Human Milk Research

Lipids: The key to optimal infant growth and cognitive performance

Aligned with the World Health Organization’s view on the importance of breastfeeding for infant health, Danone Research & Innovation advocates for exclusive breastfeeding during the first six months of life, followed by sustained breastfeeding alongside complementary foods*. Leveraging our expertise, we develop innovative nutritional solutions to guide and support breastfeeding mothers.

Lipids, more commonly referred to as ‘fats’ and ‘oils’, are critical for infant health, extending beyond the first months of life and well into childhood. They serve both as a vital source of energy and building blocks for physical growth and development, especially for the brain.

Following decades of cutting-edge research, we are excited to unveil our latest scientific discovery on lipids in human milk and in formula, along with insights into their potential to maximize health benefits for lifelong health.

Understanding the composition of lipids

Extensive studies have shown a link between the lipid composition of human milk and various infant health outcomes, such as growth, neurocognitive development and function, regulation of inflammation and infection risk, and the risk of metabolic and cardiovascular disease in adulthood1Reference: Munblit D., Verhasselt V., Warner J.O. Editorial: Human milk composition and health outcomes in children. Front. Pediatr. 2019;7:319. doi: 10.3389/fped.2019.00319..

Drawing inspiration from fifty years of human milk research, the challenge we faced in developing our innovative nutritional solution was two-fold: first, how could we gain insights into the characteristics of lipids in human milk to compose a formula for infants that offered similar health benefits? Second, could we preserve the size, structure and function of lipid droplets during the usual manufacturing process applied in the production of formula?

Milk fat globules are produced in the mammary glands. Triglycerides, which deliver energy to the infant, are found at the core of each milk fat globule and are encapsulated by a triple-layer membrane (the milk fat globule membrane). On average, milk fat globules measure approximately four micrometers in size. However, lipid droplets in standard infant formulas primarily consist of triglycerides from vegetable oils and lack the important triple-layer milk fat globule membrane. Moreover, the average diameter of these lipid droplets is only around 0.5 micrometers — about ten times smaller than those in human milk — due to the high pressures applied during manufacturing.

Nana Bartke, Head of Nutritional Science in Early Life at Danone Research & Innovation, explains: “It was by thoroughly examining the functionality and 3D structure of lipids in human milk that we achieved our breakthrough. We aimed to recreate lipid droplets in formula for infants that more closely mimic the globules found in human milk. To do this, we had to adjust three key elements of the lipid droplets: size, composition and 3D structure. This ensured triglycerides were present at the core and that a milk fat globule membrane enveloped the exterior. It required the identification of the right ingredients to compose the membrane and to transform our manufacturing process. Only then were we able to form and preserve the large lipid droplets coated with milk fat globule membrane components, while securing a well-homogenized and stable reconstituted end product.”

Replicating the size and structure of human milk lipid globules

Over the years, Danone Research & Innovation has been refining formulas to better emulate the fatty acid and lipid compositions found in human milk lipids. Approximately fifteen years ago, we initiated the development of a unique formula that mimics closer than ever before the size, structure and composition of lipid globules naturally present in human milk.

According to Nana Bartke: “Altering the size and structure of the lipid droplets, as well as bringing their composition closer to that of human milk, required not only a new ingredient but also a gentler process for mixing and spray-drying the product.”

Traditionally, formulas have incorporated small lipid droplets to circumvent the creaming effect often observed in liquid dairy products, where separated fat rises to the surface. By using a patented two-phase manufacturing process with lower pressure settings during mixing and drying, we were able to create our unique formula. This formula contains larger lipid droplets, with diameters ranging from three to five micrometres, features a triglyceride core enriched with dairy lipids and is coated with phospholipids and glycolipids. Our innovation represents a significant advancement in lipid science for early life nutrition.

Supporting those facing specific challenges at birth or later during infancy

A recent study published in the American Journal of Clinical Nutrition evaluated the impact of our innovation on infant health outcomes. Findings demonstrate that this nutritional solution can support growth patterns like those of breastfed infants well into childhood. Specifically, infants who received this formula during their first four months of life exhibited a body mass index trajectory similar to that of breastfed infants up to five years of age2Reference: Abrahamse-Berkeveld M, et al. Infant Milk Formula with Large, Milk Phospholipid-coated Lipid Droplets Enriched in Dairy Lipids Affects Body Mass Index Trajectories and Blood Pressure at … Continue reading.

While our initial focus was on supporting metabolic health and growth in healthy, term-born infants, the potential benefits of this innovation extend even further, particularly for those facing a more challenging start in life. According to Marieke Abrahamse-Berkeveld, Senior Team Leader in Infant Growth & Development: “It has shown to have the greatest impact on infants who face specific challenges at birth or later during infancy, such as having a mother with overweight or obesity. This nutritional solution holds promise for normalizing suboptimal growth and development patterns in early life, potentially preventing metabolic diseases or suboptimal health in the future.”

The growing burden of metabolic diseases like Type 2 diabetes presents a major global health concern, with obesity rates projected to double from 2019 to 20503Reference: Chong B, Kong G, Shankar K, Chew HSJ, Lin C, Goh R, Chin YH, Tan DJH, Chan KE, Lim WH, Syn N, Chan SP, Wang JW, Khoo CM, Dimitriadis GK, Wijarnpreecha K, Sanyal A, Noureddin M, Siddiqui … Continue reading. With emerging evidence supporting the hypothesis that lipid droplet size, composition and structural characteristics significantly influence the development of infants, there’s an opportunity to better understand and prevent metabolic disease.

“As infants undergo rapid growth, both externally (in their weight and height) and internally (in their metabolic organs), we hypothesized that the unique size and structure of our innovative lipid droplets allowed for more efficient digestion, absorption and utilization of lipids in the body. Our research demonstrates that early exposure to this lipid droplet structure has enduring effects on metabolic health outcomes from infancy through childhood and into adulthood, potentially mitigating the risk of overweight or excessive adiposity later in life,” she adds.

Our next step is to confirm these findings in different clinical settings, in which we’ll delve deeper into body composition and metabolic health measurements, offering promise for future preventative solutions.

Optimizing brain development in early in life

Research has also shown that breastfed infants have an advantage over their formula-fed counterparts when it comes to neurocognitive development and functioning. Our growing understanding of the crucial role lipids play in brain development underscores this.

“The brain develops over a long period and is an organ rich in lipids. We know that enhancing lipid quality in nutrition, such as by adding DHA to formula for infants, positively impacts brain development. However, we didn’t simply add an ingredient to our latest nutritional innovation; we transformed its entire lipid droplet 3D structure to bring it closer to the breast milk lipid globule structure, thereby benefitting also neurocognitive outcomes,” notes Lidewij Schipper, Principal Scientist in Nutrition and Brain Development.

An exploratory study published in Frontiers in Nutrition revealed that five-year-olds who had received our innovative formula up to four months of age demonstrated cognitive performance comparable to breastfed children4Schipper L, Bartke N, Marintcheva-Petrova M, Schoen S, Vandenplas Y, Hokken-Koelega ACS. Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive … Continue reading. Furthermore, their cognitive performance surpassed that of children who had been given a standard formula for infants.

This research offers, once more, greater insights into optimizing cognitive performance in children. Given the positive correlation between breastfeeding duration and neurocognitive outcomes, future studies could explore whether longer exposure to our innovative formula would lead to even greater cognitive benefits. Additionally, these studies may examine the link between early cognitive performance and academic skills later in life.

In the meantime, the evidence clearly indicates that better brain health in infancy is a strong predictor of greater cognitive outcomes in childhood. Lidewij Schipper concludes; “It comes down to having a good start early in life. A well-functioning brain in the early years makes it easier to acquire new skills, leading to enhanced lifelong cognitive performance.”

*Aligned with the World Health Organization’s view on the importance of breastfeeding for infant health, Danone Research & Innovation advocates for exclusive breastfeeding during the first six months of life, followed by sustained breastfeeding up to two years (and beyond) in combination with the safe introduction of appropriate complementary foods.5https://www.who.int/news-room/fact-sheets/detail/infant-and-young-child-feeding

View References

View References
1 Reference: Munblit D., Verhasselt V., Warner J.O. Editorial: Human milk composition and health outcomes in children. Front. Pediatr. 2019;7:319. doi: 10.3389/fped.2019.00319.
2 Reference: Abrahamse-Berkeveld M, et al. Infant Milk Formula with Large, Milk Phospholipid-coated Lipid Droplets Enriched in Dairy Lipids Affects Body Mass Index Trajectories and Blood Pressure at School Age: Follow-up of a Randomized Controlled Trial, The American Journal of Clinical Nutrition, Vol. 119, 1, 2024, p 87-99. https://www.sciencedirect.com/science/article/pii/S000291652366191X
3 Reference: Chong B, Kong G, Shankar K, Chew HSJ, Lin C, Goh R, Chin YH, Tan DJH, Chan KE, Lim WH, Syn N, Chan SP, Wang JW, Khoo CM, Dimitriadis GK, Wijarnpreecha K, Sanyal A, Noureddin M, Siddiqui MS, Foo R, Mehta A, Figtree GA, Hausenloy DJ, Chan MY, Ng CH, Muthiah M, Mamas MA, Chew NWS. The global syndemic of metabolic diseases in the young adult population: A consortium of trends and projections from the Global Burden of Disease 2000-2019. Metabolism. 2023 Apr;141:155402. doi: 10.1016/j.metabol.2023.155402. Epub 2023 Jan 28. PMID: 36717058.
4 Schipper L, Bartke N, Marintcheva-Petrova M, Schoen S, Vandenplas Y, Hokken-Koelega ACS. Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive performance at school age. Front Nutr. 2023 Sep 5;10:1215199. doi: 10.3389/fnut.2023.1215199. PMID: 37731397; PMCID: PMC10508340.
https://pubmed.ncbi.nlm.nih.gov/37731397/
5 https://www.who.int/news-room/fact-sheets/detail/infant-and-young-child-feeding