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The brain is the most significant and complex organ of the human body. Increasingly, we are becoming aware that certain nutrients may help to safeguard brain health. An expanse of research has investigated the effects of omega fatty acids in relation to brain health but effects across the lifespan have not been widely evaluated. The present systematic review collated evidence from 25 randomized controlled trials (n = 3633) published since 2013. Compared with control groups, omega-3 supplementation generally correlated with improvements in blood biomarkers. Subsequently, these appear to benefit those with lower baseline fatty acid levels, who are breastfeeding or who have neuropsychiatric conditions. Whilst multiple studies indicate that omega fatty acids can protect against neurodegeneration in older adults, more work is needed in the years preceding the diagnosis of such medical conditions. Bearing in mind the scale of ageing populations and rising healthcare costs linked to poor brain health, omega supplementation could be a useful strategy for helping to augment dietary intakes and support brain health across the lifespan. Ongoing research is now needed using harmonious methodologies, supplement dosages, ratios and intervention periods to help formulate congruent conclusions.