Iron-fortified lentils to improve iron (Fe) status among adolescent girls in Bangladesh - study protocol for a double-blind community-based randomized controlled trial

Fakir Md Yunus, Chowdhury Jalal, Kaosar Afsana, Rajib Podder, Albert Vandenberg, Diane M DellaValle, Fakir Md Yunus, Chowdhury Jalal, Kaosar Afsana, Rajib Podder, Albert Vandenberg, Diane M DellaValle

Abstract

Background: Lentils are generally considered to be a nutrient-dense food, and a good source of iron (Fe). This study aims to establish novel evidence of the effectiveness of the consumption of Fe-fortified lentils in improving the body Fe status and thus cognitive performance in non-pregnant adolescent girls in rural Bangladesh, compared to consumption of ordinary lentils.

Methods: We have designed a double-blind (both trial participants and outcome assessors), community-based, cluster-randomized controlled trial among 1260 Bangladeshi adolescent girls between the ages of 10-17 years who are non-smoking, not married, not pregnant, not breastfeeding, and generally healthy at the time of enrollment. The intervention will include three arms who will receive: (1) Fe-fortified lentils; (2) unfortified lentils; or (3) usual intake. Participants will be served a thick preparation of cooked Fe-fortified lentils (37.5 g raw lentils, approximately 200 g cooked lentils) 5 days per week for 85 feeding days (around 4 months) using a locally acceptable recipe. Lentils were fortified with Fe in the laboratory at the Department of Plant Sciences at the University of Saskatchewan in Canada. A subsample of participants (n = 360) will be randomly invited to be included in cognitive testing.

Discussion: Data on socio-demographic characteristics, household food security status, adolescent food habits and cognitive testing will be collected at baseline and endline (4 months). Venous blood samples will be collected at baseline, midline (2 months) and endline to measure adolescents' Fe status. Computerized cognitive testing will include five common measures of attentional (three of attention) and mnemonic functioning (two of memory) carried out using DMDX software. The results of this study will be used to garner support for and to substantiate large-scale production and market expansion of Fe-fortified lentils, and will contribute to knowledge about how to enhance Fe status in adolescents worldwide in resource-poor settings, using staple food crops.

Trial registration: ClinicalTrials.gov NCT03516734 . Registered on 24 May 2018.

Keywords: Food technology; Food-based approach; Fortification; Iron (Fe); Micronutrient deficiency.

Conflict of interest statement

Ethics approval and consent to participate

The study received ethical approval from the University of Saskatchewan, Canada (reference Bio#17–177), Marywood University, USA (reference IRB#1139116–2) and the Bangladesh Medical Research Council (BMRC: reference BMRC/NREC/2016–2019/455). Each ethical body will be informed separately about any changes to the trial protocol. Adolescents and their families will be informed separately about the purpose of the study, the procedures to be used, and the benefits to be derived from the study. Two separate written informed consent forms for parents/guardians and participants (adolescents) will be a prerequisite to recruitment of the subjects. Adolescents with severe anemia will be symptomatically treated for Fe deficiency. The study will conform to all regulations of the Government of Bangladesh (GoB). A mid-term assessment of biochemical outcomes will be independently analyzed by the members of the Data Safety Monitoring Board (DSMB) to detect any adverse outcome. All participants will receive explanations about the objectives, importance, risks, and benefits of the research before recruitment. Participation will be completely voluntary, and appropriate written informed consent will be obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests. CJ is an employee of Nutrition International (NI), which provided partial funding for the implementation of the study. However, the funding was provided after the study was conceptualized and the proposal drafted.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of iron-fortified lentil feeding trial
Fig. 2
Fig. 2
Flow chart for the 85-day iron-fortified lentil feeding trial. Demographics, food frequency questionnaire (FFQ), anthropometrics, blood test, cognitive assessment

References

    1. Rahman S, Ahmed T, Rahman AS, Alam N, Ahmed AS, Ireen S, et al. Determinants of iron status and Hb in the Bangladesh population: the role of groundwater iron. Public Health Nutr. 2016;19:1862–74 Available from: .
    1. ICDDRB, UNICEF Bangladesh, GAIN, Institute of Public Health and Nutrition. National Micronutrients Status Survey 2011-12: Final report [Internet]. Dhaka, Bangladesh; 2013. Available from: .
    1. McNulty H, Eaton-Evans J, Cran G, Woulahan G, Boreham C, Savage JM, et al. Nutrient intakes and impact of fortified breakfast cereals in schoolchildren. Arch Dis Child [Internet] BMJ. 1996;75:474–481. doi: 10.1136/adc.75.6.474.
    1. Zimmermann MB, Hurrell RF. Nutritional iron deficiency. Lancet. 2007;370:511–20 Available from: .
    1. Huma N, Salim-Ur-Rehman AFM, Murtaza MA, Sheikh MA. Food fortification strategy–preventing iron deficiency anemia: a review. Crit Rev Food Sci Nutr. 2007;47:259–65 Available from: .
    1. Hurrell RF. Preventing iron deficiency through food fortification. Nutr Rev. 1997;55:210–222. doi: 10.1111/j.1753-4887.1997.tb01608.x.
    1. Thavarajah D, Thavarajah P, Sarker A, Vandenberg A. Lentils (Lens culinaris medikus subspecies culinaris): a whole food for increased iron and zinc intake. J Agric Food Chem. 2009;57:5413–5419. doi: 10.1021/jf900786e.
    1. Thavarajah D, Thavarajah P, Wejesuriya A, Rutzke M, Glahn RP, Combs GF, et al. The potential of lentil (Lens culinaris L.) as a whole food for increased selenium, iron, and zinc intake: preliminary results from a 3 year study. Euphytica. 2011;180:123–128. doi: 10.1007/s10681-011-0365-6.
    1. DellaValle DM, Thavarajah D, Thavarajah P, Vandenberg A, Glahn RP. Lentil (Lens culinaris L.) as a candidate crop for iron biofortification: is there genetic potential for iron bioavailability? F Crop Res. 2013;144:119–25 Available from: .
    1. Thavarajah D, Thavarajah P, Sarker A, Materne M, Vandemark G, Shrestha R, et al. A global survey of effects of genotype and environment on selenium concentration in lentils (Lens culinaris L.): implications for nutritional fortification strategies. Food Chem. 2011;125:72–76. doi: 10.1016/j.foodchem.2010.08.038.
    1. Thavarajah P, Thavarajah D, Vandenberg A. Low phytic acid lentils (Lens culinaris L.): a potential solution for increased micronutrient bioavailability. J Agric Food Chem. 2009;57:9044–9049. doi: 10.1021/jf901636p.
    1. DellaValle DM, Vandenberg A, Glahn RP. Seed coat removal improves iron bioavailability in cooked lentils: studies using an in vitro digestion/Caco-2 cell culture model. J Agric Food Chem. 2013;61:8084–8089. doi: 10.1021/jf4022916.
    1. Scott SP, Murray-Kolb LE, Wenger MJ, Udipi SA, Ghugre PS, Boy E, et al. Cognitive performance in Indian school-going adolescents is positively affected by consumption of iron-biofortified pearl millet: a 6-month randomized controlled efficacy trial. J Nutr. 2018; Available from: .
    1. Murray-Kolb LE, Wenger MJ, Scott SP, Rhoten SE, Lung’aho MG, Haas JD. Consumption of iron-biofortified beans positively affects cognitive performance in 18- to 27-year-old Rwandan female college students in an 18-week randomized controlled efficacy trial. J Nutr. 2017;147:2109–17 Available from: .
    1. Yunus F. Feasibility of field implementation of fortified lentils to improve iron (Fe) status of adolescent girls in Bangladesh [Internet]. University of Saskatchewan; 2018. Available from: . [cited 2018 May 27].
    1. BRAC ranked top global NGO of 2018 [Internet]. 2018. Available from: .
    1. Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158:200 Available from: .
    1. Moja LP, Moschetti I, Nurbhai M, Compagnoni A, Liberati A, Grimshaw JM, et al. Compliance of clinical trial registries with the World Health Organization minimum data set: a survey. Trials. 2009;10:56 Available from: .
    1. Podder R, Tar’An B, Tyler RT, Henry CJ, DellaValle DM, Vandenberg A. Iron fortification of lentil (Lens culinaris medik.) to address iron deficiency. Nutrients. 2017;9:1–19. doi: 10.3390/nu9080863.
    1. Donner A, Birkett N, Buck C. Randomization by cluster. Sample size requirements and analysis. Am J Epidemiol. 1981;114:906–914. doi: 10.1093/oxfordjournals.aje.a113261.
    1. Wenger M, Murray-Kolb L, Hammons J, Venkatramanan S, Haas J. Analytic measures of perceptual and cognitive performance in measuring effects of dietary iron repletion. FASEB J. 2011;25:607–20 Available from: .
    1. Rhoten S, Wenger M, Murray-Kolb L, Gahutu J-B, Lung’aho M, Haas J. Brain dynamics and attentional control as a function of body iron status. FASEB J. 2014;28:619–4 Available from: .
    1. Wenger M, Murray-Kolb L, Hammons J, Venkatramanan S, Haas J. Improvements in perceptual and cognitive performance linked to baseline iron status and consumption of a double-fortified salt. FASEB J. 2012;26:114–5 Available from: .
    1. Wenger M, Scott S, Murray-Kolb L, Cooper E, Ghugre P, Udipi S, et al. Changes in brain dynamics as a function of changes in body iron status: effects on attentional function in Indian adolescents following consumption of iron-biofortified pearl millet. FASEB J. 2014;28:389–2 Available from: .
    1. Forster KI, Forster JC. DMDX: A Windows display program with millisecond accuracy. Behav Res Methods Instruments Comput. 2003;35:116–24 Available from: .
    1. Wickens CD, Lee J, Liu Y, Becker SG. An introduction to human factors engineering [Internet]. 2nd ed. New Jersey: Pearson Education, Inc; 2004. Available from: .
    1. Fan J, BD MC, Sommer T, Raz A, Posner MI. Testing the efficiency and independence of attentional networks. J Cogn Neurosci. 2002;14:340–7 Available from: .
    1. Wenger MK, Negash S, Petersen RC, Petersen L. Modeling and estimating recall processing capacity: sensitivity and diagnostic utility in application to mild cognitive impairment. J Math Psychol. 2010;54:73–89 Available from: .
    1. Ebbinghaus H. Über das gedächtnis: untersuchungen zur experimentellen psychologie [Internet]. Leipzig: Duncker & Humblot; 1885. Available from: .
    1. Sternberg S. High-speed scanning in human memory. Science. 1966;153:652–4 Available from: .
    1. Girum T, Wasie A. The effect of deworming school children on anemia prevalence: a systematic review and meta-analysis. Open Nurs J. 2018;12:155–61 Available from: .
    1. Welch VA, Ghogomu E, Hossain A, Awasthi S, Bhutta ZA, Cumberbatch C, et al. Mass deworming to improve developmental health and wellbeing of children in low-income and middle-income countries: a systematic review and network meta-analysis. Lancet Glob Heal. 2017;5:e40–50 Available from: .
    1. Watthanakulpanich D, Maipanich W, Pubampen S, Sa-Nguankiat S, Pooudouang S, Chantaranipapong Y, et al. Impact of hookworm deworming on anemia and nutritional status among children in Thailand. Southeast Asian J Trop Med Public Health. 2011;42:782–92 Available from: .
    1. Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood. 2003;101:3359–3364. doi: 10.1182/blood-2002-10-3071.
    1. Bacopoulou F, Efthymiou V, Landis G, Rentoumis A, Chrousos GP. Waist circumference, waist-to-hip ratio and waist-to-height ratio reference percentiles for abdominal obesity among Greek adolescents. BMC Pediatr. 2015;15 Available from: .
    1. National Health and Nutrition Examination Survey (NHANES). Anthropometry procedures manual. 2007. Available from: .
    1. World Health Organization. Physical status: the use and interpretation of anthropometry. WHO Tech. Rep. Ser. 854. World Health Organization; 1995. Available from: .
    1. Centers for Disease Control and Prevention (CDC). Body mass index BMI (BMI) percentile calculator for child and teen | DNPAO | CDC [Internet]. Centers Dis Control Prev. 2017. Available from: .
    1. Hartung C, Anokwa Y, Brunette W, Lerer A, Tseng C, Borriello G. Open Data Kit: tools to build information services for developing regions [Internet]. Available from: .
    1. Raja A, Tridane A, Gaffar A, Lindquist T, Pribadi K. Android and ODK based data collection framework to aid in epidemiological analysis. Online J Public Health Inform. 2014;5:228 Available from: .

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