Alterations in CD4+ T Cell Cytokines Profile in Female Patients with Hashimoto's Thyroiditis Following Vitamin D Supplementation: A Double-blind, Randomized Clinical Trial.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by the destruction of thyroid cells through immune processes involving T helper (Th)1 cytokines. This clinical trial investigates the impact of vitamin D supplementation on serum cytokine levels and gene expression in CD4+ T cells from HT patients, aiming to understand its effects on Th-1, Th-2, Th-17, and regulatory T (Treg) cell-associated factors. METHODS: Female patients were randomly assigned in a double-blind design to either a vitamin D-supplemented group, which received cholecalciferol [1, 25(OH)2D3] at a dose of 50,000 IU, or the placebo group, which received a weekly placebo for a duration of three months. Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA), while genes' expression levels were measured using real-time PCR. RESULTS: Serum 25-hydroxyvitamin D and levels exhibited a significant increase following vitamin D supplementation, in comparison to the placebo group. Additionally, the vitamin D supplementation resulted in a significant elevation of serum calcium (Ca) levels compared to baseline. In the vitamin D group, there was a significant decrease in both serum levels and expression of the interleukin (IL)-17 gene when compared to baseline, although no statistical difference was observed between the placebo and vitamin D groups. The gene expression of transforming growth factor-beta (TGFß) was significantly increased in the vitamin D group compared to baseline, with no significant difference between the two study groups. Vitamin D treatment had no effect on serum levels of interferon-gamma (IFNϒ) and IL-4. While the gene expression of IL-4 in the vitamin D group did not exhibit a statistically significant increase, the level of GATA3 transcription factor increased significantly when compared to the placebo group. The expression of IFNϒ and transcription factors, T-bet, RORc, and forkhead box protein 3 (FOXP3) in genes did not show significant changes following vitamin D supplementation. CONCLUSION: The findings suggest that vitamin D supplementation may hold potential benefits for autoimmune diseases, such as HT. However, further longitudinal clinical trials are necessary to gain a more comprehensive understanding of the specific effects of vitamin D on HT. CLINICAL TRIAL REGISTRATION NUMBER: IRCT2016110130644N1.

Do Postpartum Maternal Iodine Status or Supplementation Affect Thyroid Function After Delivery? A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was, for the first time, to explore whether postpartum maternal iodine status or supplementation is associated with thyroid function after delivery. The MEDLINE/PubMed, Web of Science, Embase, and Scopus were searched up to December 2021 to identify relevant studies. The pooled mean thyroid stimulating hormone (TSH), free thyroxine (fT4), and thyroxine (T4) concentrations and 95% confidence intervals (CIs) were estimated based on maternal urinary iodine concentration (UIC) (< 50, 50-100, 100-200, and > 200 µg/L) or breast milk iodine concentration (BMIC) (< 100 µg/L vs. ≥ 100 µg/L) during postpartum. A fixed/random effects model was used based on the absence/presence of heterogeneity, respectively. The study is registered with PROSPERO, number CRD42022336145. A total of 2175 studies were identified, of which 18 were eligible for the meta-analysis. The pooled values for TSH, fT4, and T4 concentrations in all subgroups were within the normal range; however, except for TSH, comparing the 95% CI showed no statistically significant difference among different subgroups. The pooled mean for TSH concentration in women with UIC > 200 µg/L was 2.23 mIU/L, whereas the corresponding values in women with UIC < 50, 50-100 and 100-200 µg/L were 0.56, 0.56 and 0.95 mIU/L, respectively. Thyroid hormones in women with BMIC < 100 µg/L and ≥ 100 µg/L were within the normal range. Iodine supplementation during postpartum was not associated with any differences in thyroid parameters, compared to non-supplemented women. In conclusion, iodine status or supplementation had no effect on thyroid hormones in postpartum women.

The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.

Effect of TCF7L2 on the relationship between lifestyle factors and glycemic parameters: a systematic review.

BACKGROUND: Among candidate genes related to type 2 diabetes (T2DM), one of the strongest genes is Transcription factor 7 like 2 (TCF7L2), regarding the Genome-Wide Association Studies. We aimed to conduct a systematic review of the literature on the modification effect of TCF7L2 on the relation between glycemic parameters and lifestyle factors. METHODS: A systematic literature search was done for relevant publications using electronic databases, including PubMed, EMBASE, Scopus, and Web of Science, from January 1, 2000, to November 2, 2021. RESULTS: Thirty-eight studies (16 observational studies, six meal test trials, and 16 randomized controlled trials (RCTs)) were included. Most observational studies had been conducted on participants with non-diabetes showing that TCF7L2 modified the association between diet (fatty acids and fiber) and insulin resistance. In addition, findings from meal test trials showed that, compared to non-risk-allele carriers, consumption of meals with different percentages of total dietary fat in healthy risk-allele carriers increased glucose concentrations and impaired insulin sensitivity. However, ten RCTs, with intervention periods of less than ten weeks and more than one year, showed that TCF7L2 did not modify glycemic parameters in response to a dietary intervention involving different macronutrients. However, two weight loss dietary RCTs with more than 1-year duration showed that serum glucose and insulin levels decreased and insulin resistance improved in non-risk allele subjects with overweight/obesity. Regarding artichoke extract supplementation (ALE), two RCTs observed that ALE supplementation significantly decreased insulin concentration and improved insulin resistance in the TT genotype of the rs7903146 variant of TCF7L2. In addition, four studies suggested that physical activity levels and smoking status modified the association between TCF7L2 and glycemic parameters. However, three studies observed no effect of TCF7L2 on glycemic parameters in participants with different levels of physical activity and smoking status. CONCLUSION: The modification effects of TCF7L2 on the relation between the lifestyle factors (diet, physical activity, and smoking status) and glycemic parameters were contradictory. PROSPERO REGISTRATION NUMBER: CRD42020196327.

The role of nutrition in the development and management of gestational diabetes among Iranian women: a systematic review and meta-analysis.

Purpose: We aimed to review existing evidence on nutrition associations with gestational diabetes mellitus (GDM) development and management among Iranian women. Methods: Web of Science, PubMed, Scopus, SID, and Magiran were searched up to August 2020. Observational studies on associations between circulatory markers of vitamins and minerals, dietary intakes, and GDM and clinical trials of the effects of nutritional supplementations or dietary modifications on management or prevention of GDM among Iranian women were selected. Results: We reviewed 49 publications. Pooled analyses revealed that GDM women had lower serum vitamin D (-8.31 nmol/l (95% CIs= -14.4, -2.19), higher serum iron (26.2 µg/dl (95% CIs= 2.52, 49.8), ferritin (24.1 ng/ml (95% CIs= 15.0, 33.4), and haemoglobin (1.14 g/dl (95% CIs: 0.32, 1.96) levels than non-GDM women. Single studies found the inverse associations of the Mediterranean diet, dietary approaches to stop hypertension diet, plant-based dietary index, and the direct associations of dietary acid load and dietary inflammatory index with the odds of GDM. Vitamin D supplementation early in pregnancy prevented GDM in two clinical trials. In two studies, iron supplementation's effect on GDM in non-anemic women was inconsistent. Pooled analyses of probiotic supplementation in women with GDM showed no significant impact on maternal glycemia. Conclusions: Vitamin D supplementation early in pregnancy may reduce the incidence of GDM. There is no compelling evidence that vitamin D or probiotics can help with GDM management. There is currently inadequate data to recommend a specific dietary pattern to prevent GDM in Iranian women. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-021-00944-7.

The association between dietary fats and the incidence risk of cardiovascular outcomes: Tehran Lipid and Glucose Study.

BACKGROUND: The association between dietary fats and the risk of cardiovascular disease (CVD) is under debate. We aimed to determine the potential effects of dietary saturated fats (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty acids on the occurrence of CVD in an adult Asian population. METHODS: This study was conducted within the framework of the Tehran Lipid and Glucose Study on 2809 CVD-free adults, aged ≥ 19 years. Dietary intakes of fats were estimated using a validated 168-items semi-quantitative food frequency questionnaire, at baseline. Adjusted hazard ratios and 95% confidence intervals of CVD were calculated in tertile categories of dietary fats. The risk of CVD was estimated with multivariable Cox regression for the substitution of total fat or SFA with other macronutrients. RESULTS: During 10.6 years of follow up, the incidence rate of CVD events was 7.1%. Mean (± SD) age of the participants was 39 (± 14) years and 43.9% were men. Total fat, animal and plant sources of fats were not associated with risk of CVD events. No significant associations were found between total SFA, lauric acid, myristic acid, stearic acid, palmitic acid as well as MUFA and PUFA and CVD incidence. Substitutions of total fats or SFA with other macronutrients were not associated with CVD risk. CONCLUSIONS: In this study, no significant associations were found between dietary fats and CVD risk. Considering the emerging body of literature that suggests no association between fats and CVD risk, reconsideration of dietary recommendations regarding low fat diets to prevent CVD, seems to be essential.

Does maternal iodine supplementation during the lactation have a positive impact on neurodevelopment of children? Three-year follow up of a randomized controlled trial.

PURPOSE: The aim of this study was to examine, for the first time, the neurodevelopmental outcomes in children whose mothers received different doses of iodine supplements during lactation. METHODS: We conducted a follow-up study on children whose mothers participated in a randomized clinical trial to receive placebo, 150 µg/day or 300 µg/day of iodine until 12 months postpartum. Child neurocognitive development was assessed at 36 months of age using the Bayley Scales of Infant and Toddler Development Third Edition. Linear mixed-model analysis was preformed to assess iodine supplement dose effects on child cognitive, language, and motor functions. RESULTS: A total of 122 children provided neurodevelopmental data as follows: 300 µg/d iodine group: 45; 150 µg/d iodine group: 35; and placebo group: 42. Cognitive scores were higher in children whose mothers received 150 µg iodine/d compared to children whose mothers received placebo [102.8 (SD 13.2) vs. 99.2 (SD 10.5); ß = 4.43, P = 0.032]. However, supplementation with 150 µg iodine/d had no effect on language or motor development. No significant differences were observed in cognitive, language, or motor functions between children whose mothers received 300 µg iodine/d and those whose mothers received 150 µg iodine/d or placebo. CONCLUSION: Maternal iodine supplementation with 150 µg/d during lactation may have a beneficial effect on child cognitive development; however, we found no evidence of either improved or delayed neurodevelopmental outcomes in children whose mothers received iodine supplements at doses higher than recommended. Further randomized controlled trials with larger sample sizes are needed to confirm these results. CLINICAL TRIAL REGISTRY: IRCT201303164794N8; registration date: 2013-05-20.

Effect of inorganic nitrate on metabolic parameters in patients with type 2 diabetes: A 24-week randomized double-blind placebo-controlled clinical trial.

AIM: In this randomized placebo-controlled clinical trial, effect of oral inorganic nitrate (NO3-) on metabolic parameters was assessed in patients with type 2 diabetes mellitus (T2DM). METHODS: Seventy-four eligible patients with T2DM were randomly assigned to NO3--rich beetroot powder (5 g/d contains ~250 mg NO3-) and placebo groups to complete intervention over a 24-week period. Blood HbA1c, fasting serum glucose, insulin, C-peptide, as well as lipid profile were assessed at baseline and again at weeks 4, 12, and 24; indices of insulin resistance were also calculated. To assess safety of long-term oral NO3-, liver and renal function tests were measured. An intention-to-treat approach was used for data analysis. To compare effect of intervention over time between the groups (time×group), repeated measures generalized estimating equation (GEE) linear regression models were used. RESULTS: Mean age of the participants was 54.0 ± 8.5 (47.9% were male) and mean duration of diabetes was 8.5 ± 6.1 years. A total of 64 patients (n = 35 in beetroot group and n = 29 in placebo group) completed at least two visits and were included in the analyses. No significant difference was observed between the groups for glycemic and lipid parameters over time. Liver and renal function tests, as safety outcome measures, showed no undesirable changes during the study follow-up. CONCLUSION: Supplementation with inorganic NO3- had no effect on metabolic parameters in patients with T2DM.

Nutrient Intake and Deficiency of Patients 1 Year After Bariatric Surgery: Tehran Obesity Treatment Study (TOTS).

PURPOSE: This study aimed at assessing nutrient adequacy after 1 year in patients who had undergone gastric bypass (GB) surgery or sleeve gastrectomy (SG) and to investigate the association of nutrient adequacy with anthropometric indices. METHODS: A total of 180 severely obese patients (BMI ≥ 35 kg/m2) were selected among the participants of Tehran Obesity Treatment Study. Nutritional assessments were performed over 3 days of 24-h dietary recall. To evaluate the nutrient adequacy ratio (NAR), the subject's nutrient intake was divided by the dietary reference intakes. The mean adequacy ratio (MAR) was also determined as the sum of NARs divided by the number of involved nutrients (n = 11). RESULTS: The mean age of SG (67%) and GB (32%) patients was 39.2 ± 12 and 41.4 ± 10 years, respectively. SG patients had more postoperative fat-free mass (52.0 ± 12 kg) than GB patients (49.7 ± 8 kg) (P < 0.05). The most common postoperative serum nutrient deficiencies were related to vitamin B12 (30%), ferritin (19%), and 25-hydroxyvitamin D (16.2%). Moreover, high inadequacy of protein (> 80%) and total fat (> 70%) intake was reported. The MAR score showed that almost 45% of the patients had possibly adequate intakes of some nutrients. The adequacy of nutrients was positively associated with fat-free mass (ß = 8.67, P < 0.05). CONCLUSION: These findings revealed that patients had inadequate nutrient intakes 1 year after bariatric surgery, which was accompanied by serum nutritional deficiencies. Compared to GB patients, SG patients had a better body composition. Overall, compliance of patients with dietary guidelines and supplementations needs to be carefully monitored in the postoperative period.

Different Pharmacokinetic Responses to an Acute Dose of Inorganic Nitrate in Patients with Type 2 Diabetes.

AIM: In this study, we aimed to compare the pharmacokinetics of nitrate (NO3) in patients with type 2 diabetes mellitus (T2DM) and healthy adults. Potential effects of salivary nitrate reductase (NR) activity on cardiometabolic responses to an acute dose of NO3 was also assessed. METHODS: Nine healthy adults and nine T2DM patients were recruited to consume a NO3-rich breakfast (~410 mg NO3). Pharmacokinetics of NO3 were examined using repeated measurements of NOx (nitrate+ nitrite) concentrations of serum and saliva over 8 hours and NO3 concentrations of spot and 24-h urine samples. Cardiometabolic parameters, including serum levels of glucose, insulin, and triglycerides as well as blood pressure were also measured. RESULTS: Compared to patients with T2DM, serum NOx concentration (Δ1= 16.7 vs. 4.4 µmol/L, P=0.057) of healthy subjects sharply increased within 1 hour after NO3 loading. Healthy subjects had a higher NR activity index, and higher peak salivary NO3 concentration with a lower time to peak. Diabetic patients with high- compared to low-NR values had a higher whole-body NOx exposure (103±31.4 vs. 58.9±22.1 µmol.h/L); they also showed a better glycemic response and more reduction of blood pressure following ingestion of a NO3-rich meal. CONCLUSION: T2DM may be associated with a different pattern of NOx pharmacokinetics (especially salivary NOx metabolism). Salivary NR activity may have a critical role in postprandial metabolism of NO3, and diabetic patients with higher NR activity may take more advantages from NO3 supplementation.

Effects of iodine supplementation during pregnancy on pregnant women and their offspring: a systematic review and meta-analysis of trials over the past 3 decades.

OBJECTIVE: The current systematic review aimed to provide comprehensive data on the effects of iodine supplementation in pregnancy and investigate its potential benefits on infant growth parameters and neurocognitive development using meta-analysis. METHODS: A systematic review was conducted on trials published from January 1989 to December 2019 by searching MEDLINE, Web of Science, the Cochrane Library, Scopus, and Google Scholar. For most maternal and neonatal outcomes, a narrative synthesis of the data was performed. For birth anthropometric measurements and infant neurocognitive outcomes, the pooled standardized mean differences (SMDs) with 95% CIs were estimated using fixed/random effect models. RESULTS: Fourteen trials were eligible for inclusion in the systematic review, of which five trials were included in the meta-analysis. Although the findings of different thyroid parameters are inconclusive, more consistent evidence showed that iodine supplementation could prevent the increase in thyroglobulin concentration during pregnancy. In the meta-analysis, no differences were found in weight (-0.11 (95% CI: -0.23 to 0.01)), length (-0.06 (95% CI: -0.21 to 0.09)), and head circumference (0.26 (95% CI: -0.35 to 0.88)) at birth, or in cognitive (0.07 (95% CI: -0.07 to 0.20)), language (0.06 (95% CI: -0.22 to 0.35)), and motor (0.07 (95% CI: -0.06 to 0.21)) development during the first 2 years of life in infants between the iodine-supplemented and control groups. CONCLUSION: Iodine supplementation during pregnancy can improve the iodine status in pregnant women and their offspring; however, according to our meta-analysis, there was no evidence of improved growth or neurodevelopmental outcomes in infants of iodine-supplemented mothers.

Iodine nutrition in pregnant and breastfeeding women: sufficiency, deficiency, and supplementation.

Iodine is a micronutrient used by the thyroid gland to produce thyroid hormones, which manage different aspects of body metabolism. Humans depend on exogenous sources of iodine to maintain the normal concentration of thyroid hormones. Pregnancy alters iodine turnover and is associated with significant changes in thyroid function. Daily iodine requirement during pregnancy increases to 250 µg, compared with 150 µg for nonpregnant women. According to recent guidelines of scientific organizations, to improve maternal thyroid status and to prevent child neurocognitive defects, all pregnant and breastfeeding women should take 150 µg of iodine supplementation, not only in iodine-deficient regions but also in iodine-sufficient areas. However, some recent studies have confirmed that iodine supplementation of mildly iodine-deficient pregnant women has no clear benefits as concerns maternal thyroid function or child neurodevelopment.

Can Supplementation with Vitamin D Modify Thyroid Autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and Thyroid Profile (T3, T4, TSH) in Hashimoto's Thyroiditis? A Double Blind, Randomized Clinical Trial.

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disorder characterized by the destruction of thyroid cells caused by leukocytes and antibody-mediated immune processes accompanied by hypothyroidism. In recent years, evidence has emerged pointing to various roles for vitamin D, including, proliferation and differentiation of normal and cancer cells, cardiovascular function, and immunomodulation. Vitamin D deficiency has been especially demonstrated in HT patients. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study and divided into vitamin D and placebo groups. Patients in the vitamin D and placebo groups received 50 000 IU vitamin D and placebo pearls, weekly for 3 months, respectively. The serum levels of 25-hydroxy vitamin D [25(OH) D], Ca++ion, anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH were measured at the baseline and at the end of the study using enzyme-linked immunosorbent assays. The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.

Lactating Mothers and Infants Residing in an Area with an Effective Salt Iodization Program Have No Need for Iodine Supplements: Results from a Double-Blind, Placebo-Controlled, Randomized Controlled Trial.

BACKGROUND: The necessity of iodine supplementation in lactating mothers residing in countries with sustained salt iodization programs for iodine sufficiency of breast-fed infants remains unclear. The aims of this study were to investigate the effect of iodine supplementation on iodine status and growth parameters of lactating mothers and breast-fed infants and to compare these data with that of formula-feeding mothers and their infants during the first year of infancy. METHODS: In this multicenter, double-blinded, randomized clinical trial conducted in four healthcare centers in Tehran (Iran), healthy lactating mothers and their term newborns aged 3-5 days were randomly assigned to treatment groups: placebo, 150 µg/day iodine, or 300 µg/day iodine. They were followed up for 12 months. Formula-fed infants aged 30-45 days and their mothers were randomly selected from the same centers. The primary outcomes were maternal and infant urinary iodine concentrations (UICs), breast-milk iodine concentrations (BMICs), and infant growth parameters, measured at 1, 2, 4, 6, 9, and 12 months during routine health visits. The formula-fed group was assessed at 2, 4, 6, 9, and 12 months of age. Analysis was by per protocol principle using mixed-effects models. RESULTS: Mother-newborn pairs (n = 180) in treatment groups and partially/exclusively formula-feeding mother-infant pairs (n = 60) participated between October 2014 and January 2016. Median baseline UICs in the treatment groups were 84 µg/L (interquartile range [IQR] 41-143 µg/L) in mothers and 208 µg/L (IQR 91-310 µg/L) in their infants. The values in the formula-fed group were 76 µg/L (IQR 40-144 µg/L) in mothers and 121 µg/L (IQR 66-243 µg/L) in infants. The 300 µg/day iodine group showed significantly higher UICs and BMICs than did the other treatment groups; infant UICs in the 150 µg/day iodine, placebo, and formula-fed groups were similar. Infants in all groups showed iodine sufficiency (median UIC ≥100 µg/L) throughout the study period. Anthropometric measurements were similar between the treatment and formula-fed groups over the study period, except at the last follow-up visit at 12 months. CONCLUSION: Supplementation of breast-feeding mothers with either 300 or 150 µg/day iodine improved their iodine status. However, the iodine status of infants in all groups studied indicated iodine sufficiency during the first year of infancy, demonstrating that in countries with effective salt iodization program, iodine supplementation for lactating mothers is unnecessary.

Effect of vitamin D supplementation on serum 25-hydroxyvitamin D concentration in children and adolescents: a systematic review and meta-analysis protocol.

INTRODUCTION: The importance of vitamin D for bone health as well as its role in non-skeletal functions has long been documented. However, review investigations on the effect of vitamin D supplementation on serum 25-hydroxyvitamin D (25(OH)D) levels in children and adolescents are scarce. The aims of the current study were to assess the impact of various doses of vitamin D supplementation on serum 25(OH)D concentrations in children and adolescents, and to identify relevant determinants of variations in the effect of vitamin D supplementation. METHODS: PubMed, Scopus, ISI Web of Science and Cochrane Central Register of Controlled Trials databases up to 27 September 2017 will systematically be searched for randomised controlled trials of vitamin D supplementation. We considered articles with the following control groups as eligible: placebo control, control group without any supplementation or a comparative arm investigation. Two reviewers will assess articles for eligibility according to prespecified selection criteria, after which data extraction and quality appraisal will be conducted by two independent reviewers. The quality assessment will be assessed using the Jadad scale. Meta-analyses will be conducted where appropriate. We will express continuous measures (ie, serum 25(OH)D concentration) as mean differences with 95% CIs. Heterogeneity of the data will be investigated via visual inspection of the forest plots and using χ2 test on N-1 df, with a significance level of α=0.1. We will also assess individual study and subgroup characteristics and perform a sensitivity analysis. Publication bias will be assessed using funnel plot and statistical analysis of Egger's test. ETHICS AND DISSEMINATION: Ethics approval is not required because the work will be carried out on published documents. The authors will publish findings from this review through peer-reviewed publication or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42017067179.

Fatty acid quality and quantity of diet and risk of type 2 diabetes in adults: Tehran Lipid and Glucose Study.

AIM: Studies suggest that fatty acid intake may be an important determinant of type 2 diabetes mellitus (T2DM). This study aims to prospectively examine the association between fatty acid quantity and quality with risk of T2DM in adults. METHODS: In this community-based prospective sample, 2139 adults, free of T2DM, aged 20-70y-old were followed for a median of 5.8 y. Diet information was collected with the use of a validated questionnaire at baseline. Cox regression and 95% confidence intervals (CI), adjusted for age, diabetes risk score (DRS), and dietary intakes of energy, fiber and magnesium, were used to evaluate the association of fatty acid intakes with incident T2DM. RESULTS: During follow-up, we identified 143 incident T2D cases. In multivariable analyses, when extreme quintiles were compared, cholesterol (HR = 0.40; 95% CI: 0.20-0.82; P-trend, 0.02), monounsaturated fatty acids (HR = 0.30; 95% CI: 0.13-0.70; P-trend, 0.02), polyunsaturated fatty acids (HR = 0.45; 95% CI: 0.24-0.93 P-trend = 0.04) and ω-3 fatty acids (HR = 0.55; 95% CI: 0.31-0.88; P-trend = 0.02) were associated with T2DM. The ratio of ω-6 to total ω-3 intake was associated with a higher risk of T2D (HR = 1.65; 95% CI: 1.05-2.86; P-trend, 0.04). We also found positive associations between the ratios of total fat to ω-3 (HR = 1.65; 95% CI: 1.02-2.46; P-trend = 0.05). CONCLUSIONS: Our findings indicate that diets with high cholesterol, monounsaturated, polyunsaturated and ω-3 fatty acids are associated with a lower risk of T2DM. Also the ratios of ω-6/ω-3 and total fat/ω-3 were positively associated with T2DM.

The Association of Potato Intake With Risk for Incident Type 2 Diabetes in Adults.

OBJECTIVES: Previous studies indicate that the risk for diabetes associated with high consumption of potato differs in various populations. We aimed to investigate the associations between total, boiled and fried potato intake and the risk for incident diabetes in Tehranian adults. METHODS: This cohort study was conducted in 1,981 adults, aged 19 to 70 years, who participated in the Tehran Lipid and Glucose Study and were followed up for 6 years. Usual dietary potato intakes were assessed using a valid and reliable food-frequency questionnaire. Anthropometric, biochemical and blood pressure data were determined, and diabetes was defined according to the criteria of the American Diabetes Association. RESULTS: The mean (± SD) age and potato intake of participants was 38.9±13.4 years and 30.2±30.7 g/day, respectively. The risk for incident diabetes in participants was 6.7% after 6 years of follow up. After adjusting for age, sex, body mass index, physical activity, smoking, family history of diabetes, hypertension, serum triglyceride levels, high-density lipoprotein cholesterol levels, energy intakes and consumption of saturated fat, fruit, whole grains, vegetables, nuts and legumes, the risk for incident diabetes was lower in subjects with higher intakes of total potato (OR=0.46; 95% CI 0.25 to 0.84) and boiled potato (OR=0.47; 95% CI 0.26 to 0.85) in comparison with those who had the lowest intakes (p for trend <0.05). However, there was no significant association between fried potato intake and risk for diabetes (OR=0.50; 95% CI 0.25 to 1.07; p for trend >0.05). CONCLUSIONS: Our findings indicate that, in Tehranian adults, a moderate intake of dietary total and boiled, but not fried, potatoes may be associated with a lower risk for incident diabetes.

Nitrate-rich dietary supplementation during pregnancy: The pros and cons.

Inorganic nitrate (NO3) due to its potential endogenous conversion to nitric oxide (NO), is suggested as a compensatory fuel for disrupted NO pathways in the case of pathological stats during pregnancy. Dietary NO3-rich supplement in the NO-deficient pregnant women is now suggested as a more appealing choice with fewer off-target effects which can attenuate hypertension and preeclampsia, improve placental blood flow and subsequently enhance maternal and neonatal health. There is also an increasing public interest and common health claims regarding beneficial effects of NO3-rich dietary supplements like beetroot byproducts in pregnant women. Conversely, NO3-rich dietary supplementation during pregnancy may be accompanied with a wide range of unexpected maternal and fatal adverse outcomes such as methemoglobinemia, alteration in embryonic cells and malignant transformation, as well as thyroid disorders. In conclusion, use of dietary inorganic NO3 as a common supplement during pregnancy is currently on a long way from bench to bedside.

Is there any difference between the iodine statuses of breast-fed and formula-fed infants and their mothers in an area with iodine sufficiency?

Despite substantial progress in the global elimination of iodine deficiency, lactating mothers and their infants remain susceptible to insufficient iodine intake. This cross-sectional study was conducted to compare iodine statuses of breast-fed and formula-fed infants and their mothers at four randomly selected health care centres in Tehran. Healthy infants <3 months old and their mothers were randomly selected for inclusion in this study. Iodine was measured in urine and breast milk samples from each infant and mother as well as commercially available infant formula. The study included 124 postpartum mothers (29·2 (sd 4·9) years old) and their infants (2·0 (sd 0·23) months old). The iodine concentrations were 50-184 µg/l for infant formula, compared with a median breast milk iodine concentration (BMIC) of 100 µg/l in the exclusive breast-feeding group and 122 µg/l in the partial formula feeding group. The median values for urinary iodine concentration in the exclusive breast-feeding group were 183 µg/l (interquartile range (IQR) 76-285) for infants and 78 µg/l (IQR 42-145) for mothers, compared with 140 µg/l (IQR 68-290) for infants and 87 µg/l (IQR 44-159) for mothers in the formula feeding group. These differences were not statistically significant. After adjustment for BMIC, ANCOVA revealed that feeding type (exclusive breast-feeding v. partial formula feeding) did not significantly affect the infants' or mother's urinary iodine levels. Thus, in an area with iodine sufficiency, there was no difference in the iodine statuses of infants and mothers according to their feeding type.

Breast Milk Iodine Concentration Rather than Maternal Urinary Iodine Is a Reliable Indicator for Monitoring Iodine Status of Breastfed Neonates.

There is no scientific consensus on whether breast milk iodine concentration (BMIC) accurately reflects iodine status in lactating mothers and breastfed infants. This study aimed to compare BMIC and maternal urinary iodine concentration (UIC) as indicators of iodine status in breastfed neonates. In this cross-sectional study, 147 lactating mothers and their neonates (3-5 days postpartum) were randomly selected from health care centers. Breast milk and urine samples were collected from each mother and neonate, and a heel-prick blood sample was taken from all neonates as part of a congenital hypothyroidism screening program. According to the World Health Organization criteria, median urinary iodine concentration (UIC) ≥ 100 µg/L in lactating mothers and neonates indicates iodine sufficiency. In areas of iodine sufficiency, median BMIC ≥ 100 µg/L is considered an adequate level. Overall, 129 (89.0%) and 16 (11.0%) mothers had BMICs ≥ 100 and ˂ 100 µg/L, respectively. Median (interquartile range [IQR]) maternal UIC was 70 µg/L (42-144 µg/L) and 37 µg/L (25-100 µg/L) in mothers with breast milk iodine levels ≥ 100 and ˂ 100 µg/L, respectively (P = 0.047); values for UIC of neonates born to mothers with BMICs ≥ 100 and ˂ 100 µg/L were 230 µg/L (114-310 µg/L) and 76 µg/L (41-140 µg/L), respectively (P < 0.001). In the linear regression model, neonate UIC was positively associated with BMIC in both unadjusted (ß = 0.558, P < 0.001) and adjusted analysis (ß = 0.541, P < 0.001). A similar result was found in logistic regression analysis, indicating that neonates born to mothers with BMIC ≥ 100 µg/L were more likely to have UIC ≥ 100 µg/L compared to those whose mothers had BMIC < 100 µg/L in both unadjusted (OR = 7.93, P < 0.001) and adjusted analysis (OR = 7.29, P = 0.001). The present findings indicate that BMIC is a more sensitive indicator than maternal UIC for assessment of iodine status in breastfed neonates. To address low levels of maternal UIC, further studies on the prescription of supplements containing 150 µg/day iodine during lactation period are warranted.