Factors determining the serum 25-hydroxyvitamin D response to vitamin D supplementation: Data mining approach.

Vitamin D supplementation has been shown to prevent vitamin D deficiency, but various factors can affect the response to supplementation. Data mining is a statistical method for pulling out information from large databases. We aimed to evaluate the factors influencing serum 25-hydroxyvitamin D levels in response to supplementation of vitamin D using a random forest (RF) model. Data were extracted from the survey of ultraviolet intake by nutritional approach study. Vitamin D levels were measured at baseline and at the end of study to evaluate the responsiveness. We examined the relationship between 76 potential influencing factors on vitamin D response using RF. We found several features that were highly correlated to the serum vitamin D response to supplementation by RF including anthropometric factors (body mass index [BMI], free fat mass [FFM], fat percentage, waist-to-hip ratio [WHR]), liver function tests (serum gamma-glutamyl transferase [GGT], total bilirubin, total protein), hematological parameters (mean corpuscular volume [MCV], mean corpuscular hemoglobin concentration [MCHC], hematocrit), and measurement of insulin sensitivity (homeostatic model assessment of insulin resistance). BMI, total bilirubin, FFM, and GGT were found to have a positive relationship and homeostatic model assessment for insulin resistance, MCV, MCHC, fat percentage, total protein, and WHR were found to have a negative correlation to vitamin D concentration in response to supplementation. The accuracy of RF in predicting the response was 93% compared to logistic regression, for which the accuracy was 40%, in the evaluation of the correlation of the components of the data set to serum vitamin D.

Effect of low-fat dairy products fortified with 1500IU nano encapsulated vitamin D3 on cardiometabolic indicators in adults with abdominal obesity: a total blinded randomized controlled trial.

BACKGROUND & AIMS: Vitamin D deficiency is widespread worldwide. In this study, we aimed to evaluate the effect of a nano encapsulated form of vitamin D used for fortifying low-fat dairy products (milk and yogurt) on anthropometric indices, glycemic status, and lipid profile in subjects with abdominal obesity. METHODS: In a totally (quadruple) blinded, randomized, and parallel-controlled trial, 306 individuals with abdominal obesity were randomly allocated to one of four groups: fortified low-fat yogurt (FY, 1500 IU nano encapsulated vitamin D3 per 150 g/d), non-fortified low-fat yogurt (nFY), fortified low-fat milk (FM, 1500 IU nano encapsulated vitamin D3 per 200 g/d), non-fortified low-fat milk (nFM), for 10 weeks (nFM and nFY, were considered as the control groups). Anthropometric and biochemical parameters were measured at baseline and after a ten-week trial in Mashhad, Iran. RESULTS: After the ten-week intervention, we found a significant increase in serum concentration of 25(OH)D in both the FM and FY groups compared to the respective control groups (19.10 ± 5.69 ng/mL and 20.88 ± 5.76 ng/mL respectively, p < .001). We observed a significant reduction in weight to hip ratio (p = .04) and a significant improvement in triglyceride (p < .001) and HDL-C (p = .01) only in FM group compared to nFM group. Also, we found a significant reduction in fasting serum insulin (p < .001), and a significant improvement of HOMA-IR (p < .001) and QUICKI (p < .001) in both intervention groups compared to their placebos. CONCLUSIONS: An intake of fortified dairy products containing nano-encapsulated vitamin D3 was associated with an improvement in some measures of anthropometric indices, glucose homeostasis, and lipid profiles, particularly in individuals receiving fortified milk. Hence, along with other benefits, fortification of dairy products with vitamin D may be an effective approach to improve some cardiometabolic indicators, such as insulin resistance. TRIAL REGISTRATION NUMBER: IRCT20101130005280N27.

Common Polymorphisms in Genes Related to Vitamin D Metabolism Affect the Response of Cognitive Abilities to Vitamin D Supplementation.

It is possible that vitamin D acts as a neurosteroid and that vitamin D deficiency may have an adverse impact on brain function and cognitive function. There are a few reports that have demonstrated an association between polymorphisms of genes involved in vitamin D metabolism and neurodegenerative disease. We aimed to evaluate the relationship between common, functional vitamin D-associated gene variants and cognitive abilities and to investigate the effect size of this polymorphism on cognitive capabilities associated with high-dose vitamin D supplementation. A total of 319 healthy adolescents received a high dose of vitamin D (50,000 IU)/week for 9 weeks. A questionnaire was used to assess cognitive abilities at baseline and after treatment. The genotypes of the CYP2R1-rs10766197 and GC-rs4588 variants were determined using TaqMan genotyping techniques. At baseline, total cognitive ability scores were higher in the AA group who were homozygous for the uncommon allele, compared with the other (AG and GG) genotypes of the CYP2R1-rs10766197 polymorphism (104.9 ± 27.8 vs. 79.1 ± 38.8 vs. 73.1 ± 25.6; p < 0.001, respectively). During the supplementation period, cognitive ability scores increased in individuals with the AG and GG genotypes, while individuals with a AA genotype did not show significant change in total score after intervention (p = 0.17). For GC SNP (rs4588), no major differences at baseline and trial-net change of cognitive tasks score were observed between the genotypes under three genetic models (pSNP = 0.67). Vitamin D supplements have trait-dependent effects on cognitive performance that suggests a causal role for vitamin D in cognitive performance. The rs10766197 variant, near the CYP2R1 gene locus, significantly modified the efficacy of high-dose vitamin D3 supplementation for its effects on improving cognitive abilities indicate that some subjects might require a higher dose to benefit from in terms of cognitive performance.

Determinants of the magnitude of response to vitamin D supplementation in adolescent girls identified using a decision tree algorithm.

Vitamin D (VitD) supplementation is an inexpensive and effective approach for improving VitD insufficiency/deficiency. However, the response to supplementation, with respect to the increase in serum 25(OH)D level varies between individuals. In this study, we have assessed the factors associated with the response to VitD supplementation using a decision-tree algorithm. Serum VitD levels, pre- and post-VitD supplementation was used as the determinant of responsiveness. The model was validated by constructing a receiver operating characteristic curve. Serum VitD at baseline levels was at the apex of the tree in our model, followed by serum low-density lipoprotein cholesterol and triglyceride, age, waist-hip ratio, and high-density lipoprotein cholesterol. Our model suggests that these determinants of responsiveness to VitD supplementation had sensitivity, specificity, and accuracy, 59.4, 75.8 and 69.3%, respectively. The decision tree model appears to be a relatively accurate, specific, and sensitive approach for identifying the factors associated with response to VitD supplementation.

The effects of vitamin D supplementation on indices of glycemic control in Iranian diabetics: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This systematic review and meta-analysis aimed to assess the effects of vitamin D supplements on indices of glycemic control [homeostatic model assessment-insulin resistance (HOMA-IR), hemoglobin A1C (HbA1C), fasting blood glucose (FBG), and quantitative insulin-sensitivity check index (QUICKI) and lipid profile in diabetic patients. METHODS: Eight databases were searched, for randomized controlled trials (RCTs) or cross-sectional and cohort studies that have been published up to December 2017. We used the comprehensive meta-analysis (CMA) software for all statistical analysis and used the I2 index for assessing heterogeneity. A p value of <0.05 was considered as statistically significant. RESULTS: We found 621 articles, and after the exclusion of ineligible publications, 82 studies remained to be assessed of which 37 were used for meta-analysis. Vitamin D supplementation was associated with a significant improvement in FBG (p = 0.001 and 95% CI: -0.526 to -0.136) and HbA1C (p = 0.003 and 95% CI: 1.719 to -0.361) in individuals with type 2 diabetes mellitus (T2DM); while in women with gestational diabetes mellitus (GDM) the reduction in FBG (p = 0.071 and 95% CI: -0.873 to -0.035) and HbA1C (p = 0.199 and 95% CI: 3.270 to 0.681) failed to reach statistical significance. Treatment with vitamin D supplements was associated with an improvement in HOMA-IR in pregnant diabetic women (p = 0.028 and 95% CI: 0.924 to -0.053) and for individuals with diabetes mellitus (p = 0.005 and 95% CI: 1.772 to -0.319). The pooled result of the cross-sectional meta-analysis indicated that serum vitamin D concentrations were significantly lower in diabetic patients than in healthy controls (p = 0.018 and 95% CI: 0.587 to -0.054). CONCLUSION: This meta-analysis suggests that vitamin D supplementation improves indices of glycemic control (FBG, HOMA-IR, and HbA1C) in patients with diabetes mellitus. Hence, vitamin D supplements may be of potential therapeutic value in diabetic patients, as an adjuvant therapy along with other treatments.

Associations of vitamin D binding protein variants with the vitamin D-induced increase in serum 25-hydroxyvitamin D.

BACKGROUND: Vitamin D deficiency is a global problem that may be improved by vitamin D supplementation; however, the individual's response to the intervention varies. We aimed to investigate possible genetic factors that may modify the impact of environmental exposure on vitamin D status. The candidate gene variant we investigated was the Gc gene-rs4588 polymorphism at the vitamin D receptor (DBP) locus. METHODS: A total of 619 healthy adolescent Iranian girls received 50000 IU of vitamin D3 weekly for 9 weeks. Serum 25(OH) D concentrations, metabolic profiles and dietary intake were measured at baseline and after 9 weeks of supplementation. The genotypes of the DBP variant (rs4588) were analyzed using the TaqMan genotyping assay. RESULTS: Our results revealed that the rs4588 polymorphism might be associated with serum 25-hydroxy vitamin D both at baseline (p value = 0.03) and after intervention (p value = 0.008). It seemed that the outcome of the intervention was gene-related so that the subjects with common AA genotype were a better responder to vitamin D supplementation (Changes (%) 469.5 (427.1) in AA carriers vs. 335.8 (530) in GG holders), and carriers of the less common GG genotype experienced a rise in fasting blood glucose after 9 weeks (Changes (%) 0 (1.5)). Our findings also showed that the statistical interaction between this variant and supplementation was statistically significant (intervention effect p-value<0.001 and p-value SNP effect = 0.03). The regression model also revealed that after adjusted for potential confounders, likelihood of affecting serum 25(OH)D in individuals who were homozygous for the uncommon allele G was less than those homozygous for the more common AA genotype (OR = 4.407 (1.82-8.89); p = 0.001). CONCLUSION: Serum vitamin 25(OH) D following vitamin 25(OH) D3 supplementation appears to be modified by genetic background. The Gc genetic variant, rs4588 encoding the vitamin D receptor seems to influence the response to vitamin D supplementation.

A genetic variant in the cytochrome P450 family 2 subfamily R member 1 determines response to vitamin D supplementation.

BACKGROUND: Globally, about 1 billion people have inadequate levels of serum vitamin D and it is prevalent in all ethnicities and age groups. Few foods naturally contain sufficient vitamin D; therefore, most people get their requirements through supplementation. Hence vitamin D status is affected by genetic and environmental determinants including season of measurement, diet habitual, health status, body mass index and concurrent medication. Further studies are necessary to understand how genetic variation influences vitamin D metabolism. We aimed to explore the association between a potential vitamin D-related polymorphism (the rs10766197 polymorphism in the CYP2R1 gene) with the response to supplementation of vitamin D in 253 healthy Iranian girls. MATERIAL AND METHOD: A total of 253 healthy subjects received 50,000 IU of vitamin D3 weekly for 9 weeks. Serum 25(OH)D concentrations and metabolic profiles were measured at baseline and after 9 weeks of supplementation. The genotypes of the CYP2R1 variant (rs10766197) were identified using TaqMan genotyping assays. RESULTS: Serum 25(OH)D during the supplementation, increased in all individuals. Subjects with a AA major genotype at this locus had higher vitamin D concentrations after intervention (Changes (%) 448.4% ± 425% in AA vs 382.7% ± 301% in GG). This genetic variant modulated the response to supplementation (p < 0.001 and p-value SNP = 0.05). Regression analysis showed that the probability of affecting serum 25(OH)D, in individuals who had homozygous major allele GG was two-fold higher than carriers of the uncommon allele A (OR = 2.1 (1-4.2); p = 0.03). Interestingly, the Hs-CRP was reduced in AA carries while was elevated in individuals with GG and AG genotypes, after high-dose vitamin D supplementation. CONCLUSION: Changes in serum vitamin D and metabolic profile following high dose supplementation with vitamin D were associated with CYP2R1 polymorphism. Although carriers of the common G allele showed a greater response in the serum vitamin D.

Relationship of Dietary and Serum Zinc with Depression Score in Iranian Adolescent Girls.

Zinc deficiency, which is common among Iranian populations, is believed to play a crucial role in the onset and progression of mood disorders such as depression in different stages of life. We have therefore investigated the relationship between serum/dietary zinc status and depression scores among adolescent girls living in northeastern Iran. Serum zinc was measured by flame atomic absorption (Varian AA240FS) and the mean zinc intake was assessed using 3-day food record. A validated Persian version of the Beck Depression Inventory (BDI) was used to determine the severity of depressive symptoms for all subjects. Data were analyzed using SPSS 18 software. There was a statistically significant correlation between dietary zinc intake and serum zinc concentration (r = 0.117, p = 0.018). Dietary intake of zinc (7.04 ± 4.28 mg/day) was significantly lower among subjects with mild to severe depression symptoms than those with no or minimal depression symptoms (8.06 ± 3.03 mg/day). Dietary zinc intake was inversely correlated with depression score (r = 0.133, p = 0.008). However, there was no significant difference in serum zinc concentrations among individuals with no or minimal and mild to severe depression symptoms (p = 0.5). Dietary zinc intake, but not serum zinc concentration, was inversely associated with depression symptoms. Therefore, controlled clinical trials are needed to determine the efficacy of zinc supplementation in the treatment of depression disorders.

High dose vitamin D supplementation can improve menstrual problems, dysmenorrhea, and premenstrual syndrome in adolescents.

Vitamin D has a crucial role in female reproduction, possibly through its effects on calcium homeostasis, cyclic sex steroid hormone fluctuations, or neurotransmitter function. We have assessed the effects of vitamin D supplementation on dysmenorrhea and premenstrual syndrome (PMS) in adolescents. In this study, 897 adolescent girls living in Mashhad and Sabzevar, Iran, received nine high-dose vitamin D supplements (as 50,000 IU/week of cholecalciferol) and were followed up over 9 weeks. We evaluated the effect of vitamin D supplementation on individuals in four categories: those with only PMS; individuals with only dysmenorrhea; subjects with both PMS and dysmenorrhea and normal subjects. The prevalence of PMS after the intervention fell from 14.9% to 4.8% (p < .001). Similar results were also found for the prevalence of subjects with dysmenorrhea (35.9% reduced to 32.4%), and in subjects with both PMS and dysmenorrhea (32.7% reduced 25.7%). Vitamin D supplementation was associated with a reduction in the incidence of several symptoms of PMS such as backache and tendency to cry easily as well as decrement in pain severity of dysmenorrhea (p < .05). High dose vitamin D supplementation can reduce the prevalence of PMS and dysmenorrhea as well as has positive effects on the physical and psychological symptoms of PMS.

Serum and dietary zinc and copper in Iranian girls.

OBJECTIVE: Girls with micronutrient deficiencies may have impaired growth and development, and furthermore this may also impact on their childbearing. We have investigated the relationship between serum zinc and copper concentrations, dietary zinc and copper intake and anthropometric and demographic parameters, and cardiovascular risk factors, in 408 girls living in northeastern Iran. METHODS: A total of 408 healthy girls, aged 12-18 years old, were included in our study. Serum zinc and copper concentrations were measured by flame atomic absorption (Varian AA240FS) and zinc and copper intake were assessed using a 3-day dietary record. RESULTS: There was a weak correlation between serum and dietary zinc intake (r = 0.117, p = 0.018). The correlation between serum and dietary copper approached significance (r = -0.094, p = 0.056). The mean serum zinc and copper concentrations were 14.61 ±â€¯2.71 µmol/L and 19.48 ±â€¯8.01 µmol/L respectively. Height, total cholesterol (TC) and low-density lipoprotein (LDL) were positively correlated with serum copper concentration. Subjects with high serum copper concentrations (>24 µmol/L) were found to have a significantly higher fasting blood glucose (FBG) compared to subjects with normal, or low serum copper concentrations (p = 0.033). Girls who were in the 5th percentile or greater for height were found to have higher serum copper concentrations than girls in other height categories. CONCLUSION: There was a weak relationship between dietary and serum concentrations of zinc. Copper status was associated with anthropometric and biochemical parameters, including FBG and lipid profile. Further studies are required to define the role of copper in metabolic health.

Assessment of the efficacy of omega-3 fatty acids on metabolic and inflammatory parameters in patients with schizophrenia taking clozapine and sodium valproate.

Omega-3 fatty acid (FA) supplementation has been reported to improve several cardio-metabolic risk factors. We aimed to assess the efficacy of omega-3 fatty acids on metabolic and inflammatory indices in patients with schizophrenia who were taking clozapine and sodium valproate. All patients were on a stable dose of 300-400mg of clozapine for 3 months. Subjects were randomized to treatment with either omega-3 fatty acid (4gr/day) or a placebo for 8 weeks. Height, weight, abdominal circumference, serum lipid profile, fasting blood glucose (FBG), and serum high sensitivity-C-reactive protein (hs-CRP) were determined at baseline and after 8 weeks of treatment. Fifty six subjects were recruited into the study. Patients with schizophrenia who were in the group receiving omega-3 FA capsules had an improvement in some anthropometric indices including weight, BMI, wrist and waist circumference, compared to the placebo group. Only changes in waist circumferences remained significantly different after adjustment for serum fasted TG. Our results showed omega-3 FA supplementation can improve some anthropometric indices in patients with schizophrenia who are taking clozapine pharmacotherapy.

Nutrients intake, and serum calcium and phosphorus levels: An evidence-based study.

INTRODUCTION: Dietary calcium and phosphorus appear to be important determinants of dyslipidemia and hypertension. We have investigated (1) the prevalence of hypocalcemia and hypophosphatemia in an Iranian population, and (2) the association between nutrient's intake and serum levels of calcium and phosphorus. METHODS: A total of 908 individuals were enrolled using a stratified-cluster sampling method from the Mashhad stroke and heart atherosclerosis disorder (MASHHAD) study. Dietplan6 software was used for 24-hour recalls and food frequency questionnaire to investigate macro- and micronutrient intakes of our population, followed by univariate analysis for evaluation of the association of dairy consumption with serum calcium and phosphorus. RESULTS: We observed that the mean dietary Ca intake was 862.4 mg/d (672.7-1052) for men and 864.2 mg/d (604.5-1123) for women in our population, which is lower than the dietary reference intake for Ca. Moreover, a significant relationship was detected between serum calcium level and dietary intakes of saturated fatty acids, copper, iodine, sucrose, potato, and juices. Of note, we observed a negative association between copper intake, and serum Ca (P˂.01). Also, a significant association was found between serum phosphorus levels and dietary intakes of chicken meat and fresh fruits. Interestingly, we observed an inverse relationship between tea and Ca/P ratio (eg, -r=.098; P=.02). CONCLUSION: We found that the dietary intake of Ca was not sufficient in our population and was associated with the dietary intake of some macro- and micronutrient, supporting further investigation on clinical impact of this condition on calcium/phosphorus deficiency related diseases.

High-dose vitamin D supplementation is associated with an improvement in several cardio-metabolic risk factors in adolescent girls: a nine-week follow-up study.

Background Vitamin D deficiency is a prevalent and important global health problem. Because of its role in growth and development, vitamin D status is likely to be particularly important in adolescent girls. Here, we explored the effects of high-dose vitamin D supplementation on cardio-metabolic risk factors. Methods We have examined the effects of vitamin D supplementation on cardio-metabolic risk factors in 988 healthy adolescent girls in Iran. Fasting blood samples and anthropometric measurements were obtained at baseline and after supplementation with high-dose vitamin D. All individuals took a capsule of 50,000 IU vitamin D/week for nine weeks. The study was completed by 940 participants. Results The prevalence of vitamin D deficiency was 90% at baseline, reducing to 16.3% after vitamin D supplementation. Vitamin supplementation was associated with a significant increase in serum concentrations of 25 (OH) vitamin D and calcium. There were significant reductions in diastolic blood pressure, heart rate, waist circumference and serum fasting blood glucose, total- and low-density lipoprotein-cholesterol after the nine-week period on vitamin D treatment, but no significant effects were observed on body mass index, systolic blood pressure or serum high-density lipoprotein cholesterol and triglyceride. Conclusion Vitamin D supplementation had beneficial effects on cardio-metabolic profile in adolescent girls.

Abdominal and auricular acupuncture reduces blood pressure in hypertensive patients.

INTRODUCTION: Hypertension is an important risk factor of cardiovascular disease (CVD), which is associated with premature death, myocardial infarction, stroke, peripheral vascular disease, and renal disease. The goal of the present study was to use a randomized controlled clinical trial to explore and compare the effectiveness of abdominal and auricular acupuncture on blood pressure in 440 subjects with and without obesity. METHODS: Four hundred participants were recruited and randomized to one of four groups: cases and controls receiving auricular acupuncture (204 subjects) and cases and controls receiving abdominal electroacupuncture (196 subjects). Blood pressure and anthropometric parameters were measured before and after the intervention period. In order to match the initial diet of the groups, participants were required to follow an isocaloric diet for two weeks before the trial, and a low-calorie diet for 6 weeks during the intervention period. RESULTS: We observed a significant time dependent improvement in the systolic blood pressure measurements in the abdominal intervention group, although this improvement was more pronounce in the first period of study. Of note, in the auricular intervention group, a significant increasing in the level of SBP was detected. Importantly no statistically significant changes were found in the corresponding sham groups. CONCLUSIONS: Our findings demonstrated that abdominal electro-acupuncture for 6 weeks reduced both systolic and diastolic blood pressure and auricular acupuncture had a short-term adverse effect on both SBP and DBP.