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Vitamin D, Diet and Musculoskeletal Health

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

Deadline for manuscript submissions: closed (12 December 2022) | Viewed by 54264

Special Issue Editors


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Guest Editor
Department of Biomolecular Sciences, University of Urbino, Urbino, Italy
Interests: molecular biology; inflammation; cancer; microbiota; nutrition
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
Interests: nutrition; food supplement; sport nutrition; microbiota; molecular biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The important role of Vitamin D in calcium and phosphorus homeostasis, bone biology, immune function, inflammation. and cell growth is well known, but there is a growing interest in its potential effect on skeletal muscle mass and strength by virtue of its action on muscle cell differentiation, metabolism, and function. Vitamin D also plays a role in the regulation and uptake of calcium in muscle cells, which is important for muscle strength, contractile activity, mitochondrial function, insulin sensitivity, and protein synthesis. This activity is both direct and indirect and involves genomic and nongenomic pathways.

Skeletal muscle affects human health and disease. Aging is associated with a decrease in muscle mass and function (sarcopenia), which is associated with a loss of independence and reduced quality of life. The gut microbiota, the bacteria, archaea, viruses, and eukaryotic microbes residing in the gastrointestinal tract are emerging as potential contributors to age-associated-changes in muscle size, composition, and function.

This Special Issue will publish either manuscripts describing original research or analytical reviews on vitamin D and musculoskeletal health, with a focus on other factors playing a role in this relationship, such as diet, ageing, diseases, gut microbiota, and exercise.

Dr. Deborah Agostini
Dr. Sabrina Donati Zeppa
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Vitamin D
  • Musculoskeletal health
  • Diet
  • Aging
  • Gut microbiota
  • Exercise

Published Papers (15 papers)

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Editorial

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3 pages, 204 KiB  
Editorial
Vitamin D, Diet and Musculoskeletal Health
by Deborah Agostini and Sabrina Donati Zeppa
Nutrients 2023, 15(13), 2902; https://doi.org/10.3390/nu15132902 - 27 Jun 2023
Cited by 3 | Viewed by 1289
Abstract
Vitamin D is a fat-soluble steroid hormone, acting through genomic and non-genomic mechanisms, obtainable via two main sources: diet and exposure to ultraviolet B rays [...] Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)

Research

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19 pages, 355 KiB  
Communication
Vitamin D Supplementation and Its Impact on Different Types of Bone Fractures
by Jakub Erdmann, Michał Wiciński, Paweł Szyperski, Sandra Gajewska, Jakub Ohla and Maciej Słupski
Nutrients 2023, 15(1), 103; https://doi.org/10.3390/nu15010103 (registering DOI) - 25 Dec 2022
Cited by 3 | Viewed by 3259
Abstract
Vitamin D helps to balance the levels of calcium and phosphorus to maintain proper bone structure. It is also involved in essential biological roles and displays a wide spectrum of potential benefits in the human body. Since there are many types of fractures [...] Read more.
Vitamin D helps to balance the levels of calcium and phosphorus to maintain proper bone structure. It is also involved in essential biological roles and displays a wide spectrum of potential benefits in the human body. Since there are many types of fractures that occur at specific ages and due to different circumstances, the influence of vitamin D on the frequency of a particular fracture may differ. Thus, the authors investigated the possible preventive effect of vitamin D on the risks of vertebral fractures, hip fractures, stress fractures and pediatric fractures. Additional aspects of vitamin D, especially on recuperation after injures and its impact on the severity of particular fractures, were also discussed. It was suggested that vitamin D supplementation may contribute to a reduction in hip fracture risk due to reduced bone turnover, decreased frequency of falls and improved muscle function. Furthermore, vitamin D appears to lower the risk of stress fractures in athletes and military recruits. Due to a nonunified protocol design, presented investigations show inconsistencies between vitamin D supplementation and a decreased risk of vertebral fractures. However, a vitamin D preventive effect on pediatric fractures seems to be implausible. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
10 pages, 1496 KiB  
Article
Direct Effects of Vitamin D Supplementation on Ultramarathon-Induced Changes in Kynurenine Metabolism
by Jan Mieszkowski, Paulina Brzezińska, Błażej Stankiewicz, Andrzej Kochanowicz, Bartłomiej Niespodziński, Joanna Reczkowicz, Tomasz Waldziński, Bartłomiej Kacprzak, Natalia Siuba-Jarosz, Miroslav Petr and Jędrzej Antosiewicz
Nutrients 2022, 14(21), 4485; https://doi.org/10.3390/nu14214485 - 25 Oct 2022
Cited by 7 | Viewed by 2181
Abstract
In humans, most free tryptophan is degraded via kynurenine pathways into kynurenines. Kynurenines modulate the immune system, central nervous system, and skeletal muscle bioenergetics. Consequently, kynurenine pathway metabolites (KPMs) have been studied in the context of exercise. However, the effect of vitamin D [...] Read more.
In humans, most free tryptophan is degraded via kynurenine pathways into kynurenines. Kynurenines modulate the immune system, central nervous system, and skeletal muscle bioenergetics. Consequently, kynurenine pathway metabolites (KPMs) have been studied in the context of exercise. However, the effect of vitamin D supplementation on exercise-induced changes in KPMs has not been investigated. Here, we analyzed the effect of a single high-dose vitamin D supplementation on KPMs and tryptophan levels in runners after an ultramarathon. In the study, 35 amateur runners were assigned into two groups: vitamin D supplementation group, administered 150,000 IU vitamin D in vegetable oil 24 h before the run (n = 16); and control (placebo) group (n = 19). Blood was collected for analysis 24 h before, immediately after, and 24 h after the run. Kynurenic, xanthurenic, quinolinic, and picolinic acids levels were significantly increased after the run in the control group, but the effect was blunted by vitamin D supplementation. Conversely, the decrease in serum tryptophan, tyrosine, and phenylalanine levels immediately after the run was more pronounced in the supplemented group than in the control. The 3-hydroxy-l-kynurenine levels were significantly increased in both groups after the run. We conclude that vitamin D supplementation affects ultramarathon-induced changes in tryptophan metabolism. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>Changes in serum KYN metabolite levels after the ultramarathon in runners who received a single high dose of vitamin D (supplemented group, green) and runners who received the placebo (control group, red). Sampling: I, 24 h before the run; II, immediately after the run; and III, 24 h after the run. (<b>A</b>) 3-HK, 3-hydroxy-<span class="html-small-caps">l</span>-kynurenine; (<b>B</b>) KYN, kynurenine; (<b>C</b>) KYNA, kynurenic acid; (<b>D</b>) PA, picolinic acid; (<b>E</b>) QA, quinolinic acid; (<b>F</b>) XANA, xanthurenic acid. †, Significant difference vs. 24 h before and 24 after the run; #, significant difference vs. supplemented group immediately after the run. The significance threshold was set at <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Changes in serum levels of (<b>A</b>) phenylalanine (PHE), (<b>B</b>) tryptophan (TRP), and (<b>C</b>) tyrosine (TYR) after the ultramarathon in runners who received a single high dose of vitamin D (supplemented group, green) and runners who received the placebo (control group, red). Sampling: I, 24 h before the run; II, immediately after the run; and III, 24 h after the run. †, Significant difference vs. 24 h before and 24 after the run; #, significant difference vs. supplemented group immediately after the run; *, significant difference vs. control group immediately after the run. The significance level was set at <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Changes in KYN metabolite and TRP ratios after the ultramarathon in runners who received a single high dose of vitamin D (supplemented group , green) and runners who received the placebo (control group, red). Sampling: I, 24 h before the run; II, immediately after the run; and III, 24 h after the run. (<b>A</b>) KYNA/KYN, kynurenic acid to kynurenine ratio; (<b>B</b>) KYNA/QA, kynurenic acid to quinolinic acid ratio; (<b>C</b>) KYN/TRP, kynurenine to tryptophan ratio; (<b>D</b>) PA/QA, picolinic acid to quinolinic acid ratio. †, Significant difference vs. 24 h before and 24 after the run; #, significant difference vs. supplemented group immediately after the run. The significance level was set at <span class="html-italic">p</span> &lt; 0.01.</p>
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11 pages, 941 KiB  
Article
Impaired Height Growth Associated with Vitamin D Deficiency in Young Children from the Japan Environment and Children’s Study
by Shohei Kuraoka, Masako Oda, Hiroshi Mitsubuchi, Kimitoshi Nakamura, Takahiko Katoh and Japan Environment and Children’s Study (JECS) Group
Nutrients 2022, 14(16), 3325; https://doi.org/10.3390/nu14163325 - 13 Aug 2022
Cited by 3 | Viewed by 4005
Abstract
Vitamin D is essential for calcium absorption and bone homeostasis. Although short-stature children were reported to have low vitamin D concentrations, there is no clear evidence of a link between vitamin D and height growth in young children not limited to those with [...] Read more.
Vitamin D is essential for calcium absorption and bone homeostasis. Although short-stature children were reported to have low vitamin D concentrations, there is no clear evidence of a link between vitamin D and height growth in young children not limited to those with short stature. We collected height and weight data at 2 and 4 years of age, serum vitamin D concentrations at 4 years, and questionnaire results on sun exposure from the Japan Environment and Children’s Study (JECS). We then analyzed the relationship between vitamin D deficiency and height growth. We also analyzed the correlation between serum vitamin D concentration and sun exposure. Overall, 3624 participants from JECS were analyzed. We identified cases of subclinical vitamin D deficiency and insufficiency. We further found that definitive vitamin D deficiency (<10 ng/mL) impaired height growth by 0.6 cm per year even in young children not limited to those with short stature. Furthermore, we clarified that children with vitamin D deficiency had reduced outdoor activity, especially during winter. In children with either short or normal stature, definitive vitamin D deficiency was associated with height growth decline, and reduction in outdoor activity, especially during winter, was a risk factor for vitamin D deficiency. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>Selection flow diagram. Participants in the Sub-Cohort Study were randomly selected from the Japan Environment and Children’s Study (JECS). Finally, participants who did not meet the exclusion criteria (incomplete data, complications, preterm birth) were included in the present study.</p>
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<p>Serum 25(OH)D3 concentrations at 4 years of age (<b>A</b>) Histogram. (<b>B</b>) Monthly transitions.</p>
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<p>Height growth for each group divided by serum 25(OH)D3 concentration. Δheight means the height growth per year (12 months). Data are shown as mean and 95% CI. ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Outdoor playing time for each group divided by serum 25(OH)D3 concentration 3 h:3 h; 1 h:1 h; rare: answer indicating that they rarely play outside. (<b>A</b>) Summer. (<b>B</b>) Winter. Dashed line, * <span class="html-italic">p</span> &lt; 0.05; solid line, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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13 pages, 1882 KiB  
Article
Nordic Walking Rather Than High Intensity Interval Training Reduced Myostatin Concentration More Effectively in Elderly Subjects and the Range of This Drop Was Modified by Metabolites of Vitamin D
by Katarzyna Micielska, Marta Flis, Jakub Antoni Kortas, Ewa Rodziewicz-Flis, Jędrzej Antosiewicz, Krystian Wochna, Giovanni Lombardi and Ewa Ziemann
Nutrients 2021, 13(12), 4393; https://doi.org/10.3390/nu13124393 - 8 Dec 2021
Cited by 10 | Viewed by 3505
Abstract
The COVID-19 pandemic and subsequent self-isolation exacerbated the problem of insufficient amounts of physical activity and its consequences. At the same time, this revealed the advantage of vitamin D. Thus, there was a need to verify the effects of those forms of training [...] Read more.
The COVID-19 pandemic and subsequent self-isolation exacerbated the problem of insufficient amounts of physical activity and its consequences. At the same time, this revealed the advantage of vitamin D. Thus, there was a need to verify the effects of those forms of training that can be performed independently. In this study, we examined the effects of Nordic walking (NW) and high intensity interval training (HIIT) with regard to the impact of the metabolite vitamin D. We assigned 32 overweight adults (age = 61 ± 12 years) to one of two training groups: NW = 18 and HIIT = 14. Body composition assessment and blood sample collection were conducted before starting the training programs and a day after their completion. NW training induced a significant decrease in myostatin (p = 0.05) concentration; however, the range was dependent on the baseline concentrations of vitamin D metabolites. This drop was accompanied by a significant negative correlation with the decorin concentration. Unexpectedly, NW caused a decrement in both forms of osteocalcin: undercarboxylated (Glu-OC) and carboxylated-type (Gla-OC). The scope of Glu-OC changes was dependent on a baseline concentration of 25(OH)D2 (r = −0.60, p = 0.01). In contrast, the HIIT protocol did not induce any changes. Overall results revealed that NW diminished the myostatin concentration and that this effect is more pronounced among adults with a sufficient concentration of vitamin D metabolites. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>Myokines (<b>A</b>,<b>B</b>) and osteokines (<b>C</b>,<b>D</b>) concentration changes in response to applied training protocols: Nordic walking (NW; <span class="html-italic">n</span> = 18) and high intensity interval training (HIIT; <span class="html-italic">n</span> = 14). Data are presented as mean ± SD; * statistically significant result (post hoc tests); Glu-OC—undercarboxylated osteocalcin; Gla-OC—carboxylated-type of osteocalcin.</p>
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<p>Myostatin concentration delta changes (∆ POST to PRE) dependant on baseline level of metabolite vitamin D in NW training group: (<b>A</b>) baseline 25(OH)D<sub>3</sub>, (<b>B</b>) baseline 24,25(OH)<sub>2</sub>D<sub>3</sub> and (<b>C</b>) baseline 3-epi-25(OH)D<sub>3</sub>; * statistically significant result (post hoc tests)—<span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Correlation of myostatin and decorin concentration delta changes (∆ POST to PRE) in response to NW training.</p>
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<p>Correlation between baseline concentration of 25(OH)D<sub>2</sub> and delta changes (∆ POST to PRE) in undercarboxylated osteocalcin (Glu-OC) among participants from NW group.</p>
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<p>The differences between NW (<span class="html-italic">n</span> = 18) and HIIT (<span class="html-italic">n</span> = 14) training programs expressed as delta changes (∆ POST to PRE) in myokines (<b>A</b>,<b>B</b>,<b>E</b>) and osteokines (<b>C</b>,<b>D</b>) concentration, before and after applied interventions. Values are statistically significant. Analysis of variance (rANOVA) was used.</p>
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12 pages, 5124 KiB  
Article
In Vitro Non-Genomic Effects of Calcifediol on Human Preosteoblastic Cells
by Simone Donati, Gaia Palmini, Cecilia Romagnoli, Cinzia Aurilia, Francesca Miglietta, Irene Falsetti, Francesca Marini, Roberto Zonefrati, Gianna Galli, Gemma Marcucci, Teresa Iantomasi and Maria Luisa Brandi
Nutrients 2021, 13(12), 4227; https://doi.org/10.3390/nu13124227 - 25 Nov 2021
Cited by 8 | Viewed by 2262
Abstract
Several recent studies have demonstrated that the direct precursor of vitamin D3, the calcifediol [25(OH)D3], through the binding to the nuclear vitamin D receptor (VDR), is able to regulate the expression of many genes involved in several cellular processes. [...] Read more.
Several recent studies have demonstrated that the direct precursor of vitamin D3, the calcifediol [25(OH)D3], through the binding to the nuclear vitamin D receptor (VDR), is able to regulate the expression of many genes involved in several cellular processes. Considering that itself may function as a VDR ligand, although with a lower affinity, respect than the active form of vitamin D, we have assumed that 25(OH)D3 by binding the VDR could have a vitamin’s D3 activity such as activating non-genomic pathways, and in particular we selected mesenchymal stem cells derived from human adipose tissue (hADMSCs) for the in vitro assessment of the intracellular Ca2+ mobilization in response to 25(OH)D3. Our result reveals the ability of 25(OH)D3 to activate rapid, non-genomic pathways, such as an increase of intracellular Ca2+ levels, similar to what observed with the biologically active form of vitamin D3. hADMSCs loaded with Fluo-4 AM exhibited a rapid and sustained increase in intracellular Ca2+ concentration as a result of exposure to 10−5 M of 25(OH)D3. In this work, we show for the first time the in vitro ability of 25(OH)D3 to induce a rapid increase of intracellular Ca2+ levels in hADMSCs. These findings represent an important step to better understand the non-genomic effects of vitamin D3 and its role in endocrine system. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>Schematic representation of the genomic and non-genomic mechanisms of the biological active form of vitamin D<sub>3</sub>, 1α,25-(OH)<sub>2</sub>D<sub>3</sub>. Abbreviations: mVDR: membrane-bound VDR; RXR: retinoid X receptor; VDRE: vitamin D<sub>3</sub> response elements; CAV1: caveolin 1; Shh: Sonic hedgehog; Pdia3: protein disulphide isomerase family A member 3; PLA2: phospholipase A2; PLAA: PLA2 activating protein; PLC: phospholipase C; PIP2: phosphatidylinositol bisphosphate; DAG: diacylglycerol; IP<sub>3</sub>: inositol trisphosphate; PKC: protein kinase C; CaMK2G: calcium/calmodulin-dependent protein kinase II gamma; MAPK: mitogen-activated protein kinase.</p>
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<p>Biopsy sample obtained by surgical resection from healthy donor (<b>A</b>) and primary hADMSCs cell line (<b>B</b>). Observation with a phase contrast microscopy (AxioVision, ZEISS). Original Magnification: 10×.</p>
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<p>Osteogenic Differentiation Assay—ALP and HA. Osteogenic differentiation at 14 days (<b>A</b>) and 35 days (<b>B</b>) of induction by cytochemical staining for ALP with Fast Red Violet B and for HA with Von Kossa staining. The ALP+ cells are in red and the grainy deposits are in black. Nuclei are counterstained in green. Observation in brightfield (AxioVision, ZEISS). Original magnification: 20×.</p>
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<p>Adipogenic Differentiation Assay. Adipogenic differentiation at 35 days (<b>A</b>) and after 0 days (<b>B</b>) of induction by cytochemical staining with Oil Red O. In red the lipidic vesicles and in violet the nuclei counterstained by Toluidine Blue. Observation in brightfield. Original magnification: 20×.</p>
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<p>Calcium imaging on hADMSCs before (<b>A</b>) and following exposure to 10<sup>−5</sup> M 25(OH)D<sub>3</sub> (<b>B</b>).</p>
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<p>Effect of 25(OH)D<sub>3</sub> on the mobilization of intracellular Ca<sup>2+</sup>. Time courses experiments has revealed the changes in intracellular Ca<sup>2+</sup> levels in response to 25(OH)D<sub>3</sub>: blue for untreated cells, red for cells exposed to 10<sup>−5</sup> M 25(OH)D<sub>3</sub>, and green for 10<sup>−5</sup> M calcium ionophore-treated cells (<b>A</b>). The bold curves represent the average intensity values for Fluo-4 signals for all the cells in response to the treatment for each time (<b>A</b>). Maximum fluorescence intensity derived from cells exposed to 25(OH)D<sub>3</sub> was compared to negative control (<b>B</b>). * = <span class="html-italic">p</span>-value &lt; 0.0005.</p>
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10 pages, 264 KiB  
Article
Could Vitamin D3 Deficiency Influence Malocclusion Development?
by Anna Leszczyszyn, Sylwia Hnitecka and Marzena Dominiak
Nutrients 2021, 13(6), 2122; https://doi.org/10.3390/nu13062122 - 21 Jun 2021
Cited by 7 | Viewed by 4310
Abstract
The abnormal growth of the craniofacial bone leads to skeletal and dental defects, which result in the presence of malocclusions. Not all causes of malocclusion have been explained. In the development of skeletal abnormalities, attention is paid to general deficiencies, including of vitamin [...] Read more.
The abnormal growth of the craniofacial bone leads to skeletal and dental defects, which result in the presence of malocclusions. Not all causes of malocclusion have been explained. In the development of skeletal abnormalities, attention is paid to general deficiencies, including of vitamin D3 (VD3), which causes rickets. Its chronic deficiency may contribute to skeletal malocclusion. The aim of the study was to assess the impact of VD3 deficiency on the development of malocclusions. The examination consisted of a medical interview, oral examination, an alginate impression and radiological imaging, orthodontic assessment, and taking a venous blood sample for VD3 level testing. In about 42.1% of patients, the presence of a skeletal defect was found, and in 46.5% of patients, dentoalveolar malocclusion. The most common defect was transverse constriction of the maxilla with a narrow upper arch (30.7%). The concentration of vitamin 25 (OH) D in the study group was on average 23.6 ± 10.5 (ng/mL). VD3 deficiency was found in 86 subjects (75.4%). Our research showed that VD3 deficiency could be one of an important factor influencing maxillary development. Patients had a greater risk of a narrowed upper arch (OR = 4.94), crowding (OR = 4.94) and crossbite (OR = 6.16). Thus, there was a link between the deficiency of this hormone and the underdevelopment of the maxilla. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
13 pages, 799 KiB  
Article
Efficacy of Vitamin D Supplementation in Addition to Aerobic Exercise Training in Obese Women with Perceived Myalgia: A Single-Blinded Randomized Controlled Clinical Trial
by Heba Ahmed Ali Abdeen, David Rodriguez-Sanz, Mahmoud Ewidea, Dina Mohamed Ali Al-Hamaky, Marwa Abd El-Rahman Mohamed and Ahmed Ebrahim Elerian
Nutrients 2021, 13(6), 1819; https://doi.org/10.3390/nu13061819 - 27 May 2021
Cited by 4 | Viewed by 4283
Abstract
Obese women were more susceptible to myalgia because of their significantly lower vitamin D concentrations; the present study investigated the efficacy of vitamin D in addition to an aerobic interval training in the management of obese women with myalgia. Forty-five obese women with [...] Read more.
Obese women were more susceptible to myalgia because of their significantly lower vitamin D concentrations; the present study investigated the efficacy of vitamin D in addition to an aerobic interval training in the management of obese women with myalgia. Forty-five obese women with vitamin D deficiency and myalgia (30 to 40 years old) were assigned randomly into three equal groups. Group A received an aerobic interval training with vitamin D supplementation, Group B received vitamin D supplementation only, and Group C received aerobic interval training only; participants in all groups were on calorie deficient diets. The study outcomes were the Visual Analog Scale (VAS) for Pain Evaluation, serum vitamin D level, and Cooper 12-Minute Walk Test for Functional Capacity Evaluation, while the Short-Form Health Survey (SF) was used for assessment of quality of life. We detected a significant improvement in pain intensity level, serum vitamin D level, and quality of life in all groups with significant difference between Group A and groups B and C. We also detected a significant improvement in functional capacity in groups A and C, with no significant change in Group B. Aerobic interval training with vitamin D supplementation was more effective for the management of obese women with perceived myalgia. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>Flow chart in accordance with the CONSORT statement.</p>
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15 pages, 2480 KiB  
Article
The Positive Impact of Vitamin D on Glucocorticoid-Dependent Skeletal Muscle Atrophy
by Mateusz Jakub Karnia, Daria Korewo, Dorota Myślińska, Ziemowit Maciej Ciepielewski, Monika Puchalska, Klaudia Konieczna-Wolska, Konrad Kowalski and Jan Jacek Kaczor
Nutrients 2021, 13(3), 936; https://doi.org/10.3390/nu13030936 - 14 Mar 2021
Cited by 12 | Viewed by 3331
Abstract
(1) The study aimed to investigate whether vitamin D3 supplementation would positively affect rats with glucocorticoids-induced muscle atrophy as measured by skeletal muscle mass in two experimental conditions: chronic dexamethasone (DEX) administration and a model of the chronic stress response. (2) The [...] Read more.
(1) The study aimed to investigate whether vitamin D3 supplementation would positively affect rats with glucocorticoids-induced muscle atrophy as measured by skeletal muscle mass in two experimental conditions: chronic dexamethasone (DEX) administration and a model of the chronic stress response. (2) The study lasted 28 consecutive days and was performed on 45 male Wistar rats randomly divided into six groups. These included two groups treated by abdominal injection of DEX at a dose of 2 mg/kg/day supplemented with vegetable oil (DEX PL; n = 7) or with vitamin D3 600 IU/kg/day (DEX SUP; n = 8), respectively, and a control group treated with an abdominal injection of saline (CON; n = 6). In addition, there were two groups of rats chronically stressed by cold water immersion (1 hour/day in a glass box with 1-cm-deep ice/water mixture; temperature ~4 °C), which were supplemented with vegetable oil as a placebo (STR PL; n = 9) or vitamin D3 at 600 IU/kg/day (STR SUP; n = 9). The last group was of sham-stressed rats (SHM; n = 6). Blood, soleus, extensor digitorum longus, gastrocnemius, tibialis anterior, and quadriceps femoris muscles were collected and weighed. The heart, liver, spleen, and thymus were removed and weighed immediately after sacrifice. The plasma corticosterone (CORT) and vitamin D3 metabolites were measured. (3) We found elevated CORT levels in both cold water-immersed groups; however, they did not alter body and muscle weight. Body weight and muscle loss occurred in groups with exogenously administered DEX, with the exception of the soleus muscle in rats supplemented with vitamin D3. Decreased serum 25(OH)D3 concentrations in DEX-treated rats were observed, and the cold water immersion did not affect vitamin D3 levels. (4) Our results indicate that DEX-induced muscle loss was abolished in rats supplemented with vitamin D3, especially in the soleus muscle. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>The level of corticosterone (CORT) in plasma. Results are expressed as mean ± SEM. CON (<span class="html-italic">n</span> = 6), SHM (<span class="html-italic">n</span> = 6), STR PL (=9), STR SUP (<span class="html-italic">n</span> = 9), **** <span class="html-italic">p</span> &lt; 0.0001 vs. CON, <span>$</span><span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.0001 vs. SHM, <span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.001 vs. SHM. CON: control group; SHM: sham cold water immersion group; STR PL: cold water immersion group supplemented with placebo; STR SUP: cold water immersion group supplemented with vitamin D<sub>3</sub>.</p>
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<p>The plasma vitamin D metabolite levels in DEX-treated rats at baseline (<b>A</b>) and the end of the experiment (<b>B</b>). Results are expressed as mean ± SEM. DEX PL (<span class="html-italic">n</span> = 7), DEX SUP (<span class="html-italic">n</span> = 8), CON (<span class="html-italic">n</span> = 6), * <span class="html-italic">p</span> &lt; 0.05 vs. CON, <span>$</span> <span class="html-italic">p</span> &lt; 0.01 vs. DEX PL, € <span class="html-italic">p</span> &lt; 0.001 vs. DEX PL, &amp; <span class="html-italic">p</span> &lt; 0.0001 vs. DEX PL; vs. CON. DEX PL: dexamethasone-treated group supplemented with placebo; DEX SUP: dexamethasone-treated group supplemented with vitamin D<sub>3</sub>; CON: control group.</p>
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<p>The plasma vitamin D metabolite levels in stressed rats at baseline (<b>A</b>) and the end of the experiment (<b>B</b>). Results are expressed as mean ± SEM. STR PL (<span class="html-italic">n</span> = 9), STR SUP (<span class="html-italic">n</span> = 9), SHM (<span class="html-italic">n</span> = 6), # <span class="html-italic">p</span> &lt; 0.01 vs. STR PL; vs. SHM, <span>$</span> <span class="html-italic">p</span> &lt; 0.0001 vs. STR PL; vs. SHM. STR PL: cold water immersion group supplemented with placebo; STR SUP: cold water immersion group supplemented with vitamin D<sub>3</sub>; SHM: sham cold water immersion group.</p>
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<p>The body mass at the end of the experiment in DEX-treated (<b>A</b>), and stressed (<b>B</b>) rats. Results are expressed as mean ± SEM. DEX PL (<span class="html-italic">n</span> = 7), DEX SUP (<span class="html-italic">n</span> = 8), CON (<span class="html-italic">n</span> = 6), STR PL (<span class="html-italic">n</span> = 9), STR SUP (<span class="html-italic">n</span> = 9), SHM (<span class="html-italic">n</span> = 6), **** <span class="html-italic">p</span> &lt; 0.0001 vs. CON. DEX PL: dexamethasone-treated group supplemented with placebo; DEX SUP: dexamethasone-treated group supplemented with vitamin D<sub>3</sub>; CON: control group; STR PL: cold water immersion group supplemented with placebo; STR SUP: cold water immersion group supplemented with vitamin D<sub>3</sub>; SHM: sham cold water immersion group.</p>
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<p>The SOL and EDL muscles mass at the end of the experiment in DEX-treated (<b>A</b>,<b>B</b>), and stressed (<b>C</b>,<b>D</b>) rats. Results are expressed as mean ± SEM. DEX PL (<span class="html-italic">n</span> = 7), DEX SUP (<span class="html-italic">n</span> = 8), CON (<span class="html-italic">n</span> = 6), STR PL (<span class="html-italic">n</span> = 9), STR SUP (<span class="html-italic">n</span> = 9), SHM (<span class="html-italic">n</span> = 6), * <span class="html-italic">p</span> &lt; 0.05 vs. DEX SUP, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. CON. DEX PL: dexamethasone-treated group supplemented with placebo; DEX SUP: dexamethasone-treated group supplemented with vitamin D<sub>3</sub>; CON: control group; STR PL: cold water immersion group supplemented with placebo; STR SUP: cold water immersion group supplemented with vitamin D<sub>3</sub>; SHM: sham cold water immersion group.</p>
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<p>Mean muscle weight: body weights ratio in DEX-treated rats in SOL (<b>A</b>), and EDL (<b>B</b>). Results are expressed as mean ± SEM. DEX PL (<span class="html-italic">n</span> = 7), DEX SUP (<span class="html-italic">n</span> = 8), CON (<span class="html-italic">n</span> = 6), * <span class="html-italic">p</span> &lt; 0.05, # <span class="html-italic">p</span> &lt; 0.01, <span>$</span> <span class="html-italic">p</span> &lt; 0.0001. DEX PL: dexamethasone-treated group supplemented with placebo; DEX SUP: dexamethasone-treated group supplemented with vitamin D<sub>3</sub>; CON: control group; EDL: extensor digitorum longus; SOL: soleus.</p>
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13 pages, 356 KiB  
Article
Vitamin D Deficiency is Associated with Handgrip Strength, Nutritional Status and T2DM in Community-Dwelling Older Mexican Women: A Cross-Sectional Study
by Luciano Mendoza-Garcés, María Consuelo Velázquez-Alva, María Fernanda Cabrer-Rosales, Isabel Arrieta-Cruz, Roger Gutiérrez-Juárez and María Esther Irigoyen-Camacho
Nutrients 2021, 13(3), 736; https://doi.org/10.3390/nu13030736 - 26 Feb 2021
Cited by 14 | Viewed by 2962
Abstract
The aim of this study was to evaluate the association between handgrip strength, nutritional status and vitamin D deficiency in Mexican community-dwelling older women. A cross sectional study in women ≥ 60 years-old was performed. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured by [...] Read more.
The aim of this study was to evaluate the association between handgrip strength, nutritional status and vitamin D deficiency in Mexican community-dwelling older women. A cross sectional study in women ≥ 60 years-old was performed. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured by a quantitative immunoassay technique. Handgrip strength was assessed using a dynamometer, while nutritional status was assessed through the Full Mini Nutritional Assessment (Full-MNA). A total of 116 women participated in the study, their mean age was 70.3 ± 5.8 years; 49.1% of the study group had plasma 25(OH)D levels lower than 40 nmol/L [16 ng/mL]. Meanwhile, 28.45% of participants had low handgrip strength (<16 kg), and 23.1% were identified at risk of malnutrition/malnourished according with Full-MNA score. Women with 25(OH)D deficiency (<40 nmol/L [16 ng/mL]) were more likely to have low handgrip strength (OR = 2.64, p = 0.025) compared with those with higher 25(OH)D values. Additionally, being malnourished or at risk of malnutrition (OR = 2.53, p = 0.045) or having type 2 diabetes mellitus (T2DM) (OR = 2.92, p = 0.044) was also associated with low 25(OH)D. The prevalence of low plasma 25(OH)D concentrations was high among Mexican active older women. Low handgrip strength, being at risk of malnutrition/malnourished, or diagnosed with T2DM was also associated with Vitamin D deficiency. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
14 pages, 1877 KiB  
Article
Vitamin D Supplementation Improves the Effects of the Rehabilitation Program on Balance and Pressure Distribution in Patients after Anterior Cervical Interbody Fusion-Randomized Control Trial
by Wojciech Skrobot, Ewelina Perzanowska, Katarzyna Krasowska, Damian J. Flis, Katarzyna P. Dzik, Wojciech Kloc, Jan Jacek Kaczor and Jędrzej Antosiewicz
Nutrients 2020, 12(12), 3874; https://doi.org/10.3390/nu12123874 - 18 Dec 2020
Cited by 4 | Viewed by 2883
Abstract
Study Design: A double-blinded, randomized controlled trial. Background: Surgery is effective in reducing pain intensity in patients with cervical disc disease. However, functional measurements demonstrated that the results have been not satisfactory enough. Thus, rehabilitation programs combined with the supplementation of vitamin D [...] Read more.
Study Design: A double-blinded, randomized controlled trial. Background: Surgery is effective in reducing pain intensity in patients with cervical disc disease. However, functional measurements demonstrated that the results have been not satisfactory enough. Thus, rehabilitation programs combined with the supplementation of vitamin D could play an essential role. Methods. The study recruited 30 patients, aged 20 to 70 years, selected for anterior cervical interbody fusion (ACIF). The patients were randomly divided into the placebo (Pl) and vitamin D (3200 IU D3/day) supplemented groups. The functional tests limits of stability (LOS), risk of falls (RFT), postural stability (PST), Romberg test, and foot pressure distribution were performed before supplementation (BS—week 0), five weeks after supplementation (AS—week 5), four weeks after surgery (BSVR—week 9), and 10 weeks after supervising rehabilitation (ASVR—week 19). Results. The concentration of 25(OH)D3 in the serum, after five weeks of supplementation, was significantly increased, while the Pl group maintained the same. The RFT was significantly reduced after five weeks of vitamin D supplementation. Moreover, a further significant decrease was observed following rehabilitation. In the Pl group, no changes in the RFT were observed. The overall postural stability index (OSI), LOS, and the outcomes of the Romberg test significantly improved in both groups; however, the effects on the OSI were more pronounced in the D3 group at the end of the rehabilitation program. Conclusions. Our data suggest that vitamin D supplementation positively affected the rehabilitation program in patients implemented four weeks after ACIF by reducing the risk of falls and improving postural stability. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>Participants flow diagram.</p>
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<p>The concentration of 25(OH)D3 in the serum, after five weeks of supplementation, was significantly increased. Columns, mean; bars SD; and a, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with BS. BS—before supplementation, AS—5 weeks after supplementation, BSVR—4 weeks after surgery, and ASVR—10 weeks after supervised rehabilitation.</p>
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<p>Vitamin D supplementation reduced the risk of falls of patients before anterior cervical interbody fusion (ACIF) surgery. The data are presented as the means and standard deviations (SDs). a, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with BS and b, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with Pl-ASVR.</p>
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<p>Vitamin D supplementation improves the effects of rehabilitation on the overall postural stability of patients after an anterior cervical interbody fusion surgery. Columns, mean and bars, standard deviations (SDs). a, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with the before supplementation (BS) control; b, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with the D3-BSVR group by one-way ANOVA; and c, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with the Pl-BSVR group.</p>
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<p>Vitamin D supplementation had no effects on the rehabilitation-induced improvement on the limits of stability of patients after anterior cervical interbody fusion surgery. Columns, mean and bars, standard deviations (SDs). a, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with the D3-BS; b, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with the Pl-BS; and c, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with and the Pl-after supplementation (AS) group, respectively by one-way ANOVA.</p>
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<p>Vitamin D supplementation had no effects on the rehabilitation-induced improvement on the ellipse sway area (mm<sup>2</sup>) of patients after anterior cervical interbody fusion surgery. Columns, mean and bars, standard deviations (SDs). a, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with D3-BS and b, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with Pl-BS by one-way ANOVA.</p>
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<p>Vitamin D supplementation decrease sway rate (mm/s) in patients after anterior cervical interbody fusion surgery. Columns, mean and bars, standard deviations (SDs). a, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with ASVR D3 by one-way ANOVA.</p>
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<p>Vitamin D supplementation decreased the center of pressure (CoP) path length (mm) in patients after anterior cervical interbody fusion surgery. Columns, mean and bars, standard deviations (SDs). a, <span class="html-italic">p</span> &lt; 0.05, significantly different compared with ASVR D3 by one-way ANOVA.</p>
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14 pages, 1136 KiB  
Article
Evaluation of Vitamin D Metabolism in Patients with Type 1 Diabetes Mellitus in the Setting of Cholecalciferol Treatment
by Alexandra Povaliaeva, Ekaterina Pigarova, Artem Zhukov, Viktor Bogdanov, Larisa Dzeranova, Olga Mel’nikova, Elena Pekareva, Natalya Malysheva, Vitaliy Ioutsi, Larisa Nikankina and Liudmila Rozhinskaya
Nutrients 2020, 12(12), 3873; https://doi.org/10.3390/nu12123873 - 18 Dec 2020
Cited by 8 | Viewed by 2658
Abstract
In this prospective controlled study, we examined 25 adults with adequately controlled (HbA1c level < 8.0%) type 1 diabetes mellitus (T1DM) and 49 conditionally healthy adults, intending to reveal the diversity of vitamin D metabolism in the setting of cholecalciferol intake at a [...] Read more.
In this prospective controlled study, we examined 25 adults with adequately controlled (HbA1c level < 8.0%) type 1 diabetes mellitus (T1DM) and 49 conditionally healthy adults, intending to reveal the diversity of vitamin D metabolism in the setting of cholecalciferol intake at a therapeutic dose. All patients received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. The studied groups had no significant differences in baseline parameters except that the patients with diabetes showed higher baseline levels of free 25(OH)D (p < 0.05). They also lacked a correlation between the measured and calculated free 25(OH)D in contrast to the patients from the control group (r = 0.41, p > 0.05 vs. r = 0.88, p < 0.05), possibly due to the glycosylation of binding proteins, which affects the affinity constant for 25(OH)D. The elevation of vitamin D levels after the administration of cholecalciferol was comparable in both groups, with slightly higher 25(OH)D3 levels observed in the diabetes group throughout the study since Day 1 (p < 0.05). Overall, our data indicate that in patients with adequately controlled T1DM 25(OH)D3 levels and the therapeutic response to cholecalciferol is similar to that in healthy individuals. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>Relationship between measured and calculated free 25(OH)D in groups.</p>
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<p>Interrelation of free 25(OH)D and 25(OH)D<sub>3</sub>, transport proteins in groups.</p>
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15 pages, 894 KiB  
Article
Vitamin D Supplementation Does Not Impact Resting Metabolic Rate, Body Composition and Strength in Vitamin D Sufficient Physically Active Adults
by Karina Romeu Montenegro, Vinicius Cruzat, Hilton Melder, Angela Jacques, Philip Newsholme and Kagan J. Ducker
Nutrients 2020, 12(10), 3111; https://doi.org/10.3390/nu12103111 - 12 Oct 2020
Cited by 7 | Viewed by 3498
Abstract
Supplementation with the most efficient form of Vitamin D (VitD3) results in improvements in energy metabolism, muscle mass and strength in VitD deficient individuals. Whether similar outcomes occur in VitD sufficient individuals’ remains to be elucidated. The aim of this study is to [...] Read more.
Supplementation with the most efficient form of Vitamin D (VitD3) results in improvements in energy metabolism, muscle mass and strength in VitD deficient individuals. Whether similar outcomes occur in VitD sufficient individuals’ remains to be elucidated. The aim of this study is to determine the effect of VitD3 supplementation on resting metabolic rate (RMR), body composition and strength in VitD sufficient physically active young adults. Participants completed pre-supplementation testing before being matched for sunlight exposure and randomly allocated in a counterbalanced manner to the VitD3 or placebo group. Following 12 weeks of 50 IU/kg body-mass VitD3 supplementation, participants repeated the pre-supplementation testing. Thirty-one adults completed the study (19 females and 12 males; mean ± standard deviation (SD); age = 26.6 ± 4.9 years; BMI = 24.2 ± 4.1 kg·m2). The VitD group increased serum total 25(OH)D by 30 nmol/L while the placebo group decreased total serum concentration by 21 nmol/L, reaching 123 (51) and 53 (42.2) nmol/L, respectively. There were no significant changes in muscle strength or power, resting metabolic rate and body composition over the 12-week period. Physically active young adults that are VitD sufficient have demonstrated that no additional physiological effects of achieving supraphysiological serum total 25(OH)D concentrations after VitD3 supplementation. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>Study design. * Familiarisation with test procedures; ↑ Resting metabolic rate (RMR), body composition and strength and jump tests; # Food intake and venous blood sample.</p>
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<p>Serum total 25(OH)D concentration pre-, middle- and post-supplementation (<b>A</b>) and free 25(OH)D concentration pre- and post-supplementation (<b>B</b>). * Difference within group (VitD3 pre-supplementation vs. VitD3 post-supplementation by ANOVA; <span class="html-italic">p</span> = 0.01); # difference between groups (VitD3 pre- and post-supplementation vs. placebo pre- and post-supplementation; <span class="html-italic">p</span> &lt; 0.001).</p>
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Review

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31 pages, 2118 KiB  
Review
An Integrated Approach to Skeletal Muscle Health in Aging
by Deborah Agostini, Marco Gervasi, Fabio Ferrini, Alessia Bartolacci, Alessandro Stranieri, Giovanni Piccoli, Elena Barbieri, Piero Sestili, Antonino Patti, Vilberto Stocchi and Sabrina Donati Zeppa
Nutrients 2023, 15(8), 1802; https://doi.org/10.3390/nu15081802 - 7 Apr 2023
Cited by 17 | Viewed by 6377
Abstract
A decline in muscle mass and function represents one of the most problematic changes associated with aging, and has dramatic effects on autonomy and quality of life. Several factors contribute to the inexorable process of sarcopenia, such as mitochondrial and autophagy dysfunction, and [...] Read more.
A decline in muscle mass and function represents one of the most problematic changes associated with aging, and has dramatic effects on autonomy and quality of life. Several factors contribute to the inexorable process of sarcopenia, such as mitochondrial and autophagy dysfunction, and the lack of regeneration capacity of satellite cells. The physiologic decline in muscle mass and in motoneuron functionality associated with aging is exacerbated by the sedentary lifestyle that accompanies elderly people. Regular physical activity is beneficial to most people, but the elderly need well-designed and carefully administered training programs that improve muscle mass and, consequently, both functional ability and quality of life. Aging also causes alteration in the gut microbiota composition associated with sarcopenia, and some advances in research have elucidated that interventions via the gut microbiota–muscle axis have the potential to ameliorate the sarcopenic phenotype. Several mechanisms are involved in vitamin D muscle atrophy protection, as demonstrated by the decreased muscular function related to vitamin D deficiency. Malnutrition, chronic inflammation, vitamin deficiencies, and an imbalance in the muscle–gut axis are just a few of the factors that can lead to sarcopenia. Supplementing the diet with antioxidants, polyunsaturated fatty acids, vitamins, probiotics, prebiotics, proteins, kefir, and short-chain fatty acids could be potential nutritional therapies against sarcopenia. Finally, a personalized integrated strategy to counteract sarcopenia and maintain the health of skeletal muscles is suggested in this review. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>A comprehensive approach to an integrated intervention to preserve musculoskeletal health in aging.</p>
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24 pages, 1073 KiB  
Review
Association between Polymorphisms in Vitamin D Pathway-Related Genes, Vitamin D Status, Muscle Mass and Function: A Systematic Review
by Ermira Krasniqi, Arben Boshnjaku, Karl-Heinz Wagner and Barbara Wessner
Nutrients 2021, 13(9), 3109; https://doi.org/10.3390/nu13093109 - 4 Sep 2021
Cited by 31 | Viewed by 5505
Abstract
An association between vitamin D level and muscle-related traits has been frequently reported. Vitamin D level is dependent on various factors such as sunlight exposure and nutrition. But also on genetic factors. We, therefore, hypothesize that single nucleotide polymorphisms (SNPs) within the vitamin [...] Read more.
An association between vitamin D level and muscle-related traits has been frequently reported. Vitamin D level is dependent on various factors such as sunlight exposure and nutrition. But also on genetic factors. We, therefore, hypothesize that single nucleotide polymorphisms (SNPs) within the vitamin D pathway-related genes could contribute to muscle mass and function via an impact on vitamin D level. However, the integration of studies investigating these issues is still missing. Therefore, this review aimed to systematically identify and summarize the available evidence on the association between SNPs within vitamin D pathway-related genes and vitamin D status as well as various muscle traits in healthy adults. The review has been registered on PROSPERO and was conducted following PRISMA guidelines. In total, 77 studies investigating 497 SNPs in 13 different genes were included, with significant associations being reported for 59 different SNPs. Variations in GC, CYP2R1, VDR, and CYP24A1 genes were reported most frequently, whereby especially SNPs in the GC (rs2282679, rs4588, rs1155563, rs7041) and CYP2R1 genes (rs10741657, rs10766197, rs2060793) were confirmed to be associated with vitamin D level in more than 50% of the respective studies. Various muscle traits have been investigated only in relation to four different vitamin D receptor (VDR) polymorphisms (rs7975232, rs2228570, rs1544410, and rs731236). Interestingly, all of them showed only very low confirmation rates (6–17% of the studies). In conclusion, this systematic review presents one of the most comprehensive updates of the association of SNPs in vitamin D pathway-related genes with vitamin D status and muscle traits in healthy adults. It might be used for selecting candidate SNPs for further studies, but also for personalized strategies in identifying individuals at risk for vitamin D deficiency and eventually for determining a potential response to vitamin D supplementation. Full article
(This article belongs to the Special Issue Vitamin D, Diet and Musculoskeletal Health)
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<p>Vitamin D pathway, candidate genes (in bold), and associated enzymes. DHCR7 (7-dehydrocholesterol) gene encodes 7-DHC (7-dehydrocholesterol) reductase enzyme, which converts 7-DHC to cholesterol; CYP2R1 (cytochrome P450 family 2 subfamily R member 1), CYP3A4 (cytochrome P450 family 3 subfamily A member 4), and CYP27A1 (cytochrome P450 family 27 subfamily A member 1) genes encode 25-hydroxylation cytochrome P450 enzymes responsible for converting provitamin D that is absorbed from the diet or synthesized from the action of sunlight on the skin to the circulating form 25(OH)D (25-hydroxyvitamin D); vitamin D is transported bound to vitamin D binding protein (DBP) (encoded by GC gene); LRP2 and CUBN genes encode plasma membrane receptors megalin and cubilin, respectively (involved in re-absorption of 25(OH)D via receptor mediated endocytosis); CYP27B1 encodes the cytochrome p450 enzyme which coverts 1-alpha-hydroxylates 25(OH)D to the active form 1,25(OH)<sub>2</sub>D (1,25-Dihydroxycholecalciferol, Calcitriol); CASR (calcium sensing receptor) binds calcium in extracellular matrix, impacting calcium homeostasis; Ca homeostasis impacts the synthesis of parathyroid hormone (PTH gene-a protein coding gene) which stimulates the synthesis of 1,25(OH)<sub>2</sub>D from 25(OH)D by upregulating renal 1-α-hydroxylase; CYP24A1 encodes a 24-hydroxylase enzyme which catalyzes the degradation of 25(OH)D and 1,25(OH)<sub>2</sub>D in inactive metabolites; VDR encodes the vitamin D receptor, a nuclear receptor which binds 1,25(OH)<sub>2</sub>D and forms a heterodimer with the gene product of RXR—the retinoid X receptor—to mediate the biological actions of vitamin D.</p>
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<p>PRISMA-Flow diagram showing the selection of studies included in the systematic review. The number of studies reporting genetic variants and vitamin D status as well as the number of studies reporting genetic variants together with muscle mass and function, are given in parenthesis (n<sub>1</sub> and n<sub>2</sub>).</p>
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