Zinc Absorption From SQ-LNS With and Without Phytase
Condition: Individuals at Risk of Zinc Deficiency
Study type: Interventional

Summary: 
      Background: Community based-intervention trials conducted among infants and young children in
      low- and middle-income countries have found that zinc supplementation of young children (in
      the form of liquid supplements or dispersible tablets) increases linear growth and weight
      gain, and reduces the prevalence of diarrhea and respiratory infections, and lowers all-cause
      mortality. Aside from supplements, additional dietary zinc can also be provided through
      "home-fortification" of complementary foods with small-quantity lipid-based nutrient
      supplements (SQ-LNS; 20g/d), which are typically formulated as a peanut-based paste enriched
      with a vitamin and mineral complex containing 8 mg elemental zinc (as ZnSO4). However, the
      efficacy of LNS as a delivery vehicle for preventive zinc supplementation remains uncertain.
      Two recent studies, which provided LNS containing 4-10 mg Zn daily for 6-9 months found no
      significant differences in plasma zinc concentrations at the end of the intervention period
      compared to placebo.

      This lack of response may be due to the reduced absorption of zinc when it is part of a
      complex food matrix and provided with cereal-based meals; both SQ-LNS and cereal grains
      contain moderate to high concentrations of phytate, the main dietary factor known to
      substantially reduce zinc absorption. The addition of exogenous phytases is an efficacious
      strategy to reduce the phytate content of foods, and increase the bioavailability of dietary
      zinc; however, the efficacy of this approach has not yet been demonstrated for SQ-LNS.

      Objective: The overall objective of the study is to assess the efficacy of adding exogenous
      phytase to SQ-LNS by investigating intra-individual differences in the fractional absorption
      of zinc (FAZ) among children who receive additional dietary zinc (8 mg/d) from SQ-LNS with or
      without phytase.

      Trial approach: The study will be a double-blind randomized controlled clinical trial,
      designed to permit within-child comparisons of zinc absorption from SQ-LNS, with or without
      exogenous phytase, by using the triple stable-isotope ratio tracer technique. The clinical
      study will enroll 34 children between the ages of 18-23 months. The main outcome of interest
      is the intra-individual difference in the FAZ from porridge-based meals containing SQ-LNS
      with and without phytase. Up to an' additional 36 children will be enrolled in a pilot
      feeding study to determine portion sizes of study meals.

      Trial setting: Keneba, The Gambia

      Trial interventions:

      The SQ-LNS (20g) used in this study will be provided by Nutriset, S.A.S. The exogenous
      phytase (DSM phytase Tolerase 20000G) is derived from Aspergillus niger; phytase will be
      added to the SQ-LNS during the production phase, and will be enzymatically active in vivo at
      the time of consumption.

      Feeding Protocol and Study Diet: The study diet for the 2day absorption study will consist of
      the following: 1) Two stable-isotope labeled test meals per day (porridge made from locally
      procured non-fermented cereal, mixed with 10 g of SQ-LNS), with children randomized to
      receive either SQ-LNS with phytase or SQ-LNS without phytase on the first day and the
      alternative product on the second; 2) One additional standardized meal per day (e.g. rice
      with sauce); 3) Low-zinc, low-phytate food (e.g. bananas) consumed ad libitum if requested
      (with the exception of 1 hour before and 2 hours after each test meal). Children will be fed
      by their caregivers under supervision by a study fieldworker. The SQ-LNS product (without
      phytase) will be provided to children twice per day for one day prior to the start of the
      stable isotope absorption studies, in order to habituate children to the study diet and
      location. Children will attend the study clinic daily for four days and will be enrolled in
      the study for a total of ten days.

      Zinc absorption studies: The FAZ of zinc will be measured by a triple-isotope tracer ratio
      technique, using orally administered extrinsic labels (Zn-67 and Zn-70) and intravenous
      Zn-68. Urine samples, collected pre- and post-isotope administration (d 1, 5-9) will be
      analyzed for zinc isotope ratios by ICP-MS. FAZ will be calculated based on the mean isotopic
      ratios obtained from the enriched urine samples, and based on the tracer:tracee ratio method.
      TAZ will be calculated by multiplying FAZ by total zinc intake from the test meals.

      Data Collection: The following information will be collected from each subject: brief medical
      history; physical examination; weight and height; daily morbidity and pre-intervention blood
      sampling for hemoglobin, complete blood count and plasma zinc concentration, malaria and
      systemic inflammation (C-reactive protein and α-1-acid glycoprotein).
    


Intervention name(s): the nutritional supplement to be used in this trial is a SQ-LNS; lipid-based nutrient supplement (SQ-LNS) with phytase; 0.9 mg isotopically enriched 67Zn,0.30 mg isotopically enriched 70Zn, 0.60 mg non-enriched zinc; 1 mg isotopically enriched 68Zn
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Small quantity lipid nutrient supplement (SQ-LNS) containing 6 mg iron and 8 mg zinc per 20 g sachet (per day; • Small quantity lipid nutrient supplement (SQ-LNS) containing 6 mg iron and 8 mg zinc per 20 g sachet (per day). Exogenous phytase (projected concentration ~500 FTU/20 g SQ-LNS) added during manufacturing; delivered orally in sugar solution; administered intravenously
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: zinc deficiency; zinc absorption