Long‐chain polyunsaturated fatty acid supplementation in the first year of life affects brain function, structure, and metabolism at age nine years

Abstract

The present study sought to determine whether supplementation of long-chain polyunsaturated fatty acids (LCPUFA) during the first year of life influenced brain function, structure and metabolism at 9 years of age. Newborns were randomly assigned to consume formula containing either no LCPUFA (control) or formula with 0.64% of total fatty acids as arachidonic acid (ARA; 20:4n6) and variable amounts of docosahexaenoic acid (DHA; 22:6n3) (0.32%, 0.64%, or 0.96% of total fatty acids) from birth to 12 mo. At age 9 years (+/− 0.6) 42 children enrolled in a follow up multimodal magnetic resonance imaging (MRI) study including functional (fMRI, Flanker task), resting state (rsMRI), anatomic, and proton magnetic resonance spectroscopy (1H MRS). fMRI analysis using the Flanker task found that trials requiring greater inhibition elicited greater brain activation in LCPUFA-supplemented children in anterior cingulate cortex (ACC) and parietal regions. rsMRI analysis showed that children in the 0.64% group exhibited greater connectivity between prefrontal and parietal regions compared to all other groups. In addition, voxel-based analysis (VBM) revealed that the 0.32% and 0.64% groups had greater white matter volume in ACC and parietal regions compared to controls and the 0.96% group. Finally, 1H MRS data analysis identified that N-acetylaspartate (NAA) and myo-inositol (mI) were higher in LCPUFA groups compared to the control group. LCPUFA supplementation during infancy has lasting effects on brain structure, function, and neurochemical concentrations in regions associated with attention (parietal) and inhibition (ACC), as well as neurochemicals associated with neuronal integrity (NAA) and brain cell signaling (mI).

Should formula for infants provide arachidonic acid along with DHA? A position paper of the European Academy of Paediatrics and the Child Health Foundation

“…On sustained attention in the first year of life, a test of rule learning requiring inhibition between 3 and 5 years, and on verbal IQ at 5 and 6 years of age, the children fed formulas with a DHA to ARA ratio of 0.5:1 and 1:1, but not the group fed a ratio of 1.5:1, performed significantly better than the no LCPUFA group. Brain evoked response potentials to a test of inhibition (Go-No Go task) at 5.5 years and brain imaging studies at 9 years were consistent with these results (48,49).…”

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

“…Previous studies have suggested that DHA and EPA may protect against peroxidation and the effects of age-related brain pathology (Hasadsri et al, 2013;Chen et al, 2017). Lipids are involved in cellular signaling, energy balance, blood-brain barrier (BBB), and inflammation (Song et al, 2008;Willis et al, 2009), and such age-dependent lipidome changes that disrupt these functions may contribute to neurodegenerative diseases (Arnoldussen et al, 2016;Bos et al, 2016;Hooper et al, 2018;Luo et al, 2018;McNamara et al, 2018;Lepping et al, 2019), such as Alzheimer's disease (AD) (Schmitt et al, 2014;Hussain et al, 2019).…”

A More Comprehensive Approach to the Neuroprotective Potential of Long-Chain Polyunsaturated Fatty Acids in Preterm Infants Is Needed—Should We Consider Maternal Diet and the n-6:n-3 Fatty Acid Ratio?

“…Follow-up at 9 years demonstrated effects on brain structure, function, and neurochemical concentrations. The group with 1:1 supplementation had greater connectivity between pre-frontal and parietal regions, and groups with 2:1 and 1:1 supplementation had greater white matter volume in regions associated with attention and inhibition (70). Results from the other center in the DIAMOND study demonstrated higher MDI, higher emotional regulation scores and higher language scores when all supplemented groups were compared to the control group (71).…”