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. Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa.
The estimated average requirement (EAR) for vitamin A (VA) of adult males is based on the amount of dietary VA required to maintain adequate function and provide a modest liver VA reserve (0.07 ...µmol/g). In the present study, the paired-deuterated retinol dilution technique was used to estimate changes in VA pool size in Bangladeshi men from low-income, urban neighborhoods who had small initial VA pool sizes (0.059 ± 0.032 mmol, or 0.047 ± 0.025 µmol/g liver; n = 16). The men were supplemented for 60 d with 1 of 8 different levels of dietary VA, ranging from 100 to 2300 µg/d (2 men/dietary VA level). VA pool size was estimated before and after the supplementation period. The mean change (plus or minus) in VA pool size in the men was plotted against their corresponding levels of daily VA intake and a regression line was fit to the data. The level of intake at which the regression line crossed the x-axis (where estimates of VA pool size remained unchanged) was used as an estimate of the EAR. A VA intake of 254–400 µg/d was sufficient to maintain a small VA pool size (0.059 ± 0.032 mmol) in the Bangladeshi men, corresponding to a VA intake of 362–571 µg/d for a 70-kg U.S. man, which is lower than their current EAR of 625 µg/d. The data suggest that the paired-deuterated retinol dilution technique could be used for estimating the EAR for VA for population subgroups for which there are currently no direct estimates.
Recommendations for vitamin A intake and liver stores are based on maintaining normal vision. We propose that higher levels may be required to maintain normal innate immune function. To test this ...hypothesis, we conducted an 8-wk residential study among 36 healthy Bangladeshi men with low vitamin A stores. Subjects were randomized to receive vitamin A (240 mg in 4 doses) or placebo during study wk 2 and 3. They received 2 vaccines during wk 5 and vitamin A stores were estimated by isotopic dilution at wk 8. The serum concentration of the chemokine interferon-γ-induced protein 10, a component of T-helper 1 (Th1) response, increased significantly after supplementation and was positively and significantly associated with vitamin A stores. Blood concentrations of natural killer (NK) and NK T-cells, which have anticancer and antiviral activity, were positively associated with stores (P < 0.05), as was monocyte oxidative burst (P < 0.05), a marker of bacterial killing ability. However, serum interleukin (IL)-6 and IL-17, cytokines that regulate the antibacterial Th 17 response, were significantly and negatively associated with stores, as was production of the regulatory cytokine IL-10 by whole-blood cultures stimulated with bacterial lipopolysaccharide. In summary, vitamin A stores were positively associated with several measures of innate immune activity across a broad range of stores, suggesting that vitamin A enhances protection against diverse pathogens even at concentrations above those needed to maintain normal vision. The negative association of stores with serum IL-6 and IL-17 suggests that not all protective responses are similarly enhanced by vitamin A. PUBLICATION ABSTRACT
A survey indicated that high-dose vitamin A (HD-VA) supplements had no apparent effect on vitamin A (VA) status, assessed by serum retinol concentrations, of Zambian children lt 5 y of age. To ...explore possible reasons for the lack of response, we quantified absorption, retention, and urinary elimination of either a single HD-VA supplement (209.8 μmol; 60 mg) or a smaller dose of stable isotope (SI)-labeled VA (17.5 μmol; 5 mg), which was used to estimate VA pool size, in 3- to 4-y-old Zambian boys (n = 4 for each VA dose). A tracer dose of 14C2-labeled VA (0.925 kBq; 25 nCi) was coadministered with the HD-VA supplement or SI-labeled VA, and 24-h stool and urine samples were collected for 3 and 7 consecutive days, respectively, and 24-h urine samples at 4 later time points. Accelerator MS was used to quantify 14C in stool and urine. Estimates of absorption, retention, and the urinary elimination rate (UER) were 83.8 ± 7.1%, 76.3 ± 6.7%, and 1.9 ± 0.6%/d, respectively, for the HD-VA supplement and 76.5 ± 9.5%, 71.1 ± 9.4%, and 1.8 ± 1.2%/d, respectively, for the SI-labeled VA. Mean estimates of absorption, retention, and the UER did not differ by size of the VA dose administered. Estimated absorption and retention were negatively associated with reported fever (r = minus 0.83; P = 0.011). The HD-VA supplement and SI-labeled VA were adequately absorbed, retained, and utilized in apparently healthy Zambian preschool-age boys; absorption and retention may be affected by recent fever.
The deuterated-retinol-dilution technique provides a quantitative estimate of total-body vitamin A (TBVA) stores in adults. To apply the technique to children, information on plasma retinol kinetics ...in this age group is needed.
We described the plasma retinol kinetics of an oral dose of (2)H(4)retinyl acetate in a population of Peruvian children (12-24 mo of age) in order to examine the relation between TBVA stores and individual plasma isotopic ratios 3 d after the dose and to estimate 1) the time required for the isotope dose to mix with endogenous vitamin A, 2) the fractional catabolic rate for retinol, and 3) TBVA stores.
An oral dose of (2)H(4)retinyl acetate (14 micromol retinol equivalents) was administered to children (n = 107) to construct a population-level kinetic curve of the plasma ratio of (2)H(4)retinol to retinol to estimate equilibration time and the fractional catabolic rate. TBVA stores were estimated by using a modification of the isotope dilution equation for adults.
The dose of (2)H(4)retinyl acetate fully mixed with endogenous vitamin A 8 d after the dose. The fractional catabolic rate was 0.022/d (95% CI: 0.014, 0.030/d). Mean (+/- SD) TBVA stores were estimated as 0.097 +/- 0.081 mmol (range: 0.016-0.392 mmol). Plasma ratios of (2)H(4)retinol to retinol 3 d after the dose were correlated with the inverse of estimated TBVA stores (r = -0.74, P < 0.0001).
Compared with previous results in adults, the equilibration time occurred earlier and the estimated system fractional catabolic rate was higher in this population of children. The modified isotope dilution equation provided estimates of hepatic vitamin A concentration that are similar to values reported in US children at autopsy.
Because of the many functions of vitamin A in human physiology, deficiency or excess of the vitamin in lactating women or their infants can adversely affect their health. Infants are born with low ...body stores of vitamin A, and rely on vitamin A in milk to meet their needs. The vitamin A content of milk is related to maternal vitamin A status and maternal dietary vitamin A intake during lactation. Low-income lactating women in non-industrialized countries have lower milk vitamin A concentrations than lactating women in industrialized countries. Supplementation of lactating women in non-industrialized countries with vitamin A or beta-carotene has resulted in increased milk vitamin A concentrations. However, the optimal timing and dose for sustaining adequate levels of vitamin A in milk throughout the lactation period has not been determined. Further research is needed to understand factors affecting the transfer of vitamin A to milk, and to evaluate various strategies for improving the vitamin A status of mothers and infants.
Vitamin A deficiency remains a global public health problem. Daily supplementation with a lipid-based nutrient supplement (LNS) has potential for increasing milk vitamin A concentrations. The ...objective of this study was to determine whether daily supplementation with approximately the recommended daily intake of vitamin A in an LNS or a multiple-micronutrient supplement (MMN) during pregnancy and the first 6 mo postpartum has an effect on breast milk retinol concentration at 6 mo postpartum. Women #20 wk pregnant (n = 1320) were randomly assigned to receive either the MMN providing 18 micronutrients, including 800 mg retinol equivalents of vitamin A, or the LNS with the same nutrients as the MMN group, plus 4 minerals and macronutrients, until 6 mo postpartum; a control group received iron and folic acid during pregnancy and a placebo (calcium tablet) during the first 6 mo postpartum. Breast milk samples collected at 6 mo postpartum were analyzed for retinol and fat concentrations by HPLC and creamatocrit, respectively, in a subsample of 756 women. The breast milk retinol concentration was (mean 6 SD) 56.3 6 2.1 nmol/g fat, with no significant differences between groups iron and folic acid (n = 243): 59.1 ± 2.8; MMN (n = 260): 55.4 ± 2.5; LNS (n = 253): 54.7 ± 2.5 nmol/g fat; P = 0.45, regardless of whether the woman had or had not received a high-dose vitamin A supplement (200,000 IU) soon after childbirth. Around 17% of participants had low milk retinol (≤28 nmol/g fat). We estimated that 41% of infants were potentially receiving vitamin A at amounts above the Tolerable Upper Intake Level (600 µg retinol activity equivalents/d), with no group differences in percentages with low or high milk retinol concentration. Daily consumption of approximately the recommended intake of vitamin A did not increase breast milk retinol concentrations in this sample of Ghanaian women. This trial was registered at clinicaltrials.gov as NCT00970866.
Background: Vitamin A deficiency remains a global public health problem. Daily supplementation with a lipid-based nutrient supplement (LNS) has potential for increasing milk vitamin A concentrations.
...Objective: The objective of this study was to determine whether daily supplementation with approximately the recommended daily intake of vitamin A in an LNS or a multiple-micronutrient supplement (MMN) during pregnancy and the first 6 mo postpartum has an effect on breast milk retinol concentration at 6 mo postpartum.
Methods: Women ≤20 wk pregnant (n = 1320) were randomly assigned to receive either the MMN providing 18 micronutrients, including 800 μg retinol equivalents of vitamin A, or the LNS with the same nutrients as the MMN group, plus 4 minerals and macronutrients, until 6 mo postpartum; a control group received iron and folic acid during pregnancy and a placebo (calcium tablet) during the first 6 mo postpartum. Breast milk samples collected at 6 mo postpartum were analyzed for retinol and fat concentrations by HPLC and creamatocrit, respectively, in a subsample of 756 women.
Results: The breast milk retinol concentration was (mean ± SD) 56.3 ± 2.1 nmol/g fat, with no significant differences between groups iron and folic acid (n = 243): 59.1 ± 2.8; MMN (n = 260): 55.4 ± 2.5; LNS (n = 253): 54.7 ± 2.5 nmol/g fat; P = 0.45, regardless of whether the woman had or had not received a high-dose vitamin A supplement (200,000 IU) soon after childbirth. Around 17% of participants had low milk retinol (≤28 nmol/g fat). We estimated that 41% of infants were potentially receiving vitamin A at amounts above the Tolerable Upper Intake Level (600 μg retinol activity equivalents/d), with no group differences in percentages with low or high milk retinol concentration.
Conclusion: Daily consumption of approximately the recommended intake of vitamin A did not increase breast milk retinol concentrations in this sample of Ghanaian women. This trial was registered at clinicaltrials.gov as NCT00970866.
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