Lactose In Human Milk Research Articles

Macronutrients in Human Milk and Early Childhood Growth-Is Protein the Main Driver?

Infant growth trajectories reflect current health status and may predict future obesity and metabolic diseases. Human milk is tailored to support optimal infant growth. However, nutrient intake rather than milk composition more accurately predicts growth outcomes. Although the role of protein leverage in infant growth is unclear, protein intake is important for early infancy growth. This study of exclusively breastfeeding mothers with allergies (n = 161) from the Infant Fish Oil Supplementation Study assessed relationships between intake of human milk macronutrients and infant growth. Human milk fat, protein and lactose concentrations were measured at 3 months postpartum, and infant daily intakes were estimated using an average milk intake of 800 mL/day. Higher human milk protein:energy ratio was associated with higher weight-for-age z-score at 2.5 years compared to 3 months and higher body mass index-for-age z-score change (6 months to 1 year compared to 3-6 months). Maternal atopy and birth season (summer) were negatively associated with human milk lactose concentration. Passive smoke exposure was associated with reduced energy and fat concentrations and increased lactose:energy ratio. Our results indicate that intake of human milk macronutrients may impact early childhood growth.

The Influence of Oligosaccharides when Measuring Lactose and Total Carbohydrates in Human Milk and Comparison of Methods

BackgroundUnderstanding how human milk impacts growth requires valid analytical methods for quantifying the composition. Lactose, the most abundant constituent in human milk and a predominant source of energy, is often assessed using methods borrowed from the bovine dairy industry. However, the carbohydrate matrices of bovine and human milk are quite different, especially as they relate to human milk oligosaccharides (HMOs), each with a terminal lactose unit that may influence analytical methods. ObjectivesOur goals were to determine the extent to which HMOs influence common analytical methods for measuring carbohydrates in human milk and to compare common methods for measuring lactose. MethodsTwo sets of experiments were performed. In the first set, native and HMO-spiked human milk samples (n = 16 each) were assessed and compared using 4 methods: AOAC 2006.06 (based on the Megazyme enzymatic assay), BioVision enzymatic assay, ultraperformance LC with MS, and infrared analysis. In the second set, human milk samples (n = 20) were assessed using 2 methods approved for measuring lactose in bovine milk: AOAC 984.22 that uses high-performance LC and refractive index detection and AOAC 2006.06 prepared using both volume and weighted dilutions. ResultsNative and HMO-spiked samples were not significantly different in lactose using AOAC 2006.06 and ultraperformance LC with MS but were significantly different using BioVision (mean difference = 0.2 g/dL; 95% CI: 0.1, 0.4; P = 0.005). Total carbohydrate measurements assessed using infrared were also higher after HMO spiking (mean difference = 0.4 g/dL; 95% CI: 0.3, 0.6; P < 0.001). Only AOAC methods 984.22 and 2006.06 for measuring lactose were very highly correlated (r > 0.90, P < 0.001). ConclusionsAOAC methods 984.22 and 2006.06 are comparable for measuring lactose in human milk and are not influenced by HMOs. HMOs influence other enzymatic methods as well as infrared analysis, which leads to an overestimate of energy values. J Nutr 2023;x:xx.

Human Milk Lactose, Insulin, and Glucose Relative to Infant Body Composition during Exclusive Breastfeeding.

Human milk (HM) components may influence infant growth and development. This study aimed to investigate relationships between infant body composition (BC) and HM lactose, insulin, and glucose (concentrations and calculated daily intakes (CDI)) as well as 24-h milk intake and maternal BC at 3 months postpartum. HM samples were collected at 2 months postpartum. Infant and maternal BC was assessed with bioimpedance spectroscopy. Statistical analysis used linear regression accounting for infant birth weight. 24-h milk intake and CDI of lactose were positively associated with infant anthropometry, lean body mass and adiposity. Higher maternal BC measures were associated with lower infant anthropometry, z-scores, lean body mass, and adiposity. Maternal characteristics including BC and age were associated with concentrations and CDI of HM components, and 24-h milk intake. In conclusion, 24-h intake of HM and lactose as well as maternal adiposity are related to development of infant BC.

The Impact of Maternal Obesity on Human Milk Macronutrient Composition: A Systematic Review and Meta-Analysis

ObjectivesThis article aimed to provide a synthesis of studies evaluating the effects of maternal overweight and obesity, including body mass index (BMI) and other measures of adiposity, on the concentrations of macronutrients (fat, protein and lactose) in human milk (HM). MethodsEMBASE, MEDLINE/PubMed, Cochrane Library, Scopus, Web of Science and ProQuest databases were searched for relevant articles. Two authors conducted screening, data extraction and quality assessment independently. Meta-analyses of eligible studies were conducted using Review Manager software version 5.3. ResultsA total of 31 studies (5078 lactating women) were included in the qualitative synthesis and 9 studies (872 lactating women) in the quantitative synthesis. The meta-analysis indicated that maternal overweight and obesity were associated with higher concentrations of fat in mature HM (p = 0.01) and lactose in colostrum (p = 0.002). While the qualitative analyses broadly supported the findings of the meta-analysis, the qualitative assessment identified considerable variability in the results between studies and low quality of many of the included studies, making it difficult to draw robust conclusions. ConclusionsOverall, maternal BMI and adiposity measurements were associated with differences in the concentrations of fat and lactose in HM, however the direction of change was dependent on the stage of lactation, whereas protein concentration in HM did not appear to differ between overweight and/or obese and normal weight women. This is particularly relevant considering potential implications of higher HM fat concentration on both growth and fat deposition during the first few months of infancy and long-term risk of obesity. Funding SourcesGEL was supported by a FOODplus Early Life Nutrition Scholarship, The University of Adelaide. BSM received a Career Development Award from the National Health and Medical Research Council of Australia (NHMRC).

Daily variation of macronutrient concentrations in mature human milk over 3 weeks

Human milk (HM) composition is known to be highly variable, both between individuals and across the duration of lactation. It is less clear, however, to what extent fat, lactose and protein concentrations in HM change daily over shorter time periods in mature HM, and no studies have evaluated this to date. The aim of this study was to systematically assess and compare HM macronutrient concentrations in samples collected at different times of day, from left and right breasts and daily across a 3-week period in the same woman. Fifteen lactating women (1.6–4.9 months postpartum) collected daily pre-feed HM samples from both breasts each morning for 21 consecutive days and completed intensive sampling once a week (morning, afternoon and evening samples) during this period. Concentrations of fat, protein and lactose in HM did not differ according to time of day, day of week or breast used for collection. The results of this study suggest that pre-feed samples collected at any point across a 3-week period and from either the left or right breast provide comparable measures of fat, protein and lactose concentrations in mature HM, in pragmatic studies where women are collecting their own HM samples.Clinical trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12619000606189).

Differences in Human Milk Lactose and Citrate Concentrations Based on Gestational Diabetes Status.

Background: Exclusive breastfeeding is the optimal manner of early infant nutrition but women with gestational diabetes mellitus (GDM) often experience challenges with lactation in the early postpartum period. Increases in the colostral metabolites of lactose and citrate have been found to indicate increased milk production. Materials and Methods: A follow-up study of 133 postpartum women with and without GDM was conducted to examine differences in specific colostral metabolite levels using enzymatic methods to determine transition to lactogenesis II during the first week postpartum. We used linear mixed models for repeated measures over time to examine the effect of GDM on colostral metabolite levels at baseline and follow-up with fixed effects of GDM status, time, covariates, and interactions between time and GDM, between time and time, and between time, time and GDM into the model allowing quadratic trends over time. Results: Over time, lactose and citrate levels increased for all mothers (p < 0.001 and p < 0.001, respectively), although mothers with GDM had consistently lower lactose and citrate levels compared with nondiabetic mothers (p = 0.004 and p = 0.014, respectively). Age, prepregnancy body mass index, mode of birth, and parity did not independently influence colostral concentrations of lactose and citrate. Conclusions: Findings suggest that the rate of change overtime in lactose and citrate concentrations differ by GDM status. Further research examining the trajectory of colostral metabolite levels by GDM status is warranted.

Markers of Oxidative Stress in Human Milk do not Differ by Maternal BMI But are Related to Infant Growth Trajectories.

Objective Obesity in adults is associated with inflammation and oxidative stress. Whether or not this phenotype is reflected in human milk (HM) composition, or may impact infant growth remains unknown. We investigated whether HM from overweight/obese (OW/Ob) mothers exhibited higher concentrations of inflammatory cytokines and markers of oxidative stress. We also correlated these bioactive components with infant growth patterns. Methods This was an observational cohort of 56 breastfeeding mothers and their infants [33 normal weight (NW) and 23 OW/Ob]. Infants were followed until 6 months of age and HM collected at 2-weeks and 4-months. Results Markers of oxidative stress, 8-hydroxy-deoxyguanosine (8OHdG) and 4-hydroxynonenol (HNE), decreased in HM over time (p < 0.001) and did not differ between NW and OW/Ob women. Concentrations of inflammatory cytokines, IL-6, IL-8, and TNF-α, were all inter-correlated (p < 0.001) but did not differ between NW and OW/Ob women. HM fat, protein, lactose, and total calories did not differ between NW and OW/Ob women. Infant growth patterns did not differ by group. In a model of infant weight-for-length-Z score trajectory, there was a significant interaction between both lactose and 8OHdG with maternal group: HM lactose and 8OHdG concentrations were both positively associated with increases in WLZ trajectory only among infants breastfed by OW/Ob mothers. Conclusions for Practice HM composition was relatively stable between NW and OW/Ob women. In exclusively breastfed infants, HM concentrations of lactose and 8OHdG, a marker of oxidative stress, may contribute to regulation of infant weight gain, especially among infants of OW/Ob women.

Lactose: a milk‐specific carbohydrate enabling homeostatic regulation of glucose and insulin (623.12)

Lactose, a disaccharide of glucose and galactose, is uniquely present in mammalian milk. Human milk provides the infant with about 40% energy as lactose and 50% from fat. With 6‐7 g/dL lactose, the breast fed infant consumes high carbohydrate/kg body wgt, suggesting carbohydrate induced hepatic lipogenesis would be problematic with a high fat milk diet. However, galactose, unlike glucose is non‐insulinogenic and shows high hepatic clearance. We propose lactose in human milk confers unique metabolic advantage to the infant by delivering non‐insulinogenic carbohydrate which can be slowly metabolized in the liver to glucose or to support fatty acid oxidation. We determined insulin, glucose, triglyceride, free fatty acid and amino acid responses in 16 healthy adult men given in random order 650 mL carbohydrate‐free infant formula reconstituted to contain 50g lactose, glucose, sucrose or corn syrup solids. The milk formula was given 3 hr after a lactose and sucrose‐free meal, then again after 3 hr, to model the carbohydrate load and continuous feeding of breast‐fed infants. Blood was drawn every 15 min, and total and incremental area‐under‐curve change in insulin and glucose determined. Lactose gave a significantly lower rise in plasma insulin and glucose, in the first and particularly second 3 hr following intake, compared to glucose or corn syrup solids (P &lt;0.001). Individual variability in triglyceride responses was high, with no difference due to carbohydrate in this 6 hr study. We show lactose enables maintenance of glucose and insulin equilibrium, avoiding high postprandial peaks achieved with glucose or corn syrups in milk fed at 3 hr intervals. We propose an important metabolic homeostatic role for lactose as carbohydrate source in human milk. Supported by Mead Johnson Nutrition.Grant Funding Source: Mead Johnson Nutrition

Comparison of mid‐infrared transmission spectroscopy with biochemical methods for the determination of macronutrients in human milk

The variability of human milk (HM) composition renders analysis of its components essential for optimal nutrition of preterm fed either with donor's or own mother's milk. To fulfil this requirement, various analytical instruments have been subjected to scientific and clinical evaluation. The objective of this study was to evaluate the suitability of a rapid method for the analysis of macronutrients in HM as compared with the analytical methods applied by cow's milk industry. Mature milk from 39 donors was analysed using an infrared human milk analyser (HMA) and compared with biochemical reference laboratory methods. The statistical analysis was based on the use of paired data tests. The use of an infrared HMA for the analysis of lipids, proteins and lactose in HM proved satisfactory as regards the rapidity, simplicity and the required sample volume. The instrument afforded good linearity and precision in application to all three nutrients. However, accuracy was not acceptable when compared with the reference methods, with overestimation of the lipid content and underestimation of the amount of proteins and lactose contents. The use of mid-infrared HMA might become the standard for rapid analysis of HM once standardisation and rigorous and systematic calibration is provided.

Variations in Oligosaccharides and Lactose in Human Milk During the First Week of Lactation

SummaryVariations in oligosaccharides and lactose in human milk were studied in 15 mothers during the first week of lactation. The neuraminyloligosaccharides and heavy neutral oligosaccharides increased slightly from days 2 to 5 postpartum and appeared to decrease until day 7. The lacto‐N‐difucohexaoses, lacto‐N‐fucopentaoses, and lacto‐N‐tetraose increased until day 5 and then decreased. Lactodifucotetraose and the fucosidolactoses decreased substantially until day 5 (p &lt; 0.05) and appeared to stabilize in the following days. Lactose increased until day 5 (p &lt; 0.05) and continued to increase thereafter. Lactose was negatively correlated with total oligosaccharides (p &lt; 0.10). The fluctuations observed in total oligosaccharides from days 2 to 5 postpartum and their subsequent stabilization and regular decrease during lactation confirm the hypothesis of Kulski and Hartmann that mammary secretion occurs in three periods: colostrum for the first 36 h postpartum, transitional milk from days 2 to 5 postpartum, and mature milk after day 5. The oligosaccharide variations we found corresponded to those of other milk constituents observed by other authors. The significance of the oligosaccharide variations is discussed.

Variations in Oligosaccharides and Lactose in Human Milk During the First Week of Lactation

Variations in oligosaccharides and lactose in human milk were studied in 15 mothers during the first week of lactation. The neuraminyloligosaccharides and heavy neutral oligosaccharides increased slightly from days 2 to 5 postpartum and appeared to decrease until day 7. The lacto-N-difucohexaoses, lacto-N-fucopentaoses, and lacto-N-tetraose increased until day 5 and then decreased. Lactodifucotetraose and the fucosidolactoses decreased substantially until day 5 (p less than 0.05) and appeared to stablize in the following days. Lactose increased until day 5 (p less than 0.05) and continued to increase thereafter. Lactose was negatively correlated with total oligosaccharides (p less than 0.10). The fluctuations observed in total oligosaccharides from days 2 to 5 postpartum and their subsequent stabilization and regular decrease during lactation confirm the hypothesis of Kulski and Hartmann that mammary secretion occurs in three periods: colostrum for the first 36 h postpartum, transitional milk from days 2 to 5 postpartum, and mature milk after day 5. The oligosaccharide variations we found corresponded to those of other milk constituents observed by other authors. The significance of the oligosaccharide variations is discussed.

Simplified and rapid methods for the determination of protein, fat and lactose in human milk and the energy intake by the breast-fed infant.

Triacylglycerides constitute the bulk of fat in human milk. By centrifuging the milk a layer of fat is obtained, the cream, the fraction of which correlates very well with the total triacylglyceride concentration. It is determined in analogy to the haematocrit and is called galactocrit). Protein is determined with the biuret method in defatted milk. The interference due to lactose in this assay is on average 2 g/l. Lactose is determined with an enzyme kit. The amount of macronutrients in milk determines the energy value. A protocol is proposed, which makes it possible to measure the quantity of human milk drunk by the infant and to calculate the daily energy intake.

Purification of the Protein of Human Milk Lactose Synthetase and Identification as a Glycoprotein

The A protein of human milk lactose synthetase (UDP-d-galactose : d-glucose 1-galaotosyltransferase EC 2.4.1.22) was purified and investigated. The A protein contained hexose (galactose, mannose fucose), hexosamiie (galactosamine and glucosamine) and sialic acid. Thus the A protein was identified as a glycoprotein enzyme. Amino acid composition determined that proline and glutamic acid were very high. Molecular weight of the A protein was estimated at 72,000 to 75,000 by gel filtration and electrophoretic mobility.

Lactose Content and Arakaa's Reaction of Human Milk

In the present paper lactose content of 392 milk samples from 200 mothers were examined and the following 10 questions were studied. 1. As to the human milk lactose content according to the inten-sity of Arakawa's reaction, human milk positive to Arakawa's reaction (7.64g/dl Cf. Table 5) is generally higher in lactose content than the Arakawa-negative milk (6.97g/dl). And lactose content of Arakawa-negative milk fluctuates in a wider range than that of Ara-kawa-positive milk. 2. Monthly variation of lactose content shows that it is slightly lower in cold seasons than in other seasons both in Arakawa-positive and -negative milks. But the seasonal difference itself is not so large as the difference between Arakawa-positive and -negative milks. 3. As to the lactose content of human milk according to Ara-kawa's reaction and according to the period of lactation (Cf. Tables 7 and 8), it is generally the highest in the middle mature period, but in Arakawa-positive milk alone lactose content keeps almost constant in every period of lactation, (colostrum is excepted, of course). Colo-strum milk (0-14 days after delivery) was excluded from this experi-ment, for, according to Pfeiffer, 11) Adriance14) and Lowenfeld39) the lactose content rises rapidly during the first few days or during the first two weeks, and then returns to the normal level. 4. Concerning the variation of lactose content of Arakawa-posi- tive and -negative milks according to the age of mothers (Cf. Table 9), there is no relation depending on the age. Of course, such a strik-ing difference as between Arakawa-positive and -negative cases is not seen among mothers of different ages. 5. As to the lactose content of human milk according to.Ara-kawa's reaction and to different sides of breast (Cf. Table 10), it is almost the same amount on either side, both in Arakawa-positive and -negative milks. That is to say, Arakawa-positive mothers secrete lactose-rich milk on both sides and Arakawa-negative mothers secrete lactose-poor milk. 6. If all the milk samples are distributed according to the in-tensity of Arakawa's reaction and according to the amount of lac-tose, , and if a dissecting line is drawn between 7.3g/dl and 7.2g/dl, 80% of Arakawa-positive milk ranks above the line, while 60% of A-rakawa-negative milk ranks below the line. 7. As to the human milk lactose according to the quantity of secretion and to Arakawa's reaction, 88% of Arakawa-positive milk secrete abundantly, and in the Arakawa-negative cases, the weaker the reaction, the smaller is the percentage of the cases with abundant secretion. 8. Concerning the difference of lactose content between both sides of the breast according to Arakawa's reaction (Cf. Table 14) the difference is twice as large a one in the Arakawa-negative case compared with the positive case. 9. In the cases of one and the same mothers with very different reaction on either side of the breast, there is almost no difference between the lactose content of positive and negative sides, and the lactose content in such cases corresponds to that of milk of the inter-mediate Arakawa reaction. 10. In the case of nutritional disturbances or under-grown ba-bies, such as atrophy or lues congenita, the lactose content is lower than that in other cases. As summarized in different items above mentioned, lactose con-tent in human milk is generally different according to a number of different factors, but such a remarkable difference as between Araka-wa-positive and Arakawa-negative milks is never seen.