Sterols in Infant Formulas: A Bioaccessibility Study.

Preparation of infant formula simulating the fat composition and structure of human milk based on MFGM and exogenous phospholipid to modulate lipid digestion.

Human milk contains nutritional, immunoprotective and developmental components that support optimal infant growth and development. The milk fat globule membrane (MFGM) is one unique component, comprised of a tri-layer of polar lipids, glycolipids, and proteins, that may be important for brain development. MFGM is not present in most infant formulas. We tested the effects of bovine MFGM supplementation on reflex development and on brain lipid and metabolite composition in rats using the “pup in a cup” model. From postnatal d5 to d18, rats received either formula supplemented with MFGM or a standard formula without MFGM; a group of mother-reared animals was used as reference/control condition. Body and brain weights did not differ between groups. MFGM supplementation reduced the gap in maturation age between mother-reared and standard formula-fed groups for the ear and eyelid twitch, negative geotaxis and cliff avoidance reflexes. Statistically significant differences in brain phospholipid and metabolite composition were found at d13 and/or d18 between mother-reared and standard formula-fed groups, including a higher phosphatidylcholine:phosphatidylethanolamine ratio, and higher phosphatidylserine, glycerol-3 phosphate, and glutamine in mother-reared compared to formula-fed pups. Adding MFGM to formula narrowed these differences. Our study demonstrates that addition of bovine MFGM to formula promotes reflex development and alters brain phospholipid and metabolite composition. Changes in brain lipid metabolism and their potential functional implications for neurodevelopment need to be further investigated in future studies.

Background: The milk fat globule membrane (MFGM) is a thin film that exists within the milk emulsion, suspended on the surface of milk fat globules, and comprises a diverse array of bioactive components. Recent advancements in MFGM research have sparked a growing interest in its biological characteristics and health-related functions. Thorough exploration and utilization of MFGM as a significant bioactive constituent in milk emulsion can profoundly impact human health in a positive manner. Scope and approach: This review comprehensively examines the current progress in understanding the structure, composition, physicochemical properties, methods of separation and purification, and biological activity of MFGM. Additionally, it underscores the vast potential of MFGM in the development of additives and drug delivery systems, with a particular focus on harnessing the surface activity and stability of proteins and phospholipids present on the MFGM for the production of natural emulsifiers and drug encapsulation materials. Key findings and conclusions: MFGM harbors numerous active substances that possess diverse physiological functions, including the promotion of digestion, maintenance of the intestinal mucosal barrier, and facilitation of nerve development. Typically employed as a dietary supplement in infant formula, MFGM’s exceptional surface activity has propelled its advancement toward becoming a natural emulsifier or encapsulation material. This surface activity is primarily derived from the amphiphilicity of polar lipids and the stability exhibited by highly glycosylated proteins.

This review provides an overview of the composition, structure, and biological activities of milk fat globule membrane (MFGM) compounds with focus on the future application of this compound as a food ingredient. MFGM is a particular component of mammalian milks and is comprised of a tri-layer of polar lipids, glycolipids and proteins. In recent years, MFGM has been extensively studied for the purpose of enhancing the efficacy of infant nutrition formula. For example, infant formulas supplemented with bovine MFGM have shown promising results with regard to neurodevelopment and defense against infections. Components of MFGM have been shown to present several health benefits as the proteins of the membrane have shown antiviral activity and a reduction in the incidence of diarrhea. Moreover, the presence of sphingomyelin, a phospholipid, implies beneficial effects on human health such as enhanced neuronal development in infants and the protection of neonates from bacterial infections. The development of a lipid that is similar to human milk fat would represent a significant advance for the infant formula industry and would offer high technology formulas for those infants that depend on infant formula. The complexity of the structure of MFGM and its nutritional and technological properties is critically examined in this review with a focus on issues relevant to the dairy industry.

*University of Lancashire, Lancashire, United Kingdom; †University of Milano, Milano, Italy; ‡University of Umea, Umea, Sweden; §Committee Chairman, University of Munich, Munich, Germany; Free University of Amsterdam, Amsterdam, The Netherlands; ¶Committee Secretary, Royal Agricultural and Veterinary University, Fredricksburg, Denmark; #University of Liege, Liege, Belgium; **University of Glasgow, Glasgow, United Kingdom

Preoperative Fasting in Children

To investigate the lipid digestive behaviors of human and infant formulas and analyze the differences between them, we investigated the fat globule particle size distribution, lipolysis rate, and fatty acid release of infant formulas with different fat sources and human milk using an in vitro infant digestion model. The results suggested that the particle size in infant formula increased rapidly during gastric digestion and decreased significantly after intestinal digestion, whereas the particle size in human milk increased slowly during gastric digestion but increased rapidly during intestinal digestion (p < 0.05). Despite having a larger droplet size, human milk demonstrated a very high lipolysis rate due to the presence of MFGM. In terms of the distribution of fatty acids in digestion products, the proportion of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) in vegetable oil-based infant formulas was close to that of human milk. The amount of SFAs in milk fat-based infant formulas was significantly higher than that in human milk, and the content of MUFAs in all infant formulas was significantly lower than that in human milk (p < 0.05). After digestion, the most abundant fatty acid released by human milk was C18:2n6c, while the fatty acids released by infant formulas were SFAs, such as C14:0, C16:0, and C18:0.

Proteomic characterization and comparison of mammalian milk fat globule proteomes by iTRAQ analysis.

A review of factors affecting the structure, compositions, and the techno-functionalities of bovine milk fat globule and membrane

Amino acid composition of human and animal milk, bovine colostrum, and infant formula: a standardized comparative analysis.

Human milk proteins, a mixture of whey proteins including caseins, milk fat globule membrane (MFGM) proteins, various peptides, and their amino acids, play a crucial role in infant growth and development, as do non-nutritional bioactive components. The extracellular nicotinamide phosphoribosyltransferase (eNAMPT) or visfatin is a conserved cytokine/enzyme released by many mammalian cells, related to multiple metabolic and immune processes. Few investigations have been reported about detecting visfatin in skimmed milk and the hypothesis of its potential role in regulating infant adiposity through breast milk. Milk samples from a donated human milk bank were analyzed. After milk fractionation by centrifugation, skimmed milk and MFGM were analyzed by SDS-PAGE, MALDI-TOF mass spectrometry ELISA and/or Western blot. The ELISA assay showed a higher visfatin content in raw skimmed milk than in pasteurized samples. Meanwhile, MFGMs revealed higher visfatin levels in pasteurized samples. This is the first time visfatin has been identified associated with MFGM, and these results could suggest an affinity of this molecule for a lipidic environment.

Fat in human milk varies during a feed, during the day and throughout the period of lactation. Fatty acid (FA) composition varies over the course of the day and during lactation. Aim: To evaluate FA composition in human milk, from 7 days (transitional milk) to 16 weeks of lactation (mature milk) and to assess the composition stability of these FA throughout this period. Methods: Mothers living in urban area of Porto who accepted to participate in the study were selected according to inclusion criteria (healthy term newborn exclusively breast-feeding). Pooled human milk was collected from all feedings over 24 hours at the following times: 7 days and 4, 8, 12 and 16 weeks of lactation. FA were analysed through capillary gas chromatography. Comparisons were made (Oneway ANOVA). Correlations between FA were made through Pearson and Spearman correlation coefficient. Results: 31 mothers completed the follow-up period. Total saturated fatty acids (SFA) progressively increased from 40.50 ± 3.72 (% wt/wt) at 7th day up to 43.08 ± 4.61 at the 16th week of lactation, whereas total monounsaturated fatty acid decreased from 33.04 ± 2.58 (% wt/wt) to 31.48 ± 3.32, in the same period. Arachidonic acid (AA) markedly decreases with the stage of lactation. Docosahexaenoic acid (DHA) content decreases lightly from the 7th day to the 4th week of lactation, remaining stable throughout the rest of the lactation period. No significant correlation was found between the levels of linonleic and a-linolenic acid, and their long-chain metabolites AA and DHA. Conclusions: Despite fluctuations in the contents of AA and DHA, the ratio AA/DHA did not significantly change throughout the period of lactation. The ratio AA/DHA remained constant during the study, suggesting a protective mechanism, as AA and DHA are essential structural components of all tissues and particularly of retina and neuronal tissues.

Precision nutrition and nutrimetabolomics are emerging omics technology applications in public health. In this context, the infant formula (IF) is a manufactured foodstuff that aims to match the composition of human milk (HM), especially the lipid profile. The IF manufacturers have achieved relative success in matching the predominant fatty acid (FAs) profiles, but the stereospecific structures of the triacylglycerides in HM require deeper analyses with system sciences. We employed NMR-based metabolomics to compare the lipid profiles of 12 commercial IF samples and 10 HM samples. Additionally, vegetables, fish, and microalgae oil as raw materials in IFs were also investigated to understand the lipid profile of IFs. We found that IF has significantly less saturated fatty acids (SFA), higher unsaturated FAs, and similar polyunsaturated fatty acid (PUFA) content, compared with HM. However, the main difference was the stereospecific distribution of FAs: HM samples were associated with a high content of SFAs in the sn-2 position (26.03% ± 2.93%) and PUFAs in the sn-1,3 position (15.35% ± 3.94%). The IF had the opposite distribution, with SFAs esterified mainly in the sn-1,3 position (33.07 ± 4.93%) and PUFAs in the sn-2 position (9.57% ± 7.05%). Consequently, the hydrolysis of HM results in SFA mainly as sn-2-monoacylglycerides, which are well absorbed. In contrast, the hydrolysis of the IF provided SFA, mainly as free FAs, which tend to bind calcium and form insoluble calcium soaps in the intestine. Taken together, these observations can inform optimal design of infant formulas with a view to precision nutrition.

The ideal feeding for infants is the breast milk because it has a balanced nutritional composition, which includes all essential nutrients, in addition to many bioactive factors that contribute to the growth and development of the child, as well as to the maturation of the gastrointestinal tract. Among them are immunological factors, antimicrobials and anti-inflammatory components, digestive enzymes, various types of hormones, and growth factors. If human milk is not available, there is an indication of infant formulas that should follow the recommendations of the Codex Alimentarius of the Food and Agriculture Organization/World Health Organization (WHO). In a century of history, infant formulas have gone from a simple combination of cow milk (evaporated or condensed) and water to highly sophisticated products, elaborated by very refined technological processes to produce lactose-free, antiregurgitation, based on soy protein, hydrolyzed protein in various grades, and only amino acids formulas. The major milestones in the modification of infant formulas were the incorporation of nutrients/ingredients such as: iron, nucleotides, alpha lactalbumin, long-chain polyunsaturated fatty acids, prebiotics, probiotics, postbiotics, oligosaccharides similar to human milk, lactoferrin, and milk fat globule membrane. Many of these ingredients have shown benefits on the immunological system. Despite the technological advances, breast milk remains irreplaceable, being the gold standard for infant feeding.

The influence of dietary structures composed of different fat globule interfaces on lipid metabolism in mice with a high-fat diet.