Special Issue "Vitamin D in the New Decade: Facts, Controversies, and Future Perspectives for Daily Clinical Practice"

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (1 January 2021).

Special Issue Editors

Dr. Spyridon N. Karras
Website
Guest Editor
Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 55535 Thessaloniki, Greece
Interests: intermittent fasting; periodic fasting; religious fasting: fasting glucose; obesity; impaired fasting glucose; non-fasting triglycerides; fasting blood glucose; caloric restriction; meal frequency; calorie restriction
Special Issues and Collections in MDPI journals
Dr. Pawel Pludowski
Website
Guest Editor
Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children's Memorial Health Institute, Warsaw, Poland.
Interests: Vitamin D (reproduction, epidemiology, cardiovascular, musculoskeletal); idiopathic infantile hypercalcemia; LC-MS/MS

Special Issue Information

Dear colleagues,

Vitamin D has been the focus of tremendous ongoing scientific research during the past two decades. Its primogenetic undisputed role in bone mineralization has been expanded to a strikingly disparate amalgamation of transparent scientific cases and observational studies, randomized controlled trials of doubtful design, and sporadically personal aphorisms and dogma. This phenomenon configures a burgeoning scientific field in which substantial controversy is inevitably reflected in daily clinical practice resulting in a precarious interpretation of not necessarily available results, lifestyle-affected vitamin D supplementation in vitamin D sufficient populations, and ineffective dosing and time regimens.

In this context, somewhere in between the dipole of inordinate enthusiasm and critical opposition, the vast majority of healthcare providers worldwide, involved in some part of the developed vitamin D daily agenda, postulate a sound individualized scientific approach unbiased from quandaries, oriented to improve long term health outcomes and patient quality of life, beyond the platonic caves of available knowledge in the field.

This Special Issue will draw attention to all intriguing and conflicting aspects of vitamin D research, including the following: Vitamin D deficiency and its widespread epidemiology, musculoskeletal, and extra-skeletal effects, critical updates on published vitamin D supplementation prevention RCTs (cancer/ CVD), with a discourse on the future agenda with the main questions: What has changed so far in the field? What are the future research milestones? In collecting the available results reported here, the editors have not endeavored to achieve any sort of completeness, but rather to shed light on the ongoing controversy of the vitamin D “friendly” perspective versus vitamin D skepticism, with a discourse on clinical implications and physicians’ daily decision making, into the beginning of the new decade.

Dr. Spyridon N. Karras
Dr. Pawel Pludowski
Guest Editors

Manuscript Submission Information

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Keywords

  • Vitamin D
  • Nutrition
  • Infections
  • Epidemiology
  • Cardiovascular disease
  • Osteomalacia
  • Fasting
  • acute infections
  • chronic metabolic diseases
  • nutrition

Published Papers (22 papers)

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Research

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Open AccessArticle
Exploring the Impact of Individual UVB Radiation Levels on Serum 25-Hydroxyvitamin D in Women Living in High Versus Low Latitudes: A Cross-Sectional Analysis from the D-SOL Study
Nutrients 2020, 12(12), 3805; https://doi.org/10.3390/nu12123805 - 11 Dec 2020
Abstract
Vitamin D can be synthesized in the skin via sunlight exposure as well as ingested through diet. Vitamin D deficiency is currently a major global public health issue, with increasing prevalence in both low and high latitude locations. This cross-sectional analysis aimed to [...] Read more.
Vitamin D can be synthesized in the skin via sunlight exposure as well as ingested through diet. Vitamin D deficiency is currently a major global public health issue, with increasing prevalence in both low and high latitude locations. This cross-sectional analysis aimed to compare the intensity of individual Ultraviolet B radiation levels between women of the same ethnicity living in England and Brazil, respectively; and to investigate the association with circulating 25(OH)D concentrations. We analysed data from 135 Brazilian women (England, n = 56, 51° N; Brazil, n = 79, 16° S) recruited for the D-SOL study (Interaction between Vitamin D Supplementation and Sunlight Exposure in Women Living in Opposite Latitudes). Serum 25(OH)D concentrations were analysed by high performance liquid chromatography tandem mass spectrometry (HPLC-MS), individual UVB radiation via UVB dosimeter badges and dietary intake via 4-day diet diaries. Anthropometric, skin phototype, sociodemographic and lifestyle patterns were also assessed. Mean serum 25(OH)D concentration of England residents was significantly lower than Brazil residents. Daily individual UVB radiation level showed a strong significant positive correlation with serum 25(OH)D concentrations. The required UVB radiation to achieve 75 nmol/L was 2.2 SED and 38.8% of the total variance in 25(OH)D concentrations was explained uniquely by daily individual UVB radiation, after controlling for the influence of age and body mass index. Thus, these results highlight the strong positive association between serum 25(OH)D concentrations and individual UVB radiation and the influence of different individual characteristics and behaviours. Collectively, these factors contribute to meaningful, country-specific, public health strategies and policies for the efficient prevention and treatment of vitamin D inadequacy. Full article
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Open AccessArticle
Ultra-Marathon-Induced Increase in Serum Levels of Vitamin D Metabolites: A Double-Blind Randomized Controlled Trial
Nutrients 2020, 12(12), 3629; https://doi.org/10.3390/nu12123629 - 25 Nov 2020
Cited by 1
Abstract
Purpose: While an increasing number of studies demonstrate the importance of vitamin D for athletic performance, the effects of any type of exercise on vitamin D metabolism are poorly characterized. We aimed to identify the responses of some vitamin D metabolites to ultra-marathon [...] Read more.
Purpose: While an increasing number of studies demonstrate the importance of vitamin D for athletic performance, the effects of any type of exercise on vitamin D metabolism are poorly characterized. We aimed to identify the responses of some vitamin D metabolites to ultra-marathon runs. Methods: A repeated-measures design was implemented, in which 27 amateur runners were assigned into two groups: those who received a single dose of vitamin D3 (150,000 IU) 24 h before the start of the marathon (n = 13) and those (n = 14) who received a placebo. Blood samples were collected 24 h before, immediately after, and 24 h after the run. Results: In both groups of runners, serum 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 levels significantly increased by 83%, 63%, and 182% after the ultra-marathon, respectively. The increase was most pronounced in the vitamin D group. Body mass and fat mass significantly decreased after the run in both groups. Conclusions: Ultra-marathon induces the mobilization of vitamin D into the blood. Furthermore, the 24,25(OH)2D3 and 3-epi-25(OH)D3 increases imply that the exercise stimulates vitamin D metabolism. Full article
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Open AccessArticle
Improving Glucose Homeostasis after Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism with Co-Existing Prediabetes
Nutrients 2020, 12(11), 3522; https://doi.org/10.3390/nu12113522 - 16 Nov 2020
Abstract
We have previously described increased fasting plasma glucose levels in patients with normocalcemic primary hyperparathyroidism (NPHPT) and co-existing prediabetes, compared to prediabetes per se. This study evaluated the effect of parathyroidectomy (PTx) (Group A), versus conservative follow-up (Group B), in a small cohort [...] Read more.
We have previously described increased fasting plasma glucose levels in patients with normocalcemic primary hyperparathyroidism (NPHPT) and co-existing prediabetes, compared to prediabetes per se. This study evaluated the effect of parathyroidectomy (PTx) (Group A), versus conservative follow-up (Group B), in a small cohort of patients with co-existing NPHPT and prediabetes. Sixteen patients were categorized in each group. Glycemic parameters (levels of fasting glucose (fGlu), glycosylated hemoglobin (HbA1c), and fasting insulin (fIns)), the homeostasis model assessment for estimating insulin secretion (HOMA-B) and resistance (HOMA-IR), and a 75-g oral glucose tolerance test were evaluated at baseline and after 32 weeks for both groups. Measurements at baseline were not significantly different between Groups A and B, respectively: fGlu (119.4 ± 2.8 vs. 118.2 ± 1.8 mg/dL, p = 0.451), HbA1c (5.84 ± 0.3 %vs. 5.86 ± 0.4%, p = 0.411), HOMA-IR (3.1 ± 1.2 vs. 2.9 ± 0.2, p = 0.213), HOMA-B (112.9 ± 31.8 vs. 116.9 ± 21.0%, p = 0.312), fIns (11.0 ± 2.3 vs. 12.8 ± 1.4 μIU/mL, p = 0.731), and 2-h post-load glucose concentrations (163.2 ± 3.2 vs. 167.2 ± 3.2 mg/dL, p = 0.371). fGlu levels demonstrated a positive correlation with PTH concentrations for both groups (Group A, rho = 0.374, p = 0.005, and Group B, rho = 0.359, p = 0.008). At the end of follow-up, Group A demonstrated significant improvements after PTx compared to the baseline: fGlu ((119.4 ± 2.8 vs. 111.2 ± 1.9 mg/dL, p = 0.021) (−8.2 ± 0.6 mg/dL)), and 2-h post-load glucose concentrations ((163.2 ± 3.2 vs. 144.4 ± 3.2 mg/dL, p = 0.041), (−18.8 ± 0.3 mg/dL)). For Group B, results demonstrated non-significant differences: fGlu ((118.2 ± 1.8 vs. 117.6 ± 2.3 mg/dL, p = 0.031), (−0.6 ± 0.2 mg/dL)), and 2-h post-load glucose concentrations ((167.2 ± 2.7 vs. 176.2 ± 3.2 mg/dL, p = 0.781), (+9.0 ± 0.8 mg/dL)). We conclude that PTx for individuals with NPHPT and prediabetes may improve their glucose homeostasis when compared with conservative follow-up, after 8 months of follow-up. Full article
Open AccessArticle
Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study
Nutrients 2020, 12(11), 3377; https://doi.org/10.3390/nu12113377 - 02 Nov 2020
Cited by 7
Abstract
Background. The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. Methods. Seventy-seven patients consecutively [...] Read more.
Background. The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. Methods. Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2). The comparator group involved participants having received no vitamin D supplements (Group 3). Outcomes were 14-day mortality and highest (worst) score on the ordinal scale for clinical improvement (OSCI) measured during COVID-19 acute phase. Potential confounders were age, gender, functional abilities, undernutrition, cancer, hypertension, cardiomyopathy, glycated hemoglobin, number of acute health issues at admission, hospital use of antibiotics, corticosteroids, and pharmacological treatments of respiratory disorders. Results. The three groups (n = 77; mean ± SD, 88 ± 5 years; 49% women) were similar at baseline (except for woman proportion, p = 0.02), as were the treatments used for COVID-19. In Group 1 (n = 29), 93.1% of COVID-19 participants survived at day 14, compared to 81.2% survivors in Group 2 (n = 16) (p = 0.33) and 68.7% survivors in Group 3 (n = 32) (p = 0.02). While considering Group 3 as reference (hazard ratio (HR) = 1), the fully-adjusted HR for 14-day mortality was HR = 0.07 (p = 0.017) for Group 1 and HR = 0.37 (p = 0.28) for Group 2. Group 1 had longer survival time than Group 3 (log-rank p = 0.015), although there was no difference between Groups 2 and 3 (log-rank p = 0.32). Group 1, but not Group 2 (p = 0.40), was associated with lower risk of OSCI score ≥5 compared to Group 3 (odds ratio = 0.08, p = 0.03). Conclusions. Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly. Full article
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Open AccessFeature PaperArticle
Associations of Vitamin D Deficiency, Parathyroid hormone, Calcium, and Phosphorus with Perinatal Adverse Outcomes. A Prospective Cohort Study
Nutrients 2020, 12(11), 3279; https://doi.org/10.3390/nu12113279 - 26 Oct 2020
Abstract
Vitamin D deficiency during pregnancy has been linked to perinatal adverse outcomes. Studies conducted to date have recommended assessing interactions with other vitamin D-related metabolites to clarify this subject. We aimed to evaluate the association of vitamin D deficiency during early pregnancy with [...] Read more.
Vitamin D deficiency during pregnancy has been linked to perinatal adverse outcomes. Studies conducted to date have recommended assessing interactions with other vitamin D-related metabolites to clarify this subject. We aimed to evaluate the association of vitamin D deficiency during early pregnancy with preterm birth. Secondary outcomes included low birth weight and small for gestational age. Additionally, we explored the role that parathyroid hormone, calcium and phosphorus could play in the associations. We conducted a prospective cohort study comprising 289 pregnant women in a hospital in Granada, Spain. Participants were followed-up from weeks 10–12 of gestation to postpartum. Serum 25-hydroxyvitamin D, parathyroid hormone, calcium, and phosphorus were measured within the first week after recruitment. Pearson’s χ2 test, Mann–Whitney U test, binary and multivariable logistic regression models were used to explore associations between variables and outcomes. 36.3% of the participants were vitamin D deficient (<20 ng/mL). 25-hydroxyvitamin D concentration was inversely correlated with parathyroid hormone (ρ = −0.146, p = 0.013). Preterm birth was associated with vitamin D deficiency in the multivariable model, being this association stronger amongst women with parathyroid hormone serum levels above the 80th percentile (adjusted odds ratio (aOR) = 6.587, 95% CI (2.049, 21.176), p = 0.002). Calcium and phosphorus were not associated with any studied outcome. Combined measurement of 25-hydroxyvitamin D and parathyroid hormone could be a better estimator of preterm birth than vitamin D in isolation. Full article
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Open AccessArticle
Vitamin D Correction Down-Regulates Serum Amyloid P Component Levels in Vitamin D Deficient Arab Adults: A Single-Arm Trial
Nutrients 2020, 12(9), 2880; https://doi.org/10.3390/nu12092880 - 21 Sep 2020
Abstract
Vitamin D (VD) has been observed to have anti-inflammatory properties. However, the effects of VD supplementation on the serum amyloid P component (SAP) has not been established. This study aimed to investigate the effect of VD supplementation on serum SAP levels in Arab [...] Read more.
Vitamin D (VD) has been observed to have anti-inflammatory properties. However, the effects of VD supplementation on the serum amyloid P component (SAP) has not been established. This study aimed to investigate the effect of VD supplementation on serum SAP levels in Arab adults. A total of 155 VD-deficient adult Saudis (56 males and 99 females) were recruited in this non-randomized, 6-month, single-arm trial. The intervention was as follows; cholecalciferol 50,000 international units (IU) every week for the first 2 months, followed by 50,000 twice a month for the next two months, and for the last two months, 1000 IU daily. Serum 25(OH)D, SAP, C-reactive protein (CRP), lipid profile, and glucose were assessed at baseline and post-intervention. At post-intervention, VD levels were significantly increased, while SAP levels significantly decreased in all study participants. Remarkably, this reduction in SAP was more significant in males than females after stratification. SAP was inversely correlated with VD overall (r = −0.17, p < 0.05), and only in males (r = −0.27, p < 0.05) after stratification according to sex after 6 months of VD supplementation. Such a relationship was not observed at baseline. VD supplementation can favorably modulate serum SAP concentrations in Arab adults, particularly in males. Full article
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Open AccessArticle
25-Hydroxycholecalciferol Concentration Is Associated with Protein Loss and Serum Albumin Level during the Acute Phase of Burn Injury
Nutrients 2020, 12(9), 2780; https://doi.org/10.3390/nu12092780 - 11 Sep 2020
Abstract
Background: Burned patients have an increased need for vitamin D supply related to the maintenance of calcium–phosphate homeostasis and the regulation of cell proliferation/differentiation. This study aimed to analyze the concentration of 25-hydroxycholecalciferol and its relationship with severe condition after burn injury. Methods: [...] Read more.
Background: Burned patients have an increased need for vitamin D supply related to the maintenance of calcium–phosphate homeostasis and the regulation of cell proliferation/differentiation. This study aimed to analyze the concentration of 25-hydroxycholecalciferol and its relationship with severe condition after burn injury. Methods: 126 patients were enrolled in the study. Patients were qualified due to thermal burns—over 10% of total body surface area. On the day of admission, the following parameters were assessed: 25-hydroxycholecalciferol concentration, total protein concentration, albumin concentration, aspartate transaminase activity, alanine transaminase activity, albumin concentration, creatinine concentration, c-reactive protein concentration, procalcitonin concentration, and interleukin-6 concentration. Results: Almost all patients (92%) in the study group had an improper level of vitamin D (<30 ng/mL), with the average of 11.6 ± 10.7 ng/mL; 17.5% of patients had levels of vitamin D below the limit of determination—under 3 ng/mL. The study showed that there are several factors which correlated with vitamin D concentration during the acute phase of burn injury, including: total protein (r = 0.42, p < 0.01), albumin, (r = 0.62, p < 0.01), percentage of body burns (r = 0.36, p < 0.05), aspartate aminotransferase (r = 0.21, p < 0.05), and c-reactive protein (r = 0.22, p < 0.05). We did not find any significant correlation between vitamin D concentration and body mass index. Conclusions: The burn injury has an enormous impact on the metabolism and the risk factors of the deficiency for the general population (BMI) have an effect on burned patients. Our study showed that concentration of 25-hydroxycholecalciferol is strongly correlated with serum albumin level, even more than total burn surface area and burn degrees as expected. We suspect that increased supplementation of vitamin D should be based on albumin level and last until albumin levels are balanced. Full article
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Open AccessArticle
Association of Vitamin D Status with Lower Limb Muscle Strength in Professional Basketball Players: A Cross-Sectional Study
Nutrients 2020, 12(9), 2715; https://doi.org/10.3390/nu12092715 - 05 Sep 2020
Abstract
Vitamin D deficiency in athletes may play a role in influencing fracture risk and athletic performance. This study aimed to examine the vitamin D status of basketball players and determine its correlation with muscle strength. We included 36 male professional basketball players (mean [...] Read more.
Vitamin D deficiency in athletes may play a role in influencing fracture risk and athletic performance. This study aimed to examine the vitamin D status of basketball players and determine its correlation with muscle strength. We included 36 male professional basketball players (mean age, 22.6 ± 3.2 years) categorized by vitamin D status. We examined the muscle strength of knee extension/flexion and ankle dorsiflexion/plantarflexion using an isokinetic dynamometer. Eleven (30.5%), fifteen (41.7%), and ten (27.8%) players had deficient (<20 ng/mL), insufficient (20–32 ng/mL), and sufficient vitamin D levels (>32 ng/mL), respectively. In the dominant side, there were no significant correlations of vitamin D level with knee extension/flexion strength (r = 0.134, p = 0.436; r = −0.017, p = 0.922, respectively), or with plantarflexion/dorsiflexion ankle strength (r = −0.143, p = 0.404; r = 1.109, p = 0.527, respectively). Moreover, the isokinetic lower limb strengths were not significantly different between the three groups in all settings (all p > 0.05). In conclusion, professional basketball players had a high prevalence of vitamin D insufficiency. Though it may not be associated with muscle strength, maintaining adequate vitamin D levels by micronutrients monitoring, regular dietician consultation, and supplementation is still a critically considerable strategy to enhance young athletes’ health. Full article
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Open AccessArticle
Vitamin D Doses from Solar Ultraviolet and Dietary Intakes in Patients with Depression: Results of a Case-Control Study
Nutrients 2020, 12(9), 2587; https://doi.org/10.3390/nu12092587 - 26 Aug 2020
Abstract
The purpose of this study to estimate cumulative vitamin D doses from solar ultraviolet and dietary intakes in patients with depression and compare it to healthy controls. Using a case-control research design, a sample of 96 patients with depression were age- and sex-matched [...] Read more.
The purpose of this study to estimate cumulative vitamin D doses from solar ultraviolet and dietary intakes in patients with depression and compare it to healthy controls. Using a case-control research design, a sample of 96 patients with depression were age- and sex-matched with 96 healthy controls. Dietary vitamin D dose was estimated from diet analysis. Vitamin D-weighted ultraviolet solar doses were estimated from action spectrum conversion factors and geometric conversion factors accounting for the skin type, the fraction of body exposed, and age factor. Patients with depression had a lower dose of vitamin D (IU) per day with 234, 153, and 81 per day from all sources, sunlight exposure, and dietary intake, respectively. Controls had a higher intake of vitamin D (IU) per day with 357, 270, and 87 per day from all sources, sunlight exposure, and dietary intake, respectively. Only 19% and 30% met the minimum daily recommended dose of ≥400 IU per day for cases and controls, respectively. The sensitivity, specificity, percentage correctly classified and receiver operating characteristic (ROC) Area for the estimated vitamin D against serum vitamin D as reference were 100%, 79%, 80%, and 89%. Physical activity level was the only predictor of daily vitamin D dose. Vitamin D doses are lower than the recommended dose of ≥400 IU (10 mcg) per day for both cases with depression and healthy controls, being much lower in the former. Full article
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Open AccessArticle
High-Dose Vitamin D Supplementation Improves Microcirculation and Reduces Inflammation in Diabetic Neuropathy Patients
Nutrients 2020, 12(9), 2518; https://doi.org/10.3390/nu12092518 - 20 Aug 2020
Cited by 2
Abstract
We assessed the effect of different doses of vitamin D supplementation on microcirculation, signs and symptoms of peripheral neuropathy and inflammatory markers in patients with type 2 diabetes (T2DM). Sixty-seven patients with T2DM and peripheral neuropathy (34 females) were randomized into two treatment [...] Read more.
We assessed the effect of different doses of vitamin D supplementation on microcirculation, signs and symptoms of peripheral neuropathy and inflammatory markers in patients with type 2 diabetes (T2DM). Sixty-seven patients with T2DM and peripheral neuropathy (34 females) were randomized into two treatment groups: Cholecalciferol 5000 IU and 40,000 IU once/week orally for 24 weeks. Severity of neuropathy (NSS, NDS scores, visual analogue scale), cutaneous microcirculation (MC) parameters and inflammatory markers (ILs, CRP, TNFα) were assessed before and after treatment. Vitamin D deficiency/insufficiency was detected in 78% of the 62 completed subjects. Following treatment with cholecalciferol 40,000 IU/week, a significant decrease in neuropathy severity (NSS, p = 0.001; NDS, p = 0.001; VAS, p = 0.001) and improvement of cutaneous MC were observed (p < 0.05). Also, we found a decrease in IL-6 level (2.5 pg/mL vs. 0.6 pg/mL, p < 0.001) and an increase in IL-10 level (2.5 pg/mL vs. 4.5 pg/mL, p < 0.001) after 24 weeks of vitamin D supplementation in this group. No changes were detected in the cholecalciferol 5000 IU/week group. High-dose cholecalciferol supplementation of 40,000 IU/week for 24 weeks was associated with improvement in clinical manifestation, cutaneous microcirculation and inflammatory markers in patients with T2DM and peripheral neuropathy. Full article
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Open AccessArticle
Circulating Levels of Muscle-Related Metabolites Increase in Response to a Daily Moderately High Dose of a Vitamin D3 Supplement in Women with Vitamin D Insufficiency—Secondary Analysis of a Randomized Placebo-Controlled Trial
Nutrients 2020, 12(5), 1310; https://doi.org/10.3390/nu12051310 - 04 May 2020
Abstract
Recently, we demonstrated negative effects of vitamin D supplementation on muscle strength and physical performance in women with vitamin D insufficiency. The underlying mechanism behind these findings remains unknown. In a secondary analysis of the randomized placebo-controlled trial designed to investigate cardiovascular and [...] Read more.
Recently, we demonstrated negative effects of vitamin D supplementation on muscle strength and physical performance in women with vitamin D insufficiency. The underlying mechanism behind these findings remains unknown. In a secondary analysis of the randomized placebo-controlled trial designed to investigate cardiovascular and musculoskeletal health, we employed NMR-based metabolomics to assess the effect of a daily supplement of vitamin D3 (70 µg) or an identically administered placebo, during wintertime. We assessed the serum metabolome of 76 postmenopausal, otherwise healthy, women with vitamin D (25(OH)D) insufficiency (25(OH)D < 50 nmol/L), with mean levels of 25(OH)D of 33 ± 9 nmol/L. Compared to the placebo, vitamin D3 treatment significantly increased the levels of 25(OH)D (−5 vs. 59 nmol/L, respectively, p < 0.00001) and 1,25(OH)2D (−10 vs. 59 pmol/L, respectively, p < 0.00001), whereas parathyroid hormone (PTH) levels were reduced (0.3 vs. −0.7 pmol/L, respectively, p < 0.00001). Analysis of the serum metabolome revealed a significant increase of carnitine, choline, and urea and a tendency to increase for trimethylamine-N-oxide (TMAO) and urinary excretion of creatinine, without any effect on renal function. The increase in carnitine, choline, creatinine, and urea negatively correlated with muscle health and physical performance. Combined with previous clinical findings reporting negative effects of vitamin D on muscle strength and physical performance, this secondary analysis suggests a direct detrimental effect on skeletal muscle of moderately high daily doses of vitamin D supplements. Full article
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Review

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Open AccessReview
Oral Vitamin D Therapy in Patients with Psoriasis
Nutrients 2021, 13(1), 163; https://doi.org/10.3390/nu13010163 - 06 Jan 2021
Abstract
Vitamin D treatment is effective when applied topically to the skin for plaque-type psoriasis. Oral vitamin D supplementation might be effective as an adjuvant treatment option in psoriasis. This umbrella review aimed to highlight the current knowledge regarding the use of oral vitamin [...] Read more.
Vitamin D treatment is effective when applied topically to the skin for plaque-type psoriasis. Oral vitamin D supplementation might be effective as an adjuvant treatment option in psoriasis. This umbrella review aimed to highlight the current knowledge regarding the use of oral vitamin D for treatment of patients with psoriasis. We performed a literature search and identified 107 eligible full-text articles that were relevant to the research interest. Among these, 10 review articles were selected, and data were extracted. A data synthesis showed that only a few studies monitored oral vitamin D efficacy in patients with psoriasis. No studies investigated the optimal dose of systemic vitamin D in psoriasis. However, most studies did not observe side effects for doses within a relatively narrow range (0.25 to 2 μg/day). These results suggest that more large-scale studies are needed to determine the efficacy, optimal dose, and adverse effects of vitamin D administration in patients with psoriasis. Full article
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Open AccessReview
The Health Effects of Vitamin D and Probiotic Co-Supplementation: A Systematic Review of Randomized Controlled Trials
Nutrients 2021, 13(1), 111; https://doi.org/10.3390/nu13010111 - 30 Dec 2020
Abstract
Evidence of synergic health effects of co-supplementation with vitamin D and probiotics is emerging. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement, scientific databases and the grey literature were searched, and a narrative review and risk of bias assessment [...] Read more.
Evidence of synergic health effects of co-supplementation with vitamin D and probiotics is emerging. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement, scientific databases and the grey literature were searched, and a narrative review and risk of bias assessment were conducted. Seven randomized controlled trials were included, which had low risk of bias. Six studies were double-blind, and once single-blind, extended over 6–12 weeks, and included 50–105 participants. Conditions explored included schizophrenia, gestational diabetes, type 2 diabetes and coronary heart disease, polycystic ovarian syndrome, osteopenia, irritable bowel syndrome (IBS), and infantile colic. Supplementation frequency was daily or bi-monthly, with mainly vitamin D3, and Lactobacillus, Bifidobacterium, and Streptococcus. Comparators were placebo, vitamin D, lower vitamin D dose, and probiotics and lower vitamin D dose. The co-supplementation yielded greater health benefits than its comparators did in all studies except in one assessing IBS. Beneficial effects included decreased disease severity, improved mental health, metabolic parameters, mainly insulin sensitivity, dyslipidemia, inflammation, and antioxidative capacity, and lower use of healthcare. Co-supplementation of vitamin D and probiotics generated greater health benefits than its comparators did. More studies in other diseases and various populations are needed to confirm these findings and to elucidate the optimal form, composition, and frequency of this co-supplementation. Full article
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Open AccessReview
The Association between Vitamin D Status and Autism Spectrum Disorder (ASD): A Systematic Review and Meta-Analysis
Nutrients 2021, 13(1), 86; https://doi.org/10.3390/nu13010086 - 29 Dec 2020
Abstract
The association between vitamin D status and autism spectrum disorder (ASD) is well-investigated but remains to be elucidated. We quantitatively combined relevant studies to estimate whether vitamin D status was related to ASD in this work. PubMed, EMBASE, Web of Science, and the [...] Read more.
The association between vitamin D status and autism spectrum disorder (ASD) is well-investigated but remains to be elucidated. We quantitatively combined relevant studies to estimate whether vitamin D status was related to ASD in this work. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to include eligible studies. A random-effects model was applied to pool overall estimates of vitamin D concentration or odds ratio (OR) for ASD. In total, 34 publications involving 20,580 participants were identified in this present study. Meta-analysis of 24 case–control studies demonstrated that children and adolescents with ASD had significantly lower vitamin D concentration than that of the control group (mean difference (MD): −7.46 ng/mL, 95% confidence interval (CI): −10.26; −4.66 ng/mL, p < 0.0001, I2 = 98%). Quantitative integration of 10 case–control studies reporting OR revealed that lower vitamin D was associated with higher risk of ASD (OR: 5.23, 95% CI: 3.13; 8.73, p < 0.0001, I2 = 78.2%). Analysis of 15 case–control studies barring data from previous meta-analysis reached a similar result with that of the meta-analysis of 24 case–control studies (MD: −6.2, 95% CI: −9.62; −2.78, p = 0.0004, I2 = 96.8%), which confirmed the association. Furthermore, meta-analysis of maternal and neonatal vitamin D showed a trend of decreased early-life vitamin D concentration in the ASD group (MD: −3.15, 95% CI: −6.57; 0.26, p = 0.07, I2 = 99%). Meta-analysis of prospective studies suggested that children with reduced maternal or neonatal vitamin D had 54% higher likelihood of developing ASD (OR: 1.54, 95% CI: 1.12; 2.10, p = 0.0071, I2 = 81.2%). These analyses indicated that vitamin D status was related to the risk of ASD. The detection and appropriate intervention of vitamin D deficiency in ASD patients and pregnant and lactating women have clinical and public significance. Full article
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Open AccessReview
The Benefits of Vitamin D Supplementation for Athletes: Better Performance and Reduced Risk of COVID-19
Nutrients 2020, 12(12), 3741; https://doi.org/10.3390/nu12123741 - 04 Dec 2020
Abstract
The COVID-19 pandemic is having major economic and personal consequences for collegiate and professional sports. Sporting events have been canceled or postponed, and even when baseball and basketball seasons resumed in the United States recently, no fans were in attendance. As play resumed, [...] Read more.
The COVID-19 pandemic is having major economic and personal consequences for collegiate and professional sports. Sporting events have been canceled or postponed, and even when baseball and basketball seasons resumed in the United States recently, no fans were in attendance. As play resumed, several players developed COVID-19, disrupting some of the schedules. A hypothesis now under scientific consideration is that taking vitamin supplements to raise serum 25-hydroxyvitamin D [25(OH)D] concentrations could quickly reduce the risk and/or severity of COVID-19. Several mechanisms have been identified through which vitamin D could reduce the risks of infection and severity, death, and long-haul effects of COVID-19: (1) inducing production of cathelicidin and defensins to reduce the survival and replication of the SARS-CoV-2 virus; (2) reducing inflammation and the production of proinflammatory cytokines and risk of the “cytokine storm” that damages the epithelial layer of the lungs, heart, vascular system, and other organs; and (3) increasing production of angiotensin-converting enzyme 2, thus limiting the amount of angiotensin II available to the virus to cause damage. Clinical trials have confirmed that vitamin D supplementation reduces risk of acute respiratory tract infections, and approximately 30 observational studies have shown that incidence, severity, and death from COVID-19 are inversely correlated with serum 25(OH)D concentrations. Vitamin D supplementation is already familiar to many athletes and sports teams because it improves athletic performance and increases playing longevity. Thus, athletes should consider vitamin D supplementation to serve as an additional means by which to reduce risk of COVID-19 and its consequences. Full article
Open AccessReview
Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity
Nutrients 2020, 12(11), 3361; https://doi.org/10.3390/nu12113361 - 31 Oct 2020
Cited by 6
Abstract
Vitamin D deficiency co-exists in patients with COVID-19. At this time, dark skin color, increased age, the presence of pre-existing illnesses and vitamin D deficiency are features of severe COVID disease. Of these, only vitamin D deficiency is modifiable. Through its interactions with [...] Read more.
Vitamin D deficiency co-exists in patients with COVID-19. At this time, dark skin color, increased age, the presence of pre-existing illnesses and vitamin D deficiency are features of severe COVID disease. Of these, only vitamin D deficiency is modifiable. Through its interactions with a multitude of cells, vitamin D may have several ways to reduce the risk of acute respiratory tract infections and COVID-19: reducing the survival and replication of viruses, reducing risk of inflammatory cytokine production, increasing angiotensin-converting enzyme 2 concentrations, and maintaining endothelial integrity. Fourteen observational studies offer evidence that serum 25-hydroxyvitamin D concentrations are inversely correlated with the incidence or severity of COVID-19. The evidence to date generally satisfies Hill’s criteria for causality in a biological system, namely, strength of association, consistency, temporality, biological gradient, plausibility (e.g., mechanisms), and coherence, although experimental verification is lacking. Thus, the evidence seems strong enough that people and physicians can use or recommend vitamin D supplements to prevent or treat COVID-19 in light of their safety and wide therapeutic window. In view of public health policy, however, results of large-scale vitamin D randomized controlled trials are required and are currently in progress. Full article
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Open AccessReview
Effects of Vitamin D Supplementation on Lipid Profile in Adults with the Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Nutrients 2020, 12(11), 3352; https://doi.org/10.3390/nu12113352 - 30 Oct 2020
Cited by 1
Abstract
Background: Metabolic syndrome (MetS) increases the risk of cardiovascular disease, with atherogenic dyslipidemia being a major contributing factor. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to assess whether vitamin D supplementation (VDS) [...] Read more.
Background: Metabolic syndrome (MetS) increases the risk of cardiovascular disease, with atherogenic dyslipidemia being a major contributing factor. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to assess whether vitamin D supplementation (VDS) alleviates dyslipidemia in adults with MetS. Scientific databases (PUBMED, MEDLINE, CINAHL, EMBASE, Cochrane Library, ClinicalTrials.gov, International Clinical Trials Registry Platform) and the gray literature were searched for randomized controlled trials of VDS, reporting on blood lipids. A narrative review, meta-analyses, sensitivity analyses, and appraisal of the risk of bias and overall quality of evidence produced were conducted. Results: Seven studies were included, and four were meta-analyzed. The risk of bias was generally low, and the final quality of evidence was low or very low. VDS, whether in high or low dose, significantly increased endline vitamin D blood levels; did not affect total, low-density, high-density cholesterol levels, and novel lipid-related biomarkers; yet, significantly increased triglycerides (TG) levels compared with placebo (MD: 30.67 (95%CI: 4.89–56.45) mg/dL; p = 0.02 for low-dose VDS; and MD: 27.33 (95%CI: 2.06–52.59) mg/dL; p = 0.03 for high-dose VDS). Pertaining heterogeneity was high (I2 = 86%; and I2 = 51%, respectively), and some included studies had significantly higher baseline TG in the intervention arm. The sensitivity analyses revealed robust results. Conclusion: VDS seems not to affect blood lipids in adults with MetS. Full article
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Open AccessReview
Vitamin D and Autoimmune Thyroid Disease—Cause, Consequence, or a Vicious Cycle?
Nutrients 2020, 12(9), 2791; https://doi.org/10.3390/nu12092791 - 11 Sep 2020
Abstract
Vitamin D is a steroid hormone traditionally connected to phosphocalcium metabolism. The discovery of pleiotropic expression of its receptor and of the enzymes involved in its metabolism has led to the exploration of the other roles of this vitamin. The influence of vitamin [...] Read more.
Vitamin D is a steroid hormone traditionally connected to phosphocalcium metabolism. The discovery of pleiotropic expression of its receptor and of the enzymes involved in its metabolism has led to the exploration of the other roles of this vitamin. The influence of vitamin D on autoimmune disease—namely, on autoimmune thyroid disease—has been widely studied. Most of the existing data support a relationship between vitamin D deficiency and a greater tendency for development and/or higher titers of antibodies linked to Hashimoto’s thyroiditis, Graves’ disease, and/or postpartum thyroiditis. However, there have also been some reports contradicting such relationships, thus making it difficult to establish a unanimous conclusion. Even if the existence of an association between vitamin D and autoimmune thyroid disease is assumed, it is still unclear whether it reflects a pathological mechanism, a causal relationship, or a consequence of the autoimmune process. The relationship between vitamin D’s polymorphisms and this group of diseases has also been the subject of study, often with divergent results. This text presents a review of the recent literature on the relationship between vitamin D and autoimmune thyroid disease, providing an analysis of the likely involved mechanisms. Our thesis is that, due to its immunoregulatory role, vitamin D plays a minor role in conjunction with myriad other factors. In some cases, a vicious cycle is generated, thus contributing to the deficiency and aggravating the autoimmune process. Full article
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Open AccessReview
Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths
Nutrients 2020, 12(4), 988; https://doi.org/10.3390/nu12040988 - 02 Apr 2020
Cited by 399
Abstract
The world is in the grip 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 the risk of respiratory [...] Read more.
The world is in the grip 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 the 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 increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the 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 the 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. Full article

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Open AccessCommentary
Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths—Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action
Nutrients 2021, 13(2), 411; https://doi.org/10.3390/nu13020411 - 28 Jan 2021
Abstract
The COVID-19 pandemic poses an unprecedented threat to human health, health care systems, public life, and economy around the globe. The repertoire of effective therapies for severe courses of the disease has remained limited. A large proportion of the world population suffers from [...] Read more.
The COVID-19 pandemic poses an unprecedented threat to human health, health care systems, public life, and economy around the globe. The repertoire of effective therapies for severe courses of the disease has remained limited. A large proportion of the world population suffers from vitamin D insufficiency or deficiency, with prevalence being particularly high among the COVID-19 high-risk populations. Vitamin D supplementation has been suggested as a potential option to prevent COVID-19 infections, severe courses, and deaths from the disease, but is not widely practiced. This article provides an up-to-date summary of recent epidemiological and intervention studies on a possible role of vitamin D supplementation for preventing severe COVID-19 cases and deaths. Despite limitations and remaining uncertainties, accumulating evidence strongly supports widespread vitamin D supplementation, in particular of high-risk populations, as well as high-dose supplementation of those infected. Given the dynamics of the COVID-19 pandemic, the benefit–risk ratio of such supplementation calls for immediate action even before results of ongoing large-scale randomized trials become available. Full article
Open AccessComment
Vitamin D Supplementation in Influenza and COVID-19 Infections Comment on: “Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths” Nutrients 2020, 12(4), 988
Nutrients 2020, 12(6), 1626; https://doi.org/10.3390/nu12061626 - 01 Jun 2020
Cited by 6
Abstract
There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment [...] Read more.
There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment aims to discuss the evidence on the use of Vitamin D in people who are at risk of developing COVID-19, focusing on safety issues of the Vitamin D supplementation. Full article
Open AccessReply
Reply: “Vitamin D Supplementation in Influenza and COVID-19 Infections. Comment on: Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Nutrients 2020, 12(4), 988”
Nutrients 2020, 12(6), 1620; https://doi.org/10.3390/nu12061620 - 01 Jun 2020
Cited by 12
Abstract
We thank Dr [...] Full article
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