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Enzymatic Synthesis of Epoxidized Metabolites of Docosahexaenoic, Eicosapentaenoic, and Arachidonic Acids
Published on: June 28, 2019
Arachidonic acid supply and metabolism in human infants born at full term
B Koletzko1, T Decsi, H Demmelmair
1Kinderpoliklinik, Ludwig-Maximilans-Universität, Munich, Germany.
Insights
Infant formula often lacks arachidonic acid (AA), crucial for development. Supplementing formula with AA and docosahexaenoic acid (DHA) improves infant plasma levels, mimicking breast milk and supporting healthy growth.
Area of Science:
- Nutritional Biochemistry
- Pediatric Nutrition
- Infant Development
Background:
- Arachidonic acid (AA) is vital for infant eicosanoid synthesis and tissue accretion, particularly in the brain.
- Human milk provides preformed AA, while conventional vegetable oil-based infant formulas do not.
- Lower AA levels in formula-fed infants may impact developmental processes.
Purpose of the Study:
- To compare plasma phospholipid arachidonic acid (AA) levels in breast-fed versus formula-fed infants.
- To evaluate the effect of supplementing infant formula with AA and docosahexaenoic acid (DHA) on plasma AA levels.
- To assess the capacity of term neonates for endogenous AA synthesis.
Main Methods:
- Analysis of plasma lipid composition in infants fed human milk or standard formula.
- Randomized trial of infants fed formula with or without AA and DHA supplementation.
- Stable isotope (13C) tracing in neonates fed a corn oil-based formula to estimate endogenous AA synthesis.
Main Results:
- Formula-fed infants had significantly lower plasma AA levels compared to breast-fed infants.
- Formula supplementation with AA and DHA maintained plasma AA levels comparable to those in breast-fed infants.
- Term neonates can synthesize AA, but endogenous synthesis contributes only an estimated 23% of total plasma AA by day four.
Conclusions:
- Conventional infant formulas result in lower plasma arachidonic acid (AA) levels compared to human milk.
- Supplementation of infant formula with both AA and DHA can achieve AA status similar to that of breast-fed infants.
- Full-term infants fed formula may require dietary preformed AA to achieve the biochemical status of breast-fed infants.
Abstract:
Infants need arachidonic acid (AA; C20:4n-6) for eicosanoid synthesis and deposition in growing tissues, including brain. Human milk supplies preformed AA in amounts considered to meet accretion in membrane-rich tissues, but vegetable oil-based infant formulas do not contain AA. We studied two groups of ten healthy infants, each fed human milk or formula, and analyzed plasma lipid composition. Percentage contributions of AA to plasma phospholipids were stable over two months after birth in breast-fed infants, but infants fed formula developed significantly (P < 0.05) lower levels at the ages of two weeks (formula 6.9% vs. breast 9.4%, w/w), one month (6.2 vs. 9.1%), and two months (5.7 vs. 8.4%). In a second trial, we randomized infants to receive (from birth to age four months) formula without or with both AA and docosahexaenoic acid (DHA; C22:6n-3) at levels typical for mature human milk. Infants fed conventional formula showed a continuous decrease of phospholipid AA over time, whereas feeding of formula supplemented with AA and DHA led to significantly higher AA levels, similar to those in breast-fed infants (two months: supplemented 9.6% vs. unsupplemented 7.1%; four months: 8.7 vs. 6.6%). In order to estimate infantile capacity for endogenous synthesis of AA, we fed four term neonates with newly diagnosed phenylketonuria (mean age 18 d) a formula with all fat contributed by corn oil, which has a higher natural 13C-enrichment than European human milk or formula. Analysis of 13C-enrichment in plasma fatty acids over four days allowed us to estimate infantile AA synthesis. We found an increased 13C-value in plasma AA of all infants, which indicates that term neonates can synthesize AA. However, with a simplified isotope balance equation, we estimate that endogenous synthesis contributed only about 23% of total plasma arachidonic acid by day four. We conclude that full-term infants fed formula may require a dietary supply of some preformed AA if the biochemical status of breast-fed infants is to be achieved.
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