Calcium status assessment at the population level: Candidate approaches and challenges.

Inadequate dietary calcium intake is a global public health problem that disproportionately affects low- and middle-income countries. However, the calcium status of a population is challenging to measure, and there are no standard methods to identify high-risk communities even in settings with an elevated prevalence of a disease caused or exacerbated by low calcium intake (e.g., rickets). The calcium status of a population depends on numerous factors, including intake of calcium-rich foods; the bioavailability of the types of calcium consumed in foods and supplements; and population characteristics, including age, sex, vitamin D status, and genetic attributes that influence calcium retention and absorption. The aim of this narrative review was to assess candidate indicators of population-level calcium status based on a range of biomarkers and measurement methods, including dietary assessment, calcium balance studies, hormonal factors related to calcium, and health outcomes associated with low calcium status. Several promising approaches were identified, but there was insufficient evidence of the suitability of any single indicator to assess population calcium status. Further research is required to develop and validate specific indicators of calcium status that could be derived from the analysis of data or samples that are feasibly collected in population-based surveys.

Interventions to improve calcium intake through foods in populations with low intake.

Calcium intake remains inadequate in many low- and middle-income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food-based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium-deficiency rickets). Specifically, some animal-source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple-food fortification with calcium can also be a cost-effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high-calcium varieties or through the application of calcium-rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population.

There should always be a free lunch: the impact of COVID-19 lockdown suspension of the mid-day meal on nutriture of primary school children in Karnataka, India.

Background: The COVID-19 pandemic lockdown in 2020 resulted in school closures with eventual suspension of the mid-day meal programme, biannual deworming and iron-folic acid supplements. One year into the lockdown, we evaluated the impact of the withdrawal of these programmes on the nutritional status of rural primary-school children, aged 6-12 years, in Karnataka, India. Methods: Anthropometry, haemoglobin, serum ferritin and C reactive protein were measured in 290 children at two time points, 1 year apart, starting from just before the lockdown (February 2020 to February 2021). Results: The prevalence of anaemia doubled from 21% to 40% (p<0.0001) with more pronounced changes in older girls (10%-53%); however, the prevalence of iron deficiency did not change (48.8%-51.9%), despite cessation of deworming and iron/folic acid supplements. Conclusion: The increase in anaemia was due to limiting intakes of other erythropoietic nutrients, possibly due to a lower dietary diversity. The mid-day lunch meal at school (MDM) is an important part of daily food intake in rural school children, and it is important to maintain dietary diversity through the delivery of MDM for such vulnerable groups.

Mid-upper arm circumference in pregnant women and birth weight in newborns as substitute for skinfold thickness: findings from the MAASTHI cohort study, India.

BACKGROUND: Estimating total body fat in public hospitals using gold-standard measurements such as air displacement plethysmography (ADP), deuterium oxide dilution, or dual-energy X-ray absorptiometry (DXA) is unaffordable, and it is challenging to use skinfold thickness. We aimed to identify the appropriate substitute marker for skinfold thickness to estimate total body fat in pregnant women and infants. METHODS: The study is part of a prospective cohort study titled MAASTHI in Bengaluru, from 2016 to 19. Anthropometric measurements such as body weight, head circumference, mid-upper arm circumference (MUAC), and skinfold thickness were measured in pregnant women between 14 and 36 weeks of gestational age; while measurements such as birth weight, head, chest, waist, hip, mid-upper arm circumference, and skinfold thickness were recorded for newborns. We calculated Kappa statistics to assess agreement between these anthropometric markers with skinfold thickness. RESULTS: We found the highest amount of agreement between total skinfold thickness and MUAC (Kappa statistic, 0.42; 95 % CI 0.38-0.46) in pregnant women. For newborns, the highest agreement with total skinfold thickness was with birth weight (0.57; 95 % CI 0.52-0.60). Our results indicate that MUAC higher than 29.2 cm can serve as a suitable alternative to total skinfolds-based assessments for obesity screening in pregnancy in public facilities. Similarly, a birth weight cut-off of 3.45 kg can be considered for classifying obesity among newborns. CONCLUSION: Mid-upper arm circumference and birth weight can be used as markers of skinfold thickness, reflecting total body fat in pregnant women and the infant, respectively. These two anthropometric measurements could substitute for skinfold thickness in low- and middle-income urban India settings.

A Natural Low Phytic Acid Finger Millet Accession Significantly Improves Iron Bioavailability in Indian Women.

Iron deficiency and anemia are common in low- and middle-income countries. This is due to a poor dietary iron density and low iron absorption resulting from the high inhibitory phytic acid content in cereal and millet-based diets. Here, we report that a naturally occurring low phytic acid finger millet accession (571 mg 100 g-1), stable across three growing seasons with normal iron content (3.6 mg 100 g-1), increases iron absorption by 3-folds in normal Indian women. The accessions differing in grain phytic acid content, GE 2358 (low), and GE1004 (high) were selected from a core collection of 623 accessions. Whole genome re-sequencing of the accessions revealed significant single nucleotide variations segregating them into distinct clades. A non-synonymous mutation in the EcABCC phytic acid transporter gene between high and low accessions could affect gene function and result in phytic acid differences. The highly sensitive dual stable-isotope erythrocyte incorporation method was adopted to assess the fractional iron absorption. The low phytic acid accession resulted in a significantly higher iron absorption compared with the high phytic acid accession (3.7 vs. 1.3%, p < 0.05). The low phytic acid accession could be effective in preventing iron deficiency in regions where finger millet is habitually eaten. With its low water requirement, finger millet leaves low environmental footprints and hence would be an excellent sustainable strategy to mitigate iron deficiency.

Fractional iron absorption from enteric-coated ferrous sulphate tablet.

Background & objectives: Iron supplementation is widely used public health measure to manage iron deficiency anaemia. In India, enteric-coated iron tablets are administered to adolescent boys and girls to avoid adverse effects such as gastritis, which reduces compliance, but this may result in poor iron absorption. Data on the absorption of iron from enteric-coated ferrous sulphate tablets are lacking. The present study using stable isotopic approach was aimed to measure iron absorption in iron deficient women. Methods: Iron absorption was measured from stable isotope-labelled enteric-coated ferrous sulphate ([57]Fe, ECFS) and uncoated ferrous sulphate ([58]Fe, UCFS) tablets in iron-deficient (n=9) women, aged 18-40 yr with no infection or inflammation. The two types of tablets (ECFS and UCFS) were administered on consecutive days, 60 min after breakfast, and the sequence being random. Blood samples were collected before dosing, and on day 15, to measure iron absorption from the shift in iron isotopic ratios in haemoglobin. Results: Eight women completed the iron absorption study. Iron absorption was found to be significantly lower in ECFS compared to UCFS (3.5 vs. 12%, P <0.05) consumption. Interpretation & conclusions: Our study showed poor iron bioavailability from ECFS, and supplementation programmes may consider UCFS tablets for better haematological outcomes.

Assessing bone mineral changes in response to vitamin D supplementation using natural variability in stable isotopes of Calcium in Urine.

Osteoporosis is a chronic disease of public health importance, particularly in low and middle income countries. Measuring the bone mineral balance (BMB) in a non-invasive manner, and its response to different interventions, is critical to the definition of optimal strategies for its prevention and management. In this study, we demonstrate the usefulness of natural variability in calcium isotopes (δ44/40Ca) of urine and the derived BMB estimates as a biomarker of bone health and its responsiveness to interventions. Vitamin D3 is commonly used as a supplement for the prevention and treatment of osteoporosis, along with calcium supplements. We studied the effect of a short term vitamin D3 supplementation on changes in urine δ44/40Ca and the derived BMB. δ44/40Ca before and after the vitamin D3 supplementation yielded a statistically significant change (p = 0.050) with a positive δ44/40Ca enrichment. The mean derived BMB was net positive (0.04 ± 0.05) in comparison to a net negative value for the control group (-0.03 ± 0.01). These results indicate the potential usefulness of urinary natural δ44/40Ca and the derived BMB, which, along with bone mineral density could be used as a sensitive marker for precision in the prevention and treatment of osteoporosis.

Effect of ascorbic acid rich, micro-nutrient fortified supplement on the iron bioavailability of ferric pyrophosphate from a milk based beverage in Indian school children.

BACKGROUND AND OBJECTIVES: Nutritional anemia is a significant public health issue with 50-80% prevalence in Indian children. Fortification of food, specifically milk, with iron is a potential approach to increase dietary iron intake. Ferric pyrophosphate [Fe4(P2O7)3] is organoleptically neutral and is less soluble in acid medium and, further, has low bioavailability in milk. However, since ascorbic acid is a potent enhancer of iron absorption, the coadministration of ascorbic acid with Fe4(P2O7)3 might enhance the absorption of iron. We evaluated the effect of ascorbic acid on iron absorption from a Fe4(P2O7)3 and an ascorbic acid fortified milk beverage with respect to milk fortified with Fe4(P2O7)3 alone. METHODS AND STUDY DESIGN: A double-blind, two-way crossover, randomized study was conducted in 25 mildly anemic children. The test group received milk fortified with beverage powder containing 7 mg isotopically labeled iron (57Fe/58Fe) as Fe4(P2O7)3, equimolar proportions of ascorbic acid and 200 mg of calcium whereas control group received milk fortified with energy, calcium and iron equivalent beverage powder. Fractional iron absorption was measured by erythrocyte incorporation of stable isotopes of iron (57Fe/58Fe) in both the groups. RESULTS: The fractional iron absorption from the control drink was 0.80% (95% CI: 0.57, 1.12). Fortifying the milk with an equimolar amount of ascorbic acid increased the fractional iron absorption almost 2-fold to 1.58% (95% CI: 1.13, 2.22). CONCLUSIONS: The presence of ascorbic acid in an equimolar ratio with that of iron from Fe4(P2O7)3 salt in milk as a fortificant enhanced iron absorption when compared to milk fortified with only Fe4(P2O7)3.

Continuous, real-time monitoring of neonatal position and temperature during Kangaroo Mother Care using a wearable sensor: a techno-feasibility pilot study.

BACKGROUND: Remote biomonitoring of vital parameters in hospitals and homes has the potential to improve coverage and quality of maternal and neonatal health. Wearable sensors coupled with modern information and communication technology now offer an opportunity to monitor temperatures and kangaroo mother care (KMC) adherence in a continuous and real-time manner remotely for several days' duration in hospital and home settings. Using an innovative remote biomonitoring device to measure both temperature and baby position, we undertook a techno-feasibility study in preparation for a clinical trial. METHODS: We designed and developed a wearable sensor for tracking KMC adherence and neonatal temperature, using social innovation design principles. After screening mother-infant dyads using clinical and logistic eligibility criteria, we piloted this wearable sensor along with a gateway device and the commercial cellular network. The dyads were recruited during hospitalization and followed up in the hospital and home phases for several days. Simple descriptive statistical analysis was undertaken. RESULTS: Recruitment rate was 50% (6/12), and consenting rate was 83% (5/6) during a 2-month period. These five neonates contributed a total of 39 study days (15 hospital days and 24 home days). Their mean [± standard deviation (S.D.)] birth weight was 1490 (± 244) g.The mean (± S.D.) of the vital signs for the five babies was temperature [36.5 °C (± 0.3)], heart rate [146.5/min (± 14)], and oxygen saturation [94% (± 4)]. No severe or moderate side-effects were noted; one baby developed mild dermatitis under the device that was transient and self-limiting, yielding an incidence proportion of 20% and incidence rate of 2.6/100 person-days.None of the mothers reported any discomfort with the use of the device. Temperatures detected from 81 paired readings revealed that those from the wearable sensor were 0.2 °C lower than those detected by clinical thermometers [36.4 (± 0.7) vs 36.6 (± 0.3); < 0.001].There was also iterative feedback that was useful for hardware and software design specifications of the wearable sensor, the gateway device, and the analytics platform. Lastly, lessons were learnt with regard to the logistics of research team interactions with healthcare professionals and study participants during the hospitalization and post-discharge home phases of the study. CONCLUSIONS: The pilot study has shown that it is feasible and acceptable to track KMC adherence as well as maternal and newborn temperatures in a potentially safe manner on a real-time mode for several days' duration during hospitalization and home phases. The pilot has also helped inform modifications in clinical monitoring, technological modifications, and logistics planning in preparation for the definitive clinical trial. TRIAL REGISTRATION: Clinical Trials Registry of India, CTRI/2017/09/009789.

Remote biomonitoring of temperatures in mothers and newborns: design, development and testing of a wearable sensor device in a tertiary-care hospital in southern India.

OBJECTIVE: Newer technologies such as wearables, sensors, mobile telephony and computing offer opportunities to monitor vital physiological parameters and tackle healthcare problems, thereby improving access and quality of care. We describe the design, development and testing of a wearable sensor device for remote biomonitoring of body temperatures in mothers and newborns in southern India. METHODS: Based on client needs and technological requirements, a wearable sensor device was designed and developed using principles of 'social innovation' design. The device underwent multiple iterations in product design and engineering based on user feedback, and then following preclinical testing, a techno-feasibility study and clinical trial were undertaken in a tertiary-care teaching hospital in Bangalore, India. Clinical trial phases I and IIa for evaluation of safety and efficacy were undertaken in the following sequence: 7 healthy adult volunteers; 18 healthy mothers; 3 healthy babies; 10 stable babies in the neonatal care intensive unit and 1 baby with morbidities. Time-stamped skin temperature readings obtained at 5 min intervals over a 1-hour period from the device secured on upper arms of mothers and abdomen of neonates were compared against readings from thermometers used routinely in clinical practice. RESULTS: Devices were comfortably secured on to adults and neonates, and data were efficiently transmitted via the gateway device for secure storage and retrieval for analysis. The mean skin temperatures in mothers were lower than the axillary temperatures by 2°C; and in newborns, there was a precision of -0.5°C relative to axillary measurements. While occasional minimal adverse events were noted in healthy volunteers, no adverse events were noted in mothers or neonates. CONCLUSIONS: This proof-of-concept study shows that this device is promising in terms of feasibility, safety and accuracy (with appropriate calibration) with potential for further refinements in device accuracy and pursuit of further phases of clinical research for improved maternal and neonatal health.

The effects of regular consumption of a multiple micronutrient fortified milk beverage on the micronutrient status of school children and on their mental and physical performance.

Multiple micronutrient deficiencies exist in school going children in India and bridging the gap between nutrient intake and requirements is an effective way to combat the deficiencies. This study aimed to test the effect of a multi-micronutrient fortified malt and cocoa based milk beverage on the micronutrient status, cognition, physical performance and nutritional deficiencies of 7-10 years old south Indian children. A randomized, double blind placebo controlled study design was used with normal healthy children from low to middle income families, aged 7-10 years randomly assigned to receive either a multi-micronutrient fortified or an unfortified milk based control drink. The drinks were provided 6 days/week for 5 months. Assessments included anthropometry, blood biochemistry, physical performance and cognition at baseline and endline. The baseline characteristics of the study groups were similar. The changes in body weight and height were similar between the groups at the end of the study. Levels of vitamin B12, red cell folate and vitamin B2 significantly improved in the intervention group, while vitamin D, selenium and body iron showed no difference. The Hemoglobin (Hb) and serum ferritin levels of the control group decreased at endline, while those in the intervention group maintained their levels. The serum transferrin receptor levels increased in both the groups. The prevalence of iron deficiency and Vitamin B2 deficiency were significantly lower in the intervention group at endline. Overall improvement in cognitive and physical performance was seen in both the groups at endline, with no significant differences between the groups. The micronutrient fortified milk based drink was efficacious in improving the micronutrient status of Vitamin B2, Vitamin B12 and red cell folate and in preventing a decline in Hb level compared to an unfortified milk based drink. It also reduced anemia and the risk of deficiencies of iron, and B12, in apparently healthy children. ClinicalTrials.gov IdentifierNCT01415557. Clinical Trial RegistryIndia - REF/2012/12/004332.

Increased risk of iron deficiency and reduced iron absorption but no difference in zinc, vitamin A or B-vitamin status in obese women in India.

PURPOSE: Two objectives were investigated: (1) to assess the risk of micronutrient deficiencies in relation to weight status in Indian women with a focus on iron but also including zinc, vitamin A and B vitamins and (2) to compare fractional iron absorption between obese (OB) and normal weight (NW) women. METHODS: Part 1 was a cross-sectional study including 146 healthy, middle-class women from Bangalore, India, with a BMI between 19 and 40 kg/m2. Anthropometrics and blood pressure were measured, and a fasting blood sample was obtained for the analysis of vitamin and mineral status, hepcidin, blood lipids and glucose. In part 2, 16 OB and 13 NW women consumed a standardized test meal labeled with the stable iron isotope 57Fe. Incorporation of the iron isotope into erythrocytes was measured 14 days later. In addition, iron status, hepcidin and inflammatory markers were determined. RESULTS: In part 1, compared to NW women, overweight/OB subjects had significantly higher C-reactive protein, serum ferritin, soluble transferrin receptor (sTfR) and hepcidin concentrations (p < 0.05). The odds ratio for having high sTfR concentrations (i.e., low iron status) with increasing BMI was 1.09 (95 % CI 1.02-1.17). None of the other micronutrients investigated showed any differences between weight status groups. In part 2, fractional iron absorption was significantly lower in the OB group compared to the NW group even after controlling for differences in iron status (10.0 ± 6.5 vs. 16.7 ± 4.6 %; p = 0.038). CONCLUSIONS: OB women in Bangalore have an increased risk of low iron status and absorb less dietary iron; however, their risk of other micronutrient deficiencies was similar to NW women. Our results clearly demonstrate the importance of considering the double burden of malnutrition in the planning of prevention strategies especially in transition countries with emerging obesity epidemics.

Inhibition of iron absorption by calcium is modest in an iron-fortified, casein- and whey-based drink in Indian children and is easily compensated for by addition of ascorbic acid.

BACKGROUND: Calcium inhibits and ascorbic acid (AA) enhances iron absorption from iron-fortified foods. Absorption efficiency depends on iron status, although the interaction is unclear. OBJECTIVE: We investigated the ability of AA to overcome calcium-induced inhibition of iron absorption in children differing in iron status. METHODS: The effect of calcium (0, 100, and 200 mg/test meal) on iron absorption in the absence and presence of AA (0, 42.5, and 85 mg/test meal) from a casein/whey-based drink fortified with ferrous sulfate was assessed in a series of randomized crossover studies both in iron-replete (IR) Indian schoolchildren and in children with iron deficiency anemia (IDA) (6-11 y; n = 14-16/group) by using stable isotopes. RESULTS: In the absence of calcium and AA, iron absorption from the casein/whey-based drink was 20% lower in IR children than in children with IDA. The addition of calcium reduced mean iron absorption by 18-27%, with the effect being stronger for high added calcium (P < 0.01). AA at a 2:1 or 4:1 molar ratio enhanced iron absorption by a factor of 2-4 and greatly overcompensated for the inhibitory effect of calcium on iron absorption in a dose-dependent manner (P < 0.001). The dose-response effect tended to be stronger (P < 0.1) in the IDA group, and iron status was of far less influence on iron absorption than the enhancing effect of AA. CONCLUSION: When adding AA to iron-fortified milk products, care should be taken not to provide absorbable iron in excess of needs.

Breast milk zinc transfer and early post-natal growth among urban South Indian term infants using measures of breast milk volume and breast milk zinc concentrations.

Zinc (Zn) deficiency in infancy and early childhood is of public health concern in developing countries. This study aimed to longitudinally assess Zn intake of urban South Indian term infants in the first 6 months of life using measures of breast milk (BM) volume and BM Zn concentrations and, additionally, to study the effect of BM Zn intake on infant length and weight gain. BM intake by the deuterium dilution technique, BM Zn concentration at months 1, 3 and 6, as well as serum Zn level at months 3 and 6 were assessed in 50 mother-infant pairs. BM intake significantly declined from 627 mL day(-1) at month 1 to 608 mL day(-1) at month 6 (P < 0.01). BM Zn concentration and intake significantly declined from month 1 to month 6 (P < 0.001 for both). Mean infant serum Zn level at months 3 and 6 were 93.0 ± 27.1 and 99.6 ± 30.1 µg dL(-1), respectively. Infant BM Zn intake at months 1 and 3 was not associated with the weight and length gain between 1-3 and 3-6 months, respectively. Zn intake from BM, maternal BM Zn content and serum Zn levels were not significantly different between small-for-gestational age and appropriate-for-gestational age infants. Therefore, among urban south Indian term infants less than 6 months of age, BM Zn intakes were low, owing to low volumes of BM intake, despite BM Zn concentrations being in the normal range. Promotion of breastfeeding and thereby increasing the volumes of milk produced is a first important step towards improving Zn intake among infants.

Effect of iron status on iron absorption in different habitual meals in young south Indian women.

BACKGROUND & OBJECTIVES: Iron deficiency (ID) affects a large number of women in India. An inverse relationship exists between iron (Fe) status and Fe absorption. Dietary inhibitory and enhancing factors exert a profound influence on bioavailability of Fe. Although the current recommended dietary allowance (RDA) for Fe is based on 8 per cent bioavailability, it is not clear if this holds good for the usual highly inhibitory Indian diet matrix. This study was aimed to determine Fe absorption from several habitually consumed south Indian food and to evaluate the interaction of Fe status with absorption. METHODS: Four Fe absorption studies were performed on 60 apparently healthy young women, aged 18-35 years. Based on blood biochemistry, 45 of them were ID and 15 were iron replete (IR). The habitual meals assessed were rice, millet and wheat based meals in the ID subjects and rice based meal alone in the IR subjects. Each subject received the test meal labelled with 3 mg of 57Fe and Fe absorption was measured based on erythrocyte incorporation of isotope label 14 days following administration. RESULTS: Mean fractional Fe absorption from the rice, wheat and millet based meals in the ID subjects were 8.3, 11.2 and 4.6 per cent, respectively. Fe absorption from the rice-based meals was 2.5 per cent in IR subjects. INTERPRETATION & CONCLUSIONS: Fe absorption is dictated by Fe status from low bioavailability meals. Millet based meals have the lowest bioavailability, while the rice and wheat based meals had moderate to good bioavailability. In millet based meals, it is prudent to consider ways to improve Fe absorption.

Addition of zinc to human ejaculate prior to cryopreservation prevents freeze-thaw-induced DNA damage and preserves sperm function.

PURPOSE: To study the effect of addition of zinc to human semen sample prior to cryopreservation on post-thaw sperm quality and function. METHODS: Semen samples were collected from men attending university infertility clinic for semen analysis (n=109). Liquefied semen samples were cryopreserved in glycerol-egg yolk- citrate medium with or without the prior addition of zinc (100 µM) and stored in liquid nitrogen. After 10 days, the semen samples were thawed to assess the outcome. Sperm motility, DNA integrity, mitochondrial potential and the ability of spermatozoa to undergo capacitation and acrosome reaction was assessed in post-thaw samples. RESULTS: Semen samples cryopreserved after addition of zinc had a significantly higher percentage of sperm with intact DNA (p<0.001), mitochondrial function (p<0.001) and progressive motility (p<0.01) compared to the semen samples cryopreserved without zinc supplementation. Apart from this, ability to undergo capacitation and acrosome reaction in vitro was significantly higher in semen samples cryopreserved with zinc (p<0.0001 and p<0.001 respectively). CONCLUSIONS: Addition of zinc to semen samples prior to cryopreservation helps in preventing the freeze-thaw-induced sperm DNA damage and loss of sperm function.

Effect of wheat flour fortified with sodium iron EDTA on urinary zinc excretion in school-aged children.

BACKGROUND: Foods fortified with sodium iron ethylenediaminetetraacetate (NaFeEDTA) have been shown to improve iron status in children, but little is known about the effect of this salt on urinary zinc excretion, particularly in children. This is particularly relevant, since zinc deficiency is known to limit growth and development in young children. OBJECTIVE: To determine the effect of NaFeEDTA-fortified wheat flour on urinary zinc excretion. METHODS: This study was a part of a randomized, controlled trial that was carried out among 6- to 13-year-old iron-depleted schoolchildren (n = 179) who had received either a NaFeEDTA-fortified wheat meal (iron group) or an identical control meal without added iron (control group) for a period of 7 months. Urinary zinc concentration was assessed at the end of the intervention period by spot urine samples. RESULTS: Iron status in the iron group was significantly improved according to measurements of hemoglobin and serum ferritin (p < .001). However, there was no significant difference in urinary zinc excretion between the iron group (median, 38.4 microg/dL; 25th-75th percentiles, 18.2-67.1 microg/dL) and the control group (median, 33.1 microg/dL; 25th-75th percentiles, 12.4-54.2 microg/dL). CONCLUSIONS: Iron fortification of foods with NaFeEDTA does not affect urinary zinc excretion in children.

Iron fortification of whole wheat flour reduces iron deficiency and iron deficiency anemia and increases body iron stores in Indian school-aged children.

Wheat is the primary staple food for nearly one-third of the world's population. NaFeEDTA is the only iron (Fe) compound suitable for fortifying high extraction flours. We tested the hypothesis that NaFeEDTA-fortified, whole wheat flour reduces Fe deficiency (ID) and improves body Fe stores (BIS) and cognitive performance in Indian children. In a randomized, double-blind, controlled, school feeding trial, 6- to 15-y-old, Fe-depleted children (n = 401) were randomly assigned to either a daily wheat-based lunch meal fortified with 6 mg of Fe as NaFeEDTA or an otherwise identical unfortified control meal. Hemoglobin (Hb) and Fe status were measured at baseline, 3.5 mo, and 7 mo. Cognitive performance was evaluated at baseline and 7 mo in children (n = 170) at one of the study sites. After 7 mo, the prevalence of ID and ID anemia in the treatment group significantly decreased from 62 to 21% and 18 to 9%, respectively. There was a time x treatment interaction for Hb, serum ferritin, transferrin receptor, zinc protoporphyrin, and BIS (all P < 0.0001). Changes in BIS differed between the groups; it increased in the treatment group (0.04 ± 0.04 mmol/kg body weight) and decreased in the control group (-0.02 ± 0.04 mmol/kg body weight) (P < 0.0001). In sensory tests, NaFeEDTA-fortified flour could not be differentiated from unfortified flour. There were no significant differences in cognitive performance tests between the groups. NaFeEDTA-fortified wheat flour markedly improved BIS and reduced ID in Fe-depleted children. It may be recommended for wider use in national school feeding programs.

Multiple micronutrient-fortified rice affects physical performance and plasma vitamin B-12 and homocysteine concentrations of Indian school children.

Fortifying rice with multiple micronutrients could be a promising strategy for combat micronutrient deficiencies in developing countries. We determined the efficacy of extruded rice grains fortified with multiple micronutrients on the prevalence of anemia, micronutrient status, and physical and cognitive performance in 6- to 12-y-old, low-income school children in Bangalore, India. In a randomized, double-blind, controlled trial, 258 children were assigned to 1 of 3 intervention groups to receive rice-based lunch meals fortified with multiple micronutrients with either low-iron (6.25 mg) or high-iron (12.5 mg) concentrations or identical meals with unfortified rice. The meals were provided 6 d/wk for 6 mo. Anthropometric, biochemical, physical performance, and cognitive assessments were taken at baseline and endpoint. At baseline, study groups were comparable, with 61% of the children being anemic. However, only <10% were deficient in iron, vitamin A, and zinc. After 6 mo, plasma vitamin B-12 and homocysteine concentrations (both P < 0.001) as well as physical performance (P < 0.05) significantly improved in the intervention arms. No between-group differences were observed in hemoglobin concentration, anemia, and deficiencies of other micronutrients or cognitive function after 6 mo, but paired analyses revealed a small reduction in anemia prevalence in children in the low-iron group. The fortified rice was efficacious in improving vitamin B-12 status and physical performance in Indian school children.

Dual fortification of salt with iodine and iron: a randomized, double-blind, controlled trial of micronized ferric pyrophosphate and encapsulated ferrous fumarate in southern India.

BACKGROUND: Dual fortification of salt with iodine and iron could be a sustainable approach to combating iodine and iron deficiencies. OBJECTIVE: We compared the efficacy of dual-fortified salt (DFS) made by using 2 proposed contrasting formulas-one fortifying with iron as micronized ground ferric pyrophosphate (MGFePP) and the other with iron as encapsulated ferrous fumarate (EFF)-with the efficacy of iodized salt (IS) in schoolchildren in rural southern India. DESIGN: After stability and acceptability testing, a double-blind, household-based intervention was conducted in 5-15-y-old children (n = 458) randomly assigned into 3 groups to receive IS or DFS with iron as MGFePP or EFF, both at 2 mg/g salt. We measured hemoglobin, iron status, and urinary iodine at baseline, 5 mo, and 10 mo. RESULTS: Median serum ferritin and calculated median body iron improved significantly in the 2 groups receiving iron. After 10 mo, the prevalence of anemia decreased from 16.8% to 7.7% in the MGFePP group (P < 0.05) and from 15.1% to 5.0% in the EFF group (P < 0.01). The median urinary iodine concentration increased significantly in the IS and EFF groups (P < 0.001) but not in the MGFePP group. Losses of iodine in salt with 1.8% moisture were high for MGFePP, whereas the EFF segregated in salt with 0.5% moisture and caused color changes in some local foods. CONCLUSIONS: Both DFSs were efficacious in reducing the prevalence of anemia and iron deficiency in school-age children. Local salt characteristics should be taken into consideration when choosing an iron fortificant for DFS to achieve optimal iodine stability and color.