Bioaccessibility of oil-soluble vitamins (A, D, E) in plant-based emulsions: impact of oil droplet size.

We systematically investigated the impact of oil droplet diameter (≈0.15, 1.6, and 11 µm) on the bioaccessibility of three oil-soluble vitamins (vitamin A palmitate, vitamin D, and vitamin E acetate) encapsulated within soybean oil-in-water emulsions stabilized by quillaja saponin. Lipid digestion kinetics decreased with increasing droplet size due to the reduction in oil-water interfacial area. Vitamin bioaccessibility decreased with increasing droplet size from 0.15 to 11 µm: 87 to 39% for vitamin A; 76 to 44% for vitamin D; 77 to 21% for vitamin E. Vitamin bioaccessibility also decreased as their hydrophobicity and molecular weight increased, probably because their tendency to remain inside the oil droplets and/or be poorly solubilized by the mixed micelles increased. Hydrolysis of the esterified vitamins also occurred under gastrointestinal conditions: vitamin A palmitate (∼90%) and vitamin E acetate (∼3%). Consequently, the composition and structure of emulsion-based delivery systems should be carefully designed when creating vitamin-fortified functional food products.

Vitamin D metabolites influence expression of genes concerning cellular viability and function in insulin producing ß-cells (INS1E).

BACKGROUND: Studies have shown that vitamin D can enhance glucose-stimulated insulin secretion (GSIS) and change the expression of genes in pancreatic ß-cells. Still the mechanisms linking vitamin D and GSIS are unknown. MATERIAL AND METHODS: We used an established ß-cell line, INS1E. INS1E cells were pre-treated with 10 nM 1,25(OH)2vitamin D or 10 nM 25(OH)vitamin D for 72 h and stimulated with 22 mM glucose for 60 min. RNA was extracted for gene expression analysis. RESULTS: Expression of genes affecting viability, apoptosis and GSIS changed after pre-treatment with both 1,25(OH)2vitamin D and 25(OH)vitamin D in INS1E cells. Stimulation with glucose after pre-treatment of INS1E cells with 1,25(OH)2vitamin D resulted in 181 differentially expressed genes, whereas 526 genes were differentially expressed after pre-treatment with 25(OH)vitamin D. CONCLUSION: Vitamin D metabolites may affect pancreatic ß-cells and GSIS through changed gene expression for genes involved in ß-cell function and viability.

Noteworthy idiosyncrasies of 1α,25-dihydroxyvitamin D3 kinetics for extrapolation from mouse to man: Commentary.

Calcitriol or 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] is the active ligand of the vitamin D receptor (VDR) that plays a vital role in health and disease. Vitamin D is converted to the relatively inactive metabolite, 25-hydroxyvitamin D3 [25(OH)D3 ], by CYP27A1 and CYP2R1 in the liver, then to 1,25(OH)2 D3 by a specific, mitochondrial enzyme, CYP27B1 (1α-hydroxylase) that is present primarily in the kidney. The degradation of both metabolites is mostly carried out by the more ubiquitous mitochondrial enzyme, CYP24A1. Despite the fact that calcitriol inhibits its formation and degradation, allometric scaling revealed strong interspecies correlation of the net calcitriol clearance (CL estimated from dose/AUC∞ ), production rate (PR), and basal, plasma calcitriol concentration with body weight (BW). PBPK-PD (physiologically based pharmacokinetic-pharmacodynamic) modeling confirmed the dynamic interactions between calcitriol and Cyp27b1/Cyp24a1 on the decrease in the PR and increase in CL in mice. Close scrutiny of the literature revealed that basal levels of calcitriol had not been taken into consideration for estimating the correct AUC∞ and CL after exogenous calcitriol dosing in both animals and humans, leading to an overestimation of AUC∞ and underestimation of the plasma CL. In humans, CL was decreased in chronic kidney disease but increased in cancer. Collectively, careful pharmacokinetic data analysis and improved definition are achieved with PBPK-PD modeling, which embellishes the complexity of dose, enzyme regulation, and disease conditions. Allometric scaling and PBPK-PD modeling were applied successfully to extend the PBPK model to predict calcitriol kinetics in cancer patients.

Randomized clinical trials of oral vitamin D supplementation in need of a paradigm change: The vitamin D autacoid paradigm.

Epidemiological studies highlight the negative correlation between vitamin D levels and the incidence of many non-skeletal diseases including inflammatory diseases, cancer, and metabolic and neurological disorders. However, most randomized controlled trials (RCTs) with oral vitamin D supplementation give mixed results or are inconclusive. It has been said that "discovery commences with the awareness of anomaly". The "anomaly" between our preclinical and clinical data provides the opportunity to propose an alternative paradigm to the vitamin D endocrine system: the vitamin D autacoid paradigm. In the vitamin D autacoid paradigm, the extra-skeletal effects of vitamin D depend on the tissue reserves of vitamin D metabolites. These vitamin D autacoid systems are inducible oscillatory ecosystems in which 1,25D is produced, acts and is inactivated locally. In the vitamin D autacoid paradigm, attaining adequacy of vitamin D in the systemic circulation is necessary but not sufficient; we must also ensure the repletion of the tissue stores. The co-existence of two different vitamin D systems, endocrine and autacoid, with different functions and regulations leads to "significant shifts in the criteria determining the legitimacy both of problems and of proposed solutions". With respect to our clinical trials of vitamin D supplementation for unconventional effects, the proposed solution is administering and quantifying vitamin D metabolites directly to the target tissue.

Influence of Vitamin D on Corneal Epithelial Cell Desmosomes and Hemidesmosomes.

Purpose: We have observed noticably weak epithelial attachment in vitamin D receptor knockout mice (VDR KO) undergoing epithelial debridement. We hypothesized that VDR KO negatively affects corneal epithelial cell desmosomes and/or hemidesmosomes. Methods: Transcript levels of desmosome and hemidesmosome proteins in VDR KO corneas were assessed by qPCR. Western blotting and immunochemistry were used to detect proteins in cultured cells exposed to 1,25(OH)2D3 and 24R,25(OH)2D3. Results: VDR KO resulted in decreased corneal desmosomal desmoglein 1 (DSG1) and desmocollin 2 (DSC2) mRNA, and hemidesmosomal plectin mRNA. DSG1 and plectin protein expression were reduced in VDR KO corneas. DSG1 protein expression increased in VDR wild types (VDR WT) and VDR KO mouse primary epithelial cells (MPCEC) treated with 1,25(OH)2D3 and 24R,25(OH)2D3. 24R,25(OH)2D3 treatment resulted in increased plectin and integrin ß4 levels in VDR WT MPCEC, and decreased levels in VDR KO MPCEC. Treatment of human corneal epithelial cells (HCEC) with 1,25(OH)2D3 and 24R,25(OH)2D3 resulted in increased DSC2 and DSG1 protein expression. Plectin and integrin ß4 were only increased in 24R,25(OH)2D3 treated HCEC. Conclusions: VDR KO results in reduced desmosomal and hemidesmosomal mRNA and protein levels. 1,25(OH)2D3 and 24R,25(OH)2D3 increased DSG1 protein in all cells tested. For hemidesmosome proteins, 24R,25(OH)2D3 increased plectin and integrin ß4 protein expression in VDR WT and HCEC, with decreased expression in VDR KO MPCEC. Thus, vitamin D3 is involved in desmosome and hemidesmosome junction formation/regulation, and their decreased expression likely contributes to the loosely adherent corneal epithelium in VDR KO mice. Our data indicate the presence of a VDR-independent pathway.

[Milk and dairy products as vehicle for calcium and vitamin D: role of calcium enriched milks]. / Leche y productos lácteos como vehículos de calcio y vitamina D: papel de las leches enriquecidas.

INTRODUCTION: Milk and dairy products are key foods during all stages of life within a balanced Western diet. In recent decades, their consumption has decreased significantly. In parallel, an increase in some pathological alterations caused by the deficit of some micronutrients present in dairy products, mainly calcium and vitamin D, has been detected, resulting in a serious public health problem in certain groups of population. In order to avoid these deficiencies, foods enriched in these components have been launched into the market. Within them, enriched milks and dairy products stand out since they allow better bioavailability of calcium and are natural sources of vitamin D. Several studies have been carried out to demonstrate the benefit of supplementation with calcium and vitamin D enriched milks in vulnerable groups such as older adults and postmenopausal women. Those studies have reported a substantial improvement of bone turnover and an increase of bone density and strength. The aim of the present work is to revise the importance of milk-derived calcium intake on health, and the usefulness of calcium-enriched milks for allowing adequate calcium consumption without dietary modifications in certain groups of population. Likewise, it is intended to clarify the errors and myths that have recently arisen in relation to certain foods that seek to replace milk and dairy product, based on their differences in composition, bioavailability and health effects.

INTRODUCCIÓN: La leche y sus derivados son alimentos fundamentales durante todas las etapas de la vida dentro de una dieta occidental equilibrada. En las últimas décadas, su consumo ha disminuido notablemente y de forma paralela se ha detectado un aumento de algunas alteraciones provocadas por la carencia de micronutrientes presentes en los productos lácteos, principalmente calcio y vitamina D, lo que está derivando en un grave problema de salud pública en determinados grupos de población. Para intentar solucionar estos problemas, se han incorporado al mercado alimentos enriquecidos en estos componentes, dentro de los que destacan los productos lácteos porque proporcionan mejor biodisponibilidad del calcio y son fuentes de vitamina D, por lo que son los más recomendables. Se han realizado diversas investigaciones que demuestran el beneficio que supone la suplementación con leche enriquecida en calcio y vitamina D en grupos vulnerables como los adultos mayores y las mujeres posmenopáusicas, en los que mejora sustancialmente el recambio óseo y aumenta la densidad y la fuerza de los huesos. El objetivo de este trabajo es revisar la importancia que tiene el consumo del calcio de la leche, así como las recomendaciones actuales de ingesta, y analizar la utilidad de las leches enriquecidas en calcio para determinados grupos de población como alternativa para aumentar las ingestas de este mineral y también de vitamina D. Asimismo, se pretende clarificar los errores y mitos que han surgido recientemente en relación a determinados alimentos que pretenden sustituir a la leche y sus derivados, basándonos en sus diferencias de composición, biodisponibilidad y efectos sobre la salud.

Myrtus Polyphenols, from Antioxidants to Anti-Inflammatory Molecules: Exploring a Network Involving Cytochromes P450 and Vitamin D.

Inflammatory response represents one of the main mechanisms of healing and tissue function restoration. On the other hand, chronic inflammation leads to excessive secretion of pro-inflammatory cytokines involved in the onset of several diseases. Oxidative stress condition may contribute in worsening inflammatory state fall, increasing reactive oxygen species (ROS) production and cytokines release. Polyphenols can counteract inflammation and oxidative stress, modulating the release of toxic molecules and interacting with physiological defenses, such as cytochromes p450 enzymes. In this paper, we aimed at evaluating the anti-inflammatory properties of different concentrations of Myrtus communis L. pulp and seeds extracts, derived from liquor industrial production, on human fibroblasts. We determined ROS production after oxidative stress induction by H2O2 treatment, and the gene expression of different proinflammatory cytokines. We also analyzed the expression of CYP3A4 and CYP27B1 genes, in order to evaluate the capability of Myrtus polyphenols to influence the metabolic regulation of other molecules, including drugs, ROS, and vitamin D. Our results showed that Myrtus extracts exert a synergic effect with vitamin D in reducing inflammation and ROS production, protecting cells from oxidative stress damages. Moreover, the extracts modulate CYPs expression, preventing chronic inflammation and suggesting their use in development of new therapeutic formulations.

Current concepts in vitamin D and orthopaedic surgery.

INTRODUCTION: Vitamin D plays an important role in the musculoskeletal system of the human body. Here, we review the most current literature on vitamin D as it relates to orthopaedic surgery and the musculoskeletal system, focusing largely on non-fracture applications. MATERIALS AND METHODS: A literature review was performed on the basic science of vitamin D metabolism, epidemiology of vitamin D levels, role of vitamin D within the musculoskeletal system, and the correlation of vitamin D with injuries and orthopaedic surgical outcomes. RESULTS: The existing literature suggests vitamin D plays multiple roles in the musculoskeletal system. Recent research has shed light on the importance of vitamin D in the setting of soft tissue healing and recovery in addition to affecting postoperative outcomes after common orthopaedic procedures. CONCLUSIONS: Given the widespread prevalence of vitamin D deficiency, orthopaedic surgeons should be aware of the current evidence regarding clinical implications in patients with musculoskeletal complaints.

Controversies Surrounding Vitamin D: Focus on Supplementation and Cancer.

There has recently been a huge number of publications concerning various aspects of vitamin D, from the physiological to therapeutic fields. However, as a consequence of this very fast-growing scientific area, some issues still remain surrounded by uncertainties, without a final agreement having been reached. Examples include the definitions of vitamin D sufficiency and insufficiency, (i.e., 20 vs. 30 ng/mL), the relationship between 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone, (i.e., linear vs. no linear), the referent to consider, (i.e., total vs. free determination), the utility of screening versus universal supplementation, and so on. In this review, the issues related to vitamin D supplementation in subjects with documented hypovitaminosis, and the role of vitamin D in cancer will be concisely considered. Daily, weekly, or monthly administration of cholecalciferol generally leads to essentially similar results in terms of an increase in 25(OH)D serum levels. However, we should also consider possible differences related to a number of variables, (i.e., efficiency of intestinal absorption, binding to vitamin D binding protein, and so on). Thus, adherence to therapy may be more important than the dose regimen chosen in order to allow long-term compliance in a sometimes very old population already swamped by many drugs. It is difficult to draw firm conclusions at present regarding the relationship between cancer and vitamin D. In vitro and preclinical studies seem to have been more convincing than clinical investigations. Positive results in human studies have been mainly derived from post-hoc analyses, secondary end-points or meta-analyses, with the last showing not a decrease in cancer incidence but rather in mortality. We must therefore proceed with a word of caution. Until it has been clearly demonstrated that there is a causal relationship, these positive "non-primary, end-point results" should be considered as a background for generating new hypotheses for future investigations.

Vitamin D intake, serum 25-hydroxy vitamin D and pulmonary function in paediatric patients with cystic fibrosis: a longitudinal approach.

Pancreatic-insufficient children with cystic fibrosis (CF) receive age-group-specific vitamin D supplementation according to international CF nutritional guidelines. The potential advantageous immunomodulatory effect of serum 25-hydroxy vitamin D (25(OH)D) on pulmonary function (PF) is yet to be established and is complicated by CF-related vitamin D malabsorption. We aimed to assess whether current recommendations are optimal for preventing deficiencies and whether higher serum 25(OH)D levels have long-term beneficial effects on PF. We examined the longitudinal relationship between vitamin D intake, serum 25(OH)D and PF in 190 CF children during a 4-year follow-up period. We found a significant relationship between total vitamin D intake and serum 25(OH)D (ß = 0·02; 95 % CI 0·01, 0·03; P = 0·000). However, serum 25(OH)D decreased with increasing body weight (ß = -0·79; 95 % CI -1·28, -0·29; P = 0·002). Furthermore, we observed a significant relationship between serum 25(OH)D and forced expiratory volume in 1 s (ß = 0·056; 95 % CI 0·01, 0·102; P = 0·018) and forced vital capacity (ß = 0·045; 95 % CI 0·008, 0·082; P = 0·017). In the present large study sample, vitamin D intake is associated with serum 25(OH)D levels, and adequate serum 25(OH)D levels may contribute to the preservation of PF in children with CF. Furthermore, to maintain adequate levels of serum 25(OH)D, vitamin D supplementation should increase with increasing body weight. Adjustments of the international CF nutritional guidelines, in which vitamin D supplementation increases with increasing weight, should be considered.

A downstream molecule of 1,25-dihydroxyvitamin D3, alpha-1-acid glycoprotein, protects against mouse model of renal fibrosis.

Renal fibrosis, the characteristic feature of progressive chronic kidney disease, is associated with unremitting renal inflammation. Although it is reported that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, elicits an anti-renal fibrotic effect, its molecular mechanism is still unknown. In this study, renal fibrosis and inflammation observed in the kidney of unilateral ureteral obstruction (UUO) mice were reduced by the treatment of 1,25(OH)2D3. The plasma protein level of alpha-1-acid glycoprotein (AGP), a downstream molecule of 1,25(OH)2D3, was increased following administration of 1,25(OH)2D3. Additionally, increased mRNA expression of ORM1, an AGP gene, was observed in HepG2 cells and THP-1-derived macrophages that treated with 1,25(OH)2D3. To investigate the involvement of AGP, exogenous AGP was administered to UUO mice, resulting in attenuated renal fibrosis and inflammation. We also found the mRNA expression of CD163, a monocyte/macrophage marker with anti-inflammatory potential, was increased in THP-1-derived macrophages under stimulus from 1,25(OH)2D3 or AGP. Moreover, AGP prevented lipopolysaccharide-induced macrophage activation. Thus, AGP could be a key molecule in the protective effect of 1,25(OH)2D3 against renal fibrosis. Taken together, AGP may replace vitamin D to function as an important immune regulator, offering a novel therapeutic strategy for renal inflammation and fibrosis.

Vitamin D and Postoperative Vasopressor Use in Cardiopulmonary Bypass.

The use of cardiopulmonary bypass (CPB) in cardiac surgery often leads to a systemic inflammatory response. Up to 25% of patients undergoing CPB for cardiac surgery are reported to develop vasoplegic syndrome in the acute postoperative period, in which the patients are refractory to vasopressors. The purpose of this study is to assess vitamin D deficiency as a risk factor for vasoplegia after using CPB. We performed a retrospective review of 1322 patients undergoing adult cardiac surgery requiring CPB. Forty-six patients with previously recorded 25-hydroxy vitamin D (25(OH)D) levels within 6 months of surgery met the conditions of this study. The mean level of 25(OH)D was 32.7 ng/mL (standard deviation [SD] = 15.1). The mean age of patients was 67 (SD = 10.1) years old, most were male (63%) and white (78%). Average CPB time was 140 ± 44 minutes. Postoperative vasopressor use was compared to individual preoperative 25(OH)D levels. As a secondary end point, postoperative vasopressor use and vasoplegia were analyzed between 3 groups: Vitamin D deficient defined as 25(OH)D ≤20 ng/mL (n = 7), vitamin D insufficient defined as 25(OH)D between 20 and 29 ng/mL (n = 15), and vitamin D sufficient defined as 25(OH)D ≥30 ng/mL (n = 24). There was no correlation between vitamin D levels and postoperative vasopressor use. The mean doses of postoperative vasopressor use were 0.088 µg/kg/min (standard error of the mean [SEM] = 0.032), 0.085 µg/kg/min (SEM = 0.037), and 0.072 µg/kg/min (SEM = 0.024) of norepinephrine equivalents for the vitamin D deficient, insufficient, and sufficient groups, respectively. Incidence of vasoplegia for each group was the following: 0.143 for vitamin D deficient, 0.067 for vitamin D insufficient, and 0.125 for vitamin D sufficient. In this pilot study, there does not appear to be a relationship between vitamin D and vasopressor use following cardiac surgery utilizing CPB; however, there appears to be a trend toward an increased vasopressor usage in patients with decreased vitamin D levels. A larger sample size and a prospective analysis are warranted to further assess the significance of the relationship between vasoplegia and vitamin D deficiency. With further investigation, vitamin D has the potential to become a low-cost, low-risk therapeutic for improving outcomes in CPB surgery.

Impact of a Vitamin D Replacement Algorithm in Children and Young Adults With Acute Lymphoblastic Leukemia.

BACKGROUND: Pediatric cancer patients have a high prevalence of vitamin D deficiency. Children and young adults with acute lymphoblastic leukemia are at high risk for associated poor bone outcomes due to contributing effects of chemotherapy and supportive care. Evidence-based vitamin D guidelines are lacking in this population. MATERIALS AND METHODS: This is a retrospective study following the implementation of an institutional guideline for standardized monitoring and supplementing vitamin D based on 25-hydroxyvitamin D levels and patient age. Goal 25-hydroxyvitamin D level was defined as ≥30 ng/mL and levels were checked every 3 months. RESULTS: Over a period of 22 months, 69 patients (median age, 6.7 y) were included. At diagnosis, 42 patients (60.8%) were insufficient. Among insufficient patients at diagnosis, 83.3% became sufficient at first repeat level following supplementation. At completion of the study 95.6% of patients were sufficient. Insufficiency was more common in winter than summer at baseline (74.3% vs. 47.1%, P=0.03), though the impact of seasonality was overcome following the algorithm. Throughout the study 4 patients had supratherapeutic but nontoxic levels. CONCLUSIONS: Vitamin D replacement guidelines implemented in the pediatric and young adult acute lymphoblastic leukemia population markedly increased the percentage of vitamin D sufficient patients in a short period of time.

Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL): Effects on Bone Structure and Architecture.

Vitamin D supplements are often used to benefit skeletal health, although data on effects of daily high-dose vitamin D alone on bone density and structure are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, randomized, placebo-controlled trial testing effects of high-dose supplemental vitamin D3 (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (FAs; 1 g/day) for the primary prevention of cancer and cardiovascular disease. The study has a mean treatment period of 5 years among 25,874 U.S. men ≥50 years and women ≥55 years old from all 50 states. The ancillary study, VITAL: Effects on Bone Structure and Architecture, is testing effects of vitamin D3 and/or omega-3 FAs on musculoskeletal outcomes and body composition in a subcohort of 771 participants. At in-person visits at the Harvard Catalyst Clinical and Translational Science Center (CTSC), participants completed bone density/architecture, body composition, and physical performance assessments at baseline and two-year follow-up. Baseline characteristics were evenly distributed among treatment groups, suggesting that any uninvestigated confounders will be evenly distributed; sex differences were also analyzed. Future analyses of the two-year follow-up visits will elucidate whether daily high-dose, supplemental vitamin D3 and/or omega-3 FAs improve musculoskeletal outcomes, helping to advance clinical and public health recommendations. CLINICAL TRIAL REGISTRATION NUMBER: NCT01747447.

A nonrandomized trial of vitamin D supplementation for Barrett's esophagus.

BACKGROUND: Vitamin D deficiency may increase esophageal cancer risk. Vitamin D affects genes regulating proliferation, apoptosis, and differentiation and induces the tumor suppressor 15-hydroxyprostaglandin dehydrogenase (PGDH) in other cancers. This nonrandomized interventional study assessed effects of vitamin D supplementation in Barrett's esophagus (BE). We hypothesized that vitamin D supplementation may have beneficial effects on gene expression including 15-PGDH in BE. METHODS: BE subjects with low grade or no dysplasia received vitamin D3 (cholecalciferol) 50,000 international units weekly plus a proton pump inhibitor for 12 weeks. Esophageal biopsies from normal plus metaplastic BE epithelium and blood samples were obtained before and after vitamin D supplementation. Serum 25-hydroxyvitamin D was measured to characterize vitamin D status. Esophageal gene expression was assessed using microarrays. RESULTS: 18 study subjects were evaluated. The baseline mean serum 25-hydroxyvitamin D level was 27 ng/mL (normal ≥30 ng/mL). After vitamin D supplementation, 25-hydroxyvitamin D levels rose significantly (median increase of 31.6 ng/mL, p<0.001). There were no significant changes in gene expression from esophageal squamous or Barrett's epithelium including 15-PGDH after supplementation. CONCLUSION: BE subjects were vitamin D insufficient. Despite improved vitamin D status with supplementation, no significant alterations in gene expression profiles were noted. If vitamin D supplementation benefits BE, a longer duration or higher dose of supplementation may be needed.

Fish oil based vitamin D nanoencapsulation by ultrasonication and bioaccessibility analysis in simulated gastro-intestinal tract.

Recently, nanoemulsions have been employed for different applications including food and drug industries for efficient nutrient delivery system. In this study, vitamin D (a lipophilic molecule) was encapsulated in fish oil for higher oral bioavailability. The oil-in-water nanoemulsion was formulated by ultrasonication technique with a droplet size range of 300-450nm and a shelf life of more than 90days. The influence of oil, water and surfactant concentration was investigated by phase diagram. The formulated nanoemulsion had encapsulation efficiency in the range of 95.7-98.2%. Further, nanoemulsion passed through simulated gastro-intestinal tract revealed an increased bioavailability than non-encapsulated vitamin. Thus, the formulation can be used as a drug delivery vehicle for various lipophilic compounds. Till date, no one have fabricated an efficient nano-vehicle for the delivery of vitamin D as well as analyzed the efficient delivery system in simulated GI-tract, this is first of its kind study in this regard. This can be scaled up further after analyzing the safety aspects.

Early pregnancy vitamin D status and risk of preeclampsia.

BACKGROUND: Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia. METHODS: We assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (10-18 weeks), on the development of preeclampsia. The effects of serum vitamin D (25-hydroxyvitamin D [25OHD]) levels on preeclampsia incidence at trial entry and in the third trimester (32-38 weeks) were studied. We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin D-associated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia. RESULTS: Of 881 women randomized, outcome data were available for 816, with 67 (8.2%) developing preeclampsia. There was no significant difference between treatment (N = 408) or control (N = 408) groups in the incidence of preeclampsia (8.08% vs. 8.33%, respectively; relative risk: 0.97; 95% CI, 0.61-1.53). However, in a cohort analysis and after adjustment for confounders, a significant effect of sufficient vitamin D status (25OHD ≥30 ng/ml) was observed in both early and late pregnancy compared with insufficient levels (25OHD <30 ng/ml) (adjusted odds ratio, 0.28; 95% CI, 0.10-0.96). Differential expression of 348 vitamin D-associated genes (158 upregulated) was found in peripheral blood of women who developed preeclampsia (FDR <0.05 in the Vitamin D Antenatal Asthma Reduction Trial [VDAART]; P < 0.05 in a replication cohort). Functional enrichment and network analyses of this vitamin D-associated gene set suggests several highly functional modules related to systematic inflammatory and immune responses, including some nodes with a high degree of connectivity. CONCLUSIONS: Vitamin D supplementation initiated in weeks 10-18 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm. However, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia. Differentially expressed vitamin D-associated transcriptomes implicated the emergence of an early pregnancy, distinctive immune response in women who went on to develop preeclampsia. TRIAL REGISTRATION: ClinicalTrials.gov NCT00920621. FUNDING: Quebec Breast Cancer Foundation and Genome Canada Innovation Network. This trial was funded by the National Heart, Lung, and Blood Institute. For details see Acknowledgments.

Appropriate vitamin D loading regimen for patients with advanced lung cancer.

BACKGROUND: Most patients attending cancer clinics have hypovitaminosis D. Correcting or preventing this abnormal condition could mitigate the emotional and physical complications of their disease, but clinical trials of vitamin D therapy in this setting are hindered by the unavailability of safe, effective and practical loading dose regimens. METHODS: In this single arm open-label pharmacokinetic trial, outpatients with advanced lung cancer consumed 20,000 IU vitamin D daily with the largest meal of the day for 14 days followed by 10,000 IU per day for a further 7 days. Plasma concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone, calcium, vitamin C and C-reactive protein were measured on protocol days 0, 14 and 21, and serum vitamin D binding protein (VDBP) concentrations on days 0 and 21. As a secondary objective, preliminary information was obtained regarding clinical effects of rapid vitamin D loading on mood and symptoms by administering appropriate questionnaires two times at baseline and after 14 and 21 days of vitamin D therapy. RESULTS: Of the 91 patients enrolled in the study, 85 % had hypovitaminosis D and 41 % had hypovitaminosis C. Plasma VDBP concentrations were in the normal range. The vitamin D load increased the average plasma 25(OH)D concentration to 116 ± 34 nmol/L (mean ± SD); the median concentration was 122 nmol/L (interquartile range 103-134); VDBP concentrations did not change. Final plasma 25(OH)D concentrations were subnormal (<75 nmol/L) for 13 % of the patients and sub-target (<120 nmol/L) for 44 % of them. In most cases, subnormal and sub-target 25(OH)D concentrations were attributable to obesity and/or a low baseline 25(OH)D concentration. Mood and symptom scores did not change significantly throughout the 3-week protocol. CONCLUSION: Hypovitaminosis D and C are very common in outpatients with advanced lung cancer. A vitamin D load of 20,000 IU per day for 14 days failed to achieve the target concentration in 44 % of the participants in this trial. These results suggest that a loading dose of 30,000 IU per day for 14 days would be safe and effective for patients who are obese or at risk of severe hypovitaminosis D. The preliminary nature of the study design, and the failure to achieve target 25(OH)D concentrations for a large proportion of the patients, do not allow any firm conclusion about the clinical effects of correcting hypovitaminosis D in this patient population. Nevertheless, no evidence was obtained that partial correction of hypovitaminosis D greatly improved mood, reduced distress or relieved cancer-related symptoms. This trial was registered at clinicaltrials.gov as NCT01631526.

A Retrospective Study in Adults with Metabolic Syndrome: Diabetic Risk Factor Response to Daily Consumption of Agaricus bisporus (White Button Mushrooms).

Adults with metabolic syndrome from different race/ethnicities are often predisposed to developing type 2 diabetes (T2D); however, growing evidence suggests that healthy diets and lifestyle choices can significantly slow or prevent progression to T2D. This poorly understood relationship to healthy dietary patterns and prevention of T2D motivated us to conduct a retrospective analysis to determine the potential impact of a minor dietary lifestyle change (daily mushroom consumption) on known T2D risk factors in racially diverse adults with confirmed features of the metabolic syndrome. Retrospectively, we studied 37 subjects who had participated in a dietary intervention focused on vitamin D bioavailability from white button mushrooms (WBM). All 37 had previously completed a 16-week study where they consumed 100 g of WBM daily and were then followed-up for one month during which no mushrooms were consumed. We analyzed differences in serum risk factors from baseline to 16-week, and from baseline to one-month follow-up. Measurement of serum diabetic risk factors included inflammatory and oxidative stress markers and the antioxidant component naturally rich in mushrooms, ergothioneine. Significant beneficial health effects were observed at 16-week with the doubling of ergothioneine from baseline, increases in the antioxidant marker ORAC (oxygen radical absorption capacity) and anti-inflammatory hormone, adiponectin and significant decreases in serum oxidative stress inducing factors, carboxymethyllysine (CML) and methylglyoxal (MG), but no change in the lipid oxidative stress marker 8-isoprostane, leptin or measures of insulin resistance or glucose metabolism. We conclude that WBM contain a variety of compounds with potential anti-inflammatory and antioxidant health benefits that can occur with frequent consumption over time in adults predisposed to T2D. Well-controlled studies are needed to confirm these findings and identify the specific mushroom components beneficial to health.