Folic Acid-Fortified Iodized Salt and Serum Folate Levels in Reproductive-Aged Women of Rural India: A Nonrandomized Controlled Trial.

Importance: India has a disproportionately high prevalence of neural tube defects, including spina bifida and anencephaly (SBA), causing a high number of stillbirths, elective pregnancy terminations, and child mortality; India contributes a large proportion of the global burden of SBA. Thirty years after folic acid was shown to be effective in reducing SBA prevalence, only about one-quarter of such births are prevented globally through cereal grain fortification. Objective: To determine the association of folic acid-fortified iodized salt with serum folate concentrations among nonpregnant and nonlactating women of reproductive age. Design, Setting, and Participants: This nonrandomized controlled trial using a preintervention and postintervention design was conducted in 4 rural villages in Southern India from July 1 to November 30, 2022. All households in the villages agreed to participate in the study. Preintervention and postintervention serum folate levels were analyzed among study participants at baseline and after 4 months, respectively. Intervention: Consumption of approximately 300 µg/d of folic acid using double fortified salt (folic acid plus iodine). Median serum folate concentrations were assessed at baseline and 4 months. Main Outcomes and Measures: Change in median serum folate levels between baseline and study end point as the primary outcome of the study. Results: A total of 83 nonpregnant nonlactating women aged 20 to 44 years (mean [SD] age, 30.9 [5.1] years) were eligible for the study and provided serum samples for analysis at baseline and the end point of the intervention. The median serum folate concentration increased from 14.6 (IQR, 11.2-20.6) nmol/L at baseline to 54.4 (IQR, 43.5-54.4) nmol/L at end of study, a 3.7-fold increase from baseline to study end point. Two-tailed Wilcoxon signed rank test showed the median difference in preintervention and postintervention serum folate concentrations to be highly significant (P < .001). The participants found the salt acceptable in color and taste. Conclusions and Relevance: Use of folic acid-fortified iodized salt was associated with increased serum folate concentrations in women of reproductive age. This novel evidence can inform public health policy to accelerate SBA prevention. Trial Registration: ClinicalTrials.gov Identifier: NCT06174883.

Multiple micronutrients fortified salt: consumers' acceptability survey, Tanzania.

BACKGROUND: Food fortification with micronutrients is an insufficiently used technology in developing countries. Salt is consumed in small, constant daily amounts by most people globally. Salt has been instrumental in delivering iodine to a wide population globally through fortification. There is a proven effective technology for fortifying iodinated salt with iron, folate, and Vitamin B12. Findings have shown that both Double (Iodine and iron) fortified salt (DFS) and quadruple (iron, iodine, folate, and vitamin B12) fortified salt (QFS) are effective in raising hemoglobin levels. AIM: To assess the acceptability and gauge consumers' willingness to use double-fortified and quadruple-fortified salt formulations. METHODS: We conducted an observational study involving 300 households at Haydom Lutheran Hospital catchment area in Northern rural Tanzania between October 2021 and April 2022. Each household was supplied with one type of salt (iodized salt (IS), DFS or QFS) for cooking common family dishes for one week. Thereafter, at least two adult members of the family who used the dishes cooked with study salt were interviewed using the adopted 5-point Hedonic scale. RESULTS: A total of 899 individuals were interviewed after using study salt for one week: 286 IS, 305 DFS, and 308 QFS. The overall acceptability for the salts was QFS (82%), DFS (78%), and IS (79%). The mean sensory (taste, color and appearance) scores of the QFS (1.7) and DFS (1.7) were comparable to standard iodized salt (1.6). CONCLUSION: Quadruple-fortified salt and double-fortified salt are equally acceptable and have similar sensory scores as standard iodized salt when used to cook commonly eaten dishes in the study population.

Sensory Trial of Quintuple Fortified Salt-Salt Fortified With Iodine, Iron, Folic Acid, Vitamin B12, and Zinc-Among Consumers in New Delhi, India.

BACKGROUND: Micronutrient deficiencies are a cause of significant public health burden and loss of gross domestic product, especially in developing countries. Multiple fortified salt can potentially address this challenge at scale and in a cost-effective manner. OBJECTIVE: This laboratory-based sensory trial evaluated the acceptability of quintuple fortified salt (Q5FS), that is, iodized salt (IS) fortified with additional 4 micronutrients: iron, folic acid, vitamin B12, and zinc. Iodized salt and double fortified salt (DFS), that is, IS fortified with iron, are used for comparison. METHODS: Forty-five respondents were recruited by open invitations to the university staff and their families. Each study participant rated 10 food items each in a set of 3 identical preparations differing only in the salt used. A 5-point hedonic scale was used to rate each dish on 6 sensory attributes: appearance, color, aroma, taste, texture, and aftertaste. Finally, the dish was rated on the attribute of overall acceptability-a subjective combined score based on all sensory attributes considered together. RESULTS: Among the 3 salt types, there was no difference in scores for the sensory attributes of appearance, aroma, taste, texture, and aftertaste, and the attribute of overall acceptability. Color in IS scored significantly higher than in Q5FS and DFS, but there was no difference between the scores of DFS and Q5FS. CONCLUSIONS: The 3 salts IS, DFS, and Q5FS are comparable to each other in all sensory properties, except for color. This study concludes that Q5FS is organoleptically acceptable under ideal conditions.

Key Considerations for Policymakers-Iodized Salt as a Vehicle for Iron Fortification: Current Evidence, Challenges, and Knowledge Gaps.

Could DFS help prevent iron deficiency and anemia? Studies in controlled settings (efficacy) demonstrate that double-fortified salt (DFS; iron added to iodized salt) reduces the prevalence of anemia and iron deficiency anemia. Studies in program settings (effectiveness) are limited and reported differing levels of DFS coverage, resulting in mixed evidence of impact on anemia. What iron formulations are available and how do they affect iodized salt? Ferrous sulfate and encapsulated ferrous fumarate (both with various enhancers and/or coating materials) are the main iron formulations currently in use for DFS. Adding iron to iodized salt may lead to adverse changes in the product, specifically discoloration and losses in iodine content. These changes are greatest when the iodized salt used in DFS production is of low quality (e.g., contain impurities, has high moisture, and is of large crystal size). DFS requires iodized salt of the highest quality and a high-quality iron formulation in order to minimize adverse sensory changes and iodine losses. Appropriate packaging of iodized salt is also important to prevent losses. What is known about the minimum requirements to manufacture DFS? DFS producers must use high-quality refined iodized salt meeting the minimum standards for DFS production (which is higher than standards for salt intended for iodization alone), and an iron formulation for which there are rigid quality-assurance measures to ensure consistent quality and blending techniques. The actual proportion of iodized salt meeting the stringent requirements necessary for DFS production is unclear, but likely to be low in many countries, especially those with fragmented salt industries and a low proportion of industrially produced salt. What are the financial implications of adding iron to iodized salt? As a result of higher input costs both for input salt and the iron compound, DFS is more expensive to produce than iodized salt and thus has a higher production cost. Various grades of iodized salt are produced and consumed in different sectors of the market. Experience in India indicates that, on average, producing DFS costs 31-40 US dollars/metric ton or 0.03-0.04 US dollars/kg more than high-quality refined iodized salt. The exact impact of this production-level cost difference on profit margins and consumer price is specific to the conditions of different salt markets. Factors such as transport costs, customary wholesale and retail mark-ups, and taxes all vary greatly and need to be assessed on a case by case basis. Is DFS in alignment with salt-reduction efforts? The WHO has long recognized that salt iodization is an important public health intervention to achieve optimal iodine nutrition and is compatible with salt-reduction goals. Fortification of salt (with any nutrient) should not be used to justify or encourage an increase in salt intake to the public. Any effort to expand salt fortification to other nutrients should be done in close consultation with WHO and those working on salt reduction. What has been the experience with DFS delivery under different platforms? To date, DFS has been introduced into the retail market and in social safety net (primarily in India) programs, but sensory changes in DFS have been raised as concerns. The higher price for DFS has limited expansion in the retail market. In social safety net programs where the cost of DFS is subsidized for beneficiaries, programs must consider long-term resourcing for sustainability. Overall: The optimal production and delivery of DFS are still under development, as many challenges need to be overcome. There is a beneficial impact on hemoglobin in efficacy trials. Thus, if those conditions can be replicated in programs or the technology can be adapted to better fit current production and delivery realities, DFS may provide an effective contribution in countries that need additional food-fortification vehicles to improve iron intake.

Impact of Double-Fortified Salt with Iron and Iodine on Hemoglobin, Anemia, and Iron Deficiency Anemia: A Systematic Review and Meta-Analysis.

Double-fortified salt (DFS) containing iron and iodine has been proposed as a feasible and cost-effective alternative for iron fortification in low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis from randomized and quasi-randomized controlled trials to 1) assess the effect of DFS on biomarkers of iron status and the risk of anemia and iron deficiency anemia (IDA) and 2) evaluate differential effects of DFS by study type (efficacy or effectiveness), population subgroups, iron formulation (ferrous sulfate, ferrous fumarate, and ferric pyrophosphate), iron concentration, duration of intervention, and study quality. A systematic search with the use of MEDLINE, EMBASE, Cochrane, Web of Science, and other sources identified 221 articles. Twelve efficacy and 2 effectiveness studies met prespecified inclusion criteria. All studies were conducted in LMICs: 10 in India, 2 in Morocco, and 1 each in Côte d'Ivoire and Ghana. In efficacy studies, DFS increased hemoglobin concentrations [standardized mean difference (SMD): 0.28; 95% CI: 0.11, 0.44; P < 0.001] and reduced the risk of anemia (RR: 0.59; 95% CI: 0.46, 0.77; P < 0.001) and IDA (RR 0.37; 95% CI: 0.25, 0.54; P < 0.001). In effectiveness studies, the effect size for hemoglobin was smaller but significant (SMD: 0.03; 95% CI: 0.01, 0.05; P < 0.01). Stratified analyses of efficacy studies by population subgroups indicated positive effects of DFS among women and school-age children. For the latter, DFS increased hemoglobin concentrations (SMD: 0.32; 95% CI: 0.03, 0.60; P < 0.05) and reduced the risk of anemia (SMD: 0.48; 95% CI: 0.34, 0.67; P < 0.001) and IDA (SMD: 0.37; 95% CI: 0.25, 0.54; P < 0.001). Hemoglobin concentrations, anemia prevalence and deworming at baseline, sample size, and study duration were not associated with effect sizes. The results indicate that DFS is efficacious in increasing hemoglobin concentrations and reducing the risk of anemia and IDA in LMIC populations. More effectiveness studies are needed.

Achievements, challenges, and promising new approaches in vitamin and mineral deficiency control.

Micronutrient deficiencies (MNDs) contribute significantly to the world's disease and mortality burden. Global efforts addressing MNDs have achieved significant yet heterogeneous progress across and within regions and countries. For vitamin A and iodine interventions, enhancing achievements in coverage require further political and financial commitment and targeting of hard-to-reach populations. Anemia control must focus on prevention among preschoolers and adolescent women and on integrated public health programs. Current international guidelines on iron supplementation and cut-off values for anemia need revision. For zinc, advocacy to accelerate the application of revised diarrhea management guidelines is critical, as are efficacy studies on food-based interventions and preventive supplementation.

A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh.

Adolescent girls have high nutrient needs and are susceptible to micronutrient deficiencies. The objective of this study was to test the effect of a multiple-micronutrient-fortified beverage on hemoglobin (Hb) concentrations, micronutrient status, and growth among adolescent girls in rural Bangladesh. A total of 1125 girls (Hb > or = 70 g/L) enrolled in a randomized, double-blind, placebo-controlled trial and were allocated to either a fortified or nonfortified beverage of similar taste and appearance. The beverage was provided at schools 6 d/wk for 12 mo. Concentrations of Hb and serum ferritin (sFt), retinol, zinc, and C-reactive protein were measured in venous blood samples at baseline, 6 mo, and 12 mo. In addition, weight, height, and mid-upper arm circumference (MUAC) measurements were taken. The fortified beverage increased the Hb and sFt and retinol concentrations at 6 mo (P < 0.01). Adolescent girls in the nonfortified beverage group were more likely to suffer from anemia (Hb <120 g/L), iron deficiency (sFt <12 microg/L), and low serum retinol concentrations (serum retinol <0.70 micromol/L) (OR = 2.04, 5.38, and 5.47, respectively; P < 0.01). The fortified beverage group had greater increases in weight, MUAC, and BMI over 6 mo (P < 0.01). Consuming the beverage for an additional 6 mo did not further improve the Hb concentration, but the sFt level continued to increase (P = 0.01). The use of multiple-micronutrient-fortified beverage can contribute to the reduction of anemia and improvement of micronutrient status and growth in adolescent girls in rural Bangladesh.

Cereal fortification programs in developing countries.

Malnutrition is a major problem among children especially in the developing world. In most developing countries children show growth faltering between 6 and 24 months of age due to inadequate complementary feeding. Complementary foods are transitional foods given in addition to breast milk, following exclusive breastfeeding during the first 6 months, to meet the full nutritional requirements of the infant. Strategies to improve the availability of and accessibility to low cost complementary foods can play an important role in improving the nutritional status of infants and young children. Cereals constitute the most suitable vehicle for delivering micronutrients to an at-risk population because of their widespread consumption, stability and versatility. To reduce the vulnerability to the health impacts of micronutrient deficiencies, several developed and developing countries have adopted various innovative, cost-effective strategies to fortify cereal-based complementary foods and to reach children through public programs. This article reviews cereal fortification programs in developing countries, with special reference to low cost fortified complementary foods, and emphasizes the need for public-private-civic sector initiatives to improve the health and wellbeing of people around the world.

Iron fortification: country level experiences and lessons learned.

Iron fortification has been used to enhance iron intake in many developed countries for more than 50 years, but only in the last decade has this strategy been applied on a large scale to other parts of the world. Iron fortification of rice is being instituted in the Philippines. Initially, the rice will be produced in government-controlled rice mills and sold at low cost mainly to low income families. Efforts to improve the technology (using coating or extrusion techniques) are currently underway to reduce cost and minimize losses during storage and washing. Effectiveness and feasibility studies are required to test the new technologies and processing/distribution systems. In Venezuela in 1993, the government instituted a mandatory program of iron fortification to enrich precooked corn flour followed by the voluntary fortification of wheat flour. Surveys in school children subsequently showed a sharp drop in iron deficiency. Fortification of fish sauce in Vietnam has shown promising initial results in reducing anemia among anemic, nonpregnant female factory workers. Iron-fortified soy sauce has been shown to reduce anemia in initial studies in children in China, and a large-scale efficacy trial is now underway. These examples indicate that iron fortification of staple foods and condiments holds great promise for the prevention of iron deficiency.