The associations of oxidative stress and inflammatory markers with obesity in Iranian population: MASHAD cohort study.

BACKGROUND: Low-grade inflammation and stress oxidative condition play a role in the pathogenesis of obesity, and the serum levels of these markers, such as pro-oxidant-antioxidant balance (PAB), high-sensitivity C-reactive protein (hs-CRP), and uric acid may indicate obesity progression. In this study, we aimed to investigate the relationship between obesity with PAB, hs-CRP, and uric acid in the Iranian population. METHODS: This study was derived from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. A total of 7985 subjects aged 35 to 65 years were divided into three groups according to body mass index (BMI) as: normal, overweight and obese groups. Anthropometric indices and biochemical parameters such as PAB, superoxide dismutase type 1 (SOD1), hs-CRP, and uric acid were measured in all the participants. We evaluated the association of obesity with inflammatory factors by using multivariate regression analysis. Also, those participants with hypertension, an endocrine disorder, history of cardiovascular diseases and diabetes mellitus were excluded from the study. RESULTS: There was a positive significant correlation between BMI and serum PAB, hs-CRP and uric acid (p < 0.001). While no statistically significant relation was observed between BMI and SOD1 (p = 0.85). Multivariate regression analysis showed that the risk of overweight and obesity increased 1.02 and 1.03-fold according to increase 10 units of PAB raise in comparison to reference group (normal weight) [(odds ratio (OR): 1.02, 95% CI (1.01-1.03)] and [OR: 1.03, 95% CI (1.01-1.04)], respectively). In addition, hs-CRP serum concentration was significantly associated with a high risk of obesity [(OR: 1.02; 95% CI (1.01-1.03)]. While the high levels of serum uric acid were associated with increased odds of overweight and obesity risk [OR: 1.4; CI (1.39-1.58) and OR: 1.76; CI (1.63-1.89), respectively]. CONCLUSIONS: Generally, we showed a significant association between BMI and serum PAB, hs-CRP values and uric acid levels, suggesting the role of these factors as risk stratification factors for obesity.

Association of a genetic variant in angiopoietin-like 3 with serum HDL-C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years.

BACKGROUND: Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). OBJECTIVE: In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. RESULTS: Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. CONCLUSION: We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.

Association between Genetic Variants Linked to Premature Ovarian Insufficiency and Inflammatory Markers: A Cross-Sectional Study.

BACKGROUND: Premature menopause (PM) is the cessation of ovarian function before age 40. PM women are more likely to have cardiovascular diseases (CVDs), diabetes, and mental disorders. This is the first study that assessed the association of single nucleotide polymorphisms (SNPs) with anti-heat shock protein 27 (Hsp27), High-sensitivity C-reactive protein (hs- CRP), and PM and serum pro-oxidant-antioxidant balance (PAB), as putative risk factors for CVDs. We aimed to explore the association of oxidative stress markers with eight different SNPs shown to be related to premature menopause. MATERIALS AND METHODS: In this cross-sectional research, we included 183 healthy women and 117 premature menopausal women. We determined baseline characteristics for all participants and measured serum hs-CRP, anti-HSP-27 antibody titer, and PAB levels using the established methods. Genotyping for eight SNPs was done using the tetra amplification refractory mutation system polymerase chain reaction (Tetra-ARMS PCR) and allele-specific oligonucleotide PCR (ASO-PCR) methods. RESULTS: We found a significant difference between mean serum PAB levels and the genetic variant of rs16991615 (P=0.03). ANCOVA showed a significant effect of the genotypes rs4806660 and rs10183486 on hs-CRP serum levels in the case and control groups, respectively (P=0.04 and P=0.007). ANCOVA also showed an association between rs244715 genotypes and anti-hsp27 serum levels in the case group (P=0.02). There was a significant effect of the genotypes of rs451417 on the serum hs-CRP level in the control group (P=0.03). CONCLUSION: There was a significant association of the genetic variants related to PM with oxidative stress and inflammatory markers (serum PAB, anti-hsp27 antibody, and hs-CRP). Accordingly, this seems to be an effective approach to predicting susceptible subjects for cardiovascular and mental disorders as well as various cancers.

Micronutrients intake and genetic variants associated with premature ovarian insufficiency; MASHAD cohort study.

BACKGROUND AND AIM: premature ovarian insufficiency (POI) is defined as the menopause before 40 years of age, and its prevalence is reported to be two-fold higher in Iranian women than the average for woman globally. POI is associated with several cardio/cerebrovascular complications as well as an increased overall mortality. Genetic factors, and serum levels of minerals and vitamin D, have been reported to be related to the prevalence of POI. We have investigated the association between some POI -related genotypes with the serum levels of some important micronutrients. METHODS: One hundred and seventeen women with POI and 183 controls without any renal, hepatic, and thyroid abnormalities were recruited as part of the MASHAD study. Demographic and anthropometric features were recorded and blood samples were collected and processed. DNA was extracted from the buffy coat of blood samples from all participants and 8 POI-related single nucleotide polymorphisms (SNPs) were determined using ASO-PCR or Tetra ARMS-PCR. Serum minerals and vitamin D concentrations were measured using routine methods. RESULTS: In women with POI, serum copper, phosphate, and calcium were significantly different for those with rs244715, rs16991615, and rs4806660 genotypes, respectively. In our control population, significant differences were also found in serum copper concentrations between different genotypes of rs4806660, rs7246479, rs1046089, and rs2303369. After adjusting for all confounding factors, the women with POI carrying TC genotype (rs4806660) had a lower risk to have serum copper levels < 80 (µg/dL) than those carrying a TT genotype. Furthermore, women with POI carrying GG genotype (rs244715) had a 6-fold higher risk to have serum copper levels > 155 than those carrying AA genotype. CONCLUSION: The C and G alleles of the rs4806660 and rs244715 polymorphisms respectively are independently associated with serum copper in women with POI. Further studies are necessary to investigate the association of serum copper and other micronutrients in women and other POI -related polymorphisms.

Age-specific reference intervals for liver function tests in healthy neonates, infants, and young children in Iran.

BACKGROUND: The reference intervals (RIs) for liver function tests (LFTs) were determined in Iranian children for the first time. METHODS: A total of 344 healthy pediatrics aged 3 days to 30 months old were recruited. Serum levels of ALT, AST, ALP, direct bilirubin, and total bilirubin were measured. RIs were determined using CLSI Ep28-A3 guidelines. RESULTS: All analytes demonstrated age-specific differences except AST. ALT and ALP demonstrated significantly elevated levels in infants 0 to <5 months relative to the remainder of the age range. Direct and total bilirubin demonstrated markedly elevated levels in early life with mean of 0.28 mg/dL and 1.64 mg/dL observed for direct and total bilirubin, respectively, decreasing by ~50% in the adjacent partition. CONCLUSION: These novel data will help improve the clinical interpretation of biochemical test results in young Iranian neonates and children and can be of value to clinical laboratories with similar populations.

Association between biochemical and hematologic factors with COVID-19 using data mining methods.

BACKGROUND AND AIM: Coronavirus disease (COVID-19) is an infectious disease that can spread very rapidly with important public health impacts. The prediction of the important factors related to the patient's infectious diseases is helpful to health care workers. The aim of this research was to select the critical feature of the relationship between demographic, biochemical, and hematological characteristics, in patients with and without COVID-19 infection. METHOD: A total of 13,170 participants in the age range of 35-65 years were recruited. Decision Tree (DT), Logistic Regression (LR), and Bootstrap Forest (BF) techniques were fitted into data. Three models were considered in this study, in model I, the biochemical features, in model II, the hematological features, and in model II, both biochemical and homological features were studied. RESULTS: In Model I, the BF, DT, and LR algorithms identified creatine phosphokinase (CPK), blood urea nitrogen (BUN), fasting blood glucose (FBG), total bilirubin, body mass index (BMI), sex, and age, as important predictors for COVID-19. In Model II, our BF, DT, and LR algorithms identified BMI, sex, mean platelet volume (MPV), and age as important predictors. In Model III, our BF, DT, and LR algorithms identified CPK, BMI, MPV, BUN, FBG, sex, creatinine (Cr), age, and total bilirubin as important predictors. CONCLUSION: The proposed BF, DT, and LR models appear to be able to predict and classify infected and non-infected people based on CPK, BUN, BMI, MPV, FBG, Sex, Cr, and Age which had a high association with COVID-19.

The effects of low-fat dairy products fortified with 1500 IU vitamin D3 on serum liver function biomarkers in adults with abdominal obesity: a randomized controlled trial.

INTRODUCTION: Vitamin D deficiency has been reported to affect liver function biomarkers. This study was aimed to investigate the effect of consuming vitamin D fortified low-fat dairy products on liver function tests in adults with abdominal obesity. METHODS: This total blinded randomized controlled trial was undertaken on otherwise healthy abdominally obese adults living in Mashhad, Iran. Milk and yogurt were fortified with 1500 IU vitamin D3 nano-capsules. Participants were randomized to receive fortified milk (n = 73), plain milk (n = 73), fortified yogurt (n = 69), and plain yogurt (n = 74) for 10 weeks. Blood samples were taken at baseline and at the end of the study to assess serum levels of vitamin D, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), and Gamma glutamyl transferase. RESULTS: A total of 289 participants completed the study (54% female). The groups were homogenous in terms of age, sex, weight, energy intake, and physical activity level (p-value > 0.05). After the trial, vitamin D serum levels were significantly increased in both groups receiving fortified products (both p < 0.001). There was a significant time*group effect only in serum ALP (p < 0.001). CONCLUSION: Consumption of dairy products fortified by 1500 IU vitamin D3 might have detrimental effects on serum levels of some liver enzymes in individuals with abdominal obesity. Further studies needed to determine these effects and underlying mechanisms. TRIAL REGISTRATION: IRCT20101130005280N27 .

Association of dietary and blood inflammatory indicators with depression, anxiety, and stress in adults with vitamin D deficiency.

BACKGROUND: There is growing evidence that vitamin D may be related to mental health. The aim of the current study was to investigate the association of dietary and blood inflammatory factors with mental health disorders in subjects with vitamin D deficiency, shedding further light on the complex interplay of these conditions. METHOD: In this cross-sectional study, 306 subjects completed the validated Depression, Anxiety, and Stress Scale questionnaire to evaluate their depression, anxiety, and stress scores. Dietary inflammatory index (DII) and healthy eating index (HEI) were calculated using a validated 65-item food frequency questionnaire. Blood samples were taken and vitamin D, cytokine, and hs-CRP levels were measured using enzyme-linked immunosorbent assay kits. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) were calculated using standard laboratory methods. RESULTS: The subjects were divided into two groups based on their vitamin D levels: a vitamin D < 20 µg/dl group (N = 257) and a vitamin D ≥ 20  µg/dl group (N = 49). Between group analysis revealed that only DII (p = 0.015), platelet (p = 0.04), and hs-CRP (p = 0.015) were significantly different. In adults with vitamin D levels below 20 µg/dl, NLR and DII were significantly higher in subjects with anxiety (p < 0.05), and this relationship remained significant only for NLR after adjusting for age and sex. Additionally, PLR and HEI were significantly different in depressed compared to non-depressed subjects, and this association remained significant only for HEI after adjusting for age and sex. CONCLUSION: In subjects with vitamin D deficiency, increased levels of PLR, NLR, and DII were associated with depression and anxiety, while HEI was negatively associated with depression. These associations were not found in subjects with vitamin D levels ≥20 µg/dl.

Pediatric reference intervals for hematology parameters in healthy infants and young children in Iran.

INTRODUCTION: Defining accurate age- and sex-specific reference intervals (RIs) for hematology parameters, especially for the pediatric population, is important for making an appropriate clinical diagnosis. To address gaps, we established age-specific RIs for 11 hematologic parameters in Iranian children younger than 30 months for the first time. METHODS: Fresh whole blood samples collected from a total of 344 participants (males: 158 and females: 186) ages 3 days to 30 months, with a mean age of 12.91 ± 7.15 months, were recruited from healthcare centers in Mashhad, Iran. Hematologic parameters, including complete blood count (CBC), were analyzed on the Sysmex auto-analyzer system (KX-21 N). RIs were calculated with 90% confidence intervals using the direct method based on CLSI Ep28-A3 and C28-A3 guidelines. RESULTS: None of the CBC parameters required sex partitioning. Of 11 CBC parameters, six required age partitions of 3 days-<4 months, 4-<10, 10-<15, and 4-<30 months. Five parameters (i.e., white blood cell count, mean corpuscular hemoglobin concentration, mean platelet volume, red cell distribution width, and platelet distribution width) did not demonstrate age-specific changes. RIs of red blood cell count and hematocrit, as well as hemoglobin, increased with age, while mean corpuscular volume, mean corpuscular hemoglobin, and platelet count, decreased with age. CONCLUSION: In this study, we established RIs for 11 hematology parameters in young children. Age partitioning was required for six parameters demonstrating marked changes during the early period of growth and development and necessitating the use of pediatric-specific reference standards.

Use of data mining approaches to explore the association between type 2 diabetes mellitus with SARS-CoV-2.

BACKGROUND AND OBJECTIVE: Corona virus causes respiratory tract infections in mammals. The latest type of Severe Acute Respiratory Syndrome Corona-viruses 2 (SARS-CoV-2), Corona virus spread in humans in December 2019 in Wuhan, China. The purpose of this study was to investigate the relationship between type 2 diabetes mellitus (T2DM), and their biochemical and hematological factors with the level of infection with COVID-19 to improve the treatment and management of the disease. MATERIAL AND METHOD: This study was conducted on a population of 13,170 including 5780 subjects with SARS-COV-2 and 7390 subjects without SARS-COV-2, in the age range of 35-65 years. Also, the associations between biochemical factors, hematological factors, physical activity level (PAL), age, sex, and smoking status were investigated with the COVID-19 infection. RESULT: Data mining techniques such as logistic regression (LR) and decision tree (DT) algorithms were used to analyze the data. The results using the LR model showed that in biochemical factors (Model I) creatine phosphokinase (CPK) (OR: 1.006 CI 95% (1.006,1.007)), blood urea nitrogen (BUN) (OR: 1.039 CI 95% (1.033, 1.047)) and in hematological factors (Model II) mean platelet volume (MVP) (OR: 1.546 CI 95% (1.470, 1.628)) were significant factors associated with COVID-19 infection. Using the DT model, CPK, BUN, and MPV were the most important variables. Also, after adjustment for confounding factors, subjects with T2DM had higher risk for COVID-19 infection. CONCLUSION: There was a significant association between CPK, BUN, MPV and T2DM with COVID-19 infection and T2DM appears to be important in the development of COVID-19 infection.

Association between the rs2241883 polymorphism of the fatty acid-binding protein-1 (FABP1) gene and obesity in a population of MASHAD study cohort.

BACKGROUND AND AIMS: The fatty acid-binding proteins (FABPs) gene polymorphisms are related to several metabolic properties. We investigated the association of SNPs rs2241883 of FABP 1 gene with obesity to evaluate the role of FABP1 gene in the pathogenesis of obesity in the population of MASHAD study cohort. METHODS: In this cross-sectional study, 2731 individuals (1883 Obese and 848 nonobese) aged 35 to 65 years old, were enrolled from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study cohort. DNA Quantitation was determined using the NanoDrop®-1000 instrument (NanoDrop-Technologies). The rs2241883 polymorphisms were genotyped by double ARMs PCR (double amplification refractory mutation system) reactions. Data analysis was carried out using SPSS 22 and a p < 0.05 was set for statistical significance. RESULTS: The results showed that after adjusting for confounding factors, subjects having the CC genotype for rs2241883 polymorphism were at a higher risk of BMI ≥ 30 mg/kg2 with OR of 1.79 (CI = 1.05-3.07; p = 0.03) and 1.76 (CI = 1.04-2.99; p = 0.04) comparing with reference group using codominant and dominant models, respectively. CONCLUSION: The results showed that CC genotype for rs2241883 polymorphism is related to an increased risk of the obesity in dominant and codominant models in a population of MASHAD study cohort.

Comparison of reference intervals for biochemical and hematology markers derived by direct and indirect procedures based on the Isfahan cohort study.

INTRODUCTION: Indirect methods for reference interval (RI) establishment apply statistical techniques to generate RIs for test result interpretation using stored laboratory data. They present unique advantages relative to traditional direct approaches such as fewer resource requirements; however, there is debate regarding their performance. Herein, we aimed to compare indirect and direct approaches for RI establishment by harnessing data from the Isfahan Cohort Study (ICS). This cohort includes both healthy individuals and those with a history of disease, enabling a direct comparison. METHODS: Participants were recruited as part of ICS, including 6504 adults aged 34 years and older. Sociodemographic characteristics, anthropometry, blood pressure, various biochemical indices, and hematology parameters were collected. The refineR method was used to establish indirect RIs (before applying exclusion criteria). Direct RIs were calculated using nonparametric methods per CLSI EP28-A3 guidelines (after applying exclusion criteria). Bias ratios were calculated for each parameter to assess significant differences in estimations. RESULTS: Direct and indirect RI estimations for most hematological and biochemical parameters were comparable. Statistically significant bias ratios between methods were observed for the upper limits of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), hemoglobin (female), and platelet count as well as the lower limits of mean corpuscular hemoglobin (female), mean corpuscular volume, hemoglobin, and hematocrit (female). CONCLUSION: Data presented indicate RIs derived from direct and indirect approaches are similar, but not identical. Further work should focus on the clinical significance of such differences as well as the investigation of necessary data-cleaning criteria before indirect method application.

The national health program for vitamin D supplementation in a developing country.

BACKGROUND: Previous studies have reported a high frequency of vitamin D deficiency (VDD) among different age groups in Iran. AIMS: In this study, the current coverage, status of vitamin D supplement taking, and program efficacy have been evaluated by the Office of Nutrition Department Society in Iran since 2014. METHODS: This study was conducted in collaboration with the International UNESCO center for Health-Related Basic Sciences and Human Nutrition and the Office of Nutrition Department Society. Sixty three medical universities were included in the current study to calculate the availability, accessibility and acceptability coverages. Furthermore, 3 medical universities including Mashhad (MUMS), Qom (QUMS) and Zahedan (ZAUMS) University of Medical Sciences were selected based on the results of the National Integrated Micronutrient Survey 2012 (NIMS-II study), in order to assess the status of vitamin D supplement intake in all age ranges. RESULTS: Quantitative analysis showed that availability coverage was 74.96% and 77.56% and accessibility was 80.70% and 83.26% in elderly and middle-aged subjects, respectively in 2018. The acceptability was approximately 43.7% and 43.9% among elderly and middle-aged participants, respectively. The availability and acceptability coverage was 80.99% and 85.0% among students in high schools. The mean vitamin D supplement uptake frequency was 27.0% (n = 387); 20.7% and 29.2% in rural and urban area, respectively (P = 0.001). The results showed that there was no significant difference in serum vitamin D levels between urban (20.41 ± 6.43 ng/ml) and rural areas, (P = 0.887). There was no significant difference in the serum vitamin D concentrations between men and women (P = 0.461). CONCLUSIONS: The frequency of taking vitamin D supplements was 27.0% in Iran in 2018. The frequency of taking of vitamin D supplements among vitamin D deficient group (serum vitamin D levels <19.99 ng/ml) was 43.6%. Lack of knowledge was the most important reason for not taking vitamin D supplement. Moreover, the serum vitamin D levels have increased in subjects aged 18-30 years old after the implementation of the vitamin D supplementary program.

Factors associated with the severity of premenstrual symptoms in women with central obesity: a cross-sectional study.

INTRODUCTION: Premenstrual syndrome (PMS) is a common condition that affects social and psychological well-being of women. The risk of PMS is higher among obese women. The aim of this study was to identify the factors that influence the severity of PMS in women with central obesity. MATERIALS AND METHODS: This cross-sectional study was performed on 30-50 year-old women with abdominal obesity (waist circumference > 80 cm). The following data were collected: demographic data, anthropometric measurements, premenstrual symptoms screening tools, semi-quantitative food frequency questionnaire, 42-item depression, anxiety, and stress questionnaire (DASS-42), as well as serum vitamin D, and renal function tests. RESULTS: A total of 139 women (mean age of 41.40 ± 7.39 years old) participated in the study. The prevalence of mild, moderate and severe premenstrual symptoms was 38.7% (55/142), 31.7% (45/142) and 27.5% (39/142), respectively. There was no significant difference between the groups in terms of anthropometric measurements and energy-adjusted nutrient intakes (p > 0.05). There was a significant relationship between moderate PMS and energy-adjusted saturated fatty acid (SFA) (p = .018, OR = .010 and 95% CI for OR: < .001 and .452), and energy-adjusted riboflavin (p = .042, OR = .005, 95% CI for OR: < .001 and .821), and between severe PMS and age (p = .034, OR = .906, 95% CI for OR: .826 and .993), and energy-adjusted monounsaturated fatty acid (MUFA) intake (p = .041, OR = 23.789, 95% CI for OR: 1.138 and 497.294). CONCLUSION: High intakes of MUFA and younger age were associated with a greater severity of PMS, while riboflavin intake was associated with reduced PMS severity.

Age-specific reference intervals for routine biochemical parameters in healthy neonates, infants, and young children in Iran.

Age and sex need to be considered in the establishment of reference intervals (RIs), especially in early life when there are dynamic physiological changes. Since data for important biomarkers in healthy neonates and infants are limited, particularly in Iranian populations, we have determined age-specific RIs for 7 laboratory biochemical parameters. This cross-sectional study comprised a total of 344 paediatric participants (males: 158, females: 186) between the ages of 3 days and 30 months (mean age: 12.91 ± 7.15 months). Serum levels of creatinine, urea, uric acid, calcium, phosphate, vitamin D and high-sensitivity C-reactive protein (hs-CRP) were measured using an Alpha classic-AT plus auto-analyser. We determined age-specific RIs using CLSI Ep28-A3 and C28-A3 guidelines. No sex partitioning was required for any of the biomarkers. Age partitioning was required for kidney function tests and phosphate. The serum concentration of urea and creatinine increased with age, while phosphate and uric acid decreased with age. Age partitioning was not required for serum calcium, vitamin D, and hs-CRP, which remained relatively constant throughout the age range. Age-specific RIs for 7 routine biochemical markers were determined to address critical gaps in RIs in early life to help improve clinical interpretation of blood test results in young children, including neonates. Established age partitions demonstrate the biochemical changes that take place during child growth and development. These novel data will ultimately better disease management in the Iranian paediatric population and can be of value to clinical and hospital laboratories with similar populations.

A Mixed Model Approach for Estimating the Optimal Food Fortification of Vitamin D: Experiment Based on Mashhad Cohort Study in Iran.

BACKGROUND: Vitamin D deficiency is a prevalent problem in worldwide healthcare related to several system disorders. Food fortification as a solution is associated with several challenges including insufficient coverage of the entire population, required degree of fortification, the vehicles used for fortification and potential toxicity. This study aimed to determine the optimal amount of vitamin D for fortification without surpassing the upper intake level (UL) of intake at the 95th percentile of the Iranian population and compare two methods of food fortification. METHODS: This study is aimed to develop a model of two different fortifying approaches related to an available dataset called MASHAD cohort study. The dataset comprised demographic and nutritional data of 9704 Iranian individuals living in the Greater Mashhad region. The first approach was a computational method necessary to implement a range of eight foods and calculate the optimal approach. In the second case, we used the European formula method called ILSI. RESULTS: To find the appropriate value for fortification, we calculated the consumption of 400 IU and 1000 IU supplements of vitamin D. Three micrograms per 100 g in each food was the optimal output. We also used Flynn and Rasmussen's formula on our data. Using these methods, we found that 2.1 micrograms per 100 kcal provides the best result. Hence, using the two different approaches, the results appear to be consistent and promising. CONCLUSION: One interesting finding was that supplement consumption did not greatly affect the impact of fortification. This observation may support the hypothesis to determine the amount of fortification, and we can ignore the study population's supplement consumption.

Factors Associated With Trabecular Bone Score and Bone Mineral Density; A Machine Learning Approach.

INTRODUCTION: Bone indexes including trabecular bone score (TBS) and bone mineral density (BMD) have been shown to be associated with wide spectrum of variables including physical activity, vitamin D, liver enzymes, biochemical measurements, mental and sleep disorders, and quality of life. Here we aimed to determine the most important factors related to TBS and BMD in SUVINA dataset. METHODS: Data were extracted from the Survey of Ultraviolet Intake by Nutritional Approach (SUVINA study) including all 306 subjects entered this survey. All the available parameters in the SUVINA database were included the analysis. XGBoost modeler software was used to define the most important features associated with bone indexes including TBS and BMD in various sites. RESULTS: Applying XGBoost modeling for 4 bone indexes indicated that this algorithm could identify the most important variables in relation to bone indexes with an accuracy of 92%, 93%, 90% and 90% respectively for TBS T-score, lumbar Z-score, neck of femur Z-score and Radius Z-score. Serum vitamin D, pro-oxidant-oxidant balance (PAB) and physical activity level (PAL) were the most important factors related to bone indices in different sites of the body. CONCLUSIONS: Our findings indicated that XGBoost could identify the most important variables with an accuracy of >90% for TBS and BMD. The most important features associated with bone indexes were serum vitamin D, PAB and PAL.

Effects of Vitamin D3 Fortified Low-fat Dairy Products on Bone Density Measures in Adults with Abdominal Obesity: A Randomized Clinical Trial.

Background: Bone disease-related fractures constitute a heavy burden on the healthcare systems and economy. Vitamin D is an important regulator of bone health and its deficiency is a global problem. This study aimed to evaluate the effect of the 1,500 IU nano-encapsulated vitamin D used for fortifying low-fat dairy products (milk and yogurt) on bone health parameters. Methods: This parallel totally blinded, randomized controlled trial was part of the Ultraviolet Intake by Nutritional Approach study and conducted on 306 individuals with abdominal obesity. Individuals were randomly assigned to four groups, including fortified low-fat milk (1,500 IU nano-encapsulated vitamin D3 per 200 g/d), non-fortified low-fat milk, fortified low-fat yogurt (1,500 IU nano-encapsulated vitamin D3 per 150 g/d), and non-fortified low-fat yogurt, for 10 weeks between January and March 2019. Bone mineral density (BMD) and trabecular bone score (TBS) were measured at the baseline and end of the trial. Trabecular bone score and BMD were defined as primary and secondary outcomes. Results: There were no significant differences in TBS and BMD between the intervention and control groups at the end of the trial (P>0.05). Conclusion: This trial demonstrated no significant effect of nano-encapsulated vitamin D fortified milk and yogurt on BMD and TBS. There remains a need for longer-term trials regarding bone health outcomes to establish optimal doses of fortification.

Association between dietary patterns and body composition in normal-weight subjects with metabolic syndrome.

Background and aims: The development of metabolic syndrome (MetS) has been proposed to be related to dietary pattern and body compostion indexes. Diet is one of the most important lifestyle-related factors which may regulate the inflammatory process. Numerous individual foods and dietary patterns can have a valuable health effect that is associated with their anti-inflammatory properties. Here we aimed to investigate the association between body composition indexes and dietary patterns in individuals with metabolic syndrome who were nnormal for weight. Methods and materials: Normal weight subjects with MetS were recruited as part of Survey of Ultraviolet Intake by Nutritional Approach (SUVINA). A validated food frequency questionnaire (FFQ) was used to determine dietary patterns that were: low-, or high in antioxidant; dietary inflammation index (DII) and health eating index (HEI) were also determined. Body composition indexes including basal metabolic rate (BMR), body free fat mass (BFFM), body fat mass (BFM), body fat percentage (BFP), trunk fat and total body water (TBW) were measured using a InBody body composition analyser. A P value <0.05 was considered significant. Results: A total 77 individuals including 29 males and 48 females were recruited into the study. A high-antioxidant dietary pattern was significantly correlated with BMR (p = 0.002), BFFM (p = 0.007) and TBW (p = 0.002). There was no significant relationship between body compostion with a low-antioxidant dietary pattern, DII and HEI. After adjusting for age and sex, our findings showed that a high-antioxidant dietary pattern were independently associated with BMR, BFFM and TBW. Conclusion: A high-antioxidant dietary pattern was independently associated with decreased BMR, BFFM and TBW, while no association was found between body composition indexes and DII and HEI in normal weight paticipants with MetS.

Efficacy of low-fat milk and yogurt fortified with vitamin D3 on systemic inflammation in adults with abdominal obesity.

BACKGROUND: The prevalence of vitamin D deficiency is increasing globally and is associated with an increased risk of metabolic syndrome, autoimmune disease, and cardiovascular disease. Vit D deficiency is also associated with increased systemic inflammation. The current study aimed to determine the efficacy of low-fat milk and yogurt fortified with 1500 IU nano-encapsulated vitamin D, on systemic inflammation in abdominal obese participants. METHOD: This multi-center study was conducted using a 2.5-month parallel total-blind randomized clinical trial design. Two hundred and eighty nine subjects were allocated to four groups: low-fat milk fortified by 1500 IU nano-encapsulated vitamin D3 (200 mL/day). Simple milk (200 mL/day), low-fat yogurt fortified by 1500 IU nano-encapsulated vitamin D3 (150 g/day), and simple yogurt (150 g/day). RESULTS: The results showed that serum levels of neutrophils, lymphocytes, platelets and red blood cell distribution width (RDW) were significantly lower before and after the intervention in fortified dairy groups. The results showed that serum levels of neutrophils, lymphocytes, platelets, and RDW before and after intervention in the fortified dairy groups were significantly lower (p < 0.05). The values of = neutrophil to lymphocyte ratio (NLR), platelets to lymphocyte ratio, and RDW to platelets ratio (RPR) reduced significantly in the fortification group (p < 0.05). CONCLUSION: Fortification with nano-encapsulated vitamin D3 of dairy products may decrease inflammation in individuals with abdominal obesity.