Omega-3
and Alzheimer’s Dementia
By
Morten Bryhn MD, Ph D
4/2/2001
Lipids account for approximately
60% of the brain's dry weight. These lipids are important
for normal brain function. Increasing amount of data demonstrate
abnormal lipid content in common brain disorders like Alzheimer's
Dementia (AD) and mental depression.
Lipids
account for approx. 60% of the brain weight. Abnormal lipid
concentrations have been found in Alzheimer Dementia and
mental depression.
Lipids account for approximately 60% of the brain's dry
weight. These lipids are important for normal brain function.
Increasing amount of data demonstrate abnormal lipid content
in common brain disorders like Alzheimer's Dementia (AD)
and mental depression. The lipids of the brain are integrated
in so called phospholipid membranes enveloping brain cells
in the gray matter and the neurons of the white matter.
Phospholipids contain two fatty acids (FA). In the brain
one FA is saturated and the other is polyunsaturated. Saturated
fatty acids are stiff molecules while the polyunsaturates
containing several double bonds forming spiral structures.
The polyunsaturated fatty acids (PUFAs) provide the brain
cells with a unique degree of elasticity and fluid binding
capacity.
DHA
and ARA are the most common fatty acids in the brain. These
fatty acids are involved in the fine-tuning of mood, sleep/alertness,
memory and emotions
The most important PUFAs of the brain are docosahexaenoic
acid (DHA) and arachidonic acid (ARA). These are the fatty
acids of the omega-3 and omega-6 series with the highest
number of double bonds. It is not fully known why the brain
requires these PUFAs as its most favored microenvironment
but increasing number of data documents the fact that the
action of DHA and ARA are essential for a series of brain
functions such as the fine-tuning of mood, sleep/alertness,
memory and emotions. External signals generate a release
of PUFAs from the internal side of the brain cells and they
act probably as so-called second messenger to trigger certain
events within the cell.
The
highest concentration of DHA is found in the retina of the
eye
In the retina of the eye we find the highest concentration
of DHA, which is directly engaged in the transformation
of light energy to electric energy that later is conducted
through the visual nerve to the posterior part of the brain.
Brain
maturation takes place mainly during the last three months
of pregnancy. During this interval the fetus accumulates
large amounts of DHA and ARA. In the unborn child brain
maturation takes place mainly during the last three months
of pregnancy. During this interval the fetus accumulates
large amounts of DHA and ARA. These PUFAs are taken from
the placenta circulation of the mother. After birth the
brain of the new-born continue accumulating DHA and ARA
and these PUFAs have to be provided with the food, either
the mother's milk or an infant formula.
Studies
in new-born given infant formula have shown a statistically
significant better visual acuity and problem solving capacity
in children given DHA and ARA compared to those given the
standard type of formulas. These studies have been confined
to the first 6 months of life and there are only little
data supporting the use of DHA and ARA to schoolchildren.
Anyway the Japanese health authorities concerned about a
possible intellectual decay in the community by changing
traditional Japanese dietary habits rich in seafood and
vegetables to junk food, launched a campaign to increase
the intake of DHA in children and youngsters.
Omega-3
and omega-6 fatty acids are essential substances meaning
that like vitamins they will have to be provided by food
or food supplements. In humans utilization of marine DHA
and EPA is more efficient than omega-3 fatty acids from
seeds.
Omega-3 and omega-6 PUFAs are essential fatty acids meaning
that like vitamins they will have to be provided by food
or food supplements. The precursors in the omega-3 and omega-6
series are the 18-carbon atom Alfa linolenic acid (ALA)
and linoleic acid (LA). ALA is found in canola oil and to
some extent in soybean oil while LA is richly present in
safflower, sunflower, corn and soybean oil. The brain is
capable of producing DHA and ARA from ALA and LA but the
capacity is restricted and subjected to changes due to our
diet. The rate-limiting enzyme in this process is delta-6-desaturase.
Humans are not ruminants but adjusted to a diet containing
also fish and meat. Fatty fish contain significant amounts
of the marine omega-3 fatty acids DHA and EPA which without
any enzymatic process may directly be provided to the brain.
The same thing is evident for ARA, which is richly present
in red meat.
Brains
of patients with dementia contains low concentrations of
DHA
The cat family has only low delta-6-desaturase capability
if any at all and is dependent on a diet containing fish
and red meat. The human brain, however, contains tissue
with delta-6-desaturase activity, which can convert ALA
and LA to DHA and ARA. In normal individuals analysis of
fatty acids reveals only trace amounts of those precursors
and large amounts of DHA and ARA. However in patients with
dementia, to be more specific Alzheimer's Dementia (AD)
this is very different. In brain tissue from these patients
the content of ALA and LA is unusual high and the concentration
of DHA is low. Sometimes also ARA is on the low side. Although
not proven this may indicate an enzyme defect in these patients
with restricted production of DHA from precursors. With
a diet containing fatty fish the DHA content of the brain
phospholipids would probably have been maintained but elderly
in the Western World are low in fish intake. The content
of ARA may still be satisfactory due to frequent intake
of red meat in our common diet. So really the potential
lack of DHA is the issue to be addressed.
A
regular intake of fish seemed to prevent from developing
Alzheimer's Dementia in the Rotterdam Study
AD is uncommon before the age of 70 but with increasing
longevity this constitutes an increasing problem for the
individual, the family and the society. About 2.5 million
people in the US suffer from advanced AD and the number
is increasing. In countries with a high fish intake these
figures are different. In Norway and Japan AD is less common.
An important piece of evidence was given to us by the so-called
Rotterdam Study from Holland. About 5500 healthy individuals
were investigated regarding dietary and smoking habits,
laboratory tests and cognition tests to reveal early dementia.
This was repeated after about two years and during that
time period about two per cent of the participants had developed
AD. From the data obtained it was clearly demonstrated that
risk factors for development of AD was very much the same
as for development of cardiovascular disease namely high
intake of saturated fat and cholesterol and smoking. What
seemed to prevent from developing AD was regular intake
of fish.
Elderly
patients with cognitive impairment should eat more fish
or take a marine omega-3 supplement
With increasing longevity the health panorama is very much
blurred by the increasing prevalence of degenerative diseases.
Our cells, enzymes and other body functions are subjected
to wear and tear but increasing evidence from epidemiological
studies and intervention studies tells us that there may
be ways of living better and perhaps even longer by adjusting
to more healthier lifestyle. It is known from studies on
children with congenital dementia, the so-called Zellweger's
Disease, that DHA supplementation can alleviate symptoms.
These children are not able to synthesize DHA due to congenital
defects of the peroxisome. It is also known that the important
enzyme delta-6-desaturase is subjected to lower activity
related to chronic high intake of fat in the diet. The ability
of conveying ALA to DHA may weaken and with increasing age
we will have to rely on direct ingestion of DHA from seafood
or marine omega-3 supplements. This is the same situation
as in the newborn child with immature enzyme systems who
will have to rely on the PUFA content of the mothers milk
hoping that the mother eats fish or at least has still active
desaturase enzymes. It has been shown that not only Alzheimer
patients but also patients with cognitive impairment of
other causes have low concentrations of DHA. Advising elderly
to eat more fish or take a marine omega-3 supplement seams
therefore warranted.
Marine
omega-3 supplements contains not only DHA but also EPA,
a fatty acid engaged in the prevention of arteriosclerosis,
the second most common cause of dementia
A large clinical study conducted by the Karolinska Hospital
in Sweden and sponsored by Pronova Biocare will test the
feasibility and efficacy of giving a DHA enriched marine
omega-3 product, the EPAX 2050 to patients with established
AD. Comprehensive laboratory tests in particular testing
the gene capacity of producing vital enzymes, especially
delta-6-desaturase will probably give new piece of evidence
to better strategies for prevention and perhaps even treatment
of dementia. While waiting for these results and other studies
to be published it seems safe to advice the elderly population
to increase the intake of DHA by eating more fatty fish
or take a DHA enriched marine omega-3 supplement. These
supplements also contain EPA, another omega-3 fatty acid
that together will positively influence risk factors for
generation of arteriosclerosis, the second most common cause
of dementia.
REFERENCES:
Nakada T et al. Membrane fatty acid composition shows delta-6-desaturase
abnormalities in Alzheimer's disease. Neuroreport 1990;
1(2):153-155
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
Martinez
M. Docosahexaenoic acid therapy in docosahexaenoic acid-deficient
patients with disorders of peroxisomal biogenesis
Versicherungsmedizin 1996;31 Suppl:145-152
back
to top
|
