Plasma 25-hydroxyvitamin D3 Research Articles

UV light exposure versus vitamin D supplementation: A comparison of health benefits and vitamin D metabolism in a pig model

There is limited data on the effect of UV light exposure versus orally ingested vitamin D3 on vitamin D metabolism and health. A 4-week study with 16 pigs (as a model for human physiology) was conducted. The pigs were either supplemented with 20 µg/d vitamin D3 or exposed to UV light for 19 min/d to standardize plasma 25-hydroxyvitamin D3 levels. Important differences were higher levels of stored vitamin D3 in skin and subcutaneous fat, higher plasma concentrations of 3-epi-25-hydroxyvitamin D3 and increases of cutaneous lumisterol3 in UV-exposed pigs compared to supplemented pigs. UV light exposure compared to vitamin D3 supplementation resulted in lower hepatic cholesterol, higher circulating plasma nitrite, a marker of the blood pressure-lowering nitric oxide, and a reduction in the release of pro- and anti-inflammatory cytokines from stimulated peripheral blood mononuclear cells. However, plasma metabolome and stool microbiome analyses did not reveal any differences between the two groups. To conclude, the current data show important health relevant differences between oral vitamin D3 supplementation and UV light exposure. The findings may also partly explain the different vitamin D effects on health parameters obtained from association and intervention studies.

Intratumoral vitamin D signaling and lethal prostate cancer.

High circulating vitamin D levels and supplementation may lower prostate cancer mortality. To probe for direct effects of vitamin D signaling in the primary tumor, we assessed how activation of intratumoral vitamin D signaling in prostate cancer is associated with lethal prostate cancer during long-term follow-up. Among 404 participants with primary prostate cancer in the Health Professionals Follow-up Study and the Physicians' Health Study, we defined a gene score of expected activated intratumoral vitamin D signaling consisting of transcriptionally upregulated (CYP27A1, CYP2R1, RXRA, RXRB, and VDR) and downregulated genes (CYP24A1 and DHCR7). We contrasted vitamin D signaling in tumors that progressed to lethal disease (metastases/prostate cancer-specific death, n = 119) over up to three decades of follow-up with indolent tumors that remained nonmetastatic for >8 years post-diagnosis (n = 285). The gene score was downregulated in tumor tissue compared with tumor-adjacent histologically normal tissue of the same men. Higher vitamin D gene scores were inversely associated with lethal prostate cancer (odds ratio for highest versus lowest quartile: 0.46, 95% confidence interval: 0.21-0.99) in a dose-response fashion and after adjusting for clinical and pathologic factors. This association appeared strongest among men with high predicted plasma 25-hydroxyvitamin D3 and men with body mass index ≥25 kg/m2. Findings were replicated with broader gene sets. These data support the hypothesis that active intratumoral vitamin D signaling is associated with better prostate cancer outcomes and provide further rationale for testing how vitamin D-related interventions after diagnosis could improve prostate cancer survival through effects on the tumor.

Enhancement of selectivity, 25-hydroxyvitamin D3 level, alkaline phosphatase activity and reproductive performance in gilts and primiparous sows using 14-epimer of 25-hydroxyvitamin D3

Selecting breed-worthy gilts as sow replacements is essential for continuity of pig production cycle. Though vitamin D3 (VD3) is known to enhance reproductive performance of multiparous sows, there is still a knowledge gap on its impact in developing gilts and primiparous sows. This study was aimed to quantify plasma 25-hydroxyvitamin D3 (25(OH)D3), serum alkaline phosphatase (ALP), and examine the reproductive performance of primiparous sows fed diets supplemented with regular VD3, and its 25(OH)D3 epimers. The study sample comprised 10-week-old replacement gilts (50 % Landrace x 50 % Yorkshire, N = 180) assigned in a randomized complete block design to three treatments [2,000 IU/kg of VD3 (T1), 25 µg/kg of 14‑epi-25(OH)D3, half dose (T2), and 50 µg/kg of 25(OH)D3 (T3)] equilibrated to 2,000 IU/kg in base diets. Selections occurred at 22, 27 and 35 weeks of age, respectively. Plasma 25(OH)D3, serum alkaline phosphatase (ALP), bone structure and reproductive performance were analyzed. Dietary treatments influenced carpus (P = 0.023), fore view stance (P = 0.017), infantile vulva (P = 0.014), inverted (P = 0.048), and prominent teat (P < 0.001). Post-partum 25(OH)D3 concentration and ALP activity were elevated by day 25 (P < 0.001). Treatment diets also influenced total born (P < 0.001), born alive (P = 0.048), and still born (P = 0.049). Two factors affect circulating 25(OH)D3 and ALP activity: physiological changes in sows during lactation, and dietary 25(OH)D3 intake. 14‑epi-25(OH)D3 is a potent metabolite for improving maturation of reproductive organs in developing gilts. It also reduces still birth in primiparous sows.

Biological variation of plasma 25-Hydroxyvitamin D3, Serum vitamin B12, folate and ferritin in Turkish healthy subject

Biological variation (BV) plays a crucial role in determining analytical performance specifications, assessing serial measurements of individuals, and establishing the use of population-based reference intervals. Our study aimed to calculate the BV and BV-based quality goals of 25-hydroxyvitamin D3 (25-OH D3), ferritin, folate and vitamin B12 tests. We included a total of 22 apparently healthy volunteers (9 women and 13 men) aged 18-55 years in the study that we conducted in Turkey. Blood samples were collected from the participants once a week for five weeks. Serum ferritin, folate and vitamin B12 levels were measured using immunochemical method, while plasma 25-OH D3 levels were determined using the high-performance liquid chromatography method. Analysis of variance (ANOVA) was used to estimate analytical variation(CVA), within-subject BV(CVI) and between-subject BV(CVG). The individuality index (II) and reference change value (RCV) were calculated based on these data. The CVI of 25-OH D3, ferritin, folate, and vitamin B12 were found to be 1.8% (0.6%-2.5%), 16.9% (14.4%-20.2%), 10.7% (9.2%-12.7%), and 8.6% (6.8%-10.5%), respectively. CVG were 44.2% (34.3%-69.9%), 132% (87.7%-238%), 19.4% (14.4%-28.8%), and 39.6% (29.8%-59.0%) for the same biomarkers, while CVA were 3.2% (2.81%-3.71%), 3.5% (3.1%-4.1%), 4.0% (3.5%-4.6%), and 7.5% (6.6%-8.6%), respectively. The II values for 25-OH D3, ferritin, folate, and vitamin B12 were calculated as 0.04, 0.13, 0.55, and 0.22, respectively. The RCV were 10.2%, 47.8%, 31.7%, and 31.6%, respectively. Because the tests analyzed in this study exhibit high individuality, RCV should be preferred rather than population-based reference ranges in clinical interpretation of results.

The effect of lactose intolerance on plasma glucose levels and related biochemical parameters

Aim: To determine the effect of lactose intolerance on serum glucose levels and related biochemical parameters in the adult population who refrain from consuming milk and milk products.&#x0D; Material and Method: This retrospective, observational study was conducted in a tertiary care hospital between January 2016 and December 2019 with 296 participants. Plasma glucose, calcium, 25-hydroxyvitamin D3, folate, vitamin B12, thyroid-stimulating hormone (TSH), and ferritin levels were controlled. Patients with positive lactose intolerance test results were accepted as the study group and negative results were accepted as the control group, and data of two groups were compared.&#x0D; Results: Of the total 296 participants 212 (71.7%) were found to have lactose intolerance and 84 (28.3%) were found to be normal. In the lactose intolerant group, blood glucose levels were significantly lower than the control group (5.14±0.53 mmol/L versus 5.47±0.54 mmol/L, p

Plasma Levels of Bioactive Vitamin D and A5 Ligands Positively Correlate with Clinical Atopic Dermatitis Markers

Background: Over the past decade, several controversial studies described a relationship between vitamin D and atopic diseases. Low plasma vitamin D levels or even vitamin D deficiency was associated with an increased incidence of atopic disease, postulating that a higher dietary intake of vitamin D may be a beneficial strategy against atopic diseases such as atopic dermatitis (AD). Objective: Our aim was to determine the relationship between plasma 25-hydroxyvitamin D3 (25(OH)D₃) levels, the levels of the ligand of the vitamin D receptor (VDR) heterodimerization partner as well as the retinoid X receptor (RXR) and the active vitamin A5 derivative 9-cis-13,14-dihydroretinoic acid (9CDHRA) and AD severity. Methods/Results: Samples from AD patients (n = 20) and healthy volunteers (n = 20) were assessed. In our study, the frequently measured VDR ligand precursor 25(OH)D₃ in addition to the VDR-ligand 1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃) and 9CDHRA displayed no different levels when compared with the plasma of AD patients and healthy volunteers. When performing further correlation studies focusing on AD patients, plasma 25(OH)D₃ levels showed a negative correlation with eosinophils in blood (EOS) and SCORing Atopic Dermatitis (SCORAD) values, while 1,25(OH)₂D₃ and 9CDHRA levels correlated positively with plasma IgE, EOS, and SCORAD values. Conclusion: In consequence, the metabolic activation of vitamin D from 25(OH)D₃ towards 1,25(OH)₂D₃ as well as the co-liganding of the RXR by 9CDHRA may be an important signalling mechanism, an important marker for AD development and severity as well as the basis for novel nutritional and pharmaceutical AD treatment options.

Plasma 25-hydroxyvitamin D3 concentrations and incident risk of ischemic stroke in rural Chinese adults: New insight on ceiling effect

ObjectiveThe aim of this study was to investigate the relationship between 25-hydroxyvitamin D3 (25[OH]D3) and ischemic stroke and its potential modifying factors in rural Chinese adults. MethodsThis nested case-control study was drawn from the H-type Hypertension and Stroke Prevention and Control Project, a community-based, prospective, observational study. Plasma 25(OH)D3 was measured by liquid chromatography with tandem quadrupole mass spectrometry. All stroke records came from the Chinese Center for Disease Control and Prevention. Multiple logistic regression models were used to evaluate the association between 25(OH)D3 and risk of ischemic stroke. ResultsWe included 1079 participants with ischemic stroke and 1079 matched controls. Due to a non-linear relationship, the analyses were stratified by 25(OH)D3. For those with 25(OH)D3 < 20 ng/mL, there was a 15% reduction in the risk of ischemic stroke for each SD increment in 25(OH)D3 (odds ratio, 0.85; 95% confidence interval, 0.73–0.99). Compared with the lowest-tertile group, the risk of ischemic stroke decreased by 39% (odds ratio, 0.61; 95% confidence interval, 0.41–0.89) in the highest-tertile group. Furthermore, two effect modifiers were identified: diabetes and homocysteine level. Although participants with 25(OH)D3 ≥ 20 ng/mL had the lowest risk of ischemic stroke overall, there was no dose-response association within that range. ConclusionsAn inverse dose-response association between 25(OH)D3 and incident risk of ischemic stroke in rural Chinese adults was only observed in those with 25(OH)D3 < 20 ng/mL, along with two effect modifiers. Higher levels of 25(OH)D3 did not confer additional benefit.

Modulation of Plasma 25-Hydroxyvitamin D3 Level by Imatinib Mesylate in Patients with Chronic Myelogenous Leukemia: The Role of Uptake and Efflux Transporters

BackgroundVitamin D deficiency is a common side effect of imatinib mesylate (IM) therapy. Transporter polypeptides involved in the disposition of IM may be required for maintenance of adequate vitamin D concentrations.ObjectiveThe aim of the present work is to study the association between the plasma concentrations of IM and plasma 25-hydroxyvitamin (25[OH]) D3 with transporter genotypes in patients with chronic myelogenous leukemia.MethodsA total of 77 adult patients with chronic myelogenous leukemia treated with IM participated in this study. Peak and trough plasma IM and 25(OH) vitamin D3 concentrations were measured and compared to the results of single nucleotide polymorphisms of the efflux transporting gene ABCB1-1236 C>T and the uptake transporting gene OATP1B3-334 T>G. Multiple linear regressions were used to examine the associations between 25(OH) vitamin D3 concentrations and a number of patient characteristics, including responses to therapy. Binary logistic regression analysis was used to predict odd ratios for the clinical response to IM.ResultsPlasma 25(OH) vitamin D3 concentration quartile values were: 25%, 8.2 ng/mL; 50%, 9.8 ng/mL; and 75%, 12 ng/mL. High IM peak concentration, being OATP1B3-334 T>G (TT), and/ or ABCB1-1236 C>T (CT) are associated with lower concentrations of 25(OH) vitamin D3. Moreover, IM peak concentration, IM trough concentration, and plasma concentration of 25(OH) vitamin D3 were associated with the clinical response to IM.Conclusionsvitamin D, IM concentration, as well as the genotype of OATP1B3-334 T>G, had an influence on the response of patients with chronic myelogenous leukemia.

Oral Intake of Lumisterol Affects the Metabolism of Vitamin D.

The treatment of food with ultraviolet-B (UV-B) light to increase the vitamin D content is accompanied by the formation of photoisomers, such as lumisterol2 . The physiological impact of photoisomers is largely unknown. Three groups of C57Bl/6 mice are fed diets containing 50µg kg-1 deuterated vitamin D3 with 0, 50 (moderate-dose) or 2000µg kg-1 (high-dose) lumisterol2 for four weeks. Considerable quantities of lumisterol2 and vitamin D2 are found in the plasma and tissues of mice fed with 2000µg kg-1 lumisterol2 but not in those fed 0 or 50µg kg-1 lumisterol2 . Mice fed with 2000µg kg-1 lumisterol2 showed strongly reduced deuterated 25-hydroxyvitamin D3 (-50%) and calcitriol (-80%) levels in plasma, accompanied by downregulated mRNA abundance of cytochrom P450 (Cyp)27b1 and upregulated Cyp24a1 in the kidneys. Increased tissue levels of vitamin D2 were also seen in mice in a second study that are kept on a diet with 0.2% UV-B exposed yeast versus those fed 0.2% untreated yeast containing iso-amounts of vitamin D2 . High doses of lumisterol2 can enter the body, induce the formation of vitamin D2 , reduce the levels of 25(OH)D3 and calcitriol and strongly impact the expression of genes involved in the degradation and synthesis of bioactive vitamin D.

Vitamin D Toxicosis in a Blue-Tongued Skink (Tiliqua scincoides) Presented with Epistaxis and Tongue Discoloration

A 10-yr-old intact blue-tongued skink (Tiliqua scincoides) of unknown sex presented for epistaxis and dyspnea. On physical examination, dysecdysis, necrosis of the tip of the tail, and a pink discoloration of the proximal third of the tongue were noted in addition to epistaxis, dyspnea, and tachypnea. Clinical pathology findings included marked polychromatophilia, moderate heterophilia with signs of toxicity, a regenerative left shift, and moderate hyperglycemia. Because of the suspicion of an infectious etiology, antibiotics were prescribed. Meloxicam was also administered without clinical improvement. Swelling of the pharyngeal area was noted on whole-body computed tomographic and magnetic resonance imaging. Oro-pharyngeal endoscopic-guided biopsies were performed under general anesthesia. Histology was consistent with moderate erosion and goblet cell hyperplasia. Plasma 25-hydroxyvitamin D3 concentration was 768 nmol/L and was interpreted as possible vitamin D toxicosis. Prednisolone was prescribed to enhance calciuresis and treat potential vasculitis, but the skink was ultimately euthanized. Histopathologic examination was consistent with vitamin D toxicosis. The diet of this skink mostly consisted of greens dusted with a supplement containing calcium and vitamin D3. This case report describes the challenges associated with antemortem diagnosis of a vitamin D toxicosis, even with current imaging techniques. It highlights that specific reference intervals should be established for 25-hydroxyvitamin D3 and ionized calcium concentrations in various reptile species. Clinicians presented with a blue-tongued skink displaying a pink tongue or tail necrosis should consider vitamin D toxicosis in their differential diagnosis.

Influence of the Biofield Energy Treatment on the Pharmacokinetics of 25-Hydroxyvitamin D3 in Male Sprague-Dawley Rats after a Single Oral Dose of Vitamin D3

Vitamin D3 reported having many important roles in bone metabolism, osteoporosis, immunity, and useful in numerous diseases, i.e., cardiovascular, cancers, and neurodegenerative diseases. Unexpectedly, there is little information available about the concentration of 25-hydroxyvitamin D3 in the blood, which is the best indicator of vitamin D3 status after its oral absorption. However, the biological activity of vitamin D3 is mediated via the formation of the active metabolite, 1-α, 25-dihydroxyvitamin D3 . There are several factors that affect its absorption and first-pass metabolism that lead to having very low plasma concentrations of both the metabolites (25-hydroxyvitamin D3 and 1-α, 25-dihydroxyvitamin D3 ) following an oral administration. Thus, the current study was executed to determine the influence of the Trivedi Effect®-Consciousness Energy Treatment on vitamin D3 and rats through the measurement of plasma 25-hydroxyvitamin D3 concentrations after the oral administration of vitamin D3 in male Sprague-Dawley rats. The test item, vitamin D3 was divided into two parts. One part was denoted as the control (without Biofield Energy Treatment/Blessing), while the other part was defined as the Biofield Energy Treated sample, which received the Biofield Energy Treatment by renowned Biofield Energy Healer, Dahryn Trivedi. Additionally, one group of animals also received Consciousness Energy Treatment per se by the Healer under similar conditions. The Biofield Energy Healer who was located in the USA, while the test samples and animals were located in the research laboratory in India. Vitamin D3 oral formulations were administrated by oral gavage at a dose of 500 µg per kg in groups viz. G1 (untreated vitamin D3 ), G2 (Biofield Treated vitamin D3 ), and G3 (Biofield Treated animals received untreated vitamin D3 ) group. The Biofield Energy Treatment increased the maximum plasma concentration (Cmax) of 25-hydroxyvitamin D3 by 3.45% and 72.77% in the G2 and G3 groups, respectively as compared with the G1 group. The area under the plasma concentration– time curve (AUC0–t) of 25-hydroxyvitamin D3 was altered by -11.19% in the G2 group and 59.45% in the G3 group as compared to the G1 group. After oral administration, the Tmax of 25-hydroxyvitamin D3 was altered by -62.97% in G2 and 55.56% in G3 groups compared to G1. The mean residence time (MRT) of 25-hydroxyvitamin D3 was also altered in the G2 group by -12.34% and G3 group by 0.18%, as compared to the G1. The relative oral bioavailability (Fr) of 25-hydroxyvitamin D3 was significantly altered by -11.19% in the G2 group and 59.45% in the G3 group compared to the G1. Biofield Energy Treatment could be an innovative strategy that opens new avenues to overcome poorly absorbed pharmaceuticals/ nutraceuticals/herbal extracts and can also improve the therapeutic performance of orally active molecules.

Plasma 25-Hydroxyvitamin D3 Concentrations and Risk of New-Onset Proteinuria in Patients With Hypertension

We aimed to evaluate the relationship of plasma 25-hydroxyvitamin D3 (25[OH]D3) with the risk of new-onset proteinuria and examine the possible effect modifiers in patients with hypertension and without chronic kidney disease at baseline. This is a post hoc analysis of the renal substudy of the China Stroke Primary Prevention Trial. A total of 1655 patients with hypertension, who had plasma 25(OH)D3 measurements, as well as without proteinuria and with an estimated glomerular filtration rate of ≥60mL/min/1.73m2 at baseline, were included in the present study. The main outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. The mean (standard deviation) 25(OH)D3 level at baseline was 18.6 (7.5) ng/mL. The median follow-up duration was 4.4years. Overall, there was a significant inverse association between plasma 25(OH)D3 and the risk of new-onset proteinuria (per standard deviation increment; [odds ratio] OR: 0.70; 95% confidence interval [CI]: 0.50, 0.97). Accordingly, when 25(OH)D3 was assessed as quartiles, a significantly lower risk of new-onset proteinuria was found in participants in quartiles 3-4 (≥17.8ng/mL; OR: 0.45; 95% CI: 0.23, 0.87), compared with those in quartile 1 (<13.1ng/mL). Furthermore, a stronger inverse relationship of plasma 25(OH)D3 and new-onset proteinuria was observed in nondiabetic participants (per standard deviation increment; OR: 0.57; 95% CI: 0.39, 0.83; vs. diabetics: OR: 1.48; 95% CI: 0.67, 3.28; P for interaction=0.028). There was a significant inverse association between plasma 25(OH)D3 and the risk of proteinuria in patients with hypertension, especially in those without diabetes.

Boron supplementation in peripartum Murrah buffaloes: The effect on calcium homeostasis, bone metabolism, endocrine and antioxidant status

BackgroundCalcium homeostasis and immuno-endocrine system undergoes drastic changes in peripartum dairy animals and failure to adapt these physiological changes causes major impact on animal health as well as productivity. Boron (B), a newer trace element, influences calcium (Ca), phosphorus (P) and magnesium (Mg) metabolism as well as immune system by manipulating several hormones or enzyme systems. Present study was conducted to determine the effect of dietary B supplementation on Ca homeostasis, bone metabolism, endocrine and antioxidant status in peripartum Murrah buffaloes. MethodsThirty advanced pregnant Murrah buffaloes (8th month pregnant) were allocated into three groups based on their most probable producing ability (MPPA) and parity (n = 10 in each group) viz. B0, B200 and B400 and supplemented with 0, 200 and 400 ppm of B in the form of boric acid. Blood samples were collected at periodic intervals (-45, -30, -21, -15, -7, 0, 7, 15, 30, 60, 90 and 120 day relative to expected date of calving) and analysed for minerals concentration, hormonal profile, bone health biomarkers and antioxidant enzymes. Results and conclusionBoron supplementation at 200 and 400 ppm increased (p < 0.05) plasma Ca, Mg and osteocalcin (OCN) concentration during postpartum stage. Higher (p < 0.05) levels of plasma 25-hydroxy vitamin D3 were observed in both B supplemented groups as compared to B unsupplemented group irrespective of physiological stages. Plasma parathyroid hormone (PTH) and cortisol levels were lower (p < 0.05) in both B supplemented groups than B unsupplemented group, especially during postpartum stage. Whereas, plasma ferric reducing total antioxidant power (FRAP) activity was found to be higher (p < 0.05) in B supplemented groups as compared to B unsupplemented group. Furthermore, antioxidant enzymes (erythrocytic superoxide dismutase; SOD, catalase, glutathione peroxidase; GPx), plasma level of total immunoglobulins (TIg), bone specific alkaline phosphatase (BALP) and tartrate resistant acid phosphatase (TRAP) remained unaffected by dietary B supplementation. Overall, it can be concluded that supplementation of B at 200 ppm in the diet of peripartum Murrah buffaloes helped to induce metabolic adaptations for improving Ca homeostasis, bone metabolism and antioxidant status without much additional benefits at higher level used in the present study.

Variation in plasma 25-hydroxyvitamin D2 and D3 in normal pregnancy with gestational age, sampling season, and complications: A longitudinal cohort study.

IntroductionLow levels of vitamin D in pregnancy have been associated with the risk of a variety of pregnancy outcomes. Few studies have investigated vitamin D concentrations throughout pregnancy in healthy women, and most guidelines recommend high vitamin D levels. In the present study, we investigated 25-hydroxyvitamin D concentrations in healthy Caucasian Danish women in relation to season, gestational age and possible vitamin D-linked complications.Materials and methodsEight hundred and one healthy Caucasian Danish women with an expected normal pregnancy were recruited among 2147 women attending first trimester screening. Seven blood samplings were planned throughout the pregnancy and delivery period. The 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3) concentrations were measured by LC-MS/MS and total 25-hydroxyvitamin D (25(OH)D) were calculated.ResultsA total of 3304 samples from 694 women were available for 25(OH)D measurements. The mean (25th-75th percentiles) concentrations of 25(OH)D, 25(OH)D3, and 25(OH)D2 were 54.6 (38.8–68.6) nmol/L, 52.2 (36.4–66.4) nmol/L, and 2.4 (2.2–2.2) nmol/L, respectively. Season was the strongest predictor of 25(OH)D concentration, with the lowest values observed in winter and spring, where only 42% and 41% of samples, respectively, were above 50 nmol/L. Nearly all women had values below the suggested optimal level of 75 nmol/L, independent of season. 25(OH)D peaked at gestational weeks 21–34. Plasma 25(OH)D2 levels were low in all seasons. Women with complications during pregnancy had higher 25(OH)D (estimated difference 9.8 nmol/L, standard error 2.7, p<0.001) than did women without complications, and women giving birth vaginally had lower 25(OH)D than did those delivering via elective (10.0 nmol/L, standard error 2.1, p<0.001) or emergency cesarean section (6.8 nmol/L, standard error 2.2, p<0.001).ConclusionThe 25(OH)D concentrations vary with both season and gestational age. Healthy women had lower 25(OH)D concentrations than recommended, without an association with an increased risk of pregnancy complications. Guidelines for vitamin D in pregnancy may require revision.

Association between 25-hydroxyvitamin D and hemoglobin A1c levels in patients with type 2 diabetic kidney disease

IntroductionVitamin D is suggested to influence glucose homeostasis. An inverse relationship between serum 25-hydroxyvitamin D (25(OH)D) and glycemic control in non-chronic kidney disease (CKD) patients with type 2 diabetes was reported. We aimed to examine this association among type 2 diabetes patients with CKD.ObjectivesTo examine the relation between plasma 25-hydroxyvitamin D3 (25(OH)D3) levels and glycemic state in diabetic patients at various stages of CKD.Patients and methodsA total of 70 participants (40 men and 30 women) with a mean age of 65.3±11.5 years suffering from type 2 diabetes mellitus with various stages of CKD were recruited. Blood for glycated hemoglobin (HbA1c), serum 25(OH)D3, renal profile, and estimated glomerular filtration rate was drawn at enrollment. Correlation and regression analyses were carried out to assess the relationship of serum 25(OH)D, HbA1c, and other metabolic traits.ResultsOur study shows the following results:Most of the participants are urban with age range from 50 to 70 years.Forty percent of the participants are with good glycemic control, 30% with moderate control, and 30% with bad control.Fifty percent of the patients were at CKD stage 3. Stage 5 patients differed significantly from stages 1 to 4 patients where they were younger, with lowest mean HbA1C value and a much higher mean 25(OH)D level (around twice of stage 1 patients).Half of the cases are vitamin D deficient, nearly a third of them are insufficient, and about 20% are sufficient.The level of 25(OH)D3 correlates inversely with the level of HbA1C irrespective of estimated glomerular filtration rate or the age of the patients.ConclusionThe present study reported a significant inverse relationship between serum 25 (OH)D3 and HbA1c levels in type 2 diabetics with suboptimal glycemic control and concomitant different stages of CKD.

Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial

Previous in vitro and in vivo studies indicate that enzymes that synthesize and metabolize vitamin D are magnesium dependent. Recent observational studies found that magnesium intake significantly interacted with vitamin D in relation to vitamin D status and risk of mortality. According to NHANES, 79% of US adults do not meet their Recommended Dietary Allowance of magnesium. The aim of this study was to test the hypothesis that magnesium supplementation differentially affects vitamin D metabolism dependent on baseline 25-hydroxyvitamin D [25(OH)D] concentration. The study included 180 participants aged 40-85 y and is a National Cancer Institute independently funded ancillary study, nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), which enrolled 250 participants. The PPCCT is a double-blind 2×2 factorial randomized controlled trial conducted in the Vanderbilt University Medical Center. Doses for both magnesium and placebo were customized based on baseline dietary intakes. Subjects were randomly assigned to treatments using a permuted-block randomization algorithm. Changes in plasma 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2 [25(OH)D2], 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by liquid chromatography-mass spectrometry. The relations between magnesium treatment and plasma concentrations of 25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 were significantly different dependent on the baseline concentrations of 25(OH)D, and significant interactions persisted after Bonferroni corrections. Magnesium supplementation increased the 25(OH)D3 concentration when baseline 25(OH)D concentrations were close to 30 ng/mL, but decreased it when baseline 25(OH)D was higher (from ∼30 to 50 ng/mL). Magnesium treatment significantly affected 24,25(OH)2D3 concentration when baseline 25(OH)D concentration was 50 ng/mL but not 30 ng/mL. On the other hand, magnesium treatment increased 25(OH)D2 as baseline 25(OH)D increased. Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status. This trial was registered at clinicaltrials.gov as NCT03265483.

A reduced protein diet modulates enzymes of vitamin D and cholesterol metabolism in young ruminants

Besides other adverse effects, a low protein diet has been shown to modulate cholesterol and vitamin D metabolism in monogastric species like rats and humans. As ruminants can increase the efficiency of the rumino-hepatic circulation of urea, it is assumed that goats should be able to compensate for a low dietary protein intake better. After a dietary protein restriction (9% vs. 20%) for six weeks, plasma concentrations of urea, albumin, 1,25-dihydroxyvitamin D3 and calcium were decreased, while plasma 25-hydroxyvitamin D3 (25−OHD3), and total cholesterol were significantly increased in young goats. Because this was not accompanied by any decrease in expression of CYP24A1 mRNA, we investigated mRNA expression of additional enzymes with known 24- and/or 25-hydroxylase activities (CYP2R1, CYP2J2, CYP3 A24, CYP27A1), receptors involved in their regulation (VDR, PXR, RXRα) and vitamin D binding protein (VDBP). CYP2R1expression was stimulated with the low dietary protein intake, negatively correlated with plasma urea and positively associated with serum 25−OHD3. The greater plasma concentrations of total cholesterol could be explained with the reduction of CYP2J2 and CYP27A1 expression. None of the receptors investigated were affected by the dietary protein restriction but mRNA expression of VDBP was slightly reduced. Taken together our results show that dietary protein restriction has an impact on vitamin D and cholesterol metabolism in ruminants, too. Therefore, further investigations are needed before dietary interventions aiming at diminishing nitrogen excretion can be implemented.

Vitamin D and Tissue-Specific Insulin Sensitivity in Humans With Overweight/Obesity.

Vitamin D deficiency in obesity has been linked to insulin resistance. However, studies that examined the association between plasma 25-hydroxyvitamin D3 [25(OH)D3] as well as plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and tissue-specific insulin sensitivity are scarce. Furthermore, vitamin D receptor (VDR) and vitamin D-metabolizing enzymes [cytochrome 450 (CYP)] expression in adipose tissue (AT) might affect AT insulin sensitivity. To investigate the association between body mass index (BMI) and plasma 25(OH)D3 and 1,25(OH)2D3, AT VDR; between plasma 25(OH)D3, 1,25(OH)2D3, AT VDR, and tissue-specific insulin sensitivity in individuals with overweight/obesity. This analysis included 92 adult individuals (BMI, >25 kg/m2). A two-step hyperinsulinemic-euglycemic clamp with a [6,6-2H2]-glucose tracer was performed to assess tissue-specific insulin sensitivity. Abdominal subcutaneous AT (SAT) mRNA expression of VDR and CYP was determined by using quantitative RT-PCR. University medical center. Plasma 25(OH)D3, 1,25(OH)2D3, 1,25(OH)2D3/25(OH)D3 ratio, SAT VDR and CYPs mRNA, and tissue-specific insulin sensitivity. BMI was inversely associated with plasma 25(OH)D3 (β = -0.274; P = 0.011) but not with plasma 1,25(OH)2D3. Plasma 25(OH)D3 was not related to CYPs or VDR expression in SAT. Plasma 1,25(OH)2D3 and 25(OH)D3 were not related to tissue-specific insulin sensitivity. Interestingly, SAT VDR mRNA was negatively associated with AT insulin sensitivity (β = -0.207; P = 0.025). BMI was inversely associated with 25(OH)D3 concentrations, which could not be explained by alterations in SAT VDR and CYP enzymes. Plasma vitamin D metabolites were not related to tissue-specific insulin sensitivity. However, VDR expression in SAT was negatively associated with AT insulin sensitivity.

Vitamin D Level in Non-Diabetic and Type II Diabetic Patients KFU Health Center: A Cross Sectional Study

Background: Widespread vitamin D deficiency all over the world has been documented by many previous studies including recent studies in KSA which revealed incidence reaching up to100%. Also, number of people with diabetes mellitus is increasing (7% of the world’s population in 2011, elevated to 9% in 2014). This number is expected to exceed 435 million by 2030. Compared to other areas of the world, diabetes prevalence was highest in Saudi Arabia (20.22%). In 2015, there were 3.4 million cases of diabetes in Saudi Arabia. Many studies showed high association between vitamin D deficiency and increased incidence of diabetes. Aim of the work: This study is planned to assess the incidence of vitamin D deficiency in non-diabetic and type II diabetic patients in KFU health center in Al-Ahsa region. Methods: Our study is a cross-sectional study done on 860 patients' data including plasma 25-hydroxy vitamin D3, fasting blood glucose and HbA1c levels. Results: Our results showed that 89.53% of the patients have vitamin D level below normal. There was higher incidence of vitamin D deficiency in females (81.67%) than in males (65.27%). The incidence of vitamin D deficiency was greater in Saudi (82.19%) than non-Saudi (68.40%) and in diabetics (89.68%) than non- diabetics (76.12%) patients. Within each group, the incidence of vitamin D deficiency was higher in females than in males. Incidence of vitamin D deficiency was highest in the 21 – 40 years group (86.19%) and lowest in the 1 – 20 years group (66.1%). The results showed inverse relationship between vitamin D level and both fasting blood glucose and HbA1c. The mean fasting glucose was higher in the deficiency group (165.55) as compared to the insufficiency group (118.67). Also, the mean HbA1c was higher in deficiency group (8.06) as compared to the insufficiency group (7.23). Conclusions: There is high incidence of vitamin D deficiency among KFU health center patients. Vitamin D level was inversely proportional to the level of fasting glucose and HbA1c. This is an evidence of the vitamin D role on glucose tolerance in diabetic patients.

Analysis of retinol, α-tocopherol, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in plasma of patients with cardiovascular disease by HPLC-MS/MS method.

Fat-soluble vitamins play a pivotal role in the progression of atherosclerosis and the development of cardiovascular disease. Therefore, plasma monitoring of their concentrations may be useful in the diagnosis of these disorders as well as in the process of treatment. The study aimed to develop and validate an HPLC-MS/MS method for determination of retinol, α-tocopherol, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in plasma of patients with cardiovascular disease. The analytes were separated on an HPLC Kinetex F5 column via gradient elution with water and methanol, both containing 0.1% (v/v) formic acid. Detection of the analytes was performed on a triple-quadrupole MS with multiple reaction monitoring via electrospray ionization. The analytes were isolated from plasma samples with liquid-liquid extraction using hexane. Linearity of the analyte calibration curves was confirmed in the ranges 0.02-2 μg/mL for retinol, 0.5-20 μg/mL for α-tocopherol, 5-100 ng/mL for 25-hydroxyvitamin D2 and 2-100 ng/mL for 25-hydroxyvitamin D3. Intra- and inter-assay precision and accuracy of the method were satisfactory. Short- and long-term stabilities of the analytes were determined. The HPLC-MS/MS method was applied for the determination of the above fat-soluble vitamin concentrations in patient plasma as potential markers of the cardiovascular disease progression.