Role of polyunsaturated fatty acids in human brain structure and function across the lifespan: An update on neuroimaging findings

Abstract

There is a substantial body of evidence from animal studies implicating polyunsaturated fatty acids (PUFA) in neuroinflammatory, neurotrophic, and neuroprotective processes in brain. However, direct evidence for a role of PUFA in human brain structure and function has been lacking. Over the last decade there has been a notable increase in neuroimaging studies that have investigated the impact of PUFA intake and/or blood levels (i.e., biostatus) on brain structure, function, and pathology in human subjects. The majority of these studies specifically evaluated associations between omega-3 PUFA intake and/or biostatus and neuroimaging outcomes using a variety of experimental designs and imaging techniques. This review provides an updated overview of these studies in an effort to identify patterns to guide and inform future research. While the weight of evidence provides general support for a beneficial effect of a habitual diet consisting of higher omega-3 PUFA intake on cortical structure and function in healthy human subjects, additional research is needed to replicate and extend these findings as well as identify response mediators and clarify mechanistic pathways. Controlled intervention trials are also needed to determine whether increasing n-3 PUFA biostatus can prevent or attenuate neuropathological brain changes observed in patients with or at risk for psychiatric disorders and dementia.

Keywords: Aging; Arachidonic acid; Brain development; Docosahexaenoic acid; Neurodegeneration; Omega-3 fatty acids; White matter.

Figure 1

Functional magnetic resonance images illustrating greater baseline-endpoint increases in blood oxygen level-dependent (BOLD) activity in the prefrontal cortex (top row, DHA>Placebo), and greater baseline-endpoint decreases in BOLD activity in parietal, temporal, and cerebellar cortices (bottom row, DHA

Figure 2

Erythrocyte DHA levels are positively correlated with blood oxygen level-dependent (BOLD) activity in prefrontal and anterior cingulate subregions of adolescent MDD patients (mean age: 16 years, n=20) during performance of a sustained attention task (CPT-IP). The color gradient reflects increasing (red → yellow) statistical significances from p≤0.05 (corrected).

Figure 3

Diagram illustrating candidate mechanisms mediating the relationship between n-3 PUFA deficiency, and associated elevations in the n-6/n-3 PUFA ratio, and gray matter atrophy, white matter pathology (e.g., WMH), and cerebral infarct burden. An elevated n-6/n-3 PUFA ratio reduces cerebral blood flow (i.e., cerebrovascular hypoperfusion) in part by increasing blood viscosity by increasing triglyceride levels and platelet aggregation, and increasing vasoconstriction via elevated platelet thromboxane A2 production. Elevated n-6/n-3 PUFA ratio also increases circulating pro-inflammatory cytokine levels which adversely impact vascular endothelial cells and have been found to be associated with white matter pathology and reduced corticolimbic gray matter volumes.