Paricalcitol attenuates oxidative stress and inflammatory response in the liver of NAFLD rats by regulating FOXO3a and NFκB acetylation.

The lack of therapeutics along with complex pathophysiology made non-alcoholic fatty liver disease (NAFLD) a research hotspot. Studies showed that the deficiency of Vitamin D plays a vital role in NAFLD pathogenesis. While several research studies focused on vitamin D supplementation in NAFLD, there is still a need to understand the regulatory mechanism of direct vitamin D receptor activation in NAFLD. In the present study, we explored the role of direct Vitamin D receptor activation using paricalcitol in choline-deficient high-fat diet-induced NAFLD rat liver and its modulation on protein acetylation. Our results showed that paricalcitol administration significantly reduced the fat accumulation in HepG2 cells and the liver of NAFLD rats. Paricalcitol attenuated the elevated serum level of alanine transaminase, aspartate transaminase, insulin, low-density lipoprotein, triglyceride, and increased high-density lipoprotein in NAFLD rats. Paricalcitol significantly decreased the increased total protein acetylation by enhancing the SIRT1 and SIRT3 expression in NAFLD liver. Further, the study revealed that paricalcitol reduced the acetylation of NFκB and FOXO3a in NAFLD liver along with a decrease in the mRNA expression of IL1ß, NFκB, TNFα, and increased catalase and MnSOD. Moreover, total antioxidant activity, glutathione, and catalase were also elevated, whereas lipid peroxidation, myeloperoxidase, and reactive oxygen species levels were significantly decreased in the liver of NAFLD after paricalcitol administration. The study concludes that the downregulation of SIRT1 and SIRT3 in NAFLD liver was associated with an increased acetylated NFκB and FOXO3a. Paricalcitol effectively reversed hepatic inflammation and oxidative stress in NAFLD rats through transcriptional regulation of NFκB and FOXO3a, respectively, by inhibiting their acetylation.

VDR restores the expression of PINK1 and BNIP3 in TECs of streptozotocin-induced diabetic mice.

Defective mitophagy in renal tubular epithelial cells is one of the main drivers of renal fibrosis in diabetic kidney disease. Our gene sequencing data showed the expression of PINK1 and BNIP3, two key molecules of mitophagy, was decreased in renal tissues of VDR-knockout mice. Herein, streptozotocin (STZ) was used to induce renal interstitial fibrosis in mice. VDR deficiency exacerbated STZ-induced renal impairment and defective mitophagy. Paricalcitol (pari, a VDR agonist) and the tubular epithelial cell-specific overexpression of VDR restored the expression of PINK1 and BNIP3 in the renal cortex and attenuated STZ-induced kidney fibrosis and mitochondrial dysfunction. In HK-2 cells under high glucose conditions, an increased level of α-SMA, COL1, and FN and a decreased expression of PINK1 and BNIP3 with severe mitochondrial damage were observed, and these alterations could be largely reversed by pari treatment. ChIP-qPCR and luciferase reporter assays showed VDR could positively regulate the transcription of Pink1 and Bnip3 genes. These findings reveal that VDR could restore mitophagy defects and attenuate STZ-induced fibrosis in diabetic mice through regulation of PINK1 and BNIP3.

Electrocardiographic, biochemical, and scintigraphic evidence for the cardioprotective effect of paricalcitol and vitamin D3 on doxorubicin-induced acute cardiotoxicity in rats.

AIM: We aimed to investigate the possible cardioprotective effects of paricalcitol (PR), its vitamin D receptor agonist, and vitamin D3 (VIT-D3) on an experimental model of doxorubicin (DX) cardiotoxicity by 99mTc-PYP scintigraphy, electrocardiographic (ECG) and biochemical methods. METHOD: Forty-two male Wistar/Albino rats (250‒300 g; aged 10‒12 weeks) were randomly separated into six groups, namely into control (CN), doxorubicin (DX), paricalcitol (PR), vitamin D3 (VIT-D3), paricalcitol + doxorubicin (PR+DX), and vitamin D3 + doxorubicin (VIT-D3+DX) groups. Cardiotoxicity was induced by three doses of DX (18 mg/kg, i.p.) at 24-hour intervals on days 18, 19 and 20. PR (0.5 ug/ kg, i.p) and VIT-D3 (5,000 IU/kg, i.p) were injected for 20 days before and after the application of DX (18 mg/kg, i.p.). On day 21 of the experiment, biochemical parameters [tumor necrosis factor TNF-alpha (TNF-α); interleukin-6 (IL-6), nitric oxide (NO), and cardiac troponin T (cTnT)], as well as ECG and scintigraphic (99mTc-PYP) features were assessed. RESULTS: Compared to CN, DX significantly raised TNF-α, IL-6, and NO in heart tissue, cTnT in serum, 99mTc-PYP uptake in the myocardium, and ECG parameters, specifically QRS complex duration, QT interval duration, and ST-segment amplitude, while also reducing heart rate (p<0.001). Pretreatment with PR and VIT-D3 mitigated these abnormalities produced by DX in the heart (p<0.001). CONCLUSION: Results show that vitamin D receptor agonist paricalcitol and vitamin D protect against DX-induced cardiotoxicity through anti-inflammatory and antioxidant effects (Fig. 4, Ref. 59). Text in PDF www.elis.sk Keywords: paricalcitol, doxorubicin, vitamin D, ECG, 99mTc-PYP scintigraphy, cardiotoxicity, inflammation.

Triple quadrupole liquid chromatography-mass spectrometry-mediated evaluation of vitamin D2 accumulation potential, antioxidant capacities, and total polyphenol content of white jelly mushroom (Tremella fuciformis Berk.).

Tremella fuciformis Berk. (TF), or the white jelly mushroom, is well known for its myriad of pharmacological properties, such as immunomodulatory, anti-inflammatory, antidiabetic, antitumor, and antioxidant activities, and hypocholesterolemic and hepatoprotective effects that boost human health. Most of the studies of TF are concentrated on its polysaccharide (glucuronoxylomannan) composition, which is responsible for its pharmacological as well as rheological properties. It is well established that mushrooms are a great source of dietary vitamin D due to the presence of ergosterol in their cell membrane. There is a lack of published data on TF as a source of vitamin D2. Therefore, this study aimed to evaluate the vitamin D2 composition of the fruiting bodies of TF using triple quadrupole liquid chromatography-mass spectrometry (LC-MS/QQQ). The results showed highest vitamin D2 content (292.02 µg/g dry weight) in the sample irradiated with ultraviolet B (UVB; 310 nm) for 180 min as compared with the control group (52.47 µg/g dry weight) (P ≤ 0.001). The results showed higher accumulation potential of vitamin D2 in TF as compared with published data available for other extensively studied culinary mushrooms, such as Agaricus bisporus, Lentinula edodes, Pleurotus ostreatus, Cordiceps militaris, and Calocybe indica. Moreover, the impact of UV treatment on antioxidant capacities and total polyphenol content of TF was also studied. The accumulation potential of vitamin D in TF reveals a novel commercial source for this nutrient.

Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients.

There is no established treatment for progressive IgA nephropathy refractory to steroids and immunosuppressant drugs (r-IgAN). Interleukin 17 (IL-17) blockade has garnered interest in immune-mediated diseases involving the gut-kidney axis. However, single IL-17A inhibition induced paradoxical effects in patients with Crohn's disease and some cases of de novo glomerulonephritis, possibly due to the complete Th1 cell response, along with the concomitant downregulation of regulatory T cells (Tregs). Seven r-IgAN patients were treated with at least six months of oral paricalcitol, followed by the addition of subcutaneous anti-IL-17A (secukinumab). After a mean follow-up of 28 months, proteinuria decreased by 71% (95% CI: 56-87), P < 0.001. One patient started dialysis, while the annual eGFR decline in the remaining patients [mean (95% CI)] was reduced by 4.9 mL/min/1.73 m2 (95% CI: 0.1-9.7), P = 0.046. Circulating Th1, Th17, and Treg cells remained stable, but Th2 cells decreased, modifying the Th1/Th2 ratio. Intriguingly, accumulation of circulating Th17.1 cells was observed. This novel sequential therapy appears to optimize renal advantages in patients with r-IgAN and elicit alterations in potentially pathogenic T helper cells.

Hypercalcaemia of malignancy: a case of vitamin-D-mediated hypercalcaemia in lymphoma.

Hypercalcaemia of malignancy (HCM) is a paraneoplastic syndrome that often portends a poor prognosis. We present an extremely rare (<1%) case of HCM due to extrarenal calcitriol (1,25-(OH)2D) production in a patient with splenic marginal zone lymphoma. A man in his 80s presented with a 3-week history of fatigue, unsteadiness and abdominal pain, and new findings of anaemia, kidney injury and hypercalcaemia. Laboratory evaluation, bone marrow biopsy and positron emission tomography/computed tomography (PET/CT) confirmed the diagnosis of splenic marginal zone lymphoma which produced calcitriol (1,25-(OH)2D3), causing the patient's hypercalcaemia.

Vitamin D supplementation in a post-pandemic era: A narrative review.

Vitamin D is a fat-soluble molecule referring to the different isoforms, ergocalciferol (D2) and cholecalciferol (D3). Its physiological functions include increasing calcium serum concentrations. 25-hydroxyvitamin D3 (25(OH)D) (Calcifediol), a non-active, circulating instant precursor is seen as a pre-hormone. Studies have shown that a deficiency in calcifediol is related to chronic conditions such as cardiovascular, musculoskeletal, immune system, neurological, and anti-neoplastic functions. Vitamin D supplementation has shown its benefit as prophylaxis and treatment during the coronavirus disease 2019 (COVID-19) pandemic and an increase in the prescribing of vitamin D supplementation has been observed. The intention of this review article is to provide guidance on the recommended dosage regimen as a prophylactic measure during COVID-19 and its use as a supplement in general. From this review article, it is clear that vitamin D has an important role to play not only in COVID-19 but also in various other health aspects of the human body.Contribution: This review article highlighted the role of vitamin D in managing vitamin D deficiency and its role as a supplement in the management of respiratory tract infections, especially COVID-19. This overview can assist physicians in optimising healthcare by optimised dosing recommendations and indications.

A Pilot Study of Paricalcitol plus Nanoliposomal Irinotecan and 5-FU/LV in Advanced Pancreatic Cancer Patients after Progression on Gemcitabine-Based Therapy.

PURPOSE: Vitamin D analogues remodel the desmoplastic stroma, and improve vascularity and efficacy of chemotherapy in preclinical pancreas cancer models. PATIENTS AND METHODS: We conducted a pilot study to evaluate the safety and preliminary efficacy of the vitamin D analogue paricalcitol in combination with nanoliposomal irinotecan (Nal-iri) plus 5-fluorouracil/leucovorin (5-FU/LV) in patients with advanced pancreatic cancer who had progressed on gemcitabine-based therapy. Two dose levels (DL) of paricalcitol were tested: fixed dose weekly (75 mcg, DL1) and weight-based weekly (7 mcg/kg, /DL2). The primary endpoint was safety, and secondary endpoints included overall response rate, progression-free survival (PFS), and overall survival (OS). Correlative objectives aimed to identify molecular predictors of response and alterations in the tumor stroma. RESULTS: Twenty patients (10 each in DL1 and DL2) enrolled between March 2019 and May 2021. No grade 3/4 adverse events related to paricalcitol were observed. The most common toxicities were nausea, diarrhea and fatigue, which were similar in both cohorts. Three patients discontinued study after one cycle and were not radiographically evaluable. Of the remaining 17 evaluable patients, 2 had partial response and 12 had stable disease. The median PFS for response-evaluable patients in DL1 was 4.14 months, for DL2 was 4.83 months. Intent-to-treat median OS was 6.15 and 6.66 months for DL1 and DL2, respectively. Correlative studies showed increased tumor vascularity in posttreatment samples in patients receiving the higher dose of paricalcitol (DL2). CONCLUSIONS: Paricalcitol at 7 mcg/kg/week in combination with Nal-iri/ 5-FU/LV is safely tolerated, may increase tumor vascularity and warrants further investigation.

Metabolism of Lumisterol2 by CYP27A1.

Lumisterol2 (L2) is a photoproduct of UVB action on the fungal membrane sterol, ergosterol. Like vitamin D2, it is present in edible mushrooms, especially after UV irradiation. Lumisterol3 is similarly produced in human skin from 7-dehydrocholesterol by UVB and can be converted to hydroxy-metabolites by CYP27A1 and CYP11A1. These products are biologically active on human cells with actions that include photoprotection and inhibition of proliferation. The aim of this study was to test the ability of CYP11A1 and CYP27A1 to metabolise L2. Purified CYP27A1 was found to efficiently metabolise L2 to three major products and several minor products, whilst CYP11A1 did not act appreciably on L2. The three major products of CYP27A1 action on L2 were identified by mass spectrometry and NMR as 24-hydroxyL2, 27-hydroxyL2 and 28-hydroxyL2. Minor products included two dihydroxy L2 species, one which was identified as 24,27(OH)2L2, and another metabolite with one oxo and one hydroxyl group added. A comparison on the kinetics of the metabolism of L2 by CYP27A1 with that of the structurally similar compounds, L3 and ergosterol, was carried out with substrates incorporated into phospholipid vesicles. CYP27A1 displayed a 12-fold lower Km with L2 as substrate compared to L3 and a 5-fold lower turnover number (kcat), resulting in a 2.2 fold higher catalytic efficiency (kcat/Km) for L2 metabolism. L2 was a much better substrate for CYP27A1 than its precursor, ergosterol, with a catalytic efficiency 18-fold higher. The major CYP27A1-derived hydroxy-L2 products, 24-hydroxyL2, 27-hydroxyL2 and 28-hydroxyL2, inhibited the proliferation of melanoma and epidermoid cancer cell lines. In conclusion, this study shows that L2 is not metabolized appreciably by CYP11A1, but it is a good substrate for CYP27A1 which hydroxylates its side chain to produce 3 major products that display anti-proliferative activity on skin-cancer cell lines.

Forecasting levels of serum 25-hydroxyvitamin D based on dietary intake, lifestyle and personal determinants in a sample of Southern Europeans.

Vitamin D is an essential nutrient to be consumed in the habitual dietary intake, whose deficiency is associated with various disturbances. This study represents a validation of vitamin D status estimation using a semi-quantitative FFQ, together with data from additional physical activity and lifestyle questionnaires. This information was combined to forecast the serum vitamin D status. Different statistical methods were applied to estimate the vitamin D status using predictors based on diet and lifestyle. Serum vitamin D was predicted using linear regression (with leave-one-out cross-validation) and random forest models. Intraclass correlation coefficients, Lin's agreement coefficients, Bland-Altman plots and other methods were used to assess the accuracy of the predicted v. observed serum values. Data were collected in Spain. A total of 220 healthy volunteers aged between 18 and 78 years were included in this study. They completed validated questionnaires and agreed to provide blood samples to measure serum 25-hydroxyvitamin D (25(OH)D) levels. The common final predictors in both models were age, sex, sunlight exposure, vitamin D dietary intake (as assessed by the FFQ), BMI, time spent walking, physical activity and skin reaction after sun exposure. The intraclass correlation coefficient for the prediction was 0·60 (95 % CI: 0·52, 0·67; P < 0·001) using the random forest model. The magnitude of the correlation was moderate, which means that our estimation could be useful in future epidemiological studies to establish a link between the predicted 25(OH)D values and the occurrence of several clinical outcomes in larger cohorts.

Effectiveness of three Vitamin D dosing protocols on raising and maintaining blood serum levels of 25-hydroxyvitamin D over a three-month period: a randomized, prospective study.

INTRODUCTION: Vitamin D has gained attention in the medical community due to its critical role in calcium homeostasis and overall bone health. No standard vitamin D dosing protocol in fracture care has been established for patients deficient in 25-hydroxyvitamin D. This prospective and randomized study aimed to find a dosing regimen that would safely achieve and maintain a therapeutic level of 25-hydroxyvitamin D in deficient patients over three months. MATERIALS AND METHODS: Between June 2016 and May 2017, 48 patients with baseline total 25-hydroxyvitamin D less than 30.0 ng/mL were randomly assigned to either group one (one dose of 100,000 international units (IU) of Vitamin D2) or group 2 (100,000 IU of Vitamin D2 once weekly for twelve weeks) or group 3 (50,000 IU of Vitamin D2 daily for ten days followed by 2,000 IU of Vitamin D3 daily for 74 days). Baseline serum levels were drawn followed by interval levels at week 2, 6 and 12. The primary outcome was to determine which protocol could achieve and maintain therapeutic levels of total 25-hydroxyvitamin D over the course of three months. Our secondary outcome was to monitor for negative side effects. RESULTS: Group 1 did not show any statistically significant increase in serum levels and had no reported side effects. There was a statistically significant increase in serum total 25-hydroxyvitamin D in group 2 between all-time points except between weeks 6 and 12. Two (12.5%) participants in group 2 reported side effects. Group 3 had the greatest change in serum levels from weeks 0 to 2 but had a significant decrease between weeks 2 and 6. No change was seen between weeks 6 and 12. Three (17.5%) participants in group 3 reported side effects. CONCLUSIONS: Group 2 sustained and maintained a satisfactory level of total 25-hydroxyvitamin D over three months without any severe side effects.

Vitamin D Supplementation Has No Impact on Cardiorespiratory Fitness, but Improves Inflammatory Status in Vitamin D Deficient Young Men Engaged in Resistance Training.

Data on the effect of vitamin D (Vit-D) supplementation on cardiorespiratory fitness (VO2max) are conflicting. A possible source of discrepancies in the literature is the heterogeneity in baseline Vit-D status among participants in previous studies. The main objectives of the present study were to assess the impact of Vit-D supplementation on VO2max and inflammatory status in Vit-D deficient young healthy men. Participants (n = 39, baseline serum Vit-D level < 50 nmol/L) were quasi-randomly assigned to one of the two groups, which, in a double-blind manner, supplemented their diet daily with either Vit-D (8000 IU; VD) or placebo (PLC) and concomitantly performed a 12-week supervised resistance training program. During the 12-week intervention, serum Vit-D concentrations increased 3.9-fold (p < 0.001) in the VD group while no changes occurred in the PLC group. Baseline VO2max did not differ in the two groups and remained unchanged during the intervention. Serum interleukin-10/tumour necrosis factor alpha ratio increased significantly (30%, p = 0.007; effect size 0.399) in VD but not in PLC group. In conclusion, 12-week Vit-D supplementation increases serum 25(OH)D levels and improves inflammatory status, but has no impact on VO2max in Vit-D deficient young men engaged in resistance training.

Associations of Serum Total 25OHD, 25OHD3, and epi-25OHD3 with Insulin Resistance: Cross-Sectional Analysis of the National Health and Nutrition Examination Survey, 2011-2016.

BACKGROUND: Vitamin D may have a role in insulin sensitivity. However, the data on the association between various metabolites of Vitamin D and insulin-related parameters have been limited. METHODS: We identified 6026 adults aged 20-80 years who participated in the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Serum total 25OHD, 25OHD3, and epi-25OHD3, fasting glucose, insulin, and HOMA2-IR were obtained from the NHANES data. The association between serum Vitamin D-related values and insulin resistance was analyzed using a generalized linear model. For risk analysis, multifactorial logistic regression was used. RESULTS: The median total 25-hydroxyvitamin D level, 25-hydroxyvitamin D3 level, and 3-epi-25-hydroxyvitamin D3 level were 62.5 nmol/L, 58.8 nmol/L, and 3.3 nmol/L, respectively. After adjustment for sex, age, race, ethnicity, and education status, the ORs for the insulin resistance of participants of total 25-hydroxyvitamin D, 25-hydroxyvitamin D3, and 3-epi-25-hydroxyvitamin D3 were 0.32 (95% CI 0.24, 0.43), 0.34 (95% CI 0.26, 0.44), and 0.64 (95% CI 0.53, 0.77), respectively. After an adjustment for body mass index, diabetes, and drinking and smoking, the ORs for the insulin resistance of the participants for total 25-hydroxyvitamin D, 25-hydroxyvitamin D3, and 3-epi-25-hydroxyvitamin D3 were 0.56 (95% CI 0.40, 0.78), 0.63 (95% CI 0.46, 0.85), and 0.99 (95% CI 0.80, 1.24), respectively. CONCLUSIONS: Our study provides suggestive evidence for the association between Vitamin D concentrations and a lower risk of insulin resistance. Evidence from larger and more adequately powered cohort studies is needed to confirm our results.

Enhanced renoprotective actions of Paricalcitol and omega-3 fatty acids co-therapy against diabetic nephropathy in rat.

Introduction: Although the synthetic vitamin D analogue, Paricalcitol, and omega-3 Fatty acids (ω-3) alleviated diabetic nephropathy (DN), their combination was not previously explored. Objectives: This study measured the potential ameliorative effects of single and dual therapies of Paricalcitol and/or ω-3 against DN. Methods: Forty rats were assigned as follow: negative (NC) and positive (PC) controls, Paricalcitol, ω-3 and Paricalcitol + ω-3 groups. Diabetes was generated by high-fat/high-fructose diet and a single streptozotocin injection (40 mg/kg). DN was confirmed by raised fasting blood glucose (FBG), polyuria, proteinuria, and decreased urine creatinine levels. Paricalcitol intraperitoneal injections (0.25 µg/Kg/day; 5 times/week) and oral ω-3 (415 mg/kg/day; 5 times/week) started at week-9 and for eight weeks. Results: The PC group showed hyperglycaemia, dyslipidaemia, abnormal renal biochemical parameters, elevated caspase-3 expression, and increased apoptosis by TUNEL technique. The mRNAs and proteins of the pathogenic molecules (TGF-ß1/iNOS) and markers of tissue damage (NGAL/KIM-1) augmented substantially in the PC renal tissues relative to the NC group. The oxidative stress (MDA/H2O2/protein carbonyl groups) and pro-inflammatory (IL1ß/IL6/TNF-α) markers increased, whereas the anti-inflammatory (IL10) and anti-oxidative (GSH/GPx1/GR/SOD1/CAT) declined, in the PC renal tissues. The monotherapy groups were associated with ameliorated FBG, lipid profile and renal functions, and diminished TGF-ß1/iNOS/NGAL/KIM-1/Caspase-3 alongside the apoptotic index than the PC group. The oxidative stress and pro-inflammatory markers decreased, whilst the anti-oxidative and anti-inflammatory molecules escalated, in the monotherapy groups than the PC group. Although the Paricalcitol renoprotective actions were better than ω-3, all the biomarkers were abnormal than the NC group. Alternatively, the Paricalcitol + ω-3 protocol exhibited the best improvements in metabolic control, renal functions, oxidative stress, inflammation, and apoptosis. However, FBG and tissue damage were persistently higher in the co-therapy group than controls. Conclusions: Both monotherapies showed modest efficacy against DN, whereas their combination displayed boosted renoprotection, possibly by enhancing renal anti-oxidant and anti-inflammatory pathways.

The Effect of Vitamin D Supplementation on Treatment-Induced Pain in Cancer Patients: A Systematic Review.

OBJECTIVES: Despite the widespread use of complementary and alternative medicine by patients and physicians alike, there is no accurate evidence regarding the effects of vitamin D supplementation on treatment-induced pain in cancer patients. Thus, the aim of this systematic review of randomized controlled trials (RCTs) was to evaluate the impact of vitamin D administration on therapy-related pain in subjects diagnosed with malignant disorders. REVIEW ANALYSIS METHODS: We searched the Web of Science, Scopus, PubMed/Medline, Embase, and Google Scholar databases up to October 2020 to identify published RCTs that investigated the use of vitamin D in the management of treatment-induced pain in individuals with cancer. RESULTS: Nine RCTs were detected. The median duration of the intervention was of 24 weeks (range 12-52 weeks) and dose of vitamin D employed was 2000-50000 IU of vitamin D3 weekly orally each day. Six RCTs reported a significant reduction in pain, whereas three did not detect a notable decrease of this variable. Of the six studies that reported an alleviation of pain, an RCT which recruited 60 participants and lasted for 24 weeks consisted of supplementation with high doses of vitamin D2 weekly for 8 weeks in women receiving anastrozole as adjuvant therapy, then supplementation with vitamin D2 monthly for 4 months, effectively alleviated the aromatase inhibitor-associated musculoskeletal syndrome (AIMSS). The results of the same RCT also suggested a beneficial effect of vitamin D on musculoskeletal pain. CONCLUSIONS: Our results suggest that the supplementation with high doses of vitamin D in cancer patients with low serum levels of vitamin D, can be effective in reducing treatment-related pain.

UVB-exposed wheat germ oil increases serum 25-hydroxyvitamin D2 without improving overall vitamin D status: a randomized controlled trial.

PURPOSE: This study investigated whether UVB-exposed wheat germ oil (WGO) is capable to improving the vitamin D status in healthy volunteers. METHODS: A randomized controlled human-intervention trial in parallel design was conducted in Jena (Germany) between February and April. Ultimately, 46 healthy males and females with low mean 25-hydroxyvitamin D (25(OH)D) levels (34.9 ± 10.6 nmol/L) were randomized into three groups receiving either no WGO oil (control, n = 14), 10 g non-exposed WGO per day (- UVB WGO, n = 16) or 10 g WGO, which was exposed for 10 min to ultraviolet B-light (UVB, intensity 500-630 µW/cm2) and provided 23.7 µg vitamin D (22.9 µg vitamin D2 and 0.89 µg vitamin D3) (+ UVB WGO, n = 16) for 6 weeks. Blood was obtained at baseline, after 3 and 6 weeks and analyzed for serum vitamin D-metabolite concentrations via LC-MS/MS. RESULTS: Participants who received the UVB-exposed WGO were characterized by an increase of circulating 25(OH)D2 after 3 and 6 weeks of intervention. However, the 25(OH)D3 concentrations decreased in the + UVB WGO group, while they increased in the control groups. Finally, the total 25(OH)D concentration (25(OH)D2 + 25(OH)D3) in the + UVB WGO group was lower than that of the non-WGO receiving control group after 6 weeks of treatment. In contrast, circulating vitamin D (vitamin D2 + vitamin D3) was higher in the + UVB WGO group than in the control group receiving no WGO. CONCLUSION: UVB-exposed WGO containing 23.7 µg vitamin D can increase 25(OH)D2 levels but do no improve total serum levels of 25(OH)D of vitamin D-insufficient subjects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03499327 (registered, April 13, 2018).

Improving vitamin D status in bariatric surgery subjects with monthly high-dose ergocalciferol.

Background: Vitamin D insufficiency is common before and after bariatric surgery. Optimal supplementation to treat vitamin D insufficiency is not clearly defined. Objective: Determine if serum 25 (OH) D levels improve by the consumption of an additional monthly ergocalciferol supplement by subjects after bariatric surgery. Study design: Thirty-two subjects were randomly divided to receive an additional 100,000 IUs of ergocalciferol monthly after bariatric surgery (n=10) or standard level vitamin D supplement after bariatric surgery (n=22). Serum 25 (OH) D, calcium, and hemoglobin A1c levels were measured preoperatively and one year after bariatric surgery. Results: Mean changes in BMI at 1-year post-operation was -18.12±6.46 kg/m2 in the control group versus -18.84±4.7 kg/m2; p=0.638 in the vitamin D group. One year after bariatric surgery, the mean changes from baseline in vitamin D levels were 2.69±9.4 and 12.4±17.0 ng/mL in control and intervention groups, respectively. The treated group showed a marginally higher mean increase in Vitamin D than the control group, p=0.059. Other mean changes at 1-year post-surgery that were not significantly different include calcium -0.264±0.45 and -0.21±0.509 mg/dl in control and intervention groups, respectively and HbA1c -1.0±1.21 and -0.95±0.071% in control and intervention groups, respectively. Conclusion: This study showed 100,000 IUs ergocalciferol once a month is a safe and effective treatment for vitamin D insufficiency in most patients having bariatric surgery.

Development and Validation of a Liquid Chromatography Mass Spectrometry Method for Simultaneous Measurement of 25(OH)D3, epi-25(OH)D3, 25(OH)D2, Vitamin A, α-Tocopherol, and γ-Tocopherol.

OBJECTIVES: Fat-soluble vitamins are measured to identify deficiencies that may lead to rickets, osteomalacia, night blindness, and reversible motor and sensory neuropathies. We present a rapid liquid chromatography-mass spectrometry (LC-MS/MS) method that simultaneously measures 25-hydroxyvitamin D3 (25[OH]D3), epi-25(OH)D3, 25(OH)D2, vitamin A, α-tocopherol, and γ-tocopherol. METHODS: We mixed 100 µL serum with internal standard and extracted it by using supported liquid extraction plates. Reconstituted specimens were analyzed by LC-MS/MS with a 10-minute gradient. RESULTS: The method was linear, covering physiological levels with r2 > 0.99, and the total precision was less than 15% at all quality control levels. The lower limit of the measuring intervals for 25(OH)D3, epi-25(OH)D3, 25(OH)D2, vitamin A, α-tocopherol, and γ-tocopherol were 4 ng/mL, 4 ng/mL, 4 ng/mL, 1 µg/dL, 0.2 µg/mL, and 0.2 µg/mL, respectively, with coefficient of variation of 20% or less. Recoveries were between 92% and 111% for National Institute of Standards and Technology reference materials and 81% and 122% for spike-recovery studies. Comparison studies for vitamin D total, vitamin A, and α-tocopherol demonstrated slopes between 1.04 and 1.11 and r2 between 0.94 and 0.96. Minimal matrix effect was observed for all analytes. CONCLUSIONS: We developed and validated a rapid LC-MS/MS method for the simultaneous measurement of 25(OH)D3, epi-25(OH)D3, 25(OH)D2, vitamin A, α-tocopherol, and γ-tocopherol.

Efficacy of high versus conventional dose of ergocalciferol supplementation on serum 25-hydroxyvitamin D and interleukin-6 levels among hemodialysis patients with vitamin D deficiency: A multicenter, randomized, controlled study.

Long-term dialysis involves a chronic inflammatory state and produces a high prevalence of vitamin D deficiency. A clinical trial was conducted in hemodialysis with serum 25-hydroxyvitamin D (25[OH]D) level <30 ng/ml. The conventional-group (N = 35) and the high-dose group (N = 35) were treated with ergocalciferol according to the K/DOQI guidelines and double dosage of ergocalciferol from the recommendation for 8 weeks, respectively. The main outcomes were measured by serum 25[OH]D and interleukin-6 (IL-6). At the end of 8 weeks, a statistically significant greater increase was observed of mean serum 25[OH]D levels and a decrease of mean parathyroid hormone levels in the high-dose group compared with the conventional-dose group. The high dose group had the higher achievement of vitamin D sufficiency than the conventional-dose group (97.4% vs. 76.4%, p = 0.012). No significant difference was found in mean changes of serum IL-6 level in both groups, except subgroup patients with vitamin D deficiency or serum 25[OH]D <20 ng/ml, high dose treatment suppressed serum IL-6 level (-2.67 pg/ml [IQR -6.56 to -0.17], p = 0.039). No differences were observed between the two groups in adverse events. Oral high-dose ergocalciferol supplementation has achieved higher vitamin D sufficiency than standard dose in end stage renal disease patients on dialysis.

Can paricalcitol increase the effectiveness of n-acetylcysteine in contrast induced acute kidney prophylaxis in rats? A biochemical and histopathological study / ¿Puede el paricalcitol aumentar la eficacia de la n-acetilcisteína en la profilaxis renal aguda inducida por contraste en ratas? Un estudio bioquímico e histopatológico

SUMMARY: N-Acetylcysteine (NAC) is used for contrast induced acut kidney injury (CI-AKI) prophylaxis because of its antioxidant effects. Paricalcitol, which has reno-protective effects, is likely to provide a more effective prophylaxis when added to NAC treatment. The study was designed based on this hypothesis. The study was organised to include 4 groups each consisting of 7 rats. Group 1 was the control group, and Group 2 included rats with CI-AKI. Rats in Group 3 were administered NAC at a dose of 100 mg/kg via oral gavage once a day for 5 days. Rats in group 4 were administered paricalcitol at a dose of 0.4 mcg/kg once a day for 5 days in addition to NAC. CI-AKI was induced after the treatments in both groups. The study was terminated on the sixth day. Samples were collected from the rats' sera and kidney tissues to study oxidant and antioxidant parameters; kidney function tests were also studied. There were significant differences between the contrast nephropathy group (Group 2) and NAC and NAC+paricalcitol groups with respect to serum urea and creatinine levels. When the same groups were compared regarding oxidant (TOS-MDA) and antioxidant (TAC-Paraoxonase) parameters, we observed that the oxidant parameters increased in serum and kidney tissue samples with NAC use, and that effect was strengthened by the addition of paricalcitol to NAC treatment. However, despite increased antioxidant effectiveness, we observed no decrease in urea and creatinine levels when paricalcitol was added for CI-AKI in rats. There was no significant difference between Group 3 and Group 4. Paricalcitol provides a more potent antioxidant effect in both serum and kidney tissue samples when added to NAC treatment in rats with CI-AKI. Despite increased antioxidant parameters, however, paricalcitol does not provide a significant decrease in urea and creatinine levels.

RESUMEN: Debido a sus efectos atioxidantes la N- acetilcisteína (NAC) se usa para la profilaxis de la lesión renal aguda inducida por contraste (CI-AKI). Es probable que el paricalcitol, que tiene efectos renoprotectores, proporcione una profilaxis más eficaz cuando se agrega al tratamiento con NAC. En base a esta hipótesis el estudio fue diseñado para incluir cuatro grupos cada uno compuesto por siete ratas. El grupo 1 fue el grupo control y el grupo 2 incluyó ratas con CI-AKI. A las ratas del Grupo 3 se les administró NAC con una dosis de 100 mg/kg por sonda oral una vez al día, durante 5 días. A las ratas del grupo 4 se les administró paricalcitol a una dosis de 0,4 mcg/kg una vez al día durante 5 días, además de NAC. Se indujo CI-AKI después de los tratamientos en ambos grupos. El estudio finalizó el sexto día. Se recolectaron muestras de suero y tejidos renales de ratas para estudiar los parámetros oxidantes y antioxidantes; También se estudiaron las pruebas de función renal. Hubo diferencias significativas entre el grupo de nefropatía por contraste (Grupo 2) y los grupos NAC y NAC+paricalcitol con respecto a los niveles séricos de urea y creatinina. Cuando se compararon los mismos grupos con respecto a los parámetros oxidantes (TOS-MDA) y antioxidantes (TAC-Paraoxonase), observamos que los parámetros oxidantes aumentaron en muestras de suero y tejido renal con el uso de NAC, y ese efecto se vio reforzado por la adición de paricalcitol a tratamiento NAC. Sin embargo, a pesar de una mayor eficacia antioxidante, no observamos una disminución en los niveles de urea y creatinina cuando se agregó paricalcitol para CI-AKI en ratas. No hubo diferencias significativas entre el Grupo 3 y el Grupo 4. El paricalcitol proporciona un efecto antioxidante más potente tanto en muestras de suero como de tejido renal cuando se agrega al tratamiento con NAC en ratas con CI-AKI. Sin embargo, a pesar del aumento de los parámetros antioxidantes, el paricalcitol no proporciona una disminución sig- nificativa en los niveles de urea y creatinina.