Free and Total Amino Acids in Human Milk in Relation to Maternal and Infant Characteristics and Infant Health Outcomes: The Ulm SPATZ Health Study

Abstract

Free amino acids (FAAs) are important regulators of key pathways necessary for growth, development, and immunity. Data on FAAs in human milk (HM) and their roles in infant development are limited. We investigated the levels of FAAs and total amino acids (TAA, i.e., the sum of conjugated amino acids and FAAs) in HM in relation to infant and maternal characteristics and immunological conditions. FAA and TAA levels in HM sampled at 6 weeks (n = 671) and 6 months (n = 441) of lactation were determined using high-performance liquid chromatography. Child growth was ascertained at 4–5 weeks and at 6–7 months of age. Child allergy and lower respiratory tract infections were assessed in the first years of life. Associations of amino acid (AA) levels in HM with child growth and health outcomes were determined by Spearman correlation and modified Poisson regression, respectively. Free glutamine, glutamate, and serine in 6-week HM positively correlated with infant weight gain in the first 4–5 weeks of age. Maternal pre-pregnancy weight and body mass index (BMI) were negatively correlated with free glutamine and asparagine in 6-week and 6-month HM and positively correlated with the sum of TAAs in 6-month HM, but significance was lost following confounder adjustment. Free glutamine was lower in 6-month HM of mothers with an allergy (either active or non-active). No consistent associations were found between FAAs in HM and child health outcomes. However, potential negative associations were observed between specific FAAs and the risk of food allergy. These results suggest that specific FAAs play a role in infant growth. Moreover, these findings warrant further investigations into the relation of FAAs in HM with infant health outcomes and maternal allergy.

Human milk nutritional composition across lactational stages in Central Africa

“…Growing interest in HM FAAs is due to the fluctuation of FAA levels over lactation in an amino acid specific manner which suggests the existence of a secretory regulation mechanism. Indeed, FAAs might have a functional role in infant development ( 97 ). FAAs are more rapidly digested and appear sooner in the circulation than protein-associated amino acids and are recognized by specific receptors at the surface of numerous cells.…”

Human Milk Macronutrients and Child Growth and Body Composition in the First Two Years: A Systematic Review

“…Five studies examined the association between essential amino acids and infant growth, with 3 studies assessing free amino acids [ 41 , 58 , 59 ], 1 examining both free and total amino acids [ 60 ], and 1 conducting untargeted metabolomics [ 38 ]. Two studies used ion-exchange chromatography [ 41 , 58 ], whereas Saben et al.…”

“…Two studies used ion-exchange chromatography [ 41 , 58 ], whereas Saben et al. (2022) [ 59 ] and van Sadelhoff (2021) [ 60 ] used liquid chromatography to analyze amino acids. Isganaitis et al.…”

“…Inclusion criteria were studies reporting on healthy, term, breastfed infants (aged 0 to 24 mo). Whereas breastfeeding exclusivity was not an inclusion criterion, it was recorded when reported by authors ( Table 1 ) [ [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , [83] , [84] , [85] , [86] , [87] , [88] , [89] ] and considered in the quality assessment (described below). Healthy was defined as term birth (37 wk, 0 d of gestation or later) with no congenital or other morbidities and no admission in the neonatal intensive care unit.…”

“… Bolivia, 2018 (LMIC) [ 39 ] Cross-sectional 18 infants 2–6 mo fat (concentrations) Exclusive BF only 2–6 mo WLZ, BMIZ, WAZ, LAZ body composition (fat mass, fat mass % using dual Energy X-ray Absorptiometry: DEXA) (WHO standards) None exclusive BF van Sadelhoff et al.The Netherlands, 2018 (HIC) [ 89 ] RCT 25 infants enrolled 16 analyzed monthly between 1, 6 mo amino acids (concentrations) Every 2 mo between birth, 6 mo weight, length None infant sex van Sadelhoff et al. 2021, Germany (HIC) [ 60 ] Longitudinal 741 infants (441 analyzed) 6 wk, 6 mo amino acids (concentrations) Mixed Feeding 6 wk, 6 mo weight, length, weight gain, length gain. (-) Association for Threonine, Glutamate, glutamine and serine and weight gain at 6 wk (-) Association for Glutamine and length gain at 6 wk (-) Association for all FAAs (free AAs) and weight gain at 6 wk none reported Xiang et al.China, 1999(LMIC) [ 81 ] Cross-sectional 41 infants (18 infants 1 mo old, 23 infants 3 mo old) 1 or 3 mo fatty acids: ARA, DHA (concentrations) Exclusive BF only 1 or 3 mo weight, length Difference for birth and 1 m (+) Association for DHA and length gain Difference for birth and 3 mo (+) Association for ARA and weight gain (+) Association for DHA and weight gain (+) Association for DHA and length gain none reported Xiang et al.Sweden, 2000(HIC) [ 80 ] Longitudinal 19 infants 1, 3 mo fatty acids (concentrations) Exclusive BF only 1, 3 mo Occipito-frontal HC Brain weight Difference for birth and 1 mo (+) Association for ARA:DHA and occipito-frontal HC increase (+) Association for ARA:DHA and brain weight increase Difference for birth and 3 mo ( +) Association for ARA:DHA and occipito-frontal HC increase (+) Association for ARA:DHA and brain weight increase none reported …”