Perspective: Moving Toward Desirable Linoleic Acid Content in Infant Formula

Abstract

Infant formula should provide the appropriate nutrients and adequate energy to facilitate healthy infant growth and development. If conclusive data on quantitative nutrient requirements are not available, the composition of human milk (HM) can provide some initial guidance on the infant formula composition. This paper provides a narrative review of the current knowledge, unresolved questions, and future research needs in the area of HM fatty acid (FA) composition, with a particular focus on exploring appropriate intake levels of the essential FA linoleic acid (LA) in infant formula. The paper highlights a clear gap in clinical evidence as to the impact of LA levels in HM or formula on infant outcomes, such as growth, development, and long-term health. The available preclinical information suggests potential disadvantages of high LA intake in the early postnatal period. We recommend performing well-designed clinical intervention trials to create clarity on optimal levels of LA to achieve positive impacts on both short-term growth and development and long-term functional health outcomes.

Keywords: LCPUFAs; human milk composition; infant development; infant formula; linoleic acid; nutritional programming.

FIGURE 1

Boxes represent the minimum and maximum recommended/stipulated levels of LA, ALA, ARA, and DHA as set by Codex and various local regulatory bodies; values are expressed as mg/100 kcal and are calculated assuming 3.5 g fat/100 mL for infant formula. (A) No maximum level defined; (B) no minimum level defined (addition is not mandatory); (C) LA/ALA ratio needs to be between 5 and 15; (D) addition at maximum of 1% of total FA; (E) ARA/DHA ratio ≥1; (F) guidance upper level is 0.5% of total FA; and (G) shall not exceed n–6 LCPUFA. The box plot at right represents the median, upper, and lower quartiles and the range (minimum to maximum) in which these FAs are present in HM; values are expressed as mg/100 kcal and are calculated assuming 3.3 g fat/100 mL and using mean values in milk of mothers of term infants (average colostrum, transitional, and mature milk) that were reported in 50 studies (60 groups varying in size from 5 to 602 subjects) published between 1985 and 2018 that were included in a recent review on HM FA composition (2). Abbreviations: ALA, α-linolenic acid; ANZ, Australia New Zealand; ARA, arachidonic acid; CN current, China standards as published in February 2021 and mandatory from February 2023 onwards; CN previous, China standards before February 2021; EFSA current, European Food Safety Authority standards mandatory from February 2020 onwards; EFSA previous, European Food Safety Authority standards before February 2020; HM, human milk; HM ref, human milk reference; LA, linoleic acid; LCPUFA, long-chain PUFA; RU, Russia.

FIGURE 2

Metabolic pathways and interconversions of PUFAs. Adapted from Gibson et al. (57) with permission from Elsevier. Not shown are the metabolic steps required for activation of FAs to enter the pathways, and the steps required to accept synthetic products from the pathway. Abbreviations: AdrA, adrenic acid; ALA, α-linolenic acid; ARA, arachidonic acid; β-oxy, β-oxydation; DGLA, di-homo-γ-linolenic acid; desat, desaturase; DPA³, docosapentaenoic acid n–3; DPA⁶, docosapentaenoic acid n–6; elong, elongase; GLA, γ-linolenic acid; LA, linoleic acid; SDA, stearidonic acid.