β-Carotene is an important dietary source of vitamin A for humans. However, the bioavailability and vitamin A equivalency of β-carotene are highly variable and can be affected by food- and ...diet-related factors, including the food matrix, food-processing techniques, size of the dose of β-carotene, and the amounts of dietary fat, fiber, vitamin A, and other carotenoids in the diet as well as by characteristics of the target population, such as vitamin A status, nutrient deficiencies, gut integrity, and genetic polymorphisms associated with β-carotene metabolism. The absorption of β-carotene from plant sources ranges from 5% to 65% in humans. Vitamin A equivalency ratios for β-carotene to vitamin A from plant sources range from 3.8:1 to 28:1, by weight. Vitamin A equivalency ratios for β-carotene from biofortified Golden Rice or biofortified maize are 3.8:1 and 6.5:1, respectively, and are lower than ratios for vegetables that have more complex food matrices (10:1 to 28:1). The vitamin A equivalency of β-carotene is likely to be context-specific and dependent on specific food- and diet-related factors and the health, nutritional, and genetic characteristics of human populations. Although the vitamin A equivalency of β-carotene is highly variable, the provision of vegetable and fruit sources of β-carotene has significantly increased vitamin A status in women and children in community settings in developing countries; these results support the inclusion of dietary interventions with plant sources of β-carotene as a strategy for increasing vitamin A status in populations at risk of deficiency.
Retinol isotope dilution (RID) methodology provides a quantitative estimate of vitamin A total body stores (TBS) and is used increasingly to evaluate the efficacy of vitamin A interventions; the ...methodology has also been used to estimate vitamin A requirements and the vitamin A equivalence of β-carotene. Here, Haskell suggests that a new modeling approach described by Ford et al increases the accuracy of estimates of total body vitamin A stores. Using the theoretical approach, they demonstrate that inclusion of vitamin A intake as a modeling input allows for accurate prediction of TBS in kinetic studies of relatively short duration (28 d for children and 56 d for adults).
Vitamin A status may influence the choice of a blood sampling time for applying the retinol isotope dilution (RID) equation to predict vitamin A total body stores (TBS) in children.
We aimed to ...identify time(s) after administration of labeled vitamin A that provide accurate estimates of TBS in theoretical children with low or high TBS.
We postulated 2- to 5-y-old children (12/group) with low (<200 μmol) or high TBS (≥700 μmol) and used compartmental analysis to simulate individual subject values for the RID equation TBS = FaS/SAp (Fa, fraction of dose in stores; S, retinol specific activity in plasma/in stores; SAp, retinol specific activity in plasma). Using individual SAp and group geometric mean FaS values from 1–28 d, we calculated individual and group mean TBS and compared them to assigned values.
Mean TBS was accurately predicted for both groups at all times. For individuals, predicted and assigned TBS were closest when the CV% for FaS was low 12–14%; 4–13 d (low), 12–28 d (high). The mean percentage error for TBS was <10% from 2–19 d (low) and 7–28 d (high). Predicted TBS was within 25% of assigned TBS for ≥80% of children from 3–23 d (low) and 9–28 d (high). Within groups, RID tended to overestimate lower TBS and underestimate higher TBS.
Using a good estimate for FaS, accurate RID predictions of TBS for individuals will be obtained at many times. If vitamin A status is low, results indicate that early sampling (e.g., 4–13 d) is optimal; if vitamin A status is high, sampling at 12–28 d is indicated. When vitamin A status is unknown, sampling at 14 d is recommended, or a super-subject design can be used to obtain the group mean FaS at various times for RID prediction of TBS in individuals.
Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its ...widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana.
This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participant's household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development.
Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa.
The trial was registered on ClinicalTrials.gov (NCT05178407) and the Pan-African Clinical Trial Registry (PACTR202206868437931). This manuscript reflects protocol version 4 (August 29, 2022).
Replacement of conventional staples with biofortified or industrially fortified staples in household diets may increase maternal breast milk retinol content and vitamin A intakes from complementary ...foods, improving infant total body stores (TBS) of vitamin A.
To determine whether biofortified or industrially fortified maize consumption by Zambian women and their breastfeeding infants could improve milk retinol concentration and infant TBS.
We randomly assigned 255 lactating women and their 9-mo-old infants to a 90-d intervention providing 0 µg retinol equivalents (RE)/d as conventional maize or ∼315 µg RE/d to mothers and ∼55 µg RE/d to infants as provitamin A carotenoid-biofortified maize or retinyl palmitate–fortified maize. Outcomes were TBS, measured by retinol isotope dilution in infants (primary), and breast milk retinol, measured by HPLC in women (secondary).
The intervention groups were comparable at baseline. Loss to follow-up was 10% (n = 230 mother-infant pairs). Women consumed 92% of the intended 287 g/d and infants consumed 82% of the intended 50 g/d maize. The baseline geometric mean (GM) milk retinol concentration was 1.57 μmol/L (95% CI: 1.45, 1.69 μmol/L), and 24% of women had milk retinol <1.05 μmol/L. While mean milk retinol did not change in the biofortified arm (β: 0.11; 95% CI: −0.02, 0.24), the intervention reduced low milk retinol (RR: 0.42; 95% CI: 0.21, 0.85). Fortified maize increased mean milk retinol (β: 0.17; 95% CI: 0.04, 0.30) and reduced the prevalence of low milk retinol (RR: 0.46; 95% CI: 0.25, 0.82). The baseline GM TBS was 178 μmol (95% CI: 166, 191 μmol). This increased by 24 µmol (± 136) over the 90-d intervention period, irrespective of treatment group.
Both biofortified and fortified maize consumption improved milk retinol concentration. This did not translate into greater infant TBS, most likely due to adequate TBS at baseline. This trial was registered at clinicaltrials.gov as NCT02804490.
Model-based compartmental analysis has been used to describe and quantify whole-body vitamin A metabolism and estimate total body stores (TBS) in animals and humans.
We applied compartmental modeling ...and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines.
Children ingested 13C10retinyl acetate and 1 or 2 blood samples were collected from each child from 6 h to 28 d after dosing. Temporal data for fraction of dose in plasma 13C10retinol were modeled using WinSAAM software and a 6-component model with vitamin A intake included as weighted data.
Model-predicted TBS was 198, 533, and 1062 mol for the Bangladeshi (age, 9–17 mo), Filipino (12–18 mo), and Guatemalan children (35–65 mo). Retinol kinetics were similar for Filipino and Guatemalan groups and generally faster for Bangladeshi children, although fractional transfer of plasma retinol to a larger exchangeable storage pool was the same for the 3 groups. Recycling to plasma from that pool was ~2.5 times faster in the Bangladeshi children compared with the other groups and the recycling number was 2–3 times greater. Differences in kinetics between groups are likely related to differences in vitamin A stores and intakes (geometric means: 352, 727, and 764 µg retinol activity equivalents/d for the Bangladeshi, Filipino, and Guatemalan children, respectively).
By collecting 1 or 2 blood samples from each child to generate a composite plasma tracer data set with a minimum of 5 children/time, group TBS and retinol kinetics can be estimated in children by compartmental analysis; inclusion of vitamin A intake data increases confidence in model predictions. The super-child modeling approach is an effective technique for comparing vitamin A status among children from different populations. These trials were registered at www.clinicaltrials.gov as NCT03000543 (Bangladesh), NCT03345147 (Guatemala), and NCT03030339 (Philippines).
The potential for small-quantity lipid-based nutrient supplements (LNS) to promote growth and development after 6 mo of age is currently being investigated. Because infants self-regulate energy ...intake, consumption of LNS may reduce breast milk intake and potentially decrease the beneficial effects of breast milk.
The objective was to test the hypothesis that the breast milk intake of 9- to 10-mo-old rural Malawian infants receiving LNS would not be lower than that of infants receiving no supplementation.
This was a substudy of the International Lipid-based Nutrient Supplements (iLiNS) DOSE trial, in which 6-mo-old infants were randomly assigned to receive 10, 20, or 40 g LNS/d containing 56, 117, or 241 kcal/d, respectively, or no LNS until 18 mo of age. A subset was randomly selected to estimate breast milk intake at 9-10 mo of age with the dose-to-mother deuterium oxide dilution method. The noninferiority margin was <10% of total energy requirements.
Baseline characteristics (n = 376) were similar across groups. The mean (± SD) daily breast milk intake of unsupplemented infants was 730 ± 226 g. The differences (95% CIs) in mean intake of infants provided with 10, 20, or 40 g LNS/d, compared with controls, were +62 (-18, +143), +30 (-40, +99), and +2 (-68, +72) g/d, respectively. Non-breast milk oral water intake did not differ by group (P = 0.39) and was inversely (r = -0.22, P < 0.01) associated with breast milk intake.
In this rural Malawian population, breast milk intake at 9-10 mo of age was not reduced by supplementation with complementary foods with 10-40 g LNS/d.
We previously compared the potential effects of different intervention strategies for achieving dietary vitamin A (VA) adequacy. The Lives Saved Tool (LiST) permits estimates of lives saved through ...VA interventions but currently only considers periodic VA supplements (VASs).
We aimed to adapt the LiST method for estimating the mortality impact of VASs to estimate the impact of other VA interventions (e.g., food fortification) on child mortality and to estimate the number of lives saved by VA interventions in 3 macroregions in Cameroon.
We used national dietary intake data to predict the effects of VA intervention programs on the adequacy of VA intake. LiST parameters of population affected fraction and intervention coverage were replaced with estimates of prevalence of inadequate intake and effective coverage (proportion achieving adequate VA intake). We used a model of liver VA stores to derive an estimate of the mortality reduction from achieving dietary VA adequacy; this estimate and a conservative assumption of equivalent mortality reduction for VAS and VA intake were applied to projections for Cameroon.
There were 2217–3048 total estimated VA-preventable deaths in year 1, with 58% occurring in the North macroregion. The relation between effective coverage and lives saved differed by year and macroregion due to differences in total deaths, diarrhea burden, and prevalence of low VA intake. Estimates of lives saved by VASs (the intervention common to both methods) were similar with the use of the adapted method (in 2012: North, 743–1021; South, 280–385; Yaoundé and Douala, 146–202) and the “usual” LiST method (North: 697; South: 381; Yaoundé and Douala: 147).
Linking effective coverage estimates with an adapted LiST method permits estimation of the effects of combinations of VA programs (beyond VASs only) on child mortality to aid program planning and management. Rigorous program monitoring and evaluation are necessary to confirm predicted impacts.
Vitamin A (VA) deficiency is prevalent in preschool-aged children in sub-Saharan Africa.
We assessed the effect of small-quantity lipid-based nutrient supplements (SQ-LNS) given to women during ...pregnancy and lactation and their children from 6 to 18 mo of age on women's plasma and milk retinol concentrations in Malawi, and children's plasma retinol concentration in Malawi and Ghana.
Pregnant women (≤20 wk of gestation) were randomized to receive daily: 1) iron and folic acid (IFA) during pregnancy only; 2) multiple micronutrients (MMN; 800 μg retinol equivalent (RE)/capsule), or 3) SQ-LNS (800 μg RE/20g) during pregnancy and the first 6 mo postpartum. Children of mothers in the SQ-LNS group received SQ-LNS (400 μg RE/20 g) from 6 to 18 mo of age; children of mothers in the IFA and MMN groups received no supplement. Plasma retinol was measured in mothers at ≤20 and 36 wk of gestation and 6 mo postpartum, and in children at 6 and 18 mo of age. Milk retinol was measured at 6 mo postpartum. VA status indicators were compared by group.
Among Malawian mothers, geometric mean (95% CI) plasma retinol concentrations at 36 wk of gestation and 6 mo postpartum were 0.97 μmol/L (0.94, 1.01 μmol/L) and 1.35 μmol/L (1.31, 1.39 μmol/L), respectively; geometric mean (95% CI) milk retinol concentration at 6 mo postpartum was 1.04 μmol/L (0.97, 1.13 μmol/L); results did not differ by intervention group. Geometric mean (95% CI) plasma retinol concentrations for Malawian children at 6 and 18 mo of age were 0.78 μmol/L (0.75, 0.81 μmol/L) and 0.81 μmol/L (0.78, 0.85 μmol/L), respectively, and for Ghanaian children they were 0.85 μmol/L (0.82, 0.88 μmol/L) and 0.88 μmol/L (0.85, 0.91 μmol/L), respectively; results did not differ by intervention group in either setting.
SQ-LNS had no effect on VA status of mothers or children, possibly because of low responsiveness of the VA status indicators.
Provitamin A carotenoid-biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating ...biofortified maize may increase vitamin A in breast milk-a critical source of vitamin A for breastfeeding infants.
We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women.
Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 μg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 μg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and β-carotene concentrations, and plasma inflammatory protein concentrations.
Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 μmol/L (95% CI: 0.86, 1.05 μmol/L); 56% of samples had milk retinol <1.05 μmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk β-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM 1.15 μmol/L (0.96, 1.39 μmol/L) and VA 1.17 μmol/L (0.99, 1.38 μmol/L) groups than in the WM group 0.91 μmol/L (0.72, 1.14 μmol/L); P = 0.13, and the proportion of women with milk retinol <1.05 μmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16).
Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713.
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