178  2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Blackwell Publishing LtdOxford, UKNBUNutrition Bulletin1471-98272006 British Nutrition Foundation? 2006313178224MiscellaneousThe health effects of dietary unsaturated fatty acidsJ. Lunn and H. E. Theobald
Correspondence: Dr Joanne Lunn, Nutrition Scientist, British Nutrition Foundation, High Holborn House, 52­54 High Holborn, London
WC1V 6RQ, UK.
E-mail: j.lunn@nutrition.org.uk
BRIEFING PAPER
The health effects of dietary
unsaturated fatty acids
J. Lunn and H. E. Theobald
British Nutrition Foundation, London, UK
Summary
1. Introduction
2. What are unsaturated fatty acids?
2.1 The chemistry of fatty acids
2.2 Digestion, absorption and metabolism
2.3 Functions of unsaturated fatty acids
3. Unsaturated fatty acids in the UK diet
3.1 Sources of fat in the diet
3.2 Dietary recommendations for fat
3.3 Intakes of unsaturated fatty acids
3.4 Major contributors to unsaturated fatty acid intake
3.5 Trends in intake
4. Unsaturated fatty acids in health and disease
4.1 Unsaturated fatty acids and cardiovascular disease
4.2 Unsaturated fatty acids and diabetes
4.3 Unsaturated fatty acids and cancer
4.4 Unsaturated fatty acids and inflammatory conditions
4.5 Unsaturated fatty acids in fetal and infant development
4.6 Unsaturated fatty acids and cognitive function and behaviour
4.7 Emerging aspects of unsaturated fatty acids and health
5. Unsaturated fatty acids and public health
5.1 Labelling of unsaturated fatty acids
5.2 Are current UK recommendations adequate?
5.3 Opportunities to increase intake of long chain n-3 PUFAs
5.4 Implications of optimising intakes of unsaturated fatty acids
6. Conclusions
Acknowledgements
References
Appendix 1
The health effects of dietary unsaturated fatty acids 179
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Summary Fat provides energy; indeed it is the most energy dense of all the macronutrients,
with 1 g providing 37 kJ (9 kcal). However, the constituent parts of fat, fatty acids,
are required by the body for many other functions than simply as an energy source,
and there is an increasing awareness of the potential health benefits of specific types
of fatty acids. Fatty acids are long hydrocarbon chains, with a methyl group at one
end (the omega or n-end) and an acid group at the other. Unsaturated fatty acids are
hydrocarbon chains containing at least one carbon­carbon double bond; monounsaturated
fatty acids contain one double bond, and polyunsaturated fatty acids
(PUFAs) contain many double bonds. The position of the double bond relative to
the omega end determines whether a PUFA is an n-3 (omega 3) or an n-6 (omega 6)
fatty acid.
Most fatty acids can be synthesised in the body, but humans lack the enzymes
required to produce two fatty acids. These are called the essential fatty acids and
must be acquired from the diet. In humans, the essential fatty acids are the n-3
PUFA -linolenic acid and the n-6 PUFA linoleic acid. Although humans can elongate
dietary -linolenic acid to the long chain n-3 PUFAs eicosapentaenoic acid and
docosahexaenoic acid, the rate of synthesis may not be sufficient to meet requirements,
and it is, therefore, recommended that good sources of these fatty acids,
namely, oil-rich fish, are also included in the diet.
Fat is found in most food groups, and foods containing fat generally provide a
range of different fatty acids, both saturated and unsaturated. In the UK, the major
dietary sources of unsaturated fatty acids include meat & meat products, cereals &
cereal products and potatoes & savoury snacks; primarily as a result of the vegetable
oil used in processing. Recommended intakes of both total fat and the different
types of fatty acids have been set for the UK population, and it is possible to
monitor fat intake from the data collected in nationwide dietary surveys. As a population,
we are not currently meeting these recommendations, so there is still scope
for dietary change. In Western diets, n-6 fatty acids are the predominant PUFAs, and
this is in line with current dietary advice to consume a minimum of 1% energy as
n-6 PUFAs and 0.2% energy as n-3 PUFAs. The balance of n-3 and n-6 PUFAs in
Western diets has changed substantially over the last 100 years or so, and as the two
families of PUFAs share a common metabolic pathway, concerns have been raised
that this might be detrimental to health; what is becoming increasingly clear is that
both n-3 and n-6 PUFAs have independent health effects in the body, and as intakes
of the n-6 PUFAs are within the guidelines for a healthy diet, concerns about
the n-6 to n-3 ratio are driven by low intakes of n-3 rather than high intakes of n6.
Currently in adults n-6 PUFAs contribute to 5.3% energy.
Detecting associations between components of the diet and risk of various diseases
is notoriously complex and in many cases, the evidence is still accumulating.
Cardiovascular disease, characterised by hardening and narrowing of blood vessels
and/or the development of blood clots, is one of the leading causes of mortality and
morbidity worldwide. The type and total amount of dietary fat has a clear part to
play in affecting an individuaľs disease risk, yet the precise mechanisms by which
unsaturated fatty acids reduce cardiovascular disease risk are still unclear. A number
of mechanisms whereby dietary fatty acids could influence the progression of
180 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
cardiovascular disease and its risk factors have been identified. These include effects
on blood lipid concentrations, blood pressure, inflammatory response, arrhythmia
and endothelial function, along with many other effects, both known and as yet
undefined. A well-established risk factor for cardiovascular disease is an elevated
plasma low density lipoprotein (LDL) cholesterol concentration. Replacing saturated
fatty acids with either monounsaturated fatty acids or n-6 PUFAs reduces LDL
(the `baď) cholesterol, and so reduces the risk of developing the disease. Unsaturated
fatty acids, such as linoleic acid or monounsaturated fatty acids, also slightly
raise high density lipoprotein (HDL) (the `gooď) cholesterol, which assists in the
removal of triacylglycerols from the bloodstream. Interest in the health effects of the
long chain n-3 PUFAs found in fish oils is also increasing. There is strong supportive,
but not yet conclusive, evidence that these fatty acids protect against fatal heart
disease. On the basis of this conclusion, in 2004 the Scientific Advisory Committee
on Nutrition advised the UK government to adopt the population-wide dietary recommendation
to eat at least two portions of fish per week, of which one should be
oil-rich, equivalent to 0.45 g of the long chain n-3 PUFAs per day. In recent years,
the potential health benefits of -linolenic acid has attracted attention, and evidence
is mounting on the role that this n-3 fatty acid may play in preventing the progression
of cardiovascular disease, although it is currently unclear what, if any, association
exists.
Brain cells are especially rich in certain long chain PUFAs. This has led to the suggestion
that dietary status of these long chain fatty acids might influence cognitive
function and behaviour. Research in this field is still in its early stages, but there is
a small amount of evidence to suggest improvements in cognitive function following
fatty acid supplementation. In contrast, it is well established that pregnant women
must have an adequate supply of the long chain n-3 PUFAs before and throughout
pregnancy and lactation to support normal growth, neurological development and
cognitive function of the baby. As n-6 PUFAs are more abundant in the diet, achieving
an adequate intake is less problematic. However, this is not the case for the n3
PUFAs; increasing fish consumption beyond two servings of oil-rich fish per week
or relying on fish oil supplementation is not appropriate during pregnancy due to
the potential problems associated with heavy metal contamination of fish, or the
high vitamin A level in some fish oil supplements.
Unsaturated fatty acids have also been associated with a number of other diseases
and although the evidence is by no means conclusive, it is an area that is attracting
a huge amount of interest. Dietary fat affects a number of different metabolic pathways,
including those involved with glycaemic control, so the types and amounts of
dietary fat may have a role to play in the management of type 2 diabetes. Unsaturated
fatty acids may also be associated with a reduced risk of developing certain
cancers, including cancers of the colon, breast and prostate, although currently the
level of evidence is not deemed sufficient by authoritative bodies, such as the World
Cancer Research Fund, World Health Organization and the Department of Health,
to make any specific dietary recommendations. There are a number of inflammatory
conditions, such as asthma, Crohn's disease and arthritis, which could potentially
be alleviated by dietary modification. The fatty acid composition of cell membranes
can be altered by consumption of both n-3 and n-6 PUFAs, and this can result in
The health effects of dietary unsaturated fatty acids 181
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
reduced inflammatory activity. However, whether this effect brings about a significant
reduction in clinical symptoms is still unclear. It is also important to note that
there are concerns that the beneficial effects on certain disease outcomes are only
observed with very high intakes of unsaturated fatty acids, which could realistically
only be achievable by supplementation. Few nutritionists would be comfortable recommending
supplement use as the only alternative to fish, as this can be expensive
and goes against the idea that all the nutrients that our bodies require can be
obtained from the food that we eat if the right choices are made.
Unsaturated fatty acids are now a nutritional hot topic, and their presence in
foods has attracted both public and industrial interest. There is currently no specific
legislation to control the use of health claims relating to the fatty acid content of
foods. However, a European Union (EU) Directive is expected imminently which
will formally set down the criteria that a product will have to meet in order to make
any nutrition or health claim. With regards to the current recommendations, those
for the UK are in line with those around the world. However, as a population, we
need to increase our consumption of long chain n-3 PUFAs and decrease intake of
saturated fatty acids. To facilitate this, food technologists are looking at ways in
which the fatty acid profile of a food can be modified in order to bring dietary
improvements without requiring a major change in dietary habits. However, public
health messages surrounding the optimum intakes of fatty acids must be clear and
consistent to ensure that a favourable change in the fatty acid profile of the UK diet
occurs.
Keywords: cardiovascular disease, cognitive function, dietary recommendations, infant
development, oil-rich fish, unsaturated fatty acids
1. Introduction
Fat is perceived to be the `baddie' of all the nutrients,
linked to obesity, cardiovascular disease (CVD) and cancer.
However, being the most energy dense of the macronutrients,
it does play an important part in ensuring that
we meet our daily energy requirements and enables the
absorption of fat-soluble vitamins and carotenoids.
Additionally, there is mounting appreciation by health
professionals, nutrition scientists and the general public
of the ever-increasing number of health benefits that
have been associated with different types of dietary fats.
This Briefing Paper was written to consolidate the
wealth of new evidence surrounding the health effects
of both mono- and polyunsaturated fatty acids into
one resource. This paper complements the Task Force
Report on CVD (Stanner 2005), and updates the
unsaturated fatty acids Task Force Report (BNF
1992) and the n-3 fatty acid Briefing Paper (BNF
1999), all published by the British Nutrition Foundation
(BNF).
In the early stages of compiling this Briefing Paper, it
was decided not to focus on the trans-unsaturated fatty
acids, instead basing the report on the cis-unsaturated
fatty acids. Trans-fatty acids are treated very differently
by the body, and their effects are more akin to the
mainly atherogenic saturated fatty acids than the cisforms
of the unsaturated fatty acids. The consensus view
of the UK Food Standards Agency is that they are harmful
to health and display no known nutritional benefits.
The BNF published a Task Force Report on trans-fatty
acids in 1995, and many of the conclusions of this
report are still relevant today (see BNF 1995). Indeed,
over the past decade, population intakes of trans-fatty
acids have fallen and are now well below the recommended
2% of total energy set by the Department of
Health in 1991 (DH 1991). This is not to say that
intakes of trans-fatty acids are not still a problem, and
182 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
dietary advice states that those individuals who are in
the top end of the distribution of intake should still
make efforts to reduce their intakes. In BNF's most
recent Task Force report on CVD, the effects of transfatty
acids were considered, and they were declared to
be as bad, if not worse, for heart health as saturated
fatty acids (Stanner 2005). Where appropriate, consideration
of trans-fatty acid intakes and recommendations
have been made in this report, but their specific health
effects have not been included.
This Briefing Paper is in four parts; the first two sections
briefly describes the chemistry, digestion, absorption
and metabolism of fatty acids (What are
unsaturated fatty acids?) before giving a detailed update
on dietary sources and current levels of intake (Unsaturated
fatty acids in the UK diet). This section has a UK
focus. The Briefing Paper then describes new research on
the role of unsaturated fatty acids, as part of a healthy
balanced diet, in the context of CVD, diabetes, cancer,
inflammatory conditions, fetal development and cognitive
function (Unsaturated fatty acids in health and disease).
The Paper concludes by discussing issues
regarding labelling and opportunities to increase intake
of unsaturated fatty acids in the diet (Unsaturated fatty
acids and public health).
2. What are unsaturated fatty acids?
2.1 The chemistry of fatty acids
Fatty acids are the building blocks from which fats (lipids)
are made. Fatty acids found in foods and fats stored
in the body are mainly present in the form of triacylglycerols
(TAGs), a glycerol molecule backbone to which
three, often different, fatty acids are attached (Fig. 1).
Fatty acids can be present at any of three positions on
the glycerol molecule (termed sn-1; sn-2 and sn-3). The
presence of different fatty acids at different positions on
the glycerol molecule will also influence its characteristics
(i.e. melting point and digestibility).
Fatty acids are made up of a backbone of carbon
atoms, with a methyl group (CH3) at one end [the
omega () or n-end] and a carboxyl group (COOH) at
the other [the delta () end; see Fig. 2]. Hydrogen atoms
are joined to the string of carbon atoms, forming a
hydrocarbon chain.
Fatty acids vary in length from 2 to 80 carbons, but
are typically present in food as 14, 16, 18, 20 and 22
carbon atom chains. Short chain fatty acids, such as
butyric acid (4 carbon atoms) or propionic acid (3 carbon
atoms) are formed in the gut when polysaccharides
are fermented by the anaerobic bacteria present in the
large intestine. Certain short chain fatty acids, namely,
butyrate, are believed to be important for gut health
(Bird et al. 2000). Technically, the long chain fatty acids
contain 12 or more carbon atoms. However, this term is
often used to describe the longer chain fatty acids that
contain more than 20 carbon atoms, which may also be
referred to as very long chain fatty acids. From this
point on, this Briefing Paper will use the term `long
chain' to describe fatty acids with more than 20 carbon
atoms.
Carbon chain length influences the characteristics of a
fatty acid, as does the presence or absence of double
bonds between carbon atoms.
* If all of the carbons in the fatty acid chain are linked
by single bonds (i.e. the fatty acid contains all the hydrogen
atoms that it can hold), the fatty acid is said to be a
saturated fatty acid (SFA).
* If one or more double bonds are present in the fatty
acid chain (i.e. the fatty acid does not hold its potential
full complement of hydrogen atoms), the fatty acid is
considered to be an unsaturated fatty acid.
* If there is only one double bond present in an unsaturated
fatty acid, it is said to be a monounsaturated
fatty acid (MUFA).
* If there is more than one double bond present, the
fatty acid is said to be a polyunsaturated fatty acid
(PUFA).
Double bonds in unsaturated fatty acids can be
arranged in one of two ways; cis- or trans- configurations
(see Fig. 3). Double bonds in foods are predominantly
found in foods in the cis- form, where both
hydrogen atoms are found on the same side of the fatty
acid. The presence of a cis- bond in a fatty acid lowers
the melting point of the fatty acid, making it more likely
to be liquid at room temperature. Trans-fatty acids,
where the hydrogen atoms are situated on opposite sides
of the fatty acid, are less common in nature, but are typFigure
1 The structure of triacylglycerol.The fatty acids in the sn-1,sn-2 and
sn-3 positions (F1, F2 and F3) will, most likely, be different.
H
C
C
C
O
O
O
H
H
H
H
O
C F1
F2
F3
C
O
O
C
The health effects of dietary unsaturated fatty acids 183
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
ically found in small amounts in the fat of ruminant
meats and in milk being formed in the rumen (part of
the gastrointestinal tract) during digestion and subsequently
absorbed as an energy source for the animal.
These fatty acids can also be produced during the hydrogenation
(hardening) of unsaturated oils as was traditionally
used in margarine manufacture. The major
unsaturated fatty acids present in the diet are shown in
Table 1.
PUFAs can be further classified as either n-3 (omega
3) or n-6 (omega 6) PUFAs; to which family a PUFA
belongs depends on the position of the first double bond
in the fatty acid chain. All members of the n-6 family of
fatty acids contain their first double bond between the
sixth and seventh carbon atoms from the terminal
methyl group, while all members of the n-3 family of
fatty acids have their first double bond between the third
and fourth carbon atoms (see Fig. 4).
2.2 Digestion, absorption and metabolism
Fat enhances the flavour and palatability of foods, and
has been shown to slow the rate at which the stomach
contents are emptied into the small intestine. As a result,
fat leads to general feelings of satiety and satisfaction
after a meal that are often difficult to mimic in reduced
Figure 3 cis- and trans-configurations.
Cis fatty acid Trans fatty acid
C
H
H
C C C C C
OH
O
H H H H
HH
H C
H
H
C C C C C
OH
O
H H
H
H
HH
H
Table 1 Main unsaturated fatty acids present in food
Trivial name Systematic name Rich dietary sources
Monounsaturated fatty acids
Palmitoleic (16:1n-7) cis-9-hexadecenoic Fish oil
Oleic (18:1n-9) cis-9-octadecenoic Olive oil, rapeseed oil, palm oil
Elaidic (18:1n-9 trans) trans-9-octadecenoic Partially hydrogenated fat
Trans-vaccenic (18:1n-7 trans) trans-11-octadecenoic Ruminant fats
Cis-vaccenic (18:1n-7) cis-11-octadecenoic Ruminant fats
Erucic (22:1n-9) cis-13-docosenoic Mustard seed oil
Polyunsaturated fatty acids
Linoleic (18:2n-6) 9,12-octadecadienoic Safflower oil, sunflower oil, corn oil
Gamma ()-linolenic (18:3n-6) 6,9,12-octadecatrienoic Evening primrose oil
Arachidonic (20:4n-6) 5,9,11,14-eicosatrienoic Ruminant meats (low levels)
Alpha ()-linolenic (18:3n-3) 9,12,15-octadecatrienoic Flaxseed oil, linseed oil, walnut oil
Eicosapentaenoic (20:5n-3) 5, 8,11,14,17-eicosapentaenoic Fish oil, oil-rich fish
Docosahexaenoic (22:6n-3) 4,7,10,13,16,19-docosahexaenoic Fish oil, oil-rich fish
Source: Sanders & Emery (2003).
Figure 2 Structure of a fatty acid.
Omega () or n- end Delta () end i
H C
H
H
C
H
H
C
H
H
C
H
H
C
H
H
C O
OH
184 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
fat products. In order to be efficiently digested and
absorbed, dietary fat must first be emulsified by bile
secreted into the small intestine from the gallbladder.
The fat droplets form small micelles that are dispersible
in water and so can be acted on by pancreatic lipases
cleaving the fatty acids at the sn-1 and sn-3 positions of
the TAGs. The end-products from the digestion of fat:
free fatty acids, a 2-monoacylglycerol, and very limited
amounts of glycerol, are absorbed by diffusion across
the gut wall into the cells of the intestine. Recently, work
by Stremmel et al. (2001) has introduced the idea that
fatty acids may be absorbed by carrier-mediated processes,
involving transport proteins in the membranes of
cells lining the small intestine. However, the importance
of this route has been questioned, as the candidate transporter
proteins are also found in other cells in the body
where they have little to do with fatty acid transport
(Tso et al. 2004). Regardless of this, the digestion of fat
is very efficient, with typically more than 95% of dietary
fat being broken down and absorbed (Sanders & Emery
2003).
The mode of transport away from the gut is dependent
on chain length; the short to medium chain fatty
acids (2­12 carbon atoms) are transported bound to the
carrier protein albumin via the hepatic portal vein to the
liver. However, dietary fat mainly consists of the longer
chain fatty acids (>12 carbon atoms), which are reassembled
in the intestinal cell into TAG. These are then
packaged into lipoprotein particles known as chylomicrons
and are transported via the lymph system into the
peripheral circulation. The rate of lipolysis (breakdown
of fat), absorption of fatty acids and transport might be
influenced by the degree of unsaturation (see BNF 1992
for more details). However, the nutritional significance
of this difference is unclear. The fatty acid at sn-2 may
influence subsequent metabolism of chylomicrons and
ultimately low density lipoprotein (LDL) cholesterol
response. It has been suggested that dietary fats containing
a predominance of sn-2 unsaturated triglycerides
might be absorbed more slowly, and cleared more rapidly
from the circulation compared with saturated fatty
acids, resulting in reduced concentrations of TAGs in
the blood after a meal (Yli-Jokipii et al. 2001). Conversely,
SFAs in the sn-2 position are preferentially
absorbed into the cells lining the intestines over SFAs at
positions sn-1 and sn-2, which also has implications for
the balance of TAGs in the blood after a meal (see Berry
& Sanders 2005). It remains controversial as to the relevance
of these findings to adults, as most of the work
has been conducted in animals, and any work that has
been carried out in humans has been conducted in
infants (in the context of infant formula composition).
Once in the bloodstream, chylomicrons acquire apolipoprotein
C (apoC) from high density lipoproteins
(HDL). At the target cell (e.g. muscle), the apoC subunit
activates the enzyme lipoprotein lipase, which is located
within the endothelial cell membrane. This results in
cleavage of the fatty acids, which are then transported
into tissues for storage or metabolism.
Fatty acids undergo -oxidation in mitochondria to
release energy. The exact energy yield of the different
fats is dependent on the chain length and the number of
double bonds in the molecule, although 1 g of fat is
assumed to release 37 kJ (9 kcal).
Most unsaturated fatty acids can be synthesised in
the body following a series of fatty acid chain elongation
and desaturation steps. This process is catalysed
by the enzyme complex, fatty acid synthase.
Plants contain desaturases capable of inserting double
bonds at positions 3, 6 and 9 from the terminal
methyl group. Animal and human desaturases are
only capable of inserting double bonds at specific
positions beyond carbon 6. Therefore, there are several
fatty acids, termed essential fatty acids (EFA),
which cannot be made in the body but are required
for normal physiological function in humans. There
are two specific EFAs: the cis n-6 PUFA linoleic acid
(LA; 18:2n-6) and cis n-3 PUFA alpha ()-linolenic
Figure 4 n-3 and n-6 fatty acids. PUFA,
polyunsaturated fatty acid.
1 n-3 PUFA
2 n-6 PUFA
H H
H
H C1 C2 C3 C4 C C C C C C O
H H H H H H H H
H H H OH
H H
H
H C1 C2 C3 C4 C5 C6 C7 C C C O
H H H H H H H H
H H H OH
The health effects of dietary unsaturated fatty acids 185
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
acid (ALNA; 18:3n-3). It is from these two `parenť
EFAs that the n-3 and n-6 fatty acid `families' are
derived through a series of enzyme catalysed desaturation
and elongation reactions, that generally take
place in the cell cytosol or in the mitochondria (see
Fig. 5).
ALNA is metabolised to docosahexaenoic acid (DHA;
22:6n-3) via eicosapentaenoic acid (EPA; 20:5n-3) and
docosapentaenoic acid (DPA; 22:5n-3), whereas LA is
metabolised to arachidonic acid (AA; 20:4n-6) via
gamma ()-linolenic acid (GLA; 18:3n-6) or eicosadienoic
acid (20:2n-6) as two pathways are active. However,
conversion is not 100% efficient. Desaturation of
DPA at the -4 position to produce DHA does not only
occur by a single step catalysed by -4 desaturase. There
is an additional pathway, the `Sprecher Pathway', which
involves elongation and desaturation of DPA and tetracosahexenoic
acid in microsomes followed by a chainshortening
step to DHA in peroxisomes (Sprecher
2000).
It has been estimated that less than 8% of ALNA is
metabolised to EPA, and the capacity for the body to
synthesise DHA appears to be particularly limited. It is
estimated that only between 0.02% and 4% of ALNA is
metabolised to DHA (Vermunt et al. 2000; Pawlosky
et al. 2001; Burdge et al. 2002), with women having
a greater capacity for DHA synthesis than men (Burdge
& Wootton 2002). Feedback inhibition of enzymes
involved in n-3 and n-6 fatty acid synthesis occurs; for
example, if the amount of DHA in the diet increases,
there is reduced metabolism of ALNA to EPA. Furthermore,
n-3 and n-6 fatty acids compete for the enzymes
involved in fatty acid elongation and desaturation, with
certain enzymes having greater affinity for n-3 fatty
acids and others having greater affinity for the n-6 series
(see BNF 1999).
The metabolites of the EFAs have many different
functions. DHA and AA are major constituents of membrane
phospholipids, especially in the retina, brain (predominantly
as DHA) and platelets (predominantly as
AA). As the capacity to synthesise EPA and DHA from
the EFA ALNA is very limited, dietary sources make a
major contribution to the amount of both these cis n-3
PUFAs in the body (Burdge & Calder 2005a).
The 20 carbon metabolites of EFAs (EPA and AA)
function as the basis for important regulatory signals
known as eicosanoids. There are several different families
of eicosanoids: the prostaglandins (which regulate
muscle contraction, immune response and inflammation),
prostacyclins (which inhibit platelet aggregation)
and thromboxanes (which bring about platelet aggregation)
are all formed by the action of cyclo-oxygenase
enzymes; the leukotrienes (which affect microvascular
and bronchial constriction or dilatation) and hydroxyfatty
acids (which regulate cell adhesion) are formed by
the action of lipoxygenases. Eicosanoids are produced
by cells to act in their immediate environment in
response to extracellular stimuli, e.g. blood vessel damFigure
5 Metabolism of essential fatty acids
(adapted from Napier & Sayanova 2005).
D
18:2n-6
Linoleic acid
(from the diet)
20:2n-6
Eicosadienoic
acid
20:3n-6
Dihomo--
Linolenic acid
9-Desaturase Pathway
22:6n-3
Docosahexaenoic
acid (DHA)
24:6n-3
Tetracosahexaenoic
acid
20:4n-6
Arachidonic
acid
24:5n-3
Tetracosapentaenoic
acid
20:5n-3
Eicosapentaenoic
acid (EPA)
20:4n-3
Eicosatetraenoic
acid
18:4n-3
Octadecatetraenoic
acid
18:3n-3
-linolenic acid
(from the diet)
`Sprecher' Pathway
6-Desaturase Pathway
22:6n-3
Docosahexaenoic
acid (DHA)
22:5n-3
Docosapentaenoic
acid (DPA)
20:3n-6
Dihomo--
Linolenic acid
18:2n-6
Linoleic acid
(from the diet)
18:3n-6
-Linolenic acid
20:4n-6
Arachidonic
acid
6-desaturase
6-elongase
5-desaturase5-desaturase
9-elongase
8-desaturase
6-desaturase
6-desaturase
5-desaturase
6-elongase
5-elongase
4-desaturase
7-elongase
Peroxisomal -oxidation
186 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
age. Eicosanoid formation from the two EFA families
follows slightly different pathways (Fig. 6). However,
they share a common set of enzymes, so the ratio of
n-3 to n-6 PUFAs in the diet will affect which pathway
is the most active. The activity of the different
eicosanoids produced from EFAs varies; eicosanoids
derived from the cis n-6 PUFAs typically exert stronger
effects than those derived from n-3. Thus the diet has a
role to play in determining the final mix and potency of
eicosanoids.
2.3 Functions of unsaturated fatty acids
The major roles of lipids in the body are: to store energy,
to provide energy, and to provide stable cellular membranes.
Energy is stored in the body as TAGs in adipose
tissue. Adipose tissue mainly consists of SFAs and
MUFAs, although to some extent this is dependent on
an individuaľs diet (see BNF 1992 for further details).
The hormone insulin ensures that fatty acids in circulating
lipoproteins are liberated and transported into adipose
tissue by activating the enzyme lipoprotein lipase.
Insulin is produced in response to glucose entering the
blood from the gut, so concentrations are high after a
meal. When the concentration of insulin in the blood
drops (i.e. during fasting), hormone-sensitive lipase is
activated and fatty acids are mobilised to meet energy
demands. The free fatty acids are carried in the bloodstream
bound to albumin to where they are needed in
the tissue cells and are broken down in mitochondria by
-oxidation.
Unsaturated fatty acids are found in membranes as
esterified phosphoglycerides (also known as phospholipids).
The degree of unsaturation introduces `kinks'
Figure 6 Mechanism of eicosanoid formation (adapted from Sanders & Emery 2003). DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid;
PG, prostaglandin;Tx, thromboxane.
18:2 n-6
Linoleic
20:3 n-6
Dihomo--linolenic
20:4 n-6
Arachidonic
Prostaglandins, prostaclyclins and thromboxanes
e.g. PGE1, PGD1, PGF1, PGE2, PGD2, PGF2, PGI2, TxA2
Leukotrienes and hydroxyfatty acids
e.g. B4, C4, D4, E4
n-6
Stimulus
Incorporation
into membrane
phospholipid
Cycloxygenase pathway
Lipoxygenase pathway
18:2 n-3
-linolenic
20:5 n-3
EPA
22:6 n-3
DHA
Prostaglandins, prostaclyclins and thromboxanes
e.g. PGE3, PGD3, PGF3, PGI3, TxA3
Leukotrienes and hydroxyfatty acids
e.g. B6, C6, D5, E5
n-3
Stimulus
Incorporation
into membrane
phospholipid
Cycloxygenase pathway
Lipoxygenase pathway
Stimulus
Stimulus
18:2 n-6
Linoleic
20:3 n-6
Dihomo--linolenic
20:4 n-6
Arachidonic
Prostaglandins, prostaclyclins and thromboxanes
e.g. PGE1, PGD1, PGF1, PGE2, PGD2, PGF2, PGI2, TxA2
Leukotrienes and hydroxyfatty acids
e.g. B4, C4, D4, E4
n-6
Stimulus
Incorporation
into membrane
phospholipid
Cycloxygenase pathway
Lipoxygenase pathway
18:2 n-3
-linolenic
20:5 n-3
EPA
22:6 n-3
DHA
Prostaglandins, prostaclyclins and thromboxanes
e.g. PGE3, PGD3, PGF3, PGI3, TxA3
Leukotrienes and hydroxyfatty acids
e.g. B6, C6, D5, E5
n-3
Stimulus
Incorporation
into membrane
phospholipid
Cycloxygenase pathway
Lipoxygenase pathway
Stimulus
Stimulus
Key points:
What are unsaturated fatty acids?
* Fatty acids are the building blocks from which lipids are made. Fatty acids are found in foods and are stored in
the body mainly in the form of triacylglycerols (a molecule of glycerol combined with three fatty acid chains).
* Unsaturated fatty acids are hydrocarbon chains containing at least one carbon­carbon double bond.
* Most fatty acids can be synthesised in the body. Those that cannot are termed EFAs and must be acquired from
the diet. In humans, the EFAs are the n-3 (omega 3) PUFA -linolenic acid (ALNA) and the n-6 (omega 6) PUFA
linoleic acid (LA).
* Oxidised metabolites of fatty acids are called eicosanoids. These compounds act as regulatory signals in the body
and can bring about inflammatory effects.
* Fatty acids are used in the body as a means of energy storage, to provide energy, and to provide stable cellular
membranes.
The health effects of dietary unsaturated fatty acids 187
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
into the hydrocarbon chain and affects the ability of the
phosphoglycerides to pack together. However, chains
containing multiple double bonds pack together better
than chains containing few double bonds, as the chains
adopt a helical configuration. Thus, membranes containing
high proportions of the long chain PUFAs are
the most stable, i.e. they are the most permeable to
water, ensuring efficient intracellular metabolism. (For
further details on the structural role of unsaturated fatty
acids, see BNF 1992.)
3. Unsaturated fatty acids in the UK diet
3.1 Sources of fat in the diet
Fat is found in most food groups, and foods containing
fat generally provide a range of different fatty acids,
both saturated and unsaturated. Table 2 outlines the
unsaturated fatty acid content of a range of different
foodstuffs that are commonly consumed in the British
diet. Further details about the contribution that these,
and other, foods make to total fat intake are included in
a following section (Major contributors to unsaturated
fatty acid intake).
Unsaturated fatty acids in meat: The fatty acid composition
of meat is dependent on whether or not the species
is a ruminant. In ruminant animals (e.g. cows), the
majority (>90%) of the dietary unsaturated fatty acids
are hydrogenated to SFAs in the rumen during digestion.
Hence, beef traditionally contains a higher proportion
of SFAs compared with some other meats. Non-ruminant
meat, e.g. pork, contains proportionally more
unsaturated fatty acids, but its composition is still
dependent on the fatty acid profile of the animal feed
(Table 3). MUFAs also contribute a considerable proportion
of the fat content of meat (approximately 25%).
In recent years, animal husbandry techniques have
been modified to produce meat with a more favourable
fatty acid profile. Initially, the aim was to reduce the SFA
content, but now scientists are developing feeds that will
increase the concentrations of the long chain n-3 PUFAs
in meat and ultimately enhance human health (see
Nugent 2005 and Unsaturated fatty acids and public
health).
Unsaturated fatty acids in milk: The lipids in milk and
other dairy products are mostly short and medium chain
SFAs and MUFAs (Table 4). Milk contains relatively
low concentrations of PUFAs. As with meat, work is ongoing
to improve the fatty acid profile of milk, and there
is particular interest in enhancing the concentration of
the long chain n-3 PUFAs (see Unsaturated fatty acids
and public health).
Unsaturated fatty acids in fish: The flesh of white
fish and seafood typically contain very low amounts
of fat (1­2%; Table 5). The fat that is present tends
to be long chain n-3 PUFAs. The flesh of oil-rich or
fatty fish is a richer source of fatty acids than white
fish (5­20% depending on the breeding cycle). Oilrich
fish include sardines, salmon, pilchards, mackerel,
herring and trout, whether canned, fresh or frozen.
However, although fresh tuna is considered to be
an oil-rich fish, during the canning process the fat
content of the fish is substantially reduced, so canned
tuna is not included in the oil-rich fish group. Examples
of white fish are cod, haddock, turbot, bream
and sea bass.
Like humans, fish are not capable of synthesising long
chain n-3 PUFAs. However, fish either feed on microorganisms
(such as algae) or on smaller fish that have
eaten these PUFA-synthesising micro-organisms themselves,
thereby acquiring long chain n-3 PUFAs via the
diet. The fish that store their fat in their flesh thus proTable
2 Fat in the diet (g fat/100 g food)
Total fat
g/100 g
MUFA
g/100 g
cis-PUFA g/100 g
n-3 n-6
Cod liver oil 99.9 44.60 24.40 3.50
Olive oil 99.9 73.00 0.70 7.50
Vegetable oil (blended) 99.9 53.20 6.50 23.26
Margarine 84.4 19.92 1.29 8.33
Butter 82.2 18.48 1.41 2.27
Polyunsaturated spread 68.5 15.12 0.16 33.40
Peanuts 46.0 22.03 0.35 12.75
Cheese (cheddar) 32.7 7.14 0.99 0.77
Chocolate (milk) 30.7 9.45 0.09 1.02
Biscuits (digestives) 20.3 7.37 0.09 1.86
Avocados 19.3 14.50 0.07 1.16
Cream (single) 19.1 4.54 0.11 0.49
Cakes (sponge) 16.7 5.51 0.31 0.81
Eggs 11.2 4.31 0.08 1.61
Chips 11.0 2.69 0.01 0.16
Lamb (raw, lean) 8.0 2.58 0.16 0.28
Oil-rich fish, e.g. salmon 7.8 3.23 1.85 0.27
Beef (raw, lean) 4.3 1.76 0.07 0.17
Pork (raw, lean) 4.0 1.50 0.09 0.61
Whole milk 4.0 0.93 0.02 0.10
Chicken (white meat) 3.7 1.58 0.13 0.60
Yogurt (whole milk) 3.0 0.71 0.05 0.07
White bread 1.9 0.25 0.04 0.62
Semi-skimmed milk 1.7 0.39 0.01 0.05
White fish, e.g. cod 0.7 0.08 0.26 0.02
Source: FSA (2002).
MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid.
188 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
vide a source of long chain n-3 PUFAs when they are
eaten. Salmon is the most popular oil-rich fish in the UK.
To provide salmon in sufficient quantities to meet public
demand, increasing amounts of the salmon available in
supermarkets are obtained from fish farms rather than
caught from wild fish stocks. Farmed fish do not have
the same direct access to a ready supply of the n-3
PUFA-synthesising algae and smaller fish as wild fish do.
Therefore, they must be provided with fish oils rich in
long chain n-3 PUFAs as part of their diet. In the opinion
of the European Food Safety Authority (EFSA),
there are no consistent differences between wild and
farmed fish in terms of either safety or nutritional value
(Question N° EFSA-Q-2004-22; Opinion adopted on
22 June 2005). Species, season, location, diet, lifestage
and age of the fish all have a major impact on both the
Table 3 The unsaturated fatty acid composition of lean, raw meat (g fatty acids/100 g meat)
Total fat (g/100 g)
MUFA (g/100 g) PUFA (g/100 g)
14:1 16:1
18:1
Oleic
18:2
LA
18:3
ALNA
20:4
AA
20:5
EPA
22:6
DHA
Beef 4.3 0.02 0.15 1.54 0.11 0.03 0.02 0.01 0
Lamb 8.0 0.01 0.13 2.37 0.13 0.09 0.02 0.02 0.01
Pork 4.0 0 0.09 1.36 0.54 0.05 0.04 0.01 0.01
Chicken 3.7 0 0.04 0.42 0.16 0.02 0.01 tr 0.01
Source: MAFF (1998).
AA, arachidonic acid;ALNA, -linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LA, linoleic acid; MUFA, monounsaturated fatty acid; PUFA,
polyunsaturated fatty acid; tr, trace.
Table 4 The unsaturated fatty acid composition of cow's milk (g fatty acids/100 g milk)
Total fat (g/100 g)
MUFA (g/100 g) PUFA (g/100 g)
14:1 16:1
18:1
Oleic
18:2
LA
18:3
ALNA
20:4
AA
20:5
EPA
22:6
DHA
Whole milk 4.0 0.04 0.07 0.80 0.07 0.02 0 0 0
Semi-skimmed 1.7 0.02 0 0.34 0.03 0.01 0 0 0
Skimmed 0.3 0 tr 0.06 0.01 tr 0 0 0
Source: MAFF (1998).
AA, arachidonic acid;ALNA, -linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LA, linoleic acid; MUFA, monounsaturated fatty acid; PUFA,
polyunsaturated fatty acid.
Table 5 The unsaturated fatty acid composition of raw, fresh fish (g fatty acids/100 g fish)
Total fat (g/100 g)
MUFA (g/100 g) PUFA (g/100 g)
14:1 16:1
18:1
Oleic
18:2
LA
18:3
ALNA
20:4
AA
20:5
EPA
22:6
DHA
Cod 0.7 0 0.01 0.05 tr tr 0.02 0.08 0.06
Herring 13.2 0.01 1.06 1.50 0.29 0.18 0.04 0.51 0.69
Salmon 6.3 n/a 0.25 1.35 0.17 0.30 0.27 0.32 1.12
Mackerel 16.1 0 0.59 1.91 0.30 0.22 0.07 0.71 1.10
Source: MAFF (1998).
AA, arachidonic acid;ALNA, -linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LA, linoleic acid; MUFA, monounsaturated fatty acid; PUFA,
polyunsaturated fatty acid.
The health effects of dietary unsaturated fatty acids 189
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
nutrient and contaminant levels. However, these levels
vary broadly within species and between species in both
wild and farmed fish.
Unsaturated fatty acids in eggs: Egg yolk is approximately
30% fat. The fatty acids present are predominantly
SFAs and MUFAs (including oleic acid ­ 4 g/
100 g). There are few PUFAs in conventionally produced
eggs.
Unsaturated fatty acids in plants: Plant cell membranes
contain some fat, mainly as palmitic, palmitoleic,
oleic, linoleic and -linolenic acids, although the exact
amounts are very small (typically less than 1 g per
100 g). Green vegetables account for much of the intake
of ALNA in the human diet.
Unsaturated fatty acids in fats and oils: Fats and
oils are differentiated by their physical characteristics;
fats being solid at room temperature and oils
liquid. Fatty acids are mainly present as TAGs (see
What are unsaturated fatty acids?) although, over
time, some hydrolysis does occur and small amounts
of free fatty acids are present. This is undesirable as
even low concentrations of free fatty acids result in
unacceptable flavours and eventually lead to rancidity.
Animal fats, such as lard, suet and butter, typically
contain a greater proportion of the SFAs. The
fish oils, including cod liver oil, are rich sources of
the long chain n-3 PUFAs; whereas oil-rich fish store
fat in their flesh, the white fish store fat in their
liver.
Plants store much of their own energy as oil in their
seeds. The fatty acid composition of the seed oils varies
widely (Table 6). Typically, one fatty acid will dominate.
Margarine was traditionally produced by the hydrogenation
of vegetable oils, often the mainly unsaturated
sunflower and rapeseed oils. However, different methods
of production are now used, and the fatty acid composition
of margarines and fat spreads can vary
considerably. Spreads have a similar composition to
margarine but are usually lower in fat, there being a
spectrum of fat contents across the product range. In
this case, water is used to bulk out these spreads, making
some of these products, especially those with lower
fat contents, unsuitable for frying. Reduced fat spreads
can be used for baking. Trans-PUFAs may be produced
during incomplete hydrogenation. However, in Europe
efforts have been made to reduce or remove transPUFAs
from margarine and spreads through product
reformulation and the use of new techniques (Upritchard
et al. 2005). Furthermore, some manufacturers
have increased the amount of n-3 fatty acids present (as
ALNA) in margarines and fat spreads, and endeavour to
incorporate long chain n-3 fatty acids (see Unsaturated
fatty acids and public health).
Unsaturated fatty acids from supplements: From a
recent nationwide dietary survey, 40% of women and
29% of men reported taking a nutritional supplement
(Henderson et al. 2002). Of them, 39% took cod liver
oil, or other fish-based supplements, which will make a
Table 6 The typical unsaturated fatty acid composition of selected fats and oils (g fatty acids/100 g oil)
Total fat (g/100 g)
MUFA (g/100 g) PUFA (g/100 g)
14:1 16:1 18:1
Oleic
18:2
LA
18:3
ALNA
20:4
AA
20:5
EPA
22:6
DHA
Butter 82.5 0.69 1.24 15.80 0.95 0.46 0.09 0.08 0
Margarine 81.7 0 0.23 29.21 12.42 3.36 0 0 0
PUFA spread 68.5 0 0.09 14.96 33.26 0.09 0 0 0
MUFA spread 62.7 0 0.18 30.51 9.65 1.98 0 0 0
Cod liver oil 99.9 0 0 18.30 2.60 1.10 0.90 1.40 8.30
Linseed oil* 99.9 0 0 20.20 12.70 53.30 0 0 0
Olive oil 99.9 0 0.70 71.90 7.50 0 0 0 0
Palm oil 99.9 0 tr 37.10 10.10 0 0 0 0
Peanut oil 99.9 0 tr 43.30 31.00 0 0 0 0
Rape oil 99.9 0 0.20 57.60 19.70 9.60 0 0 0
Soybean oil 99.9 0 0.10 20.80 51.50 7.30 0 0 0
Sunflower oil 99.9 0 0.10 20.20 63.20 0.10 0 0 0
Source: MAFF (1998) (*Data obtained from USDA 2005).
AA, arachidonic acid;ALNA, -linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LA, linoleic acid; MUFA, monounsaturated fatty acid; PUFA,
polyunsaturated fatty acid.
190 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
significant contribution to the unsaturated fatty acid
content of their diets. Supplements available typically
contain DHA and EPA in doses approximating 100­
200 mg.
3.2 Dietary recommendations for fat
Fat is the most energy-dense macronutrient, so it is
therefore important that guidelines are set to ensure that
the population consumes adequate amounts of the individual
fatty acids without encouraging people to consume
more energy than they require. Opportunities also
exist to take the potential health benefits of the unsaturated
fatty acids into consideration and aim to achieve
a more optimal ratio of the n-3 to n-6 PUFAs. Current
UK recommendations (Table 7), which were derived in
1991 by the Committee on Medical Aspects of Nutrition
Policy (COMA), state that the population average
for total fat consumption should not exceed 35% of
daily food energy intake (or 33% of daily total energy
intake, i.e. including energy consumed as alcohol). Population
averages for the different types of fatty acids are:
SFAs should not exceed 11% of daily food energy;
MUFAs should make up approximately 13% of daily
food energy and cis-PUFAs approximately 6.5%. In
order to avoid the atherogenic effects of the trans-fatty
acids, the population average should not exceed 2% of
daily food energy. In 1991, recommendations for specific
fatty acids were only made for the EFAs LA (n-6
PUFA) and ALNA (n-3 PUFA) on the basis of prevention
of deficiency. These fatty acids should contribute at least
1% and at least 0.2% of daily food energy respectively
(i.e. 2.78 g of n-6 and 0.56 g of n-3 based on a 2500
kcal diet; DH 1991). At the time these guidelines were
set, fat contributed approximately 40% of daily food
energy, so in order to achieve these targets, dietary modification
was required (Gregory et al. 1990).
In 1994, the guidelines for intakes of PUFAs were
revised to take into account the cardio-protective effects
afforded by the long chain n-3 PUFAs (see Unsaturated
fatty acids in health and disease). The COMA report on
CVD advised that there should be no further increase in
intakes of n-6 PUFA as the population target had been
achieved, and that the intake of long chain n-3 PUFA
should increase from 0.1 to 0.2 g per day (DH 1994).
Recommendations for adults over the age of 65 years
are the same as those for the general population. The
adult recommendations are also appropriate for children
over the age of 5 years. Up to the age of 5 years, the
proportion of dietary energy derived from fat and fatty
acids should fall from about 50%, as supplied by breastfeeding,
to that recommended for adults (i.e. 35% of
total energy). Any modifications of dietary fat intake
should not begin until after a chilďs second birthday.
The most recent government recommendations relating
to the consumption of unsaturated fatty acids were
issued in 2004 (SACN/COT 2004). A committee
consisting of representatives from both the Scientific
Advisory Committee on Nutrition (SACN) and the
Committee on Toxicology (COT) assessed the health
impacts of increasing intakes of the long chain n-3
PUFAs, taking into account the potential toxicological
hazards of consuming the recommended levels from
oil-rich fish, known to be the richest source of these
fatty acids. They endorsed the population recommendation
to eat at least two portions of fish per week, of
which one should be oil-rich, and agreed that this recommendation
should also apply to pregnant women.
Two portions of fish per week, one white and the
other oil-rich, equate to approximately 0.45 g/day long
chain n-3 PUFAs (3.15 g/week). The report added that:
`An increase in population oily fish consumption to
one portion a week, from the current levels of about a
third of a portion a week, would confer significant
public health benefits in terms of reduced risk of
cardiovascular disease. There is also evidence that
increased fish consumption might have beneficial
effects on fetal developmenť. It was also acknowledged
that some groups, especially men and boys,
could benefit from greater intakes. However, there was
a concern about increasing total intakes of oil-rich fish
more than 1 portion per week in girls and women of
child-bearing age because of the potential risk of contaminants
present in fish having an adverse effect on
subsequent pregnancies, although the safe upper limit
from a toxicological point of view was deemed to be 2
portions (Table 8).
Table 7 Adult UK dietary reference values for fat expressed as a
percentage of daily total energy intake (food energy in brackets)
Individual
minimum
Population
average
Individual
maximum
SFA 10 (11)
cis-PUFA 6 (6.5) 10
n-3 0.2
n-6 1.0
MUFA 12 (13)
trans-fatty acids 2 (2)
Total fat 33 (35)
Source: DH (1991).
MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; SFA,
saturated fatty acid.
The health effects of dietary unsaturated fatty acids 191
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
3.3 Intakes of unsaturated fatty acids
The average daily intake of fatty acids as reported in the
most recent National Diet and Nutrition Survey
(NDNS) of adults is shown in Table 9. The NDNS contains
data collected from a national sample of adults
aged 19­64 years, and is one of a programme of
national surveys designed to gather information about
the dietary habits and nutritional status of the British
population (Henderson et al. 2003).
The average intake of total fat in the UK population is
around the population target intake of 35% of food
energy. The average intake of SFAs in both men and
women is higher than the recommended target of 11%
of food energy, and a further reduction is required. The
recommendations for the MUFAs and total n-3 and n-6
PUFAs, listed in Table 7, are being met, on average.
The intakes of individual fatty acids are not available,
but intakes of the n-3 and n-6 PUFAs as a percentage of
food energy were well above the minimum levels set for
total n-3 and n-6 PUFAs, even at the lowest 2.5 percentile
of the distribution, suggesting that the percentage of
respondents who failed to meet the minimum intakes
recommended by the Department of Health in 1991 is
likely to be low. Nevertheless, the lack of data of the
individual fatty acids is a limitation of the NDNS, and
currently there is no way of monitoring the consumption
of the long chain n-3 PUFAs in the UK population
other than estimation from figures relating to the consumption
of oil-rich fish. Thus, currently, it is not
known whether targets for long chain n-3 PUFAs EPA
and DHA intakes are being met.
It is possible to estimate the average intake of the long
chain n-3 PUFA provided that we have knowledge of
their approximate concentrations in foods and the
amounts of the foods consumed. Using this methodology,
the average intake of the UK adult population has
been estimated to be approximately 244 mg of long
chain n-3 PUFA per day (Givens & Gibbs 2006). However,
as oil-rich fish contribute about 131 mg per day of
this total, and as only about 27% of the UK population
consume any oil-rich fish, the average intake for the vast
majority of the population will be only about 113 mg
per day. For those who consume little or no fish, the
intake will be as low as 46 mg per day, with poultry
meat being a key supplier. All of the above intake figures
are still considerably short of the recommended 450 mg
of long chain n-3 PUFA per day, and thus there is much
scope for dietary change.
Intakes of fatty acids in children aged 4­18 years
Intake data taken from the NDNS published in 2000
show that, although average intakes of total fat were
close to the 35% of food energy target (Table 10),
intakes of saturates were too high; only 8% were achieving
the target of 11% energy from SFAs.
3.4 Major contributors to unsaturated fatty acid
intake
Adults
Table 11 shows the major contributors to the intake
of different types of fat in the UK. Men acquire a
Table 8 FSA guidelines on fish intake for the UK population
(adapted from SACN/COT 2004)
Up to 2 portions of oil-rich
fish per week
Up to 4 portions of
oil-rich fish per week
Girls and women who might have
a baby one day
Other women
Women who are pregnant or
breastfeeding
Men and boys
Source: SACN/COT (2004).
Table 9 Total daily amount of fat in the diets of adult men and
women (amount as percentage of food energy in brackets)
Men Women
Total fat 86.5 g (35.8%) 61.4 g (34.9%)
SFA 32.5 g (13.4%) 23.3 g (13.2%)
trans-fatty acids 2.9 g (1.2%) 2.0 g (1.2%)
MUFA 29.1 g (12.1%) 20.2 g (11.5%)
n-3 PUFA 2.3 g (1%) 1.7 g (1%)
n-6 PUFA 12.9 g (5.4%) 9.4 g (5.3%)
Source: Henderson et al. (2003).
MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; SFA,
saturated fatty acid.
Table 10 Total daily amount of fat in the diets of boys and girls aged
4­18 years (amount as percentage food energy in brackets)
Boys Girls
Total fat 74.4 g (35.4%) 63.1 g (35.9%)
SFA 29.8 g (14.2%) 25.2 g (14.3%)
trans-fatty acids 2.9 g (1.4%) 2.4 g (1.3%)
MUFA 24.6 g (11.7%) 20.6 g (11.8%)
n-3 PUFA 1.5 g (0.8%) 1.5 g (0.8%)
n-6 PUFA 10.7 g (5.1%) 9.3 g (5.3%)
Source: Gregory & Lowe (2000).
MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; SFA,
saturated fatty acid.
192 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
higher proportion of their saturates from meat &
meat products (25%) compared with women (19%).
The main dietary sources of total n-3 PUFA are cereals
& cereal products, meat & meat products, potatoes
& savoury snacks, fish & fish dishes and
vegetables (see Appendix 1 for a description of these
groups). There are no significant differences between
men and women. For both men and women, the contribution
from fish & fish dishes increases with age
(mainly due to increasing oil-rich fish consumption).
The survey does not provide specific data for the
long chain n-3 PUFAs. Cereals & cereal products,
meat & meat products, and potatoes & savoury
snacks are the main contributors towards n-6 PUFA
intakes.
Children
Similar patterns of consumption are observed in children
aged 4­18 years. Proportionally, slightly less fat is
derived from meat & meat products and fat spreads,
and more fat is derived from potatoes & savoury
snacks, and cereal & cereal products when compared
with a typical adult diet (Table 12).
3.5 Trends in intake
Trends in intake of, and expenditure on food items are
best monitored by the Expenditure and Food Survey
(EFS). The most recent data, pertaining to expenditure
in 2003/4, were published in 2005. A variation of this
Table 11 Percentage contribution of the main sources of fat intake in the UK adult diet
Total fat SFA trans-PUFA MUFA n-3 PUFA n-6 PUFA
M F M F M F M F M F M F
Cereals & cereal products 19 20 17 19 25 26 17 18 17 16 20 20
Milk & milk products 14 15 23 25 15 16 9 11 4 4 2 3
Fat spreads 12 11 12 11 19 17 12 11 7 6 15 12
Meat & meat products 25 20 25 19 23 18 30 24 19 14 20 16
Fish & fish dishes 3 4 2 2 3 3 3 4 13 16 4 5
Potatoes & savoury snacks 10 10 7 7 7 6 11 12 17 16 13 13
Source: Henderson et al. (2002).
M, male; F, female; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; SFA, saturated fatty acid.
Table 12 Percentage contribution of the main sources of fat intake in the diet of UK children
Total fat SFA trans-PUFA MUFA n-3 PUFA n-6 PUFA
B G B G B G B G B G B G
Children aged 4­10 years
Cereals & cereal products 23 22 23 22 33 32 19 20 17 16 23 22
Milk & milk products 18 18 27 27 18 20 13 16 5 6 3 3
Fat spreads 9 10 8 8 12 13 8 8 7 7 18 18
Meat & meat products 17 17 15 15 14 14 22 20 15 15 16 16
Fish & fish dishes 2 2 1 1 2 2 2 2 5 7 3 3
Potatoes & savoury snacks 18 18 13 13 9 8 21 21 33 35 26 27
Children aged 11­18 years
Cereals & cereal products 22 21 21 21 27 38 19 22 18 16 22 21
Milk & milk products 13 13 21 20 14 15 10 11 4 4 2 2
Fat spreads 9 9 7 8 12 13 8 7 6 6 15 15
Meat & meat products 22 19 21 18 19 16 26 20 17 15 18 16
Fish & fish dishes 2 2 1 1 1 1 2 1 5 5 2 2
Potatoes & savoury snacks 18 21 13 16 11 12 21 23 35 40 27 31
Source: Gregory & Lowe (2000).
B, boys; G, girls; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; SFA, saturated fatty acid.
The health effects of dietary unsaturated fatty acids 193
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
survey (National Food Survey) has been conducted since
1940, so consumption trends over time can be monitored.
The 2005 report stated that over the past 30 years
there has been:
* a steady decrease in consumption of carcass meat;
* a slight increase in consumption of fish;
* a huge decrease in consumption of whole milk,
although the rate of this decline has lessened over the
past 3 years (Defra 2005).
Intake of total fat and the unsaturated fatty acids
appears to have been particularly affected by public
health messages and technologies to reduce total fat and
SFA and increase the proportion of unsaturated fat in
the diet. Intake of n-6 PUFAs has almost doubled as a
result of the popularity of vegetable oils and spreads rich
in these fatty acids. Semi-skimmed milk was introduced
in the 1980s, and now makes up 60% of the market
(Defra 2006). Demand for lower-fat products has
encouraged food producers to look at the systems they
use. The meat industry has modified its production systems
to favour a lower-fat end-product. As a result, over
the past 20 years the fat content of carcass meat has
reduced by more than 30% for pork, 15% for beef and
10% for lamb (Higgs 2000).
It is possible to estimate trends from the NDNS.
When data from successive surveys are compared, it is
apparent that there has been a slight decrease in n-6
PUFA consumption, which is especially apparent at the
higher end of the distribution of intakes. Looking over a
much longer period of time, there have been some quite
substantial changes to the balance of the fatty acids in
our diets. Over the last century, it has been suggested
that despite total fat intake increasing up until around
1980, our intakes of n-3 PUFAs have decreased. In the
same period of time, intakes of n-6 PUFAs have
increased. As the metabolic pathways of these two families
of fatty acids share some of the same enzymes, it is
thought that consuming what some people consider to
be higher amounts of n-6 may adversely affect the
metabolism of the n-3 PUFAs.
There are questions as to whether this may have had
an unfavourable effect on our health, which have triggered
research into the n-6 to n-3 ratio. Currently the
British diet provides these fatty acids in the ratio of 7:1.
This has increased from the 1950s when the average diet
provided n-6 and n-3 PUFAs in a ratio more like 4:1,
and is substantially different from the 1.5:1 suggested to
be consumed by Stone Age man. After considering the
health effects of these, along with other, families of
unsaturated fatty acids, the implications of this ratio
will be discussed further (see Unsaturated fatty acids
and public health).
4. Unsaturated fatty acids in health and
disease
Detecting associations between nutrition and chronic
diseases such as CVD and cancer is not an easy task.
Consequently, a number of different approaches have
been taken by researchers, attempting to link dietary
factors with disease states. Figure 7 outlines the four
main types of research: mechanistic; epidemiological;
biomarker trials; and clinical trials. Each approach
has its own strengths and weaknesses, and individuals
tackling research in this area often have to make
compromises when selecting which method to use
(Figure 7 ).
The published studies have used various approaches,
so it is very important to take into account the relative
Key points:
Unsaturated fatty acids in the UK diet
* Fat is found in most food groups, and foods containing fat generally provide a range of different fatty acids, both
saturated and unsaturated.
* Recommended intakes of both total fat and the different types of fatty acids have been set for the UK population.
We are not currently meeting these recommendations, so there is still scope for dietary changes.
* Major dietary sources of unsaturated fatty acids include meat & meat products, cereals & cereal products and
potatoes & savoury snacks.
* In Western diets, n-6 fatty acids are the predominant PUFAs, although this is in line with current dietary advice
to consume a minimum of 1% energy as n-6 PUFA and 0.2% energy as n-3 PUFA.
* The balance of n-3 and n-6 PUFAs in Western diets has changed substantially over the past 100 years or so. As
the two families of PUFAs share a common metabolic pathway, concerns that this might be detrimental to health
have been raised.
194 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
importance of each of the different types of evidence
when generating a consensus opinion on the health
effects of diet. In general, randomised controlled trials
with well-defined, clinical endpoints are considered to
be the `gold standarď, but in reality, these trials are very
difficult to conduct. Nutrition research does not especially
lend itself to this form of study, because diet as an
exposure is difficult to randomise in an effective way,
particularly throughout the long periods of time
required to investigate effects on disease. (Supplement
trials are more easily randomised, but their effects are
not always equivalent to those observed when a whole
diet is consumed.) Instead, high-quality epidemiological
studies, involving large cohorts of healthy individuals
followed over a long period of time, provide some of the
strongest evidence of any interaction. This is not to say
that the other forms of study do not offer valuable evidence,
it is just that their findings must be interpreted
with caution, especially when extrapolating from mechanistic
studies in the laboratory or in animal models to
humans.
The World Health Organisation (WHO) reviewed the
evidence relating dietary fat to the risk of developing a
number of chronic diseases in 2003. Their findings are
summarised in Table 13. As yet, there are no definitive
answers, and it is clear that more research is required in
order to fully understand the complex relationship that
fat and the individual fatty acids have in influencing the
risk of developing various diseases.
This following section will take a brief look at some
of the major studies that have been published and outline
some of the potential mechanisms whereby dietary
unsaturated fatty acids might affect disease risk. We
will begin by considering CVD as it is in this area that
diet­disease associations are thought to be the most
convincing.
4.1 Unsaturated fatty acids and cardiovascular disease
CVD, encompassing coronary heart disease (CHD),
stroke and other diseases of the cardiovascular system,
is one of the leading causes of mortality and morbidity
worldwide. Death rates have been falling in most developed
countries. However, in the UK, morbidity associated
with CVD appears to be increasing, at least in the
oldest age groups (see Frayn & Stanner 2005). More
people today survive heart attacks than ever before, but
many go on to develop chronic heart failure or angina,
which is associated with a reduced quality of life. For
this reason, it is important to reduce the incidence of
CVD and the occurrence of heart attacks or stroke and
at the same time, reduce morbidity in those who experience
CVD.
CVD is a consequence of two interrelated pathological
processes: atherosclerosis (hardening and narrowing
of blood vessels) and thrombosis (blood clotting) (see
Fig. 8). Atherosclerosis is characterised by the accumulation
of lipids in the blood vessel walls over a long
period of time. This can lead to impaired flow of blood
(and therefore oxygen) to the heart, and angina pectoris
(chest pain). A heart attack (myocardial infarction:
MI) is usually precipitated by a blockage in the coronary
artery following the rupture of an atherosclerotic
Figure 7 The various approaches available to
researchers investigating diet­disease interactions.
Type Strength Limitation
Mechanistic Insights Extrapolation
Epidemiology Hard endpoints Confounding
Biomarker
trials
Randomised Validity of
marker
Clinical trials Hard endpoints;
randomised
Cost; duration
HIGH IMPORTANCE
* Randomised controlled clinical
endpoints trial
* High-quality epidemiology;
prospective cohort studies
* Human studies on established
biomarkers
* Other epidemiology/human studies
on new or emerging biomarkers
* In vivo animal studies
* In vitro biochemical experiments
* Hypotheses, speculations, beliefs
LOW IMPORTANCE
Table 13 Strength of the evidence linking dietary fat and risk of
chronic disease
Decreased risk No relationship Increased risk
CVD
Convincing EPA/DHA; LA C14,16 SFA
Probable ALNA; Oleic acid Stearic acid
Possible C12 SFA
Type 2 diabetes
Probable SFA
Possible n-3 PUFAs Total fat
Cancer
Possible n-3 PUFAs Animal fats
Source: WHO/FAO (2003).
ALNA, -linolenic acid; CVD, cardiovascular disease; DHA, docosahexaenoic
acid; EPA, eicosapentaenoic acid; LA, linoleic acid; PUFA, polyunsaturated
fatty acid; SFA, saturated fatty acid.
The health effects of dietary unsaturated fatty acids 195
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
plaque in the arterial lumen. A stroke occurs when a
blockage disrupts the blood flow to the brain. (For an
extensive review of the aetiology, see Frayn & Stanner
2005.)
Established risk factors for CVD include age, sex, ethnicity,
hypertension, abnormal blood lipids (dyslipidaemia),
diabetes, obesity, physical inactivity and smoking.
While these established risk factors can explain a
high proportion of risk, there still remains some variability
unexplained, and a number of emerging risk factors
for CVD have been identified, e.g. endothelial
dysfunction (see Sattar & Ferns 2005), metabolic syndrome
(see Coppack et al. 2005), and fetal and maternal
nutrition (Fall 2005). Diet is recognised as an important
modifiable risk factor for CVD; for example, diets rich
in fruit and vegetables are associated with a reduced risk
of CVD (see Buttriss 2005a). The amount of fat in the
diet and type of fatty acids consumed can influence the
risk of CVD and its risk factors.
Dietary fatty acids and risk of CVD
Evidence for the association between unsaturated fatty
acid consumption and CVD comes from a wide-range
of sources: cross-cultural comparisons; prospective
(cohort) studies; case­control studies and intervention
trials.
Unsaturated fatty acids and CHD
MUFA: Studies comparing disease rates in different
countries have suggested an inverse association between
MUFA intake and death from CHD. Indeed, the mortality
rate from CHD is very low in Mediterranean
countries where the `typicaľ traditional diet is low in
SFAs and high in MUFAs (as a result of high intakes of
olive oil). Although the diets of Mediterranean countries
can vary, MUFAs typically account for 16­29% of
energy intake (Kris-Etherton 1999). Further evidence
for an inverse association between MUFA intake and
CVD comes from the Nurses' Health Study, a prospective
study with a follow-up period of 14 years conducted
in more than 80 000 women aged 34­59 years at
entry. It reported that a 5% increase in energy derived
from MUFA is associated with a significant 19% reduction
in risk of developing CHD in women with no history
of CHD (Hu et al. 1997). In the Lyon Diet Heart
Study, patients randomised to receive a Mediterraneantype
diet, including high MUFA, had significant reductions
in the risk of death from cardiovascular causes or
non-fatal acute myocardial infarction (73%), as well as
in cardiac mortality (76%) and total mortality (70%)
(de Lorgeril et al. 1994).
While there are a number of other epidemiological
studies that confirm a protective effect of MUFAs on
CHD (e.g. Artaud-Wild et al. 1993; Pietinen et al.
1997), there are also a number of studies that refute an
association, including the Framingham Heart Study
(Posner et al. 1991).
n-6 PUFA: Little research has been conducted on the
influence of n-6 PUFAs and overall risk of CHD in
recent years; rather, most research has concentrated on
the influence of n-6 PUFAs on risk factors for CHD. The
randomised clinical trials testing long-term effects of
high-LA diets on CHD incidence were conducted in the
1960s and early 1970s, and are thus often overlooked
when conducting literature searches. A statistically significant
20% decrease in the incidence of CHD was
observed in the Los Angeles Veterans' Study. In this
instance, men were randomised to a diet containing
roughly 40% of energy from fat, of which over a third
(38%) was LA in the intervention group compared with
only 10% in the control group (Dayton et al. 1969).
However, the findings over this period are inconsistent,
with four randomised controlled trials showing an independent,
protective effect of n-6 PUFA (MRC 1968;
Dayton et al. 1969; Leren 1970; Turpeinen et al. 1979)
and nine epidemiological studies showing no significant
relation (Hu et al. 2001). It should be noted that no trial
to date has shown an adverse effect of a high n-6 PUFA
diet on CHD risk. A more recent analysis of the data has
suggested that the ratio of PUFA to SFA in the diet might
be an important risk factor for CHD, and that it is diets
that are rich in n-6 PUFAs, but low in SFAs that are cardio-protective
(Garcia-Palmieri et al. 1980; Gordon
et al. 1981; McGee et al. 1984).
Figure 8 The interrelated pathologies of coronary heart disease and stroke
(adapted from Sanders & Emery 2003).
Arterial fatty streak
Atherosclerotic plaque
Plaque rupture and
thrombosis
Carotid or basillar
arteries
Coronary arteries
HEART ATTACK STROKE
INCREASING AGE
Arterial fatty streak
Atherosclerotic plaque
Plaque rupture and
thrombosis
Carotid or basillar
arteries
Coronary arteries
HEART ATTACK STROKE
Carotid or basillar
arteries
Coronary arteries
HEART ATTACK STROKE
INCREASING AGE
196 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
A number of case­control studies suggest that lower
dietary intakes, and lower plasma or adipose concentrations,
of LA are associated with a reduced risk of CHD
(Simpson et al. 1982; Wood et al. 1987); others do not
find this association (Fehily et al. 1987; Thomas et al.
1987). However, case­control studies cannot establish
cause or effect as they investigate differences after the
onset of disease. Prospective studies reporting the influence
of n-6 PUFAs on CHD risk are relatively few as the
majority tend to report on overall intake of PUFAs.
Miettinen et al. (1982) reported an inverse association
between the proportion of LA in serum phospholipids at
baseline and CHD incidence at 5-year follow-up.
Recently, the Kuopio Ischaemic Heart Study reported
that LA was strongly inversely associated with CHD
mortality (Laaksonen et al. 2005).
n-3 PUFA: A large number of epidemiological studies
report an inverse association between intakes of long
chain n-3 PUFAs from fish and risk of CHD; several ecological
studies have reported a lower incidence of CHD
in fish-eating populations, but such studies do not control
for other lifestyle factors that may influence the
CHD risk (Hirai et al. 1980; Bjerregaard & Dyerberg
1988). The Zutphen Study, a cohort of the Seven Countries
Study, was the first prospective study to report a
lower risk of CHD in men who consumed fish (Kromhout
et al. 1995), but this relationship was not confirmed
in the East Finland cohort of the Seven Countries
Study, where intakes were positively associated with risk
(Oomen et al. 2000). The Nurses' Health Study and the
Physicians' Health Study have both reported a beneficial
effect of fish consumption on sudden cardiac death. In
the Nurses' Health Study, consumption of fish was associated
with a decreased risk of CHD events and death
from CHD (Hu et al. 2002). This protective effect has
been attributed to the long chain n-3 PUFAs in fish, i.e.
EPA and DHA and confirmed in a nested case­control
study where blood concentrations were measured
(Albert et al. 2002). When comparing cases with controls,
mean blood EPA and DHA concentrations were
significantly lower, as were total long chain n-3 PUFA
concentrations. Men in the group consuming the highest
levels of n-3 PUFAs were 90% less likely to die from a
sudden cardiac event (>17 years of follow-up) than the
lowest n-3 PUFA consumers. Fish consumption in the
same study was also associated with a reduced risk of
sudden cardiac death.
Supplementation interventions with long chain n-3
PUFAs appear to have a beneficial effect on cardiac
health. A well-respected, large, randomised controlled
trial found that a fish oil concentrate providing 0.56 g of
DHA and 0.28 g of EPA per day decreased the incidence
of sudden cardiac death by 45% and all-cause mortality
by 20% (GISSI 1999). Additionally, in the Diet and
Reinfarction Trial (DART), dietary advice to eat two
portions of oil-rich fish per week, which provided 1 g of
long chain n-PUFA per day, decreased the incidence of
fatal CHD by 29% over a period of 2 years (Burr et al.
1989). A recent meta-analysis to establish whether the
individual effects found in a number of different studies
were consistent, reported that long chain n-3 PUFAs
reduced risk of sudden cardiac death by 30%, but not
risk of non-fatal MI (Bucher et al. 2002). In the 11 studies
analysed, intakes of DHA ranged 0.6­3.7 g/day and
EPA 0.3­6.0 g/day. A further randomised controlled
trial investigating the influence of long chain n-3 PUFA
supplementation and CHD incidence in patients with
suspected mycocardial infarction, reported a protective
effect of fish oil supplementation on cardiac death
(Singh et al. 1997). However, there are misgivings with
regards to the way that this study was conducted; there
has been considerable debate in the scientific community
about the reliability of the findings (White 2005).
The follow-up of the DART study (DART 2)
reported an unexpected 29% increase in CVD mortality
in the group advised to eat oil-rich fish (Burr et al.
2003). This is not consistent with other studies, and the
authors suggested that other aspects of individuals' lifestyles
may have changed when the dietary advice was
given. Additionally, the trial was halted for a short
period of time because of funding problems, which
may have adversely affected the outcome. However,
this illustrates the importance of considering all studies
when evaluating the effect of a dietary constituent on
disease risk. A recent meta-analysis reviewed 48 randomised
controlled trials and 41 cohort studies, investigating
the effect of n-3 PUFA (EPA, DHA and ALNA)
for at least 6 months in adults (both healthy and those
with some form of CVD risk factor) on CVD outcomes
(Hooper et al. 2006). Pooled estimate showed no
strong evidence of a reduced risk of: total mortality;
CVD events; or cancer. However, the findings of this
meta-analysis appear to have been influenced by the
inclusion of the DART 2 study involving more than
3000 men with angina. As mentioned previously, this
study reported an unexpected 26% increase in cardiac
deaths in the men taking the long chain n-3 PUFA supplements
(Burr et al. 2003).
However, as not all individuals consume oil-rich fish,
there is also much interest in the n-3 PUFA ALNA that
is obtained from predominantly plant-based sources.
ALNA is also associated with a reduced risk of fatal
CHD, possibly as it appears to reduce blood LDL cholesterol
concentrations in a similar manner to LA or
The health effects of dietary unsaturated fatty acids 197
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
oleic acid (Layne et al. 1996; Freese & Mutanen 1997).
A meta-analysis of five prospective cohort studies assessing
ALNA intake and CHD risk reported that intakes of
1.2 g/day are associated with a statistically non-significant
reduction in risk of fatal CHD of 21% (Brouwer
et al. 2004). There have been several clinical trials that
have investigated the influence of increased intakes of
ALNA on CHD risk (Natvig et al. 1968; de Lorgeril
et al. 1994; Singh et al. 1997). These trials comprise the
Lyon Diet Heart Study, in which individuals who had
experienced a first MI were randomised to receive
dietary advice to consume a Mediterranean-type diet,
including ALNA or no dietary advice, and followed up
for a period of 5 years. The authors reported a lower
incidence of cardiac death and non-fatal myocardial infarction
after consumption of 1.1 g ALNA/day, relative
to control treatment (de Lorgeril et al. 1994). However,
the findings from individual clinical trials have not been
consistent, and thus their findings must be interpreted
with caution. Some also consider four classic PUFA trials
as supportive of the ALNA hypothesis, as they
included soybean oil, which is rich in ALNA as well as
the n-6 PUFA LA (MRC 1968; Dayton et al. 1969;
Leren 1970; Turpeinen et al. 1979).
Unsaturated fatty acids and stroke Despite the wealth
of scientific literature on the influence of unsaturated
fatty acids on CHD, relatively few studies have investigated
the influence of unsaturated fatty acids on stroke
risk. Even fewer studies have investigated the influence
of unsaturated fatty acids on the different types of
stroke: ischaemic and haemorrhagic stroke.
MUFA: The measurement of different classes of
unsaturated fatty acids in serum, plasma or red blood
cells of ischaemic stroke cases and of controls suggests
that higher proportions of MUFAs are associated with a
reduced risk. However, the numbers of cases identified
in some of these studies have been small (Ricci et al.
1997).
n-6 PUFA: A recent prospective study reported that a
higher intake of LA, as determined by the measurement
of serum fatty acids, was associated with a reduced risk
of ischaemic stroke in Japanese men (Iso et al. 2001).
n-3 PUFA: Epidemiological evidence points towards
an inverse association between fish/long chain n-3 PUFA
consumption and total stroke (Keli et al. 1994; Zhang
et al. 1999) and ischaemic stroke (He et al. 2002, 2004;
Iso et al. 2002), but also a positive association with
haemorrhagic stroke (Bjerregaard & Dyerberg 1988). It
has been hypothesised that differences in the incidence
of ischaemic and haemorrhagic stroke can be explained
by the level of fish/n-3 PUFA consumption, although few
intervention studies have investigated their influence
and data that exist are inconsistent. However, it has
been reported that serum concentrations of ALNA are
inversely related with risk of total stroke (Simon et al.
1995), and that increased serum, plasma or red blood
cell concentrations of EPA and DHA are associated with
a reduced risk of stroke (Ricci et al. 1987). A meta-analysis
of eight randomised controlled trials, conducted in
individuals with no history of stroke, failed to show any
statistically significant association between intake of n-3
PUFAs and risk of fatal or non-fatal stroke (Briel et al.
2004).
Clearly, further clinical trials are required to confirm
or refute an association between unsaturated fatty acids
and risk of ischaemic and haemorrhagic stroke. In particular,
further studies are required to investigate the
influence of individual n-3 PUFAs on stroke risk and on
the different types of stroke.
Dietary fatty acids and the development
of CVD risk factors
Some of the beneficial effects of unsaturated fatty acids
on cardiovascular health can be explained by their influence
on established risk factors for CVD, e.g. blood lipids
and blood pressure.
Unsaturated fatty acids and blood lipoproteins Raised
blood cholesterol, particularly LDL cholesterol, is a
well-established risk factor for CHD; HDL cholesterol
concentrations are inversely associated with risk. Elevated
TAG concentrations are also associated with an
increased risk of CHD (Austin 1989; Assman et al.
1998).
Meta-analyses report that both MUFAs and, to a
greater extent, total PUFAs (i.e. n-3 and n-6 fatty acids
together), when substituted for SFAs in the diet, reduce
both total cholesterol and LDL cholesterol, and increase
HDL cholesterol (Mensink & Katan 1992; Clarke et al.
1997; Howell et al. 1997). An isocaloric substitution of
MUFA and total PUFAs for carbohydrate does not have
any influence on fasting TAG concentrations (Mensink
& Katan 1992).
n-6 PUFA: LA acts to lower total and LDL cholesterol
without influencing HDL cholesterol or TAG concentrations
(Mensink & Katan 1989). On occasion, MUFAs
have been preferentially recommended over n-6 PUFAs
as substitutes for SFAs in the diet. The rationale behind
these guidelines has been a belief that n-6 PUFAs effect
an undesirable reduction in HDL cholesterol. However,
a meta-analysis has concluded that a 1% energy substitution
of n-6 PUFAs, MUFAs and SFAs for carbohy-
198 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
drate, resulted in an increase in HDL cholesterol of
0.005, 0.006 and 0.013 mM and a change in LDL cholesterol
of -0.020, -0.008 and +0.013 mM respectively
(Fig. 9; Clarke et al. 1997). Similar effects were also calculated
in the meta-analysis of Mensink et al. (2003).
These data suggest that it is prudent to replace SFAs
with a mix of n-6 PUFAs and MUFAs in order to ensure
that an appropriate balance of fatty acids is consumed.
n-3 PUFA: A critical review of 65 trials indicated that
short-term supplementation of very high doses (7 g) of
long chain n-3 PUFAs does not influence total cholesterol
(Harris 1997). Although not significant, there was
a tendency for LDL and HDL cholesterol to rise, while
long chain n-3 PUFAs were shown to lower blood TAG
concentrations. Similar effects have been observed in a
population of Inuits in Greenland, who despite high
dietary fat intakes (especially high in n-3 PUFAs), had
lower TAG concentrations compared with the Danish
population (Dyerberg & Bang 1982; Bjerregaard et al.
1997). The n-3 PUFA, ALNA, acts in a similar way to
LA (i.e. lowers total and LDL cholesterol without influencing
HDL cholesterol). There is much interest in the
effect of the long chain n-3 PUFAs DHA and EPA on
blood lipoprotein concentrations, although the nature
of the effect is unclear and further studies are required.
There is more consensus in reported effects of EPA and
DHA on TAG concentrations; most published studies
reporting significant reductions at doses in the region on
4 g/day (Hamazaki et al. 1996; Grimsgaard et al. 1998;
Mori et al. 2000; Woodman et al. 2002; Buckley et al.
2004). Meta-analyses are clearly required once sufficient
randomised controlled trials have been conducted, to
determine the precise dose­response relationships
between intakes of long chain n-3 PUFAs and lipoprotein
concentrations.
Unsaturated fatty acids and blood pressure Elevated
blood pressure (hypertension) is another established risk
factor for CVD, although it predicts risk of stroke more
strongly than CHD. As blood pressure increases, so
does the CVD risk; in the Seven Countries Study for
every 10 mmHg rise in systolic blood pressure and every
5 mmHg rise in diastolic blood pressure, the risk of allcause
mortality rose by 28% in both normotensive and
hypertensive individuals (van den Hoogen et al. 2000).
MUFA: Several studies have investigated the influence
of MUFAs on blood pressure. Epidemiological studies
report an inverse association between MUFA intake and
blood pressure (e.g. Williams et al. 1987; Panagiotakos
et al. 2003; Psaltopoulou et al. 2004). Intervention studies
that have investigated the substitution of dietary SFA
with MUFA report a reduction in blood pressure (Mensink
et al. 1988). However, the extent of reduction was
not significantly different from that observed in individuals
fed a high-carbohydrate, low-fat diet. The current
view is that in healthy normotensive individuals,
increasing the proportion of MUFAs in the diet will have
only minor effects, if indeed any, on blood pressure.
n-6 PUFA: Few studies have investigated the influence
of n-6 PUFAs on blood pressure. Some studies report an
inverse association between intake and blood pressure
(Iacono et al. 1983; Folsom et al. 1996), while others do
not (Sacks et al. 1987). More recently, Iso et al. (2002)
reported an inverse association between serum LA concentrations
and blood pressure. However, there is very
little evidence from intervention studies. As with
MUFAs, it is unclear what effect n-6 PUFAs have on
blood pressure, and more research is needed in this area.
n-3 PUFA: Far more studies have investigated the
effect of the n-3 PUFAs on blood pressure, in an attempt
to identify how these fatty acids influence CVD risk in
light of their neutral effect on blood cholesterol. Such
studies suggest a blood-pressure-lowering effect of 2­
3 g/day long chain n-3 PUFAs in individuals with hypertension
(Appel et al. 1993; Morris et al. 1993; Geleijnse
et al. 2002). The effect of long chain n-3 PUFAs on
blood pressure in individuals with normal blood pressure
is less clear. Those studies that have looked at the
influence of DHA or EPA alone have tended to use
doses in the region of 4 g/day, or have reported conflicting
findings (Conquer & Holub 1998; Mori et al.
1999; Theobald et al. 2003). Clearly, further research is
required to determine the influence of low doses of individual
long chain n-3 PUFAs on blood pressure.
Unsaturated fatty acids and endothelial function
There has been much interest in the role of the endothelium
(the layer of cells lining the blood vessels) in
Figure 9 Change in the concentration of HDL- and LDL cholesterol when
1% energy as carbohydrate is replaced by that of n-6 PUFAs, MUFAs or SFAs
(Clarke et al. 1997). HDL, high density lipoprotein; LDL, low density
lipoprotein; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty
acid; SFA, saturated fatty acid.
­0.025
­0.02
­0.015
­0.01
­0.005
0
0.005
0.01
0.015
n-6 PUFAs MUFAs SFAs
Concentration(mM)
HDL Cholesterol LDL Cholesterol
The health effects of dietary unsaturated fatty acids 199
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
CVD over recent years (see Frayn & Stanner 2005). The
endothelium is a selective barrier between the blood and
the underlying tissue, which nutrients, solutes, hormones,
macromolecules and leukocytes (white blood
cells) can cross. The endothelium has many functions,
including: control of vascular homeostasis; maintenance
of blood flow through vessels in response to bloodborne
and locally produced chemical and physical stimuli;
regulation of vessel tone and haemostasis; and regulation
of coagulation and fibrinolysis and thrombosis.
It is thought that the loss of normal endothelial function
(endothelial dysfunction) is one of the earliest
stages of atherosclerosis. Endothelial dysfunction
describes impaired endothelium vasodilator responses
following exposure to an endogenous stimulus (vasodilatation
can also occur following the administration of
exogenous compounds, such as salbutamol or glyceryl
trinitrate, used to relieve the symptoms of angina pectoris).
It also describes altered endothelial permeability,
increased adhesion molecule expression and leukocyte
adhesion to the endothelium, increased thrombosis and
impaired fibrinolysis (see Sattar & Ferns 2005). Endothelial
dysfunction can occur following injury to the
endothelium; injury can be caused by raised blood cholesterol,
cigarette smoking, infection, hypertension,
inflammation, insulin resistance and diabetes mellitus.
Endothelial dysfunction has been observed in children
with hypercholesterolaemia and adults with risk factors
for CVD (see below) in the absence of atherosclerosis
(Celermajer et al. 1992). Furthermore, coronary endothelial
function has been shown to be a predictor of
atherosclerosis progression and coronary events
(Schächinger et al. 2000; Halcox et al. 2002). Diet is
known to modulate endothelial function (see Brown &
Hu 2001). Consumption of a high-fat meal has been
shown to impair endothelial function (Plotnick et al.
1997; Vogel et al. 1997), possibly through the increased
presence of TAG-rich particles, which have been suggested
to exert pro-oxidant effects.
MUFA: It has been suggested that MUFAs have beneficial
effects on endothelium-dependent dilatation as
determined by the measurement of markers of endothelial
function (see Sattar & Ferns 2005). Few studies have
investigated their influence in vivo. A MUFA-rich meal
has been shown to impair short-term endothelial function
in healthy subjects (Ong et al. 1999). However, in
the longer-term, beneficial effects of a MUFA-rich diet
have been reported. Fuentes et al. (2001) reported an
improvement in endothelial function in individuals with
hypercholesterolaemia receiving a MUFA-rich Mediterranean
diet compared with a diet high in SFAs. Similarly,
Esposito et al. (2004) reported beneficial effects of
a MUFA-rich Mediterranean diet in individuals with
metabolic syndrome.
n-6 PUFA: Correlations between concentrations of
individual PUFAs in plasma and endothelial function
suggest that higher concentrations of AA and dihomo--
linolenic acid are associated with endothelial dysfunction
(Pegge et al. 2001a). However, there are currently
no data available from intervention studies that support
this association.
n-3 PUFA: There is evidence to suggest that high
doses of n-3 PUFAs may have beneficial effects on
endothelial function, although this seems to be more
apparent in individuals already displaying CVD risk factors.
Both in vitro and in vivo studies looking at markers
of endothelial function support such an association (Seljeflot
et al. 1998; Johansen et al. 1999; Hjerkinn et al.
2005). Nestel et al. (2002) reported a beneficial effect of
both EPA and DHA on arterial compliance in dyslipidaemic
subjects at a dose of 3 g/day over a period of
7 weeks; greater benefit was seen with EPA.
Beneficial effects of long chain n-3 PUFAs have also
been observed on vessel wall resistance, implying an
improvement in endothelial function (Chin et al. 1993).
It has been reported that supplementation with 4 g/day
of n-3 PUFAs over a period of 4 months improved
endothelial function in hypercholesterolaemic individuals
(Goodfellow et al. 2000). A long-term intervention
study conducted in healthy male subjects reported that
2 g/day of ALNA over a period of 6 months, relative to
placebo, impaired endothelial function (Pegge et al.
2001b). On the other hand, Mori et al. (2000) noted a
benefit of both EPA and DHA at a dose of 4 g/day on
endothelial function in overweight, mildly hyperlipidaemic
men over a period of 6 weeks, with greater benefit
being observed with DHA. However, a recent study
conducted in healthy middle-aged subjects suggested
that moderate intakes of DHA did not result in any
improvement in endothelial function (H. Theobald
et al., British Nutrition Foundation, manuscript in preparation).
Thus again, further research is required to
determine the association between n-3 PUFAs and
endothelial function in the general population.
Unsaturated fatty acid and atherogenesis
Atherosclerosis, one of the key processes in the development
of CHD, is characterised by the accumulation of
lipid in the blood vessel walls. It is also a consequence of
persistent inflammation as atherosclerotic lesions contain
both inflammatory and smooth muscle cells. Diet
can influence the progression of atherosclerosis, i.e.
atherogenesis (Ross 1999).
200 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Animal studies suggest that both MUFAs and PUFAs
reduce atherogenesis, with two recent studies suggesting
that hamsters fed a MUFA-rich diet developed less early
atherosclerosis than hamsters fed a PUFA-rich diet
(Nicolosi et al. 2002, 2004). That said, further animal
studies point towards a reduction in the progression
of atherosclerosis with increased intakes of long chain
n-3 PUFAs (Weiner et al. 1986; Davis et al. 1987;
Mortensen et al. 1998). Few human studies have investigated
the influence of unsaturated fatty acids on the
progression of atherosclerosis, although it has been suggested
that n-3 PUFAs may be incorporated into atherosclerotic
plaques and thereby influence their stability,
thus influencing risk of thrombus formation (Rapp et al.
1991).
However, a recent systematic review of randomised
controlled trials investigating the impact of ALNA on
CVD risk markers reported that although supplementation
may cause a small decrease in fibrinogen and
plasma fasting glucose concentrations, most CVD risk
markers were not significantly affected. Indeed, the
authors concluded that there was insufficient evidence
to recommend dietary supplementation with ALNA to
reduce CVD risk (Wendland et al. 2006).
Unsaturated fatty acids and arrhythmia
An arrhythmia is a disturbance of the normal rhythm of
the heart. The heart normally beats 60­80 times a
minute. During arrhythmia, the heart rate becomes
abnormally rapid or slow, and/or irregular. Diseased
heart muscle is especially prone to periods of irregular
electrical activity; the subsequent arrhythmias are
potentially lethal and are often the cause of sudden cardiac
death. Arrhythmias can also be triggered when the
blood supply to the heart tissue is restricted. A restricted
blood supply can also result in the release of fatty acids
from cell membranes and thus, like the generation of
prostaglandins, the ratio of n-3 to n-6 fatty acids in the
membrane is important. In the case of arrhythmia, this
is even more pronounced as it seems that there is a preferential
release of n-3 PUFAs when they are present in
the membrane. This is of benefit as n-3 PUFAs appear to
protect against arrhythmias (O'Neill 2003). n-3 PUFAs
alter the electrical properties of the surface membrane of
the cell, raising the threshold for the generation of an
action potential. Therefore, any stimulus that could lead
to arrhythmia would have to be larger in order to exceed
the increased threshold (McLennan et al. 1992).
Evidence that demonstrates an anti-arrhythmic effect
in humans is mounting, although the picture is not yet
completely clear. Data published from a recent randomised
controlled trial suggest that daily supplementation
with fish oil does not reduce the risk of further
arrhythmia among patients with a recent episode of sustained
ventricular arrhythmia. Indeed, fish oil may even
be pro-arrhythmic in some patients (Raitt et al. 2005).
However, Geelen et al. (2005) have demonstrated that
daily supplementation with 1.5 g of n-3 PUFAs from fish
significantly decreases heart rate. Additionally, another
recent trial has reported that there is increasing evidence
that, for individuals at a high risk of fatal ventricular
arrhythmias, regular daily ingestion of fish oil fatty acids
may significantly reduce the risk of death (Leaf et al.
2005). In fact, the conclusions drawn from a recent
meta-analysis state that data from randomised controlled
trials are suggestive of a reduction in heart rate
following fish oil supplementation, which is especially
apparent in those individuals with higher baseline heart
rates (Mozaffarian et al. 2005a).
Unsaturated fatty acids and thrombogenesis
and fibrinolysis
Thrombogenesis is the process by which blood forms a
clot within intact blood vessels. Generation of a clot can
cause a heart attack or a stroke in an artery that is already
narrowed by atherosclerosis. Conversely, fibrinolysis is
the process whereby the fibrin clot is broken down. The
enzyme, plasmin, breaks up the fibrin mesh, leading to
the production of circulating fragments that are cleared
by other proteinases. The fibrinolytic system is activated
in parallel with the clotting system when a blood vessel
is damaged. Any factor that disturbs this natural balance
can produce a blood clot. Following an external `trigger'
to promote clot formation, fatty acids are released from
the platelet membrane and are converted into
eicosanoids (see What are unsaturated fatty acids?).
Diets rich in fish or fish oil have been associated with
decreased platelet aggregation and increased bleeding
time (see BNF 1999). This is believed to be due to higher
proportions of the weaker-acting eicosanoids (thromboxane
A2 and prostacyclin I3) formed from the n-3
PUFAs (Fig. 10). It is not certain whether unsaturated
fatty acids have any effect on components in the coagulation
cascade; a diet containing higher proportions of
MUFAs or PUFAs to SFAs may attenuate the acute procoagulant
effects of fatty meals (Roche et al. 1998; Kelly
et al. 2001). Similarly, there is little evidence confirming
the role of dietary fatty acids in fibrinolysis (see Frayn &
Stanner 2005). LA, EPA and the MUFA oleic acid
increase the transcription of a fibrinolytic inhibitor, plasminogen
activator inhibitor 1 (PAI-1) in vitro (Nilsson
et al. 1998). However, this effect has not consistently
The health effects of dietary unsaturated fatty acids 201
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
been observed in supplementation studies conducted in
vivo (Emeis et al. 1989; Hansen et al. 2000).
Concluding remarks
Associations between types of fat in the diet and CVD
are among the most convincing in all of nutritional epidemiology,
and it is universally accepted that a diet high
in saturated fatty acids will increase a person's risk of
suffering from some form of heart disease or stroke.
However, the influence that separate families of, or even
individual unsaturated fatty acids have both on the risk
of CVD and on development of its risk factors is beginning
to be appreciated. Increasing amounts of evidence
are now available for consideration for anyone attempting
to generate a consensus view on this issue, and the
relative importance that each type of study should be
given has been discussed.
Although not without critics, many studies seem to
support the idea that the long chain n-3 fatty acids
found in fish oils protect against fatal heart disease. This
has been suggested in cohort studies (e.g. the Nurses'
Health study), intervention trials with fish (e.g. DART
study) or interventions with fish oil supplements (e.g.
GISSI prevention trial). Manufacturers of products containing
pre-defined amounts of the long chain n-3
PUFAs are now able to make scientifically substantiated
claims related to a healthy heart (see Unsaturated fatty
acids and public health), and there is an increasing consumer
awareness of the cardiac benefits of including
these fatty acids in the diet. Questions are now being
raised as to the amount of these long chain n-3 PUFAs
that is required in the diet to gain the most benefit. Currently,
SACN has recommended intakes of 0.45 g per
day from oil-rich fish for the general population (SACN/
COT 2004). However, beneficial effects observed in secondary
prevention trials, i.e. those assessing the efficacy
of long chain n-3 PUFA supplementation to reduce the
risk of a secondary cardiac event in individuals diagnosed
with a heart condition, are at levels in the order of
1 g per day.
Alternative sources of n-3 PUFAs are plant oils, such
as linseed, rapeseed and nut oils, which are rich in the
`parenť n-3 PUFA ALNA. ALNA can theoretically be
elongated to DHA and EPA, although there are suggestions
that this pathway is not efficient enough to produce
EPA and DHA in sufficient quantities (Burdge &
Calder 2005a, 2005b; see What are unsaturated fatty
acids?). Vegetarians, who refrain from consuming fish,
will clearly be obtaining all their dietary long chain n-3
PUFA from this route. As a group, vegetarians experience
lower CVD rates than the general population,
similar to those seen in populations consuming large
amounts of oil-rich fish. Although there are other lifestyle
factors associated with being a vegetarian that protects
against CVD, there is increasing interest in the
health benefits of ALNA. As mentioned earlier, there is
conflicting evidence of the effect of ALNA supplementation
on CVD incidence from cohort studies (Wendland
et al. 2006), although this is clearly an interesting
hypothesis, and more studies are required to determine
what, if any, association exists.
Meanwhile, evidence of an effect of the n-6 PUFAs,
including LA, on CVD risk is strong and consistent.
Although many of the data are derived from trials conducted
decades ago, there has been little argument that
n-6 PUFAs favourably alter the concentrations of LDLand
HDL cholesterol, thus reducing CVD risk.
Finally, returning to the initial assertion that a diet
high in saturated fatty acids will increase a person's risk
of suffering from some form of heart disease or stroke,
we now appreciate that certain SFAs may not be as
atherogenic as was previously thought. Contrary to
expectation, blood cholesterol concentrations appear to
decrease when stearic acid is fed compared with other
SFAs. This may be a result of stearic aciďs direct effects
on cholesterol absorption and excretion, or may come
about by some unknown mechanism (Berry & Sanders
2005). This is a clear illustration of the advances that
are possible in tailoring specific diets as our understanding
of disease mechanisms and the individual nutrient
components of food increases.
4.2 Unsaturated fatty acids and diabetes
There are two major types of diabetes mellitus: type 1
and type 2 diabetes. Both are characterised by raised
Figure 10 Formation of eicosanoids from n-6 and n-3 PUFA;their effects on
platelet aggregation and the diameter of blood vessels (adapted from BNF
1999). AA, arachidonic acid; EPA, eicosapentaenoic acid; PUFA,
polyunsaturated fatty acid.
2
3
2
3
Inhibits platelet
aggregation.
Relaxes blood
vessels
Prostacyclin I220:4 n-6
AA
cells
Inhibits platelet
aggregation.
Prostacyclin I320:5 n-3
EPAEndothelial
Stimulates platelet
aggregation
(strong). Narrows
blood vessels
(strong).
Thromboxane A220:4 n-6
AA
Weak effect on
platelet aggregation.
Narrows blood
vessels.
Thromboxane A320:5 n-3
EPA
Platelets
202 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
blood glucose concentrations due to either a lack (type
1) or reduced action, or a lack (type 2) of the hormone
insulin. As unsaturated fatty acids are capable of affecting
a number of different metabolic pathways, it is not
surprising that much work has been conducted investigating
the effect of unsaturated fatty acids on the body's
response to glucose.
Individuals with diabetes are at a two- to fourfold
increased risk of CVD. Consequently, dietary management
of diabetes involves maintaining both blood glucose
and blood lipid concentrations at as near normal
levels as possible to reduce the possibility of associated
complications developing. As with individuals without
diabetes, elevated LDL cholesterol increases risk of the
formation of fatty deposits in the blood vessels, and this
affects CVD risk. MUFAs and n-6 PUFAs have similar
qualitative effects on the concentrations of circulating
TAGs and LDL- or HDL cholesterol in individuals with
diabetes as in individuals without diabetes, resulting in
reduced CVD risk (Berry 1997; Ros 2003). Conversely,
the n-3 PUFAs have a favourable effect on TAG concentrations
but no effect on total, LDL- or HDL cholesterol
in individuals with diabetes, so do not modulate CVD
risk by this mechanism (MacLean et al. 2004). However,
as in individuals without diabetes, n-3 PUFAs
result in an improvement in other risk factors for CVD,
such as the blood is less likely to clot, blood pressure is
reduced and protects against ventricular arrhythmias
(see Unsaturated fatty acids and cardiovascular disease).
To prevent other complications of diabetes, e.g. diabetic
neuropathy and retinopathy, it is necessary to regulate
blood glucose concentrations (Diabetes UK 2006).
Excessive intake of fats leads to an accumulation of
TAGs in many tissues. This can bring about a number of
metabolic disturbances, ultimately resulting in hyperglycaemia
(Fig. 11). Dietary management of diabetes
includes the recommendation to adopt a `low fať diet,
although the levels of intake of fat are not essentially
very different from those recommended for the general
population (Table 14). SFAs should provide less than
10% of total daily energy. SFAs impair insulin sensitivity,
possibly because the presence of TAGs containing
SFAs in muscle cell membranes reduces the amount of
glucose that is taken up from the bloodstream when the
concentration of insulin is raised (Montell et al. 2001).
However, there is now much interest in the fatty acid
profile of the diet and the effect that this can have on
insulin sensitivity. A low-fat diet (21% energy from fat)
and a high-MUFA diet (35% energy from fat) appear to
afford similar glycaemic control (e.g. Luscombe et al.
1999). This was assessed by fasting glucose concentrations
and glycosylated haemoglobin (a marker of longerFigure
11 The metabolic effects of circulating fatty acids on glycaemic
control.TAG, triacylglycerol.

TAG accumulation
in non-adipose
tissue
PANCREAS
Impaired insulin resistance
-cell dysfunction
ADIPOCYTE
TAG stores
lipolysis 
MUSCLE
lipid uptake and TAG storage
-oxidation
LIVER
glucose output
insulin clearance
Raised circulating fatty
acids
Key points:
Unsaturated fatty acids and cardiovascular disease
* CVD, characterised by hardening and narrowing of blood vessels and/or the development of blood clots, is one
of the leading causes of mortality and morbidity worldwide.
* The precise mechanisms by which unsaturated fatty acids reduce CVD risk are as yet unclear. Numerous mechanisms
whereby dietary fatty acids could influence the progression of CVD and its risk factors have been identified.
These include effects on blood lipid levels, blood pressure, inflammatory response, arrhythmia and endothelial
function, along with many other effects, both known and as yet undefined.
* An elevated plasma LDL cholesterol concentration is a well-established risk factor for CVD. Replacing SFAs by
either MUFAs or n-6 PUFAs reduces LDL cholesterol, thus reducing the risk of CVD. Unsaturated fatty acids, such
as LA or MUFAs, also raise HDL cholesterol, which assists in the removal of TAGs from the bloodstream. So it is
prudent to replace SFAs with a mix of n-6 PUFAs and MUFAs in order to ensure that an appropriate balance of
fatty acids is consumed.
* There is strong supportive, but not yet conclusive evidence that long chain n-3 PUFAs found in fish oils protect
against fatal heart disease, and population-wide dietary recommendations have been made to support this.
* Evidence is mounting on the role that the n-3 PUFA ALNA may play in preventing the progression of CVD,
although it is currently unclear what, if any, association exists between ALNA intake and CVD risk.
The health effects of dietary unsaturated fatty acids 203
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
term glycaemic control). In light of similar findings
reported by other researchers, it has been suggested that
provided the amount of SFAs in the diet is low, a highMUFA
diet has a similar effect on glycaemic control as
a high-carbohydrate/low-fat diet, and may confer some
additional improvement in CHD risk factors (see Ros
2003). However, it has been demonstrated that a lowfat,
high-complex carbohydrate diet caused weight loss
in individuals with type 2 diabetes, which was not
observed in individuals fed a high-MUFA diet (Gerhard
et al. 2004). The low-fat diet did not cause the plasma
TAG concentrations to increase and did not worsen glycaemic
control. Thus, the researchers concluded that
such diets may be very useful in the dietary management
of type 2 diabetes due to the improvement in metabolic
control known to occur when excess weight is lost (Gerhard
et al. 2004). Again, it is clear that more research is
needed in this area to determine whether the ratio of
unsaturated fatty acids is an important consideration
when recommending low-fat diets to individuals with
diabetes.
4.3 Unsaturated fatty acids and cancer
Approximately 30% of all human cancers may be influenced
by diet, lifestyle and physical activity, although
the estimate lies somewhere between 10% and 80%
(Doll & Peto 1981). Diet is considered to be a major
determinant of risk for certain cancers, such as colorectal
cancer, where the aetiology is well understood and it
is evident that along with physical activity, diet plays a
key role. However, for cancers at other sites, such as
lung cancer, diet plays a relatively small part in determining
the likelihood that an individual will develop the
disease, and other factors, including smoking, are better
predictors of risk. To date, very few definite relationships
between dietary factors and cancer risk have been
established; however, this has not stopped numerous
foods and food components being branded the new
`superfooď against cancer. In most cases, the strength of
the message portrayed by the media and some health
professionals is greater than the strength of the evidence
associating diet with cancer risk.
Historically, dietary fat has been considered to be one
of the main dietary risk factors, and has been reported
to influence the risk of developing breast, colon and
prostate cancers (WHO 1990). Evidence for this association
has mainly arisen from comparisons of cancer
incidence rates between populations with different
dietary habits (ecological studies); rates being higher in
the Western world where intakes of fat, often estimated
from food balance sheets, are greater (Shike et al. 1990).
This is a very imprecise method of detecting diet­disease
interactions as there are many confounding factors and
their effects are often not taken into account. Thus, the
observed association between high fat intakes and
increased cancer risk may not be causal. Following publication
of more sensitive epidemiological studies, as
well as laboratory-based experimental studies, the conTable
14 European Recommendations of the Diabetes Nutrition
Study Group related to dietary fat
Saturated and trans-unsaturated fatty acids should provide under 10% total
daily energy. A lower intake (<8% energy) may be beneficial if LDL
cholesterol is elevated.
Oils rich in MUFAs are useful fat sources and depending on individual
preferences, MUFA may provide 10­20% of total energy, provided that
total fat intake does not contribute more than 35% of total energy.
PUFAs should not exceed 10% of total daily energy.
Total fat intake should not exceed 35% of total energy.
For those who are overweight, fat intake below 30% may facilitate weight loss.
Consumption of two to three servings of fish (preferably oil-rich fish) each
week and plant sources of n-3 PUFAs (e.g. rapeseed oil, soybean oil, nuts
and some green leafy vegetables) will help ensure an adequate intake of n3
PUFAs.
Cholesterol intake should not exceed 300 mg/day and be further reduced if
LDL cholesterol is raised.
Source: Mann et al. (2004).
LDL, low density lipoprotein; MUFA, monounsaturated fatty acid; PUFA,
polyunsaturated fatty acid.
Key points:
Unsaturated fatty acids and diabetes
* Fatty acids have an effect on a number of different metabolic pathways, including those involved with glycaemic
control.
* Dietary recommendations for individuals with diabetes are to consume a low saturated fat diet because of the
increased risk of developing CVD on diets high in SFAs.
* High-MUFA diets have been associated with improvements in glycaemic control. However, currently there is
insufficient evidence to make dietary recommendations.
204 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
sensus view has drifted towards the possibility of there
being an association rather than judging the evidence to
be convincing (see Table 15; WHO/FAO 2003).
Cancer is a complex disease requiring multiple gene
mutations to occur, usually over many decades (carcinogenesis).
Certain fatty acids have the ability to prevent
the formation of, inhibit the progression of, or directly
kill cancer cells in vitro when they are taken from a
number of organs (lung, breast, colon, and UV-induced
cancer). However, other fatty acids can also promote
carcinogenesis, making the mechanism behind any possible
association between total dietary fat and cancer
more ambiguous.
MUFAs: The work of Keys et al. (1986) established
that the major explanatory factor for the differences in
cancer rates seen in the regions bordering the Mediterranean
Sea was the plant-based Mediterranean diet. Trichopoulou
et al. (2000) estimated that up to 25% of
new colorectal cancer cases, 15% of new breast cancer
cases and 10% of new prostate cancer cases could be
prevented if `Western' countries adopted a Mediterranean-style
diet, i.e. a diet rich in fruit, vegetables, fish,
legumes, whole grains and, most notably, oleic acid-rich
olive oil. Because of this, it was thought that MUFAs
might have a protective effect against the development
of cancers. In vitro studies have suggested that MUFAs
reduce the occurrence of molecular biomarkers typically
associated with carcinogenesis, e.g. lipid peroxidation
damage or oxidative stress. However, the Mediterranean
diet is different from a traditional Western diet for
more reasons than solely its MUFA content. Intakes of
fruit, vegetables and whole grains are significantly
higher in the countries bordering the Mediterranean,
and thus there might be other components of the diet or
even the lifestyle that are bringing about the observed
health benefits. This discrepancy is evident in the lack of
any distinct evidence associating MUFA intakes or
serum concentrations with a significant reduction in
cancer incidence rates.
The 1997 report of the World Cancer Research Fund
(WCRF 1997), entitled Food, Nutrition and the Prevention
of Cancer: A Global Perspective, concluded that
there was a small amount of evidence that MUFAs
might influence cancer risk based on the strength of the
evidence from epidemiological, intervention and experimental
studies.
PUFAs: The role of PUFAs in affecting cancer risk is
even less clear. Experimental, laboratory-based studies
suggest that PUFAs can act as tumour promoters. PUFAs
are susceptible to oxidation, which also generates free
radicals that can then go on to damage DNA. In contrast
with these lab-based and animal studies, studies in
humans have found little evidence of any association
between intake of polyunsaturated or vegetable fat and
risk of cancer, especially at recommended intake levels
(e.g. Hunter & Willett 1993; Giovannucci & Willett
1994). However, this is not always the case (Pearce &
Dayton 1971), and so in spite of this generally reassuring
evidence and the `no effecť conclusion of a review
and meta-analysis on this issue (Zock & Katan 1998),
many within the scientific community are still concerned
that high intakes of PUFAs may increase the risk of
cancers.
With recent interest in specific families of, or even
individual fatty acids, associations between cancer incidence
and estimated intakes or plasma concentrations of
these fatty acids are being investigated. Without doubt,
this adds confusion as studies are often not large enough
or designed well enough to detect such specific associations
and as a result, a number of contradictory findings
have been published. It would be prudent to mention
that currently, in the opinion of the WCRF (1997), the
UK's Department of Health (DH 1998) and the World
Health Organization/Food and Agriculture OrganisaTable
15 Summary of the evidence linking dietary factors with cancer at all sites
Evidence Decreased risk Increased risk
Convincing Physical activity (colorectum) Overweight and obesity (oesophagus, breast, endometrium, kidney);
alcohol (oral cavity, pharynx, larynx, oesophagus, liver, breast); aflatoxin
(liver); Chinese-style salted fish (nasopharynx)
Probable Fruit and vegetables (oral cavity, stomach, colorectum);
physical activity (breast)
Preserved meat (colorectum, oesophagus); salt-preserved foods and salt
(stomach); very hot drinks and food (oral cavity, pharynx, oesophagus)
Possible/insufficient Fibre; soya; fish; n-3 fatty acids; carotenoids; vitamins
B2, B6, folate, B12, C, D, E; calcium; zinc, selenium,
non-nutrient plant constituents (e.g. allium, lignans,
flavonoids, isoflavones)
Animal fats; heterocyclic amines; polycyclic aromatic hydrocarbons;
nitrosamines.
Source: WHO/FAO (2003).
Bold, unsaturated fatty acids.
The health effects of dietary unsaturated fatty acids 205
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
tion (WHO/FAO 2003), there is not enough evidence to
make recommendations on the intake of specific fatty
acids as a means of preventing cancer.
When cancer incidence rates are compared between
countries with very different intakes of particular fatty
acids, there is a clear suggestion that fish consumption,
providing a source of the long chain n-3 PUFAs,
decreases cancer risk (Fernandez et al. 1999). However,
this is one of the least sensitive types of studies that can
be conducted as there are so many differences inherent in
the populations that cannot be properly accounted for.
Over time, increasing numbers of case­control or cohort
studies that are assessing differences in breast (e.g. GagoDominguez
et al. 2003), prostate (e.g. Sonoda et al.
2004) and colorectal cancer incidence (e.g. Tokudome
et al. 2006) in subsets of the population exposed to varying
amounts of n-3 PUFAs are being published. Nevertheless,
there is still no consistent consensus on the effect
of n-3 PUFA, and no dietary recommendations have
been made in the context of cancer prevention.
There is very little or no evidence associating intakes
of n-6 PUFAs (AA or LA) with prostate cancer (Astorg
2004), colorectal cancer (Nkondjock et al. 2003) or
breast cancer (Kohlmeier 1997) when actual intakes in
whole populations are considered. There is certainly laboratory-based
experimental evidence showing effects on
cancer cell growth (e.g. Bartsch et al. 1999; Guthrie &
Carroll 1999), or tumour formation in animals, but this
cannot be extrapolated to the general population and certainly
is insufficient to make dietary recommendations.
4.4 Unsaturated fatty acids and inflammatory
conditions
Inflammation is a non-specific response to tissue damage.
It occurs to protect the tissue from further damage
and so, under normal circumstances, is a desirable
event. However, if the response is exaggerated, misdirected
or long-term, inflammatory conditions can lead
to further tissue damage. As mentioned previously,
eicosanoids are produced from EPA or AA, which are
released from the cell membrane phospholipids. The
eicosanoids derived from AA, including prostaglandin
E3 and leukotriene B5, are more inflammatory than those
produced from EPA. Thus a shift in the balance of EPA
and AA in the membrane phospholipids might affect the
inflammatory response, leading to either a more pro(AA)
or anti-inflammatory (EPA) environment (Calder
1998). There are, however, other mechanisms that have
been suggested that exert their effects either downstream
of altered eicosanoid production or are independent
of this. Such mechanisms include a suppression of
the production of pro-inflammatory cytokines or modulation
of adhesion molecule expression. In many
instances, these effects occur as a result of altered gene
expression (see Calder 2005).
There are a number of inflammatory conditions, such
as asthma, Crohn's disease or arthritis, which could
potentially be alleviated by dietary modification. This is
of great interest to individuals living with these chronic
conditions as many are unhappy with the prospect of a
lifetime of drug treatment. Observational epidemiological
studies have highlighted a low incidence of chronic
inflammatory or autoimmune disorders in populations
of native Greenland Inuits and in Japan, both of which
have a high dietary intake of long chain n-3 PUFA from
seafood (e.g. Takemura et al. 2002; Backer et al. 2004).
Researchers have been assessing the efficacy of long
chain n-3 PUFAs in fish oil and n-6 PUFAs found in sunflower
oil and evening primrose oil. Very little research
has been conducted using MUFAs. In general, the fatty
acid composition of cell membranes can be altered by
both the n-3 and the n-6 PUFAs tested, and this results
in reduced inflammatory activity. However, whether this
effect brings about a significant reduction in clinical
symptoms is still unclear.
Asthma
Asthma is a disease in which the circular smooth muscles
lining the air tubes of the lung are liable to go into
Key points:
Unsaturated fatty acids and cancer
* Unsaturated fatty acids, namely, n-3 PUFAs and MUFAs, may be associated with a reduced risk of developing certain
cancers, including cancers of the colon, breast and prostate.
* However, the level of evidence is not deemed sufficient by authoritative bodies, such as the WCRF, WHO and the
Department of Health, to make any specific dietary recommendations on individual fatty acids and cancer risk.
* Instead, it is prudent to eat a healthy balanced diet that contains plenty of fruit, vegetables and high-fibre, starchy
foods, and to try to keep to a healthy weight.
206 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
a state of spasm. When this occurs, the airway is narrowed
and breathing becomes difficult. Breathing may
be worsened by the excess mucus secretions from the
cells lining the lungs. Bronchospasm may be induced by
numerous stimuli, including allergic reaction, infection
or exertion. The leukotrienes and prostaglandins are
implicated in the inflammatory cascade that occurs in
asthmatic airways and therefore, as the nature of these
eicosanoids are known to be influenced by diet, there
may be the potential for dietary management. However,
intervention trials to date have been shown little
improvement in the clinical manifestation of this disorder.
Because of the formation of pro-inflammatory
eicosanoids from the n-6 PUFAs, it has been hypothesised
that the ratio of n-6 to n-3 PUFAs in the diet will
be important. Broughton et al. (1997) studied the ability
of dietary PUFAs at various ratios of n-6 to n-3 in an
asthmatic population to ameliorate respiratory distress.
Low n-3 ingestion is reported to increase respiratory distress
during an asthma attack. However, beneficial
effects of n-3 PUFAs were not observed in all individuals
who received the supplement. Instead, respiratory
improvements were only observed in people with a measurable
altered leukotriene excretion.
Clinical intervention studies have provided conflicting
results, most likely due to lack of an adequate number of
subjects in some and not taking into consideration the
background diet or genetic variation. There is a clear
need for more carefully designed and controlled clinical
trials in the therapeutic application of high doses of n-3
fatty acids for the management of asthma (Simopoulos
2002).
Inflammatory bowel disease
Crohn's disease and ulcerative colitis, collectively
known as inflammatory bowel disease (IBD), are related
but distinct complex disorders with immunologic, environmental
and genetic components. Crohn's disease is a
long-term illness that causes inflammation in the gut. It
can affect any part of the digestive system from the
mouth to the anus. The parts most often affected are the
ileum and the colon. Symptoms of Crohn's disease
include: diarrhoea; abdominal pain; fever; weight loss;
and a general feeling of being unwell. It is unknown
which factors might trigger the inflammatory response.
Ulcerative colitis affects the colon and rectum. Like
Crohn's disease, it is unknown exactly what triggers
ulcerative colitis, but it is most common in young and
middle-aged adults. It is characterised by chronic
inflammation and ulceration of the gastrointestinal
lining that can lead to anaemia, toxic megacolon (a lifethreatening
complication of intestinal conditions characterised
by a very inflated colon), or colorectal cancer.
Many studies have reported the effect of n-3 PUFA supplementation
on certain clinical outcomes, including sigmoidoscopic
score, histologic score, induced remission,
and relapse in IBD patients (Endres et al. 1999).
When the combined effect from a number of intervention
studies was assessed by meta-analysis, it was
determined that n-3 PUFAs had no effect on the relative
risk of relapse in ulcerative colitis patients. There was,
however, a statistically non-significant reduction in
requirement for corticosteroids for individuals receiving
n-3 PUFAs relative to placebo. No studies assessed in
this meta-analysis evaluated the effect of n-3 fatty acids
on requirement for other immunosuppressive agents
(MacLean et al. 2005). Relapse rates in patients with
Crohn's disease reduced substantially over a 12-month
period, during which patients received a fish oil supplementation
(Belluzzi et al. 1996).
Although these findings are promising, there have not
been sufficient studies to warrant a dietary recommendation
regarding the use of n-3 PUFAs in the management
of IBD and indeed, management of this condition
would require supplementation at doses far exceeding
those that could be obtained by increasing oil-rich fish
in the diet. It is clear that further, larger-scale intervention
trials are required before such advice can be given
to IBD patients.
Arthritis
Arthritis describes a condition involving the inflammation
of the joints. There are more than 200 different
types of arthritis, including rheumatoid arthritis, gout
and ankylosing spondylitis. The most common form is
osteoarthritis (degenerative arthritis). This is caused by
general wear and tear of the joints and is unaffected by
diet. Rheumatoid arthritis is an inflammatory condition
and occurs when the body's immune system starts to
destroy the joint lining. Due to the involvement of
inflammatory eicosanoids in the aetiology of the disorder,
diet may be a potential therapeutic agent.
Ecological studies suggest that there are lower rates of
incidence of rheumatoid arthritis in populations consuming
large amounts of fish, e.g. the Japanese population
(Pattison et al. 2004). The protective effect of a
dietary factor is made even more likely when it is considered
that the Japanese population harbours a particular
genetic polymorphism that confers susceptibility to
rheumatoid arthritis (James & Cleland. 1997). Similar
protective effects were reported by a case­control study
investigating the occurrence of the disorder in a group of
The health effects of dietary unsaturated fatty acids 207
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Japanese women (Kremer et al. 1985). There have been
no studies examining the effect of fish or n-3 PUFA
intakes on the incidence of rheumatoid arthritis. However,
several studies have reported on the effect of
dietary n-3 PUFAs as a treatment for established rheumatoid
arthritis.
A recent review of nine intervention trials has
reported various clinical outcomes in patients with
rheumatoid arthritis (MacLean et al. 2004). Supplementation
with 1­7 g of n-3 PUFAs a day had no significant
effect on patient report of pain or swollen join
count, i.e. there was very little clinical improvement in
the symptoms. However, some studies have reported a
reduced requirement for corticosteroid or anti-inflammatory
drugs, although this did not reach the level
required for statistical significance (Kremer et al. 1995).
Overall, the available data are insufficient to draw conclusions
about the effectiveness of n-3 PUFAs in the
treatment of arthritis (MacLean et al. 2004). An interesting
new approach to the dietary management of
rheumatoid arthritis is to consider a combination of
fatty acids. A small-scale randomised controlled trial in
only 43 patients reported by Berbert et al. (2005) suggested
that long chain n-3 PUFA supplementation, in
conjunction with MUFAs, may be an alternative dietary
treatment for rheumatoid arthritis. Clearly, more trials
are needed to determine whether this is in fact a significant,
reproducible effect, but is an intriguing example
of how it may be a combination rather than individual
fatty acids that are involved in the pathologies of these
inflammatory diseases.
4.5 Unsaturated fatty acids in fetal and infant
development
The developing brain grows most rapidly during the
third trimester of pregnancy and during infancy.
Although different types of brain cell, such as glial cells,
astrocytes and cerebral endothelium, can elongate and
desaturate precursor EFAs, the mother is the main
source of AA and DHA that accumulates in the developing
brain. It is therefore important that there is an
adequate supply of the long chain n-3 PUFAs to the
mother during this time to support normal growth, neurological
development and cognitive function of the
growing fetus (Al et al. 1995).
If dietary intake is low, maternal body stores can be
mobilised. AA requirements are likely to be met as there
is plenty of LA, its precursor, in adipose tissue. However,
there is less ALNA, and thus there is a reduced capacity
for synthesis of the long chain n-3 PUFAs DHA and
EPA. The PUFA status of the infant is highly correlated
with that of the mother (Smita et al. 2000). During pregnancy,
EFA concentrations in the mother's blood have
been shown to fall by approximately 40%, with a concurrent
increase in concentrations of the non-EFAs, as
body stores are mobilised and depleted (Al et al. 1995).
When more than one fetus is developing in the womb,
the DHA status of each child is low when measured
after birth. This is thought to be because the additional
demands on the mother's EFA supply cannot be met
adequately. Furthermore, the DHA concentration in the
mother's plasma decreases after closely spaced pregnancies.
Thus, pregnancy is a time when additional supplies
of long chain n-3 PUFAs may be of benefit to some
women to ensure an adequate supply of long chain n-3
PUFAs to the mother and the baby. Ideally women
should enter pregnancy well nourished in this respect,
having consumed moderate amounts of these fatty acids
on a regular basis as part of a healthy balanced diet.
This is because there is a possible risk of heavy metal or
dioxin contamination of both oil-rich fish and fish oil
supplements, which at this especially vulnerable period
may affect the development of the unborn child (Hornstra
et al. 1995). Thus, recommendations exist about
the need to restrict intakes of oil-rich fish in women of
Key points:
Unsaturated fatty acids and inflammatory conditions
* There are a number of inflammatory conditions, such as asthma, Crohn's disease and arthritis, that could potentially
be alleviated by dietary modification.
* The fatty acid composition of cell membranes can be altered by both n-3 and n-6 PUFAs, and this results in
reduced inflammatory activity. However, whether this effect brings about a significant reduction in clinical symptoms
is still unclear.
* There is a clear need for more carefully designed and controlled clinical trials in the therapeutic application of
unsaturated fatty acids for the potential management of inflammatory conditions.
* To date, beneficial effects are only observed with very high intakes of unsaturated fatty acids, which would realistically
only be achievable by supplementation.
208 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
child-bearing age to up to 2 servings a week, which is
considerably in excess of current average intakes (see
Unsaturated fatty acids in the UK diet). Also fish oil supplements
often contain added vitamin A, which is contraindicated
for pregnant women, based on teratogenic
risks associated with retinol.
The long chain n-3 PUFA status of the mother is of
interest as low intakes are believed to be associated with
premature delivery and low birthweight. This has been
observed in a number of different populations assessed
for fish intake, seafood intake and supplement use in
mothers (Allen & Harris 2001; Olsen & Secher 2002;
Oken et al. 2004). A possible mechanism by which long
chain n-3 PUFAs might affect these factors is by altering
the concentrations and types of the different prostaglandins
that are involved in parturition. Alternatively, long
chain n-3 PUFAs may bring about an improvement in
blood flow to the placenta, resulting in more efficient
transfer of nutrients from the mother to the fetus (Allen
& Harris 2001).
After birth, the unsaturated fatty acid status of the
infant also seems to be important. DHA and AA are
present in human milk at fairly consistent concentrations
(0.02 g/100 g), although women from populations
that consume diets rich in the long chain n-3 PUFAs produce
milk containing higher amounts of DHA (see BNF
1992). It is unlikely that the endogenous synthesis of
DHA and AA from ALNA and LA respectively, is able
to meet the requirements of the growing infant, thus
most of these long chain n-3 PUFAs must, at this stage,
be provided by the diet.
Infant formulas with fat derived from vegetable oil do
not contain appreciable amounts of the long chain
PUFAs (DHA and AA), and infants fed these conventional
formulas have lower plasma AA and DHA
concentrations than breastfed babies (Makrides et al.
1995). Supplementing formulas with long chain PUFAs
increases plasma concentrations and also the proportion
of DHA localised in the brain cortex (Makrides et al.
1994). Some studies using these supplemented formulas
have reported adverse effects, such as reduced post-natal
growth, when only DHA was added to the feed (Jensen
et al. 1997) but, as long as the formula provides an adequate
and balanced supply of both AA and DHA or
ALNA, there should be no adverse effects on growth
(Koletzko et al. 2001).
DHA is present in high concentrations in the phospholipids
of retinal cell membranes; hence it is believed
that the DHA intake is associated with visual function.
This is borne out by the observation of Jorgensen et al.
(2001) that there is a positive association between
DHA in human milk and sharpness of sight (visual acuity)
during infancy. As mentioned earlier, DHA and AA
are also required for healthy neural cell development,
and it has been suggested that DHA and AA intakes
during infancy may affect cognitive function. Research
in this area is still highly speculative, and some smallscale
studies have found a positive association
(McCann & Ames 2005; also see Unsaturated fatty
acids and cognitive function and behaviour). However,
two fairly recent cohort studies have found no association
between DHA or AA concentrations measured in
plasma from the umbilical vein and cognitive function
at ages 4 or 7 years (Ghys et al. 2002; Bakker et al.
2003).
In summary, there is moderate evidence that PUFAs,
and long chain n-3 PUFAs in particular, from either
breastmilk or supplemented infant formula, are beneficial
in the development of visual acuity and possibly
cognitive performance in infants (Bryan et al. 2004).
Adequate provision of the long chain PUFAs is required
throughout pregnancy and early infancy, in order to
Key points:
Unsaturated fatty acids in fetal and infant development
* It is important that pregnant women have an adequate supply of the long chain n-3 PUFAs before and throughout
pregnancy to support normal growth, neurological development and cognitive function of the growing fetus. As n6
PUFAs are more abundant in the diet, achieving an adequate intake is less problematic.
* The PUFA status of the infant is highly correlated with that of the mother.
* Increasing fish consumption beyond two servings of oil-rich fish per week or relying on fish oil supplementation
is not appropriate during pregnancy due to the potential problems associated with heavy metal contamination of
fish, or the high vitamin A levels in some fish oil supplements.
* The increased requirements for DHA and AA during pregnancy and lactation will not be met solely by endogenous
synthesis from ALNA and LA; dietary supply is also important.
* Breastmilk is a source of DHA and AA, and PUFA-supplemented infant formulas are now available.
* It is possible that the EFA status of the baby may affect visual acuity and cognitive performance during infancy.
The health effects of dietary unsaturated fatty acids 209
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
provide sufficient DHA and AA for both the growing
baby and the mother.
4.6 Unsaturated fatty acids and cognitive function and
behaviour
Cognitive function
The brain is not fully developed until late adolescence
when children can start reasoning like adults. However,
the high DHA and AA concentrations in the brain must
be maintained throughout life to ensure proper development
and functioning of the central nervous system.
Most research on the effect of DHA and AA in the
development of cognitive function has focused on preterm
infants, with some studies demonstrating beneficial
effects on mental development and problem-solving
ability (Willatts et al. 1998; Birch et al. 2000). Controlled
intervention trials assessing improvements in
older children have been limited to a single study of children
with well-defined behavioural disorders. In this
case, preliminary associations have been made between
low fatty acid intakes and poor reading ability
(Richardson & Montgomery 2005).
Epidemiological evidence suggests that dietary consumption
of EPA and DHA, commonly found in
fish or fish oil, may modify the risk for certain degenerative
or neuropsychiatric disorders. As evidence,
decreased blood concentrations of n-3 fatty acids have
been associated with several neuropsychiatric conditions,
including Alzheimer's disease, schizophrenia and
depression (see Rogers 2001). Supplementation studies,
using individual or combinations of n-3 PUFAs, suggest
the possibility of decreased symptoms associated with
some of these conditions. Thus far, however, the benefits
of supplementation, in terms of decreasing disease
risk and/or aiding in symptom management, are not
clear, and more research is needed (Young & Conquer
2005).
Any possible effect on brain function and cognitive
development is not limited to PUFAs. The Mediterranean
dietary pattern, based on complex carbohydrates,
fibre and non-animal fat, appears to be associated with
some degree of protection against age-related cognitive
decline. A clear reduction in risk of decline in cognitive
function has been found only in population samples
with very high intakes of MUFA from olive oil (>100 g
of olive oil per day). However, whether this effect of
olive oil is attributable exclusively to the high MUFA
intake or to the concomitant presence of other bioactive
food components, such as the antioxidant vitamins or
polyphenols, or indeed other aspects of the diet or lifestyle
of such individuals, remains to be clarified (Panza
et al. 2004).
Behaviour
Research in this area is still highly speculative, not least
because of the difficulties faced when assessing improvements
in behaviour. However, behavioural disorders
with well-defined aetiologies, such as attention deficit
hyperactive disorder (ADHD), dyslexia, autism and dyspraxia,
are possibly associated with errors of fatty acid
metabolism. It is proposed that such errors may include:
inefficient conversion of simple EFAs into longer chain
EPA and DHA; unusually rapid breakdown or loss of
these fatty acids; and problems in recycling, transporting
and incorporating these long chain n-3 PUFAs into
cell membranes (Richardson & Ross 2000).
There is very limited published empirical evidence for
the beneficial effects of PUFAs on cognitive performance
in children or adults. The research in this field, especially
that concerning younger children, looks promising, but
to date there have been very few published studies, and
those that have been published, have tended to be smallscale
studies, all with very different study methodologies.
For example, plasma concentrations of long chain
n-3 PUFAs were reported to be significantly lower in a
study of hyperactive children compared with controls
(Stevens et al. 1995). Supplementation studies in small
groups of children with ADHD using both long chain n3
PUFAs DHA and EPA at concentrations of approximately
500 mg per day, have shown an improvement
in ADHD symptoms after 3 months of treatment
(Richardson & Puri 2002). This is longer than observed
when conventional pharmacological treatments are
used. Childhood developmental and psychiatric disorders
are complex multifactorial disorders. However, the
study of long chain n-3 PUFAs and their metabolism
could offer important new approaches to their early
identification and management.
EFAs have been shown to benefit adult patients with
depression, schizophrenia and dementia. Individuals
whose character traits include deliberate self-harm and
violence have also seen their symptoms ameliorated by
the supplementation of EFAs from fish oil in a number
of recent clinical trials (Hallahan & Garland 2004).
In summary, emerging evidence suggests that n-3
PUFAs may have a role in the control of the symptoms
of neurological disorders such as ADHD and dyslexia
(Bryan et al. 2004). What is required now are largerscale,
well-designed, well-controlled studies to confirm
whether there really is a significant improvement in
behaviour when the diet is modified, and at what levels
210 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
of supplementation these effects are observed (Richardson
2004).
4.7 Emerging aspects of unsaturated fatty acids and
health
Natural genetic variation (polymorphisms)
The study of interactions between nutritional and
genetic factors is a new and important area of research.
Indeed, one of the explanations of the inconsistencies
between the findings of epidemiological studies may be
slight genetic differences in populations that affect how
individuals respond to changes in the fatty acid profile
of their diets. Increased knowledge in this area and new
techniques for measuring gene expression, gene polymorphisms,
protein expression and metabolic profile
will eventually allow a more refined approach to reducing
risk for many different diseases, with diet interventions
targeted towards individuals and subgroups that
are genetically susceptible and responsive to the effects
of nutritional factors. However, the search for candidate
genes has proved to be more complex and their
identification more elusive than originally thought,
largely because much of the variation in risk results
form interactions between environmental factors and
the genome.
Nevertheless, there are several candidate genes that
have been identified in the context of interactions with
dietary fat that appear to determine an individuaľs risk
of developing disease when exposed to different dietary
fatty acids. One of the best understood is the interaction
of the apoE gene. Apolipoprotein E is a component part
of chylomicrons, which facilitates binding to specific
receptors on peripheral liver cells. ApoE is essential for
the normal metabolism of TAG-rich lipoprotein constituents.
There are at least three slightly different versions
of the apoE protein; the major versions are called E2, E3
and E4. These lipoproteins are encoded by slightly different
versions of the apoE gene (alleles); the major versions
are called 2, 3 and 4. The most common allele
is 3, which is found in more than half of the population.
However, in the UK population, approximately
25­30% of the population carry at least one copy of the
apoE 4 allele. These individuals have a higher total
and LDL cholesterol concentration than individuals carrying
two copies of the apoE 3 allele, and are thus at
an increased risk of developing atherosclerosis. People
who carry two copies of the apoE 2 allele are at risk for
a condition known as hyperlipoproteinemia type III.
This condition is characterised by increased levels of
cholesterol, TAGs, and molecules called very low density
lipoproteins (VLDL), which carry cholesterol and
lipoproteins in the bloodstream. The influence of habitual
SFA intakes on blood lipoprotein concentrations
varies according to an individuaľs genetic makeup. SFAs
increase LDL cholesterol in virtually all individuals.
However, the higher SFA intake was associated with
higher VLDL cholesterol and lower HDL cholesterol in
carriers of the apoE 2 gene compared with other subgroups.
By contrast, carriers of the apoE 4 gene had
lower VLDL cholesterol and higher HDL cholesterol
concentrations (i.e. a more favourable blood lipid profile)
for the same intake of SFAs. These data demonstrate
how the effect of a high saturated fat diet could be
modulated by the apoE allele that an individual carries
(Campos et al. 2001). It has been suggested that the
apoE gene variant determines how individuals respond
to fish oil supplementation. Despite a marked reduction
in blood triglycerides, intakes of 3 g long chain n-3
PUFAs caused a 15% increase in LDL cholesterol concentrations
in subjects carrying the apoE 4 allele compare
to those homozygous for 3 (Minihane et al. 2000).
However, despite a 7% increase in LDL cholesterol following
supplementation with 0.7 g DHA, no effect of
apoE genotype was observed on LDL concentration
Key points:
Unsaturated fatty acids and cognitive function and behaviour
* Brain cells are especially rich in the long chain PUFAs DHA (n-3) and AA (n-6). This has led to the suggestion
that dietary status of these long chain fatty acids might influence cognitive function and behaviour.
* Research in this field is still in its early stages, but there is a small amount of evidence to show improvements in
cognitive function following fatty acid supplementation.
* It has been suggested that plasma concentrations of individual or combinations of fatty acids may reflect the incidence
of certain mental disorders. The relevance of this still needs to be confirmed.
* Larger-scale, well-designed studies are required to confirm whether there really is a significant improvement in
behaviour when the diet is modified.
The health effects of dietary unsaturated fatty acids 211
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
(Theobald et al. 2004). Therefore, further research is
warranted in this area to determine the true effect of n3
PUFAs on LDL cholesterol, as there may be pertinent
implications for population recommendations regarding
increased long chain n-3 intakes.
Currently, personalised dietary advice to reduce risk
of disease based on an individuaľs genetic profile is the
focus of much debate. However, before bringing individuality
to public health recommendations, numerous
research questions on the role of specific fatty acids in
the population's diet need to be addressed. Indeed, in the
short-term it may be more appropriate to better personalise
nutrition advice to the profile of CVD risk markers,
such as high blood pressure, abnormal blood lipids or
insulin resistance, instead of relying on large advances in
nutrigenomic research.
Conjugated linoleic acid (CLA)
CLA describes a group of isomers of linoleic acid (an n6
PUFA) in which the double bonds are located adjacent
to each other at carbons 10 and 12, or 9 and 11.
CLA is found naturally in the meat and milk of ruminant
animals. CLA has received considerable attention
following the publication of data from animal experiments
that report anti-carcinogenic, anti-atherogenic
and anti-diabetic properties (see Tricon et al. 2005).
There have also been reports of CLA's ability to reduce
body fat and immune function. Several studies of CLA
supplementation in human subjects have now been
published, but in contrast with animal studies, there
has been much variation between reports on the healthrelated
outcomes. Indeed, it has even been suggested
that the trans isomers of CLA may well have adverse
effects on health, especially with respect to insulin sensitivity
and blood lipids. Before recommendations for
CLA supplementation can be made, more controlled
studies in specific populations with purified isomers of
CLA are required.
Gamma linolenic acid (GLA)
GLA is an n-6 PUFA found naturally in human milk,
evening primrose oil (7­10 g GLA/100 g), blackcurrant
oil (15­20 g GLA/100 g) and borage oil (18­26 g
GLA/100 g). Interest in GLA has grown since the discovery
that some individuals have a limited capacity
for conversion of LA to GLA (see Fig. 5). It has been
suggested that reduced GLA formation may be associated
with a diversity of conditions, including: ageing;
diabetes; calcium, zinc or vitamin B6 deficiencies; high
cholesterol; rheumatoid arthritis; cancer; CVD and
pre-menstrual syndrome (Bolton-Smith et al. 1997).
GLA supplementation may be advantageous in these
individuals as it is believed that it is the elongation
product of GLA, dihomo--linolenic acid, that accumulates
after supplementation rather than AA. Thus
the production of the pro-inflammatory eicosanoids
from AA is attenuated. This may have the effect of
alleviating some of the symptoms of these various
conditions. However, not all researchers agree with
this hypothesis, and it is clear that there are large gaps
in our understanding of the effect of GLA. Thus, further
research in this area is required before dietary
recommendations can be made (Fan & Chapkin
1998).
5. Unsaturated fatty acids and public health
5.1 Labelling of unsaturated fatty acids
Currently, it is not mandatory to include information
about the nutrient content on a food item unless the
manufacturer wishes to make a nutrition claim.
Although labelling is voluntary, the format of nutrition
labelling on pre-packed foods is dictated by law (see
BNF 2002) and must take one of two formats. The minimum
amount of information that can be declared on a
label is termed a group 1 declaration (which lists the
energy, protein, carbohydrate and fat content of a food
per 100 g or 100 mL; nutrition information may also be
provided on a per-serving basis). Further information
can be included in the form of a group 2 declaration
(which lists group 1 nutrients plus sugars, saturates,
fibre and sodium; see Fig. 12). MUFAs and PUFAs may
also be declared within a food label, but only if the SFA
Figure 12 An example of the layout of a typical nutrition information panel
on a UK food item.
NUTRITION INFORMATION
Energy 689kJ 1466kJ
Protein 4.7g 10g
Carbohydrate 26.9g 57.2g
(of which sugars) 3.1g 6.6g
8.7g4.1gtaF
(of which saturates) 0.6g 1.3g
Sodium 0.2g 0.4g
Fibre 7.8g 16.6g
163kcal 347kcal
Per 47g Per 100g
212 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
content of a food is also declared (this would therefore
require a group 2 declaration). Information on any
other nutrients must be provided if a claim has been
made about it and if labelling regulations permit its
inclusion in the nutrition panel.
Currently, there are no regulations in the UK regarding
whether food manufacturers may claim that a food
is a source of, or rich in, unsaturated fatty acids.
Recently, however, the Joint Health Claims Initiative
(JHCI), having assessed the scientific data relating to
long chain n-3 PUFAs and CHD, approved the use of a
generic health claim, relating to the long chain n-3
PUFAs (EPA, DPA and DHA) on pre-packed foods and
associated advertising material. The following statement
is permitted as long as the food provides at least 0.2 g of
long chain n-3 PUFAs per serving and as long as certain
other conditions are met: `eating 3 g weekly, or 0.45 g
daily, long chain omega-3 PUFAs, as part of a healthy
lifestyle, helps maintain heart health' (JHCI 2005). The
JHCI is a joint venture between consumer organisations,
enforcement authorities and industry trade associations
in the UK to establish a Code of Practice for health
claims on food. The Code is not seeking to replace food
legislation; instead, it was established in the absence of
legislation in an attempt to provide effective consumer
protection and consistency in the use of health claims in
the UK.
However, legislation in this area is imminent, and in
preparation for this, The European Commission has
requested the EFSA to issue an opinion on the scientific
substantiation of nutrition claims relating to `omega-3
fatty acids', MUFAs, PUFAs and unsaturated fatty acids,
thereby quantifying the criteria that products would
have to meet to be labelled as a `source of omega-3' or
`high in polyunsaturated fať. The health claims directive
was presented to the European Parliament for its second
reading in January 2006.
5.2 Are current UK recommendations adequate?
Back in 1992, when the BNF established a Task Force to
evaluate the existing UK recommendations for intakes
of unsaturated fatty acids, the situation was somewhat
different from that found today. At that time, the main
driver for setting dietary fat guidelines was to achieve a
reduction in plasma LDL cholesterol, and the SFA
intake was a major focus. Little or no account had been
taken of other factors, such as plasma TAG concentrations,
HDL cholesterol, fibrinogen, platelet aggregation
and endothelial function, which are all now accepted to
influence CVD risk. Thus, many of the recommendations
made by the Task Force were: to better define
intakes of the n-3 PUFAs, to look more carefully at the
intakes of the individual n-6 PUFAs, and to consider the
implications of the n-6 to n-3 ratio.
Today, following the SACN/COT report in 2004, we
have dietary guidelines that take into account the role
of the long chain n-3 PUFAs in maintaining a healthy
heart. However, the subject of dietary fat has become
even more complex. Fat is the most energy-dense nutrient,
and some would see it as being rather irresponsible
to encourage an increase in the consumption of any
type of fat owing to the rising levels of obesity that we
are currently experiencing around the world. Unless
there is a clear message to simultaneously reduce the
total amount of fat in our diets, while also substituting
PUFAs and MUFAs for some of the remaining SFAs,
some people may inadvertently increase their intake of
total fat as well as the `good fats', resulting in an
increase in total energy intake and consequently exacerbating
the obesity problem. Also nutritionists and dietitians
recognise that consumption of oil-rich fish is not
currently acceptable to a large proportion of the population
(see Unsaturated fatty acids in the UK diet). The
SACN/COT recommendations largely assume that the
long chain n-3 PUFAs will be achieved by eating oil-rich
fish. Although the Committees acknowledged that certain
groups of the population do not eat fish, no specific
recommendations were made for these individuals.
Thus, it is pertinent to consider how the guidelines
could be translated for those individuals who choose
not to eat fish. Few health professionals would be comfortable
recommending supplement use as the only
alternative to fish, as this can be expensive and goes
against the idea that all the nutrients that our bodies
require can be obtained from the food that we eat.
Alternative options are discussed in more detail in the
subsection below.
Another point worth bearing in mind is that if supplements
or fortified foods are a solution for achieving
adequate n-3 PUFA intakes, what then is the correct
level of intake that non-fish eaters should be aiming for?
Are non-fish sources as efficient in delivering the health
benefit, or is there some other dietary factor in oil-rich
fish as well as long chain n-3 PUFA, which is bringing
about the benefit? This query has arisen because
although benefits of long chain n-3 PUFAs can be
achieved by dietary means (i.e. by eating the recommended
amounts of oil-rich fish to achieve an intake of
0.45 g/day), relying on supplements appears to require
much higher intakes according to the results of supplementation
trials (see Buttriss 2005a). The SACN/COT
report considered this and noted that intakes of approximately
1 g/day were sufficient for a beneficial effect in
The health effects of dietary unsaturated fatty acids 213
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
secondary prevention trials. However, higher levels of
intake (approximately 3 g/day) were required to see
improvements in some cardiovascular risk factors
(SACN/COT 2004).
The most recent guidelines relating to fatty acid
intakes are those published by the National Academy of
Science (USA) in 2005. Here, as well as stating intakes
to prevent deficiency, they also recommended acceptable
micronutrient distribution ranges (AMDR), which take
into account the possible health benefits while keeping
in mind the high energy content of fat (Table 16). No
dietary reference intakes have been set for MUFAs as it
was considered that they are `synthesized by the body
and have no known independent beneficial role in
human health and are not required in the dieť (FNB
2005). However, recommended dietary amounts were
set for the PUFAs LA and ALNA. The terminology used
by the National Academy of Sciences is different from
that which we use in the UK. In the USA, the acceptable
intake (AI) for the n-6 PUFA LA is 5% of energy (17 g/
day for men and 12 g/day for women). Additionally, an
acceptable range of intakes has been defined; intakes
above or below the boundaries of this range may potentially
increase the risk of chronic diseases and affect
long-term health. The upper boundary was set at 10%
of energy as: this is much higher than most individual
intakes; there is little epidemiological evidence investigating
the safety of diets containing more than 10% of
energy as n-6 PUFAs; and very high intakes of n-6 PUFA
may create a pro-oxidant state that might increase the
risk of chronic disease.
Meanwhile, for the n-3 PUFA ALNA, the AI is 0.6%
of energy (1.6 g/day for men and 1.1 g/day for women),
and they specifically state that 10% of this figure for
ALNA can be consumed as EPA and DHA (i.e. 0.16 g
using the value for men). The upper boundary of the
AMDR is 1.2% of energy, and this is defined the highest
individual intakes. The publication acknowledges the
`growing body of evidence [that] suggests that diets
higher in ALNA, EPA and DHA may afford some
degree of protection against CHĎ. Based on the suggestion
that DHA and EPA should make up 10% of the
ALNA intake, recommendations for intakes of DHA
and EPA (0.16­0.32 g/day) are, therefore, lower than
the 0.45 g per day recommended in the UK.
Looking at dietary recommendations elsewhere
around the world, in Europe an expert committee
brought together for the EURODIET project, recommended
that dietary fat should contribute no more than
30% of energy intake, that n-6 PUFA should contribute
4­8% of energy, and that diets should contain 2 g of
ALNA each day and 200 mg of the long chain n-3
PUFAs. Also, the FAO advises similar levels of intake,
although they recommend an optimal ratio of LA to
ALNA rather than a value for n-3 PUFAs alone
(Table 16).
It is apparent from Table 16 that a variety of different
approaches are currently being taken to define appropriate
intakes of unsaturated fatty acids (see Buttriss
2005b).
5.3 Opportunities to increase intakes of long
chain n-3 PUFAs
Increasing consumption of oil-rich fish (e.g. salmon and
mackerel) is the most obvious way of increasing intakes
of EPA and DHA. However, this presents a number of
barriers: many people do not like the taste of oil-rich fish
or avoid it because of lingering cooking smells; there are
concerns about the sustainability of global fish stocks;
there are concerns over the presence of persistent environmental
pollutants in oil-rich fish; and also some people
perceive oil-rich fish to be expensive although this is
not necessarily the case. Furthermore, vegans and some
vegetarians do not consume fish because of personal or
religious beliefs.
There are a number of other ways in which intake can
be increased:
* dietary supplements providing long chain n-3 PUFAs;
* foods enriched with long chain n-3 PUFAs;
* foods originating from animals fed on diets enriched
with long chain n-3 PUFAs;
* novel sources of unsaturated fatty acids.
Table 16 Dietary guidelines relating to daily fat consumption (% of energy)
USA and Canada Europe (EURODIET) FAO/WHO UK
Fat 20­35 <30 35 <35
n-3 PUFA 0.6­1.2 200 mg DHA/EPA; 2 g ALNA LA :ALNA = 5:1­10:1 >0.2 (450 mg DHA/EPA)
n-6 PUFA 5­10 4­8 4­10 >1
Source: DH (1991); FAO (1994); FNB (2005); Kafatos & Codrington (1999); SACN/COT (2004).
ALNA, -linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LA, linoleic acid; PUFA, polyunsaturated fatty acid.
214 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Supplements
Fish oil supplements are an effective way of increasing
intakes of EPA and DHA. However, supplements
should not take the place of a healthy balanced diet,
and a dietary change to increase intakes of oil-rich fish
is the preferred option. There are also concerns regarding
the potential presence of persistent environmental
contaminants in some fish oil supplements. Also, fish
oil supplements are not acceptable to some groups of
the population, such as vegans and some vegetarians.
Supplements containing DHA derived from microalgae,
which are suitable for vegetarians and vegans, are
available in the UK, but not widely, and tend to be
expensive.
Enriched foods and other functional foods
The addition of long chain n-3 PUFAs to commonly
consumed foods is one way of increasing their consumption
in the diet. Foods that have been successfully
enriched with long chain n-3 PUFAs (through
the addition of either fish oil or algal oil) include
breads, mayonnaise, margarines and fat spreads,
pasta, milk, infant formula, juice and soft drinks
(Jacobsen 2004). However, some of these foods have
suffered poor sales and are no longer available on the
global market.
There are problems associated with the addition of
long chain n-3 PUFAs to foods, as they are prone to oxidation.
This can result in fishy, metallic flavours and the
production of free radicals and reactive aldehydes, both
of which have adverse effects on human health. A number
of factors, including the presence of oxygen, antioxidants,
salt, trace metals and moisture, pH, the viscosity
of the food and temperature, all influence a fooďs susceptibility
to oxidation. Such factors need to be considered
when developing foods enriched with long chain n3
PUFAs and any problems overcome (Jacobsen &
Bruni-Let 2006).
Margarines and other spreads enriched with n-3
PUFAs are a useful vehicle for increasing intakes of
these fatty acids. Currently, such products that have
been enriched with ALNA from linseed oil are available.
Increasing the amount of ALNA, at the expense
of LA, in margarine and fat spreads increases the
chance of oxidation, as the number of unsaturated
double bonds in the molecule is greater. Manufacturers
add antioxidant compounds to spreads to combat
this problem; it is also important that good manufacturing
processes are adhered to as a number of other factors,
including temperature, can influence risk of
oxidation, and such factors must be controlled for
(Upritchard et al. 2005).
It is also possible to manipulate the fatty acid composition
of foods of animal origin by changing the diets
of livestock, resulting in foods with a fatty acid profile
more conducive to human health (Givens & Gibbs
2006). Such work forms the focus of two workpackages
within the European Union (EU)-funded Lipgene
project, which is endeavouring to find out more about
the aetiology and the role of diet in the development of
the metabolic syndrome. The project also aims to produce
plant and animal foods (i.e. seed oils, meat and
milk) with a modified fatty acid composition, which
have the potential to reduce the prevalence of the metabolic
syndrome and relieve some of the public health
pressures associated with it (see Buttriss & Nugent
2005; Nugent 2005).
Novel sources of unsaturated fatty acids
Micro-organisms, such as fungi, are capable of synthesising
PUFAs. The production of PUFAs from microorganisms
has been extensively reviewed by Sanders &
Theobald (2006). Zygomycetes, a group of lower fungi,
can accumulate the n-6 PUFA GLA. The zygomycetes
fungus, Mortierella alpina, is capable of synthesising
AA, and this has been grown in culture and commercially
exploited. The `single celľ derived oil end-product
typically contains 49% AA by weight. Such sources of
AA are currently being used in infant formulas and sold
as dietary supplements. M. alpina, if supplemented with
LA, is capable of synthesising EPA rather than AA, but
this is a costly and lengthy exercise and therefore not
economically viable.
Marine algae, notably microalgae, are capable of synthesising
long chain n-3 PUFAs, and are the primary
source of EPA and DHA present in oil-rich fish, as these
fatty acids pass up the food chain following consumption
by fish. Dinoflagallates can be grown in culture and
used commercially to produce long chain n-3 PUFAs,
but care must be taken to select strains that do not produce
toxins. The dinoflagallate species, Crypthecodinium
cohnii, is commercially exploited to produce an oil
that is 40­45% DHA and virtually devoid of EPA.
Again, this oil is used in infant formulas and also dietary
supplements. Thraustochytrids are another microalgal
source of long chain n-3 PUFAs, and Schizochytrium
spp. are able to synthesise large amounts of DHA and
also the n-6 fatty acid DPA (22:5n-6). DHA produced
from this source has been approved for use in foods, and
single cell oils produced from micro-organisms are considered
to be suitable for vegetarians and vegans.
The health effects of dietary unsaturated fatty acids 215
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
In the EU, these `single celľ oils produced from microorganisms
are considered novel foods as they do not
have a significant history of consumption within the EU
before May 1997. All novel foods must undergo a premarket
assessment for safety before they are permitted
for consumption within the EU. Certain single cell oils
have been assessed and passed by the UK's Advisory
Committee on Novel Foods and Processes and, as a
result, are considered safe and their use permitted within
the EU. The US Food and Drug Administration has also
given certain single cell oils `generally regarded as safe'
status. While it is economically viable to produce both
AA and DHA of a high purity from micro-organisms, it
is not currently possible to produce EPA in economical
amounts.
Genetic engineering of oil seed crops that synthesise
LA or ALNA is another avenue that is being
explored in a bid to find a sustainable and economically
viable source of long chain n-3 PUFAs. Higher
plants are capable of synthesising PUFAs (predominantly
n-6 PUFAs and to a lesser extent, n-3 PUFAs)
but not long chain PUFAs of carbon chain length of
20 or more. The addition of biosynthetic genes from
micro-organisms encoding for the synthesis of long
chain n-3 PUFAs into suitable oil seed crops is currently
being explored (see Graham et al. 2004; Napier
& Sayanova 2005). Genes encoding for elongase and
desaturase enzymes involved in the biosynthesis of
EPA and DHA have been identified and isolated in
fungi and algae, and inserted into suitable oilseed
crops (e.g. linseed). The synthesis of both AA and EPA
from endogenous LA and ALNA has been successful
in transgenic crops, but yields of EPA in particular
have been low.
Current research is attempting to increase yields of
EPA in transgenic plants. The ultimate goal of the
genetic engineering of oil seed crops is the synthesis of
DHA; additional genes capable of elongating and
desaturating EPA are required for this. Such genes have
been identified and functionally characterised, but there
are a number of constraints that need to be overcome
in order that transgenic oil seed crops can accumulate
DHA. Such research will form the focus of much anticipated
research, including work being conducted
within the Lipgene project (Napier & Sayanova 2005).
There is also the potential to genetically modify microorganisms
to produce specific unsaturated fatty acids.
Despite the health benefits it might provide, currently
there is a lot of resistance to genetic engineering in
Europe, and it may be some time before the practice is
accepted by the public and the potential benefits
realised.
5.4 Implications of optimising intakes of
unsaturated fatty acids
It will be clear that there are several, valid reasons why
we should be looking at increasing our intakes of certain
fatty acids. However, there are concerns that pressing
for intakes of unsaturated fatty acids to increase may,
inadvertently, bring about other problems, if the public
health message is not clear and consistent. What is
required by the majority of the public is a shift in the
proportions of the fatty acids that make up our diet,
alongside a decrease in total fat consumption. MUFAs,
n-6 and n-3 PUFAs should be substitutes for dietary
SFAs in our diets, rather than consumed in addition. If
too much emphasis is placed on the health benefits of
the `good fats', then the risk is that people may actually
increase their total fat intakes, while believing that they
are making positive dietary changes for their future
health.
Some concern has been expressed about the potential
for intakes of n-6 PUFA to exceed the upper limit set for
individuals of 10% of energy intake, despite there being
very little epidemiological evidence that considers the
risks of consuming diets high in PUFAs. To date, much
of the concern has been based on the fear that high
intakes of PUFA might lead to a pro-oxidant environment
that may increase risk of CHD and cancer. A small
minority of individuals already consume high amounts
of PUFAs, at levels close to the recommended upper
limit for individuals. The fear is that the upper limit
might be exceeded if n-6 PUFA intakes were to increase
further. However, this is not of great concern for the
majority of the population as average intakes of n-6
PUFA are just below the population recommendation of
6.5% of energy. Indeed, it has been suggested that provided
intakes of total fat are below the recommended
35% of energy, it is virtually impossible to reach n-6
PUFA intakes of 10% or higher (Astorg 2004).
As previously mentioned, although fish oil supplementation
provides a useful source of long chain n-3
PUFA, most nutritionists and dietitians prefer to advocate
dietary sources of nutrients. In this instance, product
reformulation (e.g. to incorporate oil-rich fish such
as salmon in fish-based ready meals) and enrichment of
foods with these fatty acids (e.g. eggs and meat through
modifications to animal-feeding practices) can be rational
alternative approaches. It is of some concern that
fatty acids are added to foods not usually associated
with fat, such as orange juice or bread, as this may confuse
customers about the natural sources of these fatty
acids, and consequently make it harder for them to learn
how to make appropriate substitutions elsewhere in
216 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
their diet. Such initiatives require clear labelling supported
by a strong public health message; it is not sufficient
simply to draw attention to the presence of the
`good fať using colourful messages on the front of pack.
It is also essential that upper limits of intake are considered
as, over the course of a day, individuals may
inadvertently consume a substantially higher amount of
long chain n-3 PUFAs by incorporating a number of
enriched foods into their diet. In the UK, there is currently
no recommendation for a safe upper limit for of
n-3 PUFAs, as historically intakes have been so low that
there has been little concern of overdose. In the USA, a
maximum level of intake has been set as 3 g per day, and
it is very important that this issue is also given consideration
in the UK.
Health implications of the n-6 to n-3 ratio
If the general public take on advice to increase consumption
of n-3 PUFAs, the ratio of n-6 to n-3 PUFAs in our
diets is likely to decrease. As has been mentioned previously,
it has been suggested that the ratio of n-6 to n-3
fatty acids in the diet may be an important risk factor
for CHD. This hypothesis is mainly derived from ecologic
data that suggest that as intakes of n-6 PUFAs have
increased and intakes of n-3 PUFAs have decreased over
the past 150 years, there has been a parallel increase in
the incidence of CHD in the developed world (see Simopoulos
1999; Kris-Etherton et al. 2000). Both n-6 and
n-3 PUFAs compete for the same enzymes involved in
fatty acid desaturation and elongation (see What are
unsaturated fatty acids?), so it is thought that an
increase in dietary n-6 PUFA in the diet may lead to an
increase in the production of prothrombotic rather than
antithrombotic metabolites, increasing the risk of CHD
(Chan et al. 1993; Freese et al. 1994; James et al. 2000).
Furthermore, if intakes of LA are high, there may be a
reduced capacity for ALNA conversion to the cardioprotective
fatty acids EPA and DHA.
However, few studies have investigated the influence
of the relationship between n-3 and n-6 fatty acids and
risk of CHD and, as yet, the ratio of n-6 to n-3 fatty
acids associated with a reduced risk of CHD has not
been determined. Indeed, some question whether it is
physiologically relevant. Mozaffarian et al. (2005b)
have recently reported no influence of EPA and DHA
intakes relative to n-6 PUFAs on risk of CHD in men.
Similarly, another recent large cohort study has reported
no significant increase in CVD death in men with the
highest n-6 to n-3 ratio when compared with those men
with the lowest (Laaksonen et al. 2005). What is becoming
increasingly clear is that both n-3 and n-6 PUFAs
have independent health effects in the body, and as
intakes of the n-6 PUFAs are within the guidelines for a
healthy diet, concerns about the n-6 to n-3 ratio are
driven by low intakes of n-3 rather than high intakes of
n-6. In fact, it may not be that useful to talk in terms of
a ratio, as this might bring about a reduction in intakes
of n-6, which would be unnecessary and even undesirable.
If the population were to meet the guideline
intakes for the unsaturated fatty acids, the ratio would
automatically be 5:1, so perhaps it would be more useful
to talk in terms of absolute amounts, rather than in
terms of a ratio that is very difficult to interpret.
6. Conclusions
Unsaturated fatty acids are now a nutritional hot topic,
and their presence in foods has attracted both public
and industrial interest. There are undeniable benefits, in
terms of CVD prevention, that can be obtained if dietary
SFAs are reduced, and some of the remainder subKey
points:
Unsaturated fatty acids and public health
* There is no legal requirement to include information about either total fat or the types of fatty acids on a food
label. However, if information is provided, legislation determines the format to be used.
* There is currently no specific legislation to control the use of health claims relating to the fatty acid content of
foods. However, an EU Directive is expected imminently which will formally set down the criteria that a product
will have to meet in order to make any nutrition or health claim.
* The UK recommendations on fat intakes are in line with those around the world. However, as a population, we
need to increase our consumption of long chain n-3 PUFAs and decrease SFA intakes.
* Food technologists are looking at ways in which the fatty acid profile of a food can be modified in order to bring
dietary improvements without requiring a major change in dietary habits.
* Public health messages surrounding the optimum intakes of fatty acids must be clear and consistent to ensure that
a favourable change in the fatty acid profile of the UK diet occurs.
The health effects of dietary unsaturated fatty acids 217
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
stituted with both MUFAs and PUFAs. There are also a
number of new and emerging areas where dietary unsaturated
fatty acids may play a role in affecting an individuaľs
risk of developing other diseases, including
diabetes, inflammatory conditions such as rheumatoid
arthritis or asthma, and perhaps even cancer. What we
are currently lacking is the cumulative evidence that is
needed to begin to make specific dietary recommendations.
No doubt over the next decade, increasing numbers
of trials will be conducted and will hopefully shed
some more light on these newer aspects of unsaturated
fatty acids in health and disease, so that appropriate
public health messages can be developed. However, it is
looking increasingly likely that intakes required for
improvements in some disease risk factors are substantially
higher than those that could be feasibly obtained
from the diet. This raises the issue that supplementation
might be the only way to achieve these high intakes, an
approach that is not automatically favoured by most
nutritionists or dietitians.
New developments in the determination of optimal
fatty acid status aside, there are currently many other
issues surrounding fatty acid intakes that have to be
faced. In the UK, intakes of the long chain n-3 PUFAs
are substantially below recommended intakes, and this
may have implications for heart health. As the best
sources of the long chain n-3 PUFAs are oil-rich fish and
currently only 27% of the population consumes oil-rich
fish, it is unlikely that the situation will change unless
there is a massive shift in food preferences. One possible
solution lies in food technology. Currently, food technologists
are looking at ways in which the fatty acid
profile of a food can be modified in order to bring about
dietary improvements without requiring a major change
in dietary habits. Foods commonly consumed in the UK
diet, such as milk, eggs, meat and spreads, are targets for
fatty acid enrichment, where the fatty acids are added
either during processing or at an earlier stage in the
fooďs production. Alternatively, novel sources of the
long chain n-3 PUFAs that might form the basis of
future food ingredients are being investigated.
It is clear that this is a fast-moving area of nutrition
research. It may also be influenced by our understanding
of natural human genetic variation and the interplay
between these polymorphisms and our diet. We have
already seen examples where individuals carrying specific
gene variants respond differently to dietary interventions;
advances in this area may ultimately allow
more tailored and targeted diets. However, such developments
are a long way off and in the meantime, it is
vital that public health messages surrounding the optimum
intakes of fatty acids must be clear and consistent
to ensure that a favourable change in the fatty acid profile
of the UK diet occurs.
Acknowledgements
The BNF wishes to thank the members of the Foundation's
Scientific Advisory and Industrial Scientists Committees
who have helped to shape the contents of this
Briefing Paper. The BNF also wishes to thank Unilever
plc for financial support in the publication and dissemination
of the finished report.
References
Al MDM, van Houwelingene AC & Hornstra G (1995) Long chain
polyunsaturated fatty acids, pregnancy and pregnancy outcome.
American Journal of Clinical Nutrition 71: S285­S291.
Albert CM, Campos H, Stampfer MJ et al. (2002) Blood levels of long
chain n-3 fatty acids and the risk of sudden death. New England
Journal of Medicine 346: 1113­8.
Allen KG & Harris MA (2001) The role of n-3 fatty acids in gestation
and parturition. Experimental Biological Medicine 226: 498­506.
Appel LJ, Miller ER, Seidler AJ et al. (1993) Does supplementation
of diet with `fish oiľ reduce blood pressure? A meta-analysis of controlled
clinical trials. Archives of Internal Medicine 153:
1429­38.
Artaud-Wild SM, Connor SL, Sexton G et al. (1993) Differences in
coronary mortality can be explained by differences in cholesterol
and saturated fat intakes in 40 countries but not in France and Finland.
A paradox. Circulation 88: 2771­9.
Assmann G, Schulte H, Funke H et al. (1998) The emergence of triglycerides
as a significant independent risk factor in coronary artery
disease. European Heart Journal 19: M8­14.
Astorg P (2004) Dietary n-6 and n-3 polyunsaturated fatty acids and
prostate cancer risk: a review of epidemiological and experimental
evidence. Cancer Causes and Control 15: 367­86.
Austin MA (1989) Plasma triglyceride as a risk factor for coronary
heart disease. The epidemiologic evidence and beyond. American
Journal of Epidemiology 129: 249­59.
Backer V, Nepper-Christensen S, Porsbjerg C et al. (2004) Respiratory
symptoms in greenlanders living in Greenland and Denmark: a
population-based study. Annals of Allergy Asthma and
Immunology 93: 76­82.
Bakker EC, Ghys AJ, Kester AD et al. (2003) Long-chain polyunsaturated
fatty acids at birth and cognitive function at 7 y of age.
European Journal of Clinical Nutrition 57: 89­95.
Bartsch H, Nair J & Owen RW (1999) Dietary polyunsaturated fatty
acids and cancers of the breast and colorectum: emerging evidence
for their role as risk modifiers. Carcinogenesis 20: 2209­18.
Belluzzi A, Brignola C, Campieri M et al. (1996) Effect of an entericcoated
fish-oil preparation on relapses in Crohn's disease. New
England Journal of Medicine 334: 1557­60.
Berbert AA, Kondo CR, Almendra CL et al. (2005) Supplementation
of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition
21: 131­6.
Berry EM (1997) Dietary fatty acids in the management of
diabetes mellitus. American Journal of Clinical Nutrition 66: S991­
S997.
218 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Berry SE & Sanders TAB (2005) Influence of triacylglycerol structure
of stearic acid-rich fats on postprandial lipaemia. Proceedings of the
Nutrition Society 64: 205­12.
Birch EE, Garfield S, Hoffmann DR et al. (2000) A randomized controlled
trial of early dietary supply of long-chain polyunsaturated
fatty acids and mental development in infants. Develpmental Medicine
and Childhood Neurology 42: 174­81.
Bird AR, Brown IL & Topping DL (2000) Starches, resistant starches,
the gut microflora and human health. Current Issues in Intestinal
Microbiology 1: 25­37.
Bjerregaard P & Dyerberg J (1988) Mortality from ischaemic heart
disease and cerebrovascular disease in Greenland. International
Journal of Epidemiology 17: 514­9.
Bjerregaard P, Mulvad G & Pedersen HS (1997) Cardiovascular risk
factors in Inuit of Greenland. International Journal of Epidemiology
26: 1182­90.
BNF (British Nutrition Foundation) (1992) Task Force Report. Unsaturated
Fatty Acids: Nutritional and Physiological Significance.
BNF: London.
BNF (British Nutrition Foundation) (1995) Task Force Report. TransFatty
Acids. BNF: London.
BNF (British Nutrition Foundation) (1999) n-3 Fatty Acids and
Health. BNF: London.
BNF (British Nutrition Foundation) (2002) Nutrition Labelling and
Health Claims. BNF: London.
Bolton-Smith C, Woodward M & Tavendale R (1997) Evidence for
age-related differences in the fatty acid composition of human
adipose tissue, independent of diet. European Journal of Clinical
Nutrition 51: 619­24.
Briel M, Studer M, Glass TR et al. (2004) Effects of statins on stroke
prevention in patients with and without coronary heart disease: a
meta-analysis of randomized controlled trials. American Journal of
Medicine 117: 596­606.
Broughton KS, Johnson CS, Pace BK et al. (1997) Reduced asthma
symptoms with n-3 fatty acid ingestion are related to 5-series
leukotriene production. American Journal of Clinical Nutrition
65: 1011­7.
Brouwer IA, Katan MB & Zock PL (2004) Dietary alpha-linolenic
acid is associated with reduced risk of fatal coronary heart disease,
but increased prostate cancer risk: a meta-analysis. Journal of
Nutrition 134: 919­22.
Brown AA & Hu FB (2001) Dietary modulation of endothelial function:
implications for cardiovascular disease. American Journal of
Clinical Nutrition 73: 673­86.
Bryan J, Osendarp S, Hughes D et al. (2004) Nutrients for cognitive
development in school-aged children. Nutrition Reviews 62: 295­
306.
Bucher HC, Hengstler P, Schindler C et al. (2002) n-3 polyunsaturated
fatty acids in coronary heart disease: a meta-analysis of randomized
controlled trials. American Journal of Medicine 112: 298­304.
Buckley R, Shewring B, Turner R et al. (2004) Circulating triacylglycerol
and apoE levels in response to EPA and docosahexaenoic acid
supplementation in adult human subjects. British Journal of Nutrition
92: 477­83.
Burdge GC & Calder PC (2005a) Conversion of alpha-linolenic acid
to longer-chain polyunsaturated fatty acids in humans. Reproduction,
Nutrition and Development 45: 581­97.
Burdge GC & Calder PC (2005b) Alpha-linolenic acid metabolism in
humans: the effects of gender and age on conversion to longer-chain
polyunsaturated fatty acids. European Journal of Lipid Science and
Technology 107: 426­39.
Burdge GC & Wootton SA (2002) Conversion of alpha-linolenic acid
to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids
in young women. British Journal of Nutrition 88: 411­20.
Burdge GC, Jones AE & Wootton SA (2002) Eicosapentaenoic and
docosapentaenoic acids are the principal products of alpha-linolenic
acid metabolism in young men. British Journal of Nutrition 88:
355­63.
Burr ML, Fehily AM, Gilbert JF et al. (1989) Effects of changes in fat,
fish and fibre intakes on death and myocardial reinfarction: diet and
reinfarction trial (DART). Lancet 2: 757­61.
Burr ML, Ashfield-Watt PA, Dunstan FD et al. (2003) Lack of benefit
of dietary advice to men with angina: results of a controlled trial.
European Journal of Clinical Nutrition 57: 193­200.
Buttriss J (2005a) Diet and cardiovascular disease: where are we now?
In: Cardiovascular Disease: Diet, Nutrition and Emerging Risk Factors.
The Report of the British Nutrition Foundation Task Force
(S Stanner ed.), pp. 196­233. Blackwell Publishing: Oxford.
Buttriss J (2005b) A public health approach to cardiovascular disease
risk reduction. In: Cardiovascular Disease: Diet, Nutrition and
Emerging Risk Factors. The Report of the British Nutrition Foundation
Task Force (S Stanner ed.), pp. 234­65. Blackwell Publishing:
Oxford.
Buttriss J & Nugent A (2005) LIPGENE: an integrated approach to
tackling the metabolic syndrome. Proceedings of the Nutrition Society
64: 345­7.
Calder PC (1998) Dietary fatty acids and lymphocyte functions. Proceedings
of the Nutrition Society 57: 487­502.
Calder PC (2005) Polyunsaturated fatty acids and inflammation. Biochemical
Society Transactions 33: 423­7.
Campos H, ĎAgostino M & Ordovas JM (2001) Gene-diet interactions
and plasma lipoproteins: role of apolipoprotein E and habitual
saturated fat intake. Genetics and Epidemiology 20: 117­28.
Celermajer DS, Sorensen KE, Gooch VM et al. (1992) Non-invasive
detection of endothelial dysfunction in children and adults at risk of
atherosclerosis. Lancet 340: 1111­5.
Chan JK, McDonald BE, Gerrard JM et al. (1993) Effect of dietary
alpha-linolenic acid and its ratio to linoleic acid on platelet and
plasma fatty acids and thrombogenesis. Lipids 28: 811­7.
Chin JP, Gust AP, Nestel PJ et al. (1993) Marine oils dose-dependently
inhibit vasoconstriction of forearm resistance vessels in humans.
Hypertension 21: 22­8.
Clarke R, Frost C, Collins R et al. (1997) Dietary lipids and blood
cholesterol: quantitative meta-analysis of metabolic ward studies.
British Medical Journal 314: 112­7.
Conquer JA & Holub BJ (1998) Effect of supplementation with
different doses of DHA on the levels of circulating DHA as nonesterified
fatty acid in subjects of Asian Indian background. Journal
of Lipid Research 39: 286­92.
Coppack S, Mohamed-Ali V & Karpe F (2005) Metabolic syndrome:
insulin resistance, obesity, diabetes mellitus, hypertension, physical
activity and genetic factors. In: Cardiovascular Disease: Diet, Nutrition
and Emerging Risk Factors. The Report of the British Nutrition
Foundation Task Force (S Stanner ed.), pp. 22­49. Blackwell
Publishing: Oxford.
Davis HR, Bridenstine RT, Vesselinovitch D et al. (1987) Fish oil
inhibits development of atherosclerosis in rhesus monkeys. Arteriosclerosis
7: 441­9.
The health effects of dietary unsaturated fatty acids 219
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Dayton S, Pearce ML, Hashimoto S et al. (1969) Controlled clinical
trial of a diet high in unsaturated fat in preventing complications of
atherosclerosis. Circulation 40: 1­63.
Defra (Department of the Environment Food and Rural Affairs)
(2005) The Expenditure and Food Survey. HMSO: London.
Defra (Department of the Environment Food and Rural Affairs)
(2006) Family Food 2004­05. HMSO: London.
DH (Department of Health) (1991) Dietary Reference Values for
Food Energy and Nutrients for the United Kingdom. HMSO: Lon-
don.
DH (Department of Health) (1994) Nutritional Aspects of Cardiovascular
Disease. HMSO: London.
DH (Department of Health) (1998) Nutritional Aspects of the Development
of Cancer. HMSO: London.
Diabetes UK (2006) Managing diabetes. Available at: http://www.
diabetes.org.uk/manage/index.html (accessed 10 May 2006).
Doll R & Peto R (1981) The causes of cancer: quantitative estimates
of avoidable risks of cancer in the United States today. Journal of
the National Cancer Institute 66: 1191­308.
Dyerberg J & Bang HO (1982) A hypothesis on the development of
acute myocardial infarction in Greenlanders. Scandanavian Journal
of Clinical and Laboratory Investigation. Supplementum 161: 7­
13.
Emeis JJ, van Houwelingen AC, van den Hoogen CM et al. (1989) A
moderate fish intake increases plasminogen activator inhibitor type1
in human volunteers. Blood 74: 233­7.
Endres S, Lorenz R & Loeschke K (1999) Lipid treatment of inflammatory
bowel disease. Current Opinion in Clinical Nutrition and
Metabolic Care 2: 117­20.
Esposito K, Marfella R, Ciotola M et al. (2004) Effect of a Mediterranean-style
diet on endothelial dysfunction and markers of
vascular inflammation in the metabolic syndrome: a randomized
trial. Journal of the American Medical Association 292:
1440­6.
Fall C (2005) Fetal and maternal nutrition. In: Cardiovascular Disease:
Diet, Nutrition and Emerging Risk Factors The Report of the
British Nutrition Foundation Task Force (S Stanner ed.), pp. 177­
95. Blackwell Publishing: Oxford.
Fan YY & Chapkin RS (1998) Importance of dietary gamma-linolenic
acid in human health and nutrition. Journal of Nutrition 128:
1411­4.
FAO (Food and Agriculture Organisation) (1994) Fats and Oils in
Human Nutrition: Report of a Joint Expert Consultation (JL Albert
ed.). FAO Food and Nutrition Paper No. 57, 1994.
Fehily AM, Yarnell JW & Butland BK (1987) Diet and ischaemic heart
disease in the Caerphilly Study. Human Nutrition: Applied Nutrition
41: 319­26.
Fernandez E, Chatenoud L, La Vecchia C et al. (1999) Fish consumption
and cancer risk. American Journal of Clinical Nutrition 70: 85­
90.
FNB (Food and Nutrition Board) (2005) Dietary Reference Intakes
for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein,
and Amino Acids. The National Academies Press: Washington,
DC.
Folsom AR, Ma J, McGovern PG et al. (1996) Relation between
plasma saturated fatty acids and hyperinsulinemia. Metabolism 45:
223­8.
Frayn K & Stanner S (2005) The aetiology and epidemiology of cardiovascular
disease. In: Cardiovascular Disease: Diet, Nutrition and
Emerging Risk Factors. The Report of the British Nutrition Foundation
Task Force (S Stanner ed.), pp. 1­21. Blackwell Publishing:
Oxford.
Freese R & Mutanen M (1997) Alpha-linolenic acid and marine longchain
n-3 fatty acids differ only slightly in their effects on hemostatic
factors in healthy subjects. American Journal of Clinical
Nutrition 66: 591­8.
Freese R, Mutanen M, Valsta LM et al. (1994) Comparison of the
effects of two diets rich in monounsaturated fatty acids differing in
their linoleic/alpha-linolenic acid ratio on platelet aggregation.
Thrombosis and Haemostasis 71: 73­7.
FSA (Food Standards Agency) (2002) McCance and Widdowson's
The Composition of Foods, 6th summary edn. Royal Society of
Chemistry: Cambridge.
Fuentes F, Lopez-Miranda J, Sanchez E et al. (2001) Mediterranean
and low-fat diets improve endothelial function in hypercholesterolemic
men. Annals of Internal Medicine 134: 1115­9.
Gago-Dominguez M, Yuan JM, Sun CL et al. (2003) Opposing effects
of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The
Singapore Chinese Health Study. British Journal of Cancer 89:
1686­92.
Garcia-Palmieri MR, Sorlie P, Tillotson J et al. (1980) Relationship of
dietary intake to subsequent coronary heart disease incidence: The
Puerto Rico Heart Health Program. American Journal of Clinical
Nutrition 33: 1818­27.
Geelen A, Brouwer IA, Schouten EG et al. (2005) Effects of n-3 fatty
acids from fish on premature ventricular complexes and heart rate
in humans. American Journal of Clinical Nutrition 81: 416­20.
Geleijnse JM, Giltay EJ, Grobbee DE et al. (2002) Blood pressure
response to fish oil supplementation: metaregression analysis of randomized
trials. Journal of Hypertension 20: 1493­9.
Gerhard GT, Ahmann A, Meeuws K et al. (2004) Effects of a low-fat
diet compared with those of a high-monounsaturated fat diet on
body weight, plasma lipids and lipoproteins, and glycemic control
in type 2 diabetes. American Journal of Clinical Nutrition 80: 668­
73.
Ghys A, Bakker E, Hornstra G et al. (2002) Red blood cell and plasma
phospholipid arachidonic and docosahexaenoic acid levels at birth
and cognitive development at 4 years of age. Early Human Development
69: 83­90.
Giovannucci E & Willett WC (1994) Dietary lipids and colon cancer.
Principles and Practice of Oncology 9: 1­12.
GISSI (1999) Dietary supplementation with n-3 polyunsaturated fatty
acids and vitamin E after myocardial infarction: results of the
GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza
nelľInfarto miocardico. Lancet 354: 447­55.
Givens DI & Gibbs RA (2006) Very long chain n-3 polyunsaturated
fatty acids in the food chain in the UK and the potential
of animal-derived foods to increase intake. Nutrition Bulletin 31:
104­10.
Goodfellow J, Bellamy MF, Ramsey MW et al. (2000) Dietary supplementation
with marine omega-3 fatty acids improve systemic
large artery endothelial function in subjects with hypercholesterolemia.
Journal of the American College of Cardiology 35: 265­70.
Gordon T, Kagan A, Garcia-Palmieri M et al. (1981) Diet and its relation
to coronary heart disease and death in three populations. Circulation
63: 500­15.
Graham IA, Cirpus P, Rein D et al. (2004) The use of very long chain
polyunsaturated fatty acids to ameliorate metabolic syndrome:
220 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
transgenic plants as an alternative sustainable source to fish oils.
Nutrition Bulletin 29: 228­33.
Gregory J & Lowe S (2000) National Diet and Nutrition Survey:
Young People Aged 4­18 Years. Volume 1: Report of the Diet and
Nutrition Survey. The Stationery Office: London.
Gregory J, Foster K, Tyler H et al. (1990) The Dietary and Nutritional
Survey of British Adults. The Stationery Office: London.
Grimsgaard S, Bonnaa KH, Hansen JB & Myhre ES (1998) Effects of
highly purified eicosapentaenoic acid and docosahexaenoic acid on
hemodynamics in humans. American Journal of Clinical Nutrition
68: 52­9.
Guthrie N & Carroll KK (1999) Specific versus non-specific effects of
dietary fat on carcinogenesis. Progress in Lipid Research 38: 261­
71.
Halcox JP, Schenke WH, Zalos G et al. (2002) Prognostic value of
coronary vascular endothelial dysfunction. Circulation 106:
653­8.
Hallahan B & Garland MR (2004) Essential fatty acids and their role
in the treatment of impulsivity disorders. Prostaglandins, Leukotrienes
and Essential Fatty Acids 71: 211­6.
Hamazaki T, Sawazaki S, Asaoka E et al. (1996) Docosahexaenoic
acid-rich fish oil does not affect serum lipid concentrations
of normolipidemic young adults. Journal of Nutrition 126:
2784­9.
Hansen J, Grimsgaard S, Nordoy A et al. (2000) Dietary supplementation
with highly purified eicosapentaenoic acid and docosahexaenoic
acid does not influence PAI-1 activity. Thrombosis
Research 98: 123­32.
Harris WS (1997) n-3 fatty acids and serum lipoproteins: human studies.
American Journal of Clinical Nutrition 65: S1645­S1654.
He K, Rimm EB, Merchant A et al. (2002) Fish consumption and risk
of stroke in men. Journal of the American Medical Association 288:
3130­6.
He K, Song Y, Daviglus ML et al. (2004) Fish consumption and incidence
of stroke: a meta-analysis of cohort studies. Stroke 35: 1538­
42.
Henderson L, Gregory J & Swan G (2002) The National Diet and
Nutrition Survey: Adults Aged 19 to 64 Years. Volume 1: Types
and Quantities of Foods Consumed. The Stationery Office:
London.
Henderson L, Gregory J, Irving K et al. (2003) The National Diet and
Nutrition Survey: Adults Aged 19 to 64 Years. Volume 2: Energy,
Protein, Carbohydrate, Fat and Alcohol Intake. The Stationery
Office: London.
Higgs JD (2000) The changing nature of red meat: 20 years of improving
nutritional quality. Trends in Food Science and Technology 11:
85­95.
Hirai A, Hamazaki T, Terano T et al. (1980) Eicosapentaenoic acid
and platelet function in Japanese. Lancet 2: 1132­3.
Hjerkinn EM, Seljeflot I, Ellingsen I et al. (2005) Influence of longterm
intervention with dietary counseling, long-chain n-3 fatty acid
supplements, or both on circulating markers of endothelial activation
in men with long-standing hyperlipidemia. American Journal
of Clinical Nutrition 81: 583­9.
van den Hoogen PC, Feskens EJ, Nagelkerke NJ et al. (2000) The relation
between blood pressure and mortality due to coronary heart
disease among men in different parts of the world. Seven Countries
Study Research Group. New England Journal of Medicine 342: 1­
8.
Hooper L, Thompson RL, Harrison RA et al. (2006) Risks and benefits
of omega 3 fats for mortality, cardiovascular disease, and cancer:
systematic review. British Medical Journal 332: 752­60.
Hornstra G, Al MD, van Houwelingen AC et al. (1995) Essential fatty
acids in pregnancy and early human development. European Journal
of Obstetrics and Gynecology ­ Reproductive Biology 61: 57­
62.
Howell WH, McNamara DJ, Tosca MA et al. (1997) Plasma lipid and
lipoprotein responses to dietary fat and cholesterol: a meta-analysis.
American Journal of Clinical Nutrition 65: 1747­64.
Hu FB, Stampfer MJ, Manson JE et al. (1997) Dietary fat intake and
the risk of coronary heart disease in women. New England Journal
of Medicine 337: 1491­9.
Hu FB, Manson JE & Willett WC (2001) Types of dietary fat and risk
of coronary heart disease: a critical review. Journal of the American
College of Nutrition 20: 5­19.
Hu FB, Bronner L, Willett WC et al. (2002) Fish and omega-3 fatty
acid intake and risk of coronary heart disease in women. Journal of
the American Medical Association 287: 1815­21.
Hunter DJ & Willett W (1993) Diet, body size, and breast cancer. Epidemiologic
Reviews 15: 110­32.
Iacono JM, Puska P, Dougherty RM et al. (1983) Effects of dietary fat
on blood pressure in a rural Finish population. American Journal of
Clinical Nutrition 38: 860­9.
Iso H, Rexrode KM, Stampfer MJ et al. (2001) Intake of fish and
omega-3 fatty acids and risk of stroke in women. Journal of the
American Medical Association 285: 304­12.
Iso H, Sato S, Umemura U et al. (2002) Linoleic acid, other fatty acids,
and the risk of stroke. Stroke 33: 2086­93.
Jacobsen C (2004) Developing polyunsaturated fatty acids as functional
ingredients. In: Functional Foods, Cardiovascular Disease
and Diabetes (A Arnoldi ed.), pp. 307­32. CRC Press, Woodhead
Publishing Ltd: Cambridge.
Jacobsen C & Bruni-Let M (2006) Using Polyunsaturated Fatty Acids
as Functional Ingredients. Improving the Fat Content of Foods (CM
Williams, J Buttriss, eds). Woodhead Publishing Ltd: London.
James MJ & Cleland LG (1997) Dietary n-3 fatty acids and therapy
for rheumatoid arthritis. Seminar in Rheumatoid Arthritis 27: 85­
97.
James MJ, Gibson RA & Cleland LG (2000) Dietary polyunsaturated
fatty acids and inflammatory mediator production. American Journal
of Clinical Nutrition 71: S343­S348.
Jensen CL, Prager TC, Fraley JK et al. (1997) Effect of dietary linoleic/
alpha-linolenic acid ratio on growth and visual function of term
infants. Journal of Pediatrics 131: 200­9.
Johansen O, Seljeflot I, Hostmark AT et al. (1999) The effect of supplementation
with omega-3 fatty acids on soluble markers of endothelial
function in patients with coronary heart disease.
Arteriosclerosis Thrombosis and Vascular Biology 19: 1681­6.
Joint Health Claims Initiative (2005) Final Report: Omega-3 PUFA
and Heart Health. Available at: http://www.jhci.org.uk/approv/
omega.htm (accessed 10 May 2006).
Jorgensen MH, Hernell O, Hughes E et al. (2001) Is there a relation
between docosahexaenoic acid concentration in mothers' milk and
visual development in term infants? Journal of Pediatric Gastroenterology
and Nutrition 32: 293­6.
Kafatos A & Codrington CA (1999) Nutrition and diet for healthy
lifestyles in Europe: the `Eurodieť Project. Public Health Nutrition
2: 327­8.
The health effects of dietary unsaturated fatty acids 221
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Keli SO, Feskens EJ & Kromhout D (1994) Fish consumption and risk
of stroke. The Zutphen Study. Stroke 25: 328­32.
Kelly CM, Smith RD & Williams CM (2001) Dietary monounsaturated
fatty acids and haemostasis. Proceedings of the Nutrition
Society 60: 161­70.
Keys A, Menotti A, Karvonen MJ et al. (1986) The diet and 15-year
death rate in the seven countries study. American Journal of Epidemiology
124: 903­15.
Kohlmeier L (1997) Biomarkers of fatty acid exposure and breast cancer
risk. American Journal of Clinical Nutrition 66: S1548­S1556.
Koletzko B, Agostoni C, Carlson SE et al. (2001) Long chain polyunsaturated
fatty acids (LC-PUFA) and perinatal development. Acta
Paediatrica 90: 460­4.
Kremer JM, Bigauoette J, Michalek AV et al. (1985) Effects of manipulation
of dietary fatty acids on clinical manifestations of rheumatoid
arthritis. Lancet 1: 184­7.
Kremer JM, Lawrence DA, Petrillo GF et al. (1995) Effects of highdose
fish oil on rheumatoid arthritis after stopping nonsteroidal
antiinflammatory drugs. Clinical and immune correlates. Arthritis
and Rheumatism 38: 1107­14.
Kris-Etherton PM (1999) Monounsaturated fatty acids and risk of
cardiovascular disease. Circulation 100: 1253­8.
Kris-Etherton PM, Taylor DS, Yu-Poth S et al. (2000) Polyunsaturated
fatty acids in the food chain in the United States. American Journal
of Clinical Nutrition 71: S179­S188.
Kromhout D, Feskens EJ & Bowles CH (1995) The protective effect
of a small amount of fish on coronary heart disease mortality in
an elderly population. International Journal of Epidemiology 24:
340­5.
Laaksonen DE, Nyyssonen K, Niskanen L et al. (2005) Prediction of
cardiovascular mortality in middle-aged men by dietary and serum
linoleic and polyunsaturated fatty acids. Archives of Internal Medicine
165: 193­9.
Layne KS, Goh KY, Jumpsen JA et al. (1996) Normal subjects consuming
physiological levels of 18:3 (n-3) and 20:5 (n-3) from
flaxseed or fish oils have characteristic differences in plasma lipid
and lipoprotein fatty acid levels. Journal of Nutrition 126: 2130­
40.
Leaf A, Albert CM, Josephson M et al. (2005) Prevention of fatal
arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake.
Circulation 112: 2762­8.
Leren P (1970) The Oslo diet-heart study. Eleven-year report. Circulation
42: 935­42.
de Lorgeril M, Renaud S, Mamelle N et al. (1994) Mediterranean
alpha-linolenic acid-rich diet in secondary prevention of coronary
heart disease. Lancet 343: 1454­9.
Luscombe ND, Noakes M & Clifton PM (1999) Diets high and low
in glycemic index versus high monounsaturated fat diets: effects on
glucose and lipid metabolism in NIDDM. European Journal of
Clinical Nutrition 53: 473­8.
McCann JC & Ames BN (2005) Is docosahexaenoic acid, an n-3 longchain
polyunsaturated fatty acid, required for development of normal
brain function? An overview of evidence from cognitive and
behavioral tests in humans and animals. American Journal of Clinical
Nutrition 82: 281­95.
McGee DL, Reed DM, Yano K et al. (1984) Ten-year incidence of
coronary heart disease in the Honolulu Heart Program. Relationship
to nutrient intake. American Journal of Epidemiology 119:
667­76.
MacLean CH, Mojica WA, Morton SC et al. (2004) Effects of omega3
fatty acids on lipids and glycemic control in type II diabetes and
the metabolic syndrome and on inflammatory bowel disease, rheumatoid
arthritis, renal disease, systemic lupus erythematosus, and
osteoporosis. Evidence Report/Technology Assessment (Summary)
89: 1­4.
MacLean CH, Mojica WA, Newberry SJ et al. (2005) Systematic
review of the effects of n-3 fatty acids in inflammatory bowel disease.
American Journal of Clinical Nutrition 82: 611­9.
McLennan PL, Bridle TM, Abeywardena MY et al. (1992) Dietary
lipid modulation of ventricular fibrillation threshold in the marmoset
monkey. American Heart Journal 123: 1555­61.
MAFF (Ministry of Agriculture Fisheries and Food) (1998) Fatty
Acids ­ Supplement to McCance and Widdowson's The Composition
of Foods. Royal Society of Chemistry: Cambridge.
Makrides M, Neumann MA, Byard RW et al. (1994) Fatty acid composition
of brain, retina, and erythrocytes in breast- and formulafed
infants. American Journal of Clinical Nutrition 60: 189­94.
Makrides M, Neumann M, Simmer K et al. (1995) Are long-chain
polyunsaturated fatty acids essential nutrients in infancy? Lancet
345: 1463­8.
Mann JI, De Leeuw I, Hermansen K et al. (2004) Evidence-based
nutritional approaches to the treatment and prevention of diabetes
mellitus. Nutrition Metabolism and Cardiovascular Disease 14:
373­94.
Mensink RP & Katan MB (1989) Effect of a diet enriched with
monounsaturated or polyunsaturated fatty acids on levels of lowdensity
and high-density lipoprotein cholesterol in healthy women
and men. New England Journal of Medicine 321: 436­41.
Mensink RP & Katan MB (1992) Effect of dietary fatty acids on
serum lipids and lipoproteins. A meta-analysis of 27 trials. Arteriosclerosis
and Thrombosis 12: 911­9.
Mensink RP, Janssen MC & Katan MB (1988) Effect on blood
pressure of two diets differing in total fat but not in saturated and
polyunsaturated fatty acids in healthy volunteers. American Journal
of Clinical Nutrition 47: 976­80.
Mensink RP, Zock PL, Kester AD et al. (2003) Effects of dietary fatty
acids and carbohydrates on the ratio of serum total to HDL cholesterol
and on serum lipids and apolipoproteins: a meta-analysis of
60 controlled trials. American Journal of Clinical Nutrition 77:
1146­55.
Miettinen TA, Naukkarinen V, Huttunen JK et al. (1982) Fatty-acid
composition of serum lipids predicts myocardial infarction. British
Medical Journal 285: 993­6.
Minihane AM, Khan S, Leigh-Firbank EC et al. (2000) ApoE polymorphism
and fish oil supplementation in subjects with an atherogenic
lipoprotein phenotype. Arteriosclerosis, Thrombosis, and
Vascular Biology 20: 1990­7.
Montell E, Turini M, Marotta M et al. (2001) DAG accumulation
from saturated fatty acids desensitizes insulin stimulation of glucose
uptake in muscle cells. American Journal of Physiology, Endocrinology
and Metabolism 280: E229­E237.
Mori TA, Bao DQ, Burke V et al. (1999) Docosahexaeonic acid but
not eicosapentaenoic acid lowers ambulatory blood pressure and
heart rate in humans. Hypertension 34: 253­60.
Mori TA, Watts GF, Burke V et al. (2000) Differential effects of eicosapentaenoic
acid and docosahexaenoic acid on vascular reactivity
of the forearm microcirculation in hyperlipidemic, overweight men.
Circulation 102: 1264­9.
222 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Morris MC, Sacks F & Rosner B (1993) Does fish oil lower blood
pressure? A meta-analysis of controlled trials. Circulation 88: 523­
33.
Mortensen A, Hansen BF, Hansen JF et al. (1998) Comparison of the
effects of fish oil and olive oil on blood lipids and aortic atherosclerosis
in Watanabe heritable hyperlipidaemic rabbits. British Journal
of Nutrition 80: 565­73.
Mozaffarian D, Geelen A, Brouwer IA et al. (2005a) Effect of fish oil
on heart rate in humans: a meta-analysis of randomized controlled
trials. Circulation 112: 1945­52.
Mozaffarian D, Bryson CL, Lemaitre RN et al. (2005b) Fish intake
and risk of incident heart failure. Journal of the American College
Cardiology 45: 2015­21.
MRC (Research Committee to the Medical Research Council) (1968)
Controlled trial of soya-bean oil in myocardial infarction. Lancet 2:
693­700.
Napier JA & Sayanova A (2005) The production of very-long-chain
PUFA biosynthesis in transgenic plants: towards a sustainable
source of fish oils. Proceedings of the Nutrition Society 64: 387­93.
Natvig H, Borchgrevink CF, Dedichen J et al. (1968) A controlled trial
of the effect of linolenic acid on incidence of coronary heart disease.
The Norwegian vegetable oil experiment of 1965­66. Scandinavian
Journal of Clinical Laboratory Investigation. Supplementum 105:
1­20.
Nestel P, Shige H, Pomeroy S et al. (2002) The n-3 fatty acids eicosapentaenoic
acid and docosahexaenoic acid increase systemic arterial
compliance in humans. American Journal of Clinical Nutrition
76: 326­30.
Nicolosi RJ, Wilson TA, Handelman G et al. (2002) Decreased aortic
early atherosclerosis in hypercholesterolemic hamsters fed oleic
acid-rich TriSun oil compared to linoleic acid-rich sunflower oil.
Journal of Nutritional Biochemistry 13: 392­402.
Nicolosi RJ, Woolfrey B, Wilson TA et al. (2004) Decreased aortic
early atherosclerosis and associated risk factors in hypercholesterolemic
hamsters fed a high- or mid-oleic acid oil compared to a
high-linoleic acid oil. Journal of Nutritional Biochemistry 15: 540­
7.
Nilsson L, Banfi C, Diczfalusy U et al. (1998) Unsaturated fatty acids
increase plasminogen activator inhibitor-1 expression in endothelial
cells. Arteriosclerosis, Thrombosis, and Vascular Biology 18: 1679­
85.
Nkondjock A, Shatenstein B, Maisonneuve P et al. (2003) Specific
fatty acids and human colorectal cancer: an overview. Cancer
Detection and Prevention 27: 55­66.
Nugent AP (2005) LIPGENE: an EU project to tackle the metabolic
syndrome. Biochimie 87: 129­32.
Oken E, Kleinman KP, Olsen SF et al. (2004) Associations of seafood
and elongated n-3 fatty acid intake with fetal growth and length of
gestation: results from a US pregnancy cohort. American Journal of
Epidemiology 160: 774­83.
Olsen SF & Secher NJ (2002) Low consumption of seafood in early
pregnancy as a risk factor for preterm delivery: prospective cohort
study. British Medical Journal 324: 447.
O'Neill S (2003) Anti-arrhythmic actions of polyunsaturated fatty
acids in cardiac muscle exerted via the sarcoplasmic reticulum. Biochemical
Society Transactions 31: 939­42.
Ong PJ, Dean TS, Hayward CS et al. (1999) Effect of fat and
carbohydrate consumption on endothelial function. Lancet 354:
2134.
Oomen CM, Feskens EJ, Rasanen L et al. (2000) Fish consumption
and coronary heart disease mortality in Finland, Italy, and the Netherlands.
American Journal of Epidemiology 151: 999­1006.
Panagiotakos DB, Pitsavos CH, Chrysohoou C et al. (2003) Status
and management of hypertension in Greece: role of the adoption of
a Mediterranean diet: the Attica study. Journal of Hypertension 21:
1483­9.
Panza F, Solfrizzi V, Colacicco AM et al. (2004) Mediterranean diet
and cognitive decline. Public Health Nutrition 7: 959­63.
Pattison DJ, Harrison RA & Symmons DP (2004) Does diet have
a role in the aetiology of rheumatoid arthritis? Proceedings of
the Nutrition Society 63: 137­43.
Pawlosky RJ, Hibbeln JR, Novotny JA et al. (2001) Physiological
compartmental analysis of alpha-linolenic acid metabolism in adult
humans. Journal of Lipid Research 42: 1257­65.
Pearce ML & Dayton S (1971) Incidence of cancer in men on a diet
high in polyunsaturated fat. Lancet 1: 464­7.
Pegge NC, Field RC, Twomey AM et al. (2001a) Higher plasma dihomo-gamma-linolenic
acid and arachidonic acid content are associated
with endothelial dysfunction in man. Proceedings of the
Nutrition Society 60: 236A.
Pegge NC, Twomey AM, McDowell IFW et al. (2001b) Dietary supplementation
with pure alpha-linolenic acid may worsen endothelial
function. Proceedings of the Nutrition Society 60: 216A.
Pietinen P, Ascherio A, Korhonen P et al. (1997) Intake of fatty
acids and risk of coronary heart disease in a cohort of Finnish men.
The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.
American Journal of Epidemiology 145: 876­87.
Plotnick GD, Corretti MC & Vogel RA (1997) Effect of antioxidant
vitamins on the transient impairment of endothelium-dependent
brachial artery vasoactivity following a single high-fat meal. Journal
of the American Medical Association 278: 1682­6.
Posner BM, Cobb JL, Belanger AJ et al. (1991) Dietary lipid predictors
of coronary heart disease in men. The Framingham Study. Archives
of Internal Medicine 151: 1181­7.
Psaltopoulou T, Naska A, Orfanos P et al. (2004) Olive oil, the Mediterranean
diet, and arterial blood pressure: the Greek European
Prospective Investigation into Cancer and Nutrition (EPIC) study.
American Journal of Clinical Nutrition 80: 1012­8.
Raitt MH, Connor WE, Morris C et al. (2005) Fish oil supplementation
and risk of ventricular tachycardia and ventricular
fibrillation in patients with implantable defibrillators: a randomized
controlled trial. Journal of the American Medical Association 293:
2884­91.
Rapp JH, Connor WE, Lin DS et al. (1991) Dietary eicosapentaenoic
acid and docosahexaenoic acid from fish oil. Their incorporation
into advanced human atherosclerotic plaques. Arteriosclerosis and
Thrombosis 11: 903­11.
Ricci S, Patoia L, Berrettini M et al. (1987) Fatty acid pattern of red
blood cell membranes and risk of ischemic brain infarction: a casecontrol
study. Stroke 18: 575­8.
Ricci S, Celani MG, Righetti E et al. (1997) Fatty acid dietary intake
and the risk of ischaemic stroke: a multicentre case-control study.
UFA Study Group. Journal of Neurology 244: 360­4.
Richardson AJ (2004) Long-chain polyunsaturated fatty acids in
childhood developmental and psychiatric disorders. Lipids 39:
1215­22.
Richardson AJ & Montgomery P (2005) The Oxford-Durham study:
a randomized, controlled trial of dietary supplementation with fatty
The health effects of dietary unsaturated fatty acids 223
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
acids in children with developmental coordination disorder. Pediatrics
115: 1360­6.
Richardson AJ & Puri BK (2002) A randomized double-blind, placebo-controlled
study of the effects of supplementation with highly
unsaturated fatty acids on ADHD-related symptoms in children
with specific learning difficulties. Progress in Neuro-psychopharmacology
& Biological Psychiatry 26: 233­9.
Richardson AJ & Ross MA (2000) Fatty acid metabolism in neurodevelopmental
disorder: a new perspective on associations between
attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the
autistic spectrum. Prostaglandins, Leukotrienes and Essential Fatty
Acids 63: 1­9.
Roche HM, Zampelas A, Knapper JM et al. (1998) Effect of long-term
olive oil dietary intervention on postprandial triacylglycerol and
factor VII metabolism. American Journal of Clinical Nutrition 68:
552­60.
Rogers P (2001) A healthy body, a healthy mind: long-term impact of
diet on mood and cognitive function. Proceedings of the Nutrition
Society 60: 135­43.
Ros E (2003) Dietary cis-monounsaturated fatty acids and metabolic
control in type 2 diabetes. American Journal of Clinical Nutrition
78: S617­S625.
Ross R (1999) Atherosclerosis ­ an inflammatory disease. New
England Journal of Medicine 340: 115­26.
Sacks FM, Rouse IL, Stampfer MJ et al. (1987) Effect of dietary fats
and carbohydrate on blood pressure of mildly hypertensive patients.
Hypertension 10: 452­60.
SACN/COT (Scientific Advisory Committee on Nutrition/Committee
on Toxicity) (2004) Advice on Fish Consumption: Benefits and
Risks. HMSO: London.
Sanders T & Emery P (2003) Molecular Basis of Human Nutrition.
Taylor & Francis: London.
Sanders TAB & Theobald HE (2006) Novel sources of polyunsaturated
fatty acids (PUFAs) from microorganisms. In: Improving the
Fat Content of Foods (CM Williams, J Buttriss eds), pp. 454­71.
Woodhead Publishing Ltd: Cambridge.
Sattar N & Ferns G (2005) Endothelial dysfunction. In: Cardiovascular
Disease: Diet, Nutrition and Emerging Risk Factors. The
Report of the British Nutrition Foundation Task Force (S Stanner
ed.), pp. 63­77. Blackwell Publishing: Oxford.
Schächinger V, Britten MB & Zeiher AM (2000) Prognostic
impact of coronary vasodilator dysfunction on adverse
long-term outcome of coronary heart disease. Circulation 101:
1899­906.
Seljeflot I, Arnesen H, Brude IR et al. (1998) Effects of omega-3 fatty
acids and/or antioxidants on endothelial cell markers. European
Journal of Clinical Investigation 28: 629­35.
Shike M, Winawer SJ, Greenwald PH et al. (1990) Primary prevention
of colorectal cancer. The WHO collaborating centre for the prevention
of colorectal cancer. Bulletin of the World Health Organisation
68: 377­85.
Simon JA, Fong J, Bernert JT et al. (1995) Serum fatty acids and the
risk of stroke. Stroke 26: 778­82.
Simopoulos AP (2002) Omega-3 fatty acids in inflammation and
autoimmune diseases. Journal of the American College of Nutrition
21: 495­505.
Simopoulos AP (1999) Essential fatty acids in health and
chronic disease. American Journal of Clinical Nutrition 70: S560­
S569.
Simpson HC, Barker K, Carter RD et al. (1982) Low dietary intake of
linoleic acid predisposes to myocardial infarction. British Medical
Journal (Clin Res Ed) 285: 683­4.
Singh RB, Niaz MA, Sharma JP et al. (1997) Randomized, doubleblind,
placebo-controlled trial of fish oil and mustard oil in patients
with suspected acute myocardial infarction: the Indian experiment
of infarct survival-4. Cardiovascular Drugs and Therapy 11:
485­91.
Smita EN, Oelena EA, Seeratc E et al. (2000) Breast milk docosahexaenoic
acid (DHA) correlates with DHA status of malnourished
infants. Archives of Disease in Childhood 82: 493­4.
Sonoda T, Nagata Y, Mori M et al. (2004) A case-control study of diet
and prostate cancer in Japan: possible protective effect of traditional
Japanese diet. Cancer Science 95: 238­42.
Sprecher H (2000) Metabolism of highly unsaturated n-3
and n-6 fatty acids. Biochimica et Biophysica Acta 1486:
219­31.
Stanner S (2005) Cardiovascular disease: diet, nutrition and emerging
risk factors. In: Stanner S (ed.) The Report of the British Nutrition
Foundation Task Force. Blackwell Publishing, Oxford.
Stevens LJ, Zentall SS, Deck JL et al. (1995) Essential fatty acid metabolism
in boys with attention-deficit hyperactivity disorder. American
Journal of Clinical Nutrition 62: 761­8.
Stremmel W, Pohl L, Ring A et al. (2001) A new concept of cellular
uptake and intracellular trafficking of long-chain fatty acids. Lipids
36: 981­9.
Takemura Y, Sakurai Y, Honjo S et al. (2002) The relationship
between fish intake and the prevalence of asthma: the Tokorozawa
childhood asthma and pollinosis study. Preventative Medicine 34:
221­5.
Theobald HE, Chowienczyk PJ & Sanders TAB (2003) Docosahexaenoic
acid lowers blood pressure in middle-aged men and
women. Proceedings of the Nutrition Society 62: 68A.
Theobald HE, Chowienczyk PJ, Whittal R et al. (2004) LDL cholesterol-raising
effect of low-dose docosahexaenoic acid in middleaged
men and women. American Journal of Clinical Nutrition 79:
558­63.
Thies F, Garry JM, Yaqoob P et al. (2003) Association of n-3 polyunsaturated
fatty acids with stability of atherosclerotic plaques:
a randomised controlled trial. Lancet 361: 477­85.
Thomas LH, Olpin SO, Scott RG et al. (1987) Coronary
heart disease and the composition of adipose tissue taken
at biopsy. Human Nutrition and Food Science Nutrition 41F:
167­72.
Tokudome S, Kojima M, Suzuki S et al. (2006) Marine n-3 fatty acids
and colorectal cancer: is there a real link? Cancer Epidemiology,
Biomarkers and Prevention 15: 406­7.
Trichopoulou A, Lagiou P, Kuper H et al. (2000) Cancer and Mediterranean
dietary traditions. Cancer Epidemiology, Biomarkers and
Prevention 9: 869­73.
Tricon S, Burdge GC, Williams CM et al. (2005) The effects of conjugated
linoleic acid on human health-related outcomes. Proceeding
of the Nutrition Society 64: 171­82.
Tso P, Nauli A & Lo CM (2004) Enterocyte fatty acid uptake and
intestinal fatty acid-binding protein. Biochemical Society Transactions
32: 75­8.
Turpeinen O, Karvonen MJ, Pekkarinen M et al. (1979) Dietary
prevention of coronary heart disease: the Finnish Mental Hospital
Study. International Journal of Epidemiology 8: 99­118.
224 J. Lunn and H. E.Theobald
 2006 British Nutrition Foundation Nutrition Bulletin, 31, 178­224
Upritchard JE, Zeelenberg MJ, Huizinga H et al. (2005) Modern fat
technology: what is the potential for heart health? Proceedings of
the Nutrition Society 64: 379­86.
USDA (United States Department of Agriculture) (2005) National
Nutrient Database for Standard Reference, Release 18.
Vermunt SH, Mensink RP, Simonis MM et al. (2000) Effects of
dietary alpha-linolenic acid on the conversion and oxidation of
13C-alpha-linolenic acid. Lipids 35: 137­42.
Vogel RA, Corretti MC & Plotnick GD (1997) Effect of a single
high-fat meal on endothelial function in healthy subjects. American
Journal of Cardiology 79: 350­4.
WCRF (World Cancer Research Fund) (1997) Food, Nutrition and
the Prevention of Cancer: A Global Perspective. American Institute
for Cancer Research: Washington, DC.
Weiner BH, Ockene IS, Levine PH et al. (1986) Inhibition of atherosclerosis
by cod-liver oil in a hyperlipidemic swine model. New
England Journal of Medicine 315: 841­6.
Wendland E, Farmer AJ, Paul G et al. (2006) Effect of alpha-linolenic
acid on cardiovascular risks markers: a systematic review. Heart 92:
166­9.
White C (2005) Suspected research fraud: difficulties of getting at the
truth. British Medical Journal 331: 281­8.
WHO (World Health Organization) (1990) Nutrition, and the Prevention
of Chronic Diseases. Technical Report 797. WHO: Geneva.
WHO/FAO (World Health Organization/Food and Agriculture
Organisation) (2003) Global Report on Diet, Nutrition and Prevention
of Chronic Diseases. Technical Report 916. WHO: Geneva.
Willatts P, Forsyth JS, DiModugno MK et al. (1998) Effect of longchain
polyunsaturated fatty acids in infant formula on problem
solving at 10 months of age. Lancet 352: 688­91.
Williams PT, Fortmann SP, Terry RB et al. (1987)
Associations of dietary fat, regional adiposity, and blood
pressure in men. Journal of the American Medical Association 257:
3251­6.
Wood DA, Riemersma RA, Butler S et al. (1987) Linoleic and eicosapentaenoic
acids in adipose tissue and platelets and risk of coronary
heart disease. Lancet 1: 177­83.
Woodman RJ, Mori TA, Burke V et al. (2002) Effects of purified eicosapentaenoic
and docosahexaenoic acids on glycemic control, blood
pressure, and serum lipids in type 2 diabetic patients with treated
hypertension. American Journal of Clinical Nutrition 76:
1007­15.
Yli-Jokipii K, Kallio H, Schwab U et al. (2001) Effects of palm oil and
transesterified palm oil on chylomicron and VLDL triacylglycerol
structures and postprandial lipid response. Journal of Lipid
Research 42: 1618­25.
Young G & Conquer J (2005) Omega-3 fatty acids and neuropsychiatric
disorders. Reproduction, Nutrition, Development 45: 1­28.
Zhang J, Sasaki S, Amano K et al. (1999) Fish consumption and mortality
from all causes, ischemic heart disease, and stroke: an ecological
study. Preventive Medicine 28: 520­9.
Zock PL & Katan MB (1998) Linoleic acid intake and cancer risk: a
review and meta-analysis. American Journal of Clinical Nutrition
68: 142­53.
Appendix 1
Food groups in the National Diet and Nutrition Survey ­ main contributors to fat intake are highlighted in bold
Cereals & cereal products Pasta; rice; pizza; white bread; wholemeal bread; soft grain bread; other bread; wholegrain & high fibre breakfast
cereals; biscuits; fruit pies; buns, cakes & pastries
Milk & milk products Whole milk; semi-skimmed milk; skimmed milk; cream; other milk; cheese; cottage cheese; fromage frais;
yogurt; other dairy desserts; ice cream
Eggs & egg dishes Eggs; egg dishes
Fat spreads Butter; block margarine; soft margarine; polyunsaturated margarine; polyunsaturated oils; otheroils &
cooking fats; polyunsaturated low fat spread; other low fat spread; polyunsaturated reducedfat
spread; other reduced fat spread
Meat & meat products Bacon & ham; beef, veal & dishes; lamb & dishes; pork & dishes; coated chicken & turkey; chicken & turkey
dishes; liver, liver products & dishes; burgers & kebabs; sausages; meat pies & pastries; other meat & meat
products
Fish & fish dishes Coated and/or fried white fish; other white fish & dishes; shellfish; oil-rich fish
Vegetables (excluding potatoes) Raw carrots; other raw & salad vegetables; raw tomatoes; peas; green beans; baked beans; leafy green vegetables; carrots
­ not raw; tomatoes ­ not raw; vegetable dishes; other vegetables
Potatoes & savoury snacks Potato chips; other fried or roast potatoes & products; potato products ­ not fried; other potatoes & potato
dishes; savoury snacks
Fruit & nuts Apples & pears; citrus fruits; bananas; canned fruit in juice; canned fruit in syrup; other fruit; nuts & seeds
Sugar, preserves & confectionery Table sugar; preserves; sweet spreads, fillings & icings; sugar confectionery; chocolate confectionery
Drinks Fruit juice; soft drinks; alcoholic drinks; tea; coffee; water
Miscellaneous Powdered beverages; soups; sauces; condiments and artificial sweeteners