Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

The different cell subsets of the immune system express vitamin D receptor (VDR). Through VDR, vitamin D exerts different functions which influences on immune responses, as previously shown in different preclinical models. Based on this background, retrospective studies have explored the impact of vitamin D levels on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation, showing that vitamin D deficiency is related to an increased risk of complications, especially graft-versus-host disease. These results have been confirmed in a prospective cohorts trial, although further studies are required to confirm this data. In addition, the role of vitamin D on the treatment of hematologic malignancies has also been explored. Considering this dual effect both on the immune system as well as on tumor cells in patients with hematologic malignancies, vitamin D might be useful in this setting both to decrease graft-versus-host disease and relapse rates.

Disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause epilepsy. Our study aims at revealing therapeutic potential of vitamins B1 and B6 in epilepsy by estimating effects of their combined administration on a seizure and its consequences in rats subjected to pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to Racine’s scale along with delayed physiological and biochemical consequences next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than male rats. Next day after a seizure, gender differences in behavior and brain biochemistry arise. The induced gender differences in anxiety, exploratory and locomotor activity correspond to disappearance of gender differences in the brain GABA, aspartate, alanine and serine, with appearance of those in glutamate, glutamine and tyrosine. PTZ decreases the brain malate dehydrogenase activity, glutamine and urea in the males, and phenylalanine in the females. Administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5-2 h) between the vitamins and PTZ administration. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. Delayed effects of vitamins and/or PTZ are mostly gender-specific and interacting. Our findings on the gender differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

Background & Aims: The covid19 is a world changing challenge. Furthermore, this disease challenges our capacities to change our point of view in the domain of infectiology, immunology and global public health. Many trials try some drug such as antiviral (lopinavir, remdesivir) interferon, and the chloroquine. Unfortunately, all approach is not really convincing at this time. We are proposing another approach on this issue. In infectiology there are two protagonists : the host and its immune system versus pathogens and its virulence. Our approach focuses on an intervention on the host’s immune system and how stimulate and modulate its reactions. Methods: We searched on PubMed and Google Scholar databases for French and English-language studies, without a limit of date of publications, for randomized clinical trials, meta-analyses, reviews, systematic reviews, observational studies, case report. We performed a review on the field of immunology enhancements by nutrients use. Results: We identified groups of vitamins (D and C), oligo-elements (magnesium, zinc, selenium) and nutrition advice which enhance immune system response. Indeed, these supplements have some proved properties in modulating and stimulating the immune system. For example, a recent study demonstrates that vitamin D deficiency is linked with the severity of covid19. Majority of the population has a deficiency in these elements. According to this, we propose a therapeutic protocol using these elements to reach an efficient therapy against covid19 by enhancing host’s immune system. Conclusion: Due to this serious pandemic, any solutions must not be disregarded. The nutrition way is an entire part of the solution.

The ultimate objective of this research work is to design a sensitive and selective electrochemical sensor for efficient detection of ascorbic acid (AA), a vital antioxidant found in blood serum that may serve as a biomarker for oxidative stress. To achieve this, we utilized a novel Yb2O3.CuO@rGO nanocomposite (NC) as the active material to modify the glassy carbon working electrode (GCE). The structural properties and morphological characteristics of the Yb2O3.CuO@rGO NC were investigated using various techniques to ensure their suitability for the sensor. The resulting sensor electrode was able to detect a broad range of AA concentrations (0.5 - 1571 µM) in neutral phosphate buffer solution with a high sensitivity of 0.4341 µAµM-1cm-2 and a reasonable detection limit of 0.062 µM. The sensor's great sensitivity and selectivity allowed it to accurately determine the levels of AA in human blood serum and commercial vitamin C tablets. It demonstrated high levels of reproducibility, repeatability, and stability, making it a reliable and robust sensor for the measurement of AA at low overpotential. Overall, the Yb2O3.CuO@rGO/GCE sensor showed great potential in detecting AA from real samples.

Prolonged fatigue is associated with non-pathological causes, and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve® Response) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue Severity Scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stressed conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months supplementation in healthy subjects with mild prolonged fatigue.

Maintaining an adequate micronutrient status can be achieved by following a complete, diverse diet. Yet, food trends in Western countries show suboptimal consumption of healthy nutrients. In this study we explored the prevalence of vitamin and mineral imbalances in a general population cohort of Dutch adults, and evaluated the effect of a digital lifestyle program on the nutritional status and nutrition health behaviors of these individuals. A micronutrient panel was measured in 348 participants, alongside a dietary assessment. One-hundred users subsequently underwent a remeasurement. We identified at least one nutritional imbalance in 301 individuals (86.5%). 80% improved and normalized B6, 67% improved folate, 70% improved B12, and 86% improved vitamin D. Iron abnormalities were corrected in 75% of participants. In conclusion, this study found micronutrient deficiencies of easily obtainable vitamins through diet or supplementation such as B vitamins and vitamin D were more prevalent than expected in a Dutch population. This can partly be explained by an insufficient consumption of food groups rich in B vita-mins. Our preliminary results in those remeasured after a digitally-enabled lifestyle intervention show these imbalances can be corrected with adequate behavioral support in a “food as medicine” approach complemented with supplementation where needed.

In this work a series of experiments on the retention of B1 (riboflavin), B2 (thiamine) and B3 (nicotinic acid) vitamins in the HILIC and RPLC conditions have been performed involving the effects of organic modifier type and content, pH of the eluent, and buffering salt (ammonium acetate) concentration in the mobile phase, as well as temperature of the system. For the needs of this studies three columns of different features have been chosen: Acclaim™ Mixed-Mode HILIC-1 (Dionex), Eurospher II 100-5 HILIC (Knauer) and the RPLC column Nucleodur® C18 Gravity – SB (Macherey –Nagel). The influence of acetonitrile and methanol content in the eluent and process temperature have been tested and basing on that the most promising systems have been selected regarding the possible separation of the vitamins mixture. Both pH and buffering salt concentrations in the eluent have been adjusted in order to indicate the most effective system which turned out to be the one involving the Nucleodur column and the eluent with 90% methanol, at pH 6 and Cbuff = 20 mmol/dm3 that enables separation of the mixture within the time as short as 2.5 minutes at 1.0 mL/s flowrate in isocratic conditions.

A recent review of global vitamin C status indicated a high prevalence of deficiency, particularly in low- and middle-income countries, as well as in specific subgroups within high-income countries. Here we provide a narrative of potential factors influencing vitamin C status. The in vivo status of vitamin C is primarily affected by dietary intake and supplement use. Dietary intake can be influenced by cultural aspects such as staple foods and traditional cooking practices. Environmental factors can also affect vitamin C intake and status; these include geographic region, season and climate, as well as pollution. Demographic factors such as sex, age, and race are known to affect vitamin C status, as do socioeconomic factors such as deprivation, education and social class, and institutionalization. Various health aspects affect vitamin C status; these include body weight, pregnancy and lactation, genetic variants, smoking, and disease states, including severe infections as well as various non-communicable diseases such as cardiovascular disease and cancer. Some of these factors have changed over time, therefore we also explore if vitamin C status has shown temporal changes. Overall, there are numerous factors that can affect vitamin C status to different extents in various regions of the world. Many of these factors are not taken into consideration during the setting of global recommended dietary intakes for vitamin C.

Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study; real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)₂D₃. Frist; a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10nM but not at 100nM of 1,25(OH)₂D₃ treatment; suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation; gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1; SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1; no changes in gene expression were observed. However; a concomitant decrease in CAT and SOD1 mRNA; and increase in SOD2 mRNA after 24 hours of 10nM 1,25(OH)₂D₃ treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 hours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

Higher body weight is known to negatively impact plasma vitamin C status. However, despite this well-documented inverse association, recommendations on daily vitamin C intakes by health authorities worldwide do not include particular reference values for people of higher body weight. This suggests that people of higher body weight and people with obesity may be insufficient in vitamin C in spite of ingesting the amounts recommended by their health authorities. The current preliminary investigation sought to estimate how much additional vitamin C people with higher body weights need to consume in order to attain a comparable vitamin C status to that of a lower weight person consuming an average Western vitamin C intake. Data from two published vitamin C dose-concentration studies were used to generate the relationship: a detailed pharmacokinetic study with seven healthy non-smoking men and a multiple depletion-repletion study with 68 healthy non-smoking men of varying body weights. Our estimates suggest that an additional intake of 10 mg vitamin C/day is required for every 10 kg increase in body weight to attain a comparable plasma concentration to a 60 kg individual with a vitamin C intake of ~110 mg/day, which is the daily intake recommended by the European Food Safety Authority (EFSA). Thus, individuals weighing e.g. 80 and 90 kg will need to consume ~130 and 140 mg vitamin C/day, respectively. People with obesity will likely need even higher vitamin C intakes. As poor vitamin C status is associated with increased risk of several chronic diseases including cardiovascular disease, these findings may have important public health implications. As such, dose-finding studies are required to determine optimal vitamin C intakes for overweight and obese people.

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. The role of natural antioxidant products in combating T2D is best evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control and exercise. The role of natural antioxidant compounds such as vitamin E in T2D must likewise be considered beyond their roles as inhibitors of OxS. In addition to antioxidant properties, vitamin E vitamers (tocopherols and tocotrienols) also exhibit distinct abilities to regulate cellular signal transduction pathways important to T2D progression. Most research on the role of vitamin E in T2D or prediabetes has been limited to tocopherols (Ts) but emerging trials with tocotrienols (T3s) show promise. Minimizing factors that induce chronic damaging OxS and maximizing natural antioxidant protective factors may provide a means of preventing or slowing T2D progression. This “optimal redox” (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant factors such as antioxidant products. Since early, effective intervention is critical, the OptRedox strategy would be optimally effective if implemented in the pediatric population.

Vitamin C is important in preventing and slowing the progression of many diseases. There is significant evidence linking periodontal disease and vitamin C. We aimed to systematically review studies addressing the relationship between vitamin C and periodontal disease and the preventive ability of vitamin C against periodontal disease. Electric searches were performed using PubMed, EMBASE, Cochrane Library, and Web of Science. Studies addressing the relationships between periodontal disease and vitamin C in adults aged over 18 years were included. Quality assessment was done using Critical Appraisal Skills Program guideline and GRADE-CERQual. Seventy hundred and sixteen articles were retrieved and fifteen articles (7 cross-sectional studies, 2 case-control studies, 2 cohort studies, and 4 randomized controlled trial [RCT]) were selected by reviewing all articles. Vitamin C intake and blood level were negatively related to periodontal disease in all 7 cross-sectional studies. Subjects who suffer from periodontitis presented lower vitamin C intake and lower blood vitamin C level than subjects without periodontal disease in the two case-control studies. Patients with lower dietary intake or lower blood level of vitamin C showed greater progression of periodontal disease than did the controls. Intervention using vitamin C administration improved gingival bleeding in gingivitis but not in periodontitis. Alveolar bone absorption was also not improved. The present systematic review suggested that vitamin C contributes to reduced risk of periodontal disease.

The impact of nutrition on immunity is an intense area of research. Malnutrition is linked to a higher risk of microbial infections, while severe infections usually lead to a nutritional imbalance in affected patients. The nutritional status has an impact on the severity of the ongoing SARS-CoV-2 infection. Studies conducted on small numbers of patients have shown the benefits of maintaining optimal vitamin (B12 and D) and mineral (zinc and magnesium) balance in reducing the intensity of COVID-19. Although consuming a balanced diet with a healthy lifestyle is always desirable, the importance of such practice is even more meaningful during the COVID-19 pandemic. Keeping an optimal balance of vitamins and minerals through healthy dietary habits helps to maintain a robust immune system that is essential to combat invading microbial pathogens, including SARS-CoV-2.

Specific nutrients including n-3 long chain polyunsaturated fatty acids (LCPUFAs), flavonoids, vitamin A, D and E are considered to possess protective properties on human health by impacting on immunological reactions. An ‘inflammation-suppressive’ effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as allergy. However, the majority of these promising data are from preclinical studies such as animal disease models, as the majority of clinical studies only indicate associations. PUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy. However, it should be noted and realised that PUFAs are highly susceptible to lipid oxidation. Flavonoids and fat-soluble vitamins both contain anti-inflammatory properties and are able to act as anti-oxidants as well. Here, we explore the anti-allergic properties of PUFAs, flavonoids and fat-soluble vitamins in order to create an overview and, more importantly, suggest a strategy to target food allergies using these components and combinations thereof. Dietary n-3 LCPUFAs and the above mentioned micronutrients are promising anti‐allergy agents capable of influencing the allergic immune response through multiple and different biological pathways.

Background: Nutritional rickets is still considered as a global health problem especially in low-resource countries and immigrant societies of developed countries. Generalized skeletal deformities including angular knee deformities as genu varum and genu valgum are prominent features of nutritional rickets. Angular knee deformities can cause gait difficulties. However, the true remodelling potential of the healed knee deformities is largely unknown to the pediatric and orthopedic community. Aims: The primary objective of this study protocol is to investigate the natural history of disease in regard to the remodelling potential of angular knee deformities in children and adolescents with healed nutritional rickets. And determine the potential patient- and deformity-related factors that are associated with a favorable deformity remodelling as age and sex of patients and type, severity, laterality of deformities etc. Methods: This will be a prospective observational analytical cohort natural history of disease study. A minimum of at least 140 knees with healed nutritional rickets and angular knee deformities will be observed at regular three-monthly intervals over a period of at least one year. We will report two outcome variables namely; clinical and radiological tibio-femoral angle. And independent patient and deformity-related variables as age, sex, deformity type, severity and laterality. Inferential statistics namely bivariate and multivariate analysis will be employed accordingly to identify the relation between outcome variables and the different independent variables. Ethics and dissemination: This protocol study has been approved by the institutional research ethics committee. Results will be presented at conferences and submitted to relevant international and society publications. Authors will also communicate the results to their scholarly networks and post them on scholarly networking sites. Conclusions: This study has the potential for improving the decision-making process as to which patients deserve conservative treatment and which deserve surgical deformity correction. Results are expected to have an impact on the clinical practice of pediatricians, orthopedic surgeons and family physicians alike.

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), which suggests a close association. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n=148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Se-rum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤ 16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β= -0.018, 95% CI -0.033 to -0.003, P=0.022) and 0.048 SD (standardized β= -0.048, 95% CI -0.083 to -0.014, P=0.006), respectively. Additionally, the high serum 25OHD groups (> 95.9 nmol/L) had 0.038 SD (standardized β= -0.038, 95% CI -0.072 to -0.004, P=0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusion: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Umbu is a tropical fruit with high content of bioactive compounds. However, maturation causes significant losses on nutrient density reducing the nutritional value of this highly appreciated fruit. Thus, the objective of the present work was to encapsulate the Umbu fruit bioactive compounds using spray drying and identify the variables affecting the biomolecules preservation. A Box-Behnken experimental design with 3 factors was set varying inlet temperature, atomization flow rate, and maltodextrin concentration for process otimization. Then the powder physicochemical and chemical properties were characterized, and results were modeled using a polynomial equation. Results revealed that the droplet size and maltodextrin concentration had a significant influence on the conservation of the biomolecules. Drying kinetics favoring fast formation of a particle crust increases encapsulation efficiency. Bioactive compounds retention was achieved by increasing maltodextrin even at high temperatures, where a matrix is formed hindering chemical degradation. Process optimization was validated and revealed low inlet temperatures (122ºC), high atomization flow rate (5kg/h) and high maltodextrin concentration (20%) to be the most desirable conditions for bioactive compounds retention.

Background: According to newly published studies, patients with Coronavirus Disease 2019 (COVID-19) have significantly lower serum 25-hydroxyvitamin D 25(OH)D levels than those without the SARS-CoV-2 infection. Vitamin D insufficiency may be a predictor of poor prognosis in COVID-19 patients. Vitamin D supplementation is related to improved clinical outcomes in terms of intensive care unit (ICU) admission and death, particularly in individuals with moderate-to-severe forms of COVID-19 requiring hospitalization. Materials and methods: This placebo-controlled five-day study was performed on 100 hospitalized COVID-19 patients with vitamin D insufficiency randomized into two groups. Vitamin D in the form of a sublingual sprayable microemulsion (LYL love your life® sunD3 LYLmicro™) was given three times daily after breakfast, lunch, and dinner (daily dose 12,000 IU) to 52 patients with blood vitamin D levels below 30 ng/ml. 48 patients in the control group received a placebo spray in the same daily regiment. Results: We observed a statistically significant increase by 8.6 ng/ml in median vitamin D level after five days of high-dose vitamin D3 spray therapy. 90.2% of subjects reached normal serum levels of vitamin D. There was a strong correlation between changes in vitamin D and C-reactive protein (CRP) levels in individuals with moderately severe disease (p<0.05), while mild and severe cases showed no statistical significance comparing case and control groups. There were no statistically significant changes in ferritin and interleukin-6 (IL-6) levels. Conclusions: In this study, we demonstrated the possibility to rapidly increase circulating levels of vitamin D just in 5 days of high-dose intervention and found a statistically significant decrease of CRP levels in patients with moderately severe COVID-19. We were not able to detect statistically significant changes in ferritin and IL-6 levels during the 5-day vitamin D intervention.

1) Background: The aim was to evaluate the bioefficacy of vitamin D (VitD) encapsulated in nanoemulsions developed by sonication and pH-shifting of pea protein isolate in restoring VitD status in VitD-deficient rats. 2) Methods: Weaned (3-week old), male albino rats (n = 35) were initially divided into two groups: control sufficient group (VDS; n = 7) fed on a normal AIN-93G diet and a VitD-deficient group (n = 28) fed a VitD-deficient diet for six weeks. VitD-deficient rats were divided into four subgroups: two treatment groups (Nano+VitD and Oil+VitD) and two control groups (Nano-VitD and Oil-VitD), receiving seven rats in each sub-group. Nano+VitD and Oil+VitD groups received VitD dispersed in PPI-nanoemulsions and in canola oil, respectively, while the control groups received the respective delivery vehicles without VitD. Serum 25-hydroxyvitamin D [25(OH)VitD], parathyroid hormone (PTH), calcium (Ca), phosphorus levels (P), and alkaline phosphatase (ALP) activity were measured. Femur bone was used to prepare histopathological sections. 3) Results: After one week of treatment, the VitD-deficient rats consuming Nano+VitD recovered from VitD deficiency (serum 25(OH)VitD 34.38 ± 7.00) compared to the sufficient control (36.84 ± 9.16; p > 0.05) and the deficient control consuming VitD+Oil (14.05 ± 3.08; p < 0.01). Enhancement in VitD status was followed with expected changes in serum PTH, Ca, P, and ALP levels, no difference in similar biomarkers against the sufficient control, and an improvement of the osteoid area and reduction of trabecular separation in bone. 4) Conclusions: Stabilization of VitD within PPI-based nanoemulsions enhances its absorption and restores its status and biomarkers of bone resorption in VitD-deficient rats.

Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)₂-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.

Vitamin A and E are important during pregnancy, the neonatal period, and childhood. The objective of this study was to assess whether maternal RRR-a-tocopherol supplementation affects serum and breast milk retinol. Serum was collected at baseline and twenty days later, and breast milk, at baseline, and on days 1, 7, and 20 after delivery. After the baseline serum collection, the supplemented group (n=16) received a single 400 IU of RRR-α-tocopherol. The control group (n=18) was only performed collections. Retinol and alpha tocopherol levels were determined by liquid chromatography. Serum retinol and alpha tocopherol at baseline and 20 days after delivery indicated proper vitamin A (> 20 µg/dL) and E (> 516 μg/dL) statuses in the control and supplemented groups (p > 0.05). Colostrum retinol levels on days 1 and 7 after delivery were significantly higher in the supplemented group (p = 0.018 and p = 0.012, respectively). Maternal vitamin E supplementation increased colostrum retinol by 52.23% and 111.2%, 24 hours and 7 days, respectively. However, retinol in mature milk did not differ between the groups (p > 0.05). In conclusion, the supplementation with 400 IU of RRR-α-tocopherol improved vitamin A bioavailability in breast milk.

Abstract: Hyperuricemia is commonly diagnosed in subjects with abnormal purine metabolism. Prolonged hyperuricemia often associated with gout, which is a vital risk factor for joint dysfunction. The current study was designed to determine the efficacy of vitamin C supplements for treatment of high serum uric acid (UA) among hyperuricemic and gouty patients, and finding-out the effect of supplementation on serum creatinine (Cr) level and glomerular filtration rate (GFR). This intervention study was started in April, 2013, till two months. A convenient sample of 30 adults aged between 24-75 years of both genders was assigned into two study groups: hyperuricemic (n=15) and gouty (n=15) groups. Each participant supplemented with 500 mg/day vitamin C chewable tablets for 2 months. Serum UA, Cr, and GFR were measured before and after treatment. At the end of this study, Cr and GFR enhanced insignificantly in both groups. UA increased insignificantly in gouty group after 2 months by about 0.31 mg/dl. On the other hand, hyperuricemic group showed significant (P ≤0.05) decrease in UA (-0.78 mg/dl) after 2 months duration. In conclusion, supplementation with 500 mg/day vitamin C for 2 months significantly attenuated serum UA for hyperuricemic patients and insignificantly affected serum UA in gouty patients. The uselessness of vitamin C supplements on gouty patients could be associated to a number of possible reasons.

Macro and micronutrients, essential for the maintenance of human metabolism, are daily assimilated through the diet. Wheat and other major cereals are a good source of nutrients, such as carbohydrates and proteins, but cannot supply enough amounts of essential micronutrients which includes provitamin A. As vitamin A deficiency (VAD) lead to several serious diseases spread worldwide, the biofortification of a major staple crop, such as wheat, represents an effective way to preserve human health in developing countries. In the present work, a key enzyme involved in the branch of carotenoids pathway producing β-carotene, lycopene epsilon cyclase, has been targeted by a TILLING approach in a “Block strategy” perspective. The null mutant genotype showed a strong reduction in the expression of lcyE gene and also interesting pleiotropic effects on an enzyme (β-ring hydroxylase) acting downstream in the pathway. Biochemical profiling of carotenoids in the wheat mutant lines showed an increase of roughly 75% in β-carotene in the grains of the complete mutant line vs. the control. In conclusions, here we describe the production and the characterization of a new wheat line biofortified in provitamin A obtained through a non-transgenic approach also shading new light on the molecular mechanism governing carotenoids biosynthesis in durum wheat.

(1) Background: To investigate the effect of phosphohistone H3 (PHH3) and vitamin D receptor (VDR) in the risk assessment of endometriosis, in two cohorts of women with this pathology, those receiving hormonal treatment, and those without treatment; (2) Methods: In 60 cases of women with endometriosis, the paraffin-embedded endometriosis tissue samples, retrieved after surgery, were immunohistochemically (IHC) analyzed aiming to determine the expression status of PHH3 and VDR; (3) Results: The IHC positive index of PHH3 and VDR of these two groups were compared. PHH3 levels were positively correlated with vitamin D levels, both being increased in patients without treatment. Within the group without treatment, PHH3 and VDR expressions were positively associated; (4) Conclusions: IHC analysis of PHH3 and VDR can be used as an additional tool for risk stratification and prognostic assessment in patients with endometriosis.

Understanding molecular mechanisms of neurological disorders is required for development of personalized medicine. When the diagnosis considers not only the disease symptoms, but also their molecular basis, the treatments tailored for individual patients may be suggested. The vitamins-responsive neurological disorders are induced by deficiencies in the vitamin-dependent processes. The deficiencies may occur due to genetic impairments of proteins whose functions are involved with the vitamins. This review considers the enzymes encoded by DHTKD1, PDK3 and PDXK genes, whose mutations are observed in patients with Charcot-Marie-Tooth (CMT) disease. The enzymes bind or produce the coenzyme forms of vitamins B1 (thiamine diphosphate, ThDP) and B6 (pyridoxal-5’-phosphate, PLP). Alleviation of such disorders by administration of the lacking vitamin or its derivative calls upon a better introduction of the mechanistic knowledge to medical diagnostics and therapies. Recent data on lower levels of the vitamin B3 derivative, NAD+, in the blood of patients with CMT disease, compared to the control subjects, are also considered in view of the NAD-dependent mechanisms of pathological axonal degeneration, suggesting therapeutic potential of vitamin B3. Thus, improved diagnostics of the underlying causes of the CMT disease may allow the patients with the vitamin-responsive disease forms to benefit from the administration of the vitamins B1, B3, B6, their natural derivatives or pharmacological forms.

Plant-based diets are increasingly popular for health as well as financial, ethical, and religious reasons. The medical literature clearly demonstrates that plant-based diets can be both nutritionally sufficient and medically beneficial. However, any person on an intentionally restrictive but poorly-informed diet may predispose themselves to clinically-relevant nutritional deficiencies. For persons on a poorly-informed plant-based diet, deficiencies are possible in both macronutrients (protein, essential fatty acids) and micronutrients (vitamin B12, iron, calcium, zinc and vitamin D). Practitioner evaluation of symptomatic patients on a plant-based diet requires special consideration of 7 key nutrient concerns for plant-based diets. This article translates these concerns into 7 practical questions that all practitioners can introduce into their patient assessments and clinical reasoning. Ideally, persons on plant-based diets should be able to answer these 7 questions. Each serves as a heuristic prompt for both clinician and patient attentiveness to a complete diet. As such, these 7 questions support increased patient nutrition knowledge and practitioner capacity to counsel, refer, and appropriately focus clinical resources.

Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P<0.001), thoracic aortic calcification (P<0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

Adequate serum vitamin D and iron levels are thought to positively influence physical training adaptations and mood. The purpose of this prospective, observational, study was to investigate relationships between serum 25-OH vitamin D and serum ferritin levels with body composition and athlete burnout symptoms. Seventy-three collegiate athletes (49 female) from 7 indoor and outdoor sports were tested pre-season and post-season for: nutrient biomarkers (serum 25-OH vitamin D and serum ferritin) via venipuncture; body composition (total lean mass, bone mineral densi-ty/BMD, and % body fat) via dual energy x-ray absorptiometry (DXA) scans; and athlete burnout symptoms (post-season) via the athlete burnout questionnaire (ABQ). When male and female co-horts were combined, significant relationships were noted between pre-season serum 25-OH vit-amin D versus the change (∆: post-season minus pre-season) in both BMD (r=-0.34;p=0.0003) and % body fat (r=-0.28;p=0.015). Serum ferritin ∆ was significantly associated with lean mass ∆ (r=-0.34;p=0.003). For burnout symptoms, serum 25-OH vitamin D ∆ significantly explained 20.6% of the variance for devaluation of sport in the male cohort only. Across time, serum 25-OH vitamin D levels increased while serum ferritin levels decreased, non-significantly, in both males and fe-males. Relationships between nutrient biomarkers and body composition were opposite of physio-logical expectations.

The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practice (KAP) in Iranian adults who may be at increased risk of vitamin D deficiency. This study was conducted on 527 subjects, aged ≥20 years from Public health care centers in Tehran, Iran. Based on results of literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire with four subscale was developed: 1) general knowledge; 2) nutritional knowledge; 3) attitudes; 4) behaviors. Validity of the developed vitamin D-KAP questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2±7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by the panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. The EFA suggested a four-factor construct and the results of the CFA indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0, 1.1, 2.4, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59±14.52) and nutrition knowledge, the lowest score (42.58±20.40) among the four sub-scales. Results confirm the initial validity and reliability of the vitamin D-related knowledge, attitude and practice questionnaire. Further investigations in different urban and rural population are recommended.

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to interrogate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations and the possible extent of these additional requirements. The relevant data were extracted from the NHANES 2017-2018 datasets, the final cohort of which comprised 2828 non-supplementing adult males and females (aged 18 – 80+ years) with both vitamin C serum concentrations and dietary intake data available. The data was subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: &gt;3.0, 1.36 – 3.0, ≤1.35), weight tertiles (≤72, 72-91, ≥91 kg), BMI tertiles (≤26, 26-32, ≥32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach ‘adequate’ serum concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heaver weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes &gt; 75 mg/day, at intakes &lt; 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population must consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach the same vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, are responsible for approximately 2.65 million deaths per year. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: 1) Supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; 2) Supplementation above the RDA, but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and 3) Public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

During analysis of kiwifruit derived from hybrids between the high AsA species Actinidia eriantha and A. chinensis var chinensis, we observed bimodal segregation of fruit AsA concentration suggesting major gene segregation. To test this hypothesis we performed whole-genome sequencing on pools of high and low AsA fruit from tetraploid A. chinensis var. deliciosa x A. eriantha backcross families. Pool-GWAS revealed a single QTL spanning more than 5 Mbp on chromosome 26, which we denote as qAsA26.1. A co-dominant PCR marker was used to validate this association in four diploid (A. chinensis x A. eriantha) x A. chinensis backcross families, showing that the eriantha allele at this locus increases fruit AsA levels by 250 mg/100 g fresh weight. Inspection of genome composition and recombination in other A. chinensis genetic maps confirmed that the qAsA26.1 region bears hallmarks of suppressed recombination. The molecular fingerprint of this locus was examined in leaves of backcross validation families by RNASEQ. This confirmed strong allelic expression bias across this region as well as differential expression of transcripts on other chromosomes. This evidence suggests that the region harboring qAsA26.1 constitutes a supergene, which may condition multiple pleiotropic effects on metabolism.

Background: Vitamin D was studied in regards to its possible impact on body mass reduction and metabolic changes in adults and children with obesity yet there were no studies assessing the impact of vitamin D supplementation during a weight management programme in children and adolescence. The aim of our study was to assess the influence of 26 weeks of vitamin D supplementation in overweight and obese children undergoing an integrated 12-months’ long weight loss programme on body mass reduction, body composition and bone mineral density. Methods: A double-blind randomized placebo-controlled trial. Vitamin D deficient patients ( <30 ng/ml level of vitamin D) aged 6-14, participating in multidisciplinary weight management programme were randomly allocated to receiving vitamin D (1200 IU) or placebo for the first 26 weeks of the intervention. Results: Out of the 152 qualified patients, 109 (72%) completed a full cycle of four visits scheduled in the programme. There were no difference in the level of BMI change. Although the reduction was greater in the vitamin D vs. placebo group (-4.28 ± 8.43 vs. -2.53 ±6.10) the difference was not statistically significant (p=0.319). Similarly the reduction in fat mass – assessed both using bioimpedance and DEXa was achieved, yet the differences between the groups were not statistically significant. Conclusions: Our study ads substantial results to support the thesis on no effect of vitamin D supplementation on body weight reduction in children and adolescents with vitamin D insufficiency undergoing a weight management programme. Trial registration no: NCT 02828228; trial registration date: 8 June 2016 registered in: ClinicalTrials.gov.

Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.

Vitamin D plays an essential role in embryogenesis and the course of intra- and postnatal periods and is crucially involved in the functioning of the mother-placenta-fetus system. Low quantity of Vitamin D during pregnancy can lead to the elevated risk for preeclampsia occurence. Despite the numerous studies on the association of Vitamin D deficiency and preeclampsia development, the current research on this theme is contradictory. In this review we summarize and analyze study data on the effects of vitamin D deficiency and supplementation on pregnancy, labor, fetal and neonatal outcomes.

The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydoxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by significant decrease in non enzymatic antioxidants and TAS concentrations. 8-OHdG and cell proliferation level were negatively correlated with non enzymatic antioxidants viz., Vitamin A, Vitamin C, vitamin E level and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity amongst the malignant, benign and controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. Among the oxidative stress markers and cell proliferation index, decreased level of vitamin A, vitamin C, vitamin E, TAS and increased level of 8-OHdG, cell proliferation index emerged as best predicted biomarkers for subjects with malignancy and benign breast disease.

The vegan diet excludes animal-derived product consumption and health advantages had been reported when followed. However, heterogeneous eating habits, food availability, and sociocultural characteristics among regions could lead to different physiological results. The objective of this case-control cross-sectional pilot study was to analyze body composition, daily nutrients consumption, and basic serum biomarkers as a general overview of the health status of Mexican adults with a vegan diet for ≥3 years, randomly paired with omnivores. Body composition was assessed through bioelectric impedance analysis. Eating patterns were evaluated and daily nutrients intake was calculated. A complete blood count, glycated hemoglobin, cobalamin, and creatinine serum concentrations were analyzed. We hypothesized certain nutrient deficits and specific biomarker impairments originated from cultural particularities driving food selection in Mexicans following a plant-based diet. Body composition did not differ among groups. Lower protein, niacin, pantothenic acid, pyridoxine, cobalamin, calciferol, fluoride, iodine, and selenium intake yet greater fiber, folic acid, vitamin E, copper, and molybdenum were observed in the plant-based group when compared with controls. Vegans presented lower cobalamin and creatinine serum concentrations. Hematologic abnormalities were prevalent in vegans. Insufficient consumption of several nutriments was identified in both dietary groups, suggesting that the local diet may be unbalanced, affecting both vegans and non-vegan individuals. However, vegans might present additional deficiencies, especially vitamin B₁₂, with potential repercussions. Clinical and nutritional guidance is required in this particular population to avoid possible health adverse events.

It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, mainly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was performed in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% CI: 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality, however, careful evaluation according to cancer types is critically important and recommended.

Mankind faces a coronavirus pandemic originating from a seafood market in Wuhan, China since December 2019. The pathogen was named novel coronavirus (n-CoV) and bats are the identified key reservoir. The coronavirus disease 2019 (COVID-19) quickly spread over China across the globe, turned into a pandemic with exponentially increasing numbers of cases and significant mortality rate. China reacted with lockdowns and strict control measurements to prevent spreading the virus. The treatment of severe cases was hampered by lack of specific vaccines. Vaccine-development and production is a painstaking process and can only be enforced by international cooperation. Different supportive treatment options surfaced due to combinations of antiviral agents with antibiotic drugs. Elderly, male, immune-suppressed patients with co-morbidities showed a high mortality rate. Health literacy, strong immune system, adequate serum 25-hydroxyvitamin D (25(OH)D) concentrations and healthy life style choices can support fast recovery. Antibiotic resistance needs to be addressed by development of new generation antimicrobials against nosocomial infections in preparation for future outbreaks. Plant-biosynthesis of nanomaterials and antiseptics may help in prevention and recovery rate. Prevalence of COVID-19 maybe inversely related to BCG vaccination, endemicity of malaria, humidy and temperature but directly with latitude. Recommendations to prevent the spread of COVID-19 should be followed strictly.

The aim of this single-center, open-label, non-controlled randomized study was to evaluate which formulation of vitamin D between cholecalciferol and calcifediol is most effective in the treatment of hypovitaminosis D in older adults. Demographic characteristics, clinical history and comprehensive geriatric assessment were recorded at admission. Eligible patients randomly received an equivalent vitamin D supplement either with cholecalciferol or calcifediol from hospital admission to three months after discharge. Among the 140 older patients included (mean age 83±6.6, 57.8% females), 69 received cholecalciferol and 71 calcifediol. The mean plasma values of 25OH-Vitamin D3 found at the enrollment were 16.8 ± 9.9 ng/mL in patients receiving cholecalciferol and 18.8 ± 13.3 ng/mL in those treated with calcifediol (p =0.31). At the 3-month follow up, the mean concentration of 25OH-Vitamin D3 was significantly higher in patients treated with calcifediol than in patients treated with cholecalciferol (respectively, 30.7 ± 8.4 vs 45.4 ± 9.8 ng/mL, p &lt;0.001). Supplementation with cholecalciferol or calcifediol results in both cases effective in reaching optimal circulating values of 25OH-VitaminD3 in the older patients suffering from hypovitaminosis D. However, supplementation with calcifediol led to average circulating values of 25OH- VitaminD3 significantly higher (over 50%) than those obtained with cholecalciferol.

Abstract: COVID-19 in 2020 brought challenges to the Brazilian public health system with an emerging virus with respiratory contagion called SARS-CoV-2. There are few studies in Brazil and in some countries, on the increased incidence of certain viral respiratory infections, includ-ing H1N1 and coronavirus and their association with low levels of vitamin D, zinc and iron. The aim of this study was to demonstrate that the deficit of vitamin D, zinc and iron has an impact on the infectious process of patients with COVID-19 and to establish new forms of prevention for the worsening of COVID-19 in the human body. Data were collected from medical records and test results from patients being followed up during the treatment period for COVID-19. Patients with low blood levels of vitamin D, zinc and iron during the treatment period of COVID-19 had a higher percentage of worsening and complications requiring hospitalization in intensive care beds. The ingestion of vitamin D, zinc and iron in the treatment period of patients with COVID-19 in addition to being an immunological protector against SARS-CoV-2 and alleviating the process of worsening the disease can also act as a biomarker in cases of this disease.

Vitamin D is a nutrient with anti-inflammatory properties whose role is currently being evaluated in COVID-19. Although studies are conflicting, they seem to suggest a role for vitamin D in reducing disease susceptibility but not in improving clinical outcome. In order to understand why vitamin D does not seem to have much effect on decreasing disease severity, it is essential to appreciate pulmonary vitamin D metabolism. To reach the pulmonary compartment, vascular endothelial cells would need to take up vitamin D from the blood stream, but they lack vitamin D receptor (VDR) and the activating enzyme CYP27B1. Endothelialitis – an important disease manifestation of COVID-19 – is therefore not expected to be directly affected by vitamin D. Bronchial epithelial cells are usually among the first to be infected with SARS-CoV-2. They do express both VDR and CYP27B1, but circulating vitamin D may not reach bronchial epithelial cells without transportation from the blood stream through the blood vessel wall. Inhalation therapy with vitamin D has therefore been suggested as an alternative for oral administration to bypass endothelial cells and efficaciously target bronchial epithelium. In conclusion, based on the principles of pulmonary vitamin D metabolism, it is not expected that vitamin D administration has a significant effect on COVID-19 severity. Vitamin D is more likely to reduce SARS-CoV-2 susceptibility, but reaching the airways with oral supplementation will be difficult and vitamin D inhalation therapy should be considered.

The use of vitamin D (VitD) supplements has become widespread in the last decade due not only to the dissociation between the blood levels recommended as "optimal" and those shown by the healthy population, but also to its presumed beneficial effects on multiple disorders. This work evaluated the levels of 25-hydroxyvitamin D [25(OH)D] in a healthy population of European origin living in a region with high solar irradiation. In serum samples from a population-based study conducted in the Canary Islands, levels of 25(OH)D were analyzed. In 876 individuals who had no history of kidney or malabsorption disorders and who had not been treated with calcium and/or VitD supplementation, the median 25(OH)D level was 26.3 (5th;95th percentile, 14.3;45.8)ng/mL. Notably, 65.4% of the population had 25(OH)D blood levels below 30ng/mL, 23.4% below 20ng/mL and 6.4% below 15ng/mL. Based on the lack of evidence supporting causality between 25(OH)D levels below what is recommended as optimal (≥20ng/mL, or even ≥30ng/mL) and major skeletal and non-skeletal diseases, and in light of the distribution of the concentration of this vitamin in healthy adults living under optimal conditions of solar irradiation, it seems reasonable to consider 25(OH)D levels below 20ng/mL and close to 15ng/mL as adequate for the general population.

Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation on airway remodeling in asthma. We conducted a comprehensive search of electronic databases and identified experimental studies and randomized controlled trials that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, and regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to influence many of the pathways central to asthma progression, indicating a promising potential in asthma management and prevenation of asthma progression.

Vitamin C is an essential nutrient that must be obtained through the diet in adequate amounts to prevent hypovitaminosis C and the potentially fatal deficiency disease scurvy. Global vitamin C status and prevalence of deficiency has not previously been reported, despite vitamin C’s pleiotropic roles in both non-communicable and communicable disease. This review highlights the global literature on vitamin C status and the prevalence of hypovitaminosis C and deficiency. Related dietary intake is reported if assessed in the studies. We also explore if global vitamin C status has changed over time. Overall, the review illustrates the shortage of high quality epidemiological studies of vitamin C status in many countries, particularly low- and middle-income countries. The available evidence indicates that vitamin C deficiency is common in low- and middle-income countries and not uncommon in high income settings. Further high quality studies are required to confirm these findings, including in the countries not yet represented, and to fully understand associations with a range of disease processes. Our findings suggest a need for interventions to prevent deficiency in a range of at risk groups and regions of the world.

Studies shows that, normal to high serum 25(OH)D status appears to have some beneficial influence on the incidence and severity of some, though not all, types of infections. However, studies with vitamin D supplementation on young children produced conflicting results with respect to the level of vitamin D deficiency among common medical illnesses among children. Method: A systematic review of literatures from PubMed, CINAHL, Web of science, global health and Google scholar electronic databases was conducted to assess the pooled prevalence of vitamin D deficiency among healthy and sick children in sub-Saharan Africa. The data was extracted by two authors independently using standard data extraction format and STATA Version 14 was used for analysis. The heterogeneity of the studies was assessed by using I2 test. A random-effects model was used to estimate the pooled prevalence among both healthy and sick children. Presence of publication bias was checked using Funnel plot and Egger's test. Result: A total of 1212 articles were identified by the total search of utilized data bases of which 13 papers fulfilled the inclusion criteria and accessible with full document. The meta-analysis revealed that the pooled prevalence of vitamin D deficiency among healthy children in this study was 50.06% (95%CI 33.46%, 66.67%) with mean serum vitamin D level of 41.06 nm/L (CI range from 23.82nm/L to 58.31nm/L). The pooled prevalence among the sick children was 39.36% (CI 20.57%, 57.96%) with 66.96nm/L (95% CI 54.81nm/L, 79.11nm/L) mean concentration of vitamin D. Comparing the two level of the pooled prevalence, the prevalence among the healthy children was significantly higher compared to those who have common medical illnesses and the pooled mean concentration among the sick was much higher than the mean concentration among healthy children. Conclusion: The level of pooled prevalence among both group of population was significantly of public health concern and the prevalence among the healthy children was much higher among the sick children implying the need for reconsideration of available recommendations for the prevention of vitamin D deficiency

The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).

A recent systematic review for 19 selected articles after searching through to 30 September 2017 showed vitamin D deficiency was associated with ischemic stroke (IS), not hemorrhagic stroke (HS). But a heterogeneity would be introduced with comparing the lowest and highest category of vitamin D. The aim of this article was to conduct an updated meta-analysis (UMA) with searching through to 31 March 2019. An interval collapsing method as information extraction was applied in order to decrease a heterogeneity among studies. Additional articles were selected from cited lists from 19 selected articles using citation discovery tools. Random effect model was applied if I-squared value was over 50%. A funnel plot and Egger’s test were used to detect a publication bias. After 5 new studies were added, the summary RRs [and their 95% confidence intervals] (I-squared value) were 1.52 [1.33–1.74] (0.0%) in IS, and 2.44 [1.34–4.46] (69.7%) in HS. This UMA supported the hypothesis that serum vitamin D deficiency was associated with an increased risk of HS as well as IS. Diverse public health programs against vitamin D deficiency status would be needed for higher risk group, especially elderly people.

More than 15,000 prescriptions and over the counter drugs are available according to the US Food and Drug Administration website. Moreover, several herbal medicines and dietary supplements are readily available to add to the list of possible drugs, which can potentially cause adverse drug interactions. These are a pressing concern for all as they can interfere with many dental procedures. Additionally, the number of geriatric patients seen in routine dental practice has increased over time. This implies that there are more patients with multiple diseases and health conditions like hypertension, diabetes, problems associated with the cardiovascular, renal and gastrointestinal systems, arthritis, osteoporosis, etc. All these require patients to be on certain medications. Furthermore, advancement in the dental field has led to more complex dental procedures (implants, grafts) being carried out in a general dental practice. These advanced and slightly more invasive treatments require the use of certain drugs before, during and after the treatment like local anesthetics, vasoconstrictors, anxiolytics, analgesics and antibiotics. All of these can possibly interact with medications a patient is already taking and can also interfere with the current dental treatment and create complications. This article aims to provide necessary information about commonly encountered systemic diseases and associated treating medications, their mechanism of action, possible complications and their management. The classes of drugs discussed include anti-platelet agents, vitamin K antagonists, novel oral anticoagulants, bisphosphonates, disease-modifying anti-rheumatic drugs and oral contraceptives.

Vitamin E facilitates testicular development and semen quality in farm animal. And most research tends to investigate antioxidant roles of Vitamin E in reproductive health; some research also find potential non-antioxidant roles of Vitamin E. To further uncover the mechanism by which Vitamin E modulates reproductive health, the paper reviews specific function of Vitamin E and candidate genes involved in male reproductive performance promoted by Vitamin E. The review found that cell proliferation (PDPN, BMP, Myc, AMPKa, GSK3β, PPARγ, CDK4, CDK6, Ki67, PCNA, Cyclin A2, Cyclin B1, Cyclin B3, BLM, REL, KLHL25)-, cell apoptosis (BCL-2, Caspase 9, Bax)-, spermatogenesis (CatSper1, CatSper2, NDRG1, CYP26B1, FSCN3, FLNA, SPCS3, YBX3, RARS)-, hormone receptor (PGR, FSHR, AR)-related genes are the underlying key points. And two miRNAs, miR-107 and miR-493-3p, which mediate cell cycle process, are also identified in response to Vitamin E treatment. The paper paves the way for a comprehensive understanding about effect of Vitamin E on testis development and semen quality in domestic animals.

Background: A Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/ml). Methods: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified and the library was prepared and sequenced on the Illumina Miseq platform. Results: The mean (±SD) age was 45.5 (±10.2) years with no defined co-morbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups were observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD while Parabacteroides, Butyricimonas, and Gordonibacter were abundant in the KOA_VDD group and Peptococcus, Intestimonas, Delftia, and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labeled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. Conclusion: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter, and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D, and knee osteoarthritis.

Coronavirus disease (COVID-19) is an infectious disease caused by a new virus which causes respiratory illness. Older adults and people who have previous chronic medical conditions are at higher risk for more serious complications from COVID-19.Hypovitaminosis D is attributed to the increased risk of lung injury and acute respiratory distress syndrome (ARDS) as well as diabetes, Cardiovascular event and associated comorbidities, which are the main causes of severe clinical problem in COVID-19 patients. Considering the protective role of vitamin D through modulating the innate and adaptive immune system as well as inhibition of Renin Angiotensin System (RAS), vitamin D supplementation might boost the immune system of COVID-19 patients and reduce severity of the disease in vitamin D deficient individuals.

Dietary supplements are more and more often used to increase daily intake of essential vitamins and minerals. These preparations are classified as special category of foods and are subject to food law, not pharmaceutical regulations. As a result the requirements to dietary supplements are much less restrictive than to medications. Also simple and inexpensive procedure of registration causes that the number of dietary supplements is widely spread every year. On every manufacturing phases of dietary supplements, there is a risk of contamination. One of the pollutions might be mercury which is classified as heavy metal. Its inorganic compounds damage kidneys and liver and methylmercury is easily absorbed from gastrointestinal system. Methylmercury is distributed in all tissues, also in nervous system. The aim of study was to determine the level of mercury in multivitamins and multiminerals preparations and to analyze the results. The study included 22 dietary supplements containing vitamins and minerals available on Polish market. Mercury was analyzed with atomic absorption spectrometry using AMA 254. The concentrations of Hg was 0.22–5.85 µg/kg (the average content was 2.40 µg/kg). The highest average mercury content was 4.51 µg/kg, whereas the lowest one was 0.31 µg/kg. The results was also analyzed in individual groups depending on main component and indication for use as well as pharmaceutical formulation. Also according to manufacturer’s recommendation, the dose of mercury taken with a single medicine was estimated for time of a day, a week, a month, 3 months and also a year. The findings were compared to limits defined in regulations of European Union and PTWI set by JECFA to assess the health risk. The results presented in this study proved that the amount of mercury in tested dietary supplements is much lower than the value of valid regulations. Analyzed supplements as long as they are used with the recommendation of manufacturer, do not pose a threat to human health.

Background: Vitamin B 12 deficiency has been implicated in endothelial dysfunction and cardiovascular disease via hyperhomocysteinemia. Coronary tortuosity (CorT) is a common coronary angiography finding. The etiology, clinical implication and long term prognosis are still not well clarified. This study was conducted with the aim to evaluate the relationship between CorT and vitamin B12. Subjects and Method: The medical records of consecutive patients, who underwent coronary angiography, were retrospectively reviewed. The study group consisted of 1624 patients. Taking into consideration the inclusion criteria, 212 patients with CorT and 210 patients with normal coronary angiographies (control group) were included in the study. Vitamin B12, other biochemical parameters, clinical and echocardiographic parameters, and CorT score were evaluated in all patients. CorT is defined as fixed 3 bends during both systole and diastole, with each bend ≥45 °. Results: Patients with CorT had higher prevalence of older, female gender, hypertension, current smoking. Vitamin B12 was significantly decreased in patient with CorT (134.7±47.8 vs 239.6±53.8 p<0.001). On multivariate analysis age, female gender, hypertension, diabetes mellitus and vitamin B12 were independent predictors for CorT (OR 1.56; 95% CI: 1.247–1.962; p < 0.001, OR 1.628; 95% CI: 1.376-2.048; p<0.001, OR 1.865; 95% CI: 1.387-2.695; p<0.001, OR 1.362; 95% CI: 1.184-1.726; p<0.001, OR 1.862; 95% CI: 1.486-2.674; p<0.001, respectively). Conclusion: In our study, we have founded a significant relationship between vitamin B12 deficiency and CorT.

(1) Background: Obesity and its comorbidities can cause burdens and limitations. Bariatric surgery (BS) is indicated as a safe procedure to reduce body mass and improve present comorbidities. Yet, several complications were reported, like vitamin D [25(OH)D] deficiency. We evaluated if 25(OH)D serum levels relate to clinical characteristics, symptoms, or habits in women after their BS and whether the vitamin D receptor (VDR) gene's TaqI and FokI polymorphisms affected 25(OH)D levels and the total body bone mineral density (TBBMD). (2) Methods: This cohort cross-sectional comparative analytical prospective study consisted of 27 women, 61.6 ± 5.0 years, submitted to BS one year prior at a public reference hospital, DF-Brazil. All participants were asked to follow the physical and dietary activity recommendations and received vitamin D3 supplements. Their anthropometric, biochemical, and immunological measurements and blood samples were obtained. (3) Results: 73.3% of participants had low 25(OH)D levels, and their levels correlated positively with TBBMD and negatively with systolic pressure. VDR TaqI did not affect 25(OH)D levels, whereas VDR FokI's allele f presence correlated to a median rise in 25(OH)D levels. Neither polymorphism correlated to TBBMD. (4) Conclusions: 25(OH)D levels were positively correlated with TBBMD, negatively with systolic blood pressure, and were higher in those with the VDR FokI allele f.

(1) Background: Many malignancies are driven by mutations which affect the gene for fibroblast growth factor receptor (FGFR) 1. Previously we have documented that signal transduction from FOP2–FGFR1 fusion protein in KG1 cells downregulated the expression of vitamin D receptor (VDR) gene. In this paper we investigated if also other FGFRs were responsible for the regulation of the VDR expression. (2) Methods: We used human myeloid leukemia cells U937, and bone cancer cell line U2OS, and cell transfection methods in order to address the above questions. (3) Results: In myeloid leukemia cells overexpression of FGFR 1-4 caused shift to granulocytic differentiation, upregulated expression of VDR, and sensitized these cells to 1,25-dihydroxyvitamin D (1,25D)-induced monocytic differentiation, while in bone cells, signal transduction activated by FGF1 was not responsible for regulation of VDR expression and activity. (4) Conclusions: Since the overexpression of FGFRs occurs in many neoplasms, it may be reasonable to use 1,25D analogs in these cancers, in which overexpression of FGFRs leads to VDR upregulation.

In recent years extensive studies have been continuously undertaken on the design of bioactive and biomimetic dental implant surfaces due to the need for improvement of the implant-bone interface properties. In this paper, the titanium dental implant surface was modified by a bioactive vitamin D3 coating prepared by self-assembly process. Surface characterization of the modified implant was performed by field emission scanning electron microscopy (FE-SEM), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), and contact angle measurements (CA). Implant’s electrochemical stability during exposure to an artificial saliva solution was monitored in situ by electrochemical impedance spectroscopy (EIS). Experimental results obtained were corroborated by means of quantum chemical calculations at the density functional theory level (DFT). The formation mechanism of the coating onto the titanium implant surface was proposed. During a prolonged immersion period, the bioactive vitamin D3 coating effectively prevented the underlying titanium from corrosive attack (polarization resistance in order of 10⁷ Ω cm²) with ~95% protection effectiveness.

Observational studies have linked vitamin D insufficiency to pediatric type 2 diabetes (T2D) , but evidence from vitamin D supplementation trials is sparse. Given the rising prevalence of pediatric T2D in all ethnicities, determining a protective role of vitamin D has significant public health importance. We tested whether serum 25-hydroxyvitamin D (25OHD) levels are causally linked to youth-onset T2D risk using Mendelian randomization (MR). We selected 54 single nucleotide polymorphisms (SNPs) associated with 25OHD in a European genome-wide association study (GWAS) on 443,734 individuals and obtained their effects on pediatric T2D from the multi-ethnic PRODIGY GWAS (3,006 cases/6,061 controls). We applied inverse variance weighted (IVW) MR, and a series of MR methods to control for pleiotropy. We undertook sensitivity analyses in ethnic sub-cohorts of PRODIGY, and using SNPs in core vitamin D genes or ancestry-informed 25OHD SNPs. Multivariable MR accounted for mediating effects of body mass index. We found that a standard deviation increase in 25OHD in the logarithmic scale did not affect youth-onset T2D risk (IVW MR odds ratio (OR) = 1.04, 95% CI=0.96-1.13, P=0.35) in the multi-ethnic analysis, and sensitivity, ancestry-specific and multivariable MR analyses showed consistent results. Our study had limited power to detect small/moderate effects of 25OHD (OR of pediatric T2D < 1.39 to 2.1). In conclusion, 25OHD levels are unlikely to have large effects on risk of youth-onset T2D across different ethnicities.

The recent outbreak of Coronavirus Disease 2019 (COVID-19) is a major threat to human health and the global economy. In addition to the development of vaccines there is an urgent need for preventive and therapeutic strategies towards severe COVID-19. Key to this would be a better understanding of the molecular mechanismsoiuuuu affected by SARS-COV-2. To address this, we performed a systems biology approach by integrating available RNA-seq datasets from post-mortem lung tissue of COVID-19 patients and cell culture models infected with SARS-COV-2, Respiratory Syncytial virus or influenza virus. We identified two gene-expression modules that are commonly regulated by the three viral diseases and one that is specific to COVID-19. All 3 gene-expression modules represent key inflammatory processes. We identified several proteins within these networks that can be targeted by FDA approved drugs. Key examples are TNF, NFkB, INTERLEUKIN-1 and ALOX5 signaling pathways. Our data also suggest that Vitamin D supplementation and a ketogenic diet should be further analyzed as preventive strategies. In conclusion, our data highlights the potential of transcriptomics to unravel the pathological processes related to COVID-19 and guide the initiation of clinical trials.

It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA). Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration. Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

Treatment with calcitriol, the hormonal form of vitamin D, has shown beneficial effects in ex-perimental models of acute lung injury. In this study we aimed to analyze the associations be-tween calcitriol supplementation and the risk of SARS-CoV2 infection or COVID-19 mortality. Individuals ≥18 years old living in Catalonia and supplemented with calcitriol from April 2019 to February 2020 were compared with propensity score matched controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality. Associations between calcitriol supplementation and outcome variables were analyzed using multivariable Cox proportional regression. A total of 8076 patients were identified as being on calcitriol treatment. Advanced chronic kidney disease and hypoparathyroidism were the most frequent reasons for calcitriol supplementation in our population. Calcitriol use was associated with reduced risk of SARS-CoV2 infection (HR 0.78 [CI 95% 0.64-0.94], p=0.010), reduced risk of severe COVID-19 and reduced COVID-19 mortality (HR 0.57 (CI 95% 0.41-0.80), p=0.001) in patients with advanced chronic kidney disease. In addition, an inverse association between mean daily calcitriol dose and COVID-19 severity or mortality was observed in treated patients, independently of renal function. Our findings point out that patients with advanced chronic kidney disease could benefit from calcitriol supplementation during the COVID-19 pandemic.

Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased transforming growth factor (TGF) β/interferon (IFN)-γ ratio with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4⁺ and CD8⁺ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, Varicella Zoster (VZV) aka Human Herpesvirus 3 (HHV3), HBV, HCV, …. In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF-β/IFN-γ and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis. Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.

Background: To determine vitamin D supplementation frequency among infants, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. Methods: This cross-sectional study was conducted using a questionnaire administered to the mothers via a face-to-face interview on 560 infants aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. Results: A total of 351 infants were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among infants who were exclusively formula-fed (p<.05). When the data were analyzed using logistic regression analysis, only visit family physicians seems to be a statistically significant independent variable in increasing supplementation (p<.05). Compared with family refusal, the rate of discontinuation of vitamin D by the healthcare providers was higher after the first year of life (p<.05). The rates of vitamin D discontinuation by healthcare providers, especially by nurses who considered the duration of supplementation adequate, were statistically significantly higher when compared with the fontanel closure and other reasons (p<0.05). Conclusions: The rate of vitamin D supplementation was higher among families who visited family physicians, which suggests the importance of well-baby visits. Since vitamin D supplementation was less common among exclusively breastfed infants, mothers should be educated. Healthcare professionals need further education about the importance of vitamin D supplementation and indications for discontinuation.

This study aimed to examine the vitamin D status of professional volleyball athletes and to determine its correlation with shoulder muscle strength. We finally included 52 healthy male professional volleyball players (23.2 ± 4.5 years), who were categorized by vitamin D status (<20 ng/mL: deficiency, 20-30 ng/mL: insufficiency, and >30 ng/mL: sufficiency). We examined the strength of the internal rotator (IR) and external rotator (ER) muscles of the shoulder by using isokinetic dynamometer. Fourteen players (26.9%) had vitamin D deficiency, 24 players (46.2%) were vitamin D insufficient, and 14 players (26.9%) were vitamin D sufficient. There was no significant correlation between the vitamin D level and shoulder muscle strength at 60°/s (IR, r = 0.159, p = 0.26; ER, r = 0.245, p = 0.08), and at 180°/s (IR, r = - 0.093, p = 0.51; ER, r = - 0.037, p = 0.79). Moreover, the isokinetic shoulder strengths were not significantly different across the three groups in all settings. In conclusion, vitamin D insufficiency was common in elite volleyball players. Though not being associated with isokinetic muscle weakness, vitamin D should be regularly monitored and supplemented in young elite athletes, considering its importance on musculoskeletal health.

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence or lack of thereof of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

Synechococcus sp. PCC 11901 reportedly demonstrates the highest, sustained growth of any known cyanobacterium under optimized conditions. Due to its recent discovery our knowledge of its biology, including the factors underlying sustained, fast growth, is limited. Furthermore, tools specific for genetic manipulation of PCC 11901 are not established. Here, we demonstrate that PCC 11901 shows faster growth than other model cyanobacteria, including the fast-growing species Synechococcus elongatus UTEX 2973, under optimal growth conditions for UTEX 2973. Comparative genomics between PCC 11901 and Synechocystis sp. PCC 6803 reveal conservation of most metabolic pathways but PCC 11901 has a simplified electron transport chain and reduced light-harvesting complex. This may underlie its superior light utilization, reduced photoinhibition and higher photosynthetic and respiratory rates. To aid biotechnology applications we developed a vitamin B12 auxotrophic mutant but were unable to generate unmarked knockouts using two negative selectable markers, suggesting that recombinase- or CRISPR-based approaches may be required for repeated genetic manipulation. Overall, this study establishes PCC 11901 as one of the most promising species currently available for cyanobacterial biotechnology and provides a useful set of bioinformatics tools and strains for advancing this field, in addition to insights into the factors underlying its fast growth phenotype.

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.

Thyroid hormones have a catabolic effect on bone homeostasis. Hence, this study aimed to evaluate serum vitamin D, calcium, and phosphate and bone marker levels and bone mineral density (BMD) among patients with different thyroid diseases. This cross-sectional study included patients with underlying thyroid diseases (n=64, hyperthyroid; n=53 euthyroid; and n=18, hypothyroid) and healthy controls (n=64). BMD was assessed using z-score and left hip and lumbar bone density (g/cm2). Results showed that the mean serum vitamin D Levels of all groups was low (<50 nmol/L). Thyroid patients had higher serum vitamin D levels than healthy controls. All groups had normal serum calcium and phosphate levels. The bone marker levels were significantly high in the hyperthyroid group and low in the hypothyroid group. The z-score for hip and spine did not significantly differ between thyroid patients and control groups. The hip bone density was remarkably low in the hyperthyroid group. In all groups, the serum vitamin D levels were below the cutoff value. However, thyroid patients had a higher serum vitamin D level than healthy controls. The carboxy terminal collagen crosslink and procollagen type I N-terminal propeptide levels were high in hyperthyroid patients and low in hypothyroid patients. Further, hyperthyroid patients had a low hip BMD.

Abstract Eye health is crucial and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation of patients with natural antioxidants and nutraceuticals. In particular, evidence has been accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin, in particular, has been found to protect foto-receptors thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. On the other hand, CoQ10 has been demonstrated to produce consistent effect in reducing ocular pressure thereby leding to protection in patients undergoing glaucoma. Finally, both grape seed extract rich in anthocyanosides and polynsatured fatty acids (PUFAs) seem to contribute in the prevention of retinal disorders. Thus, combination of nutraceuticals and anti-oxidants may represent the right solution for a multiaction activity in eye protection to be associated to current drug therapies, and this will be of potential interest in early stages of eye disorders.

Long-term nutritional studies in subjects undergoing bariatric surgery that have assessed weight regain and nutritional deficiencies are few. In this study, we report data 8 years after surgery on weight loss, use of dietary supplements and deficit of micronutrients in a cohort of patients from five centres in central and northern Italy. The study group consisted of 52 subjects (age: 38.1±10.6 yrs, 42 females): 16 patients had Roux-en-Y gastric bypass (RYGB), 25 patients sleeve gastrectomy (LSG) and 11 subjects adjustable gastric banding (AGB). All three bariatric procedures led to sustained weight loss: average percentage excess weight loss, defined as weight loss divided by excess weight based on ideal body weight was 60.6%±32.3. 80.7% of subjects (72.7%, AGB; 76%, SG; 93.7%, RYGB) reported at least one nutritional deficiency: iron (F 64.3% vs. M 30%), vitamin B12 (F 16.6% vs. M 10%), calcium (F 33.3% vs. M 0%) and vitamin D (F 38.1% vs. M 60%). Average weight loss was constant in RYGB and SG subjects from the third year after surgery. Long-term nutritional deficiencies were greater than the general population among men for iron and among women for vitamin B12.

These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.

Ultraviolet (UV) radiation has both harmful and beneficial effects on human health. It can cause skin damage and cancer, but also provides the primary source of vitamin D. Additionally, UV radiation affects energy metabolism in mice with metabolic diseases and has protective effects on hypertension and cardiovascular diseases.Metabolic Syndrome is a collection of metabolic dysfunctions such as dyslipidemia, hypertension, hyperglycemia, abdominal/central obesity, and insulin resistance. Chronic UVR exposure suppressed obesity and type 2 diabetes in high-fat diet-fed mice, while vitamin D supplementation did not replicate these effects. On the other hand, topical application of nitric oxide (NO) donors replicated UV effects on mice, and NO scavengers prevented the positive impact of UV. UVR may prevent the development of obesity and metabolic syndrome through mechanisms that depend on UVR-induced NO, not vitamin D. Exposure to sunshine has a protective impact on blood pressure and cardiovascular disease. Although lower vitamin D concentration is linked to increased hypertension and the incidence of CVD, oral vitamin D supplementation does not decrease blood pressure or the risk of CVD, indicating that vitamin D may not mediate the beneficial effects of sun exposure. Instead, NO plays a crucial role as an endogenous vasodilator, produced by the vascular endothelium. Solar UVA may release nitrogen oxides from skin storage into the bloodstream, lowering blood pressure and cardiovascular mortality.In conclusion, UVR exposure could be a promising non-pharmacological intervention for metabolic syndrome, hypertension, and CVD prevention, and NO may play a crucial role in mediating these effects. Further research is needed to explore the precise mechanisms and identify the optimal doses and exposure times of UVR.

Relapses and resistance to therapeutic agents are major barriers for treatment of acute myeloid leukemia (AML) patients. This unfavorable circumstance emphasizes the need for new strategies targeting drug-resistant cells. As IDH mutation is present in the preleukemic stem cells and systematically conserved at relapse, targeting mutant IDH cells would be essential to achieve a long-term remission in the AML subgroup with IDH mutation. Here, using a panel of human AML cell lines and primary AML patient specimens harboring IDH mutation, we showed that the presence of IDH mutation through the production of an oncometabolite (R)-2-HG induces vitamin D receptor related transcriptional programs, priming these AML cells to differentiate with pharmacological doses of ATRA or/and VD. This activation occurs in a CEBP-dependent manner. Accordingly, our findings illuminate potent and cooperative effects of IDH mutation and vitamin D pathway to differentiate in AML, revealing a novel therapeutic approach easily transferable/immediately applicable in clinics for this subgroup of AML patients.

: Glioblastoma (GBM) is the most common and most aggressive primary brain tumor with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evi-dence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infil-trative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the ex-pression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show using in vitro limiting dilution assays, quantita-tive real-time PCR and ex vivo adult organotypic brain slice transplantation cultures that thera-peutic doses of calcitriol, the hormonally active form of vitamin D3, reduces stemness to varying extent in a panel of investigated GSC lines and effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to com-pletely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in fol-low-up studies.

Several observational studies have indicated the potential associations between calcium, vitamin D(Vit-D) and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subjected to residual confounding factors and reverse causation. Therefore, we aim to explore the bidirectional causal effects between serum calcium, Vit-D, PTH and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs). The results of the inverse-variance-weighted method did not re-veal any causal relationship shared between genetically predisposed calcium (OR = 0.92, 95% CI: 0.80-1.06, P = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83-1.19, P = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a de-creased level of PTH (beta: -0.19, 95%CI: -0.34 to -0.04, P = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms by which IBS affects serum PTH need to be further investigated.

Vitamins are essential compounds obtained through diet that are necessary for normal devel-opment and function in an organism. One of the most important vitamins for human physiology is Vitamin A, a group of retinoid compounds and carotenoids which generally function as a mediator for cell growth, differentiation, immunity, and embryonic development, as well as serving as a key component in the phototransduction cycle in vertebrate retina. For humans, vitamin A is obtained through the diet, where provitamin A carotenoids like β-carotene, or preformed vitamin A such as retinyl esters are absorbed into the body via the small intestine and converted into all-trans retinol within the intestinal enterocytes. Specifically, once absorbed, carotenoids are cleaved by carote-noid cleavage oxygenases (CCOs), such as BCO1, to produce all-trans retinal that subsequently gets converted into all-trans retinol. CRBP2 bound retinol is then converted into retinyl esters (REs) by the enzyme lecithin retinol acyltransferase (LRAT) in the endoplasmic reticulum, which is then packaged into chylomicrons and sent into the bloodstream for storage in hepatic stellate cells in the liver or for functional use in peripheral tissues such as the retina. All-trans retinol also travels through the bloodstream bound to retinol binding protein 4 (RBP4), where it enters cells with the assistance of the transmembrane transporters, stimulated by retinoic acid 6 (STRA6) in peripheral tissues or retinol binding protein receptor 2 (RBPR2) in systemic tissues (e.g. in the retina and the liver respectively). Much is known about the intake, metabolism, storage, and function of vitamin A compounds, especially with regard to its impact on eye development and visual function in the retinoid cycle. However, there is much to learn about the role of vitamin A as a transcription factor in development and cell growth, as well as how peripheral cells signal hepatocytes to secrete all-trans retinol into the blood for peripheral cell use. This article aims to review literature re-garding the major known pathways of vitamin A intake from dietary sources into hepatocytes, vitamin A excretion by hepatocytes, as well as vitamin A usage within the retinoid cycle in the RPE and retina to provide insight on future directions of novel membrane transporters for vitamin A in retinal cell physiology and visual function.

Excessive intracellular glucose in insulin independent tissues including nerve, nephron, lens and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) formation, lipid peroxidation and failure of antioxidant defense systems in type 2 diabetes mellitus (T2DM). All these detrimental biochemical anomalies ultimately attack biological membranes and especially capillary beds of retina and glomerulus of kidney, resulting in break-down of inner blood-retinal i.e. initiation of diabetic retinopathy (DR). If these disarrays are corrected to a large extent, development of DR can be avoided or delayed. In this prospective clinical trial, 185 patients with T2DM who received B-vitamins, vitamin-C, and E along with anti-diabetic medication for five years, demonstrated a slower rate of the development of DR and reduced abnormal biochemical mediators like reactive oxygen species (ROS), malondialdehyde (MDA), AGE, and vascular endothelial growth factor (VEGF) compared to 175 T2DM individuals who were treated with only anti-hyperglycemic drugs.

The role of vitamin D in the prevention and treatment of non-skeletal health issues has received significant media and research attention in recent years. Costs associated with clinical management of low vitamin D (LVD) have increased exponentially. However, no clear evidence supports vitamin D screening to improve health outcomes. Authoritative bodies and professional societies recommend against population-wide vitamin D screening in community-dwelling adults who are asymptomatic or at low risk of LVD. In order to assess patterns of physician management of LVD in this conflicting environment, we conducted a scoping review of three electronic databases and gray literature. Thirty-eight records met inclusion criteria and were summarized in an evidence table. Results from seven countries showed a consistent increase in vitamin D lab tests and related costs. Many vitamin D testing patterns reflected screening rather than targeted testing for individuals at high risk of vitamin D deficiency or insufficiency. Interventions aimed at managing inappropriate clinical practices related to LVD were effective in the short term. Variability and controversy were pervasive in many aspects of vitamin D management, shining light on physician practices in the face of uncertainty. Future research is needed is needed to inform better clinical guidelines and to assess implementation practices that encourage evidence-based management of LVD in adult populations.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents which targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents which target multiple components of the host’s response to an infectious agent will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.

In the human organism various carotenoids are present of which, some are retinoid precursors. The bioactive derivatives of these retinoids are the retinoic acids, which can potently activate nuclear hormone receptors like the retinoic acid receptor and the retinoid X receptor. In our study using an HPLC analytical approach we aimed to assess how plasma carotenoid and retinoid concentrations along with the ratio of their isomers are altered in atopic dermatitis (AD) patients (n=20) compared to healthy volunteers (HV, n=20). We found that plasma levels of the carotenoids lutein (HV 198 ± 68 ng/ml, AD 158 ± 57 ng/ml), zeaxanthin (HV 350 ± 142 ng/ml, AD 236 ± 85) as well as the retinoids retinol (HV 216 ± 89 ng/ml, AD 167 ± 76 ng/ml) and all-trans-retinoic acid (HV 1.1 ± 0.6 ng/ml, AD 0.7 ± 0.5 ng/ml) were significantly lower in AD-patients, while lycopene, α-carotene and β-carotene levels were comparable. In addition the ratios of 13-cis vs. all-trans lycopene as well as 13-cis vs. all-trans retinoic acid were increased in the plasma of AD-patients indicating an AD-specific 13C-isomerisation. A positive correlation with SCORRAD was calculated with 13-cis vs. all-trans lycopene ratio, while a negative correlation was observed with zeaxanthin plasma levels. Based on our results we conclude that in the plasma of AD-patients various carotenoids and retinoids are at lower levels, while the ratio of lycopene isomers was also altered. The higher rate of lycopene and retinoic acid isomerisation products might be a consequence of AD or might result in an altered activation of nuclear hormone receptor signaling pathways and thus maybe partly be responsible for the AD-phenotype and additionally may represent a good plasma marker for AD.

(1) Background: The issue of human adaptation to the Arctic environmental factors is relevant. The adaptation can be assessed through dynamic monitoring of the functional state of a person during his/her stay there. The vitamin D level in blood is one of the markers of the functional reserves of the human body and can contribute to more successful adaptation in the Arctic. (2) Methods: The study involved 38 participants in the scientific and educational expeditionary project "Arctic Floating University-2021". Blood collection for determination of vitamin D content was carried out at the beginning of the expedition. A dynamic study was carried out for 20 days in the morning and in the evening during a marine scientific expedition to the Arctic. The main parameters of the functional state of the participants were assessed using instrumental psychophysiological, projective and questionnaire methods. Statistical methods: Mann-Whitney U-test, correlation analysis using the Spearman coefficient. (3) Results: It was found that at the beginning of the expedition, the functional state of participants with severe vitamin D deficiency is characterized by a shorter average duration of RR intervals and reduced SDNN values, which may indicate a higher level of regulatory mechanisms tension. The pronounced differences in the nature of the dynamic series of objective and projective working capacity parameters were manifested most clearly. According to the subjective questionnaire characteristics of well-being, activity and mood, no significant features of the participants with vitamin D deficiency were revealed. (4) Conclusion: The participants with vitamin D deficiency in blood are characterized by a reduced adaptive capacity during the expedition to the Arctic.

A 24 week-controlled trial was conducted in menopausal women (mean age:61.5) to assess serum 25-hydroyvitaminD (s25OHD) evolution in relation to three interdependent determinants: doses of supplemented (Suppl.) vitamin D₃ (VitD₃); baseline status; seasonality. Participants were randomized into 3 groups (Gr): Gr.Suppl.0, time-controls maintaining dietary habits; Gr.Suppl.5 and Gr.Suppl.10 consuming one and two 125 g servings of VitD₃-fortified yogurts with 5 and 10 µg daily doses, respectively. The 16 intervention-weeks lasted from early-January to mid-August, the 8 follow-up-weeks from late-August to mid-October. Before enrollment, subjects were randomized into two s25OHD strata: “Low stratum (LoStr)“: 25-50 nmol/L; “High stratum (HiStr)“: >50-75 nmol/L. All enrolled participants remained compliant until study end: Gr.Suppl.0 (n=45), Gr.Suppl.5 (n=44) Gr.Suppl.10 (n=44). Over the 16 intervention and 8 follow-up weeks, s25OHD increased in both supplemented groups, more in Gr.Suppl.10 than Gr.Suppl.5. The constant rate of s25OHD per supplemental VitD₃ microgram was greater in LoStr than HiStr. s25OHD increase was greater with late (mid-March) than early (mid-January) inclusion. In conclusion, this randomized trial demonstrates: -a dose-dependent s25OHD improvement related to fortified yogurt consumption; -an inversely baseline-dependent increase in s25OHD; -a seasonal effect that highlights the importance of vitamin D₃ supplementation during winter, even at 5µg/d, in healthy menopausal women.

Regulatory macrophages (Mregs) are unique in that they have anti-inflammatory and immunosuppressive properties. Thus, treating inflammatory diseases using Mregs is an area of active research. Human Mregs are usually generated by culturing peripheral blood monocytes stimulated by macrophage colony-stimulating factor with interferon (IFN)-. Here, we generated Mregs with an elongated cell morphology from THP-1 cells stimulated with phorbol 12-myristate 13-acetate and cultured with arginylglycylaspartic acid and vitamin D3. These Mregs regulated macrophage function, and respectively downregulated and upregulated the expression of pro-inflammatory and immunosuppressive mediators. They also expressed Mregs-specific marker, such as dehydrogenase/reductase 9, even when exposed to inflammatory stimulants such as IFN-, lipopolysaccharide, purified xenogeneic antigen, and xenogeneic cells. The Mregs also exerted anti- inflammatory and anticoagulatory actions in response to xenogeneic cells and immunosuppressive effects on mitogen-induced Jurkat T-cell proliferation. Our method of generating functional Mregs in vitro without cytokines is simple and cost-effective.

Deficiencies of vitamin B12 (B12) and folate (FA) are of particular interest due to their pleiotropic role in 1-carbon metabolism. In addition to adverse birth outcomes, deficiencies of B12 and FA, or an imbalance in FA/B12 status, are linked to metabolic disorders. Indian diets that are predominantly plant food-based could be deficient in these vitamins, but there are no national estimates of the prevalence of B12 and FA deficiency in Indian children and adolescents, nor of their associations with age, sex, and growth indicators. The recent Comprehensive National Nutrition Survey (CNNS-2016-18) provided estimates of the prevalence of B12 and FA deficiency at the national and state level among preschool (1-4y: 9,976 and 11,004 children respectively), school-age children (5-9y: 12,156 and 14,125) and adolescents (10-19y: 11,748 and 13,621). Serum B12 and erythrocyte FA were measured by the direct chemiluminescence method and their deficiency was defined using WHO cut-offs. The prevalence of B12 and FA deficiency was high among adolescents (31.0%, CI: 28.7-33.5 and 35.6%, CI: 33.1-8.2), compared to school-age (17.3%, CI: 15.4-19.3 and 27.6%, CI: 25.5-29.9) and preschool children (13.8%, CI: 11.7-16.2 and 22.8%, CI: 20.5-25.2, respectively). The prevalence of both B12 and FA deficiency was significantly higher by 8 and 5% points respectively, in adolescent boys compared to girls. The prevalence of B12 deficiency was higher in moderately stunted school children (by 18.9% points) than in normal children, but no such difference was observed for FA deficiency. There was wide regional variation in the prevalence of B12 and FA deficiency, but no rural-urban differences were observed across all age groups. The national prevalence of B12 deficiency among preschool or school-age children was <20% (the cut-off that indicates a public health problem). However, FA deficiency in these age groups and both FA and B12 deficiencies in adolescents were >20%, which warrants further investigation.

COVID-19 is a pandemic triggered by the coronavirus SARS-CoV-2 whose peak occurred in the years 2020 and 2021. The main target of the virus is the lung and infection is associated to an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 mice and then the evaluation of vitamin D (VitD) ability to control this process. The assays used to estimate the severity of lung involvement included total and differential number of cells in the BALF, histopathological analysis, quantification of T cell subsets and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates and flow cytometric analysis of cells recovered from lung parenchyma. IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in COVID-19 patients. This inflammatory process was significantly decreased by IN delivery of vitD, but not by its IP administration, suggesting that this hormone has therapeutic potential in COVID-19 if locally applied.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied conditions in lieu of ascertaining either the differentially expressed genes (DEGs) or variants in an individual subpopulation of diseased phenotypes associated with VK, viz. myocardial infarction, renal failure, prostate cancer, thrombosis, thrombocytopenia, coagulation related diseases to name a few. In this work, we have screened characteristic DEGs common to three VK-related diseases, viz. myocardial infarction, renal failure and prostate cancer and asked whether or not any DEGs in addition to pathogenic variants are common to these conditions. We attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

Background: Vitamin D and calcium are important dietary compounds that affect bone mass, even if other minerals (potassium, zinc, etc.) and other vitamins (A, C and K) are also involved. Vitamin D and other minerals, in fact, play an important role in calcium homeostasis and calcium absorption. Hip fractures incidence is higher in western countries, where calcium is frequently included in human diet, while the occurrence of these fractures is lower in developing countries, where diets are often poor in calcium. This situation is known as the “calcium paradox”, and may be partially explained considering phosphate toxicity, that can induce a disorder of mineral metabolism. It is important to maintain adequate dietary calcium-phosphate balance in order to perform a healthy life, reducing the risk of osteoporotic fracture in older people. Vitamin D can also act as a hormone; vitamin D2 (ergocalciferol) is derived from the UV-B radiation of ergosterol, the vitamin D precursor naturally found in plants, fungi, and invertebrates. Vitamin D3 (cholecalciferol) is originated by sunlight exposure from 7-dehydrocholesterol, a precursor of cholesterol that can also act as a provitamin D3. Dietary intake of vitamin D3 is very important when skin is exposed for short times to ultraviolet B light (UV-B) one of the three kinds of invisible light rays together with UV-A and UV-C. This can be considered the usual situation in northern latitudes and in winter season, or the typical condition for older people and/or for people with very white delicate skin. Actually, the recommended daily intake of dietary vitamin D is strictly correlated with age, ranging from 5 μg for infants, children, teen-agers and adults, including women during pregnancy and lactation, to 15 μg for people over 65 years.

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms such as diarrhea, bloating, or chronic abdominal pain, CD may also present a wide spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. This review aims to describe the role of CD in the development of skeletal alterations, underlying important clinical aspects and therapeutic implications. The etiopathology of bone lesions in CD is multifactorial and their management is challenging. Here, we provide gastroenterologists and orthopedics with an up-to-date overview on the link between CD and osteoporosis to improve the management of the CD condition.

The application of electrospray ionization mass spectrometry (ESI-MS) as a direct method for detecting reactive intermediates is a technique of developing importance in the routine monitoring of solution-phase reaction pathways. Here, we utilize a novel on-line photolysis ESI-MS approach to detect the photoproducts of riboflavin in aqueous solution under mildly alkaline conditions. Riboflavin is a constituent of many food products, so its breakdown processes are of wide interest. Our on-line photolysis setup allows for solution-phase photolysis to occur within a syringe using UVA LEDs, immediately prior to being introduced into the mass spectrometer via ESI. Gas-phase photofragmentation studies via laser-interfaced mass spectrometry of deprotonated riboflavin, [RFH], the dominant solution-phase species under the conditions of our study, are presented alongside the solution-phase photolysis. The results obtained illustrate the extent to which gas-phase photolysis methods can inform our understanding of the corresponding solution-phase photochemistry. We determine that the solution-phase photofragmentation observed for [RFH] closely mirrors the gas-phase photochemistry, with the m/z 241 ion being the only major condensed-phase photoproduct. Further gas-phase photoproducts are observed at m/z 255, 212, and 145. The value of exploring both the gas- and solution-phase photochemistry to characterize photochemical reactions is discussed.

The leading cause of illness in aging is a group known as Noncommunicable Diseases. There should be some meeting points that modify the cells homeostasis and impaired the cell physiology developing different diseases. Quantum physics studied the atomic and subatomic particles and revolutionized the reality perception with paradoxical and weird concepts. Heisenberg's uncertainty principle established that it is not possible to determine the two characteristic properties of particles with accuracy. Subatomic particles have a wave-particle duality. Two subatomic particles are entangled, something happening over here can have an instantaneous effect over there, no matter how far away there are. All these concepts have tried to apply to biology and life sciences, quantum biology is behind photosynthesis, mitochondrial respiration, enzyme activity, the sense of smell, animal migration, heredity's fidelity, and consciousness. We can apply all these concepts to diseases pathogeny. So, we describe quantum phenomena in oxidative stress, calcification, signal transduction, vitamin D production and cancer mutations. Aging diseases also could be explained by applying quantum physics concepts. It is a new, hard to believe, and an incredible path to be built, but we need to open the treatment options to our patients with new perspectives.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

Background: Nowadays investigations in the field of dental implants engineering are focused on bioactivity and osseointegration properties.Objective: In this study, the oxide-covered titanium was functionalized by vitamin D3 molecules via a simple self-assembly method with the aim to design more corrosion resistant and at the same time more bioactive surface.Methods: Surface properties of the D3-coated titanium were examined by scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, and contact angle measurements, while a long-term corrosion stability during immersion in an artificial saliva solution was investigated in situ by electrochemical impedance spectroscopy.Results: Results of all techniques confirmed a successful formation of the D3 vitamin layer on the oxide-covered titanium. Besides very good corrosion resistivity (~5 MΩcm² ) the D3-modified titanium surface induced spontaneous formation of biocompatible bone-like calcium phosphates (CaP).Conclusion: Observed in vitro CaP-forming ability as a result of D3-modified titanium/artificial saliva interactions could serve as a promising predictor of in vivo bioactivity of implant materials.