Association between Biomarkers of Inflammation and Total Liver Vitamin A Reserves Estimated by 13C-Retinol Isotope Dilution among Preschool Children in 5 African Countries.

BACKGROUND: Vitamin A (VA) assessment is important for targeting public health programs. Retinol isotope dilution (RID) is a sensitive method to estimate total body VA stores (TBSs) and total liver reserves (TLRs), but the impact of subclinical inflammation on RID is unclear. OBJECTIVE: We determined the association between TBSs and TLRs, estimated by RID, and inflammation among preschool children without clinical infection in Burkina Faso, Cameroon, Ethiopia, South Africa, and Tanzania. METHODS: Five studies (n = 532; 47.9 ± 8.3 mo; 49.0% male) included 13C-RID and measurement of inflammation markers, CRP, and α1-acid glycoprotein (AGP). Spearman correlations were used to evaluate TBSs and TLRs with inflammation biomarkers. Wilcoxon and Kruskal-Wallis tests were used to compare TBSs and TLRs by inflammation categories [normal vs. elevated CRP (>5 mg/L) or AGP (>1 g/L)] and inflammation stage [reference, incubation (elevated CRP), early convalescence (elevated CRP and AGP), and late convalescence (elevated AGP)]. RESULTS: Complete data were available for 439 children. Median (Q1, Q3) TLRs ranged from 0.12 (0.07, 0.18) µmol/g in Ethiopia to 1.10 (0.88, 1.38) µmol/g in South Africa. Elevated CRP ranged from 4% in Burkina Faso to 42% in Cameroon, and elevated AGP from 20% in Tanzania to 58% in Cameroon. Pooled analysis (excluding Cameroon) showed a negative correlation between TBSs and AGP (ρ = -0.131, P = 0.01). Children with elevated AGP had higher probability of having lower TBSs (probability = 0.61, P = 0.002). TBSs differed among infection stages (P = 0.020). Correlations between TLRs and CRP or AGP were not significant. CONCLUSIONS: No indication of systematic bias in RID-estimated TLRs was found due to subclinical inflammation among preschool children. The inverse relationship between TBSs and AGP may reflect decreased stores after infection or an effect of inflammation on isotope partitioning. Further research should investigate potential confounding variables to improve TBS-estimate validity.

Comparison of Total Body Vitamin A Stores Using Individual versus Population 13C-Natural Abundance of Serum Retinol in Preschool Children and Women Residing in 6 Diverse African Countries.

BACKGROUND: Stable isotope techniques using 13C to assess vitamin A (VA) dietary sources, absorption, and total body VA stores (TBSs) require determination of baseline 13C abundance. 13C-natural abundance is approximately 1.1% total carbon, but varies with foods consumed, supplements taken, and food fortification with synthetic retinyl palmitate. OBJECTIVES: We determined 13C variation from purified serum retinol and the resulting impact on TBSs using pooled data from preschool children in Burkina Faso, Cameroon, Ethiopia, South Africa, Tanzania, and Zambia and Zambian women. METHODS: Seven studies included children (n = 639; 56 ± 25 mo; 48% female) and one in women (n = 138; 29 ± 8.5 y). Serum retinol 13C-natural abundance was determined using GC-C-IRMS. TBSs were available in 7 studies that employed retinol isotope dilution (RID). Serum CRP and α1-acid-glycoprotein (AGP) were available from 6 studies in children. Multivariate mixed models assessed the impact of covariates on retinol 13C. Spearman correlations and Bland-Altman analysis compared serum and milk retinol 13C and evaluated the impact of using study- or global-retinol 13C estimates on calculated TBSs. RESULTS: 13C-natural abundance (%, median [Q1, Q3]) differed among countries (low: Zambia, 1.0744 [1.0736, 1.0753]; high: South Africa, 1.0773 [1.0769, 1.0779]) and was associated with TBSs, CRP, and AGP in children and with TBSs in women. 13C-enrichment from serum and milk retinol were correlated (r = 0.52; P = 0.0001). RID in children and women using study and global estimates had low mean bias (range, -3.7% to 2.2%), but larger 95% limits of agreement (range, -23% to 37%). CONCLUSIONS: 13C-natural abundance is different among human cohorts in Africa. Collecting this information in subgroups is recommended for surveys using RID. When TBSs are needed on individuals in clinical applications, baseline 13C measures are important and should be measured in all enrolled subjects.

Chronic and acute hypervitaminosis A are associated with suboptimal anthropometric measurements in a cohort of South African preschool children.

BACKGROUND: Excessive vitamin A (VA) can cause bone resorption and impair growth. Government-mandated VA supplementation (VAS) and adequate intake through dietary fortification and liver consumption led to excessive VA in South African children. OBJECTIVES: We evaluated the relation between VAS and underlying hypervitaminosis A assessed by retinol isotope dilution (RID) with measures of growth and bone turnover in this cohort. METHODS: Primary outcomes in these children (n = 94, 36-60 mo) were anthropometric measurements [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z scores], serum bone turnover markers [C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP)], and inflammation defined as C-reactive protein (CRP; ≥5 mg/L) and/or α1-acid glycoprotein (AGP; ≥1 g/L). VA status was previously measured by RID-estimated total body VA stores (TBSs) and total liver VA reserves (TLRs), and serum retinol and carotenoid concentrations, before and 4 wk after children were administered 200,000 IU VAS. Serum 25-hydroxyvitamin D3 was measured by ultra-performance LC. RESULTS: In this largely hypervitaminotic A cohort, HAZ, WAZ, and WHZ were negatively associated with increasing TLRs, where TLRs predicted 6-10% of the variation before VAS (P < 0.05), increasing to 14-19% 4 wk after VAS (P < 0.01). Bone resorption decreased after VAS (P < 0.0001), whereas formation was unaffected. Neither CTX nor P1NP were correlated with TLRs at either time. Serum carotenoids were low. One child at each time point was vitamin D deficient (<50 nmol/L). CRP and AGP were not associated with growth measurements. CONCLUSIONS: Excessive TLRs due to dietary VA intake and VAS are associated with lower anthropometric measures and bone resorption decreased after supplementation. VA supplementation programs should monitor VA status with biomarkers sensitive to TLRs to avoid causing negative consequences in children with hypervitaminosis A. This trial is registered at clinicaltrials.gov as NCT02915731.

Mean ± Standard Deviation Intake Values for 1-<10-Year-Old South African Children for Application in the Assessment of the Inflammatory Potential of Their Diets Using the DII® Method: Developmental Research.

This study aimed to develop a set of mean ± standard deviation (SD) intake values for South African (SA) children for 36 of the 45 food parameters included in the original Dietary Inflammatory Index (DII®) tool. The SA food composition database contains 30 of the 45 food parameters included in the original DII®, and a supplementary database was developed for six of the food parameters not included in the SA database. The SA child mean ± SD intake of macronutrients, micronutrients and select flavonoids was calculated by age in years, using eight data sets from dietary surveys conducted in SA in the last three decades. A total sample of 5412 children was included in the calculation of the mean ± SD. The current study sample was determined to be representative of 1-<10-year-old children in SA, and the plausibility of the mean intake values was confirmed by being in line with age-appropriate recommendations. Furthermore, an increase in energy, macronutrient, and most micronutrient intakes with increase in age was evident. The generated mean ± SD values for SA children can be used for calculation of the inflammatory potential of the dietary intake of SA children in the age range of 1-<10-year-old children.

Liver is widely eaten by preschool children in the Northern Cape province of South Africa: Implications for routine vitamin A supplementation.

Previous research has demonstrated a virtual absence of vitamin A deficiency and adequacy of vitamin A intake through consumption of liver in preschool children of a community in the Northern Cape province of South Africa where sheep farming is common, and liver, an exceptionally rich source of vitamin A, is frequently eaten. Only 60-75 g of liver per month is needed to meet the vitamin A requirement of preschool children. Because this may have implications for routine vitamin A supplementation, and because liver consumption for the rest of the province is unknown, the study aim was to establish the prevalence and frequency of liver intake in a provincial-wide survey. An unquantified liver-specific food frequency questionnaire, covering a period of 1 month, complemented by a 1-year recall, was administered to mothers of 2- to 5-year-old children (n = 2,864) attending primary health care facilities in all five districts and 26 subdistricts. A total of 86% of children were reported to eat liver, which was eaten in all districts by at least 80% of children. The overall median frequency of liver intake was 1.0 [25th, 75th percentiles: 0.5, 3.0] times per month and ranged from 1.0 [0.3, 2.0] to 2.0 [1.0, 4.0] for the various districts. Based on a previously reported portion size of 66 g, these results suggest vitamin A dietary adequacy in all districts and possibly also vitamin A intake exceeding the Tolerable Upper Intake Level in some children. Routine vitamin A supplementation in this province may not be necessary and should be reconsidered.

South African preschool children habitually consuming sheep liver and exposed to vitamin A supplementation and fortification have hypervitaminotic A liver stores: a cohort study.

BACKGROUND: In some regions, multiple vitamin A (VA) interventions occur in the same target groups, which may lead to excessive stores. Retinol isotope dilution (RID) is a more sensitive technique than serum retinol to measure VA status. OBJECTIVE: We evaluated VA status before and after a high-dose supplement in preschool children living in a region in South Africa with habitual liver consumption and exposed to VA supplementation and fortification. METHODS: After baseline blood samples, subjects (46.7 ± 8.4 mo; n = 94) were administered 1.0 µmol [14,15]-13C2-retinyl acetate to estimate total liver retinol reserves by RID with a follow-up 14-d blood sample. Liver intake was assessed with a frequency questionnaire. In line with current practice, a routine 200,000 IU VA capsule was administered after the RID test. RID was repeated 1 mo later. Serum retinyl esters were evaluated using ultra-performance liquid chromatography. RESULTS: At baseline, 63.6% of these children had hypervitaminosis A defined as total liver retinol reserves ≥1.0 µmol/g liver, which increased to 71.6% after supplementation (1.13 ± 0.43 to 1.29 ± 0.46 µmol/g; P < 0.001). Total serum VA as retinyl esters was elevated in 4.8% and 6.1% of children before and after supplementation. The odds of having hypervitaminosis A at baseline were higher in children consuming liver ≥1/mo (ratio 3.70 [95% CI: 1.08, 12.6]) and in children receiving 2 (4.28 [1.03, 17.9]) or 3 (6.45 [0.64, 65.41]) supplements in the past 12 mo. Total body stores decreased after the supplement in children in the highest quartile at baseline compared with children with lower stores, who showed an increase (P = 0.007). CONCLUSIONS: In children, such as this cohort in South Africa, with adequate VA intake through diet, and overlapping VA fortification and supplementation, preschool VA capsule distribution should be re-evaluated. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT02915731 as NCT02915731.

Overlapping vitamin A interventions in the United States, Guatemala, Zambia, and South Africa: case studies.

Vitamin A (VA) deficiency is a serious public health problem, especially in preschool children who are at risk of increased mortality. In order to address this problem, the World Health Organization recommends periodic high-dose supplementation to children 6-59 months of age in areas of highest risk. Originally, supplementation was meant as a short-term solution until more sustainable interventions could be adopted. Currently, many countries are fortifying commercialized common staple and snack foods with retinyl palmitate. However, in some countries, overlapping programs may lead to excessive intakes. Our review uses case studies in the United States, Guatemala, Zambia, and South Africa to illustrate the potential for excessive intakes in some groups. For example, direct liver analysis from 27 U.S. adult cadavers revealed 33% prevalence of hypervitaminosis A (defined as ≥1 µmol/g liver). In 133 Zambian children, 59% were diagnosed with hypervitaminosis A using a retinol isotope dilution, and 16% had ≥5% total serum VA as retinyl esters, a measure of intoxication. In 40 South African children who frequently consumed liver, 72.5% had ≥5% total serum VA as retinyl esters. All four countries have mandatory fortified foods and a high percentage of supplement users or targeted supplementation to preschool children.

Serum retinol in post-partum mothers and newborns from an impoverished South African community where liver is frequently eaten and vitamin A deficiency is absent.

Serum retinol was assessed in mothers and newborns from an impoverished South African community where liver is frequently eaten and vitamin A deficiency known to be absent. Paired cord and maternal blood (n = 201) were collected after delivery and analysed for serum retinol and C-reactive protein (CRP). Liver intake during pregnancy and intention to breastfeed were also assessed. Mean serum retinol was 1.03 µmol/L ± 0.40 in mothers and 0.73 ± 0.24 µmol/L in newborns, with 21.4% and 49.3% having serum retinol <0.70 µmol/L (<20 µg/dL), respectively. Raised CRP was found in 59.9% of mothers, with a significant negative correlation between serum retinol and CRP (r = -0.273; p < 0.0001). Liver was eaten by 87.6% of mothers, and 99% indicated their intention to breastfeed. Despite consumption of liver, serum retinol was low in both the mother and the newborn. The conventional cut-off for serum retinol, i.e. <0.70 µmol/L may therefore not apply for the mother and newborn in the period immediately after delivery. Serum retinol may be influenced by factors other than vitamin A status, e.g. the haemodilution of pregnancy, as well as the acute phase response induced by the birth process, as suggested by raised CRP in 60% of mothers. In the newborns, the low serum retinol is likely to increase rapidly, as liver is frequently eaten by mothers and practically all of them intended to breastfeed. Our results confirm the need for better indicators of vitamin A status or alternative cut-off values during this period.

Vitamin A, Iron, and Zinc Content of Fortified Maize Meal and Bread at the Household Level in 4 Areas of South Africa.

BACKGROUND: A national mandatory food fortification program, fortifying wheat flour and maize meal with various micronutrients, was introduced in South Africa in 2003 to address micronutrient deficiencies. OBJECTIVE: This study aimed to determine vitamin A, iron, and zinc content of raw maize meal and wheat flour bread sampled at household level from 2 urban and 2 rural areas in South Africa and to compare with the regulatory minimum requirements. METHODS: Maize meal (250 g) and/or supermarket/local shop bread (3 inner slices) were collected from 50 randomly selected households from each study area. Maize meal samples were reduced to 10 composite samples per area. Bread samples were composited similarly; 1 composite sample consisted of 15 intact slices. Overall, 8 composite samples were obtained for both brown and white bread. The Southern African Grain Laboratory analyzed the samples for vitamin A, iron, and zinc. RESULTS: Mean content of maize meal (100 g) represented ratios of 0.56 to 0.98 of the minimum fortification requirement for vitamin A, 0.76 to 1.08 for iron, and 0.89 to 1.00 for zinc; brown bread (100 g) represented ratios of 0.57, 1.97, and 1.67 of the minimum requirement for vitamin A, iron, and zinc, respectively, and white bread (100 g) represented ratios of 0.89, 2.22, and 2.07 for vitamin A, iron, and zinc, respectively. CONCLUSION: The variation in vitamin A, iron, and zinc content in maize meal and the higher than required iron and zinc content in wheat bread needs to be investigated in further studies.

Low intake of calcium and vitamin D, but not zinc, iron or vitamin A, is associated with stunting in 2- to 5-year-old children.

OBJECTIVES: This cross-sectional study examined the nutritional factors associated with the high levels of stunting in 2- to 5-y-old children in an impoverished South African setting where liver is frequently eaten and vitamin A deficiency known to be absent. METHODS: Children's dietary intake was assessed by a single 24-h recall. Heights and weights were measured and information was obtained on breast-feeding history, the child's habitual milk intake, as well as substance use by the mother during pregnancy (n = 150). RESULTS: The overall prevalence of stunting was 36.9% (CI 29.2, 44.6) and increased with age, being 49% in the 4- to 5-y-old age category. Birth weight correlated significantly with height-for-age z-scores (HAZ; r = 0.250, P = 0.003), and was lower in children whose mothers smoked and used alcohol during pregnancy than in children whose mothers abstained (P < 0.0001). Median intake of energy, carbohydrate and protein was adequate. Median intake for all micronutrients was at least 90% of the estimated average requirement, except for calcium, vitamin D and vitamin E, which was 21%, 15%, and 32%, respectively. Intake of fat, calcium, phosphorous, vitamin D, riboflavin, and vitamin B12 (nutrients that typically occur in milk) was significantly lower in stunted than in non-stunted children (P < 0.05). When excluding children with low birth weight, intake of calcium, vitamin D, and riboflavin were still significantly lower (P < 0.05). HAZ was higher in children who habitually drank milk compared to those who did not (P = 0.003). CONCLUSIONS: Inadequate calcium and vitamin D intake, presumably because of low intake of milk after weaning, may have contributed to stunting in this population.

Vitamin A and anthropometric status of South African preschool children from four areas with known distinct eating patterns.

OBJECTIVE: The aim of this study was to assess the vitamin A and anthropometric status of South African preschool children from four areas with known distinct eating patterns. METHODS: Serum retinol, anthropometric indicators, and dietary intake were determined for randomly selected preschool children from two rural areas, i.e. KwaZulu-Natal (n = 140) and Limpopo (n = 206); an urban area in the Northern Cape (n = 194); and an urban metropolitan area in the Western Cape (n = 207). RESULTS: Serum retinol <20 µg/dL was prevalent in 8.2% to 13.6% children. Between 3% (urban-Northern Cape) and 44.2% (rural-Limpopo) children had received a high-dose vitamin A supplement during the preceding 6 mo. Vitamin A derived from fortified bread and/or maize meal ranged from 65 µg retinol activity equivalents (24%-31% of the Estimated Average Requirement) to 160 µg retinol activity equivalents (58%-76% Estimated Average Requirement). Fortified bread and/or maize meal contributed 57% to 59% of total vitamin A intake in rural children, and 28% to 38% in urban children. Across the four areas, stunting in children ranged from 13.9% to 40.9%; and overweight from 1.2% to 15.1%. CONCLUSION: Prevalence of vitamin A deficiency was lower than national figures, and did not differ across areas despite differences in socioeconomics, dietary intake, and vitamin A supplementation coverage. Rural children benefited more from the national food fortification program in terms of vitamin A intake. Large variations in anthropometric status highlight the importance of targeting specific nutrition interventions, taking into account the double burden of overnutrition and undernutrition.

Liver intake in 24-59-month-old children from an impoverished South African community provides enough vitamin A to meet requirements.

OBJECTIVE: To assess the contribution of liver to the vitamin A intake of 24-59-month-old children from an impoverished South African community where liver is frequently consumed and vitamin A deficiency previously shown to be absent. DESIGN: Cross-sectional. SETTING: Northern Cape Province, South Africa. SUBJECTS: Children aged 24-59 months (n 150). Vitamin A intake from liver was assessed using a single 24 h recall and a quantified liver frequency questionnaire. In addition, information on vitamin A intake via the national fortification programme was obtained from the 24 h recall and information on vitamin A supplementation from the Road-to-Health Chart. Height, weight and socio-economic data were also collected. RESULTS: Stunting, underweight and wasting were prevalent in 36·9 %, 25·5 % and 12·1 % of children. Mean daily vitamin A intake from liver was 537 and 325 µg retinol equivalents measured by the 24 h recall and liver frequency questionnaire, respectively. Liver was consumed in 92·7 % of households and by 84·7 % of children; liver intake was inversely related to socio-economic status (P < 0·05). The food fortification programme contributed 80 µg retinol equivalents and the vitamin A supplementation programme 122 µg retinol equivalents to daily vitamin A intake. CONCLUSIONS: The study showed that liver alone provided more than 100 % of the Estimated Average Requirement of the pre-school children in this impoverished community. The results also challenge the notion generally held by international health bodies that vitamin A deficiency, poor anthropometric status and poverty go together, and reinforces the fact that South Africa is a culturally diverse society for which targeted interventions are required.

Effects of a multi-micronutrient-fortified beverage, with and without sugar, on growth and cognition in South African schoolchildren: a randomised, double-blind, controlled intervention.

Little is known about the effects of combined micronutrient and sugar consumption on growth and cognition. In the present study, we investigated the effects of micronutrients and sugar, alone and in combination, in a beverage on growth and cognition in schoolchildren. In a 2 × 2 factorial design, children (n 414, 6-11 years) were randomly allocated to consume beverages containing (1) micronutrients with sugar, (2) micronutrients with a non-nutritive sweetener, (3) no micronutrients with sugar or (4) no micronutrients with a non-nutritive sweetener for 8.5 months. Growth was assessed and cognition was tested using the Kaufman Assessment Battery for Children version II (KABC-II) subtests and the Hopkins Verbal Learning Test (HVLT). Micronutrients decreased the OR for Fe deficiency at the endpoint (OR 0.19; 95% CI 0.07, 0.53). Micronutrients increased KABC Atlantis (intervention effect: 0.76; 95% CI 0.10, 1.42) and HVLT Discrimination Index (1.00; 95% CI 0.01, 2.00) scores. Sugar increased KABC Atlantis (0.71; 95% CI 0.05, 1.37) and Rover (0.72; 95% CI 0.08, 1.35) scores and HVLT Recall 3 (0.94; 95% CI 0.15, 1.72). Significant micronutrient × sugar interaction effects on the Atlantis, Number recall, Rover and Discrimination Index scores indicated that micronutrients and sugar in combination attenuated the beneficial effects of micronutrients or sugar alone. Micronutrients or sugar alone had a lowering effect on weight-for-age z-scores relative to controls (micronutrients - 0.08; 95% CI - 0.15, - 0.01; sugar - 0.07; 95% CI - 0.14, - 0.002), but in combination, this effect was attenuated. The beverages with micronutrients or added sugar alone had a beneficial effect on cognition, which was attenuated when provided in combination.

Effects of iron and n-3 fatty acid supplementation, alone and in combination, on cognition in school children: a randomized, double-blind, placebo-controlled intervention in South Africa.

BACKGROUND: Little is known about the combined effects of iron and n-3 (omega-3) fatty acid (FA) supplementation on cognitive performance. The provision of either DHA/EPA or iron alone in rats with combined iron and n-3 FA deficiency has been reported to exacerbate cognitive deficits associated with deficiency. OBJECTIVE: We investigated the effects of iron and DHA/EPA supplementation, alone and in combination, in children with poor iron and n-3 FA status. DESIGN: In a 2-by-2 factorial trial, children with iron deficiency (ID) (n = 321; aged 6-11 y) were allocated to receive 1) iron (50 mg) plus DHA/EPA (420/80 mg), 2) iron plus placebo, 3) placebo plus a mixture of DHA and EPA (DHA/EPA), or 4) placebo plus placebo as oral supplements (4/wk) for 8.5 mo. Cognition was assessed at baseline and endpoint by using the Hopkins Verbal Learning Test (HVLT) and subscales of the Kaufman Assessment Battery for Children. RESULTS: Both iron and DHA/EPA significantly increased weight-for-age z scores. Iron increased the number of words recalled at HVLT recall 2 (intervention effect: 0.90; 95% CI: 0.18, 1.62), and in anemic children, iron increased scores in the Atlantis Delayed test (1.51; 95% CI: 0.03, 2.99) and HVLT recall 2 (2.02; 95% CI: 0.55, 3.49). DHA/EPA showed no benefit in any of the cognitive tests but decreased Atlantis test scores (-2.48; 95% CI: -3.99, -0.96) in children who were anemic at baseline and decreased Atlantis delayed scores (-0.9; 95% CI: -1.45, -0.36) in girls with ID, whereas boys tended to perform better. CONCLUSIONS: In children with poor iron and n-3 FA status, iron supplementation improved verbal and nonverbal learning and memory, particularly in children with anemia. In contrast, DHA/EPA supplementation had no benefits on cognition and impaired working memory in anemic children and long-term memory and retrieval in girls with ID.

Serum retinol in 1-6-year-old children from a low socio-economic South African community with a high intake of liver: implications for blanket vitamin A supplementation.

OBJECTIVE: To assess serum retinol, liver intake patterns, breast-feeding history and anthropometric status in pre-school children of a low socio-economic community where liver is regularly consumed. DESIGN: Cross-sectional study. SETTING: Northern Cape Province, South Africa. SUBJECTS: Children aged 1-6 years (n 243) who attended the local primary health-care facility and had not received a vitamin A supplement in the 6 months preceding the study. Non-pregnant female caregivers (n 225), below 50 years of age, were also assessed. RESULTS: Despite stunting, underweight and wasting being prevalent in 40·5%, 23·1% and 8·4% of the children, only 5·8% had serum retinol concentrations < 20 µg/dl, which is in sharp contrast to the national prevalence of 63·6%. None of the caregivers were vitamin A deficient. Liver was eaten by 89·2% of children, with 87% of households eating liver at least once monthly and 30% eating it at least once weekly; liver was introduced into the diet of the children at a median age of 18 months. Ninety-three per cent of the children were being breast-fed or had been breast-fed in the past; children were breast-fed to a median age of 18 months. A significant negative correlation was found between educational level of the caregiver and frequency of liver intake (r = -0·143, P=0·032). There was no correlation between serum retinol and indicators of anthropometric or socio-economic status. CONCLUSIONS: The blanket approach in applying the national vitamin A supplementation programme may not be appropriate for all areas in the country, even though the community may be poor and undernourished.

A micronutrient powder with low doses of highly absorbable iron and zinc reduces iron and zinc deficiency and improves weight-for-age Z-scores in South African children.

Micronutrient powders (MNP) are often added to complementary foods high in inhibitors of iron and zinc absorption. Most MNP therefore include high amounts of iron and zinc, but it is no longer recommended in malarial areas to use untargeted MNP that contain the Reference Nutrient Intake for iron in a single serving. The aim was to test the efficacy of a low-iron and -zinc (each 2.5 mg) MNP containing iron as NaFeEDTA, ascorbic acid (AA), and an exogenous phytase active at gut pH. In a double-blind controlled trial, South African school children with low iron status (n = 200) were randomized to receive either the MNP or the unfortified carrier added just before consumption to a high-phytate maize porridge 5 d/wk for 23 wk; primary outcomes were iron and zinc status and a secondary outcome was somatic growth. Compared with the control, the MNP increased serum ferritin (P < 0.05), body iron stores (P < 0.01) and weight-for-age Z-scores (P < 0.05) and decreased transferrin receptor (P < 0.05). The prevalence of iron deficiency fell by 30.6% (P < 0.01) and the prevalence of zinc deficiency decreased by 11.8% (P < 0.05). Absorption of iron from the MNP was estimated to be 7-8%. Inclusion of an exogenous phytase combined with NaFeEDTA and AA may allow a substantial reduction in the iron dose from existing MNP while still delivering adequate iron and zinc. In addition, the MNP is likely to enhance absorption of the high native iron content of complementary foods based on cereals and/or legumes.

A randomised control trial in schoolchildren showed improvement in cognitive function after consuming a bread spread, containing fish flour from a marine source.

BACKGROUND: In humans, n-3 long-chain polyunsaturated fatty acids play a well-documented role in brain development and function. Docosahexaenoic acid and arachidonic acid are major structural components of the brain and a deficiency thereof may bring about changes in the behaviour domains of the brain. OBJECTIVE: This trial investigated the effect of an experimental fish-flour bread spread rich in n-3 long-chain polyunsaturated fatty acids, on cognition of children (7-9yr). DESIGN: Subjects (n=183) were randomly assigned to an experimental (n=91) and control group (n=92), receiving either the fish-flour spread or a placebo spread for 6 months in a single-blind study. Plasma and red blood cell phospholipid fatty acid composition and cognition were measured at baseline and post-intervention. RESULTS: After the intervention, eicosapentaenoic and docosahexaenoic acid levels were significantly higher in the experimental group compared to the control group (p< 0.0001). Significant intervention effects were also observed for the Hopkins Verbal Learning Test Recognition (estimated effect size: 0.80; 95% confidence interval (CI): 0.15; 1.45) and Discrimination Index (estimated effect size: 1.10; 95% CI: 0.30; 1.91), as well as the Spelling test (estimated effect size: 2.81; 95% CI: 0.59; 5.02) by both per protocol and intention to treat analyses. A marginally significant (p=0.0646) effect was observed for the Reading test (estimated effect size: 2.21; 95% CI: -0.14; 4.56) only in the per protocol analysis. CONCLUSION: This study suggests improvement of verbal learning ability and memory of children when supplemented with a fish-flour spread rich in n-3 long-chain polyunsaturated fatty acids.

Fortifying brown bread with sodium iron EDTA, ferrous fumarate, or electrolytic iron does not affect iron status in South African schoolchildren.

The choice of iron fortificant usually represents a balance between bioavailability of the compound and its tendency to cause organoleptic problems. The aim of this study was to evaluate the efficacy of sodium iron EDTA (NaFeEDTA) and ferrous fumarate at levels compatible with South African brown bread (10 mg/kg flour for NaFeEDTA and 20 mg/kg flour for ferrous fumarate) in a randomized controlled trial; electrolytic iron was evaluated at the level currently used in South Africa (35 mg/kg flour). Schoolchildren (n = 361), aged 6-11 y, from a low socioeconomic community with hemoglobin (Hb) < or = 125 g/L were randomly assigned to 1 of 4 groups that received 4 slices of brown bread supplying either: 1) no fortification iron 2) 2.35 mg iron as NaFeEDTA; 3) 4.70 mg iron as ferrous fumarate; and 4) 8.30 mg iron as electrolytic iron per intervention day. These amounts simulated a bread intake of 6 slices per day over the 34-wk study period at fortification levels of 0, 10, 20, and 35 mg/kg flour, respectively. Hb concentration and iron status were assessed at baseline and after 34 wk of intervention. The iron interventions did not affect Hb concentration, transferrin saturation, or serum ferritin, iron, or transferrin receptor concentrations relative to the control group. Our results suggest that electrolytic iron at the level currently used in South Africa is not effective in improving iron or Hb status. Neither do NaFeEDTA or ferrous fumarate appear to be suitable alternatives for the fortification of wheat flour when included at levels that do not cause color changes.

Estimating the burden of disease attributable to iron deficiency anaemia in South Africa in 2000.

OBJECTIVES: To estimate the extent of iron deficiency anaemia (IDA) among children aged 0 - 4 years and pregnant women aged 15 - 49 years, and the burden of disease attributed to IDA in South Africa in 2000. DESIGN: The comparative risk assessment (CRA) methodology of the World Health Organization (WHO) was followed using local prevalence and burden estimates. IDA prevalence came from re-analysis of the South African Vitamin A Consultative Group study in the case of the children, and from a pooled estimate from several studies in the case of the pregnant women (haemoglobin level < 11 g/dl and ferritin level < 12 microg/l). Monte Carlo simulation-modelling was used for the uncertainty analysis. SETTING: South Africa. SUBJECTS: Children under 5 years and pregnant women 15 - 49 years. OUTCOME MEASURES: Direct sequelae of IDA, maternal and perinatal deaths and disability-adjusted life years (DALYs) from mild mental disability related to IDA. Results. It is estimated that 5.1% of children and 9 - 12% of pregnant women had IDA and that about 7.3% of perinatal deaths and 4.9% of maternal deaths were attributed to IDA in 2000. Overall, about 174,976 (95% uncertainty interval 150,344 - 203,961) healthy years of life lost (YLLs), or between 0.9% and 1.3% of all DALYs in South Africa in 2000, were attributable to IDA. CONCLUSIONS: This first study in South Africa to quantify the burden from IDA suggests that it is a less serious public health problem in South Africa than in many other developing countries. Nevertheless, this burden is preventable, and the study highlights the need to disseminate the food-based dietary guidelines formulated by the National Department of Health to people who need them and to monitor the impact of the food fortification programme.

Estimating the burden of disease attributable to vitamin A deficiency in South Africa in 2000.

OBJECTIVES: To estimate the burden of disease attributable to vitamin A deficiency in children aged 0 - 4 years and pregnant women aged 15 - 49 years in South Africa in 2000. DESIGN: The framework adopted for the most recent World Health Organization comparative risk assessment (CRA) methodology was followed. Population-attributable fractions were calculated from South African Vitamin A Consultative Group (SAVACG) survey data on the prevalence of vitamin A deficiency in children and the relative risks of associated health problems, applied to revised burden of disease estimates for South Africa in the year 2000. Small community studies were used to derive the prevalence in pregnant women. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. SETTING: South Africa. SUBJECTS: Children under 5 years and pregnant women 15 - 49 years. OUTCOME MEASURES: Direct sequelae of vitamin A deficiency, including disability-adjusted life years (DALYs), as well as mortality associated with measles, diarrhoeal diseases and other infections, and mortality and DALYs associated with malaria in children and all-cause maternal mortality. RESULTS: One-third of children aged 0 - 4 years and 1 - 6% of pregnant women were vitamin A-deficient. Of deaths among young children aged 0 - 4 years in 2000, about 28% of those resulting from diarrhoeal diseases, 23% of those from measles, and 21% of those from malaria were attributed to vitamin A deficiency, accounting for some 3,000 deaths. Overall, about 110,467 ( 95% uncertainty interval 86,388 - 136,009) healthy years of life lost, or between 0.5% and 0.8% of all DALYs in South Africa in 2000 were attributable to vitamin A deficiency. CONCLUSIONS: The vitamin A supplementation programme for children and the recent food fortification programme introduced in South Africa in 2003 should prevent future morbidity and mortality related to vitamin A deficiency. Monitoring the effectiveness of these interventions is strongly recommended.