The importance of Omega 3 and 6 balance - a study link http:/

The Role of Docosahexaenoic and Arachidonic


Institute of Brain Chemistry and Human Nutrition

London Metropolitan University, London N7 8DB, UK


Nuclear Magnetic Resonance Facility, Environmental Quality Laboratory

U.S. Department of Agriculture Agricultural Research Service

Beltsville, MD, USA


Department of Pharmacological Sciences, University of Milan, Italy


Department of Biomedicine University of Bergen, Norway


Institute of Neuroscience, University of Oslo, Norway


School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Australia


Research Center on Ageing, University of Sherbrooke, Quebec, Canada

*E-mail: ■■■■■■■■■■■■■■■■■■■■■■■■■■

Lipids played a major, as yet unrecognised, role as determinants in evolution. Life

originated 3 billion years ago during which time there was ample opportunity for

DNA modification. Yet there was little change in the life forms for the first 2.5 billion

years. It was not until about 600 million years ago when the oxygen tension rose to a

point where air breathing life forms became thermodynamically possible, that a major

change is seen in the fossil record. The sudden appearance of the 32 phyla in the

Cambrian fossil record which flowed from this environmental change is referred to as

the “Cambrian Explosion”. It was also associated with the appearance of intracellular

detail and cell differentiation. That detail was provided by cell membranes in which

the lipids were structural essentials. Thus not just oxygen but also the lipids were

drivers in the Cambrian explosion. Docosahexaenoic acid (DHA) provided the basic

membrane backbone of the new photoreceptors that converted photons into electricity

laying the foundation for the evolution of the nervous system and the brain.

Although there are two closely related fatty acids with only one double bond different

DHA was not replaced despite some 600 million years of genomic change. Whilst the

marine food chain is rich in long chain omega 3 fatty acids, the land food web is

dominated by omega 6 fatty acids. With the brain utilising omega 6 and 3 fatty acids

in a ratio of between 1 to 1 and 2 to 1 the injection of the omega 6 through the


M. A. CRAWFORD et al.

appearance of omega 6 rich protected seeds in the Cretaceous Period, would have

played a critical role in the advance of brain evolution. This symbiosis between land

and marine food chains, most likely created the condition that finally led to the cerebral

expansion in human evolution. Lipids are still modifying the present evolutionary

phase of our species with their contribution to a changing panorama of non communicable

disease. The contemporary lipid malnutrition is most likely contributing to

the rise in brain disorders which in the European Union has overtaken the cost of all

other burdens if ill health at 386 billion for the 25 member states at 2004 price.


evolution; genomics; lipids; docosahexaenoic; arachidonic; omega

6; omega 3; brain; vascular development; cerebral expansion; fish;

sea food; oceans

1. Introduction: The challenge of the

rise in brain disorders

Brain disorders now account for the highest

cost in the burden of ill health in Europe


et al. 2005). It follows the

rise in death from cardio-vascular disease as

predicted by Crawford and Crawford (1972).

The cause is most likely nutritional with a

similar background in the change in dietary

fats which adversely impacted on cardio and

vascular health that would logically lead to

disorders of brain development and function.

The reason for linking heart disease and brain

disorders is that during early development,

the brain relies heavily on an efficient placental

vascular and the fetal cardio-vascular

system. The fetal brain uses 70% of the energy

transferred to the fetus from the placenta.

The placenta itself is a rapidly growing

vascular system which needs to be in

place ahead of the fetal brain growth thrust

of the last trimester. This paper raises several

questions about the role of DHA in the

brain, its extreme conservation in signalling

systems with its possible relevance to human

evolution. Importantly it raises a question on

how to meet the challenge of human mental

health in face of the problems facing aquatic

food resources.

2. Docosahexaenoic Acid

Docosahexaenoic acid (all-


4,7,10,13,16,19-hexaenoic acid—C22:6


DHA) is a major, essential fatty acid

constituent of the brain (Crawford and

Sinclair 1972). DHA or its precursors have

to be provided in the diet, hence the balance

between the

ω6 and 3 fatty acids is important.

There is a paucity of DHA in the land

food chain which also contains competing

fats. The brain first evolved using the marine

food web some 500–600 million years

ago and the richest source of DHA is the

marine food chain. The movement in the 20th

and 21st centuries away from historical use

of sea foods and fish with an emphasis on

land based food supply, is a likely cause in

the rise in brain disorders now apparent

(Hibbeln 1998). A better understanding of

DHA and its function could help to motivate

the required policy changes needed to meet

this challenge.

Neural cells have a particularly high

membrane content of DHA. In different

mammalian species the profile with arachidonic

acid and DHA does not vary: it is brain

size that varies (Crawford

et al. 1976, 1993)

suggesting a high degree of evolutionary

conservation of the neural lipid profile (

Fig. 1).

DHA is rapidly and selectively incorporated

in neural membranes and is concentrated at

synaptic signalling sites (Suzuki

et al. 1997).

It is the most unsaturated of cell membrane

fatty acids (Jump 2002). DHA is synthesised


α-linolenic acid. However, the process

is rate limited (Sprecher 1993; Sprecher



1999) and moreover α-linolenic acid is

oxidised at a rapid rate (Leyton

et al. 1967).

In 1972 Crawford and Sinclair first published

evidence that DHA itself, was an independent

determinant of brain growth and


1 (Broadhurst el al. 2002). Deficiency

studies in rodents (Sinclair and