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.

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.

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.

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.

Change in health profile of refugees resettling in New Zealand, 1980-2014.

AIM: To update data previously published on the health profile of the refugees resettling in New Zealand, and to draw attention to the change in health profile over time, with a decline of infectious disease/deficiencies, and a rise of non-communicable diseases, a worldwide phenomenon. METHOD: Comparative data was extracted from (1) written annual reports prepared by medical officers at the Mangere Refugee Resettlement Centre (1978-1991), (2) a Microsoft ACCESS patient management system between 1995 and 1999 and (3) a MEDTECH patient management system between 2010 and 2014. RESULTS: Over the period 1979-2014, the rate of infectious diseases has declined markedly in resettling refugees, and the rate of non-communicable diseases has increased. For example, the incidence of tuberculosis has decreased from 4% to 0.2%, gut parasites from more than 40% to, in some intakes, 15% and iron deficiency from 22% to 10%, while the diabetes rate has gone from 0.1% to 2.7%. CONCLUSION: While management of unfamiliar infectious diseases and deficiencies (especially vitamin D) still remains an important part of the management of refugee health, their management usually involves limited time and expense, and their burden is much less than before. However, refugees now resettling in New Zealand and the rest of the world often present with familiar non-communicable diseases that require long-term management.

Can Vitamin D and L-Cysteine Co-Supplementation Reduce 25(OH)-Vitamin D Deficiency and the Mortality Associated with COVID-19 in African Americans?

Early reports indicate an association between the severity of the COVID-19 infection and the widespread 25-hydroxy vitamin D deficiency known to exist in populations around the world. Vitamin D deficiency is extremely common among African American (AA) communities, where the COVID-19 infection rate is three-fold higher, and the mortality rate nearly six-fold higher, compared with rates in predominantly white communities. COVID-19 infection primarily affects the lungs and airways. Previous reports have linked 25-hydroxy vitamin D deficiency with subclinical interstitial lung disease. AA are at risk for lower cellular glutathione (GSH) levels, and GSH deficiency epigenetically impairs VD biosynthesis pathway genes. Compared with vitamin D alone, co-supplementation of vitamin D and L-cysteine (a GSH precursor) showed a better efficacy in improving levels of GSH and VD-regulatory genes at the cellular/tissue level, increasing 25(OH) vitamin D levels, and reducing inflammation biomarkers in the blood in mice studies. We propose that randomized clinical trials are needed to examine the potential of co-supplementation with anti-inflammatory antioxidants, vitamin D and L-cysteine in correcting the 25(OH)VD deficiency and preventing the 'cytokine storm,' one of the most severe consequences of infection with COVID-19, thereby preventing the adverse clinical effects of COVID-19 infection in the vulnerable AA population.

COVID-19 breakthroughs: separating fact from fiction.

The newly recognised coronavirus SARS-CoV-2, causative agent of coronavirus disease (COVID-19), has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID-19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS-CoV-2 and discuss the evidence and explications for a disproportionately stronger impact of COVID-19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS-CoV-2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS-CoV-2.

Vitamin D deficiency in western dwelling South Asian populations: an unrecognised epidemic.

Vitamin D deficiency (25-hydroxyvitamin D; 25(OH)D) is at epidemic proportions in western dwelling South Asian populations, including severe deficiency (<12⋅5 nmol/l) in 27-60% of individuals, depending on season. The paper aimed to review the literature concerning vitamin D concentrations in this population group. Research from the UK and Europe suggests a high prevalence of South Asians with 25(OH)D concentration <25 nmol/l, with most having a 25(OH)D concentration of <50 nmol/l. In Canada, South Asians appear to have a slightly higher 25(OH)D concentration. There are few studies from the United States, South Africa and Australasia. Reasons for vitamin D deficiency include low vitamin D intake, relatively high adiposity, sun exposure avoidance and wearing of a covered dress style for cultural reasons. Possible health effects of deficiency include bone diseases such as rickets and hypocalcaemia in children and osteomalacia in adults. Vitamin D deficiency may also increase the risk of other chronic diseases. Increased fortification of food items relevant to South Asian groups (e.g. chapatti flour), as well as increased use of vitamin D supplements may help reduce this epidemic. Introducing culturally acceptable ways of increasing skin exposure to the sun in South Asian women may also be beneficial but further research is needed to assess the effectiveness of different approaches. There may be a need for a South Asian specific vitamin D dietary intake guideline in western countries. To conclude, vitamin D deficiency is epidemic in South Asians living in western countries and there is a clear need for urgent public health action.

Obesity and efficacy of vitamin D3 supplementation in healthy black adults.

PURPOSE: Results from recent clinical trials suggest that vitamin D efficacy against cancer may be influenced by body mass index. As suppression of parathyroid hormone (PTH) is one indicator of vitamin D efficacy, we examined to what extent doses of vitamin D3 supplementation suppress PTH levels in individuals with and without obesity. METHODS: A total of 328 healthy African Americans were randomized into the following four groups and treated for 3 months: placebo, 1,000, 2,000, or 4,000 IU/day of vitamin D3 supplementation. RESULTS: Among the participants, 250 individuals with PTH measurements were included in the analysis. Obese individuals (n = 141) experienced a steep reduction of 3-month PTH from placebo to 1,000 IU/day of vitamin D3 supplementation, but no further reduction at 2,000 or 4,000 IU/day. For non-obese individuals (n = 109), the reduction of 3-month PTH was approximately linear for increasing vitamin D3 doses. At supplementation of 2,000 to 4,000 IU/day, 3-month 25(OH)vitamin D levels were high in both non-obese and obese individuals, but the 3-month PTH levels remained about 10 pg/mL higher in individuals with obesity. CONCLUSION: Our findings suggest that excess adiposity confers resistance to vitamin D efficacy in suppressing PTH levels, even when given at high doses.

Serum 25-hydroxyvitamin-D and nonalcoholic fatty liver disease: Does race/ethnicity matter? Findings from the MESA cohort.

BACKGROUND AND AIMS: Low serum 25-hydroxyvitamin D (25(OH)D) is associated with higher nonalcoholic fatty liver disease (NAFLD) risk in studies of mainly white participants. Significant racial/ethnic differences exist in serum 25(OH)D and NAFLD prevalence questioning extending this association to other racial/ethnic groups. We tested whether the association between serum 25(OH)D and NAFLD vary by race/ethnicity. METHODS AND RESULTS: This was a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) that included 3484 participants (44% male; 38.4% Whites, 27.8% African-Americans, 23.5% Hispanics, and 10.3% Chinese-Americans) who had serum 25(OH)D and upper abdominal CT images available at baseline. Serum 25(OH)D was measured by high-performance liquid chromatography-tandem mass spectrometry. NAFLD was identified if liver-to-spleen Hounsfield-Unit ratio was <1. Whites had the highest 25(OH)D level and African-Americans had the lowest level (mean ± SD: 29.5 ± 10.4 vs.19.9 ± 9.1, respectively). Six hundred and eleven (17.5%) participants had NAFLD; Hispanics had the highest prevalence (26.2%) followed by Chinese-Americans (19.8%), Whites (15.8%) and African-Americans (11.7%), P < 0.0001. In adjusted model, the association of 25(OH)D with NAFLD differed by race/ethnicity (P < 0.0001). Negative association was only evident in Causations (OR (95% CI):1.23 (1.03, 1.47) per 1 SD lower serum 25(OH)D). For other racial/ethnic groups, BMI, triglycerides, diabetic status and/or smoking, but not serum 25(OH)D, were common independent risk factors for NAFLD. CONCLUSIONS: The negative association between serum 25(OH)D and NAFLD in Whites may not be broadly generalizable to other racial/ethnic groups. Modifiable risk factors including BMI, triglycerides, diabetic status and/or smoking associate with NAFLD risk in non-white racial/ethnic groups beyond 25(OH)D.

Determinants of vitamin D status among Black and White low-income pregnant and non-pregnant reproductive-aged women from Southeast Louisiana.

BACKGROUND: Vitamin D deficiency is a growing public health problem, with pregnant women being particularly vulnerable due to its influences on maternal and neonatal outcomes. However, there are limited data published about mediators of vitamin D status in Louisiana women. We aimed to assess the vitamin D status and its determinants among low-income pregnant and non-pregnant reproductive-aged women from southeast Louisiana. METHODS: This study was conducted using data from the Gulf Resilience on Women's Health (GROWH) research consortium cohort of pregnant and non-pregnant women which contained sociodemographic and dietary variables as well as blood and salivary element concentrations. Serum 25-hydroxy vitamin D was measured using an enzyme-linked immunosorbent assay in 86 pregnant and 98 non-pregnant women with an even distribution of race in both groups. RESULTS: The prevalence of deficient vitamin D levels in the total cohort (184 women) was 67% and the mean 25(OH) vitamin D3 was 24.1 ng/mL (SD 10.7). Self-identifying as White, being pregnant, autumn season, young age and high exposure to tobacco smoke measured by cotinine were significantly associated with higher serum levels of vitamin D. Visiting Women and Infant clinics (WIC) was an important determinant in improving 25(OH) vitamin D3 levels for Black women but not for White women and concentrations varied more among Black women across seasons compared to White women. CONCLUSIONS: Serum vitamin D levels are inadequate among a high proportion of Black and White low-income pregnant and reproductive-aged women living in Southeast Louisiana who were enrolled in the GROWH study. Black women who are over 35 years old and non-WIC participants constitute the subpopulation most at risk for vitamin D deficiency, especially during the winter. As an overall higher level of deficiency exists in Black women, if even small behavioral and dietary modifications are produced by WIC, this can lead to a comparatively greater improvement in vitamin D status in women from Southeast Louisiana who self-identify as Black.

Platelet Surface CD62p and Serum Vitamin D Levels are Associated with Clopidogrel Resistance in Chinese Patients with Ischemic Stroke.

BACKGROUND: To explore the association of platelet activation markers, vitamin D, and antiplatelet drugs resistance in ischemic stroke patients. METHODS: A total of 230 patients with ischemic stroke were enrolled in this study. Platelet aggregation, platelet activation marker (CD62p), and vitamin D were measured after 7-14 days of dual antiplatelet treatment (aspirin + clopidogrel). All individuals were divided into a drug resistance group and a drug sensitive group according to the platelet maximum aggregation rate induced by antagonist adenosine diphosphate or arachidonic acid. RESULTS: In this study, the prevalence of aspirin resistance was low (1.2%), while the prevalence of clopidogrel resistance (CR) was 24.8%, so we focused on CR. The percentage of CD62p on activated platelet [(25.74 ± 4.61) versus (12.41 ± 3.93), P < .001] and the prevalence of hypertension [93.0% (53) versus 79.8% (138), P = .021] in CR group were significantly higher than those in clopidogrel sensitive (CS) group, while the vitamin D concentration [(8.96 ± 4.41) versus (13.9 ± 4.84) ng/mL, P = .003] in CR group was significantly lower compared with the CS group. No significant difference was found in soluble P-selectin between these 2 groups [(56.2 ± 16.13) versus (54.2 ± 14.87) ng/mL, P = .258], neither in calcium [(2.29 ± .12) versus (2.33 ± .13) mmol/L, P = .821]. Logistic regression analysis showed that hypertension (odds ratio [OR] = 5.348, 95% confidence intervals [CI] 1.184-23.350, P = .026), expression of platelet CD62p (OR = 1.095, 95% CI 1.052-1.201, P = .018) and vitamin D level (OR = .832, 95% CI .763-.934, P = .005) were associated with CR in ischemic stroke patients. CONCLUSIONS: CR in ischemic stroke patients is associated with several independent predictors, including increased platelet activation marker CD62p, decreased vitamin D level, and hypertension.

Effects of vitamin D on disease activity and serum interleukin-6 in rheumatoid arthritis.

AIM: Vitamin D3 or 25(OH)D3 may have a potential role in rheumatoid arthritis (RA) pathogenesis by inhibiting the expression of pro-inflammatory cytokines including interleukin-6 (IL-6). The aim of this study is to determine the clinical factors of vitamin D deficiency in multi-ethnic Malaysian RA patients and its association with disease activity, functional disability and serum IL-6 levels. METHOD: One hundred RA patients and 50 healthy controls, sex- and age-matched, were recruited. Disease Activity Score of 28 joints and Health Assessment Questionnaire scores were assessed. Baseline serum 25(OH)D3 and IL-6 were measured in all subjects. RA patients who were vitamin D deficient were given loading doses of vitamin D3 and repeated assessments were done. RESULTS: Vitamin D deficiency (<50 nmol/L) was found in 63% of RA patients and 76% of healthy controls. Chinese RA patients and healthy controls had significantly more sufficient 25(OH)D3 levels compared to Malays and Indians (P < 0.001). Serum 25(OH)D3 level was still negatively associated with body mass index in RA patients (P = 0.002) after adjustment for potential confounding variables. No significant association was seen between 25(OH)D3 levels and disease activity or serum IL-6 levels in both pre- and post-treatment groups. A negative association was observed between serum 25(OH)D3 and functional disability, including a 33% improvement post-treatment (mean ± SD: 0.30 ± 0.46 to 0.20 ± 0.18). CONCLUSION: Vitamin D deficiency is prevalent in Malaysian RA patients. This study suggests that vitamin D is not associated with disease activity or serum IL-6 levels but it may have a role in functional disability in RA patients.

Vitamin D and Falls in Older African American Women: The PODA Randomized Clinical Trial.

BACKGROUND: Limited information is available on the influence of vitamin D on falls in older high-functioning black American women. Endocrine Society guidelines propose serum 25(OH)D levels over 30 ng/mL. OBJECTIVE: To determine if maintenance of serum 25(OH)D above 30 ng/mL protects against falls. DESIGN: The Physical Performance, Osteoporosis and Vitamin D in African American Women (PODA) trial had a prospective, randomized, placebo-controlled, double-dummy design with two arms: one with placebo and one with vitamin D3 adjusted to maintain serum 25(OH)D above 30 ng/mL. The primary outcomes were the prevention of bone loss and the decline in physical performance. PATIENTS: The target population was healthy black women older than 60 years with serum 25(OH)D between 8 and 26 ng/mL. The trial was 3 years in duration with a falls questionnaire administered every 3 months. A total of 260 women entered the study, and 184 completed the 3 years. Mean age was 68.2 years. SETTING: Research center in an academic health center. MAIN OUTCOMES MEASURE: Prevention of falls. INTERVENTION: Participants were randomly assigned to placebo or active vitamin D. Vitamin D3 dose was adjusted to maintain serum 25(OH)D above 30 ng/mL in the active group using a double-dummy design. RESULTS: Baseline 25(OH)D was 22 ng/mL. Mean serum 25(OH)D reached 47 ng/mL in the active group compared with 21 ng/mL in the placebo group. There were 14.2% falls in the previous year recalled at baseline. During the study, 46% reported falling in the treatment group compared with 47% in the placebo group. There was no association of serum 25(OH)D or vitamin D dose with the risk of falling. CONCLUSIONS: There is no benefit of maintaining serum 25(OH)D above 30 ng/mL compared with the Institute of Medicine recommendation (20 ng/mL) in preventing falls in healthy older black American women. J Am Geriatr Soc 67:1043-1049, 2019.

Vitamin D status and its determinants in healthy pregnant women living in Switzerland in the first trimester of pregnancy.

OBJECTIVES: Our study aimed at assessing the prevalence and determinants of vitamin D deficiency (25-hydroxy-vitamin D [25(OH)D] < 20 ng/mL) in pregnant women in the first trimester living in Switzerland. METHODS: From September 2014 through December 2015, 204 pregnant women were conveniently recruited during their first clinical appointment at the Clinic of Obstetrics of the University Hospital Zurich (between week 6 and 12 of pregnancy). Blood samples were collected and a questionnaire focusing on lifestyle and skin colour was completed face-to-face with the responsible physician. Logistic regression analyses were performed with vitamin D status as dependent variable. RESULTS: 63.2% of the participating women were vitamin D deficient, and the median vitamin D concentration in the overall sample was 17.1 ng/mL [Q1, Q3: 9.78, 22.3]. The highest proportions of vitamin D deficiency were detected in women originating from Africa and Middle East (91.4% deficient, median vitamin D concentration of 10.7 ng/mL [Q1, Q3: 6.55, 14.45]) and from South-East Asia/Pacific (88.5% deficient, median vitamin D concentration of 8.4 ng/mL [Q1, Q3: 6.10, 14.88]). Multivariable logistic regression showed that significant risk factors of vitamin D deficiency were country of origin (women born in Switzerland and Germany had a lower risk than women born in other countries), smoking status (lower risk for former smokers) and intake of vitamin D supplements. CONCLUSIONS: Our results confirm a high prevalence of vitamin D deficiency in this Swiss cohort, in particular in women coming from Asian and African countries, and underline the importance of appropriate counseling and vitamin D supplementation in early pregnancy.

Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH)2D), and decreases bone mineral density (BMD). Optimal treatment of TDF-associated BMD loss requires an understanding of the primary cause of these abnormalities. METHODS: Secondary review of data from two studies of TDF use in youth, comparing the relationship of PTH, 25-hydroxy vitamin D (25-OHD) and 1,25-(OH)2D in three groups with varying exposures to TDF: youth without HIV enrolled in a trial of TDF/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) at baseline (no TDF exposure) and after 12 weeks of TDF (short-term TDF exposure); and youth with HIV treated with TDF-containing combination antiretroviral therapy (cART) for at least 6 months at study entry (long-term TDF exposure). Relationships were evaluated by correlation analyses. RESULTS: Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH)2D had the positive correlation similar to that found in vitamin D deficiency. CONCLUSIONS: TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health. CLINICAL TRIALS REGISTRATION: NCT01751646 (ATN 109) and NCT01769469 (ATN 117).

Vitamin D supplement use and associated demographic, dietary and lifestyle factors in 8024 South Asians aged 40-69 years: analysis of the UK Biobank cohort.

OBJECTIVE: Vitamin D deficiency (serum 25-hydroxyvitamin D<25nmol/L) is extremely common in western-dwelling South Asians but evidence regarding vitamin D supplement usage in this group is very limited. This work identifies demographic, dietary and lifestyle predictors associated with vitamin D supplement use. DESIGN: Cross-sectional analysis of baseline vitamin D supplement use data. SETTING: UK Biobank cohort. SUBJECTS: In total, n 8024 South Asians (Bangladeshi, Indian, Pakistani), aged 40-69 years. RESULTS: Twenty-three % of men and 39% of women (P<0.001) [22% of Bangladeshis, 32% of Indians, 25% of Pakistanis (P<0.001)] took a vitamin D containing supplement. Median vitamin D intakes from diet were low at 1.0-3.0 micrograms per day, being highest in Bangladeshis and lowest in Indians (P<0.001). Logistic regression modelling showed that females had a higher odds of vitamin D supplement use than males (odds ratio (OR) = 2.02; 95% confidence interval (CI) 1.79 to 2.28). A lower supplement usage was seen in younger persons (40-60 years) (OR=0.75; 95% CI 0.65 to 0.86 reference= >60 years), and those living outside of Greater London (OR=0.53 to 0.77), with borderline trends for a lower body mass index, higher oily fish intake and higher household income associated with increased odds of vitamin D supplement use. CONCLUSIONS: Vitamin D supplements were not used by most South Asians and intakes from diet alone are likely to be insufficient to maintain adequate vitamin D status. Public health strategies are now urgently required to promote the use of vitamin D supplements in these specific UK South Asian subgroups.

Serum 25-hydroxyvitamin D, calcium and parathyroid hormone levels in Native and European populations in Greenland.

Ca homoeostasis is important to human health and tightly controlled by powerful hormonal mechanisms that display ethnic variation. Ethnic variations could occur also in Arctic populations where the traditional Inuit diet is low in Ca and sun exposure is limited. We aimed to assess factors important to parathyroid hormone (PTH) and Ca in serum in Arctic populations. We included Inuit and Caucasians aged 50-69 years living in the capital city in West or in rural East Greenland. Lifestyle factors were assessed by questionnaires. The intake of Inuit diet was assessed from a FFQ. 25-Hydroxyvitamin D (25OHD2 and 25OHD3) levels were measured in serum as was albumin, Ca and PTH. The participation rate was 95 %, with 101 Caucasians and 434 Inuit. Median serum 25OHD (99·7 % was 25OHD3) in Caucasians/Inuit was 42/64 nmol/l (25, 75 percentiles 25, 54/51, 81) (P<0·001). Total Ca in serum was 2·33/2·29 mmol/l (25, 75 percentiles 2·26, 2·38/2·21, 2·36) (P=0·01) and PTH was 2·7/2·2 pmol/l (25, 75 percentiles 2·2, 4·1/1·7, 2·7) (P<0·001). The 69/97 Caucasians/Inuit with serum 25OHD <50 nmol/l differed in PTH (P=0·001) that rose with lower 25OHD levels in Caucasians, whereas this was not the case in Inuit. Ethnic origin influenced PTH (ß=0·27, P<0·001) and Ca (ß=0·22, P<0·001) in multivariate linear regression models after adjustment for age, sex, BMI, smoking, alcohol and diet. In conclusion, ethnic origin influenced PTH, PTH response to low vitamin D levels and Ca levels in populations in Greenland. Recommendations are to evaluate mechanisms underlying the ethnic influence on Ca homoeostasis and to assess the impact of transition in dietary habits on Ca homoeostasis and skeletal health in Arctic populations.

Vitamin D deficiency is associated with an oxidized plasma cysteine redox potential in critically Ill children.

Critically ill populations incur high levels of oxidative stress and commonly present with vitamin D deficiency. This study aimed to investigate the relationship between vitamin D status and plasma markers of glutathione (GSH) and cysteine (Cys) redox and immunity in critically ill children. This was a cross-sectional study of n=50 PICU patients. Subjects were categorized according to their plasma 25-hydroxyvitamin D [25(OH)D] concentrations: (<20, 20-30, and ≥30ng/dL). Plasma GSH, glutathione disulfide (GSSG), Cys, and cystine (CySS) were measured with high-performance liquid chromatography, and their associated redox potentials determined (EhGSSG and EhCySS, respectively). Plasma LL-37, an indicator of innate immune function, was assayed with ELISA. Data were analyzed using general linear regression before and after adjustment for age, sex, and race. Results showed that EhCySS was more reduced in subjects with plasma 25(OH)D concentrations ≥30ng/mL compared to those with 25(OH)D concentrations <20ng/mL (P=0.009). Plasma GSH, GSSG, and total GSH decreased with increasing 25(OH)D category (P=0.06, 0.03, and 0.01, respectively), and plasma glutamine levels were lowest in subjects with plasma 25(OH)D concentrations ≥30ng/mL (P=0.004). Plasma LL-37 concentrations did not significantly differ by vitamin D status (P=0.08). In conclusion, vitamin D sufficiency was associated with more reduced plasma EhCySS, indicative of lower oxidative stress in critically ill children. Plasma GSH, GSSG, and glutamine, however, were lower in the vitamin D sufficient group. The role of vitamin D in maintaining redox status during pediatric critical illness requires further study.

Non-musculoskeletal benefits of vitamin D.

The aim of this study is to determine and critically evaluate the plausible relationships of vitamin D with extra-skeletal tissues in humans. Severe vitamin D deficiency results in rickets in children and osteomalacia in adults; these beneficial effects in the musculoskeletal system and certain physiological functions are well understood. Nevertheless, mounting reports support additional beneficial effects of vitamin D, outside the musculoskeletal system. This review explores the recent advances in knowledge about the non-skeletal effects of vitamin D. Peer-reviewed papers were extracted from research databases using key words, to assess correlations between vitamin D and extra-skeletal diseases and conditions. As per the guidelines of the Preferred Reporting Items for Systematic Reviews (PRISMA); general interpretations of results are included; taking into consideration the broader evidence and implications. This review summarizes current knowledge of the effects of vitamin D status on extra-skeletal tissues with special attention given to relationships between vitamin D status and various diseases commonly affecting adults; the effects of intervention with vitamin D and exposure to sunlight. Evidence suggests that vitamin D facilitates the regulation of blood pressure; and cardiac; endothelial; and smooth muscle cell functions; playing an important role in cardiovascular protection. In addition; 1,25(OH)2D improves immunity; subdues inflammation; and reduces the incidence and severity of common cancers; autoimmune diseases and infectious diseases. Almost all adequately powered; epidemiological and biological studies that use; adequate doses of vitamin D supplementation in D-deficient populations have reported favorable outcomes. These studies have concluded that optimizing 25(OH)D status improves the functionality of bodily systems; reduces comorbidities; improves the quality of life; and increases survival. Although accumulating evidence supports biological associations of vitamin D sufficiency with improved physical and mental functions; no definitive evidence exists from well-designed; statistically powered; randomized controlled clinical trials. Nevertheless, most studies point to significant protective effects of vitamin D in humans when the minimum 25(OH)D serum level exceeds 30ng/mL and is maintained throughout the year.