The impact of dietary supplements on blood pressure in older adults: A network meta-analysis of randomized controlled trials.

Purpose: The prevalence of hypertension (HTN) increases with age and there is a need for effective, evidence-based treatments for HTN among older adults. The objective of this study was to perform a network meta-analysis to evaluate the effectiveness of different forms of nutritional supplementation on reducing blood pressure in older adults. Methods: A systematic review using PubMed and Clinical Key was performed to identify randomized controlled trials (RCTs) evaluating the effects of dietary supplements on blood pressure in adults older than 65 years of age. Network meta-analysis (NMA) was used to compare and rank the effects of different supplements on systolic (sBP), diastolic (dBP), and mean (mBP) blood pressure. Supplements were ranked according to P score. Meta-regressions were conducted to examine whether treatment effects were moderated by baseline BP and supplementation duration. Findings: We identified 144 relevant studies in the literature, twelve of which met criteria for inclusion in NMA. The included studies were published between 2003 and 2022. In reducing sBP, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), inorganic nitrates, tart cherry juice, and vitamin D supplementation were more effective than placebo, and the effect of tart cherry juice outranked that of vitamin D, vitamin E, and vitamin K2. In reducing dBP, inorganic nitrates, DHA and EPA, protein, resveratrol, and vitamin D supplementation were more effective than placebo, and the effect of resveratrol outranked that of tart cherry juice, vitamin D, vitamin E, and vitamin K2. However, the effects of tart cherry juice on sBP and resveratrol on dPB were smaller than the pooled effect of placebo, and none of the pairwise differences between the effects of examined supplements were statistically significant. Caution is needed when interpreting these results given concerns about the risk of bias assessed in seven of the twelve studies included in this analysis.

Vitamin D and Zinc Supplementation to Improve Treatment Outcomes among COVID-19 Patients in India: Results from a Double-Blind Randomized Placebo-Controlled Trial.

Background: There remains a need to identify low-cost interventions to improve coronavirus disease 2019 (COVID-19) outcomes. Vitamin D and zinc play a role in respiratory infections and could hold value as part of therapeutic regimens. Objectives: To determine the effect of vitamin D or zinc supplementation on recovery from COVID-19. Methods: We conducted a double-blind, randomly assigned 2 x 2 factorial placebo-controlled trial with 1:1:1:1 allocation ratio, enrolling nonpregnant adults with COVID-19 from hospitals in Mumbai and Pune, India (NCT04641195). Participants (N = 181) were randomly assigned to vitamin D3 (180,000 IU bolus, then 2000 IU daily), zinc (40 mg daily), vitamin D3 and zinc, or placebo, for 8 wk. Participants were followed until 8 wk. The primary outcome was time to resolution of fever, cough, and shortness of breath. Secondary outcomes were duration of individual symptoms; need for assisted ventilation; duration of hospital stay; all-cause mortality; and blood biomarkers, including nutritional, inflammatory, and immunological markers. Results: We observed no effect of vitamin D or zinc supplementation on time to resolution of all 3 symptoms [vitamin D hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.66, 1.30; P = 0.650; zinc HR: 0.94; 95% CI: 0.67, 1.33; P = 0.745)]. Neither vitamin D nor zinc supplementation was associated with secondary outcomes, except for increased endline serum vitamin D with vitamin D supplementation [median (interquartile range) difference between endline and baseline for vitamin D: 5.3 ng/mL (-2.3 to 13.7); for no vitamin D: -1.4 ng/mL (-5.6 to 3.9); P = 0.003]. We observed nonsignificant increases in serum zinc at endline following zinc supplementation. There was no evidence of interaction between vitamin D and zinc supplementation, no effect of either on hypercalcemia, and no adverse events. Conclusions: Results suggest that neither vitamin D nor zinc supplementation improves COVID-19 treatment outcomes in this population. However, much larger-scale evidence, particularly from populations with vitamin D or zinc deficiency and severe infection, is required to corroborate our findings. This trial was registered at ClinicalTrials.gov and the Clinical Trials Registry of India as NCT04641195 and CTRI/2021/04/032593 respectively.

Influence of Vitamin D Supplementation on Growth, Body Composition, and Pubertal Development Among School-aged Children in an Area With a High Prevalence of Vitamin D Deficiency: A Randomized Clinical Trial.

Importance: Vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH)D] <20 ng/mL) is prevalent among children living in temperate climates and has been reported to associate independently with stunting, obesity, and early activation of the hypothalamic-pituitary-gonadal axis. Phase 3 randomized clinical trials to investigate the influence of long-term vitamin D replacement on growth, body composition, and pubertal development of school-aged children with vitamin D deficiency are lacking. Objective: To determine whether weekly oral vitamin D supplementation influences linear growth, body composition, or pubertal development in school-aged children living in a setting where vitamin D deficiency is highly prevalent. Design, Setting, and Participants: This secondary analysis of a double-blind, placebo-controlled randomized clinical trial was conducted from June 2016 to June 2019 at 18 grade schools in Ulaanbaatar, Mongolia. School-aged children (6 to 13 years at baseline) attending participating schools were included. Exclusion criteria included a positive QuantiFERON-TB Gold in-tube assay result, conditions or medications associated with altered vitamin D metabolism, use of vitamin D supplements, signs of rickets, or intention to move from Ulaanbaatar within 4 years. Of 11 475 children invited to participate in the study, 9814 underwent QFT testing, and 8851 with negative results were included in the study. All but 1 participant in the placebo group completed follow-up and were included in the present analysis. Data were analyzed from November 2021 to February 2022. Interventions: Weekly oral doses of vitamin D3, 14 000 IU, (n = 4418), or placebo (n = 4433) for 3 years. Main Outcomes and Measures: Mean z scores for height for age, body mass index for age, and waist-to-height ratio; mean percentage body fat, fat mass, and fat-free mass; and mean Tanner scores for pubertal development. Results: Of 8851 participants, 4366 (49.3%) were female, and 8165 (92.2%) were of Khalkh ethnicity; the mean (SD) age was 9.4 (1.6) years. A total of 8453 participants (95.5%) were vitamin D deficient at baseline, and mean end-of-study 25(OH)D concentrations among participants randomized to vitamin D vs placebo were 31.0 vs 10.7 ng/mL (mean difference, 20.3; 95% CI; 19.9-20.6). However, vitamin D supplementation did not influence mean height for age, body mass index for age, waist-to-height ratio, percentage body fat, fat mass, fat-free mass, or Tanner scores, either overall or within subgroups defined by baseline 25(OH)D concentration less than 10 ng/mL vs 10 ng/mL or greater, estimated calcium intake less than 500 mg/d vs 500 mg/d or greater, or male vs female sex. Conclusions and Relevance: In school-aged children in this study with low baseline vitamin D status, oral vitamin D3 supplementation at a dose of 14 000 IU per week for 3 years was effective in elevating 25(OH)D concentrations but did not influence growth, body composition, or pubertal development. Trial Registration: ClinicalTrials.gov Identifier: NCT02276755.

Randomised trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among patients with COVID-19 in India: trial protocol.

INTRODUCTION: Presently, there are few population-level strategies to address SARS-CoV-2 infection except preventive measures such as vaccination. Micronutrient deficiency, particularly vitamin D and zinc deficiency, has been associated with dysregulated host responses, and may play an important role in COVID-19. METHODS AND ANALYSIS: We have designed a 2×2 factorial, randomised, double-blind, multi-centre placebo-controlled trial to evaluate the effect of vitamin D and zinc on COVID-19 outcomes in Maharashtra, India. COVID-19 positive individuals are recruited from hospitals in Mumbai and Pune. Participants are provided (1) vitamin D3 bolus (180 000 IU) maintained by daily dose of 2000 IU and/or (2) zinc gluconate (40 mg daily), versus placebo for 8 weeks. Participants undergo a detailed assessment at baseline and at 8 weeks, and are monitored daily in hospital or every 3 days after leaving the hospital to assess symptoms and other clinical measures. A final follow-up telephone call occurs 12 weeks post-enrolment to assess long-term outcomes. The primary outcome of the study is to time to recovery, defined as time to resolution of all of fever, cough and shortness of breath. Secondary outcomes include: duration of hospital stay, all-cause mortality, necessity of assisted ventilation, change in blood biomarker levels and individual symptoms duration. Participant recruitment commenced on April 2021. ETHICS AND DISSEMINATION: Ethical approval was obtained from institutional ethical committees of all participating institutions. The study findings will be presented in peer-reviewed medical journals. TRIAL REGISTRATION NUMBERS: NCT04641195, CTRI/2021/04/032593, HMSC (GOI)-2021-0060.

Receipt of Weekly Iron Supplementation among Indian Children, 2005-2016.

BACKGROUND: In response to India's unacceptably high burden of anemia among children aged 6-59 mo, the central government introduced the National Iron Plus Initiative program which recommends an intervention of iron supplementation to mitigate anemia, especially iron deficiency anemia. OBJECTIVE: The objective of this study was to examine the trend (between 2005-2006 and 2015-2016) in receiving weekly iron supplementation (WIS) among children aged 6-59 mo, and factors associated with receiving WIS during 2015-2016. METHODS: Two waves of the nationally representative cross-sectional National Family Health Survey (NFHS) data collected during 2005-2006 (NFHS-3) and 2015-2016 (NFHS-4) were used. The trend was measured using both rounds of datasets, whereas factors associated with WIS receipt were assessed from NFHS-4. The trend was assessed using a sample of 35,650 children from NFHS-3 and 202,227 children from NFHS-4. After exclusion of 8978 cases, a total of 199,110 children were included to analyze the factors associated with receiving WIS. Using appropriate sample weighting, unadjusted and adjusted (multivariate) logistic regression analyses were deployed. Application of the chi-squared test and checking for multicollinearity were also part of the analysis. The possibility of sample selection bias was tested. RESULTS: An increase of WIS receipt (from 4.6% in 2005-2006 to 26% in 2015-2016) was observed. Older children, children living in rural areas, children belonging to Scheduled Tribes, children of mothers with secondary education or higher, and children whose mothers had some mass media exposure had higher odds of receiving WIS. Children of fifth or higher birth order, children who were followers of Islam and Christianity, children from the richest economic group, noninstitutional birth of children, and children from high-focus group states were negatively associated with WIS receipt. CONCLUSIONS: Despite improvement (between 2005-2006 and 2015-2016) in receiving WIS, coverage remains unacceptably low (in absolute terms). The suboptimum performance of WIS intervention demands further investigation.

Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis.

Acute respiratory tract infections (ARIs) are a leading cause of ill-health and death globally. Individual or multiple micronutrients have been shown to modulate immune function and affect the risk and severity of a number of infectious diseases. We systematically reviewed the evidence on the impact of micronutrient supplements to reduce the occurrence of ARIs and shorten the duration of ARI symptoms among adults. Random effects meta-analyses were conducted to estimate the pooled effects of vitamin D, vitamin C, zinc and multiple micronutrient supplementation (MMS) on the occurrence of ARIs and the duration of ARI symptoms. Vitamin D supplementation reduced the risk of ARI (risk ratio (RR)=0.97; 95% CI 0.94 to 1.00; p=0.028) and shortened the duration of symptoms (per cent difference: -6% (95% CI -9% to -2%; p=0.003)). The RR of vitamin D to prevent ARI was farther from the null when diagnosis was based on clinical diagnosis or laboratory testing, compared with self-report and when the loading dose was <60 000 IU. Vitamin C supplementation reduced the risk of ARIs (RR=0.96; 95% CI 0.93 to 0.99; p=0.01) and shortened the duration of symptoms (per cent difference: -9% (95% CI -16% to -2%; p=0.014)). The effect of vitamin C on preventing ARI was stronger among men and in middle-income countries, compared with women and high-income countries, respectively. Zinc supplementation did not reduce the risk of ARIs but shortened the duration of symptoms substantially (per cent difference: -47% (95% CI -73% to -21%; p=0.0004)). Our synthesis of global evidence from randomised controlled trials indicates that micronutrient supplements including zinc, vitamins C and D, and multiple micronutrient supplements may be modestly effective in preventing ARIs and improving their clinical course. Further research is warranted to better understand the effectiveness that individual or multiple micronutrients have on SARS-CoV-2 infection and treatment outcomes.

Protocol for a case-control study of vitamin D status, adult multidrug-resistant tuberculosis disease and tuberculosis infection in Mumbai, India.

INTRODUCTION: Vitamin D status may be an important determinant of multidrug-resistant tuberculosis (MDR-TB) infection, progression to disease and treatment outcomes. Novel and potentially cost-effective therapies such as vitamin D supplementation are needed to stem the tide of TB and MDR-TB globally, particularly in India, a country that accounts for the largest fraction of the world's TB incidence and MDR-TB incidence, and where vitamin D deficiency is endemic. While vitamin D has shown some promise in the treatment of MDR-TB, its role in the context of MDR-TB infection and progression to disease is largely unknown. METHODS AND ANALYSIS: Through a case-control study in Mumbai, India, we aim to examine associations between vitamin D status and active MDR-TB and to investigate vitamin D status and TB infection among controls. Cases are adult outpatient pulmonary patients with MDR-TB recruited from two public TB clinics. Controls are recruited from the cases' household contacts and from non-respiratory departments of the facilities where cases were recruited. Cases and controls are assessed for serum 25-hydroxyvitamin D concentration, nutrient intake, diet quality, anthropometry and other relevant clinical and sociodemographic parameters. Controls undergo additional clinical assessments to rule out active TB and laboratory assessments to determine presence of TB infection. Statistical analysis investigates associations between vitamin D status and active MDR-TB and between vitamin D status and TB infection among controls, accounting for potential confounding effects of diet, anthropometry and other covariates. ETHICS AND DISSEMINATION: This study has been approved by Harvard T.H. Chan School of Public Health Institutional Review Board; Foundation for Medical Research Institutional Research Ethics Committee and Health Ministry's Screening Committee of the Indian Council for Medical Research. Permission was granted by the Municipal Corporation of Greater Mumbai, India, a collaborating partner on this research. Outcomes will be disseminated through publication and scientific presentation. TRIAL REGISTRATION NUMBER: NCT04342598.

Diet and Nutrition Status of Mongolian Adults.

(1) Background: Aspects of the Mongolian food supply, including high availability of animal-source foods and few plant foods, are plausibly associated with disease in the population. Data on Mongolian diets are lacking, and these risks are poorly quantified. The purpose of this study was to provide a multifaceted nutritional analysis of the modern Mongolian diet. (2) Methods: The study population consisted of 167 male and 167 female healthy non-pregnant urban and nomadic adults (22-55 years) randomly selected from lists of residents in 8 regions. From 2011-2016, 3-day weighed diet records and serum were collected twice from each participant in summer and winter; anthropometry was collected once from each participant. Serum was analyzed for biomarkers, and nutrient intake computed using purpose-built food composition data and adjusted for within-person variation. Exploratory dietary patterns were derived and analyzed for associations with diet and nutrition measurements. (3) Results: We collected 1838 of an expected 1986 diet records (92.5%), 610/658 serum samples (92.7%), and 315/334 height and weight measurements (94.3%). Sixty-one percent of men and 51% of women were overweight or obese. Consumption of red meat, refined grains, and whole-fat dairy was high, while that of fruits, non-tuberous vegetables, eggs, nuts and seeds, fish and poultry, and whole grains was low. Dairy and red meat were more consumed in summer and winter, respectively. Dietary inadequacy of 10 of 21 assessed nutrients, including fiber, folate, and vitamin D were >50% prevalent, while protein, zinc, and vitamin B12 inadequacy were low. Biochemical evidence of iron and vitamin A deficiency was also low. Three dietary patterns (Urban, Transitional, Nomadic) explained 41% of variation in food consumption. The Urban pattern was positively associated with BMI in multivariate analysis. (4) Conclusions: Results indicate a high prevalence of key dietary inadequacies and overweight among Mongolian adults. Prior studies by our group have suggested that expanded supplementation and food fortification would be effective in addressing micronutrient inadequacies; these strategies should be coupled with measures to mitigate the growing burden of chronic disease.

Effects of Vitamin D Supplementation and Seasonality on Circulating Cytokines in Adolescents: Analysis of Data From a Feasibility Trial in Mongolia.

Vitamin D deficiency is prevalent in human populations and has been linked to immune dysfunction. Here we explored the effects of cholecalciferol supplementation on circulating cytokines in severely vitamin D deficient [blood 25(OH)D << 30 nmol/L] adolescents aged 12-15 from Mongolia. The study included 28 children receiving 800 IU daily cholecalciferol for 6 months spanning winter and spring, and 30 children receiving placebo during the same period. The levels of 25(OH)D were assessed at baseline, 3 and 6 months. Twenty-one cytokines were measured in serum at baseline and at 6 months. Changes in 25(OH)D and cytokines were assessed using paired parametric tests. The median blood 25(OH)D concentration at baseline was 13.7 nmol/L (IQR = 10.0-21.7). Supplementation tripled blood 25(OH)D levels (p < 0.001) and was associated with elevated interleukin (IL)-6 (p = 0.043). The placebo group had reduced macrophage inflammatory protein (MIP)-1α (p = 0.007) and IL-8 (p = 0.034) at 6 months. Although limited by a small sample size, these findings suggest that cholecalciferol supplementation and seasonality may impact systemic immunity in adolescents, identifying chemokines as potentially important biomarkers of vitamin D status in this Northeast Asian population. Larger clinical trials are warranted to validate these results. Clinical Trial Registration: www.ClinicalTrial.org, Identifier: NCT01244204.

Home Fortification of Rice With Lime: A Novel Potential Way to Reduce Calcium Deficiency in Bangladesh.

BACKGROUND: In order to improve calcium status, fortified rice should have acceptable organoleptic properties of that food. OBJECTIVE: We aimed to assess whether home fortification of rice with slaked lime can increase calcium content of rice and whether this fortified rice is well tolerated in a nutritionally at-risk population. METHODS: This experimental study measured the calcium content of rice cooked with different concentration of lime and assessed the acceptability of fortified rice among 400 women and children. Each participant received fortified rice with one of five concentrations of lime (0, 2.5, 5, 7.5 or 10 gm per 500 gm of rice), with or without additional foods (lentil soup or fried green papaya). All participants were asked to score the organoleptic qualities on a hedonic scale. RESULTS: Analysis showed that rice calcium content increased in a dose- response manner with increased lime during cooking (76.03, 205.58, 427.55, 614.29 and 811.23 mg/kg for given lime concentrations). Acceptability of the meal was greater when additional foods were served with rice at all lime concentrations. In both groups, the 7.5M arm reported highest overall acceptability (children, 6.25; women 6.10). This study found significant association between overall acceptability (different concentrations of lime mixed rice; with/without additional foods) and between groups (women vs. children) (p value = < 0.001) where-as no association was found within groups. CONCLUSIONS: Lime-fortified rice can be feasible considering the calcium uptake of rice and organoleptic character. Further research on bioavailability can establish a solid foundation that will support design of an effective intervention to reduce calcium deficiency in this population.

Comparison of seasonal serum 25-hydroxyvitamin D concentrations among pregnant women in Mongolia and Boston.

Adequate vitamin D status during pregnancy is important for developing fetal bone strength and density and may play a role in preventing a range of skeletal and non-skeletal diseases in both mothers and children. We previously identified Mongolian women of reproductive age to have the lowest vitamin D levels yet observed in any population globally, which renders this population uniquely important in vitamin D research. In this study, we measured the seasonal distribution of 25-hydroxyvitamin D (25(OH)D) concentration in 390 healthy third trimester pregnant women living in urban and rural Mongolia using DiaSorin LIAISON and compared this distribution to that of 206 third trimester women living in Boston, USA. Also, we analyzed seasonally-independent associations between (25(OH)D) levels and selected predictors in both groups using quantile regression. Mean 25(OH)D levels were significantly higher and less seasonal in Boston (seasonal range: 27.1 ±â€¯7.0-31.5 ±â€¯7.7 ng/ml) than in Mongolia (seasonal range: 11.2 ±â€¯3.9-19.2 ±â€¯6.7 ng/ml). Adjusting for month of blood draw, higher 25(OH)D levels were significantly associated with older age, lower gravidity, lower BMI, and lack of a college or university degree among Boston participants, however, only gravidity was robust to multivariable adjustment. No assessed characteristics were independently predictive in Mongolia, likely due to universally low 25(OH)D levels and a resulting lack of between-person variation. In conclusion, vitamin D status among pregnant Mongolians is severely depressed throughout the year and should be addressed through fortification and supplementation, while in the U.S., deficiency is associated with specific characteristics targetable through supplementation.

Awareness and Attitudes Regarding Industrial Food Fortification in Mongolia and Harbin.

This study assessed awareness and attitudes regarding industrial food fortification among adults in urban and rural Mongolia, and the city of Harbin, China. Between 2014 and 2017, surveys were collected from healthy men and women aged ≥18 years (182 Harbin residents and 129 urban and rural Mongolians participating in a nationwide nutrition survey in Mongolia). Survey reproducibility was assessed among 69 Mongolian participants to whom it was administered twice (summer and winter). Findings revealed that only 19% of rural and 30% of urban Mongolians, and 48% of Harbin residents were aware that industrial fortification is practiced in their countries. For most food groups evaluated, at least half of Mongolians and less than half of Harbin residents thought fortification was government-mandated (only the addition of iodine with salt is actually mandated in both countries). Fifty-five percent of rural and urban Mongolians favored mandatory fortification of foods, 14% disapproved of it, and 31% were uncertain (compared with 25%, 38%, and 37% respectively in Harbin). Upon learning that the primary purpose of adding vitamin D to milk is to prevent rickets, 75% of Mongolians but only 18% of Harbin residents favored mandatory fortification, while 42% of Harbin residents favored voluntary fortification (compared with <10% of Mongolians). In conclusion, in Mongolia and Harbin, awareness and understanding of food fortification is low, as is receptivity toward mandatory fortification. Health promotion and social marketing should be designed to create an enabling environment for increasing supply and demand of fortified foods, in support of upcoming program implementation in Mongolia and potential future legislation in northeern China.

Bronze Age population dynamics and the rise of dairy pastoralism on the eastern Eurasian steppe.

Recent paleogenomic studies have shown that migrations of Western steppe herders (WSH) beginning in the Eneolithic (ca. 3300-2700 BCE) profoundly transformed the genes and cultures of Europe and central Asia. Compared with Europe, however, the eastern extent of this WSH expansion is not well defined. Here we present genomic and proteomic data from 22 directly dated Late Bronze Age burials putatively associated with early pastoralism in northern Mongolia (ca. 1380-975 BCE). Genome-wide analysis reveals that they are largely descended from a population represented by Early Bronze Age hunter-gatherers in the Baikal region, with only a limited contribution (∼7%) of WSH ancestry. At the same time, however, mass spectrometry analysis of dental calculus provides direct protein evidence of bovine, sheep, and goat milk consumption in seven of nine individuals. No individuals showed molecular evidence of lactase persistence, and only one individual exhibited evidence of >10% WSH ancestry, despite the presence of WSH populations in the nearby Altai-Sayan region for more than a millennium. Unlike the spread of Neolithic farming in Europe and the expansion of Bronze Age pastoralism on the Western steppe, our results indicate that ruminant dairy pastoralism was adopted on the Eastern steppe by local hunter-gatherers through a process of cultural transmission and minimal genetic exchange with outside groups.

Projected effectiveness of mandatory industrial fortification of wheat flour, milk, and edible oil with multiple micronutrients among Mongolian adults.

Industrial fortification of wheat flour is a potentially effective strategy for addressing micronutrient deficiencies in Mongolia, given its ubiquitous consumption and centralized production. However, Mongolia has not mandated fortification of any foods except for salt with iodine. This study modeled the effectiveness and safety of mandatory industrial fortification of wheat flour alone and in combination with edible oil and milk in reducing the prevalence of multiple micronutrient intake deficiencies among healthy non-pregnant adults in Mongolia. Six days of diet records (3 summer, 3 winter) were collected from 320 urban and rural adults across the country and analyzed for food and nutrient consumption using a purpose-built food composition table, and the Intake Monitoring and Planning Program (IMAPP) was used to project the effects of fortification on summer and winter bioavailable micronutrient intake and intake deficiency under different fortification guidelines within population subgroups defined by urban or rural locality and sex. Projections showed that flour fortification would be effective in reducing intake deficiencies of thiamin and folate, while marginal benefits of fortification with iron and riboflavin would be smaller given these nutrients' higher baseline consumption, and fortification with zinc, niacin, and vitamin B12 may be unnecessary. Fortification of flour, oil, and milk with vitamins A, D, and E at levels suggested by international guidelines would substantially reduce vitamin A intake deficiency and would increase vitamin D intake considerably, with the greatest benefits elicited by flour fortification and smaller benefits by additionally fortifying oil and milk. These results support mandatory industrial fortification of wheat flour, edible oil, and milk with iron, thiamin, riboflavin, folate, and vitamins A, D, and E in Mongolia. Considerations will be necessary to ensure the fortification of these nutrients is also effective for children, for whom the potential benefit of zinc, niacin, and vitamin B12 fortification should be assessed.

High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial.

RATIONALE: Existing trials of adjunctive vitamin D in the treatment of pulmonary tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing regimens, and high baseline vitamin D status among participants. Comprehensive analyses of the effects of genetic variation in the vitamin D pathway on response to vitamin D supplementation are lacking. OBJECTIVES: To determine the effect of high-dose vitamin D3 on response to antimicrobial therapy for PTB and to evaluate the influence of single-nucleotide polymorphisms (SNPs) in vitamin D pathway genes on response to adjunctive vitamin D3. METHODS: We conducted a clinical trial in 390 adults with PTB in Ulaanbaatar, Mongolia, who were randomized to receive four biweekly doses of 3.5 mg (140,000 IU) vitamin D3 (n = 190) or placebo (n = 200) during intensive-phase antituberculosis treatment. MEASUREMENTS AND MAIN RESULTS: The intervention elevated 8-week serum 25-hydroxyvitamin D concentrations (154.5 nmol/L vs. 15.2 nmol/L in active vs. placebo arms, respectively; 95% confidence interval for difference, 125.9-154.7 nmol/L; P < 0.001) but did not influence time to sputum culture conversion overall (adjusted hazard ratio, 1.09; 95% confidence interval, 0.86-1.36; P = 0.48). Adjunctive vitamin D3 accelerated sputum culture conversion in patients with one or more minor alleles for SNPs in genes encoding the vitamin D receptor (rs4334089, rs11568820) and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1: rs4646536) (adjusted hazard ratio ≥ 1.47; P for interaction ≤ 0.02). CONCLUSIONS: Vitamin D3 did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656).

Seasonal Epidemiology of Serum 25-Hydroxyvitamin D Concentrations among Healthy Adults Living in Rural and Urban Areas in Mongolia.

Many factors put Mongolians at risk of vitamin D deficiency. Despite low levels observed in Mongolian children and pregnant women, there are few data published on the vitamin D status of non-pregnant adults. Between summer 2011 and winter 2013, paired summer and winter blood samples were collected from 320 healthy men and women (20-58 years) living in eight Mongolian provinces. Mean serum 25(OH)D concentrations were 22.5 ng/mL (95% CI: 14.5, 32.5) in summer and 7.7 ng/mL (95% CI: 4.6, 10.8) in winter, with a distribution (<10/10-20/20-30/≥30 ng/mL) of 3.1%/39.3%/39.6%/17.9% in summer and 80.1%/19.5%/0.3%/0.0% in winter. Residents of the capital, Ulaanbaatar, had lower levels in both seasons than any other region, whereas residents of the Gobi desert had the highest. In summer, indoor workers had significantly lower levels than outdoor workers (-2.3 ng/mL; 95% CI: -4.1, -5.7) while levels in males exceeded those in females (4.0 ng/mL; 95% CI: 2.3, 5.7). Effects of region, occupation, and sex were also significant in multivariable regression. In conclusion, Mongolian adults had extremely low serum 25(OH)D, particularly in winter, when 80.1% had concentrations below 10 ng/mL. These results indicate a need for effective vitamin D interventions for the Mongolian adult population, particularly among women and residents of Ulaanbaatar.

Intervention study shows suboptimal growth among children receiving a food supplement for five months in a slum in Bangladesh.

AIM: This study assessed weight and height changes among underweight children who received a locally produced, cereal-based, ready-to-use supplementary food. METHODS: We recruited 500 underweight Bangladeshi children aged 6-23 months from a Dhaka slum and individually matched them by sex and neighbourhood with 480 well-nourished controls. The intervention group received the daily food supplement for five months, and both groups received daily micronutrient supplements. Their weight, height, mid-upper-arm circumference and head circumference were measured monthly. RESULTS: The children's mean daily weight gain decreased from 1.27 to 0.66 grams per kilogram per day (g/kg/day) in the intervention group and 0.77 to 0.49 g/kg/day in the controls after adjusting for age differences between the two groups from baseline to five months of follow-up. The mean monthly height gain decreased from 1.13 to 1.03 millimetres per metre per month in the intervention children and 1.26 to 1.01 in the controls. The weight gain was highest in the intervention children who were most wasted at baseline and the controls who were least stunted. CONCLUSION: The children showed suboptimal growth despite food supplements, highlighting the need for ongoing research to develop inexpensive, locally sourced food supplements to improve the nutrition of underweight children in Bangladesh.

Calcium Deficiency in Bangladesh: Burden and Proposed Solutions for the First 1000 Days.

BACKGROUND: Bangladesh incurs among the highest prevalence of stunting and micronutrient deficiencies in the world, despite efforts against diarrheal disease, respiratory infections, and protein-energy malnutrition which have led to substantial and continuous reductions in child mortality over the past 35 years. Although programs have generally paid more attention to other micronutrients, the local importance of calcium to health has been less recognized. OBJECTIVE: To synthesize available information on calcium deficiency in Bangladesh in order to inform the design of an effective national calcium program. METHODS: We searched 3 online databases and a multitude of survey reports to conduct a narrative review of calcium epidemiology in Bangladesh, including population intake, determinants and consequences of deficiency, and tested interventions, with particular reference to young children and women of childbearing age. This was supplemented with secondary analysis of a national household survey in order to map the relative extent of calcium adequacy among different demographics. RESULTS: Intake of calcium is low in the general population of Bangladesh, with potentially serious and persistent effects on public health. These effects are especially pertinent to young children and reproductive-age women, by virtue of increased physiologic needs, disproportionately poor access to dietary calcium sources, and a confluence of other local determinants of calcium status in these groups. CONCLUSION: A tablet supplementation program for pregnant women is an appealing approach for the reduction in preeclampsia and preterm birth. Further research is warranted to address the comparative benefit of different promising approaches in children for the prevention of rickets.