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Vitamin-D: Publications and Research from SwissMixIt

Vitamin D Botanical Information

Vitamin D, first identified as a vitamin early in the 20th century, is now recognized as a prohormone. A unique aspect of vitamin D as a nutrient is that it can be synthesized by the human body through the action of sunlight. These dual sources of vitamin D make it challenging to develop dietary reference intake values. vit D, D3, 1 alpha 25(OH)2D, vitamin D deficiency, vitamin D epimers, cytochrome P450, 1,25-MARRS, stomach, covid, prevention, anti cancer, non-phosphocalcic action, cellular functions, immune regulation, clinical effect, Cancer, fat soluble vitamin, hypertension, obesity, vitamin D analogs, COVID-19, SARS-CoV2, Vitamin D, Cholecalciferol, Calcitriol, COVID-19, SARS-CoV-2, Vitamin D, Vitamin D3 or cholecalciferol, Calcifediol or 25-hydroxyvitamin D3, 1α, 25(OH)2D or 1α, 25-dihydroxyvitamin D or calcitriol, Acute respiratory distress syndrome (ARDS), Cytokine/Chemokine storm, Renin-angiotensin system, Hypercoagulability, Hydroxychloroquine, Chloroquine, Covidiol, Neutrophil activity, Vitamin D endocrine system, Cuboidal alveolar coating cells type II, Cathelicidin peptide, Defensins, TLR co-receptor CD14, Vitamin D receptor

Keywords: vit D, D3, 1 alpha 25(OH)2D, vitamin D deficiency, vitamin D epimers, cytochrome P450, 1,25-MARRS, stomach, covid, prevention, anti cancer, non-phosphocalcic action, cellular functions, immune regulation, clinical effect, Cancer, fat soluble vitamin, hypertension, obesity, vitamin D analogs, COVID-19, SARS-CoV2, Vitamin D, Cholecalciferol, Calcitriol, COVID-19, SARS-CoV-2, Vitamin D, Vitamin D3 or cholecalciferol, Calcifediol or 25-hydroxyvitamin D3, 1α, 25(OH)2D or 1α, 25-dihydroxyvitamin D or calcitriol, Acute respiratory distress syndrome (ARDS), Cytokine/Chemokine storm, Renin-angiotensin system, Hypercoagulability, Hydroxychloroquine, Chloroquine, Covidiol, Neutrophil activity, Vitamin D endocrine system, Cuboidal alveolar coating cells type II, Cathelicidin peptide, Defensins, TLR co-receptor CD14, Vitamin D receptor

Description and Research Abstract: Vitamin D, first identified as a vitamin early in the 20th century, is now recognized as a prohormone. A unique aspect of vitamin D as a nutrient is that it can be synthesized by the human body through the action of sunlight. These dual sources of vitamin D make it challenging to develop dietary reference intake values.

Vitamin D, also known as calciferol, comprises a group of fat-soluble seco-sterols. The two major forms are vitamin D2 and vitamin D3. Vitamin D2 (ergocalciferol) is largely human-made and added to foods, whereas vitamin D3 (cholecalciferol) is synthesized in the skin of humans from 7-dehydrocholesterol and is also consumed in the diet via the intake of animal-based foods. Both vitamin D3 and vitamin D2 are synthesized commercially and found in dietary supplements or fortified foods. The D2 and D3 forms differ only in their side chain structure. The differences do not affect metabolism (i.e., activation), and both forms function as prohormones.

Virgin olive oil fortified with vitamin D3 prevented such changes in terms of both bone remodeling and bone mineral density. The expression of inflammation and oxidative stress mRNA was also lower in this group. Overall, our data suggest a protective impact of virgin olive oil as a source of polyphenols in addition to vitamin D3 on bone metabolism through improvement of oxidative stress and inflammation.

Topical Solutions: Transdermal delivery of VD using aromatic oils and aloe vera gel as permeation enhancers, this prospective RCT was conducted. This randomized control study shows that vitamin D3 can safely be delivered through the dermal route. This route could be exploited in treating vitamin D deficiency.

The skin is the only tissue in the human body that represents both a target tissue for biologically active vitamin D compounds including 1,25-dihydroxyvitamin D [1,25(OH)2D] and has the capacity for the synthesis of 1,25(OH)2D from 7-dehydrocholesterol (7-DHC). Recent findings indicate that the vitamin D endocrine system (VDES), besides multiple other important functions, regulates aging in many tissues, including skin. Consequently, it has been hypothesized that thus, both hypo- and hypervitaminosis D may enhance aging. Aging seems to show a U-shaped response curve to vitamin D status, and, therefore normovitaminosis D seems to be important for preventing premature aging.

Vitamin D3 is an effective skin protective substance to prevent photoaging. Liposomes were used as a carrier to deliver vitamin D3 to improve the stability and to enhance the treatment effect of vitamin D3. The stability of vitamin D3 liposomes, average cumulative penetration, and retention of vitamin D3 in the skin were then evaluated and compared with free vitamin D3.

Vitamin D is a major steroid hormone that is gaining attention as a therapeutic molecule. Due to the general awareness of its importance for the overall well-being, vitamin D deficiency (VDD) is now recognized as a major health issue. The main reason for VDD is minimal exposure to sunlight. The vitamin D receptor (VDR) is a member of the steroid hormone receptors that induces a cascade of cell signaling to maintain healthy Ca2+ levels that serve to regulate several biological functions. Currently, there is a need to increase the vitamin D status in individuals worldwide as it has been shown to improve musculoskeletal health and reduce the risk of chronic illnesses, including some cancers, autoimmune and infectious diseases, type 2 diabetes mellitus, neurocognitive disorders, and general mortality.

It is suggested that vitamin D deficiency is associated with cardiovascular disease (CVD) via its effect on lipid profiles. The objective of this study was to determine the association between fasting serum levels of 25(OH) D and lipid profiles in patients with type 2 diabetes.

The classical function of Vitamin D, which involves mineral balance and skeletal maintenance, has been known for many years. With the discovery of vitamin D receptors in various tissues, several other biological functions of vitamin D are increasingly recognized and its role in many human diseases like cancer, diabetes, hypertension, cardiovascular, and autoimmune and dermatological diseases is being extensively explored. The non-classical function of vitamin D involves regulation of cellular proliferation, differentiation, apoptosis, and innate and adaptive immunity.

A low vitamin D status, measured as the plasma level of the transport form of vitamin D, 25(OH)D,is widespread worldwide and is mainly found in regions of northern latitudes, but also in southern countries. In Europe, vitamin D deficiency is widely prevalent during the winter months and affects mainly elderly people and migrants.

Vitamin D is a pluripotent hormone that modulates the innate and adaptive immune response. Vitamin D influences several immune pathways, with the net effect of boosting mucosal defenses while simultaneously dampening excessive inflammation. Vitamin D deficiency is a risk factor for and/or a driver of the exaggerated and persistent inflammation that is a hallmark of acute respiratory distress syndrome (ARDS). Vitamin D deficiency has been associated with an increased risk of respiratory infections such as respiratory syncytial virus infection, tuberculosis and influenza. The winter incidence of influenza closely correlates with seasonal serum vitamin D levels In a meta-analysis of randomized controlled clinical trial, Bergman and colleagues demonstrated that prophylactic vitamin D reduced the risk of developing respiratory tract infections (OR, 0.64; 95%; CI, 0.49 to 0.84). In this study, the optimal dose was between 1000 IU to 4000 IU/day and the benefit was greatest in those living at latitudes greater than 40 degrees. Vitamin D deficiency likely adversely affects the outcome of viral infections. Grant and Giovannucci reported a strong inverse correlation between UVB dose and the case fatality during the 1918–1919 influenza pandemic. As vitamin D deficiency enhances the cytokine storm, it may be particularly lethal in patients with SARS-CoV-2 infection.

Vitamin D is an immunomodulator hormone with an anti-inflammatory and antimicrobial effect with a high safety profile. A lot of COVID-19 infected patients develop acute respiratory distress syndrome (ARDS), which may lead to multiple organ damage. These symptoms are associated with a cytokine storm syndrome. The aim of this letter is to note the 5 crucial points that vitamin D could have protective and therapeutic effects against COVID-19. For that reason, COVID-19 infection-induced multiple organ damage might be prevented by vitamin D.

Important scientific link between Vitamin D levels and susceptibility to COVID-19 in patients.

Vitamin D insufficiency affects almost 50 percent of the population worldwide. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency (VDD). This pandemic of hypovitaminosis D can mainly be attributed to lifestyle (for example, reduced outdoor activities) and environmental (for example, air pollution) factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin. High prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population.

Clinical Study Covid-19 and Vit D: The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease.

T-Cells: The vitamin D receptor (VDR) is a nuclear, ligand-dependent transcription factor that in complex with hormonally active vitamin D, 1,25(OH)2D3, regulates the expression of more than 900 genes involved in a wide array of physiological functions. The impact of 1,25(OH)2D3-VDR signaling on immune function has been the focus of many recent studies as a link between 1,25(OH)2D3 and susceptibility to various infections and to development of a variety of inflammatory diseases has been suggested. As T cells are of great importance for both protective immunity and development of inflammatory diseases a variety of studies have been engaged investigating the impact of VDR expression in T cells and found that VDR expression and activity plays an important role in both T cell development, differentiation and effector function. The purpose of the immune system is to recognize and clear pathogens from the body. However, occasionally unwanted immune reactions against self-tissue that lead to autoimmune diseases occur. Autoimmune diseases are linked to geographic location with a higher incidence of these diseases at higher degrees of latitude. One explanation of this geographical distribution is low exposure to sunlight and hence lower levels of vitamin D (25(OH)D3) at higher degrees of latitude, as confirmed by studies showing an association between low serum levels of 25(OH)D3 and development of autoimmune diseases. It is therefore apparent that vitamin D plays a role in immune modulation. A recent acknowledgment that the majority of immune cells expresses the vitamin D receptor (VDR). Due to the importance of T cells in protective immunity and in development of inflammatory and autoimmune disorders, several studies have examined the impact of VDR expression on T cell development, differentiation, and function. In innate immunity, pathogen-induced signaling through Toll-like-receptors on human monocytes and macrophages up-regulate the expression of VDR. This in turn, leads to VDR-induced expression of the antimicrobial peptide cathelicidin resulting in killing of microbes.

The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.

Severe acute respiratory syndrome coronavirus type (SARS-CoV2, also known as COVID-19), which is the latest pandemic infectious disease, constitutes a serious risk to human health. SARS-CoV2 infection causes immune activation and systemic hyperinflammation which can lead to respiratory distress syndrome (ARDS). ARDS victims are characterized by a significant increase in IL-6 and IL-1. Macrophage activation, associated with the cytokine storm, promotes the dysregulation of the innate immunity. So far, without vaccines or specific therapy, all efforts to design drugs or clinical trials are worthwhile. Vitamin D and its receptor vitamin D receptor (VDR) exert a critical role in infections due to their remarkable impact on both innate and adaptive immune responses and on the suppression of the inflammatory process. The protective properties of vitamin D supplementation have been supported by numerous observational studies and by meta-analysis of clinical trials for prevention of viral acute respiratory infection. In this review, we compare the mechanisms of the host immune response to SARS-CoV2 infection and the immunomodulatory actions that vitamin D exerts in order to consider the preventive effect of vitamin D supplementation on SARS-CoV2 viral infection.

Dry Eye: Dry eye syndrome (DES) is a chronic condition of the eye with insufficient production of tears leading to inadequate lubrication of eyes. Symptoms of DES are associated with discomfort and redness of the eye, blurred vision, and tear film instability which leads to the damaged ocular surface. Inflammation and oxidative stress play a significant role in the pathogenesis of the disease. Novel multi-component oral formulation of lutein/zeaxanthin, curcumin, and vitamin D3 (LCD) was evaluated. We observed a significant improvement in tear volume, tear breakup time, tear film integrity, and reduction in overall inflammation. Furthermore, the formulation helped in lowering oxidative stress by increasing antioxidant levels and restored protective tear protein levels including MUC1, MUC4, and MUC5AC with 200 mg of LCD having the most significant effect. The results strongly suggest that the combination of lutein/zeaxanthin, curcumin, and vitamin-D3 is effective in alleviating the symptoms of dry eye condition with a multi-modal mechanism of action.

Vitamin D is a fascinating and attractive molecule that has gained particular attention in medicine in recent years. Its immunomodulatory and anti- inflammatory potential might resemble the activity of many nature-derived molecules (eg, flavonoids), but its role in biology was selected during a long evolutionary pathway to dampen the damaging effect of cell stress response and of the immune reaction. In this sense, this molecule can be considered an ancient hormone that serves, in its primary role, as a pro-survival agent. The goal of this review was to elucidate this topic. Vitamin D participates in the survival machinery used by the cell, and in particular it plays a major role in synchronizing calcium oscillatory signaling to allow cell autophagy or apoptosis during a stress response. This evidence suggests that if vitamin D initially functioned as an antioxidant and an old pro-survival molecule, it evolved later as a cytokine.13 Its role in immunity could be considered as a tolerogenic, anti-inflammatory cytokine, but vitamin D not only helps the immune system to be dampened during an excessive or chronic reaction (anti-inflammatory potential) but also to rapidly reach its completion or exhaustion, helping innate cells to kill bacteria or viruses. In this sense, vitamin D maintains its pivotal role as a pro-survival molecule. The goal of the present review was to elucidate this role.

Recent advances in vitamin D research indicate that this vitamin, a secosteroid hormone, has beneficial effects on several body systems other than the musculoskeletal system. Both 25 dihydroxy vitamin D [25(OH)2D] and its active hormonal form, 1,25-dihydroxyvitamin D [1,25(OH)2D] are essential for human physiological functions, including damping down inflammation and the excessive intracellular oxidative stresses. Vitamin D is one of the key controllers of systemic inflammation, oxidative stress and mitochondrial respiratory function, and thus, the aging process in humans.

Our results sug- gest that vitamin D3, independent of upregulation of GDNF expression, may acutely prevent zinc-induced oxidative injuries via antioxidative mechanisms.

Vitamin D Supplementation during the Non-Surgical Treatment of Periodontitis: Conclusions: In this short-term pilot study, no significant differences were observed between two groups. However, supplementation with VD tended to improve the treatment of periodontitis in patients with initial 25(OH) vitamin D3 < 30 ng/mL and proved safe and efficacious. NCT03162406.

Exhaustive exercise results in inflammation and oxidative stress, which can damage tissue. Previous studies have shown that vitamin D has both anti-inflammatory and antiperoxidative activity. In summary, postexercise intravenous injection of vitamin D can reduce the peroxidation induced by exhaustive exercise and ameliorate tissue damage, particularly in the kidneys and lungs.

Cosmetics: There are water-soluble (hydrophilic) and fat- soluble (lipophilic) vitamins. The higher the solubility in fat, the better the vitamins can be reabsorbed and retained. Water-soluble vita- mins occasionally will not be absorbed and will be discharged, if ingested in high dosages. This specifically applies for vitamin C.

It is the packaging that counts in skin care applications. Free vitamin C only has superficial effects on the skin similar to a fruit acid, or may possibly be used as an antioxidant in skin care products.

Substantial effects in the skin can only be achieved by derivatives in combination with penetration enhancing substances such as liposomes (hydrophilic) or nanodispersions (lipophilic).

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