Preventing and Controlling Zinc Deficiency Across the Life Course: A Call to Action.

Through diverse roles, zinc determines a greater number of critical life functions than any other single micronutrient. Beyond the well-recognized importance of zinc for child growth and resistance to infections, zinc has numerous specific roles covering the regulation of glucose metabolism, and growing evidence links zinc deficiency with increased risk of diabetes and cardiometabolic disorders. Zinc nutriture is, thus, vitally important to health across the life course. Zinc deficiency is also one of the most common forms of micronutrient malnutrition globally. A clearer estimate of the burden of health disparity attributable to zinc deficiency in adulthood and later life emerges when accounting for its contribution to global elevated fasting blood glucose and related noncommunicable diseases (NCDs). Yet progress attenuating its prevalence has been limited due, in part, to the lack of sensitive and specific methods to assess human zinc status. This narrative review covers recent developments in our understanding of zinc's role in health, the impact of the changing climate and global context on zinc intake, novel functional biomarkers showing promise for monitoring population-level interventions, and solutions for improving population zinc intake. It aims to spur on implementation of evidence-based interventions for preventing and controlling zinc deficiency across the life course. Increasing zinc intake and combating global zinc deficiency requires context-specific strategies and a combination of complementary, evidence-based interventions, including supplementation, food fortification, and food and agricultural solutions such as biofortification, alongside efforts to improve zinc bioavailability. Enhancing dietary zinc content and bioavailability through zinc biofortification is an inclusive nutrition solution that can benefit the most vulnerable individuals and populations affected by inadequate diets to the greatest extent.

Biofortified Yellow-Fleshed Potatoes Provide More Absorbable Zinc than a Commonly Consumed Variety: A Randomized Trial Using Stable Isotopes in Women in the Peruvian Highlands.

BACKGROUND: Zinc-biofortified potatoes have considerable potential to reduce zinc deficiency because of their low levels of phytate, an inhibitor of zinc absorption, and their high consumption, especially in the Andean region of Peru. OBJECTIVES: The purpose of this study was to measure fractional and total zinc absorption from a test meal of biofortified compared with regular potatoes. METHODS: We undertook a single-blinded randomized crossover study (using 67Zn and 70Zn stable isotopes) in which 37 women consumed 500-g biofortified or regular potatoes twice a day. Urine samples were collected to determine fractional and total zinc absorption. RESULTS: The zinc content of the biofortified potato and regular potato was 0.48 (standard deviation [SD]: 0.02) and 0.32 (SD: 0.03) mg/100 g fresh weight, respectively. Mean fractional zinc absorption (FZA) from the biofortified potatoes was lower than from the regular potatoes, 20.8% (SD: 5.4%) and 25.5% (SD: 7.0%), respectively (P < 0.01). However, total zinc absorbed was significantly higher (0.49; SD: 0.13 and 0.40; SD: 0.11 mg/500 g, P < 0.01, respectively). CONCLUSIONS: The results of this study demonstrate that biofortified potatoes provide more absorbable zinc than regular potatoes. Zinc-biofortified potatoes could contribute toward reducing zinc deficiency in populations where potatoes are a staple food. This trial was registered at clinicaltrials.gov as NCT05154500.

Total Iron Absorbed from Iron-Biofortified Potatoes Is Higher than that from Nonbiofortified Potatoes: A Randomized Trial Using Stable Iron Isotopes in Women from the Peruvian Highlands.

BACKGROUND: Yellow-fleshed potatoes biofortified with iron have been developed through conventional breeding, but the bioavailability of iron is unknown. OBJECTIVES: Our objective was to measure iron absorption from an iron-biofortified yellow-fleshed potato clone in comparison with a nonbiofortified yellow-fleshed potato variety. METHODS: We conducted a single-blinded, randomized, crossover, multiple-meal intervention study. Women (n = 28; mean ± SD plasma ferritin 21.3 ± 3.3 µg/L) consumed 10 meals (460 g) of both potatoes, each meal extrinsically labeled with either 58Fe sulfate (biofortified) or 57Fe sulfate (nonfortified), on consecutive days. Iron absorption was estimated from iron isotopic composition in erythrocytes 14 d after administration of the final meal. RESULTS: Mean ± SD iron, phytic acid, and ascorbic acid concentrations in iron-biofortified and the nonfortified potato meals (mg/per 100 mg) were 0.63 ± 0.01 and 0.31 ± 0.01, 39.34 ± 3.04 and 3.10 ± 1.72, and 7.65 ± 0.34 and 3.74 ± 0.39, respectively (P < 0.01), whereas chlorogenic acid concentrations were 15.14 ± 1.72 and 22.52 ± 3.98, respectively (P < 0.05). Geometric mean (95% CI) fractional iron absorption from the iron-biofortified clone and the nonbiofortified variety were 12.1% (10.3%-14.2%) and 16.6% (14.0%-19.6%), respectively (P < 0.001). Total iron absorption from the iron-biofortified clone and the nonbiofortified variety were 0.35 mg (0.30-0.41 mg) and 0.24 mg (0.20-0.28 mg) per 460 g meal, respectively (P < 0.001). CONCLUSIONS: TIA from iron-biofortified potato meals was 45.8% higher than that from nonbiofortified potato meals, suggesting that iron biofortification of potatoes through conventional breeding is a promising approach to improve iron intake in iron-deficient women. The study was registered at www. CLINICALTRIALS: gov as Identifier number NCT05154500.

Modeling relationships between iron status, behavior, and brain electrophysiology: evidence from a randomized study involving a biofortified grain in Indian adolescents.

BACKGROUND: Iron deficiency (ID) and iron deficiency anemia (IDA) are highly-prevalent nutrient deficiencies and have been shown to have a range of negative effects on cognition and brain function. Human intervention studies including measures at three levels-blood, brain, and behavior-are rare and our objective was to model the relationships among measures at these three levels in school-going Indian adolescents. METHODS: Male and female adolescents in rural India were screened for ID/IDA. Subjects consumed 2 meals/day for 6 months; half were randomly assigned to consume meals made from a standard grain (pearl millet) and half consumed meals made from an iron biofortified pearl millet (BPM). Prior to and then at the conclusion of the feeding trial, they completed a set of cognitive tests with concurrent electroencephalography (EEG). RESULTS: Overall, serum ferritin (sFt) levels improved over the course of the study. Ten of 21 possible measures of cognition showed improvements from baseline (BL) to endline (EL) that were larger for those consuming BPM than for those consuming the comparison pearl millet (CPM). Critically, the best model for the relationship between change in iron status and change in cognition had change in brain measures as a mediating factor, with both change in serum ferritin as a primary predictor and change in hemoglobin as a moderator. CONCLUSIONS: A dietary intervention involving a biofortified staple grain was shown to be efficacious in improving blood iron biomarkers, behavioral measures of cognition, and EEG measures of brain function. Modeling the relationships among these variables strongly suggests multiple mechanisms by which blood iron level affects brain function and cognition. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, NCT02152150 , 02 June 2014.

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.

Calcium supplementation for the prevention of hypertensive disorders of pregnancy: current evidence and programmatic considerations.

Most low- and middle-income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500-mg doses/day). WHO recommends 1.5-2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low-dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost-effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron-containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food-based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation.

Scaling Up Delivery of Biofortified Staple Food Crops Globally: Paths to Nourishing Millions.

BACKGROUND: Micronutrient deficiencies affect over one quarter of the world's population. Biofortification is an evidence-based nutrition strategy that addresses some of the most common and preventable global micronutrient gaps and can help improve the health of millions of people. Since 2013, HarvestPlus and a consortium of collaborators have made impressive progress in the enrichment of staple crops with essential micronutrients through conventional plant breeding. OBJECTIVE: To review and highlight lessons learned from multiple large-scale delivery strategies used by HarvestPlus to scale up biofortification across different country and crop contexts. RESULTS: India has strong public and private sector pearl millet breeding programs and a robust commercial seed sector. To scale-up pearl millet, HarvestPlus established partnerships with public and private seed companies, which facilitated the rapid commercialization of products and engagement of farmers in delivery activities. In Nigeria, HarvestPlus stimulated the initial acceptance and popularization of vitamin A cassava using a host of creative approaches, including "crowding in" delivery partners, innovative promotional programs, and development of intermediate raw material for industry and novel food products. In Uganda, orange sweet potato (OSP) is a traditional subsistence crop. Due to this, and the lack of formal seed systems and markets, HarvestPlus established a network of partnerships with community-based nongovernmental organizations and vine multipliers to popularize and scale-up delivery of OSP. CONCLUSIONS: Impact of biofortification ultimately depends on the development of sustainable markets for biofortified seeds and products. Results illustrate the need for context-specific, innovative solutions to promote widespread adoption.

Effects of Dose and Duration of Zinc Interventions on Risk Factors for Type 2 Diabetes and Cardiovascular Disease: A Systematic Review and Meta-Analysis.

No meta-analysis has examined the effect of dose and duration of zinc interventions on their impact on risk factors for type 2 diabetes (T2D) or cardiovascular disease (CVD). This study aimed first to compare the effects of zinc interventions dichotomized as low versus high dose (<25 mg/d and ≥25 mg/d, respectively) and short versus long duration (<12 wk and ≥12 wk, respectively) on risk factors for T2D and CVD. Second, it discusses the results from the low-dose and long-duration meta-analyses as a foundation for understanding what impact a zinc-biofortification intervention could have on these risk factors. The PubMed and Cochrane Review databases were searched through January 2020 for full-text, human studies providing zinc supplements (alone) at doses ≤75 mg/d and a placebo. Data on study and sample characteristics and several T2D and CVD risk factors were extracted. There were 1042 and 974 participants receiving zinc and placebo, respectively, from 27 studies. Low-dose zinc supplementation (<25 mg/d) significantly benefited fasting blood glucose, insulin resistance, triglycerides, total cholesterol, and LDL cholesterol. High-dose zinc supplementation (≥25 mg/d) benefited glycated hemoglobin and insulin resistance. Short-duration interventions (<12 wk) benefited fasting blood glucose, insulin resistance, and triglycerides, while long-duration studies (≥12 wk) benefited fasting blood glucose, triglycerides, and total and LDL cholesterol. Effect sizes for low-dose and long-duration interventions were of equal or greater magnitude to those from high-dose or short-duration interventions. Low-dose and long-duration zinc supplementation each improved more risk factors for T2D and CVD than high-dose and short-duration interventions, respectively. It is currently unknown whether low doses of zinc delivered over long durations via a biofortified crop would similarly impact these risk factors. However, this review suggests that low-dose, long-duration zinc intake from supplements, and potentially biofortification, can benefit risk factors for T2D and CVD.

Zinc Absorption From Agronomically Biofortified Wheat Is Similar to Post-Harvest Fortified Wheat and Is a Substantial Source of Bioavailable Zinc in Humans.

BACKGROUND: Limited data exist on human zinc absorption from wheat biofortified via foliar (FBW) or root (hydroponically fortified wheat, HBW) zinc application. Stable isotope labels added at point of consumption (extrinsic labeling) might not reflect absorption from native zinc obtained by intrinsic labeling. OBJECTIVES: We measured fractional and total zinc absorption (FAZ, TAZ) in FBW and HBW wheat, compared with control wheat (CW) and fortified wheat (FW). The effect of labeling method was assessed in HBW (study 1), and the effect of milling extraction rate (EXR, 80% and 100%) in FBW (studies 2 and 3). METHODS: Generally healthy adults (n = 71, age: 18-45 y, body mass index: 18.5-25 kg/m2) were allocated to 1 of the studies, in which they served as their own controls. In study 1, men and women consumed wheat porridges colabeled intrinsically and extrinsically with 67Zn and 70Zn. In studies 2 and 3, women consumed wheat flatbreads (chapatis) labeled extrinsically. Zinc absorption was measured with the oral to intravenous tracer ratio method with a 4-wk wash-out period between meals. Data were analyzed with linear mixed models. RESULTS: In study 1 there were no differences in zinc absorption from extrinsic versus intrinsic labels in either FW or HBW. Similarly, FAZ and TAZ from FW and HBW did not differ. TAZ was 70-76% higher in FW and HBW compared with CW (P < 0.01). In studies 2 and 3, TAZ from FW and FBW did not differ but was 20-48% higher compared with CW (P < 0.001). Extraction rate had no effect on TAZ. CONCLUSIONS: Colabeling demonstrates that extrinsic zinc isotopic labels can be used to accurately quantify zinc absorption from wheat in humans. Biofortification through foliar zinc application, root zinc application, or fortification provides higher TAZ compared with unfortified wheat. In biofortified wheat, extraction rate (100-80%) has a limited impact on total zinc absorption. These studies were registered on clinicaltrials.gov (NCT01775319).

Changes in Iron Status Are Related to Changes in Brain Activity and Behavior in Rwandan Female University Students: Results from a Randomized Controlled Efficacy Trial Involving Iron-Biofortified Beans.

BACKGROUND: Evidence suggests that iron deficiency (ID) affects cognitive performance, as measured in behavior. Although such effects must be mediated by changes in the brain, very few studies have included measures of brain activity to assess this relation. OBJECTIVE: We tested the hypothesis that provision of iron-biofortified beans would result in improvements in measures of iron status, brain dynamics, and behavior. METHODS: A double-blind, randomized, intervention study was conducted in 55 women aged 18-27 y with low iron status (serum ferritin <20 µg/L). Women were randomly assigned to consume iron-biofortified (86.1 ppm iron) or comparison beans (50.1 ppm iron) daily for 18 wk. Iron status was assessed by hemoglobin, ferritin, transferrin receptor, and body iron; cognitive performance with 5 computerized tasks; and brain dynamics by concurrent electroencephalography (EEG). All measures were taken at baseline and endline. RESULTS: The groups did not differ on any measures at baseline. Intention-to-treat analyses revealed significant (all P < 0.05) improvements in hemoglobin (partial effect size attributable to the independent variable, η2 = 0.16), ferritin (η2 = 0.17), and body iron (η2 = 0.10), speed of responding in attentional and mnemonic tasks (η2 = 0.04-0.29), sensitivity and efficiency of memory retrieval (η2 = 0.12-0.55), and measures of EEG amplitude and spectral power (η2 = 0.08 to 0.49). Mediation models provided evidence in support of the hypothesis that changes in iron status produce changes in behavior by way of changes in brain activity. CONCLUSIONS: Behavioral performance and brain activity, as measured by EEG, are sensitive to iron status, and the consumption of iron-biofortified beans for 18 wk resulted in improvements in measures of both, relative to what was obtained with a comparison bean, in a sample of female university students. Furthermore, the results support the conclusion that changes in brain activity resulting from consumption of biofortified beans mediate the relations between changes in iron biomarkers and changes in cognition. Clinical trial registry: ClinicalTrials.gov Reg No. NCT01594359.

Overlapping vitamin A interventions in the United States, Guatemala, Zambia, and South Africa: case studies.

Vitamin A (VA) deficiency is a serious public health problem, especially in preschool children who are at risk of increased mortality. In order to address this problem, the World Health Organization recommends periodic high-dose supplementation to children 6-59 months of age in areas of highest risk. Originally, supplementation was meant as a short-term solution until more sustainable interventions could be adopted. Currently, many countries are fortifying commercialized common staple and snack foods with retinyl palmitate. However, in some countries, overlapping programs may lead to excessive intakes. Our review uses case studies in the United States, Guatemala, Zambia, and South Africa to illustrate the potential for excessive intakes in some groups. For example, direct liver analysis from 27 U.S. adult cadavers revealed 33% prevalence of hypervitaminosis A (defined as ≥1 µmol/g liver). In 133 Zambian children, 59% were diagnosed with hypervitaminosis A using a retinol isotope dilution, and 16% had ≥5% total serum VA as retinyl esters, a measure of intoxication. In 40 South African children who frequently consumed liver, 72.5% had ≥5% total serum VA as retinyl esters. All four countries have mandatory fortified foods and a high percentage of supplement users or targeted supplementation to preschool children.

Cognitive Performance in Indian School-Going Adolescents Is Positively Affected by Consumption of Iron-Biofortified Pearl Millet: A 6-Month Randomized Controlled Efficacy Trial.

BACKGROUND: Iron deficiency remains the most prevalent micronutrient deficiency globally, but few studies have examined how iron status relates to cognition in adolescents. Iron biofortification of staple food crops is being scaled up, yet it is unknown whether consuming biofortified crops can benefit cognition. Objective: Our objective was to determine the efficacy of iron-biofortified pearl millet in improving attention and memory in Indian school-going adolescents. Methods: A double-blind, randomized, intervention study was conducted in 140 Indian boys and girls, aged 12-16 y, who were assigned to consume iron-biofortified [Fe = 86 parts per million (ppm)] or conventional (Fe = 21-52 ppm) pearl millet. Hemoglobin, ferritin, and transferrin receptor (TfR) were measured and body iron (BI) was calculated at baseline and after 4 and 6 mo. Five measures of cognitive function were obtained at baseline and 6 mo: simple reaction time (SRT), Go/No-Go (GNG) task, Attentional Network Task (ANT), Composite Face Effect (CFE) task, and Cued Recognition Task (CRT). Intention-to-treat analysis was used. Results: Daily iron intake from pearl millet was higher in those consuming biofortified compared with conventional pearl millet (19.6 compared with 4.8 mg/d). Effects on ferritin, TfR, and BI at 4 mo, and on TfR at 6 mo (all P < 0.05), indicated efficacy of biofortified pearl millet over conventional pearl millet in improving iron status. Compared with conventional pearl millet, the consumption of biofortified pearl millet resulted in greater improvement in attention (SRT, GNG, and ANT) and memory (CFE and CRT). Reaction time decreased twice as much from 0 to 6 mo in those consuming biofortified compared with conventional pearl millet on attention tasks (SRT: -123 compared with -63 ms; GNG: -67 compared with -30 ms; ANT double cue: -74 compared with -32 ms; all P < 0.01). Conclusion: Consuming iron-biofortified pearl millet improves iron status and some measures of cognitive performance in Indian adolescents. This trial was registered at http://www.clinicaltrials.gov as NCT02152150.

The Effect of Low Dose Iron and Zinc Intake on Child Micronutrient Status and Development during the First 1000 Days of Life: A Systematic Review and Meta-Analysis.

Adequate supply of micronutrients during the first 1000 days is essential for normal development and healthy life. We aimed to investigate if interventions administering dietary doses up to the recommended nutrient intake (RNI) of iron and zinc within the window from conception to age 2 years have the potential to influence nutritional status and development of children. To address this objective, a systematic review and meta-analysis of randomized and quasi-randomized fortification, biofortification, and supplementation trials in women (pregnant and lactating) and children (6-23 months) delivering iron or zinc in doses up to the recommended nutrient intake (RNI) levels was conducted. Supplying iron or zinc during pregnancy had no effects on birth outcomes. There were limited or no data on the effects of iron/zinc during pregnancy and lactation on child iron/zinc status, growth, morbidity, and psychomotor and mental development. Delivering up to 15 mg iron/day during infancy increased mean hemoglobin by 4 g/L (p < 0.001) and mean serum ferritin concentration by 17.6 µg/L (p < 0.001) and reduced the risk for anemia by 41% (p < 0.001), iron deficiency by 78% (ID; p < 0.001) and iron deficiency anemia by 80% (IDA; p < 0.001), but had no effect on growth or psychomotor development. Providing up to 10 mg of additional zinc during infancy increased plasma zinc concentration by 2.03 µmol/L (p < 0.001) and reduced the risk of zinc deficiency by 47% (p < 0.001). Further, we observed positive effects on child weight for age z-score (WAZ) (p < 0.05), weight for height z-score (WHZ) (p < 0.05), but not on height for age z-score (HAZ) or the risk for stunting, wasting, and underweight. There are no studies covering the full 1000 days window and the effects of iron and zinc delivered during pregnancy and lactation on child outcomes are ambiguous, but low dose daily iron and zinc use during 6-23 months of age has a positive effect on child iron and zinc status.

In Rwandese Women with Low Iron Status, Iron Absorption from Low-Phytic Acid Beans and Biofortified Beans Is Comparable, but Low-Phytic Acid Beans Cause Adverse Gastrointestinal Symptoms.

BACKGROUND: Phytic acid (PA) is a major inhibitor of iron bioavailability from beans, and high PA concentrations might limit the positive effect of biofortified beans (BBs) on iron status. Low-phytic acid (lpa) bean varieties could increase iron bioavailability. OBJECTIVE: We set out to test whether lpa beans provide more bioavailable iron than a BB variety when served as part of a composite meal in a bean-consuming population with low iron status. METHODS: Dietary iron absorption from lpa, iron-biofortified, and control beans (CBs) (regular iron and PA concentrations) was compared in 25 nonpregnant young women with low iron status with the use of a multiple-meal crossover design. Iron absorption was measured with stable iron isotopes. RESULTS: PA concentration in lpa beans was ∼10% of BBs and CBs, and iron concentration in BBs was ∼2- and 1.5-fold compared with CBs and lpa beans, respectively. Fractional iron absorption from lpa beans [8.6% (95% CI: 4.8%, 15.5%)], BBs [7.3% (95% CI: 4.0%, 13.4%)], and CBs [8.0% (95% CI: 4.4%, 14.6%)] did not significantly differ. The total amount of iron absorbed from lpa beans and BBs was 421 µg (95% CI: 234, 756 µg) and 431 µg (95% CI: 237, 786 µg), respectively, and did not significantly differ, but was >50% higher (P < 0.005) than from CBs (278 µg; 95% CI: 150, 499 µg). In our trial, the lpa beans were hard to cook, and their consumption caused transient adverse digestive side effects in ∼95% of participants. Gel electrophoresis analysis showed phytohemagglutinin L (PHA-L) residues in cooked lpa beans. CONCLUSION: BBs and lpa beans provided more bioavailable iron than control beans and could reduce dietary iron deficiency. Digestive side effects of lpa beans were likely caused by PHA-L, but it is unclear to what extent the associated digestive problems reduced iron bioavailability. This trial was registered at clinicaltrials.gov as NCT02215278.

Biofortified yellow cassava and vitamin A status of Kenyan children: a randomized controlled trial.

BACKGROUND: Whereas conventional white cassava roots are devoid of provitamin A, biofortified yellow varieties are naturally rich in ß-carotene, the primary provitamin A carotenoid. OBJECTIVE: We assessed the effect of consuming yellow cassava on serum retinol concentration in Kenyan schoolchildren with marginal vitamin A status. DESIGN: We randomly allocated 342 children aged 5-13 y to receive daily, 6 d/wk, for 18.5 wk 1) white cassava and placebo supplement (control group), 2) provitamin A-rich cassava (mean content: 1460 µg ß-carotene/d) and placebo supplement (yellow cassava group), and 3) white cassava and ß-carotene supplement (1053 µg/d; ß-carotene supplement group). The primary outcome was serum retinol concentration; prespecified secondary outcomes were hemoglobin concentration and serum concentrations of ß-carotene, retinol-binding protein, and prealbumin. Groups were compared by using ANCOVA, adjusting for inflammation, baseline serum concentrations of retinol and ß-carotene, and stratified design. RESULTS: The baseline prevalence of serum retinol concentration <0.7 µmol/L and inflammation was 27% and 24%, respectively. For children in the control, yellow cassava, and ß-carotene supplement groups, the mean daily intake of cassava was 378, 371, and 378 g, respectively, and the total daily supply of provitamin A and vitamin A from diet and supplements was equivalent to 22, 220, and 175 µg retinol, respectively. Both yellow cassava and ß-carotene supplementation increased serum retinol concentration by 0.04 µmol/L (95% CI: 0.00, 0.07 µmol/L); correspondingly, serum ß-carotene concentration increased by 524% (448%, 608%) and 166% (134%, 202%). We found no effect on hemoglobin concentration or serum concentrations of retinol-binding protein and prealbumin. CONCLUSIONS: In our study population, consumption of yellow cassava led to modest gains in serum retinol concentration and a large increase in ß-carotene concentration. It can be an efficacious, new approach to improve vitamin A status. This study was registered with clinicaltrials.gov as NCT01614483.

Review: The potential of the common bean (Phaseolus vulgaris) as a vehicle for iron biofortification.

Common beans are a staple food and the major source of iron for populations in Eastern Africa and Latin America. Bean iron concentration is high and can be further increased by biofortification. A major constraint to bean iron biofortification is low iron absorption, attributed to inhibitory compounds such as phytic acid (PA) and polyphenol(s) (PP). We have evaluated the usefulness of the common bean as a vehicle for iron biofortification. High iron concentrations and wide genetic variability have enabled plant breeders to develop high iron bean varieties (up to 10 mg/100 g). PA concentrations in beans are high and tend to increase with iron biofortification. Short-term human isotope studies indicate that iron absorption from beans is low, PA is the major inhibitor, and bean PP play a minor role. Multiple composite meal studies indicate that decreasing the PA level in the biofortified varieties substantially increases iron absorption. Fractional iron absorption from composite meals was 4%-7% in iron deficient women; thus the consumption of 100 g biofortified beans/day would provide about 30%-50% of their daily iron requirement. Beans are a good vehicle for iron biofortification, and regular high consumption would be expected to help combat iron deficiency (ID).

Retention of provitamin a carotenoids in staple crops targeted for biofortification in Africa: cassava, maize and sweet potato.

HarvestPlus, part of the Consultative Group on Internation Agriculture research (CGIAR) Program on Agriculture for Nutrition and Health (A4NH) uses conventional plant breeding techniques to develop staple food crops that are rich in micronutrients, a food-based approach to reduce micronutrient malnutrition known as biofortification. The nutritional breeding targets are established based on the food intake of target populations, nutrient losses during storage and processing and bioavailability. This review collates the evidence on the retention of provitamin A carotenoid (pVAC) after processing, cooking, and storing of the staple crops targeted for pVAC biofortification: cassava, maize, and sweet potato. Sun drying was more detrimental to the pVAC levels (27-56% retention) in cassava than shade (59%) or oven (55-91%) drying, while the pVAC retention levels (66-96%) in sweet potato were not significantly different among the various drying methods. Overall, boiling and steaming had higher pVAC retention (80-98%) compared to baking (30-70%) and frying (18-54%). Gari, the most frequently consumed form of cassava in West Africa had the lowest pVAC retention (10-30%). The pVAC retention of maize grain and cassava and sweet potato flour reached levels as low as 20% after 1-4 months of storage and was highly dependent on genotype. Therefore, we recommend that an evaluation of the pVAC degradation rate among different genotypes be performed before a high pVAC crop is promoted.

Are biofortified staple food crops improving vitamin A and iron status in women and children? New evidence from efficacy trials.

Biofortification is the breeding of crops to increase their nutritional value, including increased contents of micronutrients or their precursors. Biofortification aims to increase nutrient levels in crops during plant growth rather than during processing of the crops into foods. Emerging research from 8 human trials conducted in the past decade with staple food crops that have been biofortified by traditional plant breeding methods were presented in this symposium. Specifically, data from 6 efficacy and 2 effectiveness trials were discussed to assess the effects of regular consumption of these enhanced staple crops on improving population vitamin A and iron status and reducing the burden of micronutrient deficiencies in targeted populations living in South Asia, Sub-Saharan Africa, and Latin America. Biofortified food crops appear to have a positive impact on nutritional and functional health outcomes, as the results from the trials suggest. Additional implementation research will be needed to ensure maximization of the beneficial impact of this intervention and a smooth scaling up to make biofortification a sustainable intervention in public health. The challenge for the global health community remains how to take this efficacious intervention and implement at large scale in the real world.

Phytic acid concentration influences iron bioavailability from biofortified beans in Rwandese women with low iron status.

BACKGROUND: The common bean is a staple crop in many African and Latin American countries and is the focus of biofortification initiatives. Bean iron concentration has been doubled by selective plant breeding, but the additional iron is reported to be of low bioavailability, most likely due to high phytic acid (PA) concentrations. OBJECTIVE: The present study evaluated the impact of PA on iron bioavailability from iron-biofortified beans. METHODS: Iron absorption, based on erythrocyte incorporation of stable iron isotopes, was measured in 22 Rwandese women who consumed multiple, composite bean meals with potatoes or rice in a crossover design. Iron absorption from meals containing biofortified beans (8.8 mg Fe, 1320 mg PA/100 g) and control beans (5.4 mg Fe, 980 mg PA/100 g) was measured with beans containing either their native PA concentration or with beans that were ∼50% dephytinized or >95% dephytinized. RESULTS: The iron concentration of the cooked composite meals with biofortified beans was 54% higher than in the same meals with control beans. With native PA concentrations, fractional iron absorption from the control bean meals was 9.2%, 30% higher than that from the biofortified bean meals (P < 0.001). The quantity of iron absorbed from the biofortified bean meals (406 µg) was 19% higher (P < 0.05) than that from the control bean meals. With ∼50% and >95% dephytinization, the quantity of iron absorbed from the biofortified bean meals increased to 599 and 746 µg, respectively, which was 37% (P < 0.005) and 51% (P < 0.0001) higher than from the control bean meals. CONCLUSIONS: PA strongly decreases iron bioavailability from iron-biofortified beans, and a high PA concentration is an important impediment to the optimal effectiveness of bean iron biofortification. Plant breeders should focus on lowering the PA concentration of high-iron beans. This trial was registered at clinicaltrials.gov as NCT01521273.

Bioavailability of iron, zinc, and provitamin A carotenoids in biofortified staple crops.

International research efforts, including those funded by HarvestPlus, a Challenge Program of the Consultative Group on International Agricultural Research (CGIAR), are focusing on conventional plant breeding to biofortify staple crops such as maize, rice, cassava, beans, wheat, sweet potatoes, and pearl millet to increase the concentrations of micronutrients that are commonly deficient in specific population groups of developing countries. The bioavailability of micronutrients in unfortified staple crops in developing regions is typically low, which raises questions about the efficacy of these crops to improve population micronutrient status. This review of recent studies of biofortified crops aims to assess the micronutrient bioavailability of biofortified staple crops in order to derive lessons that may help direct plant breeding and to infer the potential efficacy of food-based nutrition interventions. Although reducing the amounts of antinutrients and the conduction of food processing generally increases the bioavailability of micronutrients, antinutrients still possess important benefits, and food processing results in micronutrient loss. In general, biofortified foods with relatively higher micronutrient density have higher total absorption rates than nonbiofortified varieties. Thus, evidence supports the focus on efforts to breed plants with increased micronutrient concentrations in order to decrease the influence of inhibitors and to offset losses from processing.