Use of a “Super-child” Approach to Assess the Vitamin A Equivalence of Moringa oleifera Leaves, Develop a Compartmental Model for Vitamin A Kinetics, and Estimate Vitamin A Total Body Stores in Young Mexican Children

Abstract

Worldwide, an estimated 250 million children <5 y old are vitamin A (VA) deficient. In Mexico, despite ongoing efforts to reduce VA deficiency, it remains an important public health problem; thus, food-based interventions that increase the availability and consumption of provitamin A-rich foods should be considered. The objectives were to assess the VA equivalence of H-labeled (MO) leaves and to estimate both total body stores (TBS) of VA and plasma retinol kinetics in young Mexican children. β-Carotene was intrinsically labeled by growing MO plants in a HO nutrient solution. Fifteen well-nourished children (17-35 mo old) consumed puréed MO leaves (1 mg β-carotene) and a reference dose of [C]retinyl acetate (1 mg) in oil. Blood (2 samples/child) was collected 10 times (2 or 3 children each time) over 35 d. The bioefficacy of MO leaves was calculated from areas under the composite "super-child" plasma isotope response curves, and MO VA equivalence was estimated through the use of these values; a compartmental model was developed to predict VA TBS and retinol kinetics through the use of composite plasma [C]retinol data. TBS were also estimated with isotope dilution. The relative bioefficacy of β-carotene retinol activity equivalents from MO was 28%; VA equivalence was 3.3:1 by weight (0.56 μmol retinol:1 μmol β-carotene). Kinetics of plasma retinol indicate more rapid plasma appearance and turnover and more extensive recycling in these children than are observed in adults. Model-predicted mean TBS (823 μmol) was similar to values predicted using a retinol isotope dilution equation applied to data from 3 to 6 d after dosing (mean ± SD: 832 ± 176 μmol; = 7). The super-child approach can be used to estimate population carotenoid bioefficacy and VA equivalence, VA status, and parameters of retinol metabolism from a composite data set. Our results provide initial estimates of retinol kinetics in well-nourished young children with adequate VA stores and demonstrate that MO leaves may be an important source of VA.

A Population-Based (Super-Child) Approach for Predicting Vitamin A Total Body Stores and Retinol Kinetics in Children Is Validated by the Application of Model-Based Compartmental Analysis to Theoretical Data

“…First, we articulated the 7-compartment model shown in Figure 2 on the basis of models previously developed for adults ( 12 , 13 ) and children ( 14 ). Compartments 1–4 (including delay component 3) represent the processing of dietary vitamin A until it is taken up by the hepatocytes (compartment 4) and secreted into plasma compartment 5 as retinol bound to retinol-binding protein.…”

“…Physiologically, compartment 7 likely includes vitamin A in tissues that do not function as long-term storage sites and which turn over vitamin A faster. A faster turning–over extravascular pool has been used to better fit plasma retinol kinetic data in some previous studies ( 11 , 14 ) but not in others ( 12 , 13 ). In light of these previous findings, we generated data for some subjects ( n = 23) using a model with one extravascular storage pool (compartment 6), whereas for others ( n = 27) we used a model with 2 extravascular compartments.…”

“…We previously used a population-based (super-rat/super-child) approach to develop whole-body models of vitamin A metabolism in rats ( 7 , 17 ) and, in collaboration with Haskell et al ( 18 ), to estimate vitamin A fractional catabolic rate and equilibration time in Peruvian children. More recently, we applied a super-child approach in collaboration with Lopez-Teros et al ( 14 ) to estimate vitamin A TBS and to describe retinol kinetics in Mexican children. In addition, the approach is being used in ongoing experiments funded by the Bill & Melinda Gates Foundation and the International Atomic Energy Agency to evaluate vitamin A status in children exposed to multiple sources of the nutrient (e.g., high-dose supplements, fortified foods, and micronutrient powders).…”

Bioactive Components in Moringa Oleifera Leaves Protect against Chronic Disease

“…A combination of antioxidants found in MO leaves was proven to be more effective than a single antioxidant, possibly due to synergistic mechanisms and increased antioxidant cascade mechanisms [ 22 , 66 , 67 ]. A recent study in children demonstrated that MO leaves could be an important source of vitamin A [ 68 ].…”

Use of Stable Isotopes to Evaluate Bioefficacy of Provitamin A Carotenoids, Vitamin A Status, and Bioavailability of Iron and Zinc

“…These super models are used to estimate mean total body retinol stores and kinetic parameters of the associated groups. Recently, a “super child” approach was used in 15 Mexican preschool children to evaluate the bioefficacy of provitamin A carotenoids from intrinsically labeled β-carotene in plants grown with 2 H 2 O; the estimated bioefficacy factor was 3.3 μg β-carotene to 1 μg retinol ( 51 † ).…”