Vitamin D and Pancreatitis: A Narrative Review of Current Evidence

Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.     

Effect of Selected Factors on the Serum 25(OH)D Concentration in Women Treated for Breast Cancer

Maintaining an optimal vitamin D concentration reduces the risk of recurrence and extends survival time in patients after breast cancer treatment. Data on vitamin D deficiency among Polish women after breast cancer therapy are limited. Thus, the aim of the study was the analysis of vitamin D status in post-mastectomy patients, considering such factors as seasons, social habits, vitamin D supplementation and its measurements. The study involved 94 women after breast cancer treatment. Serum vitamin D concentration was measured, and a questionnaire, gathering demographic and clinical data regarding cancer, diet, exposure to sun radiation, and knowledge of recommendations on vitamin D supplementation, was delivered twice, in both winter and in summer. The control group consisted of 94 age-matched women with no oncological history. In women after breast cancer treatment, 25-hydroxyvitamin D (25(OH)D) deficiency was much more frequent than in the general population. Only about half of the patients supplemented vitamin D at the beginning of the study. After the first test and the issuing of recommendations on vitamin D supplementation, the percentage of vitamin D supplemented patients increased by about 30% in study groups. The average dose of supplement also increased. None of the women that were not supplementing vitamin D and were tested again in winter had optimal 25(OH)D concentration. It was concluded that vitamin deficiency is common in women treated for breast cancer. Medical advising about vitamin D supplementation and monitoring of 25(OH)D concentration should be improved.     

Vitamin D: An overview of vitamin D status and intake in Europe

In recent years, there have been reports suggesting a high prevalence of low vitamin D intakes and vitamin D deficiency or inadequate vitamin D status in Europe. Coupled with growing concern about the health risks associated with low vitamin D status, this has resulted in increased interest in the topic of vitamin D from healthcare professionals, the media and the public. Adequate vitamin D status has a key role in skeletal health. Prevention of the well‐described vitamin D deficiency disorders of rickets and osteomalacia are clearly important, but there may also be an implication of low vitamin D status in bone loss, muscle weakness and falls and fragility fractures in older people, and these are highly significant public health issues in terms of morbidity, quality of life and costs to health services in Europe. Although there is no agreement on optimal plasma levels of vitamin D, it is apparent that blood 25‐hydroxyvitamin D [25(OH)D] levels are often below recommended ranges for the general population and are particularly low in some subgroups of the population, such as those in institutions or who are housebound and non‐Western immigrants. Reported estimates of vitamin D status within different European countries show large variation. However, comparison of studies across Europe is limited by their use of different methodologies. The prevalence of vitamin D deficiency [often defined as plasma 25(OH)D <25 nmol/l] may be more common in populations with a higher proportion of at‐risk groups, and/or that have low consumption of foods rich in vitamin D (naturally rich or fortified) and low use of vitamin D supplements. The definition of an adequate or optimal vitamin D status is key in determining recommendations for a vitamin D intake that will enable satisfactory status to be maintained all year round, including the winter months. In most European countries, there seems to be a shortfall in achieving current vitamin D recommendations. An exception is Finland, where dietary survey data indicate that recent national policies that include fortification and supplementation, coupled with a high habitual intake of oil‐rich fish, have resulted in an increase in vitamin D intakes, but this may not be a suitable strategy for all European populations. The ongoing standardisation of measurements in vitamin D research will facilitate a stronger evidence base on which policies can be determined. These policies may include promotion of dietary recommendations, food fortification, vitamin D supplementation and judicious sun exposure, but should take into account national, cultural and dietary habits. For European nations with supplementation policies, it is important that relevant parties ensure satisfactory uptake of these particularly in the most vulnerable groups of the population.     

An update on UK Vitamin D intakes and status,and issues for food fortification and supplementation

Vitamin D is unique among the essential nutrients in that it can be made in the body via exposure of the skin to sunlight. There are few rich sources of vitamin D in the diet. Vitamin D is essential for maintaining healthy bones and deficiency of vitamin D causes rickets in children and osteomalacia in adults. In the UK, there is evidence that low vitamin D status is prevalent in the population and older adults living in institutions are particularly at risk. There are two forms of vitamin D that can be added to foods and drinks: vitamin D₂ and D₃. They have somewhat different structures, and there are some differences in the way they are metabolised by the body. Overall, the evidence for the relative effectiveness of vitamin D₂ vs. D₃ is mixed, and more studies are needed to provide a clearer picture. However, there does seem to be some indication that D₃ is more effective than D₂ in raising vitamin D status.     

The Non-Genomic Actions of Vitamin D

Since its discovery in 1920, a great deal of effort has gone into investigating the physiological actions of vitamin D and the impact its deficiency has on human health. Despite this intense interest, there is still disagreement on what constitutes the lower boundary of adequacy and on the Recommended Dietary Allowance. There has also been a major push to elucidate the biochemistry of vitamin D, its metabolic pathways and the mechanisms that mediate its action. Originally thought to act by altering the expression of target genes, it was realized in the mid-1980s that some of the actions of vitamin D were too rapid to be accounted for by changes at the genomic level. These rapid non-genomic actions have attracted as much interest as the genomic actions and they have spawned additional questions in an already busy field. This mini-review attempts to summarise the in vitro and in vivo work that has been conducted to characterise the rapid non-genomic actions, the mechanisms that give rise to these properties and the roles that these play in the overall action of vitamin D at the cellular level. Understanding the effects of vitamin D at the cellular level should enable the design of elegant human studies to extract the full potential of vitamin D to benefit human health.     

维生素D与脑发育相关研究进展

近年来有关维生素D研究进展迅速,其中维生素D与大脑的发育之间的关系日益受到关注。维生素D是一种具有类固醇激素作用的物质,可参与调节细胞増殖、分化及凋亡,大量研究表明,维生素D除了具有促进钙磷吸收、骨骼发育及发挥免疫调节的作用,还可作为一类神经激素影响神经系统的发育和功能,本文将从大脑中的维生素D及维生素D受体、维生素D对脑发育可能的调控作用及维生素D与儿童神经精神障碍疾病的相关性等几方面进行阐述。     

The ODIN project: Development of food‐based approaches for prevention of vitamin D deficiency throughout life

Vitamin D deficiency has significant implications for human health throughout life and impacts on healthy growth and development and successful ageing. Persistent knowledge gaps are barriers to developing and implementing a safe and effective public health strategy to prevent vitamin D deficiency and maintain nutritional adequacy throughout the year. The European Commission‐funded ODIN project (Food‐based solutions for optimal vitamin D nutrition and health through the life cycle) will provide the evidence base to prevent vitamin D deficiency and improve nutrition and public health through food. ODIN will deliver the first internationally comparable dataset of vitamin D status and report the prevalence of vitamin D deficiency across Europe for the first time. In a series of dose‐response randomised controlled trials, ODIN will estimate dietary requirements for vitamin D in pregnant women, children, adolescents and adults of South Asian and East African origin resident in Northern European countries. Using clinically validated, disease‐specific cohorts with standardised 25(OH)D data, ODIN will investigate associations between vitamin D status and perinatal outcomes, atopic disease and bone growth in children, and cardiovascular and mortality risk in older adults. We will publish estimates of the distribution of vitamin D intake and serum 25(OH)D concentration resulting from changes in vitamin D in the food supply, accounting for latitude, sun exposure and diet. Utilising advanced food production systems and targeted animal and human feeding studies, ODIN will propose safe, novel and effective food‐based strategies to eradicate vitamin D deficiency that are inclusive, sustainable and affordable.     

Nutrition Support in Liver Transplantation and Postoperative Recovery: The Effects of Vitamin D Level and Vitamin D Supplementation in Liver Transplantation

Vitamin D plays an important role in the arena of liver transplantation. In addition to affecting skeletal health significantly, it also clinically exerts immune-modulatory properties. Vitamin D deficiency is one of the nutritional issues in the perioperative period of liver transplantation (LT). Although vitamin D deficiency is known to contribute to higher incidences of acute cellular rejection (ACR) and graft failure in other solid organ transplantation, such as kidneys and lungs, its role in LT is not well understood. The aim of this study was to investigate the clinical implication of vitamin D deficiency in LT. LT outcomes were reviewed in a retrospective cohort of 528 recipients during 2014–2019. In the pre-transplant period, 55% of patients were vitamin-D-deficient. The serum vitamin D level was correlated with the model for end-stage liver disease (MELD-Na) score. Vitamin D deficiency in the post-transplant period was associated with lower survival after LT, and the post-transplant supplementation of vitamin D was associated with a lower risk of ACR. The optimal vitamin D status and vitamin D supplementation in the post-transplant period may prolong survival and reduce ACR incidence.     

孕期鼠补充维生素D对子鼠胸腺维生素D受体表达

目的 研究给予母孕期大鼠补充不同剂量维生素D,检测子代鼠胸腺中VDR表达变化。方法 健康雌性Wistar大鼠18只,雄性Wistar大鼠9只,以每日晚间17时将雌鼠、雄鼠按2∶1合笼,次日8时对雌鼠阴道分泌物涂片,在40倍光学显微镜检查到精子表示受孕,记为妊娠0 d( gestational day 0,GD0) 。将孕鼠随机入对照组、维生素D低剂量、维生素D高剂量组。于GD 15 d起对照组每日给予肌肉注射生理盐水0.25 ml/(kg·次),低剂量组给予肌肉注射维生素D 20 μg/kg,高剂量组给予肌肉注射维生素D 100 μg/kg,直至子鼠娩出。子鼠哺乳21 d后分离子鼠胸腺,Real-time PCR检测VDRmRNA表达水平,Western blot检测VDR蛋白表达水平。结果 通过Real-tine PCR分析仔鼠胸腺VDR基因表达三组之间差异无统计学意义(P＞0.05)。Western blot检测VDR蛋白水平的表达显示,低剂量及高剂量组VDR蛋白的表达量均高于对照组,三组之间差异存在统计学意义(P＜0.05)。结论 给予母鼠补充维生素D,其仔鼠胸腺VDR蛋白表达量明显增加,与维生素D补充量呈正相关。     

Effect of Vitamin D and Docosahexaenoic Acid Co-Supplementation on Vitamin D Status,Body Composition,and Metabolic Markers in Obese Children: A Randomized,Double Blind,Controlled Study

Obese children are at high risk of developing vitamin D deficiency. Omega-3 polyunsaturated fatty acids and their derivatives might have a beneficial effect on vitamin D status of obese children, due to their anti-inflammatory action, and increasing its absorption. This multicenter, randomized, double-blind controlled study aims to investigate the effect of vitamin D and docosahexaenoic acid (DHA) co-supplementation for six months on vitamin D status, body composition, and metabolic markers of obese children with vitamin D deficiency. A total of 108 children were enrolled and 73 children completed the study: 33 were supplemented with an oral dose of 500 mg of DHA and 1200 IU/day of vitamin D3 and 41 were supplemented with 1200 IU/day of vitamin D3 + wheat germ oil. At the end of the study, more than 50% of the subjects improved their vitamin D status. However, co-supplementation was not more effective than vitamin D plus wheat germ oil. Fat mass percentage was significantly reduced, and body mass index improved in both groups, even if all the subjects were still obese at the end of the study. Children receiving both vitamin D and DHA presented a higher increase of DHA levels that could be relevant to prevent inflammatory-associated complications of obesity, but they had no effect on vitamin D levels.     

A Potential Role for Vitamin D on HIV Infection?

Despite advances in the knowledge of vitamin D's potent immunomodulatory activity, its role on HIV disease progression is unknown. Decreased concentrations of 1α,25-hydroxyvitamin D₃, or 1,25(OH)₂D, the active form of vitamin D, have been reported among HIV-infected people and attributed to defects in renal hydroxylation and increased utilization. A few studies also described low levels of 25-hydroxyvitamin D₃, 25(OH)D, the vitamin obtained from solar synthesis and diet. An inverse association between 1,25(OH)₂D concentrations and mortality has been reported from a small cohort of HIV-infected adults, and some cross-sectional studies have indicated positive correlations between 1,25(OH)₂D and CD4+ cell counts. Additional observational studies are needed to confirm the associations between vitamin D status and HIV disease progression. These investigations would provide useful insights on the potential role of vitamin D supplementation to HIV-infected persons and the planning of intervention trials.     

Vitamin D and muscle strength throughout the life course: a review of epidemiological and intervention studies

The putative role of vitamin D in muscle function and strength throughout the life course is of interest because muscle strength is required for engagement in physical activity at all ages. As vitamin D deficiency is widely reported in the population, especially in countries at high latitude, the potential importance of vitamin D in muscle function throughout life, and the potential impacts on growth and development, participation in physical activity, and effects on skeletal and cardio‐metabolic health, comprise an important topic for discussion. This review provides an overview of muscle function and summarises the role of the vitamin D receptor and the proposed molecular mechanisms of action of vitamin D in muscle cells. In addition, the review provides a comprehensive assessment of the clinical evidence surrounding the association between vitamin D and muscle strength. Among adults, particularly older adults, cross‐sectional and cohort studies reported a positive association between vitamin D status and muscle strength. These associations have been largely confirmed by intervention studies. Limited research has been carried out in adolescents and children; two cross‐sectional studies in adolescents have suggested an association between serum 25‐hydroxyvitamin D concentrations and muscle strength. However, the two intervention studies in adolescents have yielded conflicting results. Other than a single observational study, data in young children are very limited and further investigation in under 12‐year‐olds is warranted.     

住院治疗中新生儿维生素A、D、E水平单中心现况调查

目的 调查河南安阳地区住院治疗中新生儿维生素A、D、E水平及相关影响因素,为早期防治维生素A、D、E缺乏提供科学依据。方法 选取2017年5月-2019年2月在安阳市人民医院新生儿科住院治疗的329例新生儿为研究对象。采用高效液相色谱法和液相串联质谱法检测新生儿维生素A、D、E。结果 1)新生儿维生素A水平为(0.17±0.09) mg/L,维生素D水平为(14.21±12.05) ng/ml,维生素E水平为(6.50±3.80) mg/L。2) 足月儿与早产儿的维生素A水平,不同性别新生儿的维生素D水平,高危儿与非高危儿的维生素E水平差异均有统计学意义(P＜0.05)。不同体重组维生素A、D、E水平差异无统计学意义(P＞0.05)。3) 维生素A亚临床缺乏,维生素D及维生素E缺乏比例较高。4) 不同季节出生的新生儿维生素D水平差异有统计学意义(P＜0.05)。孕末期3个月补充维生素D剂量≥400 U/d与＜400 U/d的新生儿维生素D水平差异有统计学意义(P＜0.05)。结论 河南安阳地区住院治疗中新生儿大部分存在维生素A、D、E缺乏,是否足月、是否为高危儿可能分别与维生素A、E水平有关。不同性别、季节及孕末期补充维生素D的剂量与维生素D水平有关。     

Single high-dose vitamin D at birth corrects vitamin D deficiency in infants in Mexico

Abstract

This study examined the prevalence of vitamin D deficiency in mothers and infants in Tijuana, Mexico and determined the effect of a single oral dose of 50?000?IU vitamin D₃ at birth on 25-hydroxyvitamin D (25[OH]D) levels during infancy. Healthy infants were randomized to receive vitamin D₃ or placebo at birth. At birth 23% of infants were vitamin D deficient and 77% had vitamin D insufficiency (mean 25[OH]D level 18.9?ng/ml); 10% of mothers were vitamin D deficient and 61% were insufficient. Infants receiving vitamin D₃ had higher 25(OH)D levels at two months (N?=?29; 33.9 versus 24.2?ng/ml) and six months (N?=?21; 36.5 versus 27.4?ng/ml). Exclusively breastfed infants had lower 25(OH)D levels at two months (14.9 versus 33.4?ng/ml). Vitamin D deficiency is common in infants and mothers in Tijuana, Mexico. A single dose of vitamin D₃ at birth was safe and significantly increased 25(OH)D levels during infancy.     

肺炎支原体肺炎患儿血清维生素D水平与肺外脏器受累的相关性研究

目的 研究肺炎支原体肺炎(MPP)患儿血清维生素D水平与肺外脏器受累的相关性,为临床评估提供理论依据。方法 将榆林市第一医院2015年12月－2017年12月收治的158例MPP患儿分为肺外脏器受累组(n=56)和无肺外脏器受累组(n=102)。同时按照维生素D水平将患儿分为维生素D正常、不足和缺乏组,比较3组之间肺外脏器受累情况。结果 与无肺外脏器受累组比较,肺外脏器受累组热程较长、白细胞计数(WBC)、血沉(ESR)、C反应蛋白(CRP)、D-二聚体(D-D)水平较高,维生素E、25-羟基维生素D[25-(OH)D]水平较低,差异有统计学意义(P＜0.05);不同维生素D水平组肺外脏器受累发生率比较差异有统计学意义(P<0.05)。多元Logistic回归分析显示维生素D不足(OR＝1.955,95%CI:1.479~4.233,P=0.006)或缺乏(OR＝2.360,95%CI:1.687~8.125,P＜0.001)是肺外脏器受累的独立危险因素。受试者工作特征(ROC)曲线分析显示血清25-(OH)D水平预测肺外脏器受累的曲线下面积(AUC)为0.840,敏感性和特异性分别为81.45%和87.76%,最佳界限值为22.48 ng/ml。结论 维生素D不足或缺乏增加了MPP患儿肺外脏器受累的风险,可能是其发生的独立预测因素,临床应密切监测维生素D水平以评估患儿预后。     

Focus on vitamin D, inflammation and type 2 diabetes

The initial observations linking vitamin D to type 2 diabetes in humans came from studies showing that both healthy and diabetic subjects had a seasonal variation of glycemic control. Currently, there is evidence supporting that vitamin D status is important to regulate some pathways related to type 2 diabetes development. Since the activation of inflammatory pathways interferes with normal metabolism and disrupts proper insulin signaling, it is hypothesized that vitamin D could influence glucose homeostasis by modulating inflammatory response. Human studies investigating the impact of vitamin D supplementation on inflammatory biomarkers of subjects with or at high risk of developing type 2 diabetes are scarce and have generated conflicting results. Based on available clinical and epidemiological data, the positive effects of vitamin D seem to be primarily related to its action on insulin secretion and sensitivity and secondary to its action on inflammation. Future studies specifically designed to investigate the role of vitamin D on type 2 diabetes using inflammation as the main outcome are urgently needed in order to provide a more robust link between vitamin D, inflammation and type 2 diabetes.     

Vitamin D,Vitamin D-Binding Proteins,and VDR Polymorphisms in Individuals with Hyperglycaemia

Vitamin D reportedly plays an important role in the pathogenesis of diabetes mellitus; however, this role is unclear and debated. This study investigated the association between 25(OH) vitamin D, vitamin D-binding proteins, and vitamin D receptor (VDR) polymorphisms in healthy individuals and those with prediabetes and type 2 diabetes mellitus (T2D) from South Africa. A cross-sectional study was conducted involving subjects of mixed ancestry aged ≥20 years. Males presented with higher mean 25(OH) vitamin D levels than females, while females exhibited significantly higher serum vitamin D-binding protein levels. Significant differences in mean 25(OH) vitamin D levels were observed in normo-glycaemic, prediabetes, screen-detected DM, and known DM individuals. Vitamin D receptor SNPs Fok1 and Taq1 were not associated with glycaemic status. Fok1 was not associated with 25(OH) vitamin D deficiency, while Taq1 was associated with vitamin D insufficiency. This study showed a high prevalence of vitamin D deficiency/insufficiency in this South African population, with decreased vitamin D levels observed in hyperglycaemic individuals, which was not linked to either vitamin D-binding protein or polymorphisms in Fok1 of the VDR gene. These results may be used as a platform for further research into diagnosis and treatment of hyperglycaemia.     

Vitamin D deficiency and hyperparathyroidism in relation to ethnicity: a cross-sectional survey in healthy adults

Background  The study of vitamin D status at population level gained relevance since vitamin D deficiency was recently suggested to trigger chronic disease. Aim of the study  We aimed to describe vitamin D status, its association with bone and mineral metabolism and risk factors for deficiency in adults over 40 years in Belgium. Methods  We conducted a cross-sectional survey in a stratified random sample of 401 subjects aged between 40 and 60 years living in Brussels, and drawn from 4 different ethnic backgrounds: autochthonous Belgian, Moroccan, Turkish and Congolese. 25-Hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin, C-telopeptide and bone mineral density was measured. Results  Three-hundred and six subjects (77%) showed 25OHD concentrations below 50 nmol/l,135 (34%) below 25 nmol/l and 18 (5%) below 12.5 nmol/l. The proportion of subjects with vitamin D deficiency was four times greater amongst those of Moroccan or Turkish descent compared with those of Congolese or Belgian descent. Moroccan subjects showed a significant higher PTH and bone marker concentrations compared to Belgian. Ethnicity, season and sex were independently associated with vitamin D deficiency in multivariate analysis. Conclusion  The prevalence of vitamin D deficiency is very high amongst the adult population of Brussels but immigrants are at greater risk. Given the established link between population health and adequate vitamin D status, a policy of vitamin D supplementation should be considered in these risk groups.     

The Role of Vitamin D Supplementation in Children with Autism Spectrum Disorder: A Narrative Review

Children with autism spectrum disorder (ASD) present with persistent deficits in both social communication and interactions, along with the presence of restricted and repetitive behaviors, resulting in significant impairment in significant areas of functioning. Children with ASD consistently reported significantly lower vitamin D levels than typically developing children. Moreover, vitamin D deficiency was found to be strongly correlated with ASD severity. Theoretically, vitamin D can affect neurodevelopment in children with ASD through its anti-inflammatory properties, stimulating the production of neurotrophins, decreasing the risk of seizures, and regulating glutathione and serotonin levels. A Title/Abstract specific search for publications on Vitamin D supplementation trials up to June 2021 was performed using two databases: PubMed and Cochrane Library. Twelve experimental studies were included in the synthesis of this review. Children with ASD reported a high prevalence of vitamin D deficiency or insufficiency. In general, it was observed that improved vitamin D status significantly reduced the ASD severity, however, this effect was not consistently different between the treatment and control groups. The variations in vitamin D dose protocols and the presence of concurrent interventions might provide an explanation for the variability of results. The age of the child for introducing vitamin D intervention was identified as a possible factor determining the effectiveness of the treatment. Common limitations included a small number of participants and a short duration of follow-ups in the selected studies. Long-term, well-designed randomized controlled trials are warranted to confirm the effect of vitamin D on severity in children with ASD.     

Novel Intracellular Proteins Associated with Cellular Vitamin D Action

Work with vitamin D–resistant New World primates has revealed novel cellular proteins involved in vitamin D action. An "intracellular vitamin D–binding protein" functions to bind vitamin D metabolites in the cell and enhances vitamin D action. By contrast, a "vitamin D response element–binding protein" inhibits vitamin D receptor binding to the DNA and is responsible for vitamin D resistance in New World primates.