A major European trial suggests that cutting milk protein in toddler formula may not lower BMI by age 2, but it could help keep early growth on a steadier track.
Trial: The toddler milk intervention trial (ToMI): A randomized controlled trial on the effect of protein content in young child formula on BMI and growth. Image Credit: MIA Studio / Shutterstock
In a recent study published in the journal Clinical Nutrition, researchers present the results of the Toddler Milk Intervention (ToMI) trial, a multicenter (Spain and Germany), randomized controlled trial (RCT) investigating whether reducing protein intake during the second year of life could lower body mass index (BMI) at 24 months. The study followed 1,624 healthy children randomly assigned to lower (LP; 1.5 g/100 kcal) or higher (HP; 6.1 g/100 kcal) protein isocaloric formulas.
Study findings did not identify a statistically significant difference in participants’ BMI z-scores (zBMI) at 24 months. However, the higher-protein group was observed to exhibit significant upward deviations in weight and length z-scores relative to World Health Organization (WHO) standards. These findings suggest that while the critical window for adiposity programming may peak in infancy, protein intake remains a key driver of weight and linear growth through toddlerhood.
Early Protein Hypothesis and Toddler Nutrition Background
The Childhood Obesity Prevention (CHOP) trial has previously shown a causal link between high protein intake in infancy and increased obesity risk at school age, an observation thought to be mediated by the "Early Protein Hypothesis," which suggests that high concentrations of branched-chain amino acids (BCAA) may activate the mammalian target of rapamycin (mTOR) pathway.
As children enter their second year, their diet notably shifts from monotonous (breast) milk intake to a diverse array of solid and semi-solid foods. However, pediatric records highlight that despite this transition, milk products continue to provide approximately 50% of a toddler’s total protein intake.
These records further indicate that while the United States (US) and European public health guidelines recommend that toddlers and young children consume moderate amounts of dairy, often around 300 to 500 ml per day, actual intake often exceeds these levels, raising clinical concerns about unintended metabolic acceleration. Unfortunately, evidence in toddlerhood has remained less clear than in infancy.
Toddler Milk Intervention Trial Design
The Toddler Milk Intervention (ToMI) trial aimed to address these knowledge gaps and inform future pediatric recommendations by investigating whether modifying the protein content of Young Child Formula (YCF) could mitigate hypothesized metabolic risks in a population already consuming high levels of animal protein.
The trial used a randomized, double-blind, parallel-group design, which leveraged a cohort of 1,624 healthy children (age = 12 months) recruited from Munich, Germany, and the Reus/Tarragona region of Spain. Study participants were randomly assigned to receive one of two isocaloric formulas (201 kJ/48 kcal per 100 mL) until 24 months of age:
The Low Protein (LP) cohort was provided with YCF intended to approximate the protein density of human milk, 0.72 g protein/100 mL (1.5 g/100 kcal).
The High Protein (HP) cohort was provided with YCF approximating the protein density of regular cow’s milk, 2.95 g protein/100 mL (6.1 g/100 kcal).
The study tracked participants’ anthropometric measurements (particularly weight and recumbent length) at ages 12, 18, and 24 months using standardized WHO protocols. Statistical models were used to standardize these datasets into age- and sex-adjusted z-scores.
Furthermore, dietary intake was monitored using parent-reported 24-hour recalls conducted on a single day, assisted by a photographic portion guide. Statistical analysis primarily comprised analysis of covariance (ANCOVA) models, which followed an intention-to-treat (ITT) approach and were adjusted for participants’ baseline anthropometric values, sex, and country.
Protein Intake Effects on Toddler Growth
Study intervention analyses revealed a cohort-specific dietary separation at 18 months, with the LP group maintaining a protein intake of 14% of total energy, while the HP group increased to 18% (p < 0.001). At 24 months, however, the averaged zBMI scores of the two cohorts were statistically indistinguishable.
Notably, the longitudinal data did reveal three statistically significant secondary effects:
At 18 months, the LP group had a significantly lower zBMI than the HP group (mean difference [MD] = -0.07; p = 0.007), suggesting a transient effect on BMI at this age.
Both weight and length z-scores were found to be significantly lower in the LP group at 18 and 24 months (p < 0.001). At 24 months, MD in weight z-scores = -0.11, and MD in length z-scores = -0.13 for LP versus HP.
Children with lower baseline protein intake, particularly those consuming ≤15% of total energy from protein, showed a more pronounced response to the study interventions (p < 0.001). Furthermore, this response was significantly stronger in German children (p = 0.002) than their Spanish counterparts (p = 0.911), which the authors say supports the hypothesis that lower protein intake before intervention enhances the intervention effect.
Toddler Milk Recommendations and Future Follow-Up
The ToMI trial demonstrates that while modifying milk protein intake in the second year of life does not yield a sustained reduction in BMI at 24 months, it does support more stable growth trajectories. Given that most toddlers' protein intake reportedly exceeds their growth requirements, the authors suggest that regular milk intake should generally not exceed about 200 to 400 mL per day to prevent unnecessary growth acceleration.
However, the authors emphasize that further follow-up through age six is necessary to determine if these early growth deviations manifest as long-term adiposity. The findings are also limited to cow’s milk protein in the study formulas, and dietary intake was assessed using single 24-hour recalls.
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