• Journal of Animal Science and Technology
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• v.56 no.8
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• pp.33.1-33.8
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• 2014

Background: Sox 9 is a major marker of chondrocyte differentiation. When chondrocytes are cultured in vitro they progressively de-differentiate and this is associated with a decline in Sox 9 expression. The active form of vitamin D, 1, 25 $(OH)_2D_3$ has been shown to be protective of cartilage in both humans and animals. In this study equine articular chondrocytes were grown in culture and the effects of 1, 25 $(OH)_2D_3$ upon Sox 9 expression examined. The expression of the transient receptor potential vanilloid (TRPV) ion channels 5 and 6 in equine chondrocytes in vitro, we have previously shown, is inversely correlated with de-differentiation. The expression of these channels in response to 1, 25 $(OH)_2D_3$ administration was therefore also examined. Results: The active form of vitamin D (1, 25 $(OH)_2D_3$ when administered to cultured equine chondrocytes at two different concentrations significantly increased the expression of Sox 9 at both. In contrast 1, 25 $(OH)_2D_3$ had no significant effect upon the expression of either TRPV 5 or 6 at either the protein or the mRNA level. Conclusions: The increased expression of Sox 9, in equine articular chondrocytes in vitro, in response to the active form of vitamin D suggests that this compound could be utilized to inhibit the progressive de-differentiation that is normally observed in these cells. It is also supportive of previous studies indicating that $1{\alpha}$, 25-dihydroxyvitamin $D_3$ can have a protective effect upon cartilage in animals in vivo. The previously observed correlation between the degree of differentiation and the expression levels of TRPV 5/6 had suggested that these ion channels may have a direct involvement in, or be modulated by, the differentiation process in vitro. The data in the present study do not support this.

• Journal of Nutrition and Health
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• v.56 no.1
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• pp.1-11
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• 2023

Purpose: Obesity is associated with alterations in vitamin D metabolism and elevation of parathyroid hormone (PTH). Increased PTH level in obesity is likely one of the factors contributing to the dysregulation of vitamin D metabolism. We investigated the effects of lowering the PTH level in high-fat diet-induced obese mice on vitamin D metabolism. Methods: Five-week-old male C57BL/6N mice were fed either with control (10% energy as fat) or high-fat (60% energy as fat) diets ad libitum for 12 weeks, and vehicle or cinacalcet HCl (30 ㎍/g body weight) was gavaged daily during the final week of the experiment. The following groups were studied: CON (control diet + vehicle), HFD (high-fat diet + vehicle), and HFD-CIN (high-fat diet + cinacalcet HCl). PTH, 1,25-dihydroxyvitamin D (1,25[OH]₂D), 25-hydroxyvitamin D (25[OH]D), calcium, and phosphate levels in circulation, and the expression of genes related to vitamin D metabolism in the liver and kidneys were determined. Results: Renal 1α-hydroxylase expression in the HFD group was higher than that in the CON group despite the lack of a difference in the PTH levels between the 2 groups. The plasma PTH level in the HFD-CIN group was 60% lower than that in the HFD group (p < 0.05). In parallel, the HFD-CIN group had lower adipose tissue amount (9% lower), renal 1α-hydroxylase expression (48% lower), and plasma 1,25(OH)₂D concentration (38% lower) than the HFD group. Conclusion: Lowering the PTH levels in high-fat diet-induced obese mice recovered the expression of renal 1α-hydroxylase and might be associated with lower amounts of white adipose tissue.

• Nutrition Research and Practice
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• v.14 no.2
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• pp.117-126
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• 2020

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months. SUBJECTS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6-12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3 - 500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections). RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D. CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.4
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• pp.403-412
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• 2021

Purpose: This study aimed to determine the serum 25-hydroxy-vitamin D (25(OH)D) status of breastfed infants less than six months old and their mothers, and factors affecting the status. Methods: This cross-sectional study was done on breastfed, term, Filipino infants less than six months old who were seen at local health centers and clinics in an urban area. The serum 25(OH)D levels of these infants and their mothers were determined, and their demographic data, nutritional status, sun exposure behavior, and maternal vitamin D intake were analyzed for correlation using regression models. Results: Among the 131 infants, 101 (77%) had vitamin D deficiency (VDD), which was defined as having 25(OH)D levels <37.5 nmol/L, and 13 (10%) had vitamin D insufficiency (VDI), with levels >37.5-50 nmol/L. Conversely, maternal VDD with levels <50 nmol/L was seen in 31 (24%) mothers and maternal VDI with levels 50-75 nmol/L, in 63 (48%) mothers. Infant age and maternal 25(OH)D status were independent predictors of infant VDD. Infants less than three months old were found to have a six-time increased risk of infant VDD (p=0.004). Infants who had mothers with VDD had a six-time increased risk, whereas those with maternal VDI had a four-time increased risk of infant VDD (p=0.049 and p=0.020, respectively). Conclusion: Both infant and maternal VDD and VDI were seen to be highly prevalent in this tropical, urban community. Young infants and maternal VDD/VDI independently increased the risk of infant VDD, whereas lack of sun exposure of the mothers increased the risk for maternal VDI.

• Journal of Hospice and Palliative Care
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• v.18 no.2
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• pp.120-127
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• 2015

Purpose: We aimed to investigate how serum vitamin D levels are related to survival of terminally ill cancer patients. Methods: From May 2012 through June 2013, a retrospective chart review was performed on 96 hospice patients. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with severe vitamin D deficiency and Coxcy and Coxional hazard analyses were used to evaluate effects on survival. Results: The mean vitamin D level in patients was $8.60{\pm}7.16ng/ml$. Vitamin D was severely deficient (<10 ng/ml) in 75 patients (78.2%), deficient (10~20 ng/ml) in 13 patients (13.5%), relatively insufficient (21~29 ng/ml) in five patients (8.3%) and sufficient ((t ng/ml) in three patients (3.1%). Hyperbilirubinemia (${\geq}1.2g/dl$) was the only factor associated with severe vitamin D deficiency according to the multiple logistic regression analysis (Odds ratio, OR=18.48, P<0.05). Although hyperbilirubinemia showed a strong association with survival (Hazard ratio, HR=2.25, P<0.01), no association was found between severe vitamin D deficiency and survival (HR=1.15, P>0.05) in Cox's proportional hazard analysis. Conclusion: Although serum vitamin D levels were severely low in terminally ill cancer patients, we found no association between severe vitamin D deficiency and patient survival.

• Tuberculosis and Respiratory Diseases
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• v.77 no.2
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• pp.73-80
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• 2014

Background: Low levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells. Methods: HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-$1{\beta}$ (IL-$1{\beta}$) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D ($1,25(OH)_2D$) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction. Results: IL-$1{\beta}$ significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and $1,25(OH)_2D$ (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and $1,25(OH)_2D$. Conclusion: Vitamin D, 25(OH)D, and $1,25(OH)_2D$ play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-$1{\beta}$ stimulated MMP-9 production and conversion to its active form but also inhibiting IL-$1{\beta}$ inhibition on TIMP-1 and TIMP-2 production.

• Journal of Environmental Health Sciences
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• v.44 no.2
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• pp.188-195
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• 2018

Objectives: This study aimed to investigate the association between vitamin D deficiency and the risk of diabetes mellitus, and also examined whether their association is differed by sex and age. Methods: We analyzed the data from 28,135 subjects ${\geq}20years$ old who were registered for the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2014. Vitamin D was measured using serum 25-hydroxyvitamin D (25(OH)D) concentrations. Results: After adjusting for potential confounders (age, sex, education, income, total energy intake, smoking, physical activity, body mass index, and waist circumference), lower vitamin D was dose-dependently associated with a higher risk of diabetes mellitus (p-trend=0.004). When compared with the sufficient group (25(OH)D ${\geq}30ng/mL$), the severe deficient group (25(OH)D <10 ng/mL) had 1.46 (95% CI 1.11-1.94) odds ratio for the risk of diabetes mellitus. This association was markedly strong in men and adults aged ${\geq}40$, whereas no significant association was observed in women and adults aged <40. Conclusions: We found that vitamin D deficiency may be associated with an increased risk for diabetes mellitus in Korean adults. Our findings suggest that intake of higher vitamin D may help reduce the risk of diabetes mellitus.

• Nutrition Research and Practice
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• v.16 no.1
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• pp.120-131
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• 2022

BACKGROUND/OBJECTIVES: Low early pregnancy serum 25-hydroxy vitamin D (25[OH]D) levels can increase gestational diabetes mellitus (GDM) risk, although inconsistent findings related to that association have been reported. This study examined the association of serum vitamin D with GDM and the possible influencers on this association. SUBJECTS/METHODS: This study included 259 pregnant women within the Seremban Cohort Study (SECOST). Blood samples at < 14 weeks of gestation were drawn to determine serum 25(OH)D levels. GDM diagnosis was made at 24 to 32 weeks of gestation using a standard procedure. Association between serum vitamin D and GDM was tested using binary logistic regression. RESULTS: Nearly all women (90%) had mild (68.3%) or severe (32.2%) vitamin D deficiency (VDD). Non-GDM women with mild VDD had a significantly higher mean vitamin D intake than GDM women with mild VDD (t = 2.04, p < 0.05). Women with higher early pregnancy serum vitamin D levels had a greater risk of GDM. However, this significant association was only identified among those with a family history of type 2 diabetes mellitus (T2DM) and in women with a body mass index indicating overweight or obese status. CONCLUSIONS: The high prevalence of VDD in this sample of pregnant women underscores the need for effective preventive public health strategies. Further investigation of this unexpected association between serum vitamin D level and GDM risk in predominantly VDD pregnant women and the potential effects of adiposity and family history of T2DM on that association is warranted.

• Clinical and Experimental Pediatrics
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• v.60 no.7
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• pp.216-220
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• 2017

Purpose: Vitamin D is associated with various pathological conditions such as cardiovascular diseases and cancer. We investigated the relationship between vitamin D and Kawasaki disease (KD). Methods: We performed a retrospective review of the medical records of patients with KD between February 2013 and March 2016 in Daegu Fatima Hospital. Study participants were grouped according to vitamin D serum concentration. Group 1 included patients with 25(OH)-vitamin D ${\geq}20ng/mL$. Group 2 included patients with 25(OH)-vitamin D <20 ng/mL. We analyzed the clinical characteristics and laboratory data of the 2 groups. Results: Of the 91 patients, 52 were included in group 1, and 39 in group 2. Group 1 patients had significantly higher levels of calcium, phosphate, albumin and sodium than group 2 patients did. There were no differences in clinical characteristics, but the proportion of patients with polymorphic rash was significantly higher in group 2. Resistance to intravenous immunoglobulin was more frequent in group 2 (P=0.023). No significant difference in the incidence of coronary artery complications was observed. Conclusion: Low vitamin D levels are associated with resistance to intravenous immunoglobulin therapy in KD. Vitamin D deficiency might be a risk factor for immunoglobulin resistance in KD.

• Nutrition Research and Practice
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• v.15 no.sup1
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• pp.32-40
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• 2021

BACKGROUND/OBJECTIVES: Considering the high number of deaths from coronavirus disease 2019 (COVID-19) in Latin American countries, together with multiple factors that increase the prevalence of vitamin D deficiency, we aimed to determine 25-hydroxyvitamin D (25[OH]D) levels and its association with mortality in patients with critical COVID-19. SUBJECTS/METHODS: This was a prospective observational study including adult patients with critical COVID-19. Data, including clinical characteristics and 25(OH)D levels measured at the time of intensive care unit admission, were collected. All patients were followed until hospital discharge or in-hospital death. The patients were divided into those surviving and deceased patient groups, and univariate and multivariate logistic regression analyses were performed to determine independent predictors of in hospital mortality. RESULTS: The entire cohort comprised 94 patients with critical COVID-19 (males, 59.6%; median age, 61.5 years). The median 25(OH)D level was 12.7 ng/mL, and 15 (16%) and 79 (84%) patients had vitamin D insufficiency and vitamin D deficiency, respectively. The median serum 25(OH)D level was significantly lower in deceased patients compared with surviving (12.1 vs. 18.7 ng/mL, P < 0.001). Vitamin D deficiency was present in 100% of the deceased patients. Multivariate logistic regression analysis revealed that age, body mass index, other risk factors, and 25(OH)D level were independent predictors of mortality. CONCLUSIONS: Vitamin D deficiency was present in 84% of critical COVID-19 patients. Serum 25(OH)D was independently associated with mortality in critical patients with COVID-19.