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1.
Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 µg) of Vitamin D for Adults in the General Population.
Pludowski, P, Grant, WB, Karras, SN, Zittermann, A, Pilz, S
Nutrients. 2024;(3)
Abstract
Vitamin D deficiency is considered a public health problem due to its worldwide high prevalence and adverse clinical consequences regarding musculoskeletal health. In addition, vitamin D may also be crucial for the prevention of certain extraskeletal diseases. Despite decades of intensive scientific research, several knowledge gaps remain regarding the precise definition of vitamin D deficiency and sufficiency, the health benefits of improving vitamin D status, and the required vitamin D intakes. Consequently, various societies and expert groups have released heterogeneous recommendations on the dosages for vitamin D supplementation. In this brief narrative review, we outline and discuss recent advances regarding the scientific evidence arguing for a daily vitamin D supplementation with 2000 international units (IU) (50 µg) of vitamin D3 to prevent and treat vitamin D deficiency. According to data from randomized controlled trials (RCTs), such a dose may improve some health outcomes and is sufficient to raise and maintain serum 25(OH)D concentrations above 50 nmol/L (20 ng/mL) and above 75 nmol/L (30 ng/mL) in >99% and >90% of the general adult population, respectively. According to large vitamin D RCTs, there are no significant safety concerns in supplementing such a dose for several years, even in individuals with an already sufficient vitamin D status at baseline. A daily vitamin D supplementation with 2000 IU (50 µg) may be considered a simple, effective, and safe dosage to prevent and treat vitamin D deficiency in the adult general population.
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Can vitamin D be an adjuvant therapy for juvenile rheumatic diseases?
Stawicki, MK, Abramowicz, P, Sokolowska, G, Wołejszo, S, Grant, WB, Konstantynowicz, J
Rheumatology international. 2023;(11):1993-2009
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Abstract
Vitamin D, known for its essential role in calcium and bone homeostasis, has multiple effects beyond the skeleton, including regulation of immunity and modulation of autoimmune processes. Several reports have shown suboptimal serum 25 hydroxyvitamin D [25(OH)D] levels in people with different inflammatory and autoimmune rheumatic conditions, and an association between 25(OH)D levels, disease activity and outcomes. Although most available data pertain to adults, insights often are extended to children. Juvenile rheumatic diseases (JRDs) are a significant health problem during growth because of their complex pathogenesis, chronic nature, multisystemic involvement, and long-term consequences. So far, there is no definitive or clear evidence to confirm the preventive or therapeutic effect of vitamin D supplementation in JRDs, because results from randomized controlled trials (RCTs) have produced inconsistent outcomes. This review aims to explore and discuss the potential role of vitamin D in treating selected JRDs. Medline/PubMed, EMBASE, and Scopus were comprehensively searched in June 2023 for any study on vitamin D supplementary role in treating the most common JRDs. We used the following keywords: "vitamin D" combined with the terms "juvenile idiopathic arthritis", "juvenile systemic scleroderma", "juvenile systemic lupus erythematosus", "juvenile inflammatory myopathies", "Behcet disease", "periodic fever syndromes" and "juvenile rheumatic diseases". Observational studies have found that serum 25(OH)D concentrations are lower in juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile systemic scleroderma, Behcet disease and proinflammatory cytokine concentrations are higher. This suggests that vitamin D supplementation might be beneficial, however, current data are insufficient to confirm definitively the complementary role of vitamin D in the treatment of JRDs. Considering the high prevalence of vitamin D deficiency worldwide, children and adolescents should be encouraged to supplement vitamin D according to current recommendations. More interventional studies, especially well-designed RCTs, assessing the dose-response effect and adjuvant effect in specific diseases, are needed to determine the potential significance of vitamin D in JRDs treatment.
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Evidence That Increasing Serum 25(OH)D Concentrations to 30 ng/mL in the Kingdom of Saudi Arabia and the United Arab Emirates Could Greatly Improve Health Outcomes.
Grant, WB, Al Anouti, F, Boucher, BJ, Fakhoury, HMA, Moukayed, M, Pilz, S, Al-Daghri, NM
Biomedicines. 2023;(4)
Abstract
Accumulating evidence supports the potential protective effects of vitamin D against chronic diseases such as Alzheimer's disease, autoimmune diseases, cancers, cardiovascular disease (ischaemic heart disease and stroke), type 2 diabetes, hypertension, chronic kidney disease, stroke, and infectious diseases such as acute respiratory tract diseases, COVID-19, influenza, and pneumonia, as well as adverse pregnancy outcomes. The respective evidence is based on ecological and observational studies, randomized controlled trials, mechanistic studies, and Mendelian randomization studies. However, randomized controlled trials on vitamin D supplementation have largely failed to show benefits, probably due to poor design and analysis. In this work, we aim to use the best available evidence on the potential beneficial effects of vitamin D to estimate the expected reduction in incidence and mortality rates of vitamin D-related diseases in the Kingdom of Saudi Arabia and the United Arab Emirates if minimum serum 25(OH)D concentrations were to be raised to 30 ng/mL. Estimated reductions by 25% for myocardial infarction incidence, 35% for stroke incidence, 20 to 35% for cardiovascular disease mortality, and 35% for cancer mortality rates depicted a promising potential for raising serum 25(OH)D. Methods to increase serum 25(OH)D concentrations at the population level could include food fortification with vitamin D3, vitamin D supplementation, improved dietary vitamin D intake, and sensible sun exposure.
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Immunomodulatory Properties of Vitamin D in the Intestinal and Respiratory Systems.
Hamza, FN, Daher, S, Fakhoury, HMA, Grant, WB, Kvietys, PR, Al-Kattan, K
Nutrients. 2023;(7)
Abstract
Vitamin D plays a crucial role in modulating the innate immune response by interacting with its intracellular receptor, VDR. In this review, we address vitamin D/VDR signaling and how it contributes to the regulation of intestinal and respiratory microbiota. We additionally review some components of the innate immune system, such as the barrier function of the pulmonary and intestinal epithelial membranes and secretion of mucus, with their respective modulation by vitamin D. We also explore the mechanisms by which this vitamin D/VDR signaling mounts an antimicrobial response through the transduction of microbial signals and the production of antimicrobial peptides that constitute one of the body's first lines of defense against pathogens. Additionally, we highlight the role of vitamin D in clinical diseases, namely inflammatory bowel disease and acute respiratory distress syndrome, where excessive inflammatory responses and dysbiosis are hallmarks. Increasing evidence suggests that vitamin D supplementation may have potentially beneficial effects on those diseases.
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Periodontal Disease and Other Adverse Health Outcomes Share Risk Factors, including Dietary Factors and Vitamin D Status.
Grant, WB, van Amerongen, BM, Boucher, BJ
Nutrients. 2023;(12)
Abstract
For nearly a century, researchers have associated periodontal disease (PD) with risks of other adverse health outcomes such as cardiovascular disease, diabetes mellitus, and respiratory diseases, as well as adverse pregnancy outcomes. Those findings have led to the hypothesis that PD causes those adverse health outcomes either by increasing systemic inflammation or by the action of periodontopathic bacteria. However, experiments largely failed to support that hypothesis. Instead, the association is casual, not causal, and is due to shared underlying modifiable risk factors, including smoking, diet, obesity, low levels of physical activity, and low vitamin D status. Diabetes mellitus is also considered a risk factor for PD, whereas red and processed meat are the most important dietary risk factors for diabetes. Because PD generally develops before other adverse health outcomes, a diagnosis of PD can alert patients that they could reduce the risk of adverse health outcomes with lifestyle changes. In addition, type 2 diabetes mellitus can often be reversed rapidly by adopting an anti-inflammatory, nonhyperinsulinemic diet that emphasizes healthful, whole plant-based foods. This review describes the evidence that proinflammatory and prohyperinsulinemia diets and low vitamin D status are important risk factors for PD and other adverse health outcomes. We also make recommendations regarding dietary patterns, food groups, and serum 25-hydroxyvitamin D concentrations. Oral health professionals should routinely inform patients with PD that they could reduce their risk of severe PD as well as the risks of many other adverse health outcomes by making appropriate lifestyle changes.
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An Appraisal to Address Health Consequences of Vitamin D Deficiency With Food Fortification and Supplements: Time to Act!
Reichrath, J, März, W, DE Gruijl, FR, Vieth, R, Grant, WB, Slominski, AT, Holick, MF, Vogt, T, Pilz, S
Anticancer research. 2022;(10):5009-5015
Abstract
A symposium entitled "Vitamin D in Prevention and Therapy" was held on May 4-5, 2022, in Homburg, Germany to discuss important new advances in the field, including identification of new vitamin D signaling pathways, of new biologic effects of vitamin D-compounds (e.g., on the microbiome), and convincing proof of the relevance of vitamin D deficiency for the risk and outcome of many chronic diseases, including cancer, cardio-vascular, auto-immune, metabolic, and infectious diseases. Concerning the COVID-19-pandemic, an inverse association between 25(OH)D serum concentrations and SARS-CoV-2-infections, morbidity, and mortality was shown. In relation to cancer, several meta-analyses recently demonstrated an association of vitamin D-supplementation with significantly decreased mortality rates, which presumably would reduce health care costs. Considering the impressive body of evidence and the high safety of oral supplementation and food fortification with vitamin D, it was concluded that there is now an urgent need to act. In many countries worldwide, health care authorities need to increase efforts to address vitamin D deficiency, e.g., via food fortification and/or supplementation with vitamin D, and/or promoting moderate UV-exposure. It was estimated that in many countries, vitamin D intakes of the order of appr. 1,000 IE (25 μg)/day would be needed to bring and/or keep the vast majority of people over a serum 25(OH)D threshold of 20 ng/ml (50 nmol/l), which would be difficult to obtain alone from food fortification. New developments in personalized medicine may represent helpful tools to identify populations at risk for vitamin D deficiency and their responsiveness to vitamin D treatment.
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Dietary Recommendations for Post-COVID-19 Syndrome.
Barrea, L, Grant, WB, Frias-Toral, E, Vetrani, C, Verde, L, de Alteriis, G, Docimo, A, Savastano, S, Colao, A, Muscogiuri, G
Nutrients. 2022;(6)
Abstract
At the beginning of the coronavirus disease (COVID-19) pandemic, global efforts focused on containing the spread of the virus and avoiding contagion. Currently, it is evident that health professionals should deal with the overall health status of COVID-19 survivors. Indeed, novel findings have identified post-COVID-19 syndrome, which is characterized by malnutrition, loss of fat-free mass, and low-grade inflammation. In addition, the recovery might be complicated by persistent functional impairment (i.e., fatigue and muscle weakness, dysphagia, appetite loss, and taste/smell alterations) as well as psychological distress. Therefore, the appropriate evaluation of nutritional status (assessment of dietary intake, anthropometrics, and body composition) is one of the pillars in the management of these patients. On the other hand, personalized dietary recommendations represent the best strategy to ensure recovery. Therefore, this review aimed to collect available evidence on the role of nutrients and their supplementation in post-COVID-19 syndrome to provide a practical guideline to nutritionists to tailor dietary interventions for patients recovering from COVID-19 infections.
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A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health.
Grant, WB, Al Anouti, F, Boucher, BJ, Dursun, E, Gezen-Ak, D, Jude, EB, Karonova, T, Pludowski, P
Nutrients. 2022;(3)
Abstract
Vitamin D3 has many important health benefits. Unfortunately, these benefits are not widely known among health care personnel and the general public. As a result, most of the world's population has serum 25-hydroxyvitamin D (25(OH)D) concentrations far below optimal values. This narrative review examines the evidence for the major causes of death including cardiovascular disease, hypertension, cancer, type 2 diabetes mellitus, and COVID-19 with regard to sub-optimal 25(OH)D concentrations. Evidence for the beneficial effects comes from a variety of approaches including ecological and observational studies, studies of mechanisms, and Mendelian randomization studies. Although randomized controlled trials (RCTs) are generally considered the strongest form of evidence for pharmaceutical drugs, the study designs and the conduct of RCTs performed for vitamin D have mostly been flawed for the following reasons: they have been based on vitamin D dose rather than on baseline and achieved 25(OH)D concentrations; they have involved participants with 25(OH)D concentrations above the population mean; they have given low vitamin D doses; and they have permitted other sources of vitamin D. Thus, the strongest evidence generally comes from the other types of studies. The general finding is that optimal 25(OH)D concentrations to support health and wellbeing are above 30 ng/mL (75 nmol/L) for cardiovascular disease and all-cause mortality rate, whereas the thresholds for several other outcomes appear to range up to 40 or 50 ng/mL. The most efficient way to achieve these concentrations is through vitamin D supplementation. Although additional studies are warranted, raising serum 25(OH)D concentrations to optimal concentrations will result in a significant reduction in preventable illness and death.
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Vitamin D-Related Risk Factors for Maternal Morbidity during Pregnancy: A Systematic Review.
Suárez-Varela, MM, Uçar, N, Peraita-Costa, I, Huertas, MF, Soriano, JM, Llopis-Morales, A, Grant, WB
Nutrients. 2022;(15)
Abstract
Vitamin D has well-defined classical functions related to metabolism and bone health but also has non-classical effects that may influence pregnancy. Maternal morbidity remains a significant health care concern worldwide, despite efforts to improve maternal health. Nutritional deficiencies of vitamin D during pregnancy are related to adverse pregnancy outcomes, but the evidence base is difficult to navigate. The primary purpose of this review is to map the evidence on the effects of deficiencies of vitamin D on pregnancy outcome and the dosage used in such studies. A systematic search was performed for studies on vitamin D status during pregnancy and maternal outcomes. A total of 50 studies came from PubMed, 15 studies came from Cochrane, and 150 studies came from Embase, for a total of 215 articles. After screening, 34 were identified as candidate studies for inclusion. Finally, 28 articles met the inclusion criteria, which originated from 15 countries. The studies included 14 original research studies and 13 review studies conducted between 2012 and 2021. This review was finally limited to the 14 original studies. This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and the quality and strength of the evidence was evaluated using the Navigation Guide Systematic Review Methodology (SING). We found evidence that supports the idea that supplementary vitamin D for pregnant women is important for reducing the risk of gestational diabetes, hypertension, preeclampsia, early labor, and other complications. The data retrieved from this review are consistent with the hypothesis that adequate vitamin D levels might contribute to a healthy pregnancy.
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The emerging evidence for non-skeletal health benefits of vitamin D supplementation in adults.
Grant, WB, Boucher, BJ, Pludowski, P, Wimalawansa, SJ
Nature reviews. Endocrinology. 2022;(5):323