Figure - uploaded by Ieva Rinkūnaitė
Content may be subject to copyright.
Area under the curve pharmacokinetics

Area under the curve pharmacokinetics

Source publication
Article
Full-text available
Background and Objectives: The major cause of vitamin D deficiency is inadequate exposure to sunlight. It is difficult to supplement it with food because sufficient concentrations of vitamin D naturally occur only in a handful of food products. Thereby, deficiency of this vitamin is commonly corrected with oral supplements. Different supplement del...

Contexts in source publication

Context 1
... analysis confirmed that the least bioavailable delivery system was micellized vitamin D3. It was absorbed almost twice as inefficiently in comparison to microencapsulated vitamin D3 (Table 1). Additionally, the fat-soluble form of vitamin D3 was also more bioavailable to rats than micellized vitamin D3. ...
Context 2
... analysis confirmed that the least bioavailable delivery system was micellized vitamin D3. It was absorbed almost twice as inefficiently in comparison to microencapsulated vitamin D3 (Table 1). Additionally, the fat-soluble form of vitamin D3 was also more bioavailable to rats than micellized vitamin D3. ...
Context 3
... analysis confirmed that the least bioavailable delivery system was micellized vitamin D3. It was absorbed almost twice as inefficiently in comparison to microencapsulated vitamin D3 (Table 1). Additionally, the fat-soluble form of vitamin D3 was also more bioavailable to rats than micellized vitamin D3. ...

Citations

... В сравнительных исследованиях эффективности, проведенных на здоровых лабораторных крысах, было показано, что микрокапсулированная и масляная формы витамина D 3 обладают лучшей биодоступностью для организма по сравнению с мицеллярным витамином D 3 [35]. В других исследованиях дефицит при приеме водорастворимой формы сохранялся дольше, а концентрация в крови увеличивалась медленнее, чем при приеме масляной формы [36]. ...
... Research has identified VD as a breast cancer risk factor; a circulating VD level ≥ 45 ng/mL presumably protects against breast cancer [31][32][33]. Other studies revealed an inverse correlation between VD level and breast cancer risk [31][32][33][34][35][36]. Stoll et al. [34] found that elevated serum VD3 (through sun exposure and dietary intake of more than 400 IU per day) significantly decreases breast cancer incidence and recurrence, while serum VD3 deficiency can lead to breast cancer occurrence. ...
... Unfortunately, excessive VD intake is not rare and can cause severe toxicity and hospitalization [32][33][34][35][36][37][38][39][40][41][42][43]. The challenges in VD deficiency and its therapy are its low bioavailability [36], high degradation in systemic circulation [37], and toxicity (VDT) at high dosage, which can lead to hypervitaminosis D symptoms and hypercalcemia [36,37]. ...
... Surprisingly, the VD3-GNP treatment is found to downregulate ETV7, the PI3K/mTOR/ AKT cascade, along with the HIPPO pathway's key proteins YAP and TAZ, which indicates its importance in controlling breast cancer aggressiveness (Figures 8 and 9) [35,36,[39][40][41][42][43]. A recent report shows increased ETV7 expression [15][16][17][18][19][20][21][22] in all types of breast cancer, compared to normal breast tissue, along with other cancers, while ETV7 expression is correlated with tumor aggressiveness and stemness [14][15][16][17][18][19][20], though its therapeutic downregulation has not yet been seen. ...
Article
Full-text available
Metastasis in breast cancer is the major cause of death in females (about 30%). Based on our earlier observation that Vitamin D3 downregulates mTOR, we hypothesized that Vitamin D3 conjugated to gold nanoparticles (VD3-GNPs) reduces breast cancer aggressiveness by downregulating the key cancer controller PI3K/AKT/mTOR. Western blots, migration/invasion assays, and other cell-based, biophysical, and bioinformatics studies are used to study breast cancer cell aggressiveness and nanoparticle characterization. Our VD3-GNP treatment of breast cancer cells (MCF-7 and MDA-MB-231) significantly reduces the aggressiveness (cancer cell migration and invasion rates > 45%) via the simultaneous downregulation of ETV7 and the Hippo pathway. Consistent with our hypothesis, we, indeed, found a downregulation of the PI3K/AKT/mTOR pathway. It is surprising that the extremely low dose of VD3 in the nano formulation (three orders of magnitude lower than in earlier studies) is quite effective in the alteration of cancer invasiveness and cell signaling pathways. Clearly, VD3-GNPs are a viable candidate for non-toxic, low-cost treatment for reducing breast cancer aggressiveness.
... Furthermore, the patients took different vitamin D supplements. This could also have had an impact on 25(OH)D levels, due to the different bioavailability of vitamin D [58]. ...
Article
Full-text available
(1) Background: Vitamin D levels in patients remain inadequately understood, with research yielding inconsistent findings. Breast cancer patients, particularly due to oncological therapies, face an increased risk of osteopenia, which can be exacerbated by a vitamin D deficiency. (2) Methods: The prospective observational “BEGYN-1” study assessed serum 25(OH)D levels at baseline and quarterly thereafter. Clinical, pathological, nutritional, vitamin supplementation, and lifestyle data were recorded. (3) Results: Before treatment, 68.5% of patients were vitamin D deficient (<30 ng/mL), with 4.6% experiencing severe deficiency (<10 ng/mL). The median baseline 25(OH)D levels were 24 ng/mL (range: 4.8 to 64.7 ng/mL). Throughout the study, the median vitamin D levels increased to 48 ng/mL (range: 22.0 to 76.7 ng/mL). Before diagnosis, 16.7% received vitamin D substitution, and 97.8% received vitamin D substitution throughout the year with a median weekly dose of 20,000 IU. It took at least three quarterly assessments for 95% of patients to reach the normal range. A multiple GEE analysis identified associations between 25(OH)D levels and supplementation, season, age, VLDL, magnesium levels, and endocrine therapy. (4) Conclusions: Physicians should monitor 25(OH)D levels before, during, and after oncological therapy to prevent vitamin D deficiency and to adjust substitution individually. While variables such as seasons, age, VLDL, magnesium, diet, and oncological interventions affect 25(OH)D levels, supplementation has the greatest impact.
... The synthesis of vitamin D from exposure to sunlight and dietary sources requires magnesium as a cofactor; hence, its deficiency shuts down vitamin D synthesis pathways [15,16]. The activation of vitamin D by magnesium, in turn, helps in calcium and phosphate homeostasis and thereby influences bone formation. ...
Article
Full-text available
Background: Vitamin D deficiency is a major global health problem. Most previous studies focused attention on the significant role of sunlight exposure in the homeostasis of vitamin D and calcium blood levels. Magnesium is pivotal in the proper functioning of vitamin D, and the physiologic functions of different organs require a balanced vitamin D and magnesium status. The relationship between sunlight exposure and blood levels of vitamin D and magnesium has often been overlooked. The aim of this study was to evaluate vitamin D and magnesium status based on sunlight exposure and ethnicity in Bahraini and expatriate workers. Methods: A cross-sectional study was conducted between October 2018 and September 2019. One hundred and seventy-four subjects participated in this study were subdivided based on their ethnicity and work environment-dependent exposure to sunlight into four groups: (1) Bahraini exposed (n=94), (2) Bahraini non-exposed (n=25), (3) expatriate exposed (n=31), and (4) expatriate non-exposed (n=24). Blood levels of vitamin D and magnesium were evaluated for all the participants. Results: Independent of ethnicity, vitamin D levels were insignificantly different among the studied groups and were all below the normal reference range. Yet, there was still a sunlight-dependent increase in vitamin D level that could be seen only in Bahraini workers. Magnesium levels were significantly higher in expatriates when compared to Bahraini workers. Sunlight-exposed expatriates had significantly higher magnesium levels than their Bahraini counterparts, while there was no significant difference between both ethnicities in the non-exposed groups. Conclusion: Country- and ethnic-specific definitions for vitamin D status and sunlight exposure are recommended. The assessment of magnesium status is pivotal in the overall assessment of vitamin D status.
... Supplements are available in different forms, such as tablets, capsules, or oil-emulsified drops [9]. Vitamin D3 in supplements may be encapsulated in microcapsules, micelles, or liposomes to increase its bioavailability [10][11][12]. A meta-analysis of several clinical studies concluded that vitamin D3 bioavailability is better in oil vehicles (capsules or liquid) than in powder tablets (cellulose or lactose) or ethanol [13]. ...
... Many encapsulation techniques and materials, such as β-lactoglobulin [26], ovalbumin-pectin nanocomplexes [27], gum arabic, maltodextrin, whey protein concentrate, and soy isolate Supplements are available in different forms, such as tablets, capsules, or oil-emulsified drops [9]. Vitamin D 3 in supplements may be encapsulated in microcapsules, micelles, or liposomes to increase its bioavailability [10][11][12]. A meta-analysis of several clinical studies concluded that vitamin D 3 bioavailability is better in oil vehicles (capsules or liquid) than in powder tablets (cellulose or lactose) or ethanol [13]. ...
Article
Full-text available
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.
... Supplements are available in different forms, such as tablets, capsules or oil-emulsified drops [9]. Vitamin D3 in supplements may be encapsulated in microcapsules, micelles or liposomes to increase its bioavailability [10][11][12]. A meta-analysis of several clinical studies concluded that vitamin D3 bioavailability is better in oil vehicles (capsules or liquid) than in powder tablets (cellulose or lactose) or ethanol [13]. ...
... (www.preprints.org) | NOT PEER-REVIEWED | Posted: 26 February 2024 doi:10.20944/preprints202402.1468.v112 ...
Preprint
Full-text available
Vitamin D3 deficiency is a global phenomenon, which can be coped with supplementation and food fortification. However, vitamin D3 bioaccessibility may depend on factors, such as matrix composition and interactions throughout the gastrointestinal tract. This research focused on the effect of different matrices on vitamin D3 content during digestion, and 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 vitamin D3 initial content in supplements and foods, as well as after each digestion stage. Results indicated that foods exhibited higher bioaccessibility indices compared to supplements, and a higher percentage retention at the end of the gastric phase. The pH study revealed a positive correlation between increased gastric pH and the corresponding content of vitamin D3. Interestingly, exposing the matrix to 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) enhances vitamin’s bioaccessibility.
... According to multiple research projects, VitD3 absorption efficiency ranges between 55% and 99% but is independent of dietary fat amount, while bioavailability is influenced by lipid makeup [20]. Although supplements containing liposomes, microcapsules, or VitD micelles boost vitamin D absorption efficiency, the present study introduces a unique formulation, VitD3-NS, utilizing nano-complexation with cyclodextrins (CDs) to enhance bioavailability. ...
Article
Full-text available
Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin (βNS-CDI 1:4) nanosponges (NS) (defined as VitD3NS). Therefore, its activity has been evaluated on two different gut–brain axes (healthy gut/degenerative brain and inflammatory bowel syndrome gut/degenerative brain axis). At the gut level, VitD3-NS mitigated liposaccharide-induced damage (100 ng/mL; for 48 h), restoring viability, integrity, and activity of tight junctions and reducing ROS production, lipid peroxidation, and cytokines levels. Following intestinal transit, VitD3-NS improved the neurodegenerative condition in the healthy axis and the IBS model, suggesting the ability of VitD3-NS to preserve efficacy and beneficial effects even in IBS conditions. In conclusion, this study demonstrates the ability of this novel form of VitD3, named VitD3-NS, to act on the gut–brain axis in healthy and damaged conditions, emphasizing enhanced biological activity through VitD3 complexation, as such complexation increases the beneficial effect of vitamin D3 in both the gut and brain by about 50%.
... Its supplementation is important as part of recovery. Unfortunately, its bioavailability is limited by its low solubility and is strongly correlated with proper digestion of the fats that are its source [7]. ...
Article
Full-text available
Vitamin D3 and iron are important components of a balanced diet. Supplementing meals with these is essential to support the recovery of humankind’s malnutrition. It is necessary to develop effective delivery systems to ensure the high bioavailability of these hydrophobic components. For this purpose, emulsions were prepared based on hemp seed oil and with soap nut extract (Sapindus mukorossi fruits) as a natural emulsifier. To characterize the differences in the properties of the emulsions depending on the content of the oil phase and the emulsifier, measurements were performed to determine the following parameters: the color characteristics, transparency of the samples, infrared spectrum, particle size distribution, polydispersity of the system, and the rheological properties of the emulsions. The results showed that the highest stability was observed in systems with a relatively low oil concentration, i.e., 1%. These samples also had an average particle size not exceeding 200 nm. In turn, the low oil content significantly reduced the dynamic viscosity of the emulsions. At the same time, microscopic observations indicated that the presence of an oil phase was advantageous, not only because of the possibility of providing vitamin D but also because of the high hydrophobicity of the iron particles. Therefore, the realized research made it possible to identify the optimal emulsion composition. The created system can find applications in delivering dietary supplements such as vitamin D3 and iron by providing high dispersion of components and high stability.
... Consequently, deviations of label claims from actual amounts of Vitamin D in foods are common [18]. For this reason, especially in the elderly, exogenous administration through food supplements is necessary [19]. Despite its beneficial effects, Vitamin D administrations are restricted due to its poor bioavailability and very low aqueous solubility. ...
... However, it does not depend upon the fat content consumed with food. Nonetheless, lipid composition impacts Vitamin D bioavailability [19]. Actually, the absorption efficiency of Vitamin D is also increased by supplements in which Vitamin D is encapsulated into micelles, microcapsules, or liposomes. ...
... Actually, the absorption efficiency of Vitamin D is also increased by supplements in which Vitamin D is encapsulated into micelles, microcapsules, or liposomes. Emulsification of drugs or nutrients and their insertion into micelles or microcapsules have many benefits: higher stability to aggregation and gravitational separation; higher optical clarity; protection from degradation, light, and oxidation; and improved bioavailability of water-insoluble and difficultly absorbed compounds [19,21,22]. The innovative formulations by nano-complexation may include CDs, which, in this study, were used to complex and form the innovative vehicle. ...
Article
Full-text available
Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, βNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The βNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.
... The sublingual route for the absorption of vitamin D supplements should be superior to oral ingestion because sublingual absorption takes vitamin D directly into the systemic circulation, just like when vitamin D is naturally synthesized in the skin from exposure to sunlight [25]. ...