{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T01:30:37Z","timestamp":1768786237028,"version":"3.49.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>The relationship of protein intake with insulin-like growth factor 1 (IGF-1) concentrations in well-nourished children during the second year of life is poorly understood. The aim of this study was to explore the effect of a reduced-protein Growing Up Milk Lite (GUMLi) or unfortified cow's milk (CM) on protein intake, growth, and plasma IGF-1 at 2 y. An exploratory analysis of a sub-sample of Auckland-based children (<jats:italic>n<\/jats:italic> = 79) in the GUMLi trial (a double-blind, randomised control trial, <jats:italic>N<\/jats:italic> = 160) completed in Auckland and Brisbane (2015\u20132017) was conducted. One-year old children were randomised to receive a reduced-protein GUMLi (1.7 g protein\/100 mL) or a non-fortified CM (3.1 g protein\/100 mL) for 12 months. Blood sampling and anthropometric measurements were made at 1 and 2 y. Diet was assessed using a validated food frequency questionnaire. Total protein intake (g\/d) from all cow's milk sources was 4.6 g (95% CI: \u22126.7, \u22122.4; <jats:italic>p<\/jats:italic> &amp;lt; 0.005) lower in the GUMLi group after 12 months of the intervention, with a significant group-by-time interaction (<jats:italic>p<\/jats:italic> = 0.005). Length-for-age (LAZ) and weight-for-length (WLZ) <jats:italic>z<\/jats:italic>-scores did not differ between groups, however, mean body fat % (BF%) was 3.2% (95%CI: \u22126.2, \u22120.3; <jats:italic>p<\/jats:italic> = 0.032) lower in the GUMLi group at 2 y. There was no difference between the intervention groups in relation to IGF-1 and IGF-BP3 (<jats:italic>p<\/jats:italic> = 0.894 and 0.698, respectively), with no group-by-sex interaction. After combining the groups, IGF-1 concentration at 2 y was positively correlated with parameters of growth (all <jats:italic>p<\/jats:italic> &amp;lt; 0.05), total cow's milk intake (<jats:italic>p<\/jats:italic> = 0.032) after adjusting for sex, breastfeeding status, and gestation. Randomisation to a reduced protein GUMLi resulted in small reduction in %BF and lower total protein intakes but had no effect on growth. Plasma IGF-1 concentrations were independently associated with total protein intake from cow's milk at 2 y, highlighting a potential area of the diet to target when designing future protein-related nutrition interventions.<\/jats:p><jats:p><jats:bold>Clinical Trial Registration:<\/jats:bold> Australian New Zealand Clinical Trials Registry number: ACTRN12614000918628. Date registered: 27\/08\/2014.<\/jats:p>","DOI":"10.3389\/fnut.2021.666228","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T04:44:47Z","timestamp":1623300287000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Protein Intake, IGF-1 Concentrations, and Growth in the Second Year of Life in Children Receiving Growing Up Milk \u2013 Lite (GUMLi) or Cow's Milk (CM) Intervention"],"prefix":"10.3389","volume":"8","author":[{"given":"Amy L.","family":"Lovell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Milne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misa","family":"Matsuyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca J.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter S. W.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cameron C.","family":"Grant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare R.","family":"Wall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.3945\/ajcn.115.118612","article-title":"Dietary protein intake is associated with body mass index and weight up to 5 y of age in a prospective cohort of twins, 2","volume":"103","author":"Pimpin","year":"2015","journal-title":"Am J Clin Nutr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"718S","DOI":"10.3945\/ajcn.113.072603","article-title":"Protein needs early in life and long-term health\u2013","volume":"99","author":"Michaelsen","year":"2014","journal-title":"Am J Clin Nutr."},{"key":"B3","volume-title":"Protein and amino acid requirements in human nutrition","year":"2007"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1016\/j.jand.2017.03.016","article-title":"Early life protein intake: food sources, correlates, and tracking across the first 5 years of life","volume":"117","author":"Campbell","year":"2017","journal-title":"J Acad Nutr Diet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1007\/s00394-015-0978-y","article-title":"Energy and macronutrient intakes and adherence to dietary guidelines of infants and toddlers in Belgium","volume":"55","author":"Huysentruyt","year":"2016","journal-title":"Eur J Nutr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1111\/jhn.12452","article-title":"Nutrient intakes and compliance with nutrient recommendations in children aged 1\u20134 years in Ireland","volume":"30","author":"Walton","year":"2017","journal-title":"J Human Nutr Diet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1093\/ajcn\/39.1.129","article-title":"Adiposity rebound in children: a simple indicator for predicting obesity","volume":"39","author":"Rolland-Cachera","year":"1984","journal-title":"Am J Clin Nutr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/huon.200700004","article-title":"Overweight, appetite control, and the role of glutamate and excess nutritional protein during child development","volume":"1","author":"Hermanussen","year":"2007","journal-title":"Human Ontogenet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1038\/ejcn.2009.132","article-title":"BMI at 4 years of age is associated with previous and current protein intake and with paternal BMI","volume":"64","author":"\u00d6hlund","year":"2010","journal-title":"Eur J Clin Nutr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.3945\/ajcn.113.064071","article-title":"Lower protein content in infant formula reduces BMI and obesity risk at school age: follow-up of a randomized trial","volume":"99","author":"Weber","year":"2014","journal-title":"Am J Clin Nutr."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1038\/ijo.2010.64","article-title":"Stabilization in the prevalence of childhood obesity: a role for early nutrition?","volume":"34","author":"Rolland-Cachera","year":"2010","journal-title":"Int J Obes."},{"key":"B12","first-page":"573","article-title":"Influence of macronutrients on adiposity development: a follow up study of nutrition and growth from 10 months to 8 years of age","volume":"19","author":"Rolland-Cachera","year":"1995","journal-title":"Int J Obes Related Metab Disord."},{"key":"B13","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/0026-0495(95)90221-X","article-title":"Nutritional regulation of insulin-like growth factor-I","volume":"44","author":"Ketelslegers","year":"1995","journal-title":"Metab Clin Exp."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1093\/ajcn\/85.6.1626","article-title":"Protein intake during the period of complementary feeding and early childhood and the association with body mass index and percentage body fat at 7 y of age","volume":"85","author":"G\u00fcnther","year":"2007","journal-title":"Am J Clin Nutr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e21083","DOI":"10.3402\/fnr.v57i0.21083","article-title":"Protein intake from 0 to 18 years of age and its relation to health: a systematic literature review for the 5th Nordic Nutrition Recommendations","volume":"57","author":"H\u00f6rnell","year":"2013","journal-title":"Food Nutr Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1093\/ajcn\/86.6.1765","article-title":"Early protein intake and later obesity risk: which protein sources at which time points throughout infancy and childhood are important for body mass index and body fat percentage at 7 y of age","volume":"86","author":"Gunther","year":"2007","journal-title":"Am J Clin Nutr."},{"key":"B17","volume-title":"Food and Nutrition Guidelines for Healthy Infants and Toddlers (Aged 0\u20132): A background paper","year":"2012"},{"key":"B18","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/s41430-018-0108-z","article-title":"IGF-I and IGFBP-3 concentrations at 2 years: associations with anthropometry and milk consumption in an Indian cohort","volume":"72","author":"Wiley","year":"2018","journal-title":"Eur J Clin Nutr."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1776S","DOI":"10.3945\/ajcn.110.000596","article-title":"Milk protein intake, the metabolic-endocrine response, and growth in infancy: data from a randomized clinical trial","volume":"94","author":"Socha","year":"2011","journal-title":"Clin Nutr."},{"key":"B20","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jpeds.2018.10.020","article-title":"Different growth patterns persist at 24 months of age in formula-fed infants randomized to consume a meat-or dairy-based complementary diet from 5 to 12 months of age","volume":"206","author":"Tang","year":"2019","journal-title":"J Pediatr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1093\/ajcn\/nqy038","article-title":"A meat-or dairy-based complementary diet leads to distinct growth patterns in formula-fed infants: a randomized controlled trial","volume":"107","author":"Tang","year":"2018","journal-title":"Am J Clin Nutr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1038\/ejcn.2008.80","article-title":"The effects of whole milk and infant formula on growth and IGF-I in late infancy","volume":"63","author":"Larnkj\u00e6r","year":"2009","journal-title":"Eur J Clin Nutr."},{"key":"B23","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1093\/ajcn\/80.2.447","article-title":"Animal protein intake, serum insulin-like growth factor I, and growth in healthy 2.5-y-old Danish children","volume":"80","author":"Hoppe","year":"2004","journal-title":"Am J Clin Nutr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1093\/ajcn\/79.3.494","article-title":"Protein intake at 9 mo of age is associated with body size but not with body fat in 10-y-old Danish children","volume":"79","author":"Hoppe","year":"2004","journal-title":"Am J Clin Nutr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"21836","DOI":"10.3402\/fnr.v57i0.21836","article-title":"Nutritional adequacy of diets containing growing up milks or unfortified cow's milk in Irish children (aged 12\u201324 months)","volume":"57","author":"Walton","year":"2013","journal-title":"Food Nutr Res."},{"key":"B26","volume-title":"Codex standard for follow-up formula","year":"1987"},{"key":"B27","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1097\/MPG.0000000000001454","article-title":"Complementary feeding: a position paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition","volume":"64","author":"Fewtrell","year":"2017","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1093\/ajcn\/nqy302","article-title":"A multicenter, double-blind, randomized, placebo-controlled trial to evaluate the effect of consuming Growing Up Milk \u201cLite\u201d on body composition in children aged 12\u201323 mo","volume":"109","author":"Wall","year":"2019","journal-title":"Am J Clin Nutr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2014A metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"Harris","year":"2009","journal-title":"J Biomed Inform."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3265","DOI":"10.1017\/S1368980015000841","article-title":"Relative validity and reproducibility of an FFQ to determine nutrient intakes of New Zealand toddlers aged 12\u201324 months","volume":"18","author":"Watson","year":"2015","journal-title":"Public Health Nutr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.jand.2014.09.016","article-title":"Relative validity and reproducibility of a food frequency questionnaire for identifying the dietary patterns of toddlers in New Zealand","volume":"115","author":"Mills","year":"2015","journal-title":"J Acad Nutr Diet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1017\/S0007114520002664","article-title":"Validation and calibration of the Eating Assessment in Toddlers FFQ (EAT FFQ) for children, used in the Growing Up Milk\u2013Lite (GUMLi) randomised controlled trial","volume":"125","author":"Lovell","year":"2020","journal-title":"Br J Nutr"},{"key":"B33","volume-title":"MATLAB and Statistics Toolbox","year":"2018"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1093\/jn\/nxy167","article-title":"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\u2013lite (GUMLi) randomized controlled trial","volume":"148","author":"Lovell","year":"2018","journal-title":"J Nutr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/sj.ijo.0802405","article-title":"Predictors of children's body mass index: a longitudinal study of diet and growth in children aged 2\u20138 y","volume":"28","author":"Skinner","year":"2004","journal-title":"Int J Obes."},{"key":"B36","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1159\/000354431","article-title":"Nutrient intake in infancy and body mass index at six years in two population-based cohorts recruited before and after revision of infant dietary recommendations","volume":"63","author":"Thorisdottir","year":"2013","journal-title":"Ann Nutr Metab."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.3945\/ajcn.2008.27091","article-title":"Lower protein in infant formula is associated with lower weight up to age 2 y: a randomized clinical trial","volume":"89","author":"Koletzko","year":"2009","journal-title":"Am J Clin Nutr."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.3390\/ijerph15081742","article-title":"Protein intake during the first two years of life and its association with growth and risk of overweight","volume":"15","author":"Tang","year":"2018","journal-title":"Int J Environ Res Public Health."},{"key":"B39","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1159\/000438495","article-title":"Composition of follow-up formula for young children aged 12-36 months: recommendations of an International Expert Group Coordinated by the Nutrition Association of Thailand and the Early Nutrition Academy","volume":"67","author":"Suthutvoravut","year":"2015","journal-title":"Ann Nutr Metab."},{"key":"B40","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1017\/S1368980012002893","article-title":"Nutrient intakes of children aged 1\u20132 years as a function of milk consumption, cows' milk or growing-up milk","volume":"16","author":"Ghisolfi","year":"2013","journal-title":"Public Health Nutr."},{"key":"B41","volume-title":"Food and Nutrition Guidelines for Healthy Infants and Toddlers (Aged 0\u20132): A background paper (4th Ed)","year":"2008"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.3945\/ajcn.116.137752","article-title":"Usual nutrient intakes of US infants and toddlers generally meet or exceed Dietary Reference Intakes: findings from NHANES 2009\u00e2\u20ac\u201c2012","volume":"104","author":"Ahluwalia","year":"2016","journal-title":"Am J Clin Nutr."},{"key":"B43","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1079\/PHN2002257","article-title":"Dietary intakes of 6\u201324-month-old urban South Island New Zealand children in relation to biochemical iron status","volume":"5","author":"Soh","year":"2002","journal-title":"Public Health Nutr."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1038\/ejcn.2009.34","article-title":"Differential effects of casein versus whey on fasting plasma levels of insulin, IGF-1 and IGF-1\/IGFBP-3: results from a randomized 7-day supplementation study in prepubertal boys","volume":"63","author":"Hoppe","year":"2009","journal-title":"Eur J Clin Nutr."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1111\/obr.12476","article-title":"Nutritional interventions or exposures in infants and children aged up to 3 years and their effects on subsequent risk of overweight, obesity and body fat: a systematic review of systematic reviews","volume":"17","author":"Patro Go\u0142ab","year":"2016","journal-title":"Obes Rev."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2021.666228\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T04:44:53Z","timestamp":1623300293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2021.666228\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,10]]},"references-count":45,"alternative-id":["10.3389\/fnut.2021.666228"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2021.666228","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,10]]},"article-number":"666228"}}