Human milk fatty acid composition and its association with maternal blood and adipose tissue fatty acid content in a cohort of women from Europe.

PURPOSE: Human milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated. METHODS: 223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother's blood and cord blood were established. RESULTS: During lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy. CONCLUSIONS: These data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM.

Dynamics of human milk nutrient composition of women from Singapore with a special focus on lipids.

BACKGROUND: A recent report suggested that human milk (HM) composition not only changes with lactation stages but also vary according to gender of the offspring. In spite of available literature, the dynamic changes of HM composition still remain to be completely explored and characterized. Progress in analytical technologies together with quantitative sampling of HM allows for a better quantification of HM nutrients and thereby providing a deeper understanding of the dynamics of HM secretion. OBJECTIVE: To characterize and quantify HM nutrients based on appropriate for analyses sampling procedures and advanced analytical methodologies. CLINICAL STUDY DESIGN: We conducted an observatory, single center, longitudinal trial with HM collection at 30, 60, and 120 days postpartum from 50 mothers (singleton-deliveries of 25 male and 25 female infants). HM samples were analyzed for lipid, lactose, energy density, fatty acids, phospholipids, and gangliosides. Longitudinal analyses of the datasets have been carried out using linear mixed models. RESULTS: HM for male infants compared to females at 120 days, were higher for energy content and lipids by 24 and 39%, respectively. Similarly, other bioactive lipids such as linoleic acid, phospholipids and gangliosides were also significantly different based on the gender of the infant. Significant stage-based differences were observed for total lipids, energy density, phospholipids, and gangliosides. Such difference in HM composition may stem from different energy needs to cope up for individual growth and development. CONCLUSION: Collectively, the current observations affirm that HM secretion, especially the lipid composition, is a very dynamic and personalized biological process.

High or low glycemic index (GI) meals at dinner results in greater postprandial glycemia compared with breakfast: a randomized controlled trial.

INTRODUCTION: While circadian control of glucose metabolism is well known, how glycemic index (GI) of carbohydrate-rich meals interacts with time of consumption (breakfast or dinner) to influence postprandial (PP) glucose homeostasis is less well established. The objective of the study was to assess markers of PP glucose homeostasis following high or low GI test meals (TM) consumed either at breakfast or at dinner and following consumption of the subsequent standardized meals (SSM). RESEARCH DESIGN AND METHODS: Randomized crossover trial in 34 healthy, Chinese, elderly volunteers (mean±SEM age, 56.8±0.83 years), who completed 4 separate study sessions per-protocol, consisting of a high-GI breakfast, low-GI breakfast, high-GI dinner and low-GI dinner TM, followed by a SSM at the subsequent eating occasion. Blood samples were taken for 3 hours after each TM and SSM for glucose, insulin, glucagon, free fatty acids (FFA) and triglycerides (TG) measurements. RESULTS: Consuming TM at dinner produced greater PP glycemia than breakfast both after TM and SSM (both p<0.0001), irrespective of GI. High-GI TM also produced greater PP glycemia than low-GI TM, both after TM and SSM (both p<0.01), irrespective of time of consumption. No interaction between GI and time were found on PP glycemia, indicating parallel, but independent effects. Combined total areas under the curve of TM+SSM for PP glucose (p<0.0001), PP TG (p<0.0001) and PP FFA (p<0.0001) were all greater when TM taken during dinner compared with breakfast. CONCLUSIONS: Carbohydrate-rich meals consumed at dinner leads to significantly worse PP glucose homeostasis than when consumed at breakfast, on top of the independent GI effect of the meal. This may have implications to future type 2 diabetes risk. Moreover, future studies investigating GI/glycemic load (GL) and disease risk associations should factor in timing of GL consumption as an additional variable. TRIAL REGISTRATION NUMBER: NCT02927600.

Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Several intervention studies have investigated the relationship between cocoa flavanols and endothelial function. However, the shape of the association and the type of compounds responsible for the effects are largely unknown. OBJECTIVE: To examine the dose-response association between the consumption of cocoa flavanols and endothelial function, measured by flow-mediated dilation (FMD). DESIGN: Two investigators searched Scopus® for the relevant human intervention studies, which were pooled and meta-analysed. Heterogeneity in the findings was explored with various subgroup analyses. RESULTS: Fifteen published articles with 18 intervention arms met the inclusion criteria. Participants in these intervention groups received 80 to 1248 mg (mean: 704 mg) more flavanols than control groups. A significant improvement of FMD by 1.17% (95% CI: 0.76% to 1.57%) was calculated, with strong evidence of a non-linear association (inverted U-shape) between cocoa flavanols and FMD. CONCLUSIONS: This meta-analysis provides evidence that cocoa flavanols could significantly improve endothelial function, with an optimal effect observed with 710 mg total flavanols, 95 mg (-)-epicatechin or 25 mg (+)-catechin. However, there was substantial variation in the results that could not be explained by the characteristics that we explored, and there were significant risk-of-bias concerns with a large majority of the studies.

Temporal Progression of Fatty Acids in Preterm and Term Human Milk of Mothers from Switzerland.

We longitudinally compared fatty acids (FA) from human milk (HM) of mothers delivering term and preterm infants. HM was collected for 4 months postpartum at 12 time points for preterm and for 2 months postpartum at 8 time points for term group. Samples were collected from the first feed of the morning, and single breast was fully expressed. FA were analyzed by gas chromatography coupled with flame ionization detector. Oleic, palmitic and linoleic acids were the most abundant FA across lactation and in both groups. Preterm colostrum contained significantly (p < 0.05) higher 8:0, 10:0, 12:0, sum medium chain fatty acids (MCFA), 18:3 n-3 FA compared to term counterparts. Preterm mature milk contained significantly higher 12:0, 14:0, 18:2 n-6, sum saturated fatty acids (SFA), and sum MCFA. We did not observe any significant differences between the preterm and term groups for docosahexaenoic acid, arachidonic acid and eicosapentaenoic acid at any stage of lactation. Overall, preterm milk was higher for SFA with a major contribution from MCFA and higher in 18:2 n-6. These observational differences needs to be studied further for their implications on preterm developmental outcomes and on fortification strategies of either mothers' own milk or donor human milk.

Impact of maternal characteristics on human milk oligosaccharide composition over the first 4 months of lactation in a cohort of healthy European mothers.

Human milk oligosaccharide (HMO) composition varies among lactating mothers and changes during the course of lactation period. Interindividual variation is largely driven by fucosyltransferase (FUT2 and FUT3) polymorphisms resulting in 4 distinct milk groups. Little is known regarding whether maternal physiological status contributes to HMO variability. We characterized the trajectories of 20 major HMOs and explored whether maternal pre-pregnancy body mass index (ppBMI), mode of delivery, or parity may affect milk HMO composition. Using longitudinal breastmilk samples from healthy mothers (n = 290) across 7 European countries, we characterized HMO composion and employed mixed linear models to explore associations of maternal characteristics with individual HMOs. We observed HMO-specific temporal trajectories and milk group dependencies. We observed relatively small but significant differences in HMO concentrations based on maternal ppBMI, mode of delivery and parity. Our findings suggest that HMO composition to be regulated time-dependently by an enzyme as well as substrate availability and that ppBMI, mode of delivery, and parity may influence maternal physiology to affect glycosylation marginally within the initital period of lactation. Our observational study is the largest European standardized and longitudinal (up to 4 months) milk collection study assessing HMO concentrations and basic maternal characteristics. Time of lactation and milk groups had the biggest impact on HMO variation. Future studies need to elucidate these observations and assess the physiological significance for the breastfed infant.

Subclinical Mastitis in a European Multicenter Cohort: Prevalence, Impact on Human Milk (HM) Composition, and Association with Infant HM Intake and Growth.

Background: Subclinical mastitis (SCM) is an inflammatory condition of the mammary gland. We examined the effects of SCM on human milk (HM) composition, infant growth, and HM intake in a mother-infant cohort from seven European countries. Methods: HM samples were obtained from 305 mothers at 2, 17, 30, 60, 90, and 120 days postpartum. SCM status was assessed using HM Sodium (Na): Potassium (K) ratio >0.6. Levels of different macro- and micronutrients were analyzed in HM. Results: SCM prevalence in the first month of lactation was 35.4%. Mean gestational age at delivery was lower and birth by C-section higher in SCM mothers (p ≤ 0.001). HM concentrations of lactose, DHA, linolenic acid, calcium, and phosphorous (p < 0.05 for all) was lower, while total protein, alpha-lactalbumin, lactoferrin, albumin, arachidonic acid to DHA ratio, n-6 to n-3 ratio and minerals (iron, selenium, manganese, zinc, and copper) were higher (p < 0.001 for all) in mothers with SCM. There were no differences in infant growth and HM intake between non-SCM and SCM groups. Conclusion: We document, for the first time, in a large European standardized and longitudinal study, a high prevalence of SCM in early lactation and demonstrate that SCM is associated with significant changes in the macro- and micronutrient composition of HM. Future studies exploring the relation of SCM with breastfeeding behaviors and developmental outcomes are warranted.

Longitudinal change of selected human milk oligosaccharides and association to infants' growth, an observatory, single center, longitudinal cohort study.

BACKGROUND: Human milk is the recommended and sole nutrient source for newborns. One of the largest components of human milk is oligosaccharides (HMOs) with major constituents determined by the mother genotype for the fucosyltransferase 2 (FUT2, secretor) gene. HMO variation has been related with infant microbiota establishment, diarrhea incidence, morbidity and mortality, IgE associated eczema and body composition. OBJECTIVES: We investigated the (i) dependence of several major representative HMOs on the FUT2 status assessed through breast milk 2'Fucosyllactose (2'FL) and (ii) the relation of the 2'FL status with infant growth up to 4 months of life. DESIGN: From an open observatory, single center, longitudinal cohort study with quantitative human milk collection at 30, 60, and 120 days postpartum from 50 mothers, who gave birth to 25 female and 25 male singleton infants, we collected a representative sample of human milk. We quantified the following 5 representative HMOs: 2'FL, Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL) and 6'Sialyllactose (6'SL). We grouped the milk samples and corresponding infants according to the measured milk 2'FL concentrations at 30 days of lactation, which clustered around low concentrations (95% CI of mean 12-42 mg/L) and high concentrations (95% CI of mean 1880-2460 mg/L) with the former likely representing Secretor negative mothers. Infant anthropometric measures were recorded at birth, 1, 2 and 4 months of age. Relations among the quantified HMOs and the relation of the high and low 2'FL HMOs groups with infant growth parameters were investigated via linear mixed models. RESULTS: The milk samples with low 2'FL concentration had higher LNT and lower LNnT concentrations compared to the samples with high 2'FL. The milk 3'- and 6'SL concentrations were independent of 2'FL. Over lactation time we observed a drop in the concentration of 2'FL, LNT, LNnT and 6'SL, especially from 1 to 2 months, while 3'SL remained at relatively constant concentration from 1 month onwards. Up to 4 months of age, we did not observe significant differences in body weight, body length, body mass index and head circumference of the infants who consumed breast milk with low or high FUT2 associated HMO concentrations and composition. CONCLUSIONS: Our findings on HMO concentrations over time of lactation and clusters based on 2'FL concentrations confirm previous observations and suggest that LNnT and LNT are 'co-regulated' with the FUT2 dependent 2'FL concentration, with LNnT showing a positive and LNT a negative relation. Further, our findings also suggest that the relatively substantial variation in HMOs between the high and low 2'FL clusters do not impact infant growth of either sex up to 4 months of age. The study was registered in www.ClinicalTrial.gov (NCT01805011).

Temporal Changes of Protein Composition in Breast Milk of Chinese Urban Mothers and Impact of Caesarean Section Delivery.

Human breast milk (BM) protein composition may be impacted by lactation stage or factors related to geographical location. The present study aimed at assessing the temporal changes of BM major proteins over lactation stages and the impact of mode of delivery on immune factors, in a large cohort of urban mothers in China. 450 BM samples, collected in three Chinese cities, covering 8 months of lactation were analyzed for α-lactalbumin, lactoferrin, serum albumin, total caseins, immunoglobulins (IgA, IgM and IgG) and transforming growth factor (TGF) ß1 and ß2 content by microfluidic chip- or ELISA-based quantitative methods. Concentrations and changes over lactation were aligned with previous reports. α-lactalbumin, lactoferrin, IgA, IgM and TGF-ß1 contents followed similar variations characterized by highest concentrations in early lactation that rapidly decreased before remaining stable up to end of lactation. TGF-ß2 content displayed same early dynamics before increasing again. Total caseins followed a different pattern, showing initial increase before decreasing back to starting values. Serum albumin and IgG levels appeared stable throughout lactation. In conclusion, BM content in major proteins of urban mothers in China was comparable with previous studies carried out in other parts of the world and C-section delivery had only very limited impact on BM immune factors.

Temporal Changes of Human Breast Milk Lipids of Chinese Mothers.

Fatty acids (FA), phospholipids (PL), and gangliosides (GD) play a central role in infant growth, immune and inflammatory responses. The aim of this study was to determine FA, PL, and GD compositional changes in human milk (HM) during lactation in a large group of Chinese lactating mothers (540 volunteers) residing in Beijing, Guangzhou, and Suzhou. HM samples were collected after full expression from one breast and while the baby was fed on the other breast. FA were assessed by direct methylation followed by gas chromatography (GC) analysis. PL and GD were extracted using chloroform and methanol. A methodology employing liquid chromatography coupled with an evaporative light scattering detector (ELSD) and with time of flight (TOF) mass spectrometry was used to quantify PL and GD classes in HM, respectively. Saturated FA (SFA), mono-unsaturated FA (MUFA), and PL content decreased during lactation, while polyunsaturated FA (PUFA) and GD content increased. Among different cities, over the lactation time, HM from Beijing showed the highest SFA content, HM from Guangzhou the highest MUFA content and HM from Suzhou the highest n-3PUFA content. The highest total PL and GD contents were observed in HM from Suzhou. In order to investigate the influence of the diet on maternal milk composition, a careful analyses of dietary habits of these population needs to be performed in the future.

Oral administration of Lactobacillus paracasei NCC 2461 for the modulation of grass pollen allergic rhinitis: a randomized, placebo-controlled study during the pollen season.

BACKGROUND: The efficacy of Lactobacillus paracasei NCC 2461 in modulating allergic rhinitis was previously evaluated in two exploratory clinical studies. Oral administration with NCC 2461 reduced specific subjective symptoms following nasal provocation tests with controlled grass pollen allergen concentrations. Our aim was to confirm the anti-allergic effect of NCC 2461 in grass pollen allergic subjects exposed to natural doses of allergens during the pollen season. FINDINGS: A double-blind, randomized, placebo-controlled, parallel study was conducted with 131 grass pollen allergic subjects from May to July 2012 in concomitance with the pollen season in Berlin. NCC 2461 or placebo was administered daily for an 8-week period to adult subjects with clinical history of allergic rhinitis to grass pollen, positive skin prick test and IgE to grass pollen. During the 8 weeks, symptoms and quality of life questionnaires were filled out, and plasma was collected for IgE analysis at screening and at the end of the intervention. All subjects were included within a 5-day interval, ensuring exposure to similar air pollen counts for each individual during the trial period. The results obtained show that symptoms increased with pollen loads, confirming a natural exposure to the allergen and presence of pollen-induced allergic rhinitis in the subjects. However, no significant differences were observed in allergic rhinitis symptoms scores, quality of life, or specific IgE levels between subjects receiving NCC 2461 as compared to placebo administration. CONCLUSION: In contrast to previous findings, oral administration of NCC 2461 did not show a beneficial effect on allergic rhinitis in a field trial. The influence of study design, allergen exposure and intervention window on the efficacy of NCC 2461 in modulating respiratory allergy should be further evaluated.