Vitamin D3 Bioaccessibility from Supplements and Foods-Gastric pH Effect Using a Static In Vitro Gastrointestinal Model.

Vitamin D3 deficiency is a global phenomenon, which can be managed with supplementation and food fortification. However, vitamin D3 bioaccessibility may depend on factors such as matrix composition and interactions throughout the gastrointestinal (GI) tract. This research focused on the effect of different matrices on vitamin D3 content during digestion, as well as the effect of pH on its bioaccessibility. The INFOGEST protocol was employed to simulate digestion. Three different types of commercial supplements, two foods naturally rich in vitamin D3, and three fortified foods were investigated. High-Performance Liquid Chromatography was used to determine the initial vitamin D3 content in the supplements and foods, as well as after each digestion stage. The results indicate that the foods exhibited higher bioaccessibility indices compared to the supplements and a higher percentage retention at the end of the gastric phase. The pH study revealed a positive correlation between an increased gastric pH and the corresponding content of vitamin D3. Interestingly, exposing the matrix to a low pH during the gastric phase resulted in an increased intestinal content of D3. Vitamin D3 is more bioaccessible from foods than supplements, and its bioaccessibility is susceptible to changes in gastric pH. Fasting conditions (i.e., gastric pH = 1) enhance the vitamin's bioaccessibility.

Mechanisms of absorption of vitamin D3 delivered in protein nanoparticles in the absence and presence of fat.

Novel protein-based nanovehicles offer alternatives to fat for delivery of lipophilic bioactives (nutraceuticals and drugs), yet they raise important questions regarding the bioavailability and absorption mechanism of the bioactive without fat. To provide answers, we chose vitamin D3 (VD3) as a model lipophilic-nutraceutical, re-assembled casein-micelles (rCM) as model protein-based nanovehicles, and non-fat yoghurt as a model food. We prepared three yoghurt formulations: 3% fat with VD3 dissolved in milk-fat, non-fat and 3% fat, both latter enriched with VD3 within rCM. Following in vitro digestion, VD3 retention and bioaccessibility were high (∼90% and ∼70%, respectively) in all formulations. VD3 uptake by Caco-2 cells was three-fold higher (p < 0.005) in the non-fat yoghurt enriched with VD3 in rCM compared with enriched fat-containing yoghurts. SR-BI, CD36 and NPC1L1 transporters were involved in VD3 absorption irrespective of the composition. Thus, our findings demonstrate that protein nanovehicles may improve VD3 bioavailability, without altering its absorption mechanism compared to that from fat.

Analytical validation of an ultraviolet-visible procedure for determining vitamin D3 in vitamin D3-loaded microparticles and toxigenetic studies for incorporation into food.

Vitamin D is a water-insoluble compound presented in two main forms (D2 and D3), susceptible to environmental conditions. Microencapsulation is an alternative to supplements and preserve vitamin D properties in foods. Entrapment efficiency (EE) is the main property to evaluate the encapsulation effectiveness and therefore it is of interest the study of analytical methods for the identification and quantification of this compound within the particle. This paper describes a low cost UV-Vis methodology validation to the identification and quantification of vitamin D3 in microparticles produced by hot homogenization. The method was validated following the International Conference on Harmonization (ICH) guidelines. To guarantee safe application in foodstuff, microparticles toxigenicity was evaluated with Allium cepa L. in vivo model, showing no cytotoxic nor genotoxic potential. High entrapment efficiency was obtained, the results also demonstrated that the concentration of vitamin D3 in microparticles can be safely accessed by the validated method.

Nanoemulsion and emulsion vitamin D3 fortified edible film based on quince seed gum.

In this research, emulsions and nanoemulsions containing two concentrations of vitamin D were added to quince seed gum film and its properties were examined. Incorporation of emulsified oil droplets to the films structure was confirmed by FTIR. It was observed that presence of emulsion and nanoemulsion in the films, increased their thickness, opacity, and hydrophobicity and interaction of the gum chains with water molecules was decreased and so, water vapor permeability, water solubility, and moisture content decreased. Due to the penetration of oil molecules to the chain, the resultant films had higher elongation at break and lower tensile strength. SEM micrographs of samples showed instability of the oil droplets within the matrix. Vitamin content during 14 days of storage showed that it was more stable at lower concentration and in the nanoemulsion compared to emulsion. So, quince seed gum films containing vitamin can be introduces as an ideal edible packaging.

Physical and turbidimetric properties of cholecalciferol- and menaquinone-loaded lipid nanocarriers emulsified with polysorbate 80 and soy lecithin.

The present study aimed to investigate the physical and turbidimetric properties of cholecalciferol- and menaquinone-loaded lipid nanocarriers emulsified with different ratios of polysorbate 80 and soy lecithin. The lipid nanocarriers were subjected to three different heat treatments, LTLT (low temperature long time), HTST (high temperature short time), and autoclave treatments. Both cholecalciferol and menaquinone were successfully encapsulated in lipid nanocarriers and there was little loss of them during preparation. The droplet size of lipid nanocarriers emulsified with only polysorbate 80 increased and its PDI became larger than 0.3 after autoclave treatment. Moreover, 30.9% and 49.4% of cholecalciferol and menaquinone, respectively, were lost. In turbidimetric analysis, the destabilization by creaming formation in the upper layer of the lipid nanocarriers emulsified with a high polysorbate ratio was observed. However, the use of combination of both emulsifiers inhibited destabilization by flocculation as well as retained the cholecalciferol and menaquinone after all heat treatments.

Development and Characterization of an Orodispersible Film for Vitamin D3 Supplementation.

Vitamin D plays a crucial and very well-known role in regulation of calcium homeostasis and bone metabolism and mineralization. However, a huge and more recent body of evidence supports the positive influence of vitamin D on the regulation of immune response, ranging from protection against respiratory tract infections to prevention and management of asthma. Nevertheless, vitamin D deficiency is a very common condition and there is an increasing need for suitable products for proper supplementation, allowing good compliance also in specific populations. Orally disintegrating tablets (ODT) were first developed to overcome the difficulty experienced by pediatric and geriatric patients of swallowing traditional oral dosage forms and, recently, orodispersible films (ODF) are gaining popularity as novel dosage form for assuming active pharmaceutical ingredients, vitamins, and ingredients for food supplements. This study describes a 2000 IU Vitamin D3 ODF for daily intake, consisting of hydrophilic polymers and suitable excipients, manufactured by film-casting process. Elongation-at-break (E%), Young's modulus (Y), and tensile strength (TS) were investigated using a dynamometer. Chemical stability was evaluated assaying the vitamin D3 in the films stored at different environmental conditions. In addition, in vitro disintegration and dissolution studies were performed. Correlation existed between the mechanical properties of the film and the residual water, acting as plasticizer. The stability study showed that vitamin D3 assay was ≥90% also after 3 months at 40 °C. The film disintegrated in less than 1 min and the vitamin D3 released was ≥75% after 15 min. An ODF with suitable properties can be manufactured and used as innovative dosage form for vitamin D3 food supplements.

Encapsulation of vitamin D3 in gum arabic to enhance bioavailability and stability for beverage applications.

Delivery of vitamin D3 (VD3 ) in foods should exhibit desirable physicochemical characteristics and improves absorption. In this study, gum arabic (GA) was investigated as a VD3 carrier to encapsulate VD3 . VD3 dissolved in 5 mL ethanol corresponding to 0.3 to 6.0% mass of GA, was blended in 5.0% w/v GA solution, followed by freeze drying. The encapsulation efficiency decreased while loading capacity increased with an increased amount of VD3 . At the highest VD3 level, the loading capacity (3.47%) was the highest, and the encapsulation efficiency (61.24%) was satisfactory, and the treatment was further studied. The magnitude of negative zeta-potential increased from 3.1 to 31.0 mV at pH 2.0 to 7.4. During the 100-day storage at 3 °C of capsules reconstituted at pH 2.0 to 7.4, the hydrodynamic diameter decreased at all pH conditions, most evident for reduction to 81.3 nm at pH 7.4, and no precipitation was observed, indicating the significance of steric repulsion on capsule stability. Bioaccessibility of VD3 in capsules (95.76%) was significantly higher than the nonencapsulated VD3 (68.98%). The in vivo pharmacokinetic study in Sprague-Dawley rats after a single-dose of 300 µg VD3 showed the area-under-curve of serum 25(OHD) level in 48 hr of the encapsulation treatment was 4.32-fold of the nonencapsulated VD3 and more than twice higher than the VD3 -GA physical mixture. During 2-week supplementation of 60 µg VD3 /d, rats receiving capsules or physical mixture had 25(OH)D levels of at least 81 ng/mL higher than that of the nonencapsulated VD3 group. The studied encapsulation system holds great potential as a value-added ingredient to supplement VD3 in beverages with a wide pH range. PRACTICAL APPLICATION: The findings of this study demonstrated the improved dispersion stability and absorption of vitamin D3 after encapsulation in gum arabic. The capsules exhibited good dispersion stability across a pH range between 2.0 and 7.4, showing potential application in beverages. Furthermore, the enhanced absorption of VD3 after encapsulation highlights the nutritional benefits of the studied encapsulation system.

Association Between Bat Vitamin D Receptor 3' Haplotypes and Vitamin D Levels at Baseline and a Lower Response After Increased Vitamin D Supplementation and Exposure to Sunlight.

Objective: The aim of this study was to evaluate the relationship between vitamin D levels at baseline and after 12 weeks of supplementation/exposure to sunlight and VDR genotypes (BsmI, TaqI and ApaI) and haplotypes in a homogeneous population of postmenopausal women. Methods: We made a prospective study in which 151 women were randomized to two groups: One with 1000 mg of calcium and 800 IU vitamin D supplementation (102 women) and a placebo group with neither calcium or vitamin D supplementation (49 women). The follow-up was from May to September 2012.Vitamin D was determined by chemiluminescent immunoassay. Genotypes were determined using the Sequenomi Plexplatform and haplotypes using PHASE software. Results: Baseline (25 ± 10 ng/mlvs.23 ± 9 ng/ml, p > 0.05) and 12-week (32 ± 8 ng/mlvs.29 ± 10 ng/ml, p > 0.05) vitamin D levels were similar between the two groups. The genetic study was made in the total population. There were no differences in baseline and final levels of vitamin D in terms of genotypes and haplotypes, except for the Bat haplotype, whose baseline values were lower (25OHD: 21 ± 10 ng/mlvs. 21 ± 10 ng/ml, p = 0.038). The rate of nonresponders in this group was 15 % (p = 0.001), compared with 9 %, 2 % and 3 % in the other groups. Conclusions: The Bat haplotype was associated with lower baseline levels of vitamin D and a worse response to supplementation and, therefore, may be a risk factor for vitamin D deficiency.

Thermal Stability and Kinetic Study on Thermal Degradation of Vitamin D3 in Fortified Canola Oil.

Nowadays, fortified vegetable oils with vitamin D3 are widely available in different countries and are consumed daily. The reduction rate of added vitamin D3 in fortified canola oil during heating process, the changes in oxidative status, and the thermal kinetic degradation of vitamin D3 in the fortified oil were investigated. For this purpose, canola oil was fortified at two levels of vitamin D3 with 5.625 µg/mL (low concentration or LC) and 13.585 µg/mL (a high concentration or HC). Samples were heated isothermally at 100, 150, and 180 °C for 30 min. The vitamin D3 concentration was determined by the high-performance liquid chromatographic method. The retention of vitamin D3 in samples treated at 100 °C for 30 min showed no significant reduction. Samples treated at 150 and 180 °C depending on the initial concentration showed the retention of 67.5% to 72.97% and 33.16% to 40.35% of vitamin D3 , respectively. An inverse relationship was found between the increment of lipid oxidation products (peroxide and anisidine values) and the retention of vitamin D3 . Kinetic parameters such as rate constant, activation energy, decimal reduction time, and quotient indicator were also calculated. An Arrhenius relationship was used for the assessment of temperature dependence of vitamin D3 degradation. Activation energies for vitamin D3 in LC and HC between 100 and 180 °C were found to be 44.01 and 38.77 kJ/mol, respectively. PRACTICAL APPLICATION: The oil can be fortified with vitamin D3 at low cost and offers a good bioavailability. A high-temperature cooking method may not be appropriate for the fortified products containing high lipid content.

Fabrication of nano-structured lipid carrier for encapsulation of vitamin D3 for fortification of 'Lassi'; A milk based beverage.

A phase inversion based cold water dilution method was developed to encapsulate Vitamin D3 (Vit D) in nano-structured lipid carrier (NLC) by blending caprylic-/capric triglyceride, Leciva S70 and Kolliphor HS®15, Vit D and sodium chloride. To optimize the process; a total of forty one formulations prepared by varying in their composition were tested for presence of NLC. Out of forty one formulations, only thirteen formulations resulted in NLC formation which were further evaluated for their physico-chemical attributes (particle size, zeta potential, transmittance, encapsulation efficiency and Vit D release). During principal component analysis using XLstats it was found that NLC-19, fabricated with 20% (v/v) Kolliphor, 20% (v/v) CCTG and 60% (v/v) water, 2.5% (w/v) Leciva, 2% (w/v) Vit D and 5% (w/v) sodium chloride was the most suitable for purpose of encapsulating Vitamin D. Hence, NLC-19 formulation was further taken up for stability studies under the following environmental stress conditions: (a) Temperature and humidity: accelerated condition: 45 ±â€¯2 °C and RH 75 ±â€¯5%, ambient condition: 25 ±â€¯3 °C and RH 65 ±â€¯5% and refrigerated condition: 6 ±â€¯2 °C and RH 55 ±â€¯5%, (b) pH: 3, 4, 5, 6, and 7, and (c) Ionic strength (NaCl concentration): 0 mM, 250 mM, 500 mM and 750 mM. The sensory evaluation of 'Lassi' (fortified with NLC-19) and its acceptability further confirmed the suitability of NLC-19 for the purpose of fortification of Vitamin D3 in 'Lassi' (A milk based beverage).

Vitamin D: A Micronutrient Regulating Genes.

BACKGROUND: At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the transcription factor vitamin D receptor (VDR). METHODS: This review discusses the biological effects of micronutrient vitamin D ranging from calcium homeostasis and bone formation to the modulation of innate and adaptive immunity. RESULTS: Since normal human diet is sufficient in vitamin D, the need for efficient vitamin D3 synthesis in the skin acts as an evolutionary driver for its lightening during the migration out of Africa towards North. Via activating the VDR, vitamin D has direct effects on the epigenome and the expression of more than 1000 genes in most human tissues and cell types. CONCLUSIONS: The pleiotropic action of vitamin D in health and disease prevention is explained through complex gene regulatory events of the transcription factor VDR.

Activation of human insulin by vitamin E: A molecular dynamics simulation study.

Lack of perfect insulin signaling can lead to the insulin resistance, which is the hallmark of diabetes mellitus. Activation of insulin and its binding to the receptor for signaling process initiates via B-chain C-terminal hinge conformational change through an open structure to "wide-open" conformation. Observational studies and basic scientific evidence suggest that vitamin D and E directly and/or indirectly prevent diabetes through improving glucose secretion and tolerance, activating calcium dependent endopeptidases and thus improving insulin exocytosis, antioxidant effect and reducing insulin resistance. On the contrary, clinical trials have yielded inconsistent results about the efficacy of vitamin D supplementations for the control of glucose hemostasis. In this work, best binding modes of vitamin D3 and E on insulin obtained from AutoDock Vina were selected for Molecular Dynamic, MD, study. The binding energy obtained from Molecular Mechanics- Poisson Boltzman Surface Area, MM-PBSA method, revealed that Vitamins D3 and E have good affinity to bind to the insulin and vitamin E has higher binding energy (-46 kj/mol) by engaging more residues in binding site. Distance and angle calculation results illustrated that vitamin E changes the B-chain conformation and it causes the formation of wide-open/active form of insulin. Vitamin E increases the ValB12-TyrB26 distance to ∼15 Šand changes the hinge angle to ∼65°. Consequently, essential hydrophobic residues for binding to insulin receptor exposed to surface in the presence of vitamin E. However, our data illustrated that vitamin D3 cannot change B-chain conformation. Thus our MD simulations propose a model for insulin activation through vitamin E interaction for therapeutic approaches.

Natural Ingredients-Based Gummy Bear Composition Designed According to Texture Analysis and Sensory Evaluation In Vivo.

The increased interest in functional materials of natural origin has resulted in a higher market demand for preservative-free, "clean label", or natural ingredients-based products. The gummy bear food supplements are more acceptable to consumers and have fewer limitations compared to other dosage forms. The aim of our study was to produce natural ingredients-based gummy bear composition, and evaluate the influence of the selected ingredients on the product's textural properties, its acceptance in vivo, and the gummy bear's quality. The optimal base composition was determined using a surface response design: gelatin 4.3 g and agave syrup 6.3 g. The investigated sweeteners did not affect the textural properties (p > 0.05). However, further studies demonstrated that a 100% increase of agave results in up to 27% higher flexibility (p < 0.05). The addition of calcium and cholecalciferol reduced firmness by 59.59 ± 1.45% (p < 0.05). On the other hand, acai berry extract had no significant effect. The presence of calcium resulted in a decreased smell and taste; however, the data indicated that experimental texture analysis is a more accurate technique than in vivo evaluation. The acai berry extract did not improve all of the tested sensory properties. We can conclude that the suggested gummy bear base can be supplemented with various active ingredients and commercialized, though further studies are needed to investigate the other natural sources to mask the unpleasant taste of active ingredients and avoid water loss.

Fabrication of plant-based vitamin D3-fortified nanoemulsions: influence of carrier oil type on vitamin bioaccessibility.

The influence of carrier oil type (corn, fish, or flaxseed oil) on the production, stability, and simulated gastrointestinal behavior of vitamin-fortified nanoemulsions was studied. The nanoemulsions were formulated using pea protein as an emulsifier since there is increasing interest in substituting artificial and animal-based food ingredients with natural plant-based alternatives. Lipid digestion and vitamin D3 bioaccessibility were measured when the nanoemulsions were subjected to a three-stage in vitro gastrointestinal tract: oral, gastric, and small intestinal. The majority of all three lipids were digested within the first few minutes in the simulated small intestine, with the corn oil nanoemulsions being digested faster than the fish or flaxseed oils. Moreover, a greater fraction of triglycerides were digested by the end of the small intestine for the corn oil than for the fish and flaxseed oils. For the different carrier oils, vitamin bioaccessibility was ranked: corn oil > flaxseed oil ≈ fish oil. These results suggest that monounsaturated-rich oils (such as corn oil) are better for encapsulating and delivering vitamin D3 than polyunsaturated-rich ones (such as flaxseed or fish oil). The insights gained here may aid in the formulation of more efficacious vitamin-fortified foods and beverages from plant-derived ingredients.

Improved Stability of Polyglycerol Polyricinoleate-Substituted Nanostructured Lipid Carrier Cholecalciferol Emulsions with Different Carrier Oils.

Cholecalciferol, also known as vitamin D3 , is a recognized therapeutic agent for treatment of bone diseases and cancer. However, instability and poor bioavailability have been major challenges for delivering Vitamin D3 . The objective of this study was to formulate improved nanostructured lipid carrier (NLC) vitamin D3 emulsions. We tested the effect of different carrier oils and the use of a solid lipid nanoparticle emulsifier, polyglycerol polyricinoleate (PGPR) on the stability of the vitamin D3 emulsions. In contrast to the control that used glyceryl monostearate (GMS) the PGPR substitution resulted in relatively small particle sizes (0.30 to 0.43 µm), with high absolute value of zeta potentials (39.5 to 67.8 mV) and high encapsulation efficiency (85.2% to 90.4%). The stability of the NLC emulsions against environmental stresses was evaluated under varying conditions of ionic strength, pH, freeze-thaw cycles, and storage at different temperatures. Although NLC emulsions were stable at high ionic strengths, they were found to be unstable at low pH (<3), which led to aggregation and coalescence of emulsion droplets. In case of freeze-thaw stress, although relatively stable compared to control NLC, the PGPR substituted groups exhibited a slight increase in particle size and a decrease in zeta potential when the cycle was repeated five times. Additionally, we found that PGPR-substituted emulsions showed higher liquid dispersion stability than controls at 25 and 65 °C. Thus, we have formulated a modified NLC vitamin D3 emulsion that can be widely used in the food industry. PRACTICAL APPLICATION: Vitamin D3 , an essential micronutrient, is often added as supplements in food products and beverages for added health benefits. However, the stability of vitamin D3 emulsions that are used in the preparation of such products has been a major concern. We have developed a modified emulsion that has improved stability against environmental stresses. We believe, in future, this formulation can be efficiently used in the food industry.

Effects of six compounds with different chemical structures on melanogenesis.

Several chemical compounds can restore pigmentation in vitiligo through mechanisms that vary according to disease etiology. In the present study, we investigated the melanogenic activity of six structurally distinct compounds, namely, scopoletin, kaempferol, chrysin, vitamin D3, piperine, and 6-benzylaminopurine. We determined their effectiveness, toxicity, and mechanism of action for stimulating pigmentation in B16F10 melanoma cells and in a zebrafish model. The melanogenic activity of 6-benzylaminopurine, the compound identified as the most potent, was further verified by measuring green fluorescent protein concentration in tyrp1 a: eGFP (tyrosinase-related protein 1) zebrafish and mitfa: eGFP (microphthalmia associated transcription factor) zebrafish and antioxidative activity. All the tested compounds were found to enhance melanogenesis responses both in vivo and in vitro at their respective optimal concentration by increasing melanin content and expression of TYR and MITF. 6-Benzyamino-purine showed the strongest re-pigmentation action at a concentration of 20 µmol·L-1in vivo and 100 µmol·L-1in vitro, and up-regulated the strong fluorescence expression of green fluorescent protein in tyrp1a: eGFP and mitfa: eGFP zebrafish in vitro. However, its relative anti-oxidative activity was found to be very low. Overall, our results indicated that 6-benzylaminopurine stimulated pigmentation through a direct mechanism, by increasing melanin content via positive regulation of tyrosinase activity in vitro, as well as up-regulating the expression of the green fluorescent protein in transgenic zebrafish in vivo.

Is Vitamin D3 Transdermal Formulation Feasible? An Ex Vivo Skin Retention and Permeation.

Vitamin D3 supplementation is important to prevent and treat hypovitaminosis that is a worldwide public health issue. Most types of supplementation are by oral route or fortification foods. The alternative route must be investigated, as transdermal route, for people with fat malabsorption or other diseases that impair the absorption of vitamin D3. This study focused on verifying the feasibleness of vitamin D3 skin retention and permeation with the presence of chemical penetration enhancers (soybean lecithin, isopropyl palmitate, propylene glycol, ethoxydiglycol, and cereal alcohol) at different pharmaceutical forms (gel and cream) through a human skin. The integrity of skin was evaluated by transepidermal water loss (TEWL) during the skin retention and permeation test. The combination of chemical penetration enhancers presented in cream did not compromise the skin, different from the gel that association of cereal alcohol and propylene glycol compromised the skin in 24 h. Gel formulation showed vitamin D3 detection at stratum corneum in 4 h and at epidermis and dermis in 24 h. Vitamin D3 demonstrated an affinity with the vehicle in the cream formulation and was detected at the skin surface. No active was found at receptor fluid for both formulations. In conclusion, the vitamin D3 did not indicate feasibleness for transdermal use probably due to its physical-chemical characteristics such as high lipophilicity since it was not permeated through a human skin. Nevertheless, the transdermal route should be continuously investigated with less lipophilic derivates of vitamin D3 and with different combination of penetration enhancers.

Vitamin D3 supplementation improves serum SFRP5 and Wnt5a levels in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

Objective: To explore the effect of vitamin D3 on novel serum adipokines, secreted frizzled-related protein 5 (SFRP5) and Wingless-Type MMTV Integration Site Family Member 5a (Wnt5a) levels in Type 2 Diabetes Mellitus (T2DM) patients. Methods: Forty patients (16 women and 24 men) with type 2 diabetes participated in this double-blind, randomized, placebo-controlled clinical trial study. Participants were randomly assigned to receive 4000 IU vitamin D3 (n = 20) or placebo (n = 20) daily for 2 months. Anthropometric indices, fasting blood glucose (FBS), hemoglobin A1c (HbA1c), insulin, serum tumor necrosis factor (TNF)-α, Wnt5a, SFRP5, physical activity, lipid profile, dietary intake, and serum calcidiol were assessed at the baseline and after 8 weeks. Results: In the group receiving Vitamin D, a significant increase in Calicidiol (15.03 ± 10.44 vs. 27.33 ± 11.2 ng/dl; P = < 0.001), SFRP5 (3.6 ± 0.46 vs. 3.98 ± 0.59 ng/ml; P = 0.01), and Wnt5a (0.33 ± 0.129 vs. 0.29 ± 0.047; P = 0.03) was observed. After two months supplementation, there were significant between-group differences in Calicidiol (27.33 ± 11.2 vs. 17.9 ± 12.95 ng/dl; P = 0.01), TNF-α (89.22 ± 34.28 vs. 164.93 ± 120.45 ng/ml; P = 0.006), Wnt5a (0.29 ± 0.047 vs. 0.33 ± 0.09; P = 0.04), and HbA1c (6.6 ± 0.96 % vs. 7.64 ± 1.15 %; p = 0.002). Moreover, the net changes (end - baseline) of Calicidiol (P = < 0.001), SFRP5 (P = 0.04), Wnt5a (P = 0.005), TNF-α (P = 0.01), insulin (P = 0.03), and QUICKI (P = 0.01) was significant between the groups. There were no significant effects on FBS and homeostasis model of assessment-estimated insulin resistance (HOMA-IR). Conclusion: 8 weeks of vitamin D3 supplementation for patients with type 2 diabetes may increase serum anti-inflammatory adipokine SFRP5 but decrease serum pro-inflammatory Wnt5a and TNF-α.

Effect of Vitamin D Supplementation in Prostate Cancer: A Systematic Review of Randomized Control Trials.

Vitamin D is important in many cellular functions including cell cycling and proliferation, differentiation, and apoptosis. Via the induction of cell cycle arrest and/or apoptosis, vitamin D inhibits normal prostatic epithelial cells growth. Review the evidence of the effect of vitamin D supplementation on prostate cancer (PC) biomarkers and patient survival and assess optimal dosage, formulation and duration. Pubmed, Medline and Ebsco Host databases were systematically searched for relevant literature. 8 Randomized Controlled Trials were included in this review. All studies, besides one, were of high methodological quality. 4 studies used calcitriol (0,5-45 µg/weekly), 2 studies have used vitamin D3 (150-1000 µg/daily) and 2 other studies have used 1α-hydroxy Vitamin D2 (10 µg/ daily or weekly). Duration of supplementation varied between 28 days up to 18.3 months. Two studies had positive effects on prostate specific antigen (PSA) (p < .05), 1 study had a significant positive effect on median survival (p < .05) and 1 study showed a significant reduction of vitamin D receptor (VDR) expression (p < .05). The remaining studies showed negative or no effect on PC characteristics, clinical outcomes and/or survival. Current evidence suggests that vitamin D supplementation in conjunction with standard of care (e.g. chemotherapy, radiation therapy) may confer clinical benefits such as a decrease in serum PSA levels and VDR expression but further research is required to ascertain these results. Calcitriol supplementation in doses ranging from 250-1000 mg for 3-8 weeks or a lower dose of 45 mg for 18.3 months, appear most beneficial regarding outcomes of PC progression and survival.

Development of transdermal vitamin D3 (VD3) delivery system using combinations of PLGA nanoparticles and microneedles.

Although vitamin D3 (VD3), which is the main form of vitamin D, can be produced in human skin under the sunlight, vitamin D deficiency emerged as a major public health problem worldwide. Mainly, oral supplements or vitamin D-fortified foods are distributed to help supplementation of vitamin D. However, those oral methods are limitedly supplied in the Middle East countries, and oral absorption has low efficiency due to many barriers and various changes of conditions along the route. Then, it is recommended to take them every day in order to maintain the adequate serum level of vitamin D. Alternatively, transdermal delivery system could provide a convenient way to get sustained supplement of vitamin D by its advantages like avoiding first-pass effect of the liver and providing release for long periods of time. In this study, we introduced transdermal delivery system for sustained vitamin D release using coating microneedles that easily pierce the skin layer with enough mechanical strength and allow the localization of drugs within the dermal region. According to the experimental results, poly (lactic-co-glycolic acid) (PLGA) successfully encapsulated VD3 as a nanoparticle form with appropriate properties for transdermal delivery such as size distribution, skin compatibility, and effective release of encapsulated compound. Finally, PVD3 layers coated on solid microneedles were completely dissolved into intradermal region in porcine skin model and revealed better performance for VD3 release into plasma compared to ointment base transdermal method.