Should infant formula lipids contain cholesterol?

Authors: Laurence Eyres, Anny Dentener, Sally Xiong, Jing Zhou

See Tables and illustrations in FoodNZ, October/November 2020, page 25

Big business

Infant nutrition is a major food industry segment especially in strong dairy-orientated countries like New Zealand and Australia. The latest figures from Statistics NZ show infant formula exports in 2019 of about 120,000 tonnes. The business grew by 30% over the year before to earn export revenue of more than $1.7 billion NZD. For comparison, exports in 2015 were worth $450 million. Four major blenders, packers and exporters dominate the trade – Fonterra, Synlait, Danone Nutricia and GMP. A2 Milk markets and sells a major brand of infant formula in China but is not a manufacturer. New Zealand accounts for about 7% of the global trade in formula.

Considerations

The nutritional superiority of human breast milk has instigated much research over the last 50 years and lipids have been a major part of that work, especially in New Zealand.

The lipid work has explored options for matching the fatty acid composition and adding both arachidonic acid (omega-6) and

DHA (omega-3). Modified triglycerides and complex lipids such as phospholipids and gangliosides that simulate the human milkfat globule membrane (MFGM) have also been studied but as far as we know few studies have investigated adding fats with known cholesterol levels to attain a certain targeted value.

The original infant formula, based on bovine, ovine or caprine milks, has had little modification of the fat structure nor ingredient implementation over the years. Animal fats have been substituted by vegetable fats because of theoretical nutritional advantages and, in the case of anhydrous milkfat (AMF), cost and the commercial opportunity in AMF sales.

Several aspects are significant about this substitution. Milk fats are present in milk as droplets surrounded by the milkfat globule membrane. They also contain cholesterol and its esters whilst vegetable fats contain little or no cholesterol in any form.

An early and popular global formula “Enfamil”, (Eyres,1989) had a traditional fat blend of soft beef fat, maize oil, and coconut oil to produce a refined blend with a fatty acid profile closer to typical human milkfat combined with skim milk powder.

The major differences between breast milk and formulae lie in the variety of component saturated fatty acids (such as palmitic acid, including its structural position) and unsaturated fatty acids (including arachidonic acid and docosahexaenoic acid). The functional outcomes of these differences during infancy and for later child and adult life are still largely unknown, but there is consensus that opportunities exist for improvements in the qualitative lipid supply to infants through the mother's diet or infant formulae. Much work has occurred on PUFA, structured lipids (OPO, OPL) and MFGM complex lipids such as gangliosides, however, little has been done to study the effects of adding cholesterol or its complex lipids. The triglyceride structure (i.e., the position of the fatty acids on the glycerol molecule) is also of importance because it has been shown that long-chain saturated fatty acids in the centre (sn-2) position are more efficiently digested and absorbed. Human milk and bovine milk are rich in the saturated fatty acid palmitic acid (C16:0, approximately 25% of fatty acids), of which approximately 70% of molecules in human milk and 45% in bovine milk, but <20% in most plant oils are esterified in the sn-2 position of triglycerides (Bracco U, 1994). In infant formulae, this translates into a lower proportion of palmitic acid in the sn-2 position in formulae containing only vegetable oils compared with formulae containing milk fat or β-palmitate (a structured triglyceride with palmitic acid esterified preferentially in the sn-2 position).

Mammary alveolar cells produce milk fat globules containing a core predominantly consisting of triglycerides (comprising 98%–99% of milk lipids) and small amounts of monoglycerides, diglycerides, and nonesterified fatty acids, surrounded by a milk fat membrane with different phospholipids, esterified cholesterol, glycosylated polypeptides, filaments, mucin, lactadherin (Milk fat globule-EGF factor 8 protein), and other components.

Cholesterol benefits

Human milk contains 90 to 150 mg/L cholesterol, in contrast to no appreciable cholesterol content in vegetable oil–based infant formulae and to approximately 40 mg/L in dairy fat–based infant formulae (Kamelska et al., 2013). The range of observed total cholesterol in made-up milks seems to be 0-10mg/L. Some of these values have been calculated from label declarations in per 100g, then assumed a standard conversion to ml. of 13.2g powder in 100ml liquid IF.

Over the past several years, the market share of sheep and goat infant formula has grown in New Zealand as well as export markets. Sheep milk contains around 14-29 mg/L and goat milk contains around 10- 18mg/L cholesterol, respectively (Renata PF and Anna M KS, 2020). The majority of goat and sheep infant formulae in New Zealand market contain goat whole milk and sheep whole milk. The cholesterol level for those infant formula is approximately less than 50mg/L which depends on the goat whole milk and sheep whole milk usage in the formula.

Cholesterol is the substrate for the synthesis of bile acids, lipoproteins, vitamin D, and hormones. It also acts by stabilising the structure of cellular membranes and is incorporated into brain lipids, mainly during the first months of life (Kinney HC et al., 1994). The balance and interaction between DHA and cholesterol might modulate membrane rafts and functions of channels, enzymes, and receptors associated with membranes, but clinical consequences in infants are not known.

The higher cholesterol concentration of human milk is most likely the reason for the higher blood levels of cholesterol and low-density lipoprotein cholesterol levels in breast-fed infants compared with formula-fed infants.

Lasting effects were reported in meta-analyses of studies on the association of breast-feeding with modestly but significantly reduced concentrations of total cholesterol and low-density lipoprotein cholesterol in adults. A greater difference (0.15 mmol/L) was observed for exclusive, rather than partial breast-feeding, suggesting that exclusive breast-feeding of 30% of infants could reduce population prevalence of cardiovascular disease by 5% (Owen CG et al., 2008). Indeed, the longitudinal study of 87,252 nurses born in the first half of the 20th century found being breast-fed is associated with a 10% risk reduction for cardiovascular disease (Rich-Edwards JW et al., 2004).

Conclusion

Research is required in several areas, including the needs of term and preterm infants for cholesterol, the sites of action and clinical effects of lipid mediators on immunity and inflammation, the role of lipids on metabolic, neurological, and immunological outcomes, and the mechanisms by which lipids act on both short and long-term health.

We feel that overall, however, cholesterol should be a key component of modern and effective infant formula products.

Laurence Eyres and Anny Dentener are consultants and are part of FoodInc Dr. Sally Xiong is Chief Food Technologist, Synergy Nutrition Limited Jing Zhou is R&D Innovation Manager, Winston Nutritional Limited. Thanks are due to Angela Rowan of Fonterra for valuable commercial insights and for nutritional information.

References

Eyres, L. Linking product development of milkfat with the marketplace, Fats for the future,1989, Ed. R.C. Cambie, IUPAC, p 233-250.

Bracco U. Effect of triglyceride structure on fat absorption. Am J Clin Nutr 1994; 60(6 suppl):1002S–1009S. [PubMed] [Google Scholar]

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Renata PF, Anna M. KS. The Comparison of Nutritional Value of Human Milk with Other Mammals’ Milk. Nutrients 2020, 12, 1404; doi:10.3390/ nu12051404

Abbreviations

MFGM - Milkfat globule membrane

AMF - Anhydrous milkfat

OPO- Oleic-Palmitic-oleic triglyceride

OPL - Oleic-Palmitic-linoleic triglyceride