DOCOSAHEXAENOIC ACID (DHA) AND OTHER LONG-CHAIN POLYUNSATURATED FATTY ACIDS (PUFAs) AND THEIR NEUROPHYSIOLOGICAL FUNCTIONS

Fats are complex molecules composed of fatty acids (chains of carbon and hydrogen atoms, with a carboxylic acid group at one end) and glycerol. The body needs fats for growth and energy. Fats are chemically described as either unsaturated, monounsaturated or polyunsaturated. The saturated fatty acids elevate serum cholesterol and low density lipoprotein (LDL) levels. Monounsaturated fatty acids (MUFA) raise high density lipoproteins (HDL). Polyunsaturated fatty acids (PUFA) moderately reduce serum cholesterol and LDL levels. (1)

Long Chain (LC) PUFA :

Linoleic acid (LA) and alpha linolenic acid (ALA) are long chain PUFA that are essential fatty acids as they cannot be synthesized in the body and must be consumed in the diet. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (omega 3 fatty acid), which are fatty acids essential for brain development, are synthesized from ALA whereas arachidonic acid (ARA) which is an omega 6 fatty acid is formed from LA. Both omega 6 (n-6)and omega 3 (n-3) essential fatty acids compete for the same enzymes and have different biological roles, the balance between the n-6 and the n-3 fatty acids in the diet is of considerable importance.

Role of long chain PUFA :

These long chain PUFAs have critical roles in the membrane phospholipids and are structural and functional components of cell membranes. These fatty acids are indispensable for cell membrane synthesis. The brain, retina and others neural tissues are particularly rich in long chain PUFA (2,3). n-3 fatty acids also play a central role in the functioning of the brain and central nervous system. Together with n-6 fatty acids, they are not only involved in the development and maturation of neuronal structures, but are essential throughout the entire life span for maintaining normal brain and nervous system function (4). Both DHA and ARA are concentrated in the membrane lipids of gray matter and in the visual elements of the retina (5). EPA is not stored in significant quantity in the brain or retina. EPA may play a more important role in cardiovascular and immunological health. (6)

These fatty acids serve as specific precursors for eicosanoids, which exert hormonal and immunological activity. n-6 PUFA are the precursors for pro-inflammatory molecules-the molecules that promote and maintain inflammatory reactions whereas n-3 fats, in contrast, are the precursors for anti-inflammatory molecules (2,3).

In particular, the vascular-protective effects of long-chain n-3 fatty acids are well documented. EPA und DHA are known to affect the lipid profile, vascular tone and blood coagulation. (4)

DHA and other LC-PUFA and physiological functions in the
nervous system :

LC-PUFAs play a central role in the normal functioning of the brain and nervous system. As structural components of neuronal cell membranes, LC-PUFAs—in particular AA and DHA—have a considerable influence on signal transduction. Studies with rats, for example, demonstrated that chronic n-3 fatty acid deficiency induces abnormalities in dopaminergic and serotonergic neurotransmission systems, which are closely involved in the modulation of attention, motivation and emotion. (4) The exact mechanisms explaining these effects are not completely understood. However, these studies suggest that an increasing proportion in favour of n-3 fatty acids modifies the physical properties of the neuronal cell membranes, which influences the proteins (receptors, transporters) enclosed in the membrane. (4) LC-PUFAs are able to influence cellular signal processes and transmissions, for example by changing the binding or release of neurotransmitters. (4) Another mechanism by which LC-PUFAs—especially n-3 fatty acids—exert their function in the nervous system is their potential to regulate brain gene expression (4).

Dietary Intake of DHA, EPA :

The ratio of LA to ALA in the diet should be between 5:1 and 10:1. However a typical diet has a ratio of 25:1. Thus, it is important to decrease the amount of n-6 fatty acids in the diet, while increasing the amount of n-3 fatty acids like EPA, DHA, and ALA. This can be accomplished by reducing consumption of meats, dairy products, and refined foods, while increasing consumption of the n-3 rich foods such as flaxseed oil, walnuts, and leafy green vegetables. (2,3). During early life, there is limited metabolic capacity to convert ALA to DHA. Prior to birth, the DHA and ARA required for fetal development are provided by placental transfer. Thereafter, long chain- PUFAs are provided in breast milk. With the introduction of weaning foods, the child shifts gradually from dependence on human milk to complete dependence on a diet of table foods often low in long chain PUFA. After weaning, the child’s diet varies considerably depending on food choices made by the parent/caretaker. Without dietary DHA, blood levels of DHA in children aged 18–60 months are low. (6) In infancy and early childhood, DHA should be acquired from dietary sources to maintain optimal health. (7) Consequently, it is not surprising that a lack of n-3 fatty acids, or an imbalance between n-3 and n-6 fatty acids, is associated with a number of behavioural abnormalities, as well as neurological and psychiatric disorders in both children and adults. Corresponding associations can be found with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders, as well as with unipolar and bipolar disorders (4)

Conclusion :

LC-PUFAs play a central role in the normal development and functioning of the brain and central nervous system. DHA and AA, in particular, are involved in numerous neuronal processes. Deficiencies and imbalances of these nutrients, not only during the developmental phase but throughout the whole life span, have significant effects on brain function. An adequate supply of long-chain n-3 fatty acids, such as DHA in particular, is therefore indispensable for normal brain development.

References :

1.	Fats oils in human nutrition. Available at URL: http://www.fao.org/docrep/v4700e/V4700E0d.htm. Accessed on 17th September 2010
2.	ISSFAL: 2009, January, ISSFAL Official Statement Number 5 "α-Linolenic Acid Supplementation and Conversion to n-3 Long Chain Polyunsaturated Fatty Acids in Humans.
3.	Docosahexaenoic acid - Wikipedia. Available at URL http://en.wikipedia.org. Accessed on 25th November 2009.
4.	Schuchardt JP, Huss M, Stauss-Grabo M, Hahn A. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr. 2010;169:149-64.
5.	Innis M. Dietary omega 3 fatty acids and the developing brain, Brain Res. 2008; 1237: 35–43
6.	Ryan AS, Astwood JD, Gautier S, Kuratko CN, Nelson EB, Salem N Jr. Effects of long-chain polyunsaturated fatty acid supplementation on neurodevelopment in childhood: a review of human studies. Prostaglandins Leukot Essent Fatty Acids. 2010; 82: 305-314
7.	Singh M. Essential fatty acids, DHA and human brain. Indian J Pediatr. 2005; 72: 239-242