Effect of β-casein A2 cow milk supplementation on physical growth, inflammation, growth-related hormones, and nutritional biomarkers in stunted children

Abstract

Purpose: Previous studies have suggested that milk consumption can promote growth in children. However, limited studies have been performed on the effects of cow milk varieties, especially β-casein A2 milk. This study aims to investigate the effect of β-casein A2 cow milk supplementation on physical growth, inflammation, and growth-related hormone and nutritional biomarker profiles in growth-stunted children.

Methods: This is a quasi-experimental study with only one group and a pre-and posttest design. This research is divided into 3 stages: allele testing in the β-casein gene, processing into ready-to-drink milk, and a clinical trial. The participants were children aged 12-36 months who were given 200-mL β-casein A2 cow milk supplementation once a day for 3 months. The outcome assessments were physical growth (body weight and height), inflammation (tumor necrosis factor-alpha [TNF-α] and cortisol levels), and biological markers related to growth and nutrition (insulin-like growth factor-1 [IGF-1], growth hormone [GH], and transferrin) that were measured during pre-, mid (week 6)-, and post (week 12)-intervention periods.

Results: This study included 30 study participants. Significant body weight and height improvements were observed at week 6 and postintervention (week 12) compared to preintervention. There were significant reductions in the inflammation markers TNF-α and cortisol levels postintervention. Additionally, IGF-1 and GH levels increased significantly, and transferrin levels also rose, potentially reflecting improved nutritional status.

Conclusion: This study suggests that β-casein A2 milk supplementation was associated with improvements in physical growth and related biomarkers in stunted children. Additionally, β-casein A2 milk may produce fewer BCM-7 metabolites compared to β-casein A1 milk, which has been hypothesized to be associated with certain adverse health outcomes. However, further controlled studies are needed to confirm its efficacy as a dietary intervention.

Keywords: Caseins; Growth; Growth regulation; Hormones; Inflammation; Milk; Nutrition.

Fig. 1.

Physical growth, inflammation markers, and growth-related and nutritional biomarker profiles during the study period. Data are presented as mean (±standard deviation) and individual values. Differences in body weight and height were analyzed using repeated measures analysis of variance with Bonferroni post hoc test (data were normally distributed; Shapiro-Wilk test, P≥0.05). TNF-α, cortisol, IGF-1, transferrin, and GH levels were analyzed using the paired samples Wilcoxon test (data not normally distributed; Shapiro-Wilk test, P<0.05). TNF, tumor necrosis factor; IGF, insulin-like growth factor; GH, growth hormone. *P<0.05, statistically significant difference.

Fig. 2.

Differences in protein hydrolysis products between β-casein A1 and β-casein A2. A1 β-casein contains histidine (H) at position 67, which permits enzymatic cleavage and release of β-casomorphin-7 (BCM-7, YPFPGPI), a bioactive peptide. In contrast, A2 β-casein contains proline (P) at this position, which limits enzymatic cleavage and BCM-7 release.

Fig. 3.

Proposed biological pathway of β-casein A2 cow milk supplementation on growth, inflammation, and nutritional biomarkers. This schematic illustrates a hypothesized pathway whereby β-casein A2 milk intake may influence physical growth and health markers. β-casein A2 milk potentially stimulates increased secretion of GH and IGF-1, which contribute to enhanced bone mass, growth, and maturation. Concurrently, β-casein A2 milk may elevate transferrin levels, reflecting improved iron status and nutritional condition, while reducing inflammation through decreased TNF-α and cortisol levels. This model is based on associative evidence from the present study and existing literature and has not been experimentally confirmed. GH, growth hormone; IGF, insulin-like growth factor; TNF, tumor necrosis factor.