The
Healthy Fats
by
Morten Bryhn, MD, Ph D
12/22/2003
A fat-rich diet is associated with an increased risk of
cardio-vascular disease and even some types of cancer. But
it is important to realise that fat are different things
and, to make it even more complicated, the same fat may
be utilised differently among healthy individuals. The bulk
of fat contained in our diet are the triglycerides (or triacylglycerol),
TG. The TG?s contain three fatty acids (FA?s) connected
to a glycerol backbone (Fig. 1).
These
FA?s may be saturated or unsaturated depending on the source.
Beef tallow, butter, coconut and palm oil contain mainly
saturated FA?s. They are the most calorie dense foodstuff
there is with the potential of providing the highest yield
of metabolic energy per gram of all types of food. If you
plan to cross Greenland on skies you should pack your sack
with such energy-rich foodstuff. But if you attend a more
sedentary lifestyle the metabolic consequences of such a
diet will be very different. Since saturated fatty acids
is mainly used for production of energy-rich compounds,
they will be stored as depot fat if not utilised for physical
work. Furthermore, high intake of foodstuff containing saturated
fat also provide significant amount of cholesterol and also
require more bile for absorption in the small gut increasing
the cholesterol burden even more. Therefore, a diet rich
in saturated fat is right for only a few in our society
today: the physical hard working labourers. It?s a pity,
though, that saturated fat is the number one provider of
food taste!
Due
to the increased risk of cardio-vascular disease and even
cancer by a high intake of saturated fat ambitious national
health programs have been trying to make us reduce intake
of fat to about 30% of total energy intake. This strategy
has not been successful. Instead saturated fat has been
exchanged for unsaturated fats, mainly vegetable oils.
Unsaturated
FA?s are either the monounsaturated oils containing omega-9
fatty acid or the polyunsaturated oils of the omega-3 or
omega-6 type. The most common omega-9 fatty acid is the
oleic acid naturally occurring in olive, rapeseed and peanut
oil. The omega-3 FA?s are derived from seeds like flaxseed
(linseed) but even more important from fatty fish. The omega-3
FA?s utilised for a series of effects in the human body
are eicosapentaenoic acid, EPA, and docosahexaenoic acid,
DHA. Both are abundantly found in fat fish and sea mammals.
Omega-3 FA?s from seeds is a poor source for production
of EPA and especially DHA (1). The use of fish in the diet
has decreased significantly and today the intake of EPA
and DHA is much lower than recommended (2). This may be
due to the fact that people don?t like fish, don?t have
access to fresh fish or that people are afraid of being
poisoned by the content of environmental pollutants enriched
in fish flesh.
Omega-6
on the other hand is provided in surplus by the frequent
use of soybean, corn, safflower, sunflower and walnut oil.
These oils are cheap, stable and have almost no odour and
taste, ideal for processing of food products. The most common
omega-6 FA is linoleic acid but the omega-6 FA utilised
in the body is arakidonic acid (ARA) richly provided in
red meat.
EPA,
DHA and ARA are essential for a series of physiological
functions related to the immune system, the cardio-vascular
system, brain, retina of the eyes, testicles, and many more.
Omega-3 and omega-6 FA?s cannot be produced by mammals and
therefore have to be provided by the diet. The polyunsaturated
FA?s of the 3 and 6 series have in general opposite actions
and compete for the same cells or enzyme systems. The uptake
into cells is very specific due to the selective actions
of free fatty acid receptors (FFAR) on the cell surface.
Cell membrane phospholipids are the first halt for these
FA?s. Phospholipids, the main constituent of many cell membranes,
bind as a rule one saturated and one polyunsaturated FA.
If the diet is poor on polyunsaturates, they can bind two
saturated FA?s. FA?s are carbon atom chains connected by
single or double bonds. The single bonds as in saturated
FA?s make the chain rigid and the cell wall stiff. At the
site of each double bond, however, there is an angulation
of 120 degrees. ARA has 4, EPA has 5, and DHA has even 6
double bonds rendering these carbon chains a circular or
semi-circular shape (fig. 2).
This
shape is the key to the perfect fit to the pertinent receptor.
EPA has very often the strongest affinity to many enzymes
and cells competing successfully with ARA. Integrated in
the phospholipid membrane the polyunsaturated FA?s provide
elasticity to the cell. This is an important feature for
blood cells, nerve cells and even other cells interacting
with other tissues. ARA and DHA in particular have important
actions in the eyes and in the brain and lack of these FA?s
may cause diseases.
The
second effect of polyunsaturated FA?s is brought into action
when they are released from the phospholipid membrane by
phospholipases upon stimulation (fig. 3).
This
stimulation may be due to infections, chemical compounds,
hormones etc. leading to a release of fatty acids which
may bind to enzymes regulating immune response, vascular
tone, thrombocytes adhesion and many other important actions.
Usually ARA augments the action and EPA/DHA decrease the
same. In essence the polyunsaturated FA?s are fine-tuning
immune activation, vascular tone, blood clotting capability
and there should be a balanced presence of ARA and EPA/DHA
in the cell walls in order to have an optimal response.
The
modern diet with a too high intake of omega-6 compared to
omega-3 has important consequences for the magnitude of
this response. Immunological activation in connection to
for example a simple virus infection may cause an overshoot
of actions due to the fact that ARA in surplus will augment
the immunological response. In a situation of optimal balance
between omega-6 and omega-3 the response would be exactly
tuned in order to have a proper action against the virus
and no side effects from an overactive immune response.
EPA has a strong affinity to these enzyme systems but since
our intake of plant oils and red meat is so high and the
number of fishmeals so few, the dampening effects related
to EPA is curtailed.
Many
nutritionists believe that the overshoot reaction of the
immune system by the constant overloading of omega-6 FA?s
is responsible for the high prevalence of allergic diseases
and autoimmune inflammatory diseases today (3). 30-40% of
the children in industrialised countries now have allergic
reactions like eczema, conjunctivitis, rhinitis and asthma.
This number has doubled over the past 30 years, which is
a rather short time for such a dramatic increase. Inflammatory
bowel disease was uncommon in Japan but now the number of
patients is increasing approaching the prevalence in the
Western communities (4). The high intake of omega-6 FA?s
may even have consequences for the development of atherosclerotic
disease and certain cancers.
The
third main action of the polyunsaturated FA?s are related
to messenger actions within the cell and between cells.
Released from the cell wall FA?s are bound to transport
proteins called fatty acid binding proteins (FABP). These
structures made of two protein moieties form a binding site
with a shape, which will allow only the right FA to dock
with the FABP (fig.4).
Using
this specific intracellular transport system the FA is transported
to different intracellular structures. Many polyunsaturates
bind to transcription factors in the nucleus, which will
turn on or off genes. These genes may code for a series
of proteins with different effects. Only the effects on
lipid metabolism and immune system will be discussed.
The
main site for making energy rich phosphates from fatty acids
is the mitochondrion. Saturated as well as unsaturated FA?s
are utilised in this organelle to provide metabolic energy
for any purpose in the human body. But the polyunsaturated
FA?s have a second power station, the peroxisome. If the
diet is rich in polyunsaturated FA?s, some of those will
bind to transcription factors in the nucleus inducing the
production of growth factors making the peroxisome proliferate.
Over time the peroxisomes will take care of a large portion
of the polyunsaturated FA?s. Peroxisomes produce mainly
heat instead of energy rich phosphates distinguishing them
from the mitochondria?s. This means that polyunsaturates
will provide less metabolic energy available for physical
work compared to the saturated fats. Since our intake of
fat is not fully utilised for physical work anymore this
implicates that polyunsaturates provides less risk of weight
increase in the sedentary.
This
is an observation known for many years but now there is
a scientific rationale for advocating plant oils or omega-3
oils for prevention of obesity. Increased production of
heat will be energy lost. Body temperature will not increase
since this is kept very stable by perspiration from the
skin and expiration from the lungs.
The
polyunsaturates also engage in turning off/turning on genes
producing proteins engaged in the immune response, recruiting
of inflammatory cells and production of tissue degrading
enzymes, the so called metalloproteinases. Omega-3 FA?s
especially DHA seems to be the most active FA tuning off
genes (5). Cytokines are potent activators of the immune
response and they are mainly produced in white blood cells.
High concentrations can be measured in patients with autoimmune
diseases like rheumatoid arthritis and inflammatory bowel
disease and they activate a series of mechanisms inducing
pain and destruction of tissue. DHA seems to reduce the
production of these cytokines, which is very relevant for
treatment of many inflammatory diseases. Even the production
of cyclooxygenase producing potent immunoactivators from
fatty acids (se above), is reduced by DHA which adds to
the effects on cytokines (6).
White
blood cells are responsible for destroying microbes but
they also sustain the inflammatory process activated in
atherosclerosis, inflammatory diseases and many other non-infectional
diseases. White blood cells are recruited to the site of
action by so called adhesion molecules. These are compounds
present on the arterial endothelium as well as on the white
blood cell itself. By activation of the immune system more
adhesion molecules are being produced in order to recruit
a significant number of white blood cells. This is very
relevant in cases of infections even when the number of
white blood cells is increased but this may be a foe in
many non-infectious inflammatory diseases. Omega-3 fatty
acids, and again it seems that DHA is the most active, reduce
the presentation of adhesion molecules, which represent
a potent principle for anti-inflammatory treatment (7).
Metalloproteinases
are tissue-degrading enzymes with the physiological role
of breaking down tissue that is going to be removed. In
an inflammatory process directed towards normal tissue such
as in rheumatoid arthritis metalloproteinases break down
healthy cartilage destructing joint function. It has been
demonstrated that omega-3 fatty acids reduce the presentation
of metalloproteinases a mechanism, which could be very relevant
for protection of the inflamed joint preventing invalidity
(6).
In conclusion
fats are very different things. Some are healthy and other
may create chronic diseases. The most significant dietary
change that has been introduced to man during the last 100
years is related to the intake and use of fat (8). Less
physical work reduce the need for fat intake and in an industrial
population energy from fat should be 30% or less of total
energy intake. We have not adapted to this but merely changed
the type of fat in the diet from saturated to mono- and
polyunsaturated fatty acids derived from plants and seed.
On the other hand the portion of polyunsaturated fatty acids
coming from seafood has decreased creating an imbalance
between omega-6 and omega-3 fatty acids. This imbalance
has given rise to a new panorama of diseases mostly related
to an over reactive immune response, such as allergies and
autoimmune diseases. A sound strategy would be to continue
the struggle to reduce fat intake in general but increase
the intake of omega-3 fatty acids from seafood. This change
of strategy has the potential of improving morbidity and
reduce mortality from many of the most common diseases related
to the unhealthy eating practised by the majority today.
REFERENCES
1)Sanderson
P, et al. UK Food Standards Agency alfa-linolenic workshop
report. Br J Nutr 2002;88:573-579
2)Simopoulos AP. Omega-3 fatty acids in health and disease
and in growth development. Am J Clin Nutr 1991;54:438-463
3)Duchén KM. Human milk factors and atopy in early
childhood. Medical dissertation no. 580 Linkoping University
1999
4)Kuroki F, et al. Serum n-3 polyunsaturated fatty acids
are depleted in Chrohn?s disease. Digest Dis and Sci 1997;42:1137-1141
5)De Caterina, et al. The omega-3 fatty acid docosahexaenoate
reduces cytokine-induced expression of proatherogenic and
proinflammatory proteins in human endothelial cells. Atheroscler
and Thromb 1994;14:1829-1836
6)Curtis CL, et al. Pathologic indicators of degradation
and inflammation in human osteoarthritic cartilage are abrogated
by exposure to n-3 fatty acids. Arthr & Rheumat 2002;46:1544-1553
7)Khalfoun B, et al. Docosahexaenoic and eicosapentaenoic
acids inhibit in vitro human lymphocyte-endothelial cell
adhesion. Transplantation 1996;62:1649-1657
8)Simopoulos AP. Modern agriculture and aquaculture and
the n-6/n-3 balance. Current Topics in Cardiovascular Disease.
Springer Verlag 1992:15-23
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