Development of a Compartmental Model for Studying Vitamin A Kinetics and Status in Theoretical Lactating Women

Lopez-Teros, Veronica
Green, Michael H
Avila-Prado, Jessica
Green, Joanne B

¹ Department of Chemical and Biological Sciences, University of Sonora, Hermosillo, Mexico
² Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA, USA

Address correspondence to MHG (E-mail: [email protected]).

Received January 15, 2022; revision received February 18, 2022; Accepted March 23, 2022

JA-P was supported by a Mexican National Council for Science and Technology (CONACyT) scholarship; publication costs were paid by the International Atomic Energy Agency (Project Number 24817). This work was done in anticipation of studies being implemented by several research groups under funding from the International Atomic Energy Agency (Project Number 24817).

Author disclosures: The authors report no conflicts of interest.

Supplemental Tables 1-4, Supplemental WinSAAM Deck, and Supplemental Figures 1 and 2 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/.

VL-T and MHG contributed equally to this work as first authors.

Abbreviations used: FSD, fractional standard deviation; L, lactating; NL, nonlactating; RBP, retinol-binding protein-4; RID, retinol isotope dilution; SA_m, specific activity of vitamin A (retinol + retinyl esters) in milk; SA_p, specific activity of retinol in plasma; SA_s, specific activity of vitamin A (retinol + retinyl esters) in stores; TBS, vitamin A total body stores; WinSAAM, Windows version of the Simulation, Analysis and Modeling software.

The Journal of Nutrition 152(7):p 1621-1628, July 2022. | DOI: 10.1093/jn/nxac078

ABSTRACT

Background:

Low vitamin A status and suboptimal milk vitamin A concentrations are problems in many populations worldwide. However, limited research has been done on whole-body vitamin A kinetics in women of reproductive age, especially during lactation.

Objectives:

Goals were to develop compartmental models describing retinol kinetics in theoretical nonlactating (NL) and lactating (L) women and to determine whether the retinol isotope dilution (RID) method accurately predicted vitamin A total body stores (TBS) in the groups and individuals.

Methods:

We adapted 12 previously-used theoretical females with assigned values for retinol kinetic parameters and TBS (225-1348 μmol); subjects were NL or L (nursing one 3- to 6-mo-old infant) during 49-d kinetic studies after isotope dosing. We used an established compartmental model, adding a compartment for chylomicrons and, for L, another for mammary gland milk with inputs from holo-retinol-binding protein and chylomicron retinyl esters and output to milk. Using compartmental analysis, we simulated tracer responses in compartments of interest and calculated TBS using the RID equation TBS = FaS/SA_p [Fa, fraction of dose in stores; S, retinol specific activity in plasma/specific activity in stores; SA_p, specific activity of retinol in plasma].

Results:

Models for both groups were well identified. Simulated plasma tracer responses were similar for NL and L, with L always below NL; milk tracer paralleled plasma from 10 d postdosing. Geometric mean FaS ratios (L/NL) were ˜0.75 during days 2-30. Using appropriate group FaS, RID provided accurate TBS predictions for >80% of NL and L subjects after day 18 when CV% for FaS was ˜10%.

Conclusions:

These new physiologically-based models for vitamin A kinetics may be useful for future research in women of reproductive age. Results indicate that, in groups like these, RID to assess an individual's vitamin A status should be done at 21-28 d after isotope dosing.