Effects
of Omega-3 Fatty Acids on Mental Health
by
Morten Bryhn, MD, Ph D
6/11/2003
BRAIN PHYSIOLOGY
The brain contains about 100 billion brain cells interrelated
by axons and dendrites leading electrical impulses coding
for information from or to the periphery.
 Aging
results in a gradual loss of brain cells, but this is usually
not accompanied by significant intellectual decline in the
absence of disease. Dementia, however, is characterized
by atrophy of cortical brain structures, mainly confined
to the gray matter with loss of memory function such as
language, perception and calculation. In Alzheimer's disease,
which is the most common cause of dementia, symptoms result
from loss of cortical tissue especially in the temporal
and frontal lobes responsible for intellectual functions.
In psychiatric diseases brain anatomy is usually unaffected
but anomalies are rather related to the concentrations and
effects of neurotransmitters such as serotonin. Recently
it has been scientifically established that the concentration
of certain fatty acids (FS’s), and phospholipases
may be altered in schizophrenia and severe mental depression.
Lipids
comprise about 60% of the brain’s dry weight making
brain tissue the second most lipid-dense tissue after adipose
tissue. Phospholipids (PL) are besides cholesterol the main
lipid component of the neurons. PL are phosphodiesters linked
to a base, in the brain usually etanolamin, as phosphatidyl-etanolamine
(PE). PE binds two different types of fatty acids (FA’s)
in position sn-1 and sn-2 (Fig 2): Saturated FA’s
in sn-1 and unsaturated/ polyunsaturated FA’s in sn-2.
Fig. 2
Section of cell membrane with phospholipids in a bilayer
The
most common saturated FA’s in the brain are palmitic
acid (C16:0) and stearic acid (C18:0), which are the two
most common saturated fatty acids in our diet. The most
common unsaturated FA’s are oleic acid (C18:1n-9),
OA, arachidonic acid (C20:4n-6), ARA, docosatetraenoic acid
(C22:4n-3), DTA, and docosahexaenoic acid (C22:6n-3), DHA.
The omega-3 and omega-6 FA’s are essential and have
to be provided by the diet. Interestingly, there is an only
sparse amount of eicosapentaenoic acid (C20:5n-3), EPA,
which is together with DHA the most common omega-3 fatty
acid in fatty fish and richly present in other cells, especially
blood cells. This indicates that brain phospholipids are
highly selective regarding incorporation of FA’s in
order to deliver the exact fatty acid composition for optimal
brain functions. Recently it has been postulated that incorporation
of fatty acids in PL’s is subjected to receptor-mediated
mechanisms specific for individual FA’s (Nunez EA
et al).
The
fatty acid pattern differs inside the brain with different
concentrations in the gray and white matter. The gray matter
localized to the brain cortex with mainly brain cells, contain
more saturated fatty acids and DHA compared to the white
matter in the sub-cortical region containing more OA and
DTA (Söderberg et al). The white matter have functions
related to trafficking of electrical charges which may require
other fatty acids in the PL’s compared to the neuron
bodies mainly located in the cortex.
Even
if PL’s have important mechanical function providing
important membrane qualities other functions are essential
for normal brain functions as well. The myelin sheet covering
the nerve axon, which is very rich in polyunsaturated FA’s,
facilitates conduction of electrical impulses along the
axons (Fig. 3). Conductivity is about 50 times higher compared
to non-myelinated axons. Degenerative diseases of the myelin
sheet such as in multiple sclerosis may therefore cause
serious neurological defects.
Fig.
3
Brain cell with axon, myelin sheet and dendrites
In
the synapse (Fig. 4) the electrical charge induces release
of neurotransmitters, such as serotonin and dopamine.
Fig.
4
Synapse
These
compounds are recognized by specific receptors at the dendrites
of the next nerve cell influencing conductivity of the following
neuron. Being absorbed from the synaptic gap and recycled,
physical properties of the synapse PL’s are of importance
for the kinetics of neurotransmitters. Furthermore FA’s
from PL’s are released by activation of specific phospholipases.
In certain psychiatric diseases such as schizophrenia and
major depression, the concentration of phospholipases is
increased (Peet M et al). The FA’s and the rest-PL
after cleavage of the molecule, called lysophospholipid,
also have psychotropic effects, which may augment or dampen
the effects of the neurotransmitters. Interestingly EPA,
which is only present in small amounts in the brain, has
shown positive effects in the treatment of major depression
in controlled clinical trials while DHA has not.
In conclusion
the FA’s in the brain have mechanical, and even metabolic
functions as well as actions related to transmission underlining
their importance in the very basic effects of brain function:
generation and conduction of electrical potentials.
DEMENTIA
Dementia is common, affecting about 4 million people in
the United States alone, and the major cause of long-term
disability in old age. Incidence increases rapidly with
age and about 2 % of the population between the ages of
65 and 70 and 20 % of persons over 80 suffer from the disorder.
With the increasing longevity of the population and the
decreasing birth rate, dementia will become increasingly
prevalent.
Cerebral
infarction, caused by obliteration of an atherosclerotic
brain or neck artery, contributes to intellectual loss in
5-10 % of cases and there may also be mixed forms of both
types. Dementia attributed to alcohol abuse may account
for another 5-10 % of cases. Other causes, such as Creutzfeldt-Jakob’s
disease, with a suspected causal relationship with mad-cow
disease, account for less than 1 % of all cases.
In Alzheimer's
disease the onset is insidious and subtle. In most cases
insight is lost early and the patient attributes failures
to old age. Some have no spontaneous complaints but become
disturbed when unable to answer simple questions. Vascular
dementia results from multiple areas of discrete infarction
(Vermeer SE et al). The diagnosis is strongly indicated
by an abrupt onset, especially if there is a history of
previous stroke. Typically, the disease will fluctuate,
with periods of improvement and stepwise deterioration,
in contrast to the steady progression of Alzheimer's disease.
While
vascular dementia is associated with the same risk factors
as coronary heart disease, often coinciding with general
signs and symptoms of atherosclerosis, Alzheimer's disease
is caused by a primary degeneration of the brain cortex.
The cause of the disease has not been fully revealed. Markers
of inflammation are usually present. Deposition of amyloid
material in the brain cells is a regular finding.
People
with regular intake of fish seem to have lower risk of developing
Alzheimer’s dementia but also atherosclerotic dementia.
These diseases have been rare in the coastal population
of Japan and other countries with easy access to fresh seafood.
Two cohort studies, the Rotterdam study (Kalmijn S et al)
and the Bordeaux study (Barberger-Gateau P et al) following
a defined population have confirmed that regular intake
of fish have preventive effects on Alzheimer’s dementia.
A study recently published from Ireland has given the same
results. Interestingly elderly with dementia but also minor
cognitive impairment have lower values of DHA in their red
blood cell PL’s compared to controls (Conquer JA et
al). Ongoing clinical studies, which will be published in
2004 and 2005, will shed more light on the possible therapeutic
effects of omega-3 treatment and whether effects are attributed
to DHA, EPA or both in combination. While waiting for these
results the population should be encouraged to increase
the intake of fatty fish or nutritional supplements containing
omega-3 fatty acids. It may be so that the main opportunity
lies in the prevention of dementia and not in the treatment
when severe defects are already established.
MENTAL
DEPRESSION
Mental depression is very common affecting 8-10% of the
population at any time. Statistics show that the prevalence
of major depression has increased and the age of onset has
decreased in every decade during the 2000 century in the
Western World. Anti-depressive medication is on the top
list of social expenditure for drugs in many countries.
Severe
mental depression is a complex disorder with psychological
as well as hereditary factors. Recently it has been convincingly
demonstrated that nutritional factors may be present as
well. Populations with a low intake of seafood, have a higher
prevalence for severe depression (Hibbeln JR). Along the
same line a population study from the US examining the prevalence
of depression after delivery demonstrated that low seafood
consumption increased the risk of having depression (Hibbeln
JR). Interestingly the population of Iceland having a high
intake of seafood does not have winter depressions like
they have in Canada (Magnusson A et al). And a study from
Finland showed that people with a low intake of fish developed
depression more often than those with a regular intake of
fish (Tanskanen A et al). Analysis of reed blood cell content
of omega-3 fatty acids has shown that depressive patients
have significantly lower content of EPA and DHA compared
to normal controls (Maes M et al). So there may be a good
basis for examining the effects of omega-3 fatty acids in
depression.
Three
placebo-controlled studies in patients with severe depression
have been published. Stoll and colleagues in Boston (Stoll
AL et al) studied the effects in manic depressive patients
in remission on their habitual treatment and found that
a high dose of omega-3 fatty acids could keep the omega-3
treated patients stable significantly better compared to
the placebo group. In a study from Israel (Nemets B et al)
major depressive patients on their habitual medication were
randomly given EPA or placebo. The active treatment group
reduced their depressive symptoms significantly better compared
to the placebo group. Recently a study from the UK with
DHA did not show any beneficial effect compared to placebo
(Marangell et al). Other studies are ongoing but clearly
it seems that EPA is more important than DHA for treatment
or prevention of mental depression.
CONCLUSIONS
During The Brain Decade much knowledge about basic mechanisms
have been explored and the presence and actions of FA’s
and PL’s are one of the most interesting fields. The
prospect is that mental health is dependent upon diet and
not least of the lipid content of our diet. Intake of inferior
food may over time deplete the storage of FA’s essential
for normal brain function. Preservation of mental health
is indeed a matter of proper dietary habits not least with
regard to intake of seafood. But there may also be new therapies
in the near future based on EPA or DHA, the two most abundant
marine FA’s. EPA has important psychotropic actions,
which could be used for treatment of depression and even
schizophrenia in combination with drugs. DHA may be used
for preservation of brain cell membranes perhaps useful
for prevention or even treatment of dementia.
Several
important clinical studies with omega-3 fatty acids on psychiatric
diseases and dementia are ongoing and the results of these
studies may add new modalities to the present treatment
of these diseases.
REFERENCES
Barberger-Gateau
P, et al. Fish, meat, and risk of dementia: cohort study.
BMJ.2002;325:932-933
Conquer
JA et al. Fatty acid analysis of blood plasma in patients
with Alzheimer's disease, other types of dementia, and cognitive
impairment LIPIDS 2000;35:1305-1321
Hibbeln
JR. Fish consumption and major depression. The Lancet 1998;351:1213-1215
Hibbeln
JR. Seafood consumption, the DHA content of mother’s
milk and prevalence rates of post partum depression: a cross-national
ecological analysis. J Affective Disorders 2001
Kalmijn
S et al. Dietary fat intake and the risk of incident dementia
in the Rotterdam Study. Ann of Neurol 1997;42(5):776-782
Maes
M, et al. Fatty acid composition in major depression. J
Affective Disorders 1996;38:35-46
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