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.
ABSTRACT: 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, ?2 = 0.16), ferritin (?2 = 0.17), and body iron (?2 = 0.10), speed of responding in attentional and mnemonic tasks (?2 = 0.04-0.29), sensitivity and efficiency of memory retrieval (?2 = 0.12-0.55), and measures of EEG amplitude and spectral power (?2 = 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.
Project description:Background: Evidence shows that iron deficiency in adulthood may affect cognitive performance, possibly by disrupting neurotransmitter regulation or brain energy metabolism. Women of reproductive age (WRA) are among those who are most vulnerable to iron deficiency; however, they have been largely ignored in the literature relating iron status to cognition.Objective: Our aim was to determine the efficacy of iron-biofortified beans in improving cognition in WRA compared with control beans.Methods: A double-blind, randomized intervention study was conducted in 150 women aged 18-27 y with low iron status (ferritin <20 ?g/L). Women were randomly assigned to consume iron-biofortified beans (86.1 ppm iron) or control beans (50.1 ppm iron) daily for 18 wk. Iron status was assessed based on hemoglobin, ferritin, transferrin receptor, and body iron values and on cognitive performance on 5 computerized tasks at baseline and endline.Results: Groups did not differ on any variables at baseline. Per protocol analyses revealed that consumption of the biofortified beans resulted in a 17% larger improvement in the speed of spatial selective attention; a nearly 7-fold larger improvement in the speed, a 68% greater improvement in the efficiency, and a >2-fold greater improvement in the specificity of memory retrieval; and a >2-fold larger improvement in the speed and a >3-fold larger improvement in the efficiency of memory search-all of which are relative to consumption of the control beans (P < 0.01 for all comparisons).Conclusions: Cognitive performance is sensitive to iron status, and consumption of iron-biofortified beans for 18 wk improved cognitive performance, especially the efficiency of search and the speed of retrieval on memory tasks, in young adult women. This trial was registered at clinicaltrials.gov as NCT01594359.
Project description:<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>Registered at ClinicalTrials.gov, NCT02152150 , 02 June 2014.
Project description:BACKGROUND:Iron-biofortified staple foods can improve iron status and resolve iron deficiency. However, whether improved iron status from iron biofortification can improve physical performance remains unclear. OBJECTIVE:This study aimed to examine whether changes in iron status from an iron-biofortified bean intervention affect work efficiency. METHODS:A total of 125 iron-depleted (ferritin <20 ?g/L) female Rwandan university students (18-26 y) were selected from a larger sample randomly assigned to consume iron-biofortified beans (Fe-Bean; 86.1 mg Fe/kg) or conventional beans (control: 50.6 mg Fe/kg) twice daily for 18 wk (average of 314 g beans consumed/d). Blood biomarkers of iron status (primary outcome) and physical work efficiency (secondary outcome) were measured before and after the intervention. Work performed was assessed during 5-min steady-state periods at 0-, 25-, and 40-W workloads using a mechanically braked cycle ergometer. Work efficiency was calculated at 25 W and 40 W as the work accomplished divided by the energy expended at that workload above that expended at 0 W. General linear models were used to evaluate the relation between changes in iron status biomarkers and work efficiency. RESULTS:The Fe-Bean intervention had significant positive effects on hemoglobin, serum ferritin, and body iron stores but did not affect work efficiency. However, 18-wk change in hemoglobin was positively related to work efficiency at 40 W in the full sample (n = 119; estimate: 0.24 g/L; 95% CI: 0.01, 0.48 g/L; P = 0.044) and among women who were anemic (hemoglobin <120 g/L) at baseline (n = 43; estimate: 0.64 g/L; 95% CI: 0.05, 1.23 g/L; P = 0.036). Among women who were nonanemic at baseline, change in serum ferritin was positively related to change in work efficiency at 40 W (n = 60; estimate: 0.50 ?g/L; 95% CI: 0.06, 0.95 ?g/L; P = 0.027). CONCLUSIONS:Increasing iron status during an iron-biofortified bean feeding trial improves work efficiency in iron-depleted, sedentary women. This trial was registered at clinicaltrials.gov as NCT01594359.
Project description:Iron deficiency is a major public health problem worldwide, with the highest burden among children. The objective of this randomized efficacy feeding trial was to determine the effects of consuming iron-biofortified beans (Fe-Beans) on the iron status in children, compared to control beans (Control-Beans). A cluster-randomized trial of biofortified beans (Phaseolus vulgaris L), bred to enhance iron content, was conducted over 6 months. The participants were school-aged children (n = 574; 5?12 years), attending 20 rural public boarding schools in the Mexican state of Oaxaca. Double-blind randomization was conducted at the school level; 20 schools were randomized to receive either Fe-Beans (n = 10 schools, n = 304 students) or Control-Beans (n = 10 schools, n = 366 students). School administrators, children, and research and laboratory staff were blinded to the intervention group. Iron status (hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), total body iron (TBI), inflammatory biomarkers C-reactive protein (CRP) and -1-acid glycoprotein (AGP)), and anthropometric indices for individuals were evaluated at the enrollment and at the end of the trial. The hemoglobin concentrations were adjusted for altitude, and anemia was defined in accordance with age-specific World Health Organization (WHO) criteria (i.e., Hb <115 g/L for <12 years and Hb <120 g/L for 12 years). Serum ferritin concentrations were adjusted for inflammation using BRINDA methods, and iron deficiency was defined as serum ferritin at less than 15.0 µg/L. Total body iron was calculated using Cook's equation. Mixed models were used to examine the effects of Fe-Beans on hematological outcomes, compared to Control-Beans, adjusting for the baseline indicator, with school as a random effect. An analysis was conducted in 10 schools (n = 269 students) in the Fe-Beans group and in 10 schools (n = 305 students) in the Control-Beans group that completed the follow-up. At baseline, 17.8% of the children were anemic and 11.3% were iron deficient (15.9%, BRINDA-adjusted). A total of 6.3% of children had elevated CRP (>5.0 mg/L), and 11.6% had elevated AGP (>1.0 g/L) concentrations at baseline. During the 104 days when feeding was monitored, the total mean individual iron intake from the study beans (Fe-bean group) was 504 mg (IQR: 352, 616) over 68 mean feeding days, and 295 mg (IQR: 197, 341) over 67 mean feeding days in the control group (p < 0.01). During the cluster-randomized efficacy trial, indicators of iron status, including hemoglobin, serum ferritin, soluble transferrin receptor, and total body iron concentrations improved from the baseline to endline (6 months) in both the intervention and control groups. However, Fe-Beans did not significantly improve the iron status indicators, compared to Control-Beans. Similarly, there were no significant effects of Fe-Beans on dichotomous outcomes, including anemia and iron deficiency, compared to Control-Beans. In this 6-month cluster-randomized efficacy trial of iron-biofortified beans in school children in Mexico, indicators of iron status improved in both the intervention and control groups. However, there were no significant effects of Fe-Beans on iron biomarkers, compared to Control-Beans. This trial was registered at clinicaltrials.gov as NCT03835377.
Project description:Iron deficiency is the most common micronutrient deficiency globally and represents a major threat to public health. Biofortification, the process of enhancing micronutrient content and bioavailability in staple crops, represents an exciting sustainable food-based strategy to combat and prevent iron deficiency, particularly in resource-limited settings. In this review, we examine the evidence to date of the efficacy of iron-biofortified staple food crops on improving iron status in at-risk populations, including rice, pearl millet, and beans. Three randomized efficacy trials of iron biofortified interventions were included in this analysis, conducted in the Philippines, India, and Rwanda. Iron status (hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), C-reactive protein, alpha-1 acid glycoprotein) was measured at enrollment, midline, and endline in each trial. The primary outcomes evaluated included hemoglobin, serum ferritin, sTfR, and total body iron. A meta-analysis using random effects models was conducted to examine the effects of interventions on hematological outcomes, with the DerSimonian and Laird method. In meta-analyses of data from the three trials, iron-biofortified interventions significantly increased serum ferritin concentrations and total body iron. Evidence to date from randomized trials suggest that iron-biofortified crops are an efficacious intervention to improve iron status. In particular, findings from all three trials also indicate that the effects of biofortified staple crops were highest among individuals who were iron deficient at baseline, suggesting the greatest potential to benefit. Assessment of functional outcomes and consideration of other high-risk populations such as young children, are warranted to elucidate the impact of iron-biofortified interventions on human health.
Project description:Iron (Fe) deficiency is a highly prevalent micronutrient insufficiency predominantly caused by a lack of bioavailable Fe from the diet. The consumption of beans as a major food crop in some populations suffering from Fe deficiency is relatively high. Therefore, our objective was to determine whether a biofortified variety of cream seeded carioca bean (Phaseolus vulgaris L.) could provide more bioavailable-Fe than a standard variety using in-vivo (broiler chicken, Gallus gallus) and in-vitro (Caco-2 cell) models. Studies were conducted under conditions designed to mimic the actual human feeding protocol. Two carioca-beans, a standard (G4825; 58 ?g Fe/g) and a biofortified (SMC; 106 ?g Fe/g), were utilized. Diets were formulated to meet the nutrient requirements of Gallus gallus except for Fe (33.7 and 48.7 ?g Fe/g, standard and biofortified diets, respectively). In-vitro observations indicated that more bioavailable-Fe was present in the biofortified beans and diet (P<0.05). In-vivo, improvements in Fe-status were observed in the biofortified bean treatment, as indicated by the increased total-body-Hemoglobin-Fe, and hepatic Fe-concentration (P<0.05). Also, DMT-1 mRNA-expression was increased in the standard bean treatment (P<0.05), indicating an upregulation of absorption to compensate for less bioavailable-Fe. These results demonstrate that the biofortified beans provided more bioavailable Fe; however, the in vitro results revealed that ferritin formation values were relatively low. Such observations are indicative of the presence of high levels of polyphenols and phytate that inhibit Fe absorption. Indeed, we identified higher levels of phytate and quercetin 3-glucoside in the Fe biofortified bean variety. Our results indicate that the biofortified bean line was able to moderately improve Fe-status, and that concurrent increase in the concentration of phytate and polyphenols in beans may limit the benefit of increased Fe-concentration. Therefore, specific targeting of such compounds during the breeding process may yield improved dietary Fe-bioavailability. Our findings are in agreement with the human efficacy trial that demonstrated that the biofortified carioca beans improved the Fe-status of Rwandan women. We suggest the utilization of these in vitro and in vivo screening tools to guide studies aimed to develop and evaluate biofortified staple food crops. This approach has the potential to more effectively utilize research funds and provides a means to monitor the nutritional quality of the Fe-biofortified crops once released to farmers.
Project description:Staple food crops tend to be low in micronutrients; therefore, individuals whose diets rely heavily on them can suffer from micronutrient deficiency. Biofortification addresses this issue through the breeding of staple crops that are micronutrient-dense and high yielding. One such crop is iron-biofortified beans. Ten iron-biofortified bean varieties were released between 2010 and 2012 in Rwanda, a country with high rates of bean production and consumption, to address iron deficiency. This study evaluates the effect of the most widely adopted of these varieties, RWR2245, on household yield, land cultivated under beans, bean consumption, purchases, and sales. Because the adoption decision could be endogenous, we use a control function approach to quantify the impacts of adoption. RWR2245 provides a yield gain of 20%-49% over traditional bush bean varieties. In our preferred model specification, we find that over a 12-month period, growing RWR2245 for at least one out of two annual growing seasons increases the length of time beans are consumed from own production by 0.64 months (19-20 days), reduces the length of time beans are purchased for consumption by 0.73 months (22-23 days), and increases the probability of selling beans by 12%. Adoption can thus improve household nutrition via two channels: primarily by increasing iron intake via substituting biofortified harvested beans for less nutrient-dense beans from the market, and additionally by increasing household income that can be spent on nutritious foods through the reduction in bean purchases and increased likelihood of selling beans. Moreover, the sale of iron-biofortified beans implies the availability of iron-dense food in markets, also benefiting households that purchase beans. These findings are promising for the continued adoption of iron-biofortified beans in Rwanda and elsewhere and provide evidence that biofortified crops are an effective investment for nutrition, food security, and poverty reduction.
Project description:Biofortification is an effective method to improve the nutritional content of crops and nutritional intake. Breeding for higher micronutrient mineral content in beans is correlated with an increase in phytic acid, a main inhibitor of mineral absorption in humans. Low phytic acid (lpa) beans have a 90% lower phytic acid content compared to conventional beans. This is the first study to investigate mineral and total phytic acid retention after preparing common household recipes from conventional, biofortified and lpa beans. Mineral retention was determined for two conventional, three biofortified and two lpa bean genotypes. Treatments included soaking, boiling (boiled beans) and refrying (bean paste). The average true retention of iron after boiling was 77.2-91.3%; for zinc 41.2-84.0%; and for phytic acid 49.9-85.9%. Soaking led to a significant decrease in zinc and total phytic acid after boiling and refrying, whereas for iron no significant differences were found. lpa beans did not exhibit a consistent pattern of difference in iron and phytic acid retention compared to the other groups of beans. However, lpa beans had a significantly lower retention of zinc compared to conventional and biofortified varieties (p < 0.05). More research is needed to understand the underlying factors responsible for the differences in retention between the groups of beans, especially the low retention of zinc. Combining the lpa and biofortification traits could further improve the nutritional benefits of biofortified beans, by decreasing the phytic acid:iron and zinc ratio in beans.
Project description:Micronutrient deficiencies, also known as hidden hunger, affect two billion people worldwide, curtailing their ability to lead healthy, productive lives. Biofortified staple crops, bred to be rich in micronutrient content, are a cost-effective and scalable solution to alleviating micronutrient deficiency, particularly among rural households who consume what they produce. Delivery of biofortified planting material in Rwanda began in 2012, and it is important to learn from the efforts undertaken to date to inform the design of higher impact - lower cost delivery strategies for scaling up these crops. In this paper, we use a nationally representative household survey of bean producers and delivery data from seven consecutive seasons and apply duration analysis to estimate the impact of different delivery approaches on household time to adoption, disadoption and readoption of iron-biofortified beans in Rwanda. Proximity to formal delivery via sales of small packets of planting material quickens adoption and readoption, while delivery of larger quantities of planting material to small-scale producers within a village slows disadoption of iron-biofortified beans. Informal dissemination within social networks and access to extension are also major drivers of rapid adoption. In addition, households whose main decision maker for bean production is a woman, has some formal education, and more years of experience growing beans disadopt iron-biofortified beans more slowly than other households. These findings provide evidence that current efforts to promote iron-biofortified crops have been successful and are expected to inform future development of sustainable and cost-effective delivery models for biofortified crops in Rwanda and elsewhere.
Project description:<h4>Background</h4>Inadequate nutritional status contributes to substantial losses in human health and productivity globally. A multiple biofortified food crop trial targeting iron, zinc, and vitamin A deficiencies among young children and their breastfeeding mothers is being conducted in India.<h4>Objective</h4>We sought to determine the relative iron bioavailability from biofortified and conventional crops and crop combinations representative of a cyclical menu using crops targeted for inclusion in the feeding trial.<h4>Methods</h4>Crops were procured from India, cooked, freeze-dried, and analyzed with an established in vitro digestion/Caco-2 iron bioavailability assay using a fixed sample weight. Crop proportions representative of meals planned for the human study were determined and combined such that samples included either all biofortified or all control crops. Crops were analyzed as single crops (<i>n </i>= 4) or crop combinations (<i>n </i>= 7) by variety (biofortified or control) in triplicate. The primary outcome was iron uptake measured by Caco-2 ferritin production normalized to total Caco-2 protein (nanograms of ferritin/milligrams of cell protein) analyzed for effects of crop variety and crop proportion using generalized linear models.<h4>Results</h4>Biofortified pearl millet alone demonstrated higher iron uptake than conventional varieties (5.01 ± 1.66 vs. 2.17 ± 0.96; <i>P</i> = 0.036). Addition of sweet potato or sweet potato + pulse improved iron uptake for all proportions tested in control varieties and select proportions for biofortified varieties (<i>P</i> ≤ 0.05). Two multiple crop combinations demonstrated modestly higher iron uptake from biofortified crops.<h4>Conclusions</h4>Optimizing total iron delivery should consider matrix effects, processing, and promoters/inhibitors of iron absorption in addition to total iron concentration. Future directions include evaluating recipes as prepared for consumption and comparison against human iron bioavailability studies.