Very long-chain n-3 polyunsaturated fatty acids: a head start to win some years between the ears?

Very long-chain n-3 (or omega-3) polyunsaturated fatty acids have attracted considerable public interest during the past few years for their potential beneficial role in cognitive performance. The proposed benefits stretch from advantages in developing brains of infants and children to preventing cognitive decline at old age. In this thesis, we first examined the role of very long-chain n-3 PUFA at the beginning of the lifespan. We investigated the effects of dietary very long-chain n-3 PUFA on the fatty acid composition of the several brain lobes in juvenile pigs, and showed that a diet enriched with fish oil resulted in higher proportions of DHA in the frontal, parietal and occipital brain lobes compared with the temporal brain lobe. These findings suggest a region-specific incorporation of DHA in the developing brain, which may guide future research into the mechanism by which very long-chain n-3 PUFA may in involved in brain development and function. Subsequently, we investigated the role of very long-chain n-3 PUFA near the end of the lifespan. In a population of older adults, we investigated the association between very long-chain n-3 PUFA and cognitive decline over three years in multiple cognitive domains. We demonstrated that higher plasma proportions of very long-chain n-3 PUFA were associated with less decline in the cognitive domains sensorimotor speed and complex speed, but not in memory, information-processing speed and word fluency, compared with lower plasma proportions of very long-chain n-3 PUFA. These results suggest a beneficial role of very long-chain n-3 PUFA in the speed-related cognitive domains, which justifies future research in this area with sensitive cognitive outcome measurements that provide domain-specific information. Finally, we touched upon the role of very long-chain n-3 PUFA in the macrovascular and the microvascular blood supply in the head region. We showed that plasma very long-chain n-3 PUFA were not associated with changes in carotid intima-media thickness and common carotid distension in a healthy older adult population. This may suggest that the role of very long-chain n-3 PUFA in a healthy population extends in particular to the smaller blood vessels. The role of very long-chain n-3 PUFA in the microcirculation of the brain could therefore be an interesting future direction of research. Although we did not directly investigate the role of very long-chain n-3 PUFA in the brain microcirculation, we did investigate whether plasma very long-chain n-3 PUFA were associated with age-related hearing loss over a period of three years in older adults. Since microvascular disease may decrease the blood supply to the highly vascularised cochlea, this may result in age-related hearing loss. We showed that higher plasma proportions of very long-chain n-3 PUFA were indeed associated with less age-related hearing loss compared with lower plasma proportions of very long-chain n-3 PUFA which implies that the hypothesis of improved microcirculation, if proven correct, may have far-reaching consequences. In summary, this thesis showed that very long-chain n-3 PUFA have region-specific effects on the developing brain and that higher plasma proportions of very long-chain n-3 PUFA were associated with less decline in the speed-related cognitive domains and less age-related hearing loss. Further research is required to establish the role of very long-chain n-3 PUFA in the developing as well as the aging brain and to investigate the underlying mechanisms. “Very long-chain n-3 polyunsaturated fatty acids: a head start to win some years between the ears?” PhD-thesis by Carla Dullemeijer, Top Institute Food and Nutrition and Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands, May 15, 200