Advancements in infant nutrition

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Infant nutrition products are evolving. A string of regulatory approvals of human milk oligosaccharide (HMO) ingredients across numerous jurisdictions, including the United Kingdom, European Union,¹ and China, as well as GRAS affirmation in the United States,² are going to have major implications on the contents of infant formula, bringing these products closer to the nutritional value of breast milk. Technological advancements like precision fermentation are also changing the way manufactures can make ingredients like lactoferrin, potentially lowering costs.

HMOs

HMOs are the third most abundant component of breast milk after lactose and lipids, and are a complex mixture of 200 non-digestible and non-nutritional carbohydrates.³ Significantly, these non-digestible and non-nutritional carbohydrates are virtually absent from bovine milk. In breast milk, there are three major HMOs: fucosylated HMOs, sialylated HMOs, and nonfucosylated neutral HMOs. The two most abundant are fucosylated HMOs and nonfucosylated neutral HMOs, and include 2’-fucosyllactose (2’-FL) and lacto-N-neotetraose (LNnT), respectively. 2’-FL is the most abundant HMO, and accounts for 30% of the total HMOs.³

The benefits of HMOs for infant includes the modulation of gut bacteria, protection from pathogens, and the development of the immune system.When it comes to gut bacteria, HMOs have been shown in in vitro studies to promote the growth of certain Bifidobacteria, including Bifidobacterium longum subsp. Bifidobacterium infantis, even when 2’-FL was the sole source of carbohydrates.3 In infants fed infant formula with 2’-FL and LNnT, stool samples showed that they had a bacterial profile similar to that of breast-fed infants. After three months, they also had increased colonization of beneficial bacteria and decreased colonization of pathogenic bacteria.

Research has also shown that HMOs strengthen the gut barrier functions of infants, attenuating the colonization of pathogenic bacteria such as Campylobacter jejuni, inhibiting the release of pro-inflammatory mucosal signals. HMOs may even reduce preterm mortality by protecting the microbiome against necrotizing enterocolitis, candidiasis, and several immune-related diseases.³

Immune modulation may be the most crucial role of HMOs, as they modulate “the gene expression of intestinal cells, leading to changes in the expression of cell surface glycans and other cell responses.”³

Lactoferrin

Another important component of breast milk that contributes to the immune system of infants is lactoferrin. Lactoferrin is a component of whey protein found in the milk of most mammals.⁴ That makes it different from HMOs in that it can be isolated from bovine milk, while HMOs are only found endogenously in humans.

“Lactoferrin has been shown to support a normal immune response against viruses and bacteria,^{5, 6} play an immune-modulatory role,⁷ and even reduce the risk of gastro-intestinal and respiratory tract infections in infants and young children.^8,9,10,11,12 This powerful protein acts as a key mediator in a baby’s immune system, helping them stay healthy in their early, most vulnerable stages of life,” explains Jouke Veldman, marketing director of Early Life Nutrition at FrieslandCampina Ingredients (Amersfoort, The Netherlands). “And for babies that can’t be breastfed, lactoferrin can be effectively isolated from cow’s milk and added to infant milk formulas – giving peace of mind to the 60% of parents who rank immunity as their top concern for their infant’s health.”¹³

Lactoferrin is an iron-binding milk protein which allows it to balance iron content in the body, and related to this is its antioxidant abilities with research showing that it can reduce the level of cytotoxins H₂O₂ and increase the levels of FRAP (ferric reducing antioxidant power) both in the intra- and extracellular space.⁴ Research has shown that lactoferrin “supports normal tissue development in the fetus, including normal ossification, adequate iron availability and absorption, protects against infection and inflammation, and benefits both mother and fetus.” When it comes to immunity, lactoferrin is particularly important for innate immunity which is non-specific and depends on inherited genes, providing some protection from birth.⁴

As mentioned before, currently bovine milk is used for the production of lactoferrin to be used in infant formula. Research suggests that the clinical effects in newborns is the same as human milk.⁴ Veldman says that FrieslandCampina was among the first companies to produce lactoferrin 25 years ago, and the company recently expanded its lactoferrin facility in The Netherlands, increasing its capacity to 80 metric tons from 20 metric tons. Clearly, there is a profound demand for lactoferrin, but it’s also a resource intensive ingredient to produce.

Paola Delgado, chief operating officer of Helaina (New York) explained¹⁴ to Nutritional Outlook that it takes 10,000 liters of cow’s milk to make 1 kg of lactoferrin. FrieslandCampina acknowledges this and therefore improves efficiencies in its processes to compensate.

“Our Vivinal Lactoferrin is sourced directly from high-quality fresh skimmed milk delivered daily from FrieslandCampina member farmers, rather than from whey. This allows us to remove an extra step in the product process, making it more efficient and streamlined,” explains Veldman. “In addition, to create powder-based ingredients like Vivinal Lactoferrin, we use a specialized spray drying process that dries liquids with hot air. While this method allows us to create a diverse array of nutritious ingredients in accessible formats, it’s also one of the most energy intensive processes in our factories. Our new lactoferrin production facility runs on 100% green electricity.”

Veldman says that the new facility runs on 100% green electricity. He explains that, “The majority of this electricity is generated by FrieslandCampina’s member farms and certified under the EU’s Guarantee of Origin scheme. Water and salt residues produced during the manufacturing process are also reused as far as we can to ensure maximum efficiency of raw materials and byproducts. By integrating these technologies, we’re creating a more efficient and sustainable production process that aligns with our commitment to nourishing the planet for generations to come.”

Technology is also evolving to allow manufacturers to synthesize lactoferrin via precision fermentation. Helaina, for example, manufactures a branded lactoferrin called effera that Delgado says has the “same amino acid sequence and glycosylation that what is found in human colostrum.”

The idea is that because the lactoferrin has the same composition of the lactoferrin found in human breast milk, it will be more bioavailable and effective. This hypothesis is supported by some evidence. One study¹⁵ that has yet to be peer-reviewed found that after 28 days effera was safe and had a lower immunogenic response from participants compared to bovine lactoferrin. This means that the bodies of participants taking effera did not experience a material change in antibodies in response to the recombinant human lactoferrin at multiple doses.

According to Delgado, using precision fermentation also has the potential to lower costs since it is less resource intensive to make while also being more consistent in quality and supply since it is not dependent on the quality of the source material or subject to supply-chain constraints.

Not everyone is able to breast feed their children, therefore advances that give all children access to these essential forms of nutrition are welcome progress. Ingredients like HMOs and lactoferrin help set the stage for people’s lives and health.

References

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2. Krawiec, S. FrieslandCampina Ingredients announces Chinese MARA approval and self-affirmation of GRAS for LNT ingredient. Nutritional Outlook. June 28, 2024. https://www.nutritionaloutlook.com/view/frieslandcampina-ingredients-announces-chinese-mara-approval-and-self-affirmation-of-gras-for-lnt-ingredient (accessed 2024-10-29)
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