Clinical Studies on IronBiotics
IronBiotics is Danone's patent-filed combination of Iron, Prebiotics and Vitamin C that supports iron absorption.
GUMLi Randomized Control Trial
Compared with Cow Milk, a Growing-Up Milk Increases Vitamin D and Iron Status in Healthy Children at 2 Years of Age: The Growing-Up Milk–Lite (GUMLi) Randomized Controlled Trial
Amy L Lovell, Peter SW Davies, Rebecca J Hill, Tania Milne, Misa Matsuyama, Yannan Jiang, Rachel X Chen, Trecia A Wouldes, 2Anne-Louise M Heath, Cameron C Grant, and Clare R Wall
Abstract
Iron deficiency (ID) and vitamin D deficiency (VDD) are significant pediatric health issues in New Zealand and Australia and remain prevalent micronutrient deficiencies in young children globally.
We aimed to investigate the effect of a micronutrient-fortified, reduced-energy growing-up milk (GUMLi) compared with cow milk (CM) consumed for 1 y on dietary iron and vitamin D intakes and the status of New Zealand and Australian children at 2 y of age.
The GUMLi Trial was a multicenter, double-blind, randomized controlled trial in 160 healthy 1-y-old New Zealand and Australian children conducted in 2015–2017. Participants were randomly assigned 1:1 to receive GUMLi (1.7 mg Fe/100 mL; 1.3 µg cholecalciferol/100 mL) or CM (0.02 mg Fe/100 mL; 0.06 µg cholecalciferol/ 100 mL) for 12 mo. Secondary outcomes, reported here, included change in dietary iron and vitamin D intakes, iron status, and 25-hydroxyvitamin D [25(OH)D] concentrations from blood samples at age 2 y. All regression models were adjusted for baseline outcome and study center.
GUMLi was a large contributor to dietary intakes of iron and vitamin D after 12 mo when compared with intakes from food and CM. The adjusted mean difference between groups for serum ferritin concentrations was 17.8 µg/L (95% CI: 13.6, 22.0 µg/L; P < 0.0001), and for 25(OH)D it was 16.6 nmol/L (95% CI: 9.9, 23.3 nmol/L; P < 0.0001). After 12 mo, ID was present in 16 (24%) participants in the CM group and 5 (7%) participants in the GUMLi group (P = 0.009), and the prevalence of VDD in the CM group increased to 14% (n = 10) and decreased to 3% (n = 2) (P = 0.03) in the GUMLi group.
In comparison with CM, GUMLi significantly improved dietary iron and vitamin D intakes and the iron and vitamin D status of healthy children at 2 y of age. This trial was registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12614000918628. J Nutr 2018;148:1570–1579.
IDEA Study
A micronutrient-fortified young-child formula improves the iron and vitamin D status of healthy young European children: a randomized, double-blind controlled trial
Marjolijn D Akkermans, Simone RBM Eussen, Judith M van der Horst-Graat, Ruurd M van Elburg, Johannes B van Goudoever, and Frank Brus
Abstract
Iron deficiency (ID) and vitamin D deficiency (VDD) are common among young European children because of low dietary intakes and low compliance to vitamin D supplementation policies. Milk is a common drink for young European children. Studies evaluating the effect of milk fortification on iron and vitamin D status in these children are scarce.
We aimed to investigate the effect of a micronutrientfortified young-child formula (YCF) on the iron and vitamin D status of young European children.
In this randomized, double-blind controlled trial, healthy German, Dutch, and English children aged 1–3 y were allocated to receive either YCF (1.2 mg Fe/100 mL; 1.7 mg vitamin D/100 mL) or nonfortified cow milk (CM) (0.02 mg Fe/100 mL; no vitamin D) for 20 wk. Blood samples were taken before and after the intervention. The primary and secondary outcomes were change from baseline in serum ferritin (SF) and 25-hydroxyvitamin D [25(OH)D], respectively. ID was defined as SF ,12 mg/L in the absence of infection (high-sensitivity C-reactive protein ,10 mg/L) and VDD as 25(OH)D ,50 nmol/L. Statistical adjustments were made in intention-to-treat analyses for sex, country, age, baseline micronutrient status, and micronutrient intake from food and supplements (and sun exposure in the case of vitamin D outcomes).
The study sample consisted of 318 predominantly Caucasian (w95%) children. The difference in the SF and 25(OH)D change between the treatment groups was 6.6 mg/L (95% CI: 1.4, 11.7 mg/L; P = 0.013) and 16.4 nmol/L (95% CI: 9.5, 21.4 nmol/L; P , 0.001), respectively. The probability of ID (OR 0.42; 95% CI:0.18, 0.95; P = 0.036) and VDD (OR 0.22; 95% CI: 0.01, 0.51; P , 0.001) after the intervention was lower in the YCF group than in the CM group.
Micronutrient-fortified YCF use for 20 wk preserves iron status and improves vitamin D status in healthy young children in Western Europe. This trial was registered at www.trialregister.nl as NTR3609. Am J Clin Nutr 2017;105:391–9.
KIF Study
Prebiotics increase iron absorption and reduce the adverse effects of iron on the gut microbiome and inflammation: a randomized controlled trial using iron stable isotopes in Kenyan infants
Nadja Mikulic, Mary A Uyoga, Nicole U Stoffel, Muriel Derrien, Suzane Nyilima, Ioannis Kostopoulos, Guus Roeselers, Empar Chenoll, Edith Mwasi, Giulia Pironaci, Simon Karanja, Raphaelle Bourdet-Sicard, Michael B Zimmermann
Abstract
Iron fortificants tend to be poorly absorbed and may adversely affect the gut, especially in African children.
We assessed the effects of prebiotic galacto-oligosaccharides/fructo-oligosaccharides (GOS/FOS) on iron absorption and gut health when added to iron-fortified infant cereal.
We randomly assigned Kenyan infants (n ¼ 191) to receive daily for 3 wk a cereal containing iron and 7.5 g GOS/FOS (7.5 g þ iron group), 3 g (3-g þ iron group) GOS/FOS, or no prebiotics (iron group). A subset of infants in the 2 prebiotic þ iron groups (n ¼ 66) consumed 4 stable iron isotope–labeled test meals without and with prebiotics, both before and after the intervention. Primary outcome was fractional iron absorption (FIA) from the cereal with or without prebiotics regardless of dose, before and after 3 wk of consumption. Secondary outcomes included fecal gut microbiota, iron and inflammation status, and effects of prebiotic dose.
Median (25th–75th percentiles) FIAs from meals before intervention were as follows: 16.3% (8.0%–27.6%) without prebiotics compared with 20.5% (10.4%–33.4%) with prebiotics (Cohen d ¼ 0.53; P < 0.001). FIA from the meal consumed without prebiotics after intervention was 22.9% (8.5%–32.4%), 41% higher than from the meal without prebiotics before intervention (Cohen d ¼ 0.36; P ¼ 0.002). FIA from the meal consumed with prebiotics after intervention was 26.0% (12.2%–36.1%), 60% higher than from the meal without prebiotics before intervention (Cohen d ¼ 0.45; P ¼ 0.007). After 3 wk, compared with the iron group, the following results were observed: 1) Lactobacillus sp. abundances were higher in both prebiotic þ iron groups (P < 0.05); 2) Enterobacteriaceae sp. abundances (P ¼ 0.022) and the sum of pathogens (P < 0.001) were lower in the 7.5-g þ iron group; 3) the abundance of bacterial toxin-encoding genes was lower in the 3-g þ iron group (false discovery rate < 0.05); 4) fecal pH (P < 0.001) and calprotectin (P ¼ 0.033) were lower in the 7.5-g þ iron group.
Adding prebiotics to iron-fortified infant cereal increases iron absorption and reduces the adverse effects of iron on the gut microbiome and inflammation in Kenyan infants.
Ferric Study
Prebiotic fibers as a strategy to improve iron status: enhancing in vitro iron absorption through prebiotic fermentation
Fernanda Olguin-Diaz, Gabriel Thomassen, Ioannis Kostopoulos, Guus Roeselers, Marion Jourdan, Jan Knol, Ingrid Renes
Abstract
Iron deficiency is common during early life. Prebiotics may enhance iron bioavailability (IB) in the small intestine and in the colon.
To study this, IMF was supplemented with inulin, lcFOS, their combinations (1:1 or 2:1), or scGOS:lcFOS (9:1). IMFs were digested in vitro, or fermented ex vivo yielding short-chain fatty acids (SCFA) and altering microbiota composition. Digested IMF containing either prebiotics or SCFA were incubated on Caco-2 cells to assess IB under simulated small-intestinal or colonic conditions respectively. Fermentation of inulin:lcFOS and scGOS:lcFOS increased Bifidobacteriaceae, reduced Enterobacteriaceae, and enhanced acetic acid (AA) production. Inulin:lcFOS increased small-intestinal IB (1.2-fold). SCFA from Inulin:lcFOS and scGOS:lcFOS increased colonic IB by 3.7- and 5.0-fold, respectively.
When combining small-intestinal and colonic IB, overall IB increased ∼1.5-fold versus the control. Prebiotic-induced AA production played a key role in enhancing IB. Combining inulin or scGOS with lcFOS in IMF may improve iron absorption and support beneficial infant gut microbiota.
Algeria
Food consumption, nutritional intakes and the role of milk formulas in nutrient adequacy among young children from birth to 2 years living in urban Algeria
Alice Busnel, Marine Domet, Khaoula Ramchani Ben Othman, Caroline Desclée De Maredsous, Hanane Ghomari-Boukhatem, Malika Bouchenak, Karim Bouziane-Nedjadi and Peggy Drouillet-Pinard
Abstract
Undernutrition, stunted growth and obesity remain a concern in Algeria. Currently, limited data are available on nutrient intakes among children. Our study aimed to describe food and nutrient intakes and the role of milk formulas among Algerian children.
Dietary intakes were collected using a 4-d interview-based survey for children aged 0–24 months, living in urban areas in Algeria in 2019.
Food consumptions were described. For children aged 6–24 months, nutrient intakes and adequacy were estimated. Modelling was used to estimate the nutritional impact of substituting cow’s milk for age-appropriate infant formulas (IF). Participants: Totally, 446 children aged 0–24 months.
Before 6 months, 91·6 % of infants were breastfed. Breastmilk was also the main milk consumed between 6 and 12 months, whereas cow’s milk predominated after 12 months. In children aged 6–24 months, nutrient adequacy prevalence was above 75 % for the majority of nutrients. However, less than 30 % of the children had adequate intakes for total fats, Fe and vitamin D. Simulated substitution of cow’s milk for IF led to improved adequacy for proteins, Fe, and vitamins D and E. Conclusions: Our study showed that breast-feeding rates were high until 6 months, then declined with age. Consumed foods allowed Algerian children aged 6–24 months to meet most of their nutritional needs, but inadequate intakes were reported for some key nutrients. Our modelling suggested that milk formulas may help to improve nutrient adequacy among non-breastfed infants. Other dietary changes could also be further investigated to enable children to meet all nutritional recommendations.
China (2019)
The contribution of milks and formulae to micronutrient intake in 1-3 years old children in urban China: a simulation study
Tao Li MD, Jialu You PhD, Joséphine Pean MSc, Anne Lluch PhD, Simone Eussen PhD, Fabien Delaere PhD, Jacques G Bindels PhD, Yaohua Dai MD
Abstract
A recent dietary survey in 5 big cities in China provided information on various milk options consumed by 1-3 years old children. To investigate the nutritional role of these milks (young-child formula (YCF), cow’s milk, others), simulation analyses based on this survey were performed.
We studied daily intakes of calcium, iron, zinc, vitamins A, B-1, B-2, C and E and compared these to the Chinese DRIs. In Scenario 1, consumption of cow’s milk, kid’s milk and/or soy milk was replaced with matching amounts of YCF (n=66 children). In Scenario 2, where 348 children exclusively consumed YCF, YCF was replaced with matching amounts of cow’s milk.
Scenario 1 revealed significant increases in total dietary intakes of iron, vitamins A, B-1, C and E upon substitution of the various milks with YCF. The proportions of children not meeting the Estimated Average Requirement (EAR) for these nutrients dropped from 29, 26, 61, 53 and 54 % to 12, 11, 50, 27 and 24%, respectively. In Scenario 2, the hypothetical substitution of YCF by cow’s milk increased the proportions of children not meeting the EAR for these nutrients, calcium and zinc from 11, 6, 49, 15, 28, 42, and 8 to 45, 24, 78, 69, 59, 44, and 20, respectively. Execution of Scenario 2 in subgroups of 1-2- and 2-3 years old children revealed similar results.
YCF may help to reduce the risk of insufficient intake of several key micronutrients for toddlers, independent of age.
China (2022)
Dairy fortification as a good option for dietary nutrition status improvement of 676 preschool children in China: A simulation study based on a cross-sectional diet survey (2018–2019)
Ye Ding, Fei Han, Zhencheng Xie , Genyuan Li, Yiding Zhuang, Jia Yin, Mingxian Fu, Jialu You and Zhixu Wang
Abstract
Chinese children are deficient in several essential nutrients due to poor dietary choices. Dairy products are a source of many underconsumed nutrients, but preschool children in China consume dairy products significantly less than the recommended level.
From the cross-sectional dietary intake survey of infants and young children aged 0–6 years in China (2018–2019), preschool children (age: 3–6 years) (n = 676) were selected. The four-day dietary data (including 2 working days and 2 weekends) collected through an online diary with reference to the food atlas were used for analysis and simulation. In scenario 1, individual intake of liquid milk equivalents was substituted at a corresponding volume by soymilk, cow’s milk, or formulated milk powder for preschool children (FMP-PSC). In scenario 2, the amount of cow’s milk or FMP-PSC increased to ensure each child’s dairy intake reached the recommended amount (350 g/day). In both scenarios, the simulated nutrient intakes and nutritional inadequacy or surplus were compared to the survey’s actual baseline data.
It was suggested suggested that replacing dairy foods with FMPPSC at matching volume is better than replacing them with soymilk or cow’s milk to increase the intake of DHA, calcium, iron, zinc, iodine, vitamin A, vitamin B 1 , vitamin B 3 , vitamin B 12 , vitamin C and vitamin D. Moreover, our results suggested that adding FMP-PSC to bring each child’s dairy intake to the recommended amount can bring the intakes of dietary fiber, DHA, calcium, iron, zinc, iodine, vitamin A, vitamin B 1 , vitamin B 3 , vitamin B 9 , vitamin B 12 , vitamin C and vitamin D more in line with the recommendations when compared with cow’s milk.
Accurate nutrition information should be provided to the parents of preschool children so as to guide their scientific consumption of dairy products and the usage and addition of fortified dairy products can be encouraged as needed.
United Kingdom
Theoretical Impact of Replacing Whole Cow’s Milk by Young-Child Formula on Nutrient Intakes of UK Young Children: Results of a Simulation Study
Simone R.B.M. Eussen, Josephine Pean, Leanne Oliviera, Fabien Delaere, Anne Lluch
Abstract
Research into the role of young-child formulae (YCF) in a child’s diet is limited and there is no consensual recommendation on its use. We evaluated the theoretical nutritional impact of replacing the existing practice of consuming cow’s milk by YCF.
From the UK Diet and Nutrition Survey of Infants and Young Children, whole cow’s milk consumers, aged 12–18 months (n = 591) were selected for simulation scenarios. In Scenario 1, we tested the replacement of all whole cow’s milk (434 ± 187 ml/day) by a matching volume of YCF, and in Scenario 2, all whole cow’s milk was replaced by the on-pack recommended daily intake of 300 ml. Nutrient intakes before and after simulation scenarios were compared and evaluated against nutrient recommendations.
Intakes of protein and saturated fatty acids were significantly decreased, whereas essential fatty acid intakes were increased. The prevalence of nutrient inadequacy before simulation was 95.2% for vitamin D and 53.8% for iron. After simulation, inadequacy decreased to 4.9% (Scenario 1) and 0% (Scenario 2) for vitamin D and to 2.7% (Scenario 1) and 1.1% (Scenario 2) for iron.
Replacement of habitual cow’s milk intake by a matching volume or 300 ml of YCF may lead to nutritional intakes more in line with recommendations in young children.