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1.
Changes of serum 25(OH) D3 and IGF-1 levels in patients with thyroid nodules.
Du, X, Liu, Y, Zhao, C, Fang, J, Wang, X, Wei, L
BMC endocrine disorders. 2019;(1):48
Abstract
BACKGROUND The present study aimed to study the relationship between serum 25 hydroxyvitamin D3(25(OH)D3) and insulin-like growth factor-1 (IGF-1) and thyroid nodules. METHODS Two hundred eighty-nine cases with thyroid nodules and 109 health subjects (control group) who admitted to the Hebei General Hospital during June 2016 to December 2016 were included in the study. Basic clinical information (age, sex, thyroid function, liver and kidney function, hypertension history, etc.) of patients were collected. Serum 25(OH) D3 and Serum IGF-1 were detected by electrochemiluminescence and radioimmunoassay methods, respectively. The relationship between the above-mentioned factors and thyroid nodules was statistically analyzed. RESULTS Serum 25(OH)D3, IGF-1, fasting blood glucose (FBG), total cholesterol (TC), waist circumference (WC), total triiodothyronine (TT3), total thyroxine (TT4), hypertension history, and drinking history were significantly different between the nodules group and the control group (P < 0.05). Logistic regression analysis showed that there was a negative correlation between thyroid nodules and levels of 25(OH)D3, IGF-1, TT3, as well as a positive correlation with FBG, TC, TT4, and hypertension. There was a positive correlation between IGF-1 and serum 25(OH)D3 in thyroid nodules (P < 0.05). After correcting the aforementioned factors, high-level of serum 25(OH)D3 was significantly correlated with the decreased incidence of thyroid nodules. CONCLUSIONS The incidence of thyroid nodules is relatively lower in a high-level of serum 25(OH)D3, and serum 25(OH)D3 may be a direct protective factor for thyroid nodules. Serum IGF-1 can be one of the indirect protective factors for thyroid nodules as well.
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Effect of Monthly High-Dose Vitamin D on Mental Health in Older Adults: Secondary Analysis of a RCT.
Gugger, A, Marzel, A, Orav, EJ, Willett, WC, Dawson-Hughes, B, Theiler, R, Freystätter, G, Egli, A, Bischoff-Ferrari, HA
Journal of the American Geriatrics Society. 2019;(6):1211-1217
Abstract
OBJECTIVES To test the effect of monthly high-dose vitamin D supplementation on mental health in pre-frail older adults. DESIGN Ancillary study of a 1-year double-blind randomized clinical trial conducted in Zurich, Switzerland. SETTING AND PARTICIPANTS A total of 200 community-dwelling adults 70 years and older with a prior fall event in the last year. Participants were randomized to receive 24 000 IU vitamin D3 (considered standard of care), 60 000 IU vitamin D3 , or 24 000 IU vitamin D3 plus 300 μg calcifediol per month. MEASURES The primary end point was the Mental Component Summary (MCS) of the SF-36. Secondary end points were the SF-36 Mental Health (MH) subscale and the Geriatric Depression Scale (GDS-15). RESULTS Participants' mean age was 78 years (67% women), and 58% were vitamin D deficient (<20 ng/mL). Over time, primary and secondary end points did not differ significantly among the three treatment groups or in subgroups by vitamin D status at baseline. Given the lack of a true placebo group, we explored in a predefined observational analysis the change in mental health scales by achieved 25(OH)D levels at 12 months. After adjusting for confounders, participants achieving the highest 25(OH)D quartile (Q) at 12 months (44.7-98.9 ng/mL) had the greatest improvements in MCS (Q4 = 0.79 vs Q1 = -2.9; p = .03) and MH scales (Q4 = 2.54 vs Q1 = -3.07; p = .03); these associations were strongest among participants who were vitamin D deficient at baseline. No association was found for GDS (p = .89). CONCLUSIONS For mental health, our study suggests no benefit of higher monthly doses of vitamin D3 compared with the standard monthly dose of 24 000 IU. However, irrespective of vitamin D treatment dose, achieving higher 25(OH)D levels at 12-month follow-up was associated with a small, clinically uncertain but statistically significant improvement in mental health scores.
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3.
Effects of Weekly Supplementation of Cholecalciferol and Calcifediol Among the Oldest-Old People: Findings From a Randomized Pragmatic Clinical Trial.
Ruggiero, C, Baroni, M, Bini, V, Brozzetti, A, Parretti, L, Zengarini, E, Lapenna, M, Antinolfi, P, Falorni, A, Mecocci, P, et al
Nutrients. 2019;(11)
Abstract
Vitamin D inadequacy is pervasive in the oldest-old. Many vitamin D metabolites are available for supplementation, their effects on the recovery of adequate serum levels remain unknown. We investigate the effects of supplementation with cholecalciferol (D3) and calcifediol (25D3) on serum levels of 25(OH)D, 1-25(OH)D, bone and inflammatory markers, ultimately identifying clinical predictors of successful treatment. Sixty-seven oldest-old individuals were randomized to weekly administration of 150 mcg of 25D3 or D3, from hospital admission to 7 months after discharge. Supplementation of 25D3 and D3 were associated with increasing serum levels of 25(OH)D (p < 0.001) and 1-25(OH)D (p = 0.01). Participants on 25D3 experienced a steeper rise than those on D3 (group*time interaction p = 0.01), after adjustment for intact parathyroid hormone (iPTH) levels the differences disappeared (intervention*iPTH interaction p = 0.04). Vitamin D supplementation was associated with a decreasing trend of iPTH and C-reactive protein (CRP) (p < 0.001). Polypharmacy and low handgrip strength were predictors of failure of intervention, independent of vitamin D metabolites. In conclusion, D3 and 25D3 supplementation significantly increase vitamin D serum levels in the oldest-old individuals, with a tendency of 25D3 to show a faster recovery of acceptable iPTH levels than D3. Polypharmacy and low muscle strength weaken the recovery of adequate vitamin D serum levels.
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Classes of vitamin D status and functional outcome after hip fracture: a prospective, short-term study of 1350 inpatients.
Di Monaco, M, Castiglioni, C, Di Carlo, S, La Marmora, E, Filipovic, I, Milano, E, Minetto, MA, Massazza, G
European journal of physical and rehabilitation medicine. 2019;(1):56-62
Abstract
BACKGROUND Vitamin D depletion is associated with unfavourable outcomes after hip fracture. However, the classes of vitamin D status currently in use, which are defined according to serum calcifediol levels, have not been validated for their predictive capability of the functional recovery. AIM: To investigate the association between serum calcifediol categorized into 4 classes and the functional recovery after hip fracture. DESIGN Prospective, short-term observational study. SETTING Rehabilitation hospital in Italy. POPULATION We evaluated 1350 of 1412 inpatients with hip fracture. METHODS Serum calcifediol was measured by an immunoenzymatic assay 14.7±4.4 (mean±SD) days after surgery and categorized into 4 classes: I class <12 ng/mL; II class 12-20 ng/mL; III class 21-29 ng/mL; IV class ≥30ng/mL. The functional outcome was assessed by using the Barthel Index. RESULTS We found a significant difference in Barthel index scores at the end of inpatient rehabilitation across the 4 classes of vitamin D status: χ2 (3, N.=1350) 27.2; P<0.001. The difference persisted after adjustment for 8 covariates (P=0.004). By comparing pairs of classes, we found that Barthel index scores were lower in the 829 patients of the I class than in the 275 of the II (P=0.005) who had in turn Barthel index scores lower than the 132 patients of the III class (P=0.038). Conversely, no significant differences emerged between the patients of the III class and the 114 patients of the IV class (P=0.421). The results did not materially change when Barthel Index effectiveness was substituted for Barthel Index scores as the outcome measure. CONCLUSIONS Calcifediol levels below 12ng/mL were associated with a worse recovery than those between 12 and 20ng/mL that were in turn associated with a worse recovery than those between 21 and 29 ng/mL. Conversely, no significant differences were found between the patients with calcifediol between 21 and 29ng/mL and those with calcifediol ≥30 ng/mL. CLINICAL REHABILITATION IMPACT Despite caution due to the observational design, our study suggests that vitamin D depletion should be treated after hip fracture to optimize the functional outcome, with a target level for serum calcifediol of 21-29ng/mL and no further advantages associated with calcifediol levels of 30ng/mL or higher.
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Analysis of Association between Vitamin D Deficiency and Insulin Resistance.
Szymczak-Pajor, I, Śliwińska, A
Nutrients. 2019;(4)
Abstract
Recent evidence revealed extra skeleton activity of vitamin D, including prevention from cardiometabolic diseases and cancer development as well as anti-inflammatory properties. It is worth noting that vitamin D deficiency is very common and may be associated with the pathogenesis of insulin-resistance-related diseases, including obesity and diabetes. This review aims to provide molecular mechanisms showing how vitamin D deficiency may be involved in the insulin resistance formation. The PUBMED database and published reference lists were searched to find studies published between 1980 and 2019. It was identified that molecular action of vitamin D is involved in maintaining the normal resting levels of ROS and Ca2+, not only in pancreatic β-cells, but also in insulin responsive tissues. Both genomic and non-genomic action of vitamin D is directed towards insulin signaling. Thereby, vitamin D reduces the extent of pathologies associated with insulin resistance such as oxidative stress and inflammation. More recently, it was also shown that vitamin D prevents epigenetic alterations associated with insulin resistance and diabetes. In conclusion, vitamin D deficiency is one of the factors accelerating insulin resistance formation. The results of basic and clinical research support beneficial action of vitamin D in the reduction of insulin resistance and related pathologies.
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Relationship between Serum Vitamin D and Calcium Levels and Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer.
Al-Ghafari, AB, Balamash, KS, Al Doghaither, HA
BioMed research international. 2019;:8571541
Abstract
BACKGROUND Many epidemiological studies have shown that vitamin D deficiency is associated with various types of human cancers. The biological action of vitamin D and its metabolites is mediated by the transcription factor vitamin D receptor (VDR). The VDR gene is highly expressed in the colon and is involved in many biological functions. The aim of the current study was to assess the relationship between serum vitamin D metabolite and calcium levels with VDR polymorphisms in normal and colorectal cancer (CRC) patients. METHODS Fifty Saudi CRC patients and fifty controls were enrolled in the study. The levels of total vitamin D, 25(OH)D3, and calcium were measured in serum. RESULTS The homozygous genotype (aa) of the ApaI VDR polymorphism (rs7975232) was found to correlate with total serum vitamin D levels of CRC patients, while the heterozygous (Tt) TaqI VDR polymorphism (rs731236) was associated with serum calcium levels. In contrast, the BsmI and FokI VDR polymorphisms (rs1544410 and rs2228570, resp.) did not affect the serum levels of total vitamin D, 25-hydroxyvitamin D3, and calcium. CONCLUSION Appropriate vitamin D levels were shown to be important in preventing the onset of CRC.
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Serum 25(OH)D levels after oral vitamin D3 supplementation and UVB exposure correlate.
Datta, P, Philipsen, PA, Olsen, P, Andersen, JD, Morling, N, Wulf, HC
Photodermatology, photoimmunology & photomedicine. 2019;(5):344-353
Abstract
BACKGROUND The inter-individual variation in 25(OH)D3 increase (Δ25(OH)D3 ) after vitamin D3 supplementation was determined and compared with the UVB irradiation response. METHODS Nineteen Danish participants received 85 μg vitamin D3 (cholecalciferol) daily for nine weeks with regular serum 25(OH)D3 measurements. These participants had three years earlier taken part in a 9-week controlled UVB study. The Δ25(OH)D3 was not confounded by ambient UVB, BMI or ethnicity. RESULTS Δ25(OH)D3 was 53 nmol L-1 and almost identical to Δ25(OH)D3 (52 nmol L-1 ) after UVB. Δ25(OH)D3 ranged from 17 to 91 nmol L-1 (span 74 nmol L-1 ) and was about half of that observed after UVB irradiation (span 136 nmol L-1 ). The interquartile ranges for vitamin D3 supplementation (38.8-71.4 nmol L-1 , span: 32.6 nmol L-1 ) and UVB irradiation (35.7-65.4 nmol L-1 , span: 29.7 nmol L-1 ) were similar indicating a comparable response of the two interventions. As the 25(OH)D3 start levels (R2 = 0.398, P = 3.8 × 10-3 ), 25(OH)D3 end levels (R2 = 0.457, P = 1.5 × 10-3 ) and Δ25(OH)D3 (R2 = 0.253, P = 0.028) between both interventions were correlated, this suggested a possible common individual background for the variation. Four pigment SNPs influenced the variation in the vitamin D3 -induced and UVB-induced Δ25(OH)D3 . A combined model including the influence of these four SNPs and the 25(OH)D3 start level explained 86.8% (P = 1.6 × 10-35 ) of the individual variation after vitamin D3 supplementation. CONCLUSION The inter-individual variation in the two interventions was comparable and had no common demographic but a partly common genetic background.
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Influence of genetic variation in the vitamin D pathway on plasma 25-hydroxyvitamin D3 levels and survival among patients with metastatic colorectal cancer.
Yuan, C, Renfro, L, Ambadwar, PB, Ou, FS, McLeod, HL, Innocenti, F, Meyerhardt, JA, Wolpin, BM, Goldberg, RM, Grothey, A, et al
Cancer causes & control : CCC. 2019;(7):757-765
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Abstract
PURPOSE The relationships of genetic variation in the vitamin D pathway with circulating 25-hydroxyvitamin D3 [25(OH)D] levels and survival remain largely unknown for patients with metastatic colorectal cancer (mCRC). METHODS Among 535 patients participating in a randomized trial of chemotherapy for mCRC, we prospectively measured baseline plasma 25(OH)D and examined 124 tagging single-nucleotide polymorphisms (SNPs) within seven genes in the vitamin D pathway, including five SNPs associated with circulating 25(OH)D levels in previous genome-wide association studies (GWAS). We evaluated whether these SNPs were associated with plasma 25(OH)D levels and patient outcome (overall survival, time to progression, and tumor response), using linear, logistic, and Cox proportional hazards regression. RESULTS We observed a significant association between 25(OH)D levels and an additive genetic risk score determined by the five GWAS-identified SNPs (p = 0.0009). We did not observe any direct association between 25(OH)D-associated SNPs, individually or as a genetic risk score, and patient outcome. However, we found a significant interaction between 25(OH)D levels and rs12785878 genotype in DHCR7 on overall survival (pinteraction = 0.02). CONCLUSION Germline genetic variation in the vitamin D pathway informs baseline 25(OH)D levels among patients with mCRC. The association between 25(OH)D levels and overall survival may vary by DHCR7 genotype. ClinicalTrials.gov Identifier: NCT00003594 ( https://clinicaltrials.gov/ct2/show/NCT00003594 ).
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Vitamin D and Falls in Older African American Women: The PODA Randomized Clinical Trial.
Aloia, JF, Rubinova, R, Fazzari, M, Islam, S, Mikhail, M, Ragolia, L
Journal of the American Geriatrics Society. 2019;(5):1043-1049
Abstract
BACKGROUND Limited information is available on the influence of vitamin D on falls in older high-functioning black American women. Endocrine Society guidelines propose serum 25(OH)D levels over 30 ng/mL. OBJECTIVE To determine if maintenance of serum 25(OH)D above 30 ng/mL protects against falls. DESIGN The Physical Performance, Osteoporosis and Vitamin D in African American Women (PODA) trial had a prospective, randomized, placebo-controlled, double-dummy design with two arms: one with placebo and one with vitamin D3 adjusted to maintain serum 25(OH)D above 30 ng/mL. The primary outcomes were the prevention of bone loss and the decline in physical performance. PATIENTS The target population was healthy black women older than 60 years with serum 25(OH)D between 8 and 26 ng/mL. The trial was 3 years in duration with a falls questionnaire administered every 3 months. A total of 260 women entered the study, and 184 completed the 3 years. Mean age was 68.2 years. SETTING Research center in an academic health center. MAIN OUTCOMES MEASURE Prevention of falls. INTERVENTION Participants were randomly assigned to placebo or active vitamin D. Vitamin D3 dose was adjusted to maintain serum 25(OH)D above 30 ng/mL in the active group using a double-dummy design. RESULTS Baseline 25(OH)D was 22 ng/mL. Mean serum 25(OH)D reached 47 ng/mL in the active group compared with 21 ng/mL in the placebo group. There were 14.2% falls in the previous year recalled at baseline. During the study, 46% reported falling in the treatment group compared with 47% in the placebo group. There was no association of serum 25(OH)D or vitamin D dose with the risk of falling. CONCLUSIONS There is no benefit of maintaining serum 25(OH)D above 30 ng/mL compared with the Institute of Medicine recommendation (20 ng/mL) in preventing falls in healthy older black American women. J Am Geriatr Soc 67:1043-1049, 2019.
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Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease.
Strugnell, SA, Sprague, SM, Ashfaq, A, Petkovich, M, Bishop, CW
American journal of nephrology. 2019;(4):284-293
Abstract
BACKGROUND Vitamin D repletion is recommended for secondary hyperparathyroidism (SHPT) and associated vitamin D insufficiency (VDI) in chronic kidney disease (CKD), but optimal levels of serum total 25-hydroxyvitamin D remain undefined. Clinical practice guidelines target sufficiency, whereas recent data indicate that higher levels are required to control the elevation of intact parathyroid hormone (iPTH) as CKD advances. This secondary analysis of 2 randomized controlled trials seeks to identify the minimum level of mean serum 25-hydroxyvitamin D required to control SHPT arising from VDI in stage 3 or 4 CKD. METHODS Adult subjects (n = 429) with SHPT, VDI, and stage 3 or 4 CKD were stratified by stage and treated daily with either extended-release calcifediol (ERC) or placebo in 2 identical, parallel, randomized, double-blind studies. After treatment for 26 weeks, all subjects were ranked by the level of serum total 25-hydroxyvitamin D and divided into quintiles in order to examine the relationships between the degree of vitamin D repletion and the associated changes in plasma iPTH, serum bone turnover markers, calcium, phosphorus, intact fibroblast growth factor 23 (FGF23) and vitamin D metabolites, estimated glomerular filtration rate (eGFR), and urine calcium:creatinine (Ca:Cr) ratio. RESULTS Progressive increases in serum 1,25-dihydroxyvitamin D and reductions in plasma iPTH and serum bone turnover markers were observed as mean posttreatment serum 25-hydroxyvitamin D rose from 13.9 ng/mL (in Quintile 1) to 92.5 ng/mL (in Quintile 5), irrespective of CKD stage. Mean serum calcium, phosphorus and FGF23, eGFR, and urine Ca:Cr ratio (collectively "safety parameters") did not significantly change from Quintile 1. Suppression of iPTH and bone turnover markers was not observed until serum 25-hydroxyvitamin D rose to at least 50.8 ng/mL (Quintile 3). CONCLUSION ERC therapy produced exposure-dependent reductions in plasma iPTH and bone turnover markers only when mean serum total 25-hydroxyvitamin D reached at least 50.8 ng/mL, indicating that current targets for vitamin D repletion therapy in CKD are too low. Gradual elevation of mean serum 25-hydroxyvitamin D to 92.5 ng/mL was not associated with significant adverse changes in safety parameters.