Nutritional Lipids in Focus: ARA and DHA

This article was first published in the October/November 2019 edition of The World of Food Ingredients.

The importance of nutrition during the first 1,000 days of a child’s life continues to be an essential topic of study due to its impact on long-term health. Although breast milk is widely recognized as the gold standard for infants, some situations necessitate the use of infant formula and supplementary early life nutrition. Nutritional lipid R&D plays a pivotal role as researchers seek to mimic the composition of human breast milk more closely.  

DHA vs. ARA

Two ingredients included in many infant nutrition offerings currently on the market are the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (ARA). While both components are linked to cognitive development, there has arguably been a stronger focus on the addition of DHA in infant formula.

However, in the June 2019 edition of Réalités Pédiatriques, Professor Patrick Tounian and fellow researchers present an interesting argument to emphasize that when breastfeeding is not possible, infants are best fed early-life nutrition supplemented with both DHA and ARA.

DHA is mainly present in brain cell membranes, where it concentrates in phospholipids in the prefrontal cortex. Since humans cannot synthesize this essential fatty acid, it must be obtained through the diet. ARA is similarly present in the brain, but it is also the primary unsaturated fatty acid in the heart, muscle, vascular endothelium, T-lymphocytes, adrenal, kidneys, liver and the placenta. Although both these fatty acids play a role in a variety of physical processes – such as membrane structure and function, cell signaling and communication, lipid mediator production and gene expression – ARA is also the precursor of eicosanoids. These signaling molecules influence the release of somatostatin, the principal hormone that stimulates cell proliferation and growth. Eicosanoids also support the immune system as well as vasculature development and function.

For children up to the age of six months, intakes of 100 mg DHA and 140 mg ARA per day, respectively, are generally considered by experts and certain health bodies as appropriate. Still, guidelines on the mandatory addition of DHA and ARA in infant formulas, either at the global level or by the EU, were until recently lacking. 

ARA: to add or not to add?

In 2014, the European Food Safety Authority (EFSA) issued a scientific opinion on the essential composition of infant and follow-on formulas, which put forward that such products should contain amounts of 20-50 mg DHA/100 kcal. The accompanying addition of ARA, however, was not deemed necessary. The Commission Delegated Regulation (EU) 2016/127 that defines the latest compositional criteria for infant and follow-on formulas subsequently mandated the addition of DHA according to the levels recommended by EFSA in 2014, while the addition of ARA remains optional for producers of infant formula. This regulation will be fully effective across the EU in February 2020.

However, in their recent recommendation, Professor Patrick Tounian, lead author and Professor in Pediatric Nutrition and Gastroenterology at Trousseau Hospital in Paris, France, says that there are numerous arguments underscoring the physiological roles played by ARA in infant formula.

“The main reason to add both ARA and DHA to infant formulas is that breast milk contains both these components,” Tounian explains. Breast milk samples from across the globe have shown a “robust consistency” in the amounts of ARA, while DHA is always present, but at a more variable rate. In most breast milk samples, the ARA concentration is, in fact, higher than that of DHA, with the levels of ARA:DHA in some cases reaching 2:1, he says.

Professor Patrick Tounian, Professor in Pediatric Nutrition and Gastroenterology at Trousseau Hospital.

Tounian et al. state that despite certain discrepancies in study results into the role of LCPUFAs added in infant formulas on the development of infants, there is enough scientific evidence to conclude that a well balanced dietary supply of ARA and DHA ensures that infant and young child LCPUFA status, growth, brain and immune development remain similar to that seen in breastfed infants.

“Formulas containing DHA only, specifically at the high doses advised by the recent EFSA panel and European regulation, have not been subjected to preclinical evaluation of nutritional adequacy and safety yet,” Tounian et al. note. Their precautionary advice, therefore, endorses the addition of ARA in infant formulas, pending further evidence that formulas based on a composition that differs from that of human milk are safe and suitable for infants and young children.

Ongoing research potential

According to the UN World Health Organization, across the globe, approximately 30% of children under the age of five are stunted due to poor feeding and repeated infections. Improved feeding practices can promote a better nutritional status, making infant feeding practices a cornerstone of many governments and health organizations’ strategies to alleviate the global health burden.

What is clear is that there is scope for ongoing research into creating optimal infant nutrition, and hence a strong need for further insights into the role of nutritional lipids. “Human milk, the gold standard diet for infants, as a fluid biologically active, should be studied in deep,” explains  Professor Cristina Campoy, M.D., Department of Pediatrics at the University of Granada in Spain. “Lipids present in human milk are currently being extensively studied on account of new metabolomics technology. New lipid components continue to be discovered and investigated.” 

In this space, the conservation of milk lipids, to replace the often-used vegetal lipids, is one area ripe for innovation, Tounian notes. Innova Market Insights data show that the fastest-growing ingredient in terms of use in the infant nutrition category is indeed a vegetal oil. There was an average annual growth of 31% in the use of rapeseed oil in infant nutrition product launches between 2014 and 2018 (Global). 

“Many industry players avoid the use of milk lipids and instead add palm oil and certain flower oils. The profile of saturated fatty acids in dairy is closer to that of breast milk than what the industry can offer with only vegetal oils. It is important to further innovate in maintaining dairy lipids, particularly the saturated fatty acids in dairy, as this would be closer to breast milk,” Tounian affirms.

The cholesterol content of infant formulas is another topic currently undergoing further research. Breast milk naturally contains cholesterol and some industry players are considering adding it to infant formulas with an eye on preventing hypercholesterolemia in later adulthood.

“Since severe hypercholesterolemia is genetic, the addition of cholesterol in infant formula is not likely to make a difference,” Tounian notes. “Cholesterol is, however, essential in terms of neurological development, making it an interesting area for the industry to explore in the next years.” 

Fat and the immune system 

Catherine Field, Ph.D. RD, Professor of Nutrition at the University of Alberta, Canada, pinpoints the impact of medium-chain fatty acids on infant health as an area of interest. “Medium-chain fatty acids are those of 8 to 10 carbons in length that can make up 10 to 30% of the fatty acids in breast milk. The quantity is determined by the proportion of carbohydrate and fat in the mother’s diet. There are more of these if there is less fat and more carbohydrate in a mother’s diet,” she says.

Further research and development should also target the all-important immune system and seek solutions to improve its development in the early stages of an infant’s life. A focus here is the amount and type of fat.

“The child’s immune system develops during the first to the third year of their life and dietary fat is known to influence immune function and development,” Field states. “Likewise, not much is known about the importance of phosphatidylcholine on immune development. This form of choline varies considerably in the diet, and we know it can impact the function of the immune system.” 

Tips for the nutritional sector 

Infant nutrition product launches are on the rise. Innova Market Insights data have shown that the infant nutrition category has seen an average annual growth in product launches of 13% between 2014 and 2018 (Global). Baby formula/milk remained the top subcategory (2014-2018, Global), although infant snacks is also a growing subcategory.

According to Tounian, in terms of improving the nutritional profile of products aimed at infants, the main industry takehome message is that lipids – either from butter or vegetal oils – should be systematically added to infant nutrition. “Each savory meal an infant consumes should contain some added lipids,” he says, as the recommended intake of lipids for infants between 6 and 12 months is about 40% of the total energy intake. 

“To reach this, the only solution is to add lipids to all of an infant’s meals. Industry and parents should also be aware that infants between 6 and 12 months that are fed infant formula should drink at least several hundreds of milliliters to reach the right amount of essential fatty acids. This usually amounts to at least three bottles or 700 milliliters of follow-up formula per day to reach the total daily requirements of essential fatty acids,” he adds. 

Personalized approach 

However, improvements to infant nutrition are not just to be found through the addition of certain ingredients or the development of catch-all early life nutrition products. There is a strong potential for optimizing early life nutrition offerings in a personalized fashion. “Human milk lipid content and quality changes through the day, within each feed, depending on maternal diet, on a mother’s metabolic status or maternal FADS genotype,” explains Campoy.

The amount and quality of human milk lipids that reach the infant may also be influenced by maternal microbiota or by the xenobiotics introduced by human breast milk to the baby, among other factors. Human milk “adapts” itself depending on different circumstances, such as the nutritional status of the mother, but this capacity and complexity have not yet been mimetized in infant nutrition products.

Advances in new product development could thus support better infant growth patterns and cognitive development to become more similar to breastfed babies.

“If we understand clearly the biological capacity of adaptation and the complexity of human milk, we will be able to develop new infant formulas and infant food products that will contribute to the development of an individualized diet for infants, and at the end, prevent the long-term development of common chronic diseases,” she continues. “Lipids will be essential nutrients involved in the design of the individualized diets for infants. The relationship between n-3 and n-6 fatty acids series and their metabolites, need further research with well-designed studies and long-term followup,” says Campoy. Examples of products that could meet different consumer needs include infant formulas for different genders or gestational ages.

Personalized nutritional products for infants born to obese or diabetic mothers, products for mothers during pregnancy or lactation based on maternal health, as well as maternal and baby genotype, are other examples worth exploring, Campoy notes.

“We need to develop products that improve immune system development and can help solve the early mal-programming that can happen intra-utero or during early postnatal life. [Another issue that can inform product development is] the gut dysbiosis imprinted in babies born to obese mothers or treated with antibiotics,” she continues. 

Concluding remarks

Considering the established long-term impact of nutrition on the development of infants, improvements in infant formulas and foods can exert a significant economic impact on society. Campoy notes, “There is an exciting future in early life nutrition, and every day new windows of opportunity are opening up which stimulate researchers continuously.”

To more closely mimic human breast milk, there is ongoing space to optimize the nutritional lipid profiles of products offered. Moreover, the food and beverage industry can support parents in offering their children an ideal diet by developing follow-up products that suit an infant’s changing needs – whether that be in lipid profiles, convenience of use or by offering a personalized approach.

By Lucy Gunn

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