Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: New dietary sources
Introduction
Strong and wealth information have been accumulated about the essentiality of n-6 and n-3 fatty acids since the first studies of George and Mildred Burr in the late 1920s, demonstrating the importance of lipids in the growth and development of the rat [1]. In the mid-1960s, Hansen et al., regarded the essentiality of linoleic (C18: 2n-6, LA) and alpha-linolenic (C18: 3n-3, ALA) fatty acids [2]. Later, the reports from Bang and Dyerberg demonstrated the cardio protective role of n-3 long-chain polyunsaturated fatty acids (C20-22; n-3, LCPUFA) from marine origin [3]. Then, research from Bazan and Joel identified that docosahexaenoic acid (C22: 6n-3, DHA) and arachidonic acid (C20: 4n-6, AA) are accreted in significant amounts into the brain tissue [4], [5]. Up to day, multiple and robust experimental, clinical and epidemiological evidence have been established about the health and nutritional importance to humans of polyunsaturated fatty acids (PUFAs), especially those of long-chain (20 or more carbon atoms) [6], [7]. It is in this context that in the last three decades, one of these fatty acids, DHA, has acquired special interest for researchers due to their unique physicochemical characteristics and from the biochemical and physiological effects resulting from the presence of the fatty acid at cellular membranes [8]. DHA is of particular interest due to its highly unsaturated structure (six double bonds, being the fatty acid most unsaturated in our body) and cell location, which is mostly concentrated at the sn-2 position of phospholipids forming cell membranes, thus providing a great fluidity to these structures [9].
DHA is almost exclusively present in significant amount in diverse seafood (fish, shellfish, micro- and macroalgae and even some mammals). Precisely, it has been proposed that was the incorporation of these seafoods to the human nutrition which marked a significant turning point in human evolution [10], a process that was characterized by the increase in size and complexity of the brain tissue and by the development of mental, behavioral and motor skills with strong cognitive components [11]. Additionally to the evolutionary importance of DHA for our specie, its relevance is magnified during pregnancy and the early stage of childhood where the fatty acid plays a crucial role in brain and retinal development [12], and function, directly affecting the cognitive function [13] and the visual acuity of child [14]. Along with the benefits for brain and visual development, which transform DHA into an essential fatty acid in the perinatal period, most recently several studies have demonstrated a neuroprotective role for the fatty acid, specifically during aging and in neurodegenerative diseases and brain ischemia-reperfusion episodes [15], [16]. It is now accepted that neuroprotectin D-1 (NPD-1), a structural derivative of DHA, shows significant neuroprotective actions, particularly in the preservation of the structure and physiology of neurons and glial cells [17]. This paper reviews the current information, from different backgrounds, supporting the importance of DHA for humans, particularly in brain development and in the neuroprotective properties of the fatty acid, as well as how to get a sustainable way to increase the consumption of DHA by the population.
Section snippets
DHA, diet and evolution
The strong evidence supporting the crucial role of DHA in the evolution of our specie, mainly on the growth and physiology of the central nervous system [18], [19], was obtained by studies from fossils indicating that the turning point in human evolution was precisely produced after early humans began the consumption of seafood, mainly fish, shellfish, some mammals and algae [20], [21]. It is estimated that late archaic humans (Neanderthals) consumed protein from terrestrial hunted animals or
DHA and brain development
As discussed above, DHA is the most abundant n-3 LCPUFA in the central and peripheral nervous system, representing the major proportion of PUFAs in brain and retina. This fatty acid is present in large amounts in phospholipids of brain gray matter [28]. DHA takes an important role in neurogenesis and synaptogenesis, particularly in fetal development and during the first two years of life [26]. Fetal DHA accretion occurs actively along pregnancy but is most active during the third trimester as
DHA and neuroprotection
DHA is a fundamental fatty acid not only for the neuronal structure, but also for the neuronal signaling [15]. This fatty acid has been most recently identified as a neuroprotective agent against cerebral aging, neurodegenerative diseases and cerebrovascular diseases, especially in the injury produced by ischemia-reperfusion episodes [15], [17]. Postmenopausal women having low blood n-3 LCPUFA levels, especially DHA, and high levels of saturated, monounsaturated and trans fatty acids, show
Intake of n-3 PUFA and n-3 LCPUFA and nutritional relevance of DHA
Despite the several studies that supported the nutritional and metabolic significance of n-3 PUFA, until the early 1980s there were some doubts about the real importance of these fatty acids, particularly about the essentiality of ALA, the precursor of n-3 LCPUFA. This doubt was dispelled after the first report on deficiency of ALA recorded in 1982, related to the case of a 6 year-old girl who had undergone surgical resection of part of her small intestine, who received total parenteral
Dietary sources of DHA
Traditionally the best way to ingest DHA is through the consumption of sea foods. However some concerns have been aroused because of the presence of heavy metals (mercury, lead, cadmium) and organic material (polychlorinated biphenyls, PCBs) in some fish, especially those captured at the north hemisphere [158], [159]. Health professionals (Medical and Nutritionist) now currently recommend pregnant women to reduce or avoid the consumption of fish and shellfish due this possible and not even
Conclusions and perspectives
The important physical-chemical features of DHA, i.e., high unsaturation and very low melting point (−20 °C) give the fatty acid their biological functions as major structural component of membrane of neuronal and glial cells, acquiring both a structural and a functional role in these brain cells. In recent decades, many studies have reported the important biochemical and nutritional functions of this fatty acid, particularly in the brain, highlighting the possible involvement of DHA in the
Author contributions
Rodrigo Valenzuela, Francisca Echeverría, María Hernandez-Rodas and Alfonso Valenzuela collected different manuscripts regarding the work of review, and wrote the manuscript. All authors reviewed and approved the final version of the manuscript.
Declaration of interest
The authors declare that there is no conflict of interest regarding the publication of this paper.
Acknowledgements
This work was supported by the Department of Nutrition, Nutrition and Dietetics School, Faculty of Medicine, University of Chile, and by Grant (11140174) from Initiation FONDECYT (National Fund for Scientific and Technological Development) to Rodrigo Valenzuela, Department of Nutrition, Faculty of Medicine, Chile.
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