Introducing double fortified salt in social safety net programmes in Madhya Pradesh and Gujarat in India: Success factors, challenges and lessons learned.

Double fortified salt (DFS; with iron and iodine) was introduced in social safety net programmes (SSNPs) in Madhya Pradesh (MP) and Gujarat states in 2018. Nutrition International (NI) provided critical support for the intervention. An impact evaluation in MP found high DFS uptake, exceeding 90%. Conduct a process evaluation of the DFS programmes in MP and Gujarat states to identify success factors, challenges, and recommend considerations for scale-up. Twenty-eight qualitative interviews were conducted with NI staff, national and state level government officials, and DFS producers in 2022. Enabling environmental factors included national-level support for food fortification, consensus that anaemia was essential to address, and institutional trust in NI for technical assistance. In programme implementation, the primary challenges were reports of black specks in DFS and the darkening of food cooked with DFS. NI supported the government in improving handling practices, ensuring a regular and stable supply, introducing quality monitoring efforts and launching targeted behaviour change communication (BCC) campaigns regarding the value of DFS. Long-term implementation of the programmes is a weak point, as DFS production is more expensive than iodised salt, there is no existing market outside of institutional demand, and BCC must be long-term, high-quality, and requires resourcing for continued high uptake among SSNP beneficiaries. Strong government buy-in and technical support along the supply chain to address quality issues and beneficiary acceptance were key factors for the successful introduction of DFS. Comparative studies of DFS programmes should be conducted to improve confidence in the success factors that lead to high DFS uptake.

Expanding Fortification with Folic Acid: Thinking Outside the Cereal-Grain Box.

(1) Background: Fortifying maize and wheat flours with folic acid has effectively reduced neural tube defect-affected births. However, maize and wheat flours may not be widely consumed in all countries; further reduction in neural tube defect-affected births could benefit from the identification of alternative food vehicles. We aimed to use dietary intake or apparent consumption data to determine alternative food vehicles for large-scale fortification with folic acid in low-income and lower-middle-income countries (LILMICs) and identify current research related to examining the technological feasibility of fortifying alternative foods with folic acid. (2) Methods: We identified 81 LILMICs, defined by the World Bank's (WB) 2018 income classifications. To identify dietary intake or apparent consumption, we reviewed WB's Microdata Library and Global Health Data Exchange for national surveys from 1997-2018. We reviewed survey reports for dietary intake or apparent consumption data and analyzed survey datasets for population coverage of foods. We defined alternative food vehicles as those that may cover/be consumed by ≥30% of the population or households; cereal grains (maize and wheat flours and rice) were included as an alternative food vehicle if a country did not have existing mandatory fortification legislation. To identify current research on fortification with folic acid in foods other than cereal grains, we conducted a systematic review of published literature and unpublished theses, and screened for foods or food products. (3) Results: We extracted or analyzed data from 18 national surveys and countries. The alternative foods most represented in the surveys were oil (n = 16), sugar (n = 16), and salt (n = 14). The coverage of oil ranged from 33.2 to 95.7%, sugar from 32.2 to 98.4%, and salt from 49.8 to 99.9%. We found 34 eligible studies describing research on alternative foods. The most studied alternative foods for fortification with folic acid were dairy products (n = 10), salt (n = 6), and various fruit juices (n = 5). (4) Conclusions: Because of their high coverage, oil, sugar, and salt emerge as potential alternative foods for large-scale fortification with folic acid. However, except for salt, there are limited or no studies examining the technological feasibility of fortifying these foods with folic acid.

Rice as a vehicle for micronutrient fortification: a systematic review of micronutrient retention, organoleptic properties, and consumer acceptability.

CONTEXT: Previous reviews have focused on evaluating the efficacy and effectiveness of rice fortification, despite the need to also understand the outcomes of micronutrient retention, organoleptic properties, and acceptability to inform nutrition programs. OBJECTIVE: This systematic review aims to consolidate existing evidence on micronutrient retention, organoleptic properties, and acceptability of fortified rice. DATA SOURCES: Eligible articles were identified from 22 electronic databases and personal referrals and reviews. STUDY SELECTION: Studies on rice fortified via extrusion or coating technologies were included in the review if they reported outcomes in at least 1 of 3 domains: micronutrient retention, organoleptic or physicochemical properties, and acceptability (evaluated by sensory tests and consumer surveys). Any years of publication and study populations were considered for inclusion. A total of 15 391 articles were screened, yielding 49 for inclusion. DATA EXTRACTION: Study results were summarized descriptively through discussions by intervention conditions, study population, measurement methods, and key findings. The included studies were independently reviewed by 2 of the 3 authors, and all 3 authors reached consensus on the quality and major findings from the included articles. RESULTS: Extrusion and coating fortification technologies were found to be comparable across studies that assessed retention, organoleptic properties, and acceptability. Cooking fortified rice in excess water increased micronutrient loss for both technologies. Fortified kernels containing ferric pyrophosphate, zinc oxide, or zinc sulfate showed the most positive results for all outcomes reviewed, while retention rates of vitamin A in multiple-micronutrient-fortified rice were variable. CONCLUSIONS: The current practice of fortifying rice with ferric pyrophosphate provides high micronutrient stability and results in rice with organoleptic properties and consumer acceptance levels comparable to those of unfortified milled rice, although it presents challenges regarding the effect of vitamin A-fortified rice on vitamin A status.

Effects of Foods Fortified with Zinc, Alone or Cofortified with Multiple Micronutrients, on Health and Functional Outcomes: A Systematic Review and Meta-Analysis.

Seventeen per cent of the world's population is estimated to be at risk of inadequate zinc intake, which could in part be addressed by zinc fortification of widely consumed foods. We conducted a review of efficacy and effectiveness studies to ascertain the effect of zinc fortification [postharvest fortification of an industrially produced food or beverage; alone or with multiple micronutrients (MMN)] on a range of health outcomes. Previous reviews have required that the effect of zinc be isolated; because zinc is always cofortified with MMN in existing fortification programs, we did not impose this condition. Outcomes assessed were zinc-related biomarkers (plasma or serum, hair or urine zinc concentrations, comet assay, plasma fatty acid concentrations, and the proportion of and total zinc absorbed in the intestine from the diet), child anthropometry, morbidity, mortality, cognition, plasma or serum iron and copper concentrations, and for observational studies, a change in consumption of the food vehicle. Fifty-nine studies were included in the review; 54 in meta-analyses, totaling 73 comparisons. Zinc fortification with and without MMN increased plasma zinc concentrations (efficacy, n = 27: 4.68 µg/dL; 95% CI: 2.62-6.75; effectiveness, n = 13: 6.28 µg/dL; 95% CI: 5.03-7.77 µg/dL) and reduced the prevalence of zinc deficiency (efficacy, n = 11: OR: 0.76, 95% CI: 0.60-0.96; effectiveness, n = 10: OR: 0.45, 95% CI: 0.31-0.64). There were statistically significant increases in child weight (efficacy, n = 11: 0.43 kg, 95% CI: 0.11-0.75 kg), improvements in short-term auditory memory (efficacy, n = 3: 0.32 point, 95% CI: 0.13-0.50 point), and decreased incidence of diarrhea (efficacy, n = 3: RR: 0.79, 95% CI: 0.68-0.92) and fever (efficacy, n = 2: RR: 0.85, 95% CI: 0.74-0.97). However, these effects cannot be solely attributed to zinc. Our review found that zinc fortification with or without MMN reduced the prevalence of zinc deficiency and may provide health and functional benefits, including a reduced incidence of diarrhea.

Systematic Process Framework for Conducting Implementation Science Research in Food Fortification Programs.

Food fortification has proven to be an effective approach for preventing micronutrient deficiencies in many settings. Factors that lead to successful fortification programs are well established. However, due to the multisectoral nature of fortification and the added complexities present in many settings, the barriers to success are not always evident and the strategies to address them are not always obvious. We developed a systematic process for identifying and addressing gaps in the implementation of a food fortification program. The framework is composed of 4 phases: (1) connect program theory of change to program implementation; (2) develop an implementation research agenda; (3) conduct implementation research; and (4) analyze findings and develop/disseminate recommendations for next steps. We detail steps in each phase to help guide teams through the process. To our knowledge, this is the first attempt to outline a systematic process for applying implementation science research to food fortification. The development of this framework is intended to promote implementation research in the field of food fortification, thus improving access to and effectiveness of this key public health intervention.

The Potential Contribution of Fortified Maize Flour, Oil, Rice, Salt, and Wheat Flour to Estimated Average Requirements and Tolerable Upper Intake Levels for 15 Nutrients in 153 Countries.

Food fortification is designed to improve the nutritional profile of diets. The purpose of this research was to estimate the potential nutrient contribution of fortified maize flour, oil, rice, salt, and wheat flour in 153 countries, using the national intake (or availability) of the food and the nutrient levels required for fortification. This was done under two scenarios-maximum, where 100% of the food is assumed to be industrially processed and fortified, and realistic, where the maximum value is adjusted based on the percent of the food that is industrially processed and fortified. Under the maximum scenario, the median Estimated Average Requirements (EARs) met ranged from 22-75% for 14 nutrients (vitamins A, B1, B2, B3, B6, B12, D, E, folic acid and calcium, fluoride, iron, selenium and zinc), and 338% for iodine. In the realistic scenario, the median EARs met were 181% for iodine and <35% for the other nutrients. In both scenarios, the median Tolerable Upper Intake Levels (ULs) met were <55% for all nutrients. Under the realistic scenario, no country exceeded 100% of the UL for any nutrient. Current fortification practices of the five foods of interest have the global potential to contribute up to 15 nutrients to the diets of people, with minimal risk of exceeding ULs.

The Double-Fortified Salt (Iodized Salt with Iron) Consultation: A Process for Developing Evidence-Based Considerations for Countries.

The addition of iodine to edible salt has been one of the most important public health successes of the past half century, enabling most countries to achieve optimal iodine intake and protect the brains of unborn children from the adverse consequences of iodine deficiency. Salt has been an ideal vehicle for this effort because of its near universal and narrow range of consumption, relative ease of technology for salt iodization, and capacity for virtually all salt producers to add iodine. As a result of the success of salt iodization, there has been growing interest in using salt as a vehicle for other important micronutrients, particularly the addition of iron to iodized salt to produce double-fortified salt (DFS), to combat the persistent problem of iron deficiency and iron deficiency anemia. Because of this growing interest in DFS and the need for a comprehensive review of evidence to support the viability of this intervention, the Iodine Global Network (IGN) initiated a global consultation to gather all available data on different aspects of DFS. IGN identified 4 key areas considered essential to understand for a successful fortification intervention: 1) efficacy and effectiveness, or how well DFS produces a health impact in controlled and real-life settings; 2) technical considerations for production, or what are the minimum requirements to manufacture DFS; 3) program implementation to describe experiences thus far with the delivery of DFS across multiple platforms; and 4) comparison of DFS with other iron fortification efforts to determine the comparative advantage of DFS to improve iron intake and prevent iron deficiency anemia. This preface provides an overview of the DFS Consultation objectives, process, and objectives.

Modeling shows high potential of folic acid-fortified salt to accelerate global prevention of major neural tube defects.

BACKGROUND: We estimated the global proportion of folic acid-preventable spina bifida and anencephaly (FAP SBA) potentially prevented through mandatory double fortification of iodized salt with folic acid. METHODS: Using United Nations Children's Fund (UNICEF) and Global Fortification Data Exchange (GFDx) data sets, we modeled country-specific number of FAP SBA cases prevented annually using (a) current coverage of the salt in households worldwide and (b) expected daily amount of folic acid intake from folic acid-fortified iodized salt. Our evidence-based modeling strategy assumed mandatory folic acid fortification of salt at 20 ppm, and that at 200 µg/day intake of folic acid through fortified salt, should achieve 100% prevention of all FAP SBA in countries. RESULTS: One hundred countries that have data on percent of households consuming iodized salt globally were examined; 55 of them have ≥80% households consuming iodized salt. Our model estimated approximately 180,000 cases of FAP SBA could be prevented in these 100 countries through folic acid-fortified iodized salt, and 150,000 of them would be in countries where ≥80% households consuming iodized salt that can be potentially fortified with folic acid. Salt fortification with folic acid could contribute to the prevention of about 65% global FAP SBA cases annually. CONCLUSIONS: Our evidence-based model shows that there is high potential to prevent FAP SBA using folic acid-fortified iodized salt. Prevention will reach countries where there is a limited reach of centrally processed folic acid-fortified wheat or maize flour. If this intervention is made feasible by the salt industry, it can accelerate the prevention of FAP SBA significantly.

Potential Dietary Contributions From Rice and Wheat Flour Fortification in the Solomon Islands: Results From the 2012-2013 Household Income and Expenditure Survey.

BACKGROUND: Solomon Islands (SI) mandated wheat flour fortification in 2010. Rice is a key staple food in SI, and its fortification may provide an opportunity to deliver additional micronutrients to the population. OBJECTIVE: To determine whether fortified rice (proposed) and fortified wheat flour potentially benefit women of reproductive age (WRA). METHODS: We analyzed data from the 2012-2013 Household Income and Expenditure Survey to quantify food purchases, which served as a proxy for food consumption. We accounted for varied household composition by using adult male equivalent (AME) adjustments. RESULTS: Among 4478 households, 95.6% purchased rice and 86.6% purchased at least 1 food containing fortified wheat flour in the previous 14 days. Median apparent intake of rice among WRA was 205 g/d/AME. If fortified according to proposed standards, this apparent intake could result in the consumption of 12.3 mg iron/d, fulfilling 44% of the estimated average requirement (EAR), and 226 µg folic acid/d, satisfying 57% of World Health Organization's recommended intake of 400 µg/d. Overall, apparent rice consumption could fulfill 113%, 114%, and 131% of the EAR for WRA for zinc, thiamin, and niacin, respectively. Fortified wheat flour was consumed in much lower quantities, with an estimated apparent median intake of 22 g/d/AME among WRA and 78 g/d/AME among women in urban populations. CONCLUSIONS: The potential benefit of fortified wheat flour in SI is likely limited to urban populations. Apparent consumption of fortified rice in SI could contribute considerably to daily intake of iron, B vitamins including folic acid, and zinc among WRA.

Global folate status in women of reproductive age: a systematic review with emphasis on methodological issues.

Inadequate folate status in women of reproductive age (WRA) can lead to adverse health consequences of public health significance, such as megaloblastic anemia (folate deficiency) and an increased risk of neural tube defect (NTD)-affected pregnancies (folate insufficiency). Our review aims to evaluate current data on folate status of WRA. We queried eight databases and the World Health Organization Micronutrients Database, identifying 45 relevant surveys conducted between 2000 and 2014 in 39 countries. Several types of folate assays were used in the analysis of blood folate, and many surveys used folate cutoffs not matched to the assay. To allow better comparisons across surveys, we attempted to account for these differences. The prevalence of folate deficiency was >20% in many countries with lower income economies but was typically <5% in countries with higher income economies. Only 11 surveys reported the prevalence of folate insufficiency, which was >40% in most countries. Overall, folate status data for WRA globally are limited and must be carefully interpreted due to methodological issues. Future surveys would benefit from using the microbiologic assay to assess folate status, along with assay-matched cutoffs to improve monitoring and evaluation of folic acid interventions, thus informing global efforts to prevent NTDs.

Public and Private Sector Dynamics in Scaling Up Rice Fortification: The Colombian Experience and its Lessons.

BACKGROUND: Fortification of cereal grains with at least iron or folic acid is legislated in 85 countries worldwide. Relative to wheat and maize flour, rice fortification is relatively new and provides an opportunity to deliver essential micronutrients to populations that consume rice as a dietary staple. OBJECTIVE: To describe miller and public sector experiences and perspectives on rice fortification with micronutrients in Colombia and offer recommendations for policy makers. METHODS: Interviews with Colombian rice millers, research and development personnel, and public sector leaders; desk review of key documents. RESULTS: In Colombia, rice fortified with micronutrients is market driven and a few very large rice millers, currently representing about 35% of the market, have voluntarily fortified rice since 2002. The technology used (spraying) is unique to Colombia and to date there is no independent verification of nutrient retention after washing and cooking rice fortified through this technology. Millers are unwilling to switch to more proven methods, such as extrusion or coating, which will incur higher capital investment and recurring costs. Despite interest from multiple stakeholders between 2002 and 2011, mandatory rice fortification is not part of the Colombian government policy as of July 2015. CONCLUSION: Rice fortified with micronutrients through spraying technology has achieved moderate coverage in Colombia, but the technology is unproven, its effectiveness unknown, and public health impact likely limited. For rice fortification to be an effective nutrition intervention to improve micronutrient status, policy makers should explore standards to guide industry and improvements to regulatory capacity.

Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review.

BACKGROUND: Folate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data. METHODS AND FINDINGS: We conducted a systematic review and searched multiple databases for NTD prevalence estimates and abstracted data from peer-reviewed literature, birth defects surveillance registries, and reports published between January 1990 and July 2014 that had greater than 5,000 births and were not solely based on mortality data. We classified countries according to World Health Organization (WHO) regions and World Bank income classifications. The initial search yielded 11,614 results; after systematic review we identified 160 full text manuscripts and reports that met the inclusion criteria. Data came from 75 countries. Coverage by WHO region varied in completeness (i.e., % of countries reporting) as follows: African (17%), Eastern Mediterranean (57%), European (49%), Americas (43%), South-East Asian (36%), and Western Pacific (33%). The reported NTD prevalence ranges and medians for each region were: African (5.2-75.4; 11.7 per 10,000 births), Eastern Mediterranean (2.1-124.1; 21.9 per 10,000 births), European (1.3-35.9; 9.0 per 10,000 births), Americas (3.3-27.9; 11.5 per 10,000 births), South-East Asian (1.9-66.2; 15.8 per 10,000 births), and Western Pacific (0.3-199.4; 6.9 per 10,000 births). The presence of a registry or surveillance system for NTDs increased with country income level: low income (0%), lower-middle income (25%), upper-middle income (70%), and high income (91%). CONCLUSIONS: Many WHO member states (120/194) did not have any data on NTD prevalence. Where data are collected, prevalence estimates vary widely. These findings highlight the need for greater NTD surveillance efforts, especially in lower-income countries. NTDs are an important public health problem that can be prevented with folic acid supplementation and fortification of staple foods.

Assessing the association between natural food folate intake and blood folate concentrations: a systematic review and Bayesian meta-analysis of trials and observational studies.

Folate is found naturally in foods or as synthetic folic acid in dietary supplements and fortified foods. Adequate periconceptional folic acid intake can prevent neural tube defects. Folate intake impacts blood folate concentration; however, the dose-response between natural food folate and blood folate concentrations has not been well described. We estimated this association among healthy females. A systematic literature review identified studies (1 1992-3 2014) with both natural food folate intake alone and blood folate concentration among females aged 12-49 years. Bayesian methods were used to estimate regression model parameters describing the association between natural food folate intake and subsequent blood folate concentration. Seven controlled trials and 29 observational studies met the inclusion criteria. For the six studies using microbiologic assay (MA) included in the meta-analysis, we estimate that a 6% (95% Credible Interval (CrI): 4%, 9%) increase in red blood cell (RBC) folate concentration and a 7% (95% CrI: 1%, 12%) increase in serum/plasma folate concentration can occur for every 10% increase in natural food folate intake. Using modeled results, we estimate that a natural food folate intake of ≥ 450 µg dietary folate equivalents (DFE)/day could achieve the lower bound of an RBC folate concentration (~ 1050 nmol/L) associated with the lowest risk of a neural tube defect. Natural food folate intake affects blood folate concentration and adequate intakes could help women achieve a RBC folate concentration associated with a risk of 6 neural tube defects/10,000 live births.

Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies.

BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is a risk factor for neural tube defects. The T allele produces an enzyme with reduced folate-processing capacity, which has been associated with lower blood folate concentrations. OBJECTIVE: We assessed the association between MTHFR C677T genotypes and blood folate concentrations among healthy women aged 12-49 y. DESIGN: We conducted a systematic review of the literature published from January 1992 to March 2014 to identify trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We conducted a meta-analysis for estimates of percentage differences in blood folate concentrations between genotypes. RESULTS: Forty studies met the inclusion criteria. Of the 6 studies that used the microbiologic assay (MA) to measure serum or plasma (S/P) and RBC folate concentrations, the percentage difference between genotypes showed a clear pattern of CC > CT > TT. The percentage difference was greatest for CC > TT [S/P: 13%; 95% credible interval (CrI): 7%, 18%; RBC: 16%; 95% CrI: 12%, 20%] followed by CC > CT (S/P: 7%; 95% CrI: 1%, 12%; RBC: 8%; 95% CrI: 4%, 12%) and CT > TT (S/P: 6%; 95% CrI: 1%, 11%; RBC: 9%; 95% CrI: 5%, 13%). S/P folate concentrations measured by using protein-binding assays (PBAs) also showed this pattern but to a greater extent (e.g., CC > TT: 20%; 95% CrI: 17%, 22%). In contrast, RBC folate concentrations measured by using PBAs did not show the same pattern and are presented in the Supplemental Material only. CONCLUSIONS: Meta-analysis results (limited to the MA, the recommended population assessment method) indicated a consistent percentage difference in S/P and RBC folate concentrations across MTHFR C677T genotypes. Lower blood folate concentrations associated with this polymorphism could have implications for a population-level risk of neural tube defects.

Nutritional status of young children with inherited blood disorders in western Kenya.

To determine the association between a range of inherited blood disorders and indicators of poor nutrition, we analyzed data from a population-based, cross-sectional survey of 882 children 6-35 months of age in western Kenya. Of children with valid measurements, 71.7% were anemic (hemoglobin < 11 g/dL), 19.1% had ferritin levels < 12 µg/L, and 30.9% had retinol binding protein (RBP) levels < 0.7 µmol/L. Unadjusted analyses showed that compared with normal children, homozygous α(+)-thalassemia individuals had a higher prevalence of anemia (82.3% versus 66.8%, P = 0.001), but a lower prevalence of low RBP (20.5% versus 31.4%, P = 0.024). In multivariable analysis, homozygous α(+)-thalassemia remained associated with anemia (adjusted odds ratio [aOR] = 1.8, P = 0.004) but not with low RBP (aOR = 0.6, P = 0.065). Among young Kenyan children, α(+)-thalassemia is associated with anemia, whereas G6PD deficiency, haptoglobin 2-2, and HbS are not; none of these blood disorders are associated with iron deficiency, vitamin A deficiency, or poor growth.