Faecal microbiota of schoolchildren is associated with nutritional status and markers of inflammation: a double-blinded cluster-randomized controlled trial using multi-micronutrient fortified rice.

Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419)).

Solutions to Enhance Health with Alternative Treatments (SEHAT) protocol: a double-blinded randomised controlled trial for gut microbiota-targeted treatment of severe acute malnutrition using rice bran in ready-to-use therapeutic foods in Indonesia.

INTRODUCTION: Current formulations of ready-to-use therapeutic foods (RUTFs) to treat severe acute malnutrition (SAM) in children focus on nutrient density and quantity. Less attention is given to foods targeting gut microbiota metabolism and mucosal barrier functions. Heat-stabilised rice bran contains essential nutrients, prebiotics, vitamins and unique phytochemicals that have demonstrated favourable bioactivity to modulate gut microbiota composition and mucosal immunity. This study seeks to examine the impact of RUTF with rice bran on the microbiota during SAM treatment, recovery and post-treatment growth outcomes in Jember, Indonesia. Findings are expected to provide insights into rice bran as a novel food ingredient to improve SAM treatment outcomes. METHODS AND ANALYSIS: A total of 200 children aged 6-59 months with uncomplicated SAM (weight-for-height z-scores (WHZ) <-3, or mid-upper arm circumference (MUAC) <115 mm or having bilateral pitting oedema +/++) or approaching SAM (WHZ<-2.5) will be enrolled in a double-blinded, randomised controlled trial. Children in the active control arm will receive a locally produced RUTF; those in the intervention arm will receive the local RUTF with 5% rice bran. Children will receive daily RUTF treatment for 8 weeks and be monitored for 8 weeks of follow-up. Primary outcomes include the effectiveness of RUTF as measured by changes in weight, WHO growth z-scores, MUAC and morbidity. Secondary outcomes include modulation of the gut microbiome and dried blood spot metabolome, the percentage of children recovered at weeks 8 and 12, and malnutrition relapse at week 16. An intention-to-treat analysis will be conducted for each outcome. ETHICS AND DISSEMINATION: The findings of this trial will be submitted to peer-reviewed journals and will be presented at relevant conferences. Ethics approval obtained from the Medical and Health Research Ethical Committee at the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Madain Yogyakarta Ref. No.: KE/FK/0546/EC/2022 and KE/FK/0703/EC/2023 and from Colorado State University IRB#1823, OHRP FWA00000647. TRIAL REGISTRATION NUMBER: NCT05319717.

Association of both Water, Sanitation and Hygiene (WASH) and Infant and Young Child Feeding (IYCF) practices with childhood malnutrition in Lao PDR: a cross-sectional study of the 2017 Lao Social Indicator Survey II.

OBJECTIVE: We assessed whether Water, Sanitation and Hygiene (WASH) and Infant and Young Child Feeding (IYCF), either alone or combined, were associated with malnutrition among Lao People's Democratic Republic (Lao PDR) children aged 6 to <24 months. DESIGN: This is a secondary analysis of the 2017 Lao Social Indicator Survey II (LSIS II), which used multistage probability proportional to size sampling. Logistic regression analyses were conducted with OR and its corresponding 95% CI. SETTING: The LSIS II was conducted a nationwide household-based survey covering all 18 provinces in Lao PDR. PARTICIPANTS: We had a total of 3375 children (weighted sample 3345) and 357 households with data on drinking water. OUTCOME MEASURES: The outcomes of this study were stunting and wasting. RESULTS: The prevalence of stunting and wasting was 28.9% and 10.1%, respectively. Even though households with access to a basic or improved water source were high (82.5%), over 83% of drinking water was contaminated with Escherichia coli. Access to improved sanitation, basic hygiene and adequate IYCF gave a significant lower risk of becoming stunted. The combined effect of these practices on stunting was (adjusted OR (AOR)=0.54; 95% CI=0.41 to 0.73) greater than each practice alone (improved sanitation: AOR=0.75; 95% CI=0.61 to 0.93; basic hygiene: AOR=0.69; 95% CI=0.57 to 0.83; adequate IYCF: AOR=0.79; 95% CI=0.64 to 0.98). Access to improved sanitation and adequate IYCF was associated with a significant lower risk for being wasted, and again the combined effect of these practices was (AOR=0.64; 95% CI=0.44 to 0.92) greater than each practice alone (improved sanitation: AOR=0.68; 95% CI=0.49 to 0.93 and adequate IYCF: AOR=0.66; 95% CI=0.47 to 0.92). CONCLUSION: Given the strong associations with both stunting and wasting, and the added benefits when combining WASH and IYCF, there is a need of multisectoral interventions to reduce early childhood malnutrition in Lao PDR.

Short-Term Acceptability of Ready-to-Use Therapeutic Foods in Two Provinces of Lao People's Democratic Republic.

BACKGROUND: In Lao PDR, acute malnutrition remains a public health problem, with around 9% of children under 5 being affected. Outpatient treatment of severe acute malnutrition requires ready-to-use therapeutic foods (RUTFs), but concerns have been raised about the acceptability of globally available products. Culturally acceptable RUTFs could be locally developed, but data are lacking on RUTF preferences in Lao PDR. METHODS: In a crossover-designed study, four different RUTFs were tested for short-term acceptability and organoleptic qualities (two globally available: peanut-based, which is the current standard, and wheat-milk-based RUTFs; two regionally produced: a mung-bean-based and a fish-rice-based RUTF). Organoleptic properties were evaluated by 83 caretaker-child pair participants through a taste test and a 30 min consumption test. Short-term acceptability was assessed through a 3-day intake test. The study sites were in Phongsaly (North Laos) and Attapeu (South Laos). Focus group discussions were conducted at the beginning and the end of the study. RESULTS: The mung bean RUTF was the favorite among caretakers, with an acceptability percentage of 96.2%, and scored better (p-value < 0.05) for all organoleptic variables than the other three RUTFs. Overall, 3 days after receiving take-home rations, the mean percentage of consumption was above 80% for all the RUTFs, with the mung bean product being the most consumed. CONCLUSIONS: The regionally produced mung bean RUTF was the most accepted, whereas the other regionally produced fish-based RUTF was the least accepted, showing the complexity of finding culturally acceptable solutions to fight malnutrition. For Lao PDR, a mung-bean-based RUTF seems the way forward, even if the current standard peanut-based RUTF appeared to be acceptable, albeit not the most preferred.

Changes in polyunsaturated fatty acids during treatment of malnourished children may be insufficient to reach required essential fatty acid levels - A randomised controlled trial.

BACKGROUND & AIMS: Severe acute malnutrition (SAM) is a global concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on polyunsaturated fatty acids (PUFA) are almost non-existent. The aim was to investigate the change in whole-blood PUFA and nutrition and health markers among Cambodian children with SAM after treatment with RUTFs. METHODS: The trial was an 8-week randomised clinical trial of the effectiveness of locally produced fish-based RUTF (L-RUTF) vs standard milk-based RUFT (S-RUTF). Whole-blood fatty acids were analysed using dried blood spots. Nutrition and health markers were assessed using anthropometric assessment and blood samples for markers of inflammation. The trial was conducted at the National Pediatric Hospital, Phnom Penh, Cambodia, with one hundred and twenty-one 6-59-month-old children in treatment for SAM. RESULTS: L-RUTF had a higher content of n-3 PUFA and a higher content of arachidonic acid (AA) and docosahexaenoic acid (DHA), while S-RUTF had the highest content of n-6 PUFA. At baseline, the children presented with a Mead acid level in whole-blood of around 0.08% of total fatty acids (FA%) and an omega-3 index of ∼0.91 ± 0.44. After eight weeks of S-RUTF treatment, linoleic acid (LA), AA, n-6/n-3 PUFA ratio, and Mead acid levels were increased. The L-RUTF intervention did not change the whole-blood PUFAs from baseline. At discharge, the children in the L-RUTF group had a lower n-6/n-3 PUFA ratio than the children in the S-RUTF group, driven by a lower alpha-linolenic acid (ALA) (0.20 vs 0.27 FA%, p = 0.004) and lower LA (15.77 vs 14.21 FA%, p = 0.018) with no significant differences in AA or DHA levels. Weight-for-height z-score at discharge was negatively associated with total PUFA (ß -1.4 FA%, 95%CI. -2.7; -0.1), n-6 LCPUFA (ß -1.3 FA%, 95%CI. -1.3; -0.3), and AA (ß -0.6 FA%, 95%CI. -1.0; -0.2). Age-adjusted height was negatively associated with the Mead acid:AA ratio (ß -1.2 FA%, 95%CI. -2.2; -0.2). No significant change was seen in inflammation markers within groups or between groups during treatment, and n-3 and n-6 PUFAs were not associated with markers of inflammation or haemoglobin status at discharge. CONCLUSION: The trial found that whole-blood markers of PUFA status were low in children at admission and discharge from SAM treatment, indicating that the currently recommended composition of RUTFs are not able to correct their compromised essential fatty acid status. The higher content of DHA and AA in L-RUTF did not give rise to any improvement in PUFA status. No changes in health markers or associations between PUFA and health markers were found. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02907424.

Ready-to-Use Therapeutic Foods (RUTFs) Based on Local Recipes Are as Efficacious and Have a Higher Acceptability than a Standard Peanut-Based RUTF: A Randomized Controlled Trial in Indonesia.

To strengthen community-based treatment of severe acute malnutrition (SAM) in Indonesia, locally produced ready-to-use therapeutic foods (RUTFs) are needed, but data on their acceptability and effectiveness are lacking. We conducted an individually randomized controlled trial in 302 children (6-59 months old) with uncomplicated SAM receiving 8 weeks of a standard RUTF (CON) or one of four alternative RUTFs produced with locally available ingredients: soybean (SOY), mungbean (MUN1, MUN2) or peanuts (PEA). The main outcomes were weight gain and product acceptability. Children consumed on average 2.2 kg of standard RUTF, but up to 4.5 kg of the local products (MUN2, p < 0.05). Mean weight gain did not differ across the groups (p > 0.05). Controlled for consumption, children receiving either CON or SOY RUTF gained >2 g/kg body weight (BW)/day compared with 1.6 g/kg BW/day in children receiving the other RUTF products (p > 0.05). Overall drop-out was 29.1%, ranging from 21.3% (MUN2) to 38.3% (CON, p > 0.05). Mean time to drop out was 19 days in the CON group, significantly shorter than in the PEA group (33.6 days, p < 0.05). Thus, with no difference in weight gain and better acceptance, the development of locally produced RUTFs in Indonesia is warranted to strengthen the community-based treatment of SAM.

Restricting diet for perceived health benefit: A mixed-methods exploration of peripartum food taboos in rural Cambodia.

Food taboos encompass food restrictions practiced by a group that go beyond individual preferences. During pregnancy and lactation, food taboos may contribute to inadequate nutrition and poor maternal and infant health. Restriction of specific fish, meat, fruits and vegetables is common among peripartum women in many Southeast Asian countries, but data from Cambodia are lacking. In this mixed-methods study, 335 Cambodian mothers were asked open-ended questions regarding dietary behaviours during pregnancy and up to 24 weeks postpartum. Descriptive statistics and content analysis were used to characterize food taboos and multiple logistic regression analyses were conducted to identify predictors of this practice. Participants were 18-44 years of age, all of Khmer ethnicity and 31% were primiparous. Sixty-six per cent of women followed food taboos during the first 2 weeks postpartum, whereas ~20% of women restricted foods during other peripartum periods. Pregnancy taboos were often beneficial, including avoidance of sugar-sweetened beverages, coffee and alcohol. Conversely, postpartum avoidances typically included nutrient-dense foods such as fish, raw vegetables and chicken. Food taboos were generally followed to support maternal and child health. No significant predictors of food taboos during pregnancy were identified. Postpartum, each additional live birth a woman had reduced her odds of following food taboos by 24% (odds ratio [95% confidence interval]: 0.76 [0.61-0.95]). Specific food taboo practices and rationales varied greatly between women, suggesting that food taboos are shaped less by a strict belief system within the Khmer culture and more by individual or household understandings of food and health during pregnancy and postpartum.

Ready-to-Use Therapeutic Foods Fail to Improve Vitamin A and Iron Status Meaningfully during Treatment for Severe Acute Malnutrition in 6-59-Month-old Cambodian Children.

Severe acute malnutrition (SAM) remains a global health concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on micronutrient status during SAM treatment are almost nonexistent. The objective was to investigate the impact of RUTFs on the iron and vitamin A status of 6-59-month-old children receiving SAM treatment. Biomarkers of vitamin A status (retinol-binding protein, RBP), iron status (ferritin and soluble transferrin receptor, sTfR), and inflammation (C-reactive protein, CRP, and alpha-1 acid glycoprotein, AGP) were collected at admission and discharge (week 8) during an RUTF effectiveness trial. Vitamin A deficiency was defined as RBP <0.70 µmol/L, low body iron as body iron (BI) <0 mg/kg and deficient iron stores as ferritin <12 µg/L. Data were available for 110 and 75 children at admission and discharge, respectively. There was no significant difference in haemoglobin, ferritin, sTfR, BI or RBP concentrations between admission and discharge. At discharge, BI was 0.2 mg/kg lower, and there was a tendency towards a slightly lower RBP concentration, but the prevalence of vitamin A deficiency was low at admission and discharge (6% and 3%, respectively). The small impact of both RUTFs on improving vitamin A and iron status during SAM treatment calls for further research on the bioavailability of micronutrients to enhance the effectiveness of SAM treatment on micronutrient status.

Comparing two simplified questionnaire-based methods with 24-h recalls for estimating fortifiable wheat flour and oil consumption in Mandaluyong City, Philippines.

Information on fortifiable food consumption is essential to design, monitor and evaluate fortification programmes, yet detailed methods like 24-h recalls (24HRs) that provide such data are rarely conducted. Simplified questionnaire-based methods exist but their validity compared with 24HRs has not been shown. We compared two simplified methods (i.e., a household food acquisition and purchase questionnaire [FAPQ] and a 7-day semiquantitative food frequency questionnaire [SQ-FFQ]) against 24HRs for estimating fortifiable food consumption. We assessed the consumption of fortifiable wheat flour and oil using a FAPQ and, for wheat flour only, a 7-day SQ-FFQ and compared the results against 24HRs. The participants included children 12-18 months (n = 123) and their mothers 18-49 years selected for a study assessing child vitamin A intake and status in Mandaluyong City, Philippines. For fortifiable wheat flour, the FAPQ estimated considerably lower mean intakes compared to 24HRs for children and mothers (2.2 vs. 14.1 g/day and 5.1 vs. 42.3 g/day, respectively), while the SQ-FFQ estimated slightly higher mean intakes (15.7 vs. 14.1 g/day and 51.5 vs. 42.3 g/day, respectively). For fortifiable oil, the FAPQ estimated considerably higher mean intakes compared to 24HRs for children and mothers (4.6 vs. 1.8 g/day and 12.5 vs. 6.1 g/day, respectively). The SQ-FFQ, but not the FAPQ, generated useful information on fortifiable food consumption that can inform fortification programme design and monitoring decisions in the absence of more detailed individual-level data. Potential adaptations to improve the FAPQ, such as additional questions on foods prepared away from home and usage patterns, merit further research.

Micronutrient intake of children in Ghana and Benin: Estimated contribution of diet and nutrition programs.

We estimated how micronutrient needs of young children, aged 6-24 months were covered by the standard (traditional) diets in Ghana and Benin, and the contributions of partial breastfeeding and national nutrition programs aimed at improving micronutrient status to overall micronutrient intakes. Estimates of micronutrient intake from standard diets were based on previous surveys, using the food composition table of West Africa (INFOOD). Recommended micronutrient intakes were based on World Health Organization recommendations. Children were grouped in three age groups (6-8, 9-12, and 13-24 months) to capture the changing dynamics of the complementary feeding period. As expected, from 6 months of age onwards, breastmilk didn't cover the micronutrient needs. The standard diets contributed only minimal to micronutrient intakes of children ranging from 0% to 37% of recommended intakes for Ca, Fe, Zn, vitamin A, vitamin D and iodine depending on the micronutrient considered. The contribution of mass (bio)-fortification programs to the coverage of micronutrient needs varied widely, depending on the staple food considered and the country, but overall did not allow to fill the gap in micronutrient needs of children except for vitamin A in some contexts. In contrast, consumption of voluntary fortified complementary food, especially formulated for the needs in this age groups, contributed substantially to overall micronutrient intake and could fill the gap for several micronutrients. The development of young child-targeted programs including micronutrient-dense foods, associated with interventions to increase the diet diversity and meal frequency, could significantly improve micronutrients intakes of children in both Ghana and Benin.

The associations between stunting and wasting at 12 months of age and developmental milestones delays in a cohort of Cambodian children.

Worldwide, over 250 million children under 5 years do not reach their developmental potential due to several causes, including malnutrition. In Cambodia, the prevalence of stunting and wasting among children remains high. This prospective cohort study aimed to assess acquisition of motor and cognitive developmental milestones in early childhood and their associations with stunting and wasting. Children aged from 0 to 24 months were recruited from three provinces in Cambodia and followed up to seven times from March 2016 to June 2019, until their 5 years. Data collection included anthropometry and developmental milestones. Seven motor and seven cognitive milestones were evaluated using the Cambodian Development Milestone Assessment Tool. Associations were assessed with parametric survival models. Hazard ratios (HR) below 1 stood for lower probabilities for achieving developmental milestones. Data were available for 7394 children. At 12 months, the prevalence of stunting and wasting were 23.7% and 9.6% respectively. Both were consistently associated with delays in most motor and cognitive milestones. Stunting was strongly associated with delays in gross motor milestones (HR < 0.85; p < 0.001). Wasting was more strongly associated with delays in fine motor development and most cognitive milestones (HR < 0.75; p < 0.001). Promoting nutritional programs in the first 1000 days to prevent malnutrition is essential to further the optimal growth and motor and cognitive development of Cambodian children.

Decisions to Start, Strengthen, and Sustain Food Fortification Programs: An Application of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence to Decision (EtD) Framework in Nigeria.

Background: Although the potential impact of food fortification to improve the micronutrient status of populations has been demonstrated beyond a doubt, it is constrained in practice by critical gaps in program design and implementation. These are partly linked to suboptimal decision making. Objectives: We aimed to demonstrate how the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence to Decision (EtD) framework for health system and public health decisions can be applied to formulate recommendations and make decisions in national food fortification programming. Methods: Following a program impact pathway, we reviewed the literature to define the key decision types and identify the corresponding decision makers necessary for designing and implementing effective food fortification programs. We then applied the GRADE EtD framework to the Nigerian fortification program to illustrate how evidence-informed assessments and conclusions can be made. Results: Fortification program decisions were classified into 5 types: 1) program initiation; 2) program design; 3) program delivery; 4) program impact; and 5) program continuation. Policymakers, food processors, and (in cases dependent on or considering external funding) development partners are the main decision makers in a fortification program, whereas technical partners play important roles in translating evidence into contextualized recommendations. The availability and certainty of evidence for fortification programs are often low (e.g., quality and coverage data are not routinely collected and there are challenges evaluating impact in such population-based programs using randomized controlled trials) yet decisions must still be made, underscoring the importance of using available evidence. Furthermore, when making program initiation and continuation decisions, coordination with overlapping micronutrient interventions is needed where they coexist. Conclusions: This framework is a practical tool to strengthen decision-making processes in fortification programs. Using evidence in a systematic and transparent way for decision making can improve fortification program design, delivery, and ultimately health impacts.

The relationship between wasting and stunting in Cambodian children: Secondary analysis of longitudinal data of children below 24 months of age followed up until the age of 59 months.

The interrelationship between wasting and stunting has been poorly investigated. We assessed the association between two indicators of linear growth, height-for-age Z-score (HAZ) change and occurrence of accelerated linear growth, and selected indicators of wasting and wasting reversal in 5,172 Cambodian children aged less than 24 months at enrolment in the 'MyHealth' study. The specific objectives were to evaluate the relationship between temporal changes in wasting and 1) change in HAZ and 2) episodes of accelerated linear growth. At enrolment, the stunting and wasting prevalence were 22.2 (21.0;23.3) % and 9.1 (8.1;10.1) %, respectively, and reached 41.4 (39.3;43.6) %, and 12.4 (11.5;13.3) % respectively, two years later. Between 14-19% of stunted children were also wasted throughout the whole study period. For each centimetre increase in Mid-Upper Arm Circumference (MUAC) from the previous assessment, the HAZ increased by 0.162 (0.150; 0.174) Z-score. We also observed a delayed positive association between the weight for height Z score (WHZ) unit increase and HAZ change of +0.10 to +0.22 units consistent with a positive relationship between linear growth and an increase in WHZ occurring with a lag of approximately three months. A similar positive correlation was observed for the occurrence of an episode of accelerated linear growth. These results show that interventions to prevent and treat wasting can contribute to stunting reduction and call for integrated wasting and stunting programming.

Thiamine supplementation holds neurocognitive benefits for breastfed infants during the first year of life.

Women reliant on mostly rice-based diets can have inadequate thiamine intake, placing breastfed infants at risk of thiamine deficiency and, in turn, physical and cognitive impairments. We investigated the impact of maternal thiamine supplementation doses on infants' cognitive, motor, and language development across the first year. In this double-blind, four-parallel-arm, randomized controlled trial, healthy mothers of exclusively breastfed newborn infants were recruited in Kampong Thom, Cambodia. At 2 weeks postnatal, women (n = 335) were randomized to one of four treatment groups to consume one capsule/day with varying amounts of thiamine for 22 weeks: 0, 1.2, 2.4, and 10 mg. At 2, 12, 24, and 52 weeks of age, infants were assessed with the Mullen Scales of Early Learning (MSEL) and the Caregiver Reported Early Development Instrument (CREDI). Multiple regression and mixed effects modeling suggest that by 6 months of age, the highest maternal thiamine dose (10 mg/day) held significant benefits for infants' language development, but generally not for motor or visual reception development. Despite having achieved standardized scores on the MSEL that approximated U.S. norms by 6 months, infants showed a significant drop relative to these norms in both language domains following trial completion, indicating that nutritional interventions beyond 6 months may be necessary.

Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial.

BACKGROUND: Infantile beriberi-related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown. OBJECTIVES: We sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers. METHODS: In this double-blind, 4-parallel arm randomized controlled dose-response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a nonlinear least squares model in an intention-to-treat analysis. Linear mixed-effects models were used to test for differences between treatment groups. Maternal and infant blood thiamine biomarkers were also assessed. RESULTS: In total, each of 335 women was randomly assigned to1 of the following thiamine-dose groups: placebo (n = 83), 1.2 mg (n = 86), 2.4 mg (n = 81), and 10 mg (n = 85). The estimated dose required to reach 90% of the maximum average total thiamine concentration in human milk (191 µg/L) is 2.35 (95% CI: 0.58, 7.01) mg/d. The mean ± SD milk thiamine concentrations were significantly higher in all intervention groups (183 ± 91, 190 ± 105, and 206 ± 89 µg/L for 1.2, 2.4, and 10 mg, respectively) compared with the placebo group (153 ± 85 µg/L; P < 0.0001) and did not significantly differ from each other. CONCLUSIONS: A supplemental thiamine dose of 2.35 mg/d was required to achieve a milk total thiamine concentration of 191 µg/L. However, 1.2 mg/d for 22 wk was sufficient to increase milk thiamine concentrations to similar levels achieved by higher supplementation doses (2.4 and 10 mg/d), and comparable to those of healthy mothers in regions without beriberi. This trial was registered at clinicaltrials.gov as NCT03616288.

Associations between Zinc and Hemoglobin Concentrations in Preschool Children and Women of Reproductive Age: An Analysis of Representative Survey Data from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) Project.

BACKGROUND: Anemia is a worldwide concern. Nutritional deficiencies and inflammation are considered main contributors, but zinc deficiency has only recently been associated with anemia. OBJECTIVES: In this study we assessed associations between zinc status and hemoglobin (Hb) concentrations and anemia in preschool children 6-59 mo old (PSC) and nonpregnant women of reproductive age 15-49 y old (WRA) in population-based nutrition surveys. METHODS: Cross-sectional data from 13 (PSC) and 12 (WRA) countries within the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were used. Multivariable linear models were constructed that included zinc status (plasma/serum zinc concentrations), Hb concentrations and anemia, iron status, age, sex, and inflammation (C-reactive protein and α-1-acid glycoprotein). Zinc was adjusted for inflammation in PSC according to the BRINDA algorithm. RESULTS: Data were available for 18,658 PSC and 22,633 WRA. Prevalence of anemia ranged from 7.5% to 73.7% and from 11.5% to 94.7% in PSC and WRA, respectively. Prevalence of zinc deficiency ranged from 9.2% to 78.4% in PSC and from 9.8% to 84.7% in WRA, with prevalence of zinc deficiency >20% in all countries except Azerbaijan (PSC), Ecuador (PSC), and the United Kingdom (WRA). Multivariable linear regression models showed that zinc concentrations were independently and positively associated with Hb concentrations in 7 of 13 countries for PSC and 5 of 12 countries for WRA. In the same models, ferritin concentration was also significantly associated with Hb among PSC and WRA in 9 and 10 countries, respectively. Zinc deficiency was significantly associated with anemia in PSC and WRA in 5 and 4 countries respectively. CONCLUSIONS: Zinc deficiency was prevalent in most countries and associations between zinc and Hb in roughly half of the countries examined suggesting that strategies to combat zinc deficiency may help reduce anemia prevalence. More research on mechanisms by which zinc deficiency is associated with anemia and the reasons for the heterogeneity among countries is warranted.

Thiamine fortification strategies in low- and middle-income settings: a review.

Thiamine (vitamin B1 ) is an essential micronutrient in energy metabolism and cognitive and neurological health. Thiamine deficiency disorders (TDDs) have a range of clinical presentations that result in various morbidities and can be fatal if not promptly recognized and treated, especially in infants. To intervene, thiamine intakes by breastfeeding mothers and others at risk of thiamine deficiency should be increased to ensure adequate thiamine intake. Although thiamine fortification programs have a long history in high-income countries, there are few mandatory fortification programs to address TDDs in low- and middle-income countries (LMICs), particularly in the regions of greatest concern, South and Southeast Asia. This review highlights essential aspects for consideration in the development of a mandatory fortification program in LMICs, including an overview of the data required to model fortification dosing schemes, available thiamine fortificants, and potential fortification vehicles, as well as identifies current knowledge gaps.

Assessment of salt intake to consider salt as a fortification vehicle for thiamine in Cambodia.

Thiamine deficiency is a public health issue in Cambodia. Thiamine fortification of salt has been proposed; however, the salt intake of lactating women, the target population, is currently unknown. We estimated salt intakes among lactating women (<6 months postpartum) using three methods: repeat observed-weighed intake records and 24-h urinary sodium excretions (n = 104), and household salt disappearance (n = 331). Usual salt intake was estimated by adjusting for intraindividual intakes using the National Cancer Institute method, and a thiamine salt fortification scenario was modeled using a modified estimated average requirement (EAR) cut-point method. Unadjusted salt intake from observed intakes was 9.3 (8.3-10.3) g/day, which was not different from estimated salt intake from urinary sodium excretions, 9.0 (8.4-9.7) g/day (P = 0.3). Estimated salt use from household salt disappearance was 11.3 (10.7-11.9) g/person/day. Usual (adjusted) salt intake from all sources was 7.7 (7.4-8.0) g/day. Assuming no stability losses, a modeled fortification dose of 275 mg thiamine/kg salt could increase thiamine intakes from fortified salt to 2.1 (2.0-2.2) mg/day, with even low salt consumers reaching the EAR of 1.2 mg/day from fortified salt alone. These findings, in conjunction with future sensory and stability research, can inform a potential salt fortification program in Cambodia.