Determination of Pre-Absorptive Dissociation of Zinc From a Zinc Amino Acid Complex in Healthy Men
Condition: Fractional Zinc Absorption
MeSH terms: Dissociative Disorders
Study type: Interventional

Summary: 
      Zinc may be absorbed from diet via zinc transporter mediated pathways, or, when coupled with
      amino acids, via amino acid transporter pathways. When zinc is coupled with amino acids in
      diet, it may dissociate from those amino acids in the acidic environment of the stomach prior
      to entering the small intestine. An experimentally-determined value for any pre-absorptive
      dissociation of zinc from a zinc amino acid complex (ZnAA) is necessary for the accurate
      compartmental modeling of zinc metabolism when provided as ZnAA compared with ionic zinc,
      which the investigators will perform in a future study. The current study will allow us to
      determine the dissociation of zinc from ZnAA, while serving as a pilot test of a novel
      technique to determine for the first time an individual's zinc transport kinetics.
    

Detailed description: 
      An experimentally-determined value for any pre-absorptive dissociation of zinc from ZnAA is
      necessary for the accurate compartmental modeling of zinc metabolism when provided as ZnAA
      compared with zinc chloride, which the investigators will perform in a future study.

      The current study will allow us to determine the pre-absorptive dissociation of zinc from
      ZnAA, while serving as a pilot test of a novel technique to determine for the first time an
      individual's zinc transport kinetics. Since zinc absorption kinetics follow a saturable
      process, the zinc transport maximum (Tr_max) and transport rate (K_Tr) can be determined by
      fitting Hill transport equation to measurements of absorbed zinc at 3 or more levels of zinc
      intake (mg zinc/d):

      Total Absorbed Zinc (TAZ) = (Zinc Intake * Tr_max) / (Zinc Intake + K_Tr)

      Although population data have been used to estimate zinc transport kinetics (Tran, et al.
      AJCN 2004), Tr_max and K_tr have never been determined in individual subjects. The
      investigators plan to determine the fractional zinc absorption (FZA) from multiple levels of
      dietary zinc in rapid succession (Chung, et al. AJCN 2004) and, therefore, estimate an
      individual's transport maximum and rate, Tr_max and K_Tr. Once Tr_max and K_Tr are known, the
      FZA can be used to determine an unknown zinc intake from zinc chloride and any zinc
      dissociated from the ZnAA complex using the following equation:

      Zinc Intake = (Tr_max / FZA) - K_Tr

      Since zinc that dissociates from the ZnAA complex will compete for absorption with the
      inorganic zinc stable isotopic oral tracer (70-zinc chloride), reducing the amount of that
      tracer absorbed, the investigators can therefore determine the total zinc intake (the sum of
      the known zinc in the controlled study diet and the unknown quantity of zinc dissociated from
      ZnAA pre-absorption) based on the transport kinetics (FZA, Tr_max and KTr).

      In other words, for the meal with added ZnAA, the zinc intake is the sum of the zinc in the
      test meal (3.6 mg zinc and 0.4 mg 70-Zn tracer) and the zinc that dissociates from the ZnAA
      complex pre-absorption. Since the intact ZnAA (i.e. that zinc that does not dissociate
      pre-absorption from the ZnAA complex) is absorbed by a different transport mechanism (Sauer,
      et al. Biometals 2017), it does not compete with the stable isotope tracer for absorption via
      zinc cation transporters and is, therefore, not part of the "zinc intake" for the purpose of
      these calculations.

      If the hypothesized 20% dissociation is correct (i.e. 3 mg zinc dissociated from an initial
      15 mg ZnAA), the total amount of ionic zinc will be 7 mg (the 3.6 mg base diet, 0.4 mg zinc
      stable isotope tracer, and 3 mg dissociated zinc), and the FZA will therefore be the same as
      that from a 7 mg test diet (the 3.6 mg base diet, 0.4 mg zinc tracer, and 3 mg zinc as zinc
      chloride).
    

Intervention name(s): Zinc amino acid complex
Intervention type(s): Other
Intervention description(s): Zinc in the form of a Zinc Amino Acid Complex (ZnAA) is provided with a test diet, and the amount of zinc that dissociates from the ZnAA and is thus absorbed via an ionic zinc transport pathway is determined based on the Hill transport kinetics for the respective subject.
Intervention model: Single Group Assignment
Intervention model description: Nonlinear regression of fractional zinc absorption from 3 test diets using the Hill transport equation, and determination of an unknown amount of zinc based on fractional absorption from a single test diet. Order of the four test diets is randomized, with the constraint that the same oral zinc stable isotope tracer is not given on consecutive days.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: zinc; absorption; kinetics; amino acid chelate