The Role of Docosahexaenoic and Arachidonic
1
Institute of Brain Chemistry and Human Nutrition
London Metropolitan University, London N7 8DB, UK
2
Nuclear Magnetic Resonance Facility, Environmental Quality Laboratory
U.S. Department of Agriculture Agricultural Research Service
Beltsville, MD, USA
3
Department of Pharmacological Sciences, University of Milan, Italy
4
Department of Biomedicine University of Bergen, Norway
5
Institute of Neuroscience, University of Oslo, Norway
6
School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Australia
7
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
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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.
KEYWORDS
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
(Andlin-Sobocki
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-
cis-docosa-
4,7,10,13,16,19-hexaenoic acid—C22:6
ω3,
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
from
α-linolenic acid. However, the process
is rate limited (Sprecher 1993; Sprecher
et
al.
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
evolution
1 (Broadhurst el al. 2002). Deficiency
studies in rodents (Sinclair and
Docosahexaenoic