Vitamin D in autophagy signaling for health and diseases: Insights on potential mechanisms and future perspectives.

Vitamin D regulates the pleiotropic effect to maintain cellular homeostasis and epidemiological evidence establishes an association between vitamin D deficiency and various human diseases. Here, the role of autophagy, the cellular self-degradation process, in vitamin D-dependent function is documented in different cellular settings and discussed the molecular aspects for treating chronic inflammatory, infectious diseases, and cancer. Vitamin D activates autophagy through a genomic and non-genomic signaling pathway to influence a wide variety of physiological functions of different body organs along with bone health and calcium metabolism. Moreover, it induces autophagy as a protective mechanism to inhibit oxidative stress and apoptosis to regulate cell proliferation, differentiation, and immune modulation. Furthermore, vitamin D and its receptor regulate autophagy signaling to control inflammation and host immunity by activating antimicrobial defense mechanisms. Vitamin D has been revealed as a potent anticancer agent and induces autophagy to increase the response to radiation and chemotherapeutic drugs for potential cancer therapy. Increasing vitamin D levels in the human body through timely exposure to sunlight or vitamin D supplements could activate autophagy as part of the homeostasis mechanism to prevent multiple human diseases and aging-associated dysfunctions.

Evidences suggesting a possible role of Vitamin D in COVID 19: The missing link.

The severe acute respiratory syndrome coronavirus 2 is spreading like wildfire with no specific recommended treatment in sight. While some risk factors such as the presence of comorbidities, old age, and ethnicity have been recognized, not a lot is known about who the virus will strike first or impact more. In this hopeless scenario, exploration of time-tested facts about viral infections, in general, seems to be a sound basis to prop further research upon. The fact that immunity and its various determinants (e.g., micronutrients, sleep, and hygiene) have a crucial role to play in the defense against invading organisms, may be a good starting point for commencing research into these as yet undisclosed territories. Herein, the excellent immunomodulatory, antiviral, and anti-inflammatory roles of Vitamin D necessitate thorough investigation, particularly in COVID-19 perspective. This article reviews mechanisms and evidence suggesting the role Vitamin D plays in people infected by the newly identified COVID-19 virus. For this review, we searched the databases of Medline, PubMed, and Embase. We studied several meta-analyses and randomized controlled trials evaluating the role of Vitamin D in influenza and other contagious viral infections. We also reviewed the circumstantial and anecdotal evidence connecting Vitamin D with COVID-19 emerging recently. Consequently, it seems logical to conclude that the immune-enhancing, antiviral, anti-inflammatory, and lung-protective role of Vitamin D can be potentially lifesaving. Hence, Vitamin D deserves exhaustive exploration through rigorously designed and controlled scientific trials. Using Vitamin D as prophylaxis and/or chemotherapeutic treatment of COVID-19 infection is an approach worth considering. In this regard, mass assessment and subsequent supplementation can be tried, especially considering the mechanistic evidence in respiratory infections, low potential for toxicity, and widespread prevalence of the deficiency of Vitamin D affecting many people worldwide.

Déficit de vitamina D en una población pediátrica sana. La importancia de una adecuada profilaxis / Vitamin D insufficiency in a healthy pediatric population. The importance of early prophylaxis

Introducción: la vitamina D mantiene la concentración de calcio y fósforo dentro del rango fisiológico, permitiendo un metabolismo normal y la correcta mineralización de los huesos. Recientemente, la deficiencia de vitamina D se ha relacionado no solo con el raquitismo sino también con el aumento del riesgo de otras patologías. El objetivo de este estudio descriptivo, observacional y transversal fue conocer los niveles de concentración de vitamina D en una población pediátrica sana y la situación actual en cuanto a la profilaxis. La determinación de la vitamina D se midió mediante la concentración sérica de 25-hidroxivitamina D (25(OH)D). Material y métodos: se inscribieron 258 pacientes sanos de entre 3 meses y 15 años (6,77 ± 3,95 años; 73,6 % de hombres). Resultados: el valor medio de 25(OH)D fue de 26,60 ng/ml ± 8,02 ng/ml; el 20,9 % de la población mostró un nivel insuficiente. Se observaron diferencias estadísticamente significativas entre los niveles de vitamina D de las distintas edades (p = 0,002), grupos étnicos (p = 0,038) y fototipos (p = 0,000). Además, se observó una mayor prevalencia de la insuficiencia de vitamina D en los niños que nunca antes habían recibido suplementos de vitamina D (41,6 %) en comparación con los que habían tomado suplementos en el primer año de vida (16,7 %). Conclusiones: el presente estudio muestra una alta prevalencia del déficit de vitamina D en los niños sanos y el beneficio de una correcta profilaxis en edades tempranas con suplementos de vitamina D. (AU)

Introduction: vitamin D maintains the concentration of calcium and phosphorus within the physiological range, allowing normal metabolism and bone mineralization. Recently, vitamin D deficiency has been related not only with rickets but also with an increased risk of other pathologies. The aim of this descriptive, observational, cross-sectional study was to assess vitamin D concentration levels in a healthy pediatric population, as well as the current situation of prophylaxis. Vitamin D determination was measured by serum 25-hydroxyvitamin D (25(OH)D) concentration. Material and methods: a total of 258 healthy patients between 3 months and 15 years of age were enrolled (6.77 ± 3.95 years; 73.6 % were male). Results: the mean value of 25-hydroxyvitamin D was 26.60 ng/mL ± 8.02 ng/mL, and up to 20.9 % of the population showed insufficient levels. Statistically significant differences in vitamin D levels were observed between ages (p = 0.002), ethnicity groups (p = 0.038), and skin types (p = 0.000). In addition, a higher prevalence of vitamin D insufficiency in children who had never previously received vitamin D supplementation (41.6 %) was observed compared to those that had taken supplementation in the first year of life (16.7 %). Conclusion: our study shows a high prevalence of vitamin D deficiency among healthy children, and the benefit of prophylaxis with vitamin D supplementation. (AU)

Vitamin D Status in Children With Short Stature: Accurate Determination of Serum Vitamin D Components Using High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Objective: Vitamin D is critical for calcium and bone metabolism. Vitamin D insufficiency impairs skeletal mineralization and bone growth rate during childhood, thus affecting height and health. Vitamin D status in children with short stature is sparsely reported. The purpose of the current study was to investigate various vitamin D components by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to better explore vitamin D storage of short-stature children in vivo. Methods: Serum circulating levels of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], and 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3, C3-epi] were accurately computed using the LC-MS/MS method. Total 25(OH)D [t-25(OH)D] and ratios of 25(OH)D2/25(OH)D3 and C3-epi/25(OH)D3 were then respectively calculated. Free 25(OH)D [f-25(OH)D] was also measured. Results: 25(OH)D3 and f-25(OH)D levels in short-stature subgroups 2 (school age: 7~12 years old) and 3 (adolescence: 13~18 years old) were significantly lower compared with those of healthy controls. By contrast, C3-epi levels and C3-epi/25(OH)D3 ratios in all the three short-stature subgroups were markedly higher than the corresponding healthy cases. Based on cutoff values developed by Endocrine Society Recommendation (but not suitable for methods 2 and 3), sufficient storage capacities of vitamin D in short-stature subgroups 1, 2, and 3 were 42.8%, 23.8%, and 9.0% as determined by Method 3 [25(OH)D2/3+25(OH)D3], which were lower than those of 57.1%, 28.6%, and 18.2% as determined by Method 1 [25(OH)D2+25(OH)D3+C3-epi] and 45.7%, 28.5%, and 13.6% as determined by Method 2 [25(OH)D2/3+25(OH)D3+C3-epi]. Levels of 25(OH)D2 were found to be weakly negatively correlated with those of 25(OH)D3, and higher 25(OH)D3 levels were positively correlated with higher levels of C3-epi in both short-stature and healthy control cohorts. Furthermore, f-25(OH)D levels were positively associated with 25(OH)D3 and C3-epi levels in children. Conclusions: The current LC-MS/MS technique can not only separate 25(OH)D2 from 25(OH)D3 but also distinguish C3-epi from 25(OH)D3. Measurement of t-25(OH)D [25(OH)D2+25(OH)D3] alone may overestimate vitamin D storage in children, and short-stature children had lower vitamin D levels compared with healthy subjects. Ratios of C3-epi/25(OH)D3 and 25(OH)D2/25(OH)D3 might be alternative markers for vitamin D catabolism/storage in short-stature children. Further studies are needed to explore the relationships and physiological roles of various vitamin D metabolites.

Vitamin D association with the renin angiotensin system in polycystic ovary syndrome.

Vitamin D deficiency is a negative endocrine renin-angiotensin system (RAS) modulator and PCOS women are often vitamin D deficient, leading to RAS overactivation in PCOS. A cross-sectional study was performed in 99 PCOS and 68 control women who presented sequentially. Circulating plasma levels of RAS proteins (Angiotensin-converting enzyme 2 (ACE2), renin and angiotensinogen) were measured by Slow Off-rate Modified Aptamer (SOMA)-scan and 25-hydroxyvitamin D [25(OH)D] was measured by tandem mass spectroscopy. The RAS system was found to be overactivated in the PCOS women compared to non-PCOS control women with increased renin and decreased angiotensinogen (p < 0.05); 25-hydroxyvitamin D was also significantly lower in the PCOS group (p < 0.0001). In PCOS women, plasma renin was increased in vitamin D deficient and insufficient groups compared with the vitamin D sufficient group (p < 0.005), but did not differ across non-PCOS control subgroups. In non-PCOS controls, plasma ACE2 decreased from vitamin D insufficiency to deficiency (p < 0.05). Angiotensinogen was not different across the vitamin D sufficiency, insufficiency and deficiency strata for either PCOS or non-PCOS controls. These data show that RAS activation through increased plasma renin levels was seen in vitamin D insufficient and deficient PCOS subjects compared to non-PCOS control women. In addition, decreased plasma ACE2 levels were seen in vitamin D deficiency in non-PCOS controls, which may predispose these vitamin D deficient subjects to increased cardiovascular risk and susceptibility to infectious agents such as COVID-19 where this is a risk factor.

The relationship between vitamin D status and islet function in patients with type 2 diabetes mellitus.

BACKGROUND: The aim of the study was to explore the relationship between vitamin D status and islet function in patients with type 2 diabetes mellitus. METHODS: The participants were recruited from Hebei General Hospital. Basic characteristics and blood indicators were collected after fasting overnight. The data were analyzed statistically using SPSS 22.0. Analysis of variance, a nonparametric test, or a trend Chi-square test was used for the comparisons. The association between 25-hydroxy vitamin D and modified homeostasis model assessment-ß was assessed using multivariate ordinal logistic regression. RESULTS: One hundred seventy-four patients aged 26 to 79 years with type 2 diabetes mellitus were included in this study. Patients with vitamin D deficiency had a lower modified homeostasis model assessment-ß level compared with those without vitamin D deficiency. There were differences in body mass index, diabetes course, glycosylated hemoglobin, fasting blood glucose, fasting blood C-peptide, triglyceride, and 25-hydroxy vitamin D among different modified homeostasis model assessment-ß groups based upon the tertiles. 25-hydroxy vitamin D, as continuous or categorical variables, was positively related to modified homeostasis model assessment-ß whether or not cofounding factors were adjusted. CONCLUSION: There is an association between increased 25-hydroxy vitamin D levels and improvement in modified homeostasis model assessment-ß function in patients with type 2 diabetes mellitus. TRIAL REGISTRATION: Cross-sectional trails ChiCTR2000029391 , Registration Date: 29/01/2020.

The association between 25-hydroxyvitamin D levels and muscle strength in adolescents.

INTRODUCTION: Background: since the discovery of the vitamin D receptor in muscle cells, relatively few studies conducted in adolescents have reported with conflicting results the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and muscle strength. Methods: the National Health and Nutrition Examination Survey during the period 2011-2014 was analyzed to examine the association between vitamin D status and the combined maximum grip strength, as a proxy for overall muscle strength in participants aged 10 to 19 years. According to the American Endocrine Society guidelines, subjects with 25(OH)D levels < 20 ng/mL, 20 to 30 ng/mL, and > 30 ng/mL were defined as having deficient, insufficient, and sufficient vitamin D, respectively. General linear models were assembled to examine this association. Results: of 2,528 participants with a mean age of 14.5 years, the prevalence of vitamin D deficiency and sufficiency was 25.6 % and 25.9 %, respectively. As expected, maximum grip strength increased with age and was stronger in boys than that in girls. Notably, after adjusting for potential confounders, boys and girls with vitamin D sufficiency were on average 2.9 kg and 2.1 kg stronger than their counterparts with vitamin D deficiency, respectively. Moreover, boys defined as having severe vitamin D deficiency (< 12 ng/mL) were 4.1 kg weaker than those who did not. Conclusion: in adolescents, vitamin D sufficiency was significantly associated with stronger combined maximum grip strength. The present findings should be further investigated to determine if maintaining optimal 25(OH)D concentrations might result in greater muscle strength in adolescents.

INTRODUCCIÓN: Antecedentes: desde el descubrimiento del receptor de la vitamina D en las células musculares, relativamente pocos estudios realizados en adolescentes han reportado, con resultados contradictorios, la relación entre los niveles séricos de 25-hidroxivitamina D [25(OH)D] y la fuerza muscular. Métodos: la Encuesta Nacional de Salud y Nutrición durante el periodo 2011-2014 se analizó para determinar la relación entre los niveles séricos de 25(OH)D vitamina D y la fuerza de agarre máxima combinada, usada como un aproximado de la fuerza muscular general, entre participantes de edades comprendidas entre los 10 y los 19 años. De acuerdo con las directrices de la Sociedad Americana de Endocrinología, los participantes con niveles de 25(OH)D < 20 ng/ml, de 20 a 30 ng/ml y > 30 ng/ml se definieron como deficiencia, insuficiencia, y suficiencia de vitamina D, respectivamente. Modelos generalizados lineales ajustados por cofactores se usaron para examinar esta asociación. Resultados: de 2528 participantes con una edad promedio de 14,5 años, la prevalencia de la deficiencia y la suficiencia de vitamina D fue del 25,6 % y del 25,9 %, respectivamente. Como era de esperar, la fuerza máxima de agarre aumentó con la edad y fue más fuerte en los niños que en las niñas. En general, los niños y niñas con suficientes niveles de 25(OH)D fueron en promedio 2,9 kg y 2,1 kg más fuertes que sus homólogos con deficiencia de vitamina D, respectivamente. Además, los niños con deficiencia severa de vitamina D (< 12 ng/ml) fueron en promedio 4,1 kg más débiles que los que no la tenían. Conclusión: en adolescentes, los niveles suficientes de vitamina D se asociaron a una mayor fuerza de agarre máxima combinada. Los hallazgos actuales deben investigarse más a fondo para determinar si mantener niveles óptimos de 25(OH)D podría resultar en una mayor fuerza muscular en los adolescentes.

Vitamin D Deficiency and Gender Alter Vasoconstrictor and Vasodilator Reactivity in Rat Carotid Artery.

The vitamin-D-sensitivity of the cardiovascular system may show gender differences. The prevalence of vitamin D (VD) deficiency (VDD) is high, and it alters cardiovascular function and increases the risk of stroke. Our aim was to investigate the vascular reactivity and histological changes of isolated carotid artery of female and male rats in response to different VD supplies. A total of 48 male and female Wistar rats were divided into four groups: female VD supplemented, female VDD, male VD supplemented, male VDD. The vascular function of isolated carotid artery segments was examined by wire myography. Both vitamin D deficiency and male gender resulted in increased phenylephrine-induced contraction. Acetylcholine-induced relaxation decreased in male rats independently from VD status. Inhibition of prostanoid signaling by indomethacin reduced contraction in females, but increased relaxation ability in male rats. Functional changes were accompanied by VDD and gender-specific histological alterations. Elastic fiber density was significantly decreased by VDD in female rats, but not in males. Smooth muscle actin and endothelial nitric oxide synthase levels were significantly lowered, but the thromboxane receptor was elevated in VDD males. Decreased nitrative stress was detected in both male groups independently from VD supply. The observed interactions between vitamin D deficiency and sex may play a role in the gender difference of cardiovascular risk.

[Vitamin D insufficiency in a healthy pediatric population. The importance of early prophylaxis]. / Déficit de vitamina D en una población pediátrica sana. La importancia de una adecuada profilaxis.

INTRODUCTION: Introduction: vitamin D maintains the concentration of calcium and phosphorus within the physiological range, allowing normal metabolism and bone mineralization. Recently, vitamin D deficiency has been related not only with rickets but also with an increased risk of other pathologies. The aim of this descriptive, observational, cross-sectional study was to assess vitamin D concentration levels in a healthy pediatric population, as well as the current situation of prophylaxis. Vitamin D determination was measured by serum 25-hydroxyvitamin D (25(OH)D) concentration. Methods: a total of 258 healthy patients between 3 months and 15 years of age were enrolled (6.77 ± 3.95 years; 73.6 % were male). Results: the mean value of 25-hydroxyvitamin D was 26.60 ng/mL ± 8.02 ng/mL, and up to 20.9 % of the population showed insufficient levels. Statistically significant differences in vitamin D levels were observed between ages (p = 0.002), ethnicity groups (p = 0.038), and skin types (p = 0.000). In addition, a higher prevalence of vitamin D insufficiency in children who had never previously received vitamin D supplementation (41.6 %) was observed compared to those that had taken supplementation in the first year of life (16.7 %). Conclusion: our study shows a high prevalence of vitamin D deficiency among healthy children, and the benefit of prophylaxis with vitamin D supplementation.

INTRODUCCIÓN: Introducción: la vitamina D mantiene la concentración de calcio y fósforo dentro del rango fisiológico, permitiendo un metabolismo normal y la correcta mineralización de los huesos. Recientemente, la deficiencia de vitamina D se ha relacionado no solo con el raquitismo sino también con el aumento del riesgo de otras patologías. El objetivo de este estudio descriptivo, observacional y transversal fue conocer los niveles de concentración de vitamina D en una población pediátrica sana y la situación actual en cuanto a la profilaxis. La determinación de la vitamina D se midió mediante la concentración sérica de 25-hidroxivitamina D (25(OH)D). Material y métodos: se inscribieron 258 pacientes sanos de entre 3 meses y 15 años (6,77 ± 3,95 años; 73,6 % de hombres). Resultados: el valor medio de 25(OH)D fue de 26,60 ng/ml ± 8,02 ng/ml; el 20,9 % de la población mostró un nivel insuficiente. Se observaron diferencias estadísticamente significativas entre los niveles de vitamina D de las distintas edades (p = 0,002), grupos étnicos (p = 0,038) y fototipos (p = 0,000). Además, se observó una mayor prevalencia de la insuficiencia de vitamina D en los niños que nunca antes habían recibido suplementos de vitamina D (41,6 %) en comparación con los que habían tomado suplementos en el primer año de vida (16,7 %). Conclusiones: el presente estudio muestra una alta prevalencia del déficit de vitamina D en los niños sanos y el beneficio de una correcta profilaxis en edades tempranas con suplementos de vitamina D.

Musculoskeletal Health in Active Ambulatory Men with Cerebral Palsy and the Impact of Vitamin D.

PURPOSE: (1) To determine the contribution of diet, time spent outdoors, and habitual physical activity (PA) on vitamin D status in men with cerebral palsy (CP) compared to physical activity matched controls (TDC) without neurological impairment; (2) to determine the role of vitamin D on musculoskeletal health, morphology, and function in men with CP compared to TDC. MATERIALS AND METHODS: A cross-sectional comparison study where 24 active, ambulant men with CP aged 21.0 ± 1.4 years (Gross Motor Function Classification Score (I-II) and 24 healthy TDC aged 25.3 ± 3.1 years completed in vivo assessment of musculoskeletal health, including: vastus lateralis anatomical cross-sectional area (VL ACSA), isometric knee extension maximal voluntary contraction (KE iMVC), 10 m sprint, vertical jumps (VJ), and radius and tibia bone ultrasound (US) Tus and Zus scores. Assessments of vitamin D status through venous samples of serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone, dietary vitamin D intake from food diary, and total sun exposure via questionnaire were also taken. RESULTS: Men with CP had 40.5% weaker KE iMVC, 23.7% smaller VL ACSA, 22.2% lower VJ, 14.6% lower KE iMVC/VL ACSA ratio, 22.4% lower KE iMVC/body mass (BM) ratio, and 25.1% lower KE iMVC/lean body mass (LBM) ratio (all p < 0.05). Radius Tus and Zus scores were 1.75 and 1.57 standard deviations lower than TDC, respectively (p < 0.05), whereas neither tibia Tus nor Zus scores showed any difference compared to TDC (p > 0.05). The 25(OH)D was not different between groups, and 90.9% of men with CP and 91.7% of TDC had low 25(OH)D levels when compared to current UK recommendations. The 25(OH)D was positively associated with KE iMVC/LBM ratio in men with CP (r = 0.500, p = 0.020) but not in TDC (r = 0.281, p = 0.104). CONCLUSION: Musculoskeletal outcomes in men with CP were lower than TDC, and despite there being no difference in levels of 25(OH)D between the groups, 25 (OH)D was associated with strength (KE iMVC/LBM) in the CP group but not TDC. The findings suggest that vitamin D deficiency can accentuate some of the condition-specific impairments to musculoskeletal outcomes.

Vitamin D deficiency attenuates endothelial function by reducing antioxidant activity and vascular eNOS expression in the rat microcirculation.

This study examined the effects of vitamin D deficiency on vascular function and tissue oxidative status in the microcirculation; and whether or not these effects can be ameliorated with calcitriol, the active vitamin D metabolite. Three groups (n = 10 each) of male Sprague Dawley rats were fed for 10 weeks with control diet (CR), vitamin D-deficient diet without (DR), or with oral calcitriol supplementation (0.15 µg/kg) for the last four weeks (DSR). After 10 weeks, rats were sacrificed; mesenteric arterial rings were studied using wire myograph. Oxidative stress biomarkers malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured in the mesenteric arterial tissue. Vascular protein expression of endothelial nitric oxide synthase (eNOS) was determined by Western blotting. Acetylcholine-induced endothelium-dependent relaxation of DR was lower than CR. eNOS expression and SOD activity were lower in mesenteric arterial tissue of DR compared to CR. Calcitriol supplementation to DSR did not ameliorate the above parameters; in fact, augmented endothelium-dependent contraction was observed. Serum calcium was higher in DSR compared to CR and DR. In conclusion, vitamin D deficiency impaired microvascular vasodilation, associated with eNOS downregulation and reduced antioxidant activity. Calcitriol supplementation to vitamin D-deficient rats at the dosage used augmented endothelium-dependent contraction, possibly due to hypercalcaemia.

Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents.

BACKGROUND/OBJECTIVES: Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess adiposity may begin early in life. Obesity is concurrent with a state of chronic inflammation, a well-known aetiological factor for DNA damage. In addition, obesity has been associated with micro-nutritional deficiencies. Vitamin D has attracted attention for its anti-inflammatory properties and role in genomic integrity and stability. The aim of this study was to determine a novel approach for predicting genomic instability via the combined assessment of adiposity, DNA damage, systemic inflammation, and vitamin D status. SUBJECTS/METHODS: We carried out a cross-sectional study with 132 participants, aged 10-18, recruited from schools and paediatric obesity clinics in London. Anthropometric assessments included BMI Z-score, waist and hip circumference, and body fat percentage via bioelectrical impedance. Inflammation and vitamin D levels in saliva were assessed by enzyme-linked immunosorbent assay. Oxidative DNA damage was determined via quantification of 8-hydroxy-2'-deoxyguanosine in urine. Exfoliated cells from the oral cavity were scored for genomic instability via the buccal cytome assay. RESULTS: As expected, comparisons between participants with obesity and normal range BMI showed significant differences in anthropometric measures (p < 0.001). Significant differences were also observed in some measures of genomic instability (p < 0.001). When examining relationships between variables for all participants, markers of adiposity positively correlated with acquired oxidative DNA damage (p < 0.01) and genomic instability (p < 0.001), and negatively correlated with vitamin D (p < 0.01). Multiple regression analyses identified obesity (p < 0.001), vitamin D (p < 0.001), and oxidative DNA damage (p < 0.05) as the three significant predictors of genomic instability. CONCLUSIONS: Obesity, oxidative DNA damage, and vitamin D deficiency are significant predictors of genomic instability. Non-invasive biomonitoring and predictive modelling of genomic instability in young patients with obesity may contribute to the prioritisation and severity of clinical intervention measures.

Does vitamin D supplementation improve ovarian reserve in women with diminished ovarian reserve and vitamin D deficiency: a before-and-after intervention study.

OBJECTIVE: Evaluation of vitamin D supplementation on ovarian reserve in women with diminished ovarian reserve and vitamin D deficiency. METHODS: The study is a before-and-after intervention study that was performed on women with diminished ovarian reserve referred to Shahid Mofteh Clinic in Yasuj, Iran. Eligible women were prescribed vitamin D tablets at a dose of 50,000 units weekly for up to 3 months. Serum levels of vitamin D and AMH were evaluated at the end of 3 months. Significance level was also considered P ≤ 0.05. RESULTS: Our results have been showed there was a statistically significant difference in vitamin D levels of participants before [12.1(6.5)] and after [26(9.15)] the intervention (P < 0.001). Moreover, there was a statistically significant difference in serum AMH levels of participants before [0.50(0.44)] and after [0.79(0.15)] the intervention (P=0.02 ). CONCLUSION: In conclusion, the results of the current study support a possible favorable effect of vitamin D on increase AMH expression by acting on the AMH gene promoter. Therefore, it is possible that vitamin D increases AMH levels without changing the antral follicle count/ovarian reserve.

Influence of vitamin D supplementation on the quality of life of asthma patients: Findings from ACVID randomised clinical trial.

Published data on vitamin D and the quality of life of asthma patients are scarce and disparate. The ACVID clinical trial, published in 2020, showed the efficacy of calcifediol in improving asthma control in asthma patients with vitamin D deficiency. Data on vitamin D and quality of life measured by the Mini-AQLQ questionnaire were analysed: supplemented patients showed improved quality of life compared with a placebo group, and the initial mini-AQLQ scores were improved for both groups.

Shedding light on vitamin D: the shared mechanistic and pathophysiological role between hypovitaminosis D and COVID-19 risk factors and complications.

Severe acute respiratory syndrome coronavirus (SARS-COV-2) is the culprit of the Coronavirus Disease (COVID-19), which has infected approximately 173 million people and killed more than 3.73 million. At risk groups including diabetic and obese patients are more vulnerable to COVID-19-related complications and poor outcomes. Substantial evidence points to hypovitaminosis D as a risk factor for severe disease, the need for ICU, and mortality. 1,25(OH)D, a key regulator of calcium homeostasis, is believed to have various immune-regulatory roles including; promoting anti-inflammatory cytokines, down regulating pro-inflammatory cytokines, dampening entry and replication of SARS-COV-2, and the production of antimicrobial peptides. In addition, there are strong connections which suggest that dysregulated 1,25(OH)D levels play a mechanistic and pathophysiologic role in several disease processes that are shared with COVID-19 including: diabetes, obesity, acute respiratory distress syndrome (ARDS), cytokine storm, and even hypercoagulable states. With evidence continuing to grow for the case that low vitamin D status is a risk factor for COVID-19 disease and poor outcomes, there is a need now to address the public health efforts set in place to minimize infection, such as lock down orders, which may have inadvertently increased hypovitaminosis D in the general population and those already at risk (elderly, obese, and disabled). Moreover, there is a need to address the implications of this evidence and how we may apply the use of cheaply available supplementation, which has yet to overcome the near global concern of hypovitaminosis D. In our review, we exhaustively scope these shared pathophysiologic connections between COVID-19 and hypovitaminosis D.

Effect of vitamin D supplementation on microvascular reactivity in obese adolescents: A randomized controlled trial.

BACKGROUND AND AIM: Childhood obesity is associated with vitamin D (VD) deficiency and vascular dysfunction. Considering evidence indicates that VD may improve vascular function, this study, for the first time, assessed the effect of VD supplementation on microvascular reactivity in obese adolescents (OA). METHODS AND RESULTS: This randomized controlled trial included 26 OA, receiving fruit juice with (n = 13) or without VD (4000 IU/d; n = 13) over a 3-month lifestyle program, as well as 23 normal-weight adolescents (controls). The primary outcome was the pre-to-post-program change in microvascular reactivity determined by laser speckle contrast imaging with acetylcholine and sodium nitroprusside iontophoresis. Changes in 25 hydroxyvitamin D (25(OH)D), flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), insulin resistance (HOMA-IR) and inflammatory markers (C-reactive protein [CRP]) were monitored. At inclusion, in comparison to controls, OA exhibited lower total and free 25(OH)D, impaired microvascular responses, and impaired FMD, but similar NMD. After the lifestyle program, total and free 25(OH)D increased in all OA, with a greater increase in those receiving VD supplements. HOMA-IR and CRP decreased in all OA. Neither FMD nor NMD were altered in either group. Endothelium-dependent microvascular reactivity only increased in the VD-supplemented group, reaching values comparable to that of controls. Similar results were found when analyzing only OA with a VD deficiency at baseline. CONCLUSION: VD supplementation during a lifestyle program attenuated microvascular dysfunction in OA without altering macrovascular function. REGISTRATION NUMBER FOR CLINICAL TRIAL: NCT02400151.

Coronavirus disease 2019, vitamin D and kidney function.

PURPOSE OF REVIEW: The purpose of this review is to summarize the emerging studies analyzing the association between vitamin D and risk of COVID-19 infection and severity, as well as the early interventional studies investigating the protective effect of vitamin D supplementation against COVID-19. RECENT FINDINGS: Studies investigating the association between vitamin D levels and risk of COVID-19 infection and risk of severe disease and mortality among those infected have yielded mixed results. Thus far, the majority of studies investigating the association between vitamin D and COVID-19 have been observational and rely on vitamin D levels obtained at the time of admission, limiting causal inference. Currently, clinical trials assessing the effects of vitamin D supplementation in individuals with COVID-19 infection are extremely limited. Randomized, interventional trials may offer more clarity on the protective effects of vitamin D against COVID-19 infection and outcomes. SUMMARY: Decreased levels of vitamin D may amplify the inflammatory effects of COVID-19 infection, yet, data regarding the mortality benefits of vitamin D supplementation in COVID-19-infected individuals are still limited. Current observational data provides the impetus for future studies to including randomized controlled trials to determine whether vitamin D supplementation in COVID-19-infected individuals with kidney disease can improve mortality outcomes.

[Nutrient Status of Vitamin D among Cancer Patients].

BACKGROUND: There is a certain correlation between vitamin nutritional status and cancer patients. Studies have shown that vitamin deficiency increases the risk of cancer. The purpose of this study is to understand the vitamin D nutritional status of cancer patients and to provide scientific basis for further nutritional intervention. METHODS: Cancer patients who visited Shandong Cancer Hospital from July 2017 to June 2019 were included in this retrospective study. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured. Univariate analysis and multiple linear regression analysis were carried out using SPSS 20.0. RESULTS: A total of 2,487 cancer patients were evaluable for this analysis. Mean 25(OH)D concentration was (12.70±6.82) ng/mL; the prevalence of vitamin D deficiency [25(OH)D concentration less than 20.00 ng/mL] was of 92.20%. In univariate analysis, age, body mass index (BMI), season and types of cancer were associated with 25(OH)D concentrations. In the multivariate analysis, BMI (ß=0.71), age (ß=-0.56), season (ß=-0.99 for winter; ß=-0.76 for autumn vs summer) and types of cancer (ß=-1.17 for lung cancer; ß=-1.45 for esophageal-gastric cancer; ß=-1.05 for colorectal cancer vs other types of cancer) were independently and significantly associated with 25(OH)D levels (P<0.05). CONCLUSIONS: Vitamin D deficiency was highly prevalent among cancer patients. Age, BMI, season and types of cancer may be associated with 25(OH)D levels, which indicate that monitoring of vitamin D level for cancer survivor should be taken into account.

Vitamin D deficiency and lung function decline in healthy individuals: A large longitudinal observation study.

AIM: A reliable evidence from a comprehensive large-scale study supporting associations between serum vitamin D (25-hydroxyvitamin D) level (SVDL) and lung function decline (LFD) in healthy individuals has been unavailable. Using a well-established health screening database, we assessed the associations between SVDL and LFDs, measured as the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. METHODS: Serial SVDL and lung function data were analyzed using linear mixed models, which were performed in smokers and non-smokers, separately. Vitamin D-deficient individuals (VDDs) were defined when their SVDLs were consistently lower than 20 ng/mL at all measurements. RESULTS: A total of 1371 individuals were analyzed. The mean FEV1 decline rates of VDDs and vitamin D-normal individuals (VDNs) in smokers were -33.35 mL/year (95% CI: 39.44 to -27.26 mL/year) and -15.61 mL/year (95% CI: 27.29 to -4.21 mL/year) respectively, over a mean of 6.29 years of observation with statistical significance (P < 0.001). However, there was no significant differences observed between decline rates of FEV1 in non-smokers. Similarly, FVC decline rates of VDDs were significantly greater than those of VDNs only in smokers (P < 0.001). However, FEV1/FVC ratio decline rates showed no significant difference between VDDs and VDNs regardless of their smoking status. CONCLUSIONS: Consistently low SVDLs predicted more rapid FEV1 and FVC declines in smokers. However, FEV1/FVC decline rate was not associated with SVDL. SVDL may be used to identify healthy smoking individuals at high risk for accelerated LFD.