title: Efficacy of highly bioavailable zinc from fortified water: a randomized controlled trial in rural Beninese children.
abstract: BACKGROUND
  Zinc deficiency and contaminated water are major contributors to diarrhea in developing countries. Food fortification with zinc has not shown clear benefits, possibly because of low zinc absorption from inhibitory food matrices. We used a novel point-of-use water ultrafiltration device configured with glass zinc plates to produce zinc-fortified, potable water.
  
  
  OBJECTIVE
  The objective was to determine zinc bioavailability from filtered water and the efficacy of zinc-fortified water in improving zinc status.
  
  
  METHODS
  In a crossover balanced study, we measured fractional zinc absorption (FAZ) from the zinc-fortified water in 18 healthy Swiss adults using zinc stable isotopes and compared it with zinc-fortified maize porridge. We conducted a 20-wk double-blind randomized controlled trial (RCT) in 277 Beninese school children from rural settings who were randomly assigned to receive a daily portion of zinc-fortified filtered water delivering 2.8 mg Zn (Zn+filter), nonfortified filtered water (Filter), or nonfortified nonfiltered water (Pump) from the local improved supply, acting as the control group. The main outcome was plasma zinc concentration (PZn), and the 3 groups were compared by using mixed-effects models. Secondary outcomes were prevalence of zinc deficiency, diarrhea prevalence, and growth.
  
  
  RESULTS
  Geometric mean (-SD, +SD) FAZ was 7-fold higher from fortified water (65.9%; 42.2, 102.4) than from fortified maize (9.1%; 6.0, 13.7; P < 0.001). In the RCT, a significant time-by-treatment effect on PZn (P = 0.026) and on zinc deficiency (P = 0.032) was found; PZn in the Zn+filter group was significantly higher than in the Filter (P = 0.006) and Pump (P = 0.025) groups. We detected no effect on diarrhea or growth, but our study did not have the duration and power to detect such effects.
  
  
  CONCLUSIONS
  Consumption of filtered water fortified with a low dose of highly bioavailable zinc is an effective intervention in children from rural African settings. Large community-based trials are needed to assess the effectiveness of zinc-fortified filtered water on diarrhea and growth. These trials were registered at clinicaltrials.gov as NCT01636583 and NCT01790321.
authors.affiliation: Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland; valeria.galetti@hest.ethz.ch.
authors.forename: Valeria
authors.identifier: http://orcid.org/0000-0002-7867-9960
authors.initials: V
authors.lastname: Galetti
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, Netherlands;
authors.forename: Prosper
authors.identifier: http://orcid.org/0000-0003-3824-2788
authors.initials: P
authors.lastname: Kujinga
authors.affiliation: Laboratory of Human Nutrition, Faculty of Agricultural Sciences, Abomey-Calavi University, Cotonou, Benin;
authors.forename: Comlan Evariste S
authors.initials: CE
authors.lastname: Mitchikpè
authors.affiliation: Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland;
authors.forename: Christophe
authors.identifier: http://orcid.org/0000-0001-6675-3708
authors.initials: C
authors.lastname: Zeder
authors.affiliation: Clinical Trials Center, Center for Clinical Research, University Hospital of Zurich, Zurich, Switzerland; and.
authors.forename: Fabian
authors.identifier: http://orcid.org/0000-0002-9685-1752
authors.initials: F
authors.lastname: Tay
authors.affiliation: Natitingou Health Zone, Ministry of Health, Natitingou, Benin.
authors.forename: Félicien
authors.initials: F
authors.lastname: Tossou
authors.affiliation: Laboratory of Human Nutrition, Faculty of Agricultural Sciences, Abomey-Calavi University, Cotonou, Benin;
authors.forename: Joseph D
authors.identifier: http://orcid.org/0000-0002-3677-4986
authors.initials: JD
authors.lastname: Hounhouigan
authors.affiliation: Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland;
authors.forename: Michael B
authors.initials: MB
authors.lastname: Zimmermann
authors.affiliation: Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland;
authors.forename: Diego
authors.identifier: http://orcid.org/0000-0002-7366-2182
authors.initials: D
authors.lastname: Moretti
mesh_terms: D000328:Adult; D001541:Benin / Q000453:epidemiology; D002648:Child; D002664:Child Nutritional Physiological Phenomena; D018592:Cross-Over Studies; D003677:Deficiency Diseases / Q000178:diet therapy / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D003967:Diarrhea / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D004311:Double-Blind Method; D060766:Drinking Water / Q000008:administration & dosage*; D005527:Food, Fortified; D006801:Humans; D007408:Intestinal Absorption; D008137:Longitudinal Studies; D010949:Plasma / Q000737:chemistry; D015995:Prevalence; D012423:Rural Health; D016037:Single-Blind Method; D013557:Switzerland; D014462:Ultrafiltration; D014556:Urine / Q000737:chemistry; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use; D015033:Zinc Isotopes
chemical_list: D060766:Drinking Water; D015033:Zinc Isotopes; D015032:Zinc
keywords: Benin; school-age children; water fortification; zinc absorption; zinc fortification