Background: Despite possible benefits for growth, milk is costly to include in foods for undernourished children. Furthermore, the relative effects of different milk components, milk protein (MP), and whey permeate (WP) are unclear. We aimed to assess the effects of MP and WP in lipid-based nutrient supplement (LNS), and of LNS itself, on linear growth and body composition among stunted children. Methods and findings: We performed a randomized, double-blind, 2 × 2 factorial trial among 12 to 59 months old stunted children in Uganda. Children were randomized to 4 formulations of LNS with MP or soy protein isolate and WP or maltodextrin (100 g/day for 12 weeks) or no supplementation. Investigators and outcome assessors were blinded; however, participants were only blinded to the ingredients in LNS. Data were analyzed based on intention-to-treat (ITT) using linear mixed-effects models adjusted for age, sex, season, and site. Primary outcomes were change in height and knee-heel length, and secondary outcomes included body composition by bioimpedance analysis (ISRCTN13093195). Between February and September 2020, we enrolled 750 children with a median age of 30 (interquartile range 23 to 41) months, with mean (± standard deviation) height-for-age z-score (HAZ) −3.02 ± 0.74 and 12.7% (95) were breastfed. The 750 children were randomized to LNS (n = 600) with or without MP (n = 299 versus n = 301) and WP (n = 301 versus n = 299), or no supplementation (n = 150); 736 (98.1%), evenly distributed between groups, completed 12-week follow-up. Eleven serious adverse events occurred in 10 (1.3%) children, mainly hospitalization with malaria and anemia, all deemed unrelated to the intervention. Unsupplemented children had 0.06 (95% confidence interval, CI [0.02, 0.10]; p = 0.015) decline in HAZ, accompanied by 0.29 (95% CI [0.20, 0.39]; p < 0.001) kg/m² increase in fat mass index (FMI), but 0.06 (95% CI [−0.002; 0.12]; p = 0.057) kg/m² decline in fat-free mass index (FFMI). There were no interactions between MP and WP. The main effects of MP were 0.03 (95% CI [−0.10, 0.16]; p = 0.662) cm in height and 0.2 (95% CI [−0.3, 0.7]; p = 0.389) mm in knee-heel length. The main effects of WP were −0.08 (95% CI [−0.21, 0.05]; p = 220) cm and −0.2 (95% CI [−0.7; 0.3]; p = 403) mm, respectively. Interactions were found between WP and breastfeeding with respect to linear growth (p < 0.02), due to positive effects among breastfed and negative effects among non-breastfed children. Overall, LNS resulted in 0.56 (95% CI [0.42, 0.70]; p < 0.001) cm height increase, corresponding to 0.17 (95% CI [0.13, 0.21]; p < 0.001) HAZ increase, and 0.21 (95% CI [0.14, 0.28]; p < 0.001) kg weight increase, of which 76.5% (95% CI [61.9; 91.1]) was fat-free mass. Using height-adjusted indicators, LNS increased FFMI (0.07 kg/m², 95% CI [0.0001; 0.13]; p = 0.049), but not FMI (0.01 kg/m², 95% CI [−0.10, 0.12]; p = 0.800). Main limitations were lack of blinding of caregivers and short study duration. Conclusions: Adding dairy to LNS has no additional effects on linear growth or body composition in stunted children aged 12 to 59 months. However, supplementation with LNS, irrespective of milk, supports linear catch-up growth and accretion of fat-free mass, but not fat mass. If left untreated, children already on a stunting trajectory gain fat at the expense of fat-free mass, thus nutrition programs to treat such children should be considered. Trial registration: ISRCTN13093195

This second article in the series establishing reference values (RVs) for nutrients in human milk describes RVs for protein, carbohydrate, fat, and energy. To establish RVs, the mothers, infants, and lactation quality (MILQ) and early-MILQ studies collected human milk samples throughout the first 8.5 mo of lactation in 1242 well-nourished women in Bangladesh, Brazil, Denmark, and The Gambia. Macronutrients were measured by near-infrared spectroscopy. Protein concentrations decreased from 12.4 g/L at 4-17 d to a 7.7-7.9 g/L plateau by 4-5 mo. Carbohydrate concentrations were stable throughout lactation, ranging from 68.2 to 70.1 g/L. Fat concentrations decreased from 37.0 g/L at 4-17 d to 31.2-32.8 g/L after 2-3 mo. Energy density mirrored fat trends, decreasing from 665 kcal/L at 4-17 d to 597-602 kcal/L by 3-4 mo. Compared with estimates used by the Institute of Medicine (IOM)--renamed the National Academy of Medicine (NAM) in 2015--to set nutrient intake recommendations for infants, MILQ values were ∼90% of concentrations used for carbohydrate and energy, and 70%-80% for protein and fat. Total daily median intakes (concentrations × milk volumes) from 1 to 6 mo were on par with IOM adequate intakes (AIs) for carbohydrate and energy, 65% of the AI for protein, and 84% of the AI for fat. These RVs offer a critical resource for understanding the nutritional contributions of human milk and informing public health practices to support infant growth and development.

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type 2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised crossover study consisting of two 4-week dietary interventions: Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western diet, the Traditional diet reduced mean and maximum daily blood glucose by 0·17 mmol/l (95 % CI 0·05, 0·29; P = 0·006) and 0·26 mmol/l (95 % CI 0·06, 0·46; P = 0·010), respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0·5 kg (95 % CI; 0·09, 0·90; P = 0·016) relative to the Western diet and 4 % (95 % CI 1, 9; P = 0·018) lower LDL:HDL-cholesterol, which after adjustment for weight loss appeared to be driven by HDL elevation (0·09 mmol/l (0·03, 0·15), P = 0·006). A diet–gene interaction was indicated on insulin sensitivity in the OGTT (p = 0·093), which reflected a non-significant increase of 1·4 (–0·6, 3·5) mmol/l in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.

Aim We investigated associations between newborn body composition and anthropometry and body composition at 3 years in Danish children born from obese mothers. Methods Analyses are based on data from the observational cohort study SKOT II (SKOT; small children's diet and well-being (Danish)). Body composition at birth and at 3 years was assessed by dual-energy X-ray absorptiometry (DXA) scans and bioelectrical impedance analysis (BIA), respectively. Multiple linear regression models were applied to determine associations between newborn body composition and anthropometry and body composition at 3 years. Results Birthweight z-score (BWZ) was positively associated with fat-free mass (FFM), height, fat-free mass index (FFMI), fat mass (FM) and fat mass index (FMI) at 3 years. Newborn FFM was positively associated with FFM, height, FFMI and FM at 3 years, and positive trends were seen between newborn FM and FM and FMI at 3 years. Conclusion We showed that infants born with a higher BWZ go on to be taller at 3 years. They also grow to be heavier, to which FM and FFM both contribute, independently of linear growth. Additionally, it seems that FFM tracks into early childhood, thus supporting intrauterine programming of later health.