title: Bioavailability of enteric-coated microencapsulated calcium during pregnancy: a randomized crossover trial in Bangladesh.
abstract: BACKGROUND
  Prenatal calcium and iron supplements are recommended in settings of low dietary calcium intake and high prevalence of anemia. However, calcium administration may inhibit iron absorption. To overcome calcium-iron interactions, we developed a multi-micronutrient powder containing iron (60 mg), folic acid (400 μg), and calcium carbonate granules microencapsulated with a pH-sensitive enteric coating to delay intestinal release.
  
  
  OBJECTIVE
  We aimed to establish in vivo evidence that enteric-coated (EC) calcium is bioavailable in pregnant women and to explore the dose-responsiveness of fractional calcium absorption (FCA) in pregnancy.
  
  
  METHODS
  This was a randomized crossover trial in pregnant women (26-28 wk of gestation) in Dhaka, Bangladesh. Participants were allocated to 1 of 3 dose groups (500, 1000, or 1500 mg elemental Ca). FCA was estimated in random order for EC and non-EC (control) granules by a dual-stable-isotope method ((44)Ca-labeled granules and intravenous (42)Ca) on the basis of the relative recovery of (44)Ca compared with (42)Ca in urine over 48 h.
  
  
  RESULTS
  Forty-nine participants with FCA for both EC and non-EC granules were included in the primary analyses. FCA geometric means were as follows: 21.8% (500 mg), 9.2% (1000 mg), and 11.7% (1500 mg) for non-EC granules compared with 3.3% (500 mg), 1.2% (1000 mg), and 2.1% for EC granules. Cumulative 48-h FCA of EC calcium was 85% lower (P < 0.001) than that of non-EC calcium, after adjustment for dose. In comparison to 500 mg, the FCA for the 1000-mg dose was 61% lower (P < 0.001) and was 42% lower (P = 0.002) for the 1500-mg dose, after adjustment for formulation.
  
  
  CONCLUSIONS
  A pH-sensitive enteric coating substantially reduced calcium absorption from a prenatal multi-micronutrient powder. In its current formulation, this novel supplement is not suitable for clinical use. FCA was highly dose-dependent, such that doses of 1000 and 1500 mg delivered only negligibly more bioavailable calcium than the 500-mg dose. This trial was registered at clinicaltrials.gov as NCT01678079.
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Roth
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Brendon
authors.initials: B
authors.lastname: Pezzack
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Mahmud
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Steven A
authors.initials: SA
authors.lastname: Abrams
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Munirul
authors.initials: M
authors.lastname: Islam
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Ashley
authors.initials: A
authors.lastname: Aimone Phillips
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Jo-Anna B
authors.initials: JA
authors.lastname: Baxter
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Dimitris
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Keli M
authors.initials: KM
authors.lastname: Hawthorne
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Tahmeed
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: From the Department of Pediatrics and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada (DER, BP, AAP, J-ABB, MCD, and SHZ); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (DER and SHZ); the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh (AAM, MI, and TA); and the USDA/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (SAA and KMH).
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Zlotkin
mesh_terms: D000293:Adolescent; D000328:Adult; D001459:Bangladesh; D001682:Biological Availability; D002118:Calcium / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D006801:Humans; D019266:Iron, Dietary / Q000008:administration & dosage; D016014:Linear Models; D039382:Maternal Nutritional Physiological Phenomena; D018977:Micronutrients / Q000008:administration & dosage; D010281:Parathyroid Hormone / Q000097:blood; D011247:Pregnancy; D014807:Vitamin D / Q000097:blood; D055815:Young Adult
chemical_list: D019266:Iron, Dietary; D018977:Micronutrients; D010281:Parathyroid Hormone; D014807:Vitamin D; D005492:Folic Acid; D002118:Calcium
keywords: calcium; fractional absorption; micronutrient supplementation; pregnancy; stable isotopes