Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

F07MA32 Essential fatty acids in human nutrition

Quadrant-I

7.32 Introduction

The human body is capable of manufacturing most of the fats needed for carrying out
normal physiological processes. Fats such as cholesterol, saturated fatty acids and unsaturated
fatty acids can be synthesized within the body. There are two families of fatty acids such as
omega-6 and omega-3 fatty acids. These are considered to be the most essential fatty acids
because these cannot be synthesized in the body and have to be obtained either through diet or
supplementation. Omega-3 fatty acids play a vital role during the various phases of life such as
during pregnancy it supports normal growth and development of fetus. It is also known to play a
major role in the prevention and treatment of diseases such as cardiovascular problems, diabetes
mellitus, arthritis, inflammatory diseases and cancer. Omega-3 fatty acid is also required for
protecting the health of the brain, eyes and nervous system.

Omega-6 fatty acids are abundantly found in nature. It is partially responsible for the
inflammatory immune response. α- linolenic (ALA) acid is an omega omega-3 fatty acids and
linoleic acid (LA) is omega-6 fatty acids. Essential fatty acids are required for maintaining the
structures of cell membrane as these are unsaturated they also help maintain the flexibility of
membranes. They also act as precursors of long chain fatty acids. Some of which could get
converted into powerful compounds that affects many vital biological processes including
inflammation and cell signaling.

7.32.1 Objectives

 Differential the types of omega-6 and omega-3 fatty acids

 Their major dietary sources
 Physiological roles of omega-3 and omega-6 fatty acids
 Biochemistry and metabolism
 Factors affecting the rate of conversion
Dietary sources of omega -3 and omega-6 fatty acids
Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

Omega-3 fatty acids are predominantly found in plant oils such as walnuts, legumes,
vegetables, flax seed, vegetable oils and cereals walnut oil, fenugreek seeds, dry fruits, oily cold
water fishes like mackerel, sardine and salman. Flax seed is one of the richest sources containing
over 50%. Fish, fish oils are also known as the richest sources of other types of omega -3 fatty
acids namely EPA and DHA. The major sources of omega-6 or linolenic acid are the meat and
vegetables and plant oils such as sunflower, soy, lin seed, milk, etc. are known to contain
significant amount. Strict vegetarians who do not consume milk and egg are more likely to
consume lower quantities of ALA than compared to linoleic acid. In most of the developing
countries there is a greater increase in the consumption of omega-6 because they are abundantly
available and are less expensive. The ideal ratio between omega-6 and omega-3 is 5-10:1. The
estimated consumption ratio for Indians ranges between 30-70:1. Japan is the only country where
they consume essential fatty acid in an ideal ratio of 2-4:1 as their diet comprises more of sea
foods.
7.32.2 The omega-3 fatty acids

The omega-3 fatty acids such as α-linolenic acid (ALA), eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA) are proposed to have many health benefits such as it plays a
pivotal role in preventing cardiovascular diseases, inflammation, allergies, cancer, immune
response, diabetes, hypertension and renal disorders. Several epidemiological studies have
revealed the positive relationship of high dietary intake of omega-3 PUFA (poly unsaturated
fatty acid) among Eskimos who were shown to have lower incidences of coronary heart diseases.
The essential role of DHA has been determined by several researchers who have confirmed its
integral role in the appropriate functioning of central nervous system and visual acuity of infants.
These omega-3 fatty acids are needed throughout the various stages of human life cycle and have
to be included in the daily diet. Extensive research has been carried out on the beneficial role of
omega-3 fatty acid in reducing the prevalence of cardiovascular disorders. The mechanism by
which it prevents cardio vascular disorder remains unknown. But, experimental investigations
have provided evidences that the fatty acids in marine oils help to prevent cardiovascular
Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

diseases by lowering serum triglyceride level. Apart from this it also acts as antiatherogenic and
antithrombotic agent.

The omega-3 fatty acids especially EPA and DHA are found in abundance in marine oils.
Other major sources include; cod liver oil, menhaden and sardine oils are also considered as
important sources which contain approximately 30% of the EPA and DHA. α- linolenic acid is
the principal component of omega-3 fatty acid which can be metabolically converted to DHA via
reactions involving the processes such as desaturation and elongation. In adult humans the extent
of conversion of EPA to DHA is said to be vey restricted an on an average approximately 4% is
known to be converted. While among infants it is even more restricted which is just about <1%.
The rate of conversion of ALA to DHA/EPA under certain pathological conditions has been
reported to be much lower. Hence, the long chain fatty acids such as DHA and EPA are
considered as conditionally essential nutrients and have to be obtained from dietary sources. The
flax seed oil is the major constituent of ALA (alpha linolenic acid) which contains 50-60%.
When dietary ALA is absorbed into the animal body it transforms into long chain fatty acid
yielding omega-3 terminal structure. DHA is one of the major constituent of gray matter in brain
and even the retina of the eye. Human milk also comprises considerable amounts of DHA.

The infants who consume mother’s milk are shown to have higher IQ and intelligence
level in comparison to those fed commercial formulas which may be lacking DHA. In addition to
the vital physiological roles EPA also acts as a precursor for series of eicosanoids which are vital
for affording protection against heart attack because it exerts antithrombotic effect. EPA is also
known to affect bleeding time by which the time duration for clot formation also increases.
Another unique role is that it helps to reduce serum cholesterol level.

7.32.3 Functions of omega-3 fatty acids

These are known to exert positive effect on heart health and other diseases mainly cancer,
diabetes and certain neurological disorders. Specific physiological conditions benefit from
omega-3 fatty acids consumption particularly during pregnancy and lactation. Adequate
Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

consumption is known to improve general health. Dietary deficiency of omega-3 fatty acids may
increase the risk of developing neurological abnormalities, growth retardation, weakness,
reduced learning ability, disturbances in motor coordination and altered behavior, increased
triglycerides, hypertension, oedema, dry skin, mental retardation and immune dysfunction. These
symptoms can be relieved with omega-3 supplementation.

7.32.4 The omega-6 fatty acids

These fatty acids perform wide variety of physiological roles in the human body. They
mainly function to regulate the membrane structure and facilitate the biosynthesis of short lived
eicosanoids which are integral for regulating cellular activity. The omega-6 fatty acids are
considered to be vital for maintaining the integrity of water impermeability barrier of the skin.
They are also responsible for regulating the cholesterol transport in the body. Linoleic acid (LA)
belongs to this particular class of fatty acids. It is commonly found in all vegetable oils and is
reported to be essential for supporting normal growth, reproduction and health. LA also acts as a
precursor for fatty acids belonging to omega-6 family that are synthesized through desaturation
and elongation reactions which may also retain the terminal structure (omega-6). Of all these
arachidonic acid (AA) is basically considered as an important constituent found in membrane
phospholipids. It also functions as a precursor of eicosanoids. Another important fatty acid is γ –
linoleic acid which is obtained as an intermediary product during the biosynthesis of arachidonic
acid from linoleic acid. It is naturally present in certain seed oils namely borage and evening
primrose.

A daily intake of 1-2% linoleic acid through the diet is proposed to be adequate to
protect infants from chemical and clinical disorders. A diet devoid of linoleic acid is known to be
associated with the occurrence of several disorders such as impaired growth and reproduction,
excessive water loss through the skin, scaly dermatitis and poor wound healing.
Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

7.32.5 Functions of omega-6 fatty acids

A severe long standing dietary deficiency of omega-6 fatty acids is considered to be fatal.
The conjugated linoleic acid (CLA) is one of the most important fatty acids belonging to this
family. One of unique role of CLA is that it influences the reduction of body fat particularly the
abdominal fat, improves serum lipid profile and reduces the total flow rate of glucose. Under
severe deficiency it leads to the development of several condition including eczema, hair loss
liver degeneration, altered behavior, degenerative diseases of kidney, increased infection,
delayed wound healing, male sterility, abortions in women, arthritis, impaired cardiac function
and growth retardation.

7.32.6 Biochemistry of omega-3 and omega-6 fatty acids

The dietary PUFAs are rapidly absorbed by intestinal cells. Subsequently it produces of
different metabolites. The processes such as elongation and desaturation facilitate the
transformation of PUFAs into long-chain PUFAs. Another process called retrocovnersion results
in a shortening of two carbon units found in longest linoleic acid (LA) and linolenic (LNA)
derivatives. On the other hand cyclooxygenases (COX) and lipoxygenases (LOX) initiates the
process of generation of different prostanoids from EPA and AA. These derivatives are indicated
to play a vital role in the maintenance of good health. The long chain PUFAs such as AA, EPA
and DHA are incorporated into the cell membrane in particular onto the lipid bilayer of the
plasma membrane. The changes in the fluidity and their capacity to house wide variety of
enzymes, receptors, channels and pores is thought to be highly dependent on the proportion of
each fatty acid that may be present in the membrane. Through this mechanism it tends to
improve the adaptation of cell functions according to the physiological needs. Prostanoids have
been shown to play a major role as mediators of certain local symptoms of inflammation mainly;
vasoconstriction, vasodilation, coagulation, pain and fever. Thus it could be implied that the
relationship between derivatives is thought to be very important for the maintenance of
homeostatis.
Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

The enzyme δ-6 desaturase is known to play a key role as it exerts greater affinity
towards linolenic acid than that for linoleic and would competitively inhibit the formation of its
unsaturated derivatives. Accordingly the proportion of linoleic acid should be 10 fold greater
than the LNA to inhibit the formation of derivatives associated with linolenic acid. This is
deemed to be necessary in order to block the transformation of LA into AA by about 50%. For
this mechanism to occur the LNA must be present in amount which is equivalent to 0.5% of the
total caloric content. In contrast to this, the reduction in the rate of LNA transformation into EPA
is estimated to require LA as the source of energy supply at an equivalent value of approximately
7% of the total caloric content of the diet. The experimental evidences have provided substantial
evidences with respect to the optimum ratio between these acids and it should be close to 4:1 –
5:1 and is suggested that it should not exceed 10:1.

Both EPA as well as DHA has been reported to play a key role in several metabolic
processes. The degree of conversion of LNA to EPA in humans is not very efficient and it said to
be in the range of 5-10% only and a very mere value of 2-5% conversion to DHA takes place.
The process of conversion appears to be much more efficient in females than those for males.

7.32.7 Metabolism of alpha linolenic acid (ALA)

About 96% of the ingested dietary ALA is found to be absorbed in the gut. Immediately
after absorption it passes through several metabolic fates. Initially it undergoes β-oxidation in
which the carbon chain or back bone of fatty acid is broken down into smaller fragments. ALA
metabolism contributes for the energy production. The degree of β-oxidation is known to differ
among men and women for instance the estimated level can be 21-33% in men and 19-22% for
women. The carbon fragments that are produced during β-oxidation do not undergo oxidation
rather they would be recycled into saturated and monounsaturated fatty acids (MUFA). This
recycling process is predicted to be a vital source of fatty acid during pregnancy.

In the next step it is utilized for producing ketone bodies. ALA is the preferred substrate
in the process of ketogenesis. Brain utilizes ketone bodies as an alternative energy source. The
Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

ALA will be stored in adipose tissue as reserve supply. A typical 75kg man with a 15% fat mass
is known to contain 79g of ALA. While a women of 65kg with 23% adipose tissue has been
estimated to contain 105g ALA. This is reflective of greater fat mass found in women. In the
next step the ALA is incorporated into membrane phospholipids. Conversion into long chain
omega-3 fatty acid is the final step which mainly takes place by a series of desaturation and
elongation processes. This process results in the formation of EPA, DHA and DPA. An
estimated 2-8% conversion is known to occur in young women. For DPA it ranges from 0.13-6%
and DHA around 0.05%.

7.32.8 Factors affecting the conversion of ALA

i) Gender – women of child bearing age are reported to have the greatest potential of converting
ALA to EPA and DHA in comparison to men. This could be due to the highest level of estrogen
which exercises control over DHA synthesis.

ii) Diet – a diet with a highest level of LA is postulated to reduce the conversion rate as much as
by 40%. Other dietary factors such as high cholesterol, saturated fats, oleic acid, transfats and
alcohol, and the ratio between PUFA and SF are known to impair the conversion rate.
Consuming more than 12g ALA can reduce the total rate of conversion.

iii) Cigarette smoking – smoking is known to impair the overall metabolism of omega-3 fatty
acids. The enzyme desaturase is said to be greatly affected. Exposure to even low doses could
affect the rate of metabolism.

7.32.9 Metabolism of omega-6 fatty acids

The metabolism of LA is known to occur in similar way as that of ALA. The metabolism
involves a series of processes mainly the desaturation and elongation. It is worth noting that
omega-6 fatty acid metabolism results in the production of gamma linolenic acid (GLA) which is
further converted to Dihono-gamma linolenic acid (DGLA) which is a precursor of certain
eicosanoids. GLA is principally present in evening primrose, borage and black currant oils.
Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

Another important fatty acid, arachidonic acid (AA) is postulated to be a very powerful
precursor of eicosanoids. AA is thought to be very strictly regulated in cell membrane
phospholipids because it can exert far reaching effect on the cell behavior. Diets containing
higher amounts of either LA or AA might result in higher levels of AA derived eicosaoids which
may cause over active immune system and can serve as contributory factors for the development
of chronic diseases like cardio vascular diseases and cancer.

7.32.10 Biological effects of omega-3 and omega-6 fatty acids

The linoleic acid (omega-6) and ALA (omega-3) are considered as the most integral
components of animal and plant cell membranes. When a fish or fish oil is ingested the EPA
(omega-3) and DHA would tend to be partially replaced by omega-6 fatty acids mainly in
specific sites like platelets, erythrocytes, neutrophils, monocytes and liver cells. The ingestion of
EPA and DHA from fish and fish oil is known to afford several health benefits which are
discussed below;

 Lowering of the production of porstaglandins and E2 metabolites

 It brings about a decrease in the concentration of thromboxane A2 which is considered as

a potent platelet aggregator and vasoconstrictor

 Reduces the formation of leukotriene B4 which is a factor that induces inflammation and
chemotaxis of leukocytes

 Increases the concentration of thromboxane A3 which is a weak platelet aggregator and

vasoconstrictor

 Enhances the overall concentration of prostacyclin PGI3. It is a well known vasodilator

and also acts as a platelet aggregation inhibitor

 Increase PGI3 without affecting the level of PGI2

Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

 Improves the concentration of leukotriene B5 which is a weak inducer of inflammation

and also acts as a chemotactic agent.

The eicosanoids from AA are proposed to be biologically active in small quantities. If

present in larger amount it tends to form thrombi and atheromas. This may cause several adverse
effects such as the development of allergy and inflammatory disorders and cell proliferation
among highly susceptible individuals. Thus it could be inferred that a diet rich in omega-6 fatty
acids would tend to shift the normal physiologic state to a condition where it acts as a
prothrombotic and proaggregatory factor leading to increased blood viscosity, vasospasm,
vasoconstriction, reduced bleeding time in patients with hypercholesterolemia,
hyperlipoproteinemia, myocardial infarction, atherosclerotic diseases, type-2 diabetes mellitus,
obesity and hypertriglyceridemia. α-linolenic acid is the major precursor of omega-3 fatty acid
that in turn can be converted to long chain omega-3 PUFAs and hence could be substituted for
fish oils. In order to obtain the maximum beneficial effects the minimum intake of long chain
omega-3 PUFAs should be determined based on the concentration of other fatty acids. The total
amount of LA as well as the ratio between LA to ALA is predicted to be important for the
normal metabolic processes.

If the ratio of omega-6/omega-3 fatty acids in platelet phospholipids is higher it increases

the risk of death from cardiovascular diseases. Western diets are mainly characterized by high
proportion of omega-6 PUFS along with very high omega-6/omega-3 ratio. This is known to
play a key role in the pathogenesis of various life threatening diseases including cardiovascular
diseases, cancer inflammatory and auto immune diseases. While an increased level of omega-3
PUFA which comprises lower omega-6/omega-3 ratio is reported to exert suppressive effect.

7.32.11 Summary

Essential fatty acids cannot be synthesized by the body and have to be obtained through
the diet or supplementation. Both omega-6 and omega-3 fatty acids are known to play major role
in the human physiology. They could be considered as agents for preventing life threatening
Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N

diseases like diabetes, cancer and cardiovascular problems. They can be obtained by consuming
dry fruits, fish and fish oil, vegetables, soy bean, milk and meat in adequate amounts.

References

1. Simopoulos AP. New products from the agri-food industry: The return of n-3 fatty acids into
the food supply. Lipids 34(suppl):S297–S301, 1999.

2. Simopoulos AP. Overview of evolutionary aspects of w3 fatty acids in the diet. World Rev
Nutr Diet 83:1–11, 1998.

3. Shannon J, King IB, Moshofskky R, Lampe JW, Li Gao D, Ray RM, Thomas DB. Erythrocyte
fatty acids and breast cancer risk: a casecontrol study in Shanghai, China. Am J Clin Nutr
85:1090–1097, 2007.

4. Simopoulos AP. Omega-3 fatty acids in wild plants, seeds and nuts. Asian Pacific J Clin Nutr
11(S6):S163–S173, 2002.

5. Simopoulos AP. Omega-3 fatty acids and antioxidants in edible wild plants. Biological
Research 37(2):263–277, 2004.

6. HARRIS W.S., ASSAAD B., POSTON W.C. (2006): Tissue omega-6/omega-3 fatty acid ratio
and risk for coronary artery disease. Am J Cardiol., 21, 98, 4A, 19i-26i.

7. RISÉRUS U., SMEDMAN A., BASU S., VESSBY B. (2003). "CLA and body weight
regulation in humans". Lipids 38, 2, 133–137.

8. BLANKSON H., STAKKESTAD J.A., FAGERTUN H., THOM E., WADSTEIN J.,
GUDMUNDSEN O. (2000): "Conjugated linoleic acid reduces body fat mass in overweight and
obese humans". Journal of Nutrition, 130, 12, 2943-2948.
Code and title of the paper: F07MA Macronutrients

Code and title of the module: F07MA32 Essential fatty acids in human nutrition

Name of the content writer: Prabhavathi S.N