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Journal: The Journal of steroid biochemistry and molecular biology


The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19.


Vitamin D may be a central biological determinant of COVID-19 outcomes. The objective of this quasi-experimental study was to determine whether bolus vitamin D3 supplementation taken during or just before COVID-19 was effective in improving survival among frail elderly nursing-home residents with COVID-19. Sixty-six residents with COVID-19 from a French nursing-home were included in this quasi-experimental study. The “Intervention group” was defined as those having received bolus vitamin D3 supplementation during COVID-19 or in the preceding month, and the “Comparator group” corresponded to all other participants. The primary and secondary outcomes were COVID-19 mortality and Ordinal Scale for Clinical Improvement (OSCI) score in acute phase, respectively. Age, gender, number of drugs daily taken, functional abilities, albuminemia, use of corticosteroids and/or hydroxychloroquine and/or antibiotics (i.e., azithromycin or rovamycin), and hospitalization for COVID-19 were used as potential confounders. The Intervention (n = 57; mean ± SD, 87.7 ± 9.3years; 79%women) and Comparator (n = 9; mean,87.4 ± 7.2years; 67%women) groups were comparable at baseline, as were the COVID-19 severity and the use of dedicated COVID-19 drugs. The mean follow-up time was 36 ± 17days. 82.5% of participants in the Intervention group survived COVID-19, compared to only 44.4% in the Comparator group (P = 0.023). The full-adjusted hazard ratio for mortality according to vitamin D3 supplementation was HR = 0.11[95%CI:0.03;0.48],P = 0.003. Kaplan-Meier distributions showed that Intervention group had longer survival time than Comparator group (log-rank P = 0.002). Finally, vitamin D3 supplementation was inversely associated with OSCI score for COVID-19 (β=-3.84[95%CI:-6.07;-1.62], P = 0.001). In conclusion, bolus vitamin D3 supplementation during or just before COVID-19 was associated in frail elderly with less severe COVID-19 and better survival rate.


Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged ≥20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the Grassroots Health (GRH) cohort was 41ng/ml (N=4933) while in the 2005-6 National Health and Nutrition Examination Survey (NHANES) it was 22ng/ml (N=4078) (P<0.0001). The adjusted annual incidence rate of type 2 diabetes was 3.7 per 1000 population (95% confidence interval=1.9, 6.6) in the GRH cohort, compared to 9.3 per 1000 population (95% confidence interval=6.7, 12.6) in NHANES. In the NHANES cohort, the lowest 25(OH)D tertiles (<17, 17-24ng/ml) had higher odds of developing diabetes than the highest tertile (OR: 4.9, P=0.02 and 4.8, P=0.01 respectively), adjusting for covariates. Differences in demographics and methods may have limited comparability. Raising serum 25(OH)D may be a useful tool for reducing risk of diabetes in the population.

Concepts: Epidemiology, Nutrition, Diabetes mellitus type 2, Diabetes mellitus, Demography, Obesity, Concentration, Incidence


Nutritional rickets is a major public health problem in many countries of the world. The disease is characterised by deformities of the long bones, enlargement of the wrists and costochondral junctions, hypotonia and, in infants, craniotabes and delayed fontanelle closure. Predominantly caused by severe vitamin D deficiency, rickets can also be associated with hypocalcemic seizures and cardiac failure. First presentation is typically at 6-24 months of age, although hypocalcemia may be evident in younger infants. In many affluent industrialized countries, the prevalence of rickets in the general population diminished after the introduction of clean-air legislation and dietary supplementation. However, in such countries, vitamin-D deficiency rickets has re-emerged in recent years, particularly among groups with limited exposure to UVB-containing sunshine. Infants at risk of rickets tend to be those whose mothers had poor vitamin D status during pregnancy and those exclusively breast-fed for a prolonged period with little skin exposure to UVB. In other countries of the world, the prevalence of rickets can be high, even in regions with abundant year-round UVB-containing sunshine. In general, this is also due to vitamin D deficiency related to limited sun exposure. However, reports from Africa and Asia suggest that there may be other etiological factors involved. Studies in South Africa, Nigeria, The Gambia and Bangladesh have identified rickets in children, typically 3-4 years old at first presentation, in whom plasma 25-hydroxyvitamin D concentrations are higher than those characteristic of primary vitamin D deficiency. Calcium deficiency has been implicated, and in some, but not all, disturbances of phosphate metabolism, renal compromise and iron deficiency may also be involved. Continuing studies of the etiology of nutritional rickets will provide evidence to underpin guidelines for the prevention and treatment of rickets world-wide.

Concepts: Vitamin D, Ultraviolet, Nutrition, Calcium, Vitamin, Sunlight, Rickets, Sunscreen


This study was designed to investigate the impact of 1,25 dihydroxyvitamin D (1,25(OH)2D) on glucose metabolism during early cancer progression. Untransformed and ras-oncogene transfected (ras) MCF10A human breast epithelial cells were employed to model early breast cancer progression. 1,25(OH)2D modified the response of the ras cells to glucose restriction, suggesting 1,25(OH)2D may reduce the ras cell glucose addiction noted in cancer cells. To understand the 1,25(OH)2D regulation of glucose metabolism, following four-day 1,25(OH)2D treatment, metabolite fluxes at the cell membrane were measured by a nanoprobe biosensor, [(13)C6]glucose flux by (13)C-mass isotopomer distribution analysis of media metabolites, intracellular metabolite levels by NMR, and gene expression of related enzymes assessed. Treatment with 1,25(OH)2D reduced glycolysis as flux of glucose to 3-phosphoglycerate was reduced by 15% (P=0.017) and 32% (P<0.003) in MCF10A and ras cells respectively. In the ras cells, 1,25(OH)2D reduced lactate dehydrogenase activity by 15% (P<0.05) with a concomitant 10% reduction in the flux of glucose to lactate (P=0.006), and reduction in the level of intracellular lactate by 55% (P=0.029). Treatment with 1,25(OH)2D reduced flux of glucose to acetyl-coA 24% (P=0.002) and 41% (P<0.001), and flux to oxaloacetate 34% (P=0.003) and 33% (P=0.027) in the MCF10A and ras cells, respectively, suggesting a reduction in tricarboxylic acid (TCA) cycle activity. The results suggest a novel mechanism involving the regulation of glucose metabolism by which 1,25(OH)2D may prevent breast cancer progression.

Concepts: Protein, Gene, Gene expression, Cancer, Adenosine triphosphate, Enzyme, Cell membrane, Cellular respiration


Hormone therapy is the most effective treatment for patients with estrogen receptor α-positive breast cancers. However, although resistance occurs during treatment in some cases and often reflects changed estrogen receptor α status, the relationship between changes in estrogen receptor α expression and resistance to therapy is poorly understood. In this study, we identified a mechanism for altered estrogen receptor α expression during disease progression and acquired hormone therapy resistance in aromatase inhibitor-resistant breast cancer cell lines. Subsequently, we investigated promoter switching and DNA methylation status of the estrogen receptor α promoter, and found marked changes of methylation at a single CpG site (CpG4) in resistant cells. In addition, luciferase reporter assays showed reduced transcriptional activity from this methylated CpG site. This CpG region was also completely conserved among species, suggesting that it acts as a methylation-sensitive Ets-2 transcription factor binding site, as confirmed using chromatin immunoprecipitation assays. In estrogen receptor α-positive tumors, CpG4 methylation levels were inversely correlated with estrogen receptor α expression status, suggesting that single CpG site plays an important role in the regulation of estrogen receptor α transcription.

Concepts: DNA, Protein, Gene, Gene expression, Cancer, Breast cancer, Transcription, Transcription factor


In recent years, clinical trials increasingly have given large doses of vitamin D supplements to investigate possible health benefits beyond bone at high 25-hydroxyvitamin D levels. However, there are few publications on the safety of high-dose vitamin D given long term. The study objective was to investigate the cumulative relative risk (RR) of total adverse events, kidney stones, hypercalcemia and hypercalciuria from ≥2800 IU/d vitamin D2 or D3 supplementation, followed for one year or more in randomized controlled trials (RCTs). A systematic review was conducted in Medline Ovid, EMBASE and Cochrane in March 2018 to update results of studies published since a previous review in October 2015. RCTs were included if they gave vitamin D2 or D3 at ≥2800 IU/d for at least one year and reported on total adverse events or at least one calcium-related adverse event. There were a total of 32 studies that met the inclusion criteria. Of these, only 15 studies (3,150 participants) reported one or more event of the outcomes of interest. Long-term high-dose vitamin D supplementation did not increase total adverse events compared to placebo in 1,731 participants from 10 studies (RR = 1.05; 95% CI = 0.88, 1.24; p = 0.61), nor kidney stones in 1,336 participants from 5 studies (RR = 1.26; 95% CI = 0.35, 4.58; p = 0.72). However, there was a trend for vitamin D to increase risk of hypercalcemia in 2,598 participants from 10 studies (RR = 1.93; 95% CI = 1.00, 3.73; p = 0.05); while its effect on hypercalciuria in only 276 participants from 3 studies was inconclusive (RR = 1.93; 95% CI = 0.83, 4.46; p = 0.12). In conclusion, one year or longer supplementation with a large daily, weekly or monthly dose of vitamin D2 /D3 did not significantly increase a risk of total adverse events or kidney stones, although there was a trend towards increased hypercalcemia, and possibly for hypercalciuria.


Two vitamin D pregnancy supplementation trials were recently undertaken in South Carolina: The NICHD (n=346) and Thrasher Research Fund (TRF, n=163) studies. The findings suggest increased dosages of supplemental vitamin D were associated with improved health outcomes of both mother and newborn, including risk of preterm birth (<37 weeks gestation). How that risk was associated with 25(OH)D serum concentration, a better indicator of vitamin D status than dosage, by race/ethnic group and the potential impact in the community was not previously explored. While a recent IOM report suggested a concentration of 20 ng/mL should be targeted, more recent work suggests optimal conversion of 25(OH)D to 1,25(OH)2D takes place at 40 ng/mL in pregnant women.

Concepts: Pregnancy, Childbirth, Embryo, Prenatal development, Fetus, Uterus, Dietary supplement, Folic acid


Hot flashes (HFs) are a rapid and exaggerated heat dissipation response, consisting of profuse sweating, peripheral vasodilation, and feelings of intense, internal heat. They are triggered by small elevations in core body temperature (Tc) acting within a greatly reduced thermoneutral zone, i.e., the Tc region between the upper (sweating) and lower (shivering) thresholds. This is due in part, but not entirely, to estrogen depletion at menopause. Elevated central sympathetic activation, mediated through α2-adrenergic receptors, is one factor responsible for narrowing of the thermoneutral zone. Procedures which reduce this activation, such as paced respiration and clonidine administration, ameliorate HFs as will peripheral cooling. HFs are responsible for some, but not all, of the sleep disturbance reported during menopause. Recent work calls into question the role of serotonin in HFs.

Concepts: Hormone, Menopause, Estrogen, Endocrinology, Sleep, Thermodynamics, Heat, Hot flash


Vitamin D deficiency is a major public health problem worldwide in all age groups, even in those residing in countries with low latitude, where it was generally assumed that UV radiation was adequate enough to prevent this deficiency, and in industrialized countries, where vitamin D fortification has been implemented now for years. However, most countries are still lacking data, particularly population representative data, with very limited information in infants, children, adolescents and pregnant women. Since the number of recent publications is escalating, with a broadening of the geographic diversity, the objective of the present report was to conduct a more recent systematic review of global vitamin D status, with particular emphasis in at risk groups. A systematic review was conducted in PubMed/Medline in April-June 2013 to identify articles on vitamin D status worldwide published in the last 10 years in apparently healthy individuals. Only studies with vitamin D status prevalence were included. If available, the first source selected was population-based or representative samples studies. Clinical trials, case-control studies, case reports or series, reviews, validation studies, letters, editorials, or qualitative studies were excluded. A total of 103 articles were eligible and included in the present report. Maps were created for each age group, providing an updated overview of global vitamin D status. In areas with available data, the prevalence of low vitamin D status is a global problem in all age groups, in particular in girls and women from the Middle East. These maps also evidenced the regions with missing data for each specific population groups. There is striking lack of data in infants, children and adolescents worldwide, and in most countries of South America and Africa. In conclusion, vitamin D deficiency is a global public health problem in all age groups, particularly in those from the Middle East.

Concepts: Vitamin D, Epidemiology, Ultraviolet, Demography, Middle East, Asia, Israel, Arabic language