = 2.92, p = 0.044) was also associated with low 25(OH)D. The prevalence of low plasma 25(OH)D concentrations was high among Mexican active older women. Low handgrip strength, being at risk of malnutrition/malnourished, or diagnosed with T2DM was also associated with Vitamin D deficiency.

Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-19 Test Results.

Importance: Deficient (ie, <20 ng/mL) or insufficient (ie, 20 to <30 ng/mL) 25-hydroxyvitamin D (also known as calcifediol) levels are more common in Black individuals than White individuals and are associated with increased coronavirus disease 2019 (COVID-19) risk. Whether COVID-19 risk is associated with differences in vitamin D levels of 30 ng/mL or greater is not known. Objective: To examine whether COVID-19 test results are associated with differences in vitamin D levels of 30 ng/mL or greater, including for White individuals and for Black individuals. Design, Setting, and Participants: This retrospective cohort study was conducted at an academic medical center in Chicago, Illinois. Participants included individuals with data on vitamin D level within 365 days before COVID-19 testing, which was conducted from March 3 to December 30, 2020. Data were analyzed from September 11, 2020, to February 5, 2021. Exposures: The last vitamin D level before COVID-19 testing was categorized as less than 20 ng/mL (ie, deficient), 20 to less than 30 ng/mL (ie, insufficient), 30 to less than 40 ng/mL, or 40 ng/mL or greater. Treatment was defined by vitamin D type and dose 14 days before COVID-19 testing and treatment changes after last vitamin D level. Main Outcomes and Measures: The main outcome was a positive result for COVID-19 in polymerase chain reaction testing. Multivariable analyses tested whether previously measured vitamin D level was associated with having test results positive for COVID-19 in White individuals and in Black individuals, controlling for months and treatment changes since the vitamin D level was measured, as well as demographic characteristics and comorbidity indicators. Results: A total of 4638 individuals (mean [SD] age 52.8 [19.5] years; 3205 [69%] women) had data for a vitamin D level within 1 year before COVID-19 testing, including 2288 (49%) Black individuals, 1999 (43%) White individuals, and 351 individuals (8%) who were another race/ethnicity (eg, Asian, Mideast Indian, >1 race). Stratified by vitamin D level, 1251 individuals (27%) had less than 20 ng/mL, 1267 individuals (27%) had 20 to less than 30 ng/mL, 1023 individuals (22%) had 30 to less than 40 ng/mL, and 1097 individuals (24%) had 40 ng/mL or greater. Lower vitamin D levels were more common in Black individuals (<20 ng/mL: 829 of 2288 Black individuals [36%]) than White individuals (<20 ng/mL: 315 of 1999 White individuals [16%]). A total of 333 individuals (7%) had test results positive for COVID-19, including 102 White individuals (5%) and 211 Black individuals (9%). Multivariate analysis controlling for time since last vitamin D level measurement was used to estimate the outcomes associated with levels 14 days before COVID-19 testing. A positive test result for COVID-19 was not significantly associated with vitamin D levels in White individuals but was associated with vitamin D levels in Black individuals (compared with ≥40 ng/mL: <20 ng/mL incidence rate ratio [IRR], 2.55 [95% CI, 1.26-5.15]; P = .009; 20 to <30 ng/mL IRR, 1.69 [95% CI, 0.75-3.84]; P = .21; 30 to <40 ng/mL IRR, 2.64 [95% CI, 1.24-5.66]; P = .01). Stratified by vitamin D level, estimated COVID-19 positivity rates in Black individuals were 9.72% (95% CI, 6.74%-13.41%) for individuals with a vitamin D level less than 20 ng/mL, 6.47% (95% CI, 3.33%-10.28%) for individuals with a vitamin D level of 20 to less than 30 ng/mL, 10.10% (95% CI, 6.00%-15.47%) for individuals with a vitamin D level of 30 to less than 40 ng/mL, and 3.82% (95% CI, 1.78%-6.68%) for individuals with a vitamin D level of 40 ng/mL or higher. Multivariate analysis in individuals with a vitamin D level of 30 ng/mL or greater found that the IRR of a positive COVID-19 test result was 0.97 (95% CI, 0.94-0.99; P = .008) per 1-ng/mL increase in vitamin D overall and 0.95 (95% CI, 0.91-0.98; P = .003) per 1-ng/mL increase in vitamin D in Black individuals. Conclusions and Relevance: In this single-center retrospective cohort study, COVID-19 risk increased among Black individuals with vitamin D level less than 40 ng/mL compared with those with 40 ng/mL or greater and decreased with increasing levels among individuals with levels greater than 30 ng/mL. No significant associations were noted for White individuals. Randomized clinical trials should examine whether increasing vitamin D level to greater than 40 ng/mL affects COVID-19 risk.

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer's disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.

Peritraumatic Vitamin D Levels Predict Chronic Pain Severity and Contribute to Racial Differences in Pain Outcomes Following Major Thermal Burn Injury.

Major thermal burn injuries result in approximately 40,000 hospitalizations in the United States each year. Chronic pain affects up to 60% of burn survivors, and Black Americans have worse chronic pain outcomes than White Americans. Mechanisms of chronic pain pathogenesis after burn injury, and accounting for these racial differences, remain poorly understood. Due to socioeconomic disadvantage and differences in skin absorption, Black Americans have an increased prevalence of Vitamin D deficiency. We hypothesized that peritraumatic Vitamin D levels predict chronic pain outcomes after burn injury and contribute to racial differences in pain outcomes. Among burn survivors (n = 77, 52% White, 48% Black, 77% male), peritraumatic Vitamin D levels were more likely to be deficient in Blacks vs Whites (27/37 [73%] vs 14/40 [35%], P < .001). Peritraumatic Vitamin D levels were inversely associated with chronic post-burn pain outcomes across all burn injury survivors, including those who were and were not Vitamin D deficient, and accounted for approximately one-third of racial differences in post-burn pain outcome. Future studies are needed to evaluate potential mechanisms mediating the effect of Vitamin D on post-burn pain outcomes and the potential efficacy of Vitamin D in improving pain outcomes and reducing racial differences.

Genetic loci associated with skin pigmentation in African Americans and their effects on vitamin D deficiency.

A recent genome-wide association study (GWAS) in African descent populations identified novel loci associated with skin pigmentation. However, how genomic variations affect skin pigmentation and how these skin pigmentation gene variants affect serum 25(OH) vitamin D variation has not been explored in African Americans (AAs). In order to further understand genetic factors that affect human skin pigmentation and serum 25(OH)D variation, we performed a GWAS for skin pigmentation with 395 AAs and a replication study with 681 AAs. Then, we tested if the identified variants are associated with serum 25(OH) D concentrations in a subset of AAs (n = 591). Skin pigmentation, Melanin Index (M-Index), was measured using a narrow-band reflectometer. Multiple regression analysis was performed to identify variants associated with M-Index and to assess their role in serum 25(OH)D variation adjusting for population stratification and relevant confounding variables. A variant near the SLC24A5 gene (rs2675345) showed the strongest signal of association with M-Index (P = 4.0 x 10-30 in the pooled dataset). Variants in SLC24A5, SLC45A2 and OCA2 together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (P for interaction = 0.009). However, West African Ancestry (WAA) also accounts for a large proportion of M-Index variance (23%). M-Index also varies among AAs with high WAA and high Genetic Score calculated from top variants associated with M-Index, suggesting that other unknown genomic factors related to WAA are likely contributing to skin pigmentation variation. M-Index was not associated with serum 25(OH)D concentrations, but the Genetic Score was significantly associated with vitamin D deficiency (serum 25(OH)D levels less than 12 ng/mL) (OR, 1.30; 95% CI, 1.04-1.64). The findings support the hypothesis suggesting that skin pigmentation evolved responding to increased demand for subcutaneous vitamin D synthesis in high latitude environments.

Examining chronic inflammatory markers on blood pressure measures in the presence of vitamin D insufficiency among indigenous cree adults: results from the cross-sectional Multi-Community Environment-and-Health Study in Eeyou Istchee, Quebec, Canada.

OBJECTIVE: High blood pressure (BP) is a risk factor for cardiovascular disease. Examining the role of inflammatory mediators on BP is important since vitamin D (VD) is a modifiable risk factor, which possibly modulates inflammatory cytokines. This study simulated what are known as average 'controlled direct effects (CDE)' of inflammatory markers, C reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interlukin-6 (IL-6) on continuous BP measures, while fixing VD, an intermediate variable to specific level. DESIGN: Cross-sectional study. SETTING: We analysed data from the Multi-Community Environment-and-Health Study, 2005-2009, conducted in Eeyou Istchee, Quebec, Canada. PARTICIPANTS: This study recruited 1425 study Indigenous Cree participants from seven Cree communities. Only adults with serum VD levels, inflammatory markers and BP measures were included in this data analysis. PRIMARY AND SECONDARY OUTCOMES MEASURES: Inflammatory markers examined the top 25th exposure percentiles. VD 'insufficiency' (ie, 25-hydroxyvitamin-D levels<50 nmol/L) defined by the Institute of Medicine. CDE for each inflammatory marker in the presence and absence of population VD insufficiency simulated the average direct effect change for systolic and diastolic BP (SBP and DBP) measures. All models were adjusted for exposure-and-mediator outcome relationship. RESULTS: Among 161 participants, 97 (60 %) were female. The prevalence of VD insufficiency was 32%. CDE estimates show in the presence and absence of population vitamin D insufficiency, inflammatory markers have a slightly different association on BP. TNF-α significantly and inversely associated with SBP in the presence of vitamin D insufficiency, fully adjusted model ß = -13.61 (95% CI -24.42 to -2.80); however, TNF-α was not associated with SBP in the absence of vitamin D insufficiency. CRP, IL-6 were also not significantly associated with BP measures, although the magnitude of association was greater for those with elevated inflammation and VD insufficiency. CONCLUSION: This novel analysis shows in the presence of VD insufficiency, inflammation (particularly TNF-α) may affect SBP. Additional research is needed to elucidate these findings, and the temporal relationship between these variables.

Very high prevalence of 25-hydroxyvitamin D deficiency in 6433 UK South Asian adults: analysis of the UK Biobank Cohort.

Little research has assessed serum 25-hydroxyvitamin D (25(OH)D) concentration and its predictors in Western-dwelling South Asians in a relatively large sample size. This observational, cross-sectional analysis assessed baseline prevalence of 25(OH)D deficiency in UK-dwelling South Asians (aged 40-69 years, 2006-2010) from the UK Biobank Cohort. Serum 25(OH)D measurements were undertaken using the DiaSorin Liaison XL assay. Of 6433 South Asians with a 25(OH)D measurement, using commonly used cut-off thresholds, 55 % (n 3538) had 25(OH)D < 25 nmol/l (severe deficiency) and 92 % (n 5918) had 25(OH)D < 50 nmol/l (insufficiency). Of the participants with a measurement, 20 % (n 1287) had 25(OH)D concentration <15 nmol/l (very severe deficiency). When 824 participants with undetectable (<10 nmol/l) 25(OH)D measurements were included (total n 7257), 29 % (n 2105) had 25(OH)D < 15 nmol/l, 60 % (n 4354) had 25(OH)D < 25 nmol/l and 93 % (n 6749) had 25(OH)D < 50 nmol/l. Logistic regression predictors of 25(OH)D < 25 nmol/l included the following characteristics: being male; Pakistani; higher BMI; 40-59 years old; never consuming oily fish; summer sun exposure <5 h/d, not using a vitamin D-containing supplement, measurement in winter or spring and vegetarianism. In terms of region, median 25(OH)D concentration was 19-20 nmol/l in Scotland, Northern England, the Midlands and Wales. Across Southern England and London, it was slightly higher at 24-25 nmol/l. Our analyses suggest the need for increased awareness of vitamin D deficiency in South Asians as well as urgent public health interventions to prevent and treat vitamin D deficiency in this group.

Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis.

BACKGROUND: SARS-CoV-2 coronavirus infection ranges from asymptomatic through to fatal COVID-19 characterized by a 'cytokine storm' and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID-19. METHODS: Narrative review. RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID-19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P = 0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID-19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin-converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID-19 severity but it is all indirect. Community-based placebo-controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID-19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile, vitamin D supplementation should be strongly advised for people likely to be deficient.