Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

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than 95% of dietary fat. Each triacylglycerol mol-

ecule is composed of three fatty acids esterified to a

glycerol backbone, making fatty acids a major con-

stituents of dietary fat. In recent years, it has become

clear that fatty acids are more than just a source of

energy. Fatty acids, especially long-chain polyunsat-

urated fatty acids (PUFA), are important regulators of

many biological processes important in maintaining

health and preventing disease.

Types of Fat in the Diet

0002 Because of the wide range of foods consumed, the

human diet contains a great variety of fatty acids.

The chain length and degree of saturation are used

to classify fatty acids, and these characteristics confer

physiological properties. Fatty acids in the diet

can therefore be saturated fatty acids (SFA) and con-

tain no double bonds with the maximum number

of hydrogen molecules attached, monounsaturated

(MUFA) and contain a single double bond or PUFA

and contain two or more double bonds. All dietary

fats and oils contain a mixture of saturated and un-

saturated fatty acids. Individual fatty acids are often

referred to by their common names, but are more

correctly identified by a systematic nomenclature

that classifies them according to their chain length,

position and number of double bonds (Table 1). This

nomenclature indicates the number of carbon atoms

in the acyl chain of the molecule, followed by a colon

and then the number of unsaturated bonds. This is

followed by the letter ‘n’ (or o) and the number of

carbon atoms from the methyl end to the first double

bond. Mammalian cells are able to synthesize (from

nonfat precursors) saturated and unsaturated fatty

acids of the n-9 and n-7 series but lack the D-12 and

D-15 desaturase enzymes (which is found in most

plants) for insertion of a double bond at the n-6 or

tbl0001 Table 1 Nomenclature of fatty acids and major sources in the diet

Chemicalname Common name Fatty acidnotation Sources

Butanoic Butyric C4:0 Butter fat

Octanoic Caprylic C8:0 Palm kernel oil

Decanoic Capric C10:0 De-novo synthesis; coconut oil

Dodecanoic Lauric C12:0 De-novo synthesis; coconut oil

Tetradecanoic Myrsitic C14:0 De-novo synthesis; milk fat, coconut oil

Hexadecanoic Palmitic C16:0 De-novo synthesis and most plant and animal fats,

including milk, eggs, animal fats, meat, coca

butter, palm oil (other vegetable oils contain some

but lesser amounts), and fish oils

Octadecanoic Stearic C18:0 De-novo synthesis and most plant and animal fats,

including milk, eggs, animal fats, meat, and cocoa

butter

9-Hexadecenoic Palmitoleic C16:1n-7 Desaturation of palmitic acid, fish oils, animal fats

9-Octadecenoic Oleic C18:1n-9 Desaturation of stearic acid and all plant and animal

fats, including milk; eggs; animal fats; meat; cocoa

butter; most vegetable oils, especially olive oil

9,12-Octadecadienoic Linoleic C18:2n-6 Cannot be synthesized in mammals; some milks,

eggs, animal fats, meat; most vegetable oils,

especially corn, sunflower, safflower, cottonseed

and soybean oils; green leaves

9,12,15-Octadecatrienoic a-Linolenic C18:3n-3 Cannot be synthesized in mammals; green leaves;

some vegetable oils, especially canola, soybean,

walnut, mustard and linseed oils

6,9,12-Octadecatrienoic g-Linolenic C18:3n-6 Synthesized from linoleic acid, borage, blackcurrant

and evening primrose oils

11,14,17-Eicosatrienoic Mead C20:3n-9 Synthesized from oleic acid; indicator of essential

fatty acid deficiency

Eicosanoic Arachidic C20:0 De-novo synthesis; peanut oil

8,11,14-Eicosatrienoic Dihomo-g-linolenic C20:3n-6 Synthesized from g-linolenic

5,8,11,14-Eicosatetraenoic Arachidonic C20:4n-6 Synthesized from linoleic acid via g-linolenic and

dihomo-g-linolenic acids; small amount in meat

5,8,11,14,17-Eicosapentaenoic Eicosapentaenoic (EPA) C20:5n-3 Synthesized from a-linolenic acid; fish oils

7,10,13,16,19-Docosapentaenoic Docosapentaenoic C22:5n-3 Synthesized from a-linolenic acid via EPA; fish oils

and animal tissues (brain)

4,7,10,13,16,19-Docosahexaenoic Docosahexaenoic (DHA) C22:6n-3 Synthesized from a-linolenic acid via EPA; fish oils

and animal tissues (brain)

2318 FATTY ACIDS/Dietary Importance

n-3 position (Figure 1). As the two types of PUFA, n-6

and n-3 fatty acids, are essential substrates for many

of the regulatory lipids in the body, the precursor fatty

acids linoleic (18:2n-6) and a-linolenic (18:3n-3)

must be consumed in the diet (Figure 1). For the most

part, the longer chain and more unsaturated n-6 and

n-3 fatty acids such as arachidonic acid (20:4n-6),

eicosapentaenoic acid (EPA, 20:5n-3), and docosa-

hexaenoic acid (DHA, 22:6n-3) can be synthesized

from either linoleic or linolenic acid (Figure 2).

Sources of Fat in the Diet

0003The quantities and types of fatty acids ingested vary

greatly, depending on the dietary source (Table 1).

Animal fats contain about 40–60% saturated fatty

acids. Some plant oils also contain SFA (i.e., palm

oil, palm kernel oil, and coconut oil), which are

widely used in processed foods. MUFA are found in

animal fats and plant oils, with olive oil being a rich

source. Plant oils like corn, soybean, cottonseed, sun-

flower, and safflower generally have more than 50%

of their fatty acids as linoleic acid and are considered

excellent sources of PUFA. Poultry and game also

contain a small amount of linoleic acid. Linolenic

acid, which comprises the majority of most people’s

n-3 fatty acid intake, is found in high amounts in

Mammals cannot insert double bonds in these positions

Methyl end Carboxyl end

COOH

Stearic acid

18:0

Oleic acid

18:1 n-9

Linoleic acid

18:2 n-6

α-Linolenic acid

18:3 n-3

fig0001 Figure 1 Double-bond location in major dietary fatty acids.

12:0 18:016:014:0

18:1n-9

18:3n-318:2n-6

20:3n-6

20:4n-6

20:5n-3

22:6n-3

20:4n-3

18:3n-6 18:4n-3

∆9-desaturase

Diet or de novo synthesis

∆12-desaturase

not in humans

but found in plants

∆15-desaturase

plants only

Diet

∆6-desaturase

∆5-desaturase ∆5-desaturase

∆6-desaturase

Arachidonic acid

Eicosapentaenoic acid (EPA)

Docosahexaenoic acid (DHA)

fig0002 Figure 2 Elongation and desaturation of the major dietary fatty acids.

FATTY ACIDS/Dietary Importance 2319

several plant oils (e.g., canola and flax) and, to a

lesser extent, in other plant oils, green leafy vege-

tables, soybeans, and nuts. The more polyunsaturated

long-chain n-3 fatty acids, eicosapentaenoic acid

(EPA) and docosahexaenoic acid (DHA), comprise

20–30% of the fatty acids in cold water fish (particu-

larly fatty fish such as herring, mackerel, fresh tuna,

sardines, salmon, eel), other marine animals, and in

oils extracted from the livers of fish which live in

warmer waters (e.g., cod). There are new sources of

EPA and DHA, made from single cell organisms,

which are available to the food industry to supple-

ment food. Most natural fats contain fatty acids in the

cis form, but a small number of trans fatty acids also

occur naturally, principally in meat and dairy prod-

ucts. The majority of the trans fatty acids in the diet

come from foods made with hydrogenated vegetable

oils. Generally, most fruits and vegetables contribute

insignificant amounts or no fat to our diets.

Dietary Importance

0004 The dietary importance of fatty acids is listed in

Figure 3.

Energy and Essential Fatty Acids

0005 In addition to contributing to the texture, flavor, and

aroma of foods, fatty acids are an important concen-

trated source of energy (9 kcal or 37 kJ g

1

) for most

cells in the body. Fat is a particularly important

energy source for infants and young children, and

restriction is associated with poor growth and

delayed development. Although the biological

importance is not completely clear, there is evidence

suggesting that individual fatty acids are oxidized,

metabolized, stored, and released at different rates.

Fat slows down the digestion of foods, thus con-

tributing to meal satiety. Dietary fat aids in the

absorption of the fat-soluble vitamins. Specific fatty

acids have important structural, biochemical, and

regulatory functions that are required for optimal

tissue function, growth, and repair. Insufficient con-

sumption of the dietary essential fatty acids (linoleic

and linolenic acid) results in a deficiency syndrome

characterized by immune dysfunction, infections,

scaly dermatitis, growth retardation, hair loss, throm-

bocytopenia, diarrhea, and poor wound healing.

Membrane and Cellular Function

0006Fatty acids, particularly PUFA, when consumed in the

diet, integrate into cell membrane lipids. Although

membranes can vary in their lipid content, most cell

membranes contain approximately 50% lipid and

50% protein. Phospholipids, the major lipid found

in cell membranes, are particularly high in long-

chain (18–26-carbon) PUFA. The type of fatty acid

incorporated into cell membranes is influenced by

dietary fatty acids. It can be assumed that all of the

n-6 and n-3 fatty acids found in cell membranes are

derived from dietary sources. Changing the relative

amount and type of PUFA in cell membranes has been

shown to affect many membrane-related functions

such as membrane fluidity, ion channel flow, trans-

porter activity, signal transduction, enzyme activity,

hormone binding, cell-receptor action, cell-to-cell

communication, release of mediators, and suscepti-

bility to microbial invasion and cancer.

Eicosanoid Synthesis

0007Linoleic acid and a-linolenic acid are substrates for

the synthesis of physiological regulators called eicosa-

noids. Eicosanoids include prostaglandins, prostacy-

clins, thromboxanes, and leukotrienes. These ‘local

hormones’ are potent mediators of many biochemical

processes and play key roles in the regulation of blood

clots, blood pressure, blood lipid levels, immune

function, inflammation, pain and fever, and repro-

duction. The two major pathways for eicosanoid syn-

thesis are via the enzymes cyclooxygenase (produce

prostaglandins and thromboxanes) and lipooxygen-

ase (produce leukotrienes, hydroxyeicosatrienoic

acids, and lipoxins).

0008Dietary fat composition influences eicosanoid syn-

thesis by changing the supply of substrates for the

synthesis of the longer-chain n-3 and n-6 PUFA. Con-

suming large amount of linoleic acid increases the

quantity of arachidonic acid in cell membranes. Upon

activation, in a variety of cells, arachidonic acid is

converted to eicosanoids of the 2 series and leuko-

trienes of the 4 series. However, dietary a-linolenic

acid is converted to EPA in the membrane, and when

cells are activated, EPA is converted to eicosanoids of

the 3 series and leukotrienes of the 5 series. In general,

eicosanoids formed from n-3 PUFA oppose, or have

weaker effects than, eicosanoids formed from n-6

PUFA. In addition to competing as substrates for

cyclooxygenase, n-3 fatty acids can directly suppress

the activity of this enzyme. n-3 fatty acids also inhibit

D-6 and D-5 desaturase activity, reducing the synthe-

sis of arachidonic acid in the membrane. Indeed, it

has been shown that increasing the proportions of n-3

in relation to n-6 PUFAs in the diet decreases the

Energy

Source of essential fatty acids

Membrane structure & function

Gene regulation

Neurological and retinal

structure and function

Immune function

Disease prevention &

treatment

fig0003 Figure 3 Dietary importance of fatty acids.

2320 FATTY ACIDS/Dietary Importance

quantity of proinflammatory, vasoconstrictive, plate-

let aggregatory, and immunosuppressive compounds

that are regulated by eicosanoids. Recent investiga-

tions have shown that g-linolenic acid (20:3n-6)

present in some plants (i.e., evening primrose oil,

borage, and flaxseed) may also influence the type

of eicosanoid synthesized by a cell.

Gene Regulation

0009 PUFA have been shown to alter the expression of

numerous genes involved in the metabolic function

of the cell. It has been demonstrated that specific

dietary fatty acids can modulate the expression of a

variety of genes (and transcription regions on genes)

coding for key regulatory proteins in metabolic path-

ways such as those involved in digestion, lipogenesis,

glycolysis, glucose transport, inflammation, and cel-

lular communications. For example, dietary n-6 and

n-3 PUFA suppress hepatic lipogenesis by suppressing

transcription of fatty acid synthase. Suppression is

greater with DHA, EPA, and arachidonic acid than

with linoleic acid or a-linolenic acid, whereas SFA

and MUFA have little effect. In the future, fatty

acid–gene interactions will likely be translated to

dietary prescriptions to maintain health and modu-

late both the response to injury and the progression of

diseases in genetically susceptible individuals.

Neurological Development and Function

0010 DHA and arachidonic acid selectively accumulate

during fetal and infant brain development and are

found concentrated in the brain and retina. Fetal

accretion of these lipids occurs during the last trimes-

ter of gestation, and a deficiency can result in visual

impairment and brain dysfunction. Although DHA

and arachidonic acid can be synthesized from dietary

precursors, the efficiency of this conversion in young

infants (particularly preterm infants) may not be

sufficient to meet their high need. Postnatally,

human milk provides high amounts of both arachido-

nic acid and DHA to the infant, but the amount of

these lipids in milk can be influenced by the mixture

of fatty acids in the maternal diet. The preterm, and

perhaps fullterm, infant not fed mother’s milk may be

at risk of deficiency if these lipids are not provided.

Animal studies have clearly illustrated that provision

of arachidonic acid and DHA to young animals im-

proves visual and neurological function. Despite con-

siderable evidence of improved visual function in

formula infants provided DHA (and in some studies

also arachidonic acid), the dietary requirements for

these fatty acids in the infant vary greatly between

countries. Recently, animal studies have provided evi-

dence that DHA obtained from plasma is involved

both in dopamine and serotonin metabolism in the

brain and in the retina for the function of rhodopsin.

These findings should guide clinical studies to more

sensitive measures of the functional roles of dietary n-

3 fatty acids. At present, there are promising prelim-

inary results regarding the efficacy of treating various

visual disorders and forms of depression with dietary

DHA.

Immune Function

0011There is now considerable scientific evidence, from

animal and human studies, that the amount and type

of fatty acids in the diet can modulate immune func-

tion. A deficiency of either n-6 or n-3 essential fatty

acids is associated with a reduced immune function.

Amongst the fatty acids, the n-3 fatty acids possess

the most potent immunomodulatory activities, and

amongst the n-3 fatty acids, those from fish oil (EPA

and DHA) are more potent than a-linolenic acid. In

particular, it has been demonstrated that feeding

DHA and EPA (often in a mixture of ‘immunoactive’

nutrients) decreases the rate of infections and im-

proves outcome (i.e., reduced complications, length

of stay, hospital cost) in immunosuppressed patients.

These effects are likely mediated through mechanisms

that involve indirect (i.e., via eicosanoids, hormone

action) and direct (regulation of transcription factors)

effects on genes in immune cells.

0012Many of the detrimental and lethal effects of infec-

tion and injury (especially detrimental effects) are

mediated by the proinflammatory cytokines (e.g.,

tumor necrosis factor a (TNF-a), interleukin (IL)-1

and IL-6) and eicosanoids. Thus, a reduction in the

synthesis of proinflammatory mediators would be

beneficial during critical illness and autoimmune

states. In both clinical trials and animal studies, feed-

ing DHA and EPA has been demonstrated to decrease

the expression of proinflammatory cytokines, genes,

eicosanoids, and adhesion molecules, whereas n-6

PUFAs increase the expression of proinflammatory

genes. These observations have formed the basis for

successful interventions with oral EPA and DHA to

treatacuteandchronicinflammation,andfordisorders

that involve an inappropriately activated immune

response (i.e., inflammatory bowel disease, rheuma-

toid arthritis, psoriasis, asthma, multiple sclerosis,

systemic lupus erythematosus, and atopic dermatitis).

0013A number of studies have also reported suppressed

cell-mediated immunity, but not generally humoral

immunity, in humans or animals fed very high levels

of DHA and EPA. One might conclude that consump-

tion of long-chain n-3 PUFA might be contraindicated

in those with poorly functioning immune systems.

However, the very low level of DHA and EPA and

the high level of linoleic acid currently in the diet of

most people questions the physiological relevance of

FATTY ACIDS/Dietary Importance 2321

n-3 immunosuppression in a healthy individual. To

support this, there are many studies reporting benefits

to the immune system when EPA/DHA are fed to

immunosuppressed individuals, such as those with

cancer or recovering from surgery. This suggests that

the effect of n-3 PUFA on immune function may

depend on the composition and content of other

fatty acids in the diet.

Disease Prevention and Treatment

0014 Epidemiological studies have concluded that con-

sumption of different amounts and types of fatty

acids over a lifetime can alter the risk for many chronic

diseases (e.g., heart disease, cancer). There is also

scientific evidence to support that dietary fatty acid

composition can be used in the prevention/treatment

of diseases such as coronary heart disease (CHD) and

cancer. Both n-6 and n-3 PUFA have been shown to be

of potential benefit in the treatment of acute respira-

tory distress syndrome and asthma. Beneficial effects

of feeding n-3 fatty acids have been shown in the

secondary prevention of CHD, hypertension, type 2

diabetes, and, in some patients with renal disease,

rheumatoid arthritis, inflammatory bowel diseases,

and chronic obstructive pulmonary disease.

0015 Coronary heart disease Individual fatty acids differ

in their ability to change blood cholesterol and lipo-

protein levels, two major risk factors for CHD.

0016 SFA For the past 30 years, epidemiological and ex-

perimental studies have found that the consumption

of a high SFA diet increases low-density lipoprotein

(LDL)-cholesterol levels, a major risk factor for

CHD. The precise mechanism for these effects has

not been established, but high intakes of SFA decrease

the removal of plasma LDL by LDL receptors, and

they may promote endogenous cholesterol synthesis.

More recently, studies have found that SFA have

varying effects on plasma lipid levels, depending on

their chain length. Much of this work has been

carried out on animals, and there is considerable

controversy as to the effect of stearic, palmitic,

myristic, and lauric acids on plasma lipid levels and

cholesterol synthesis. It is likely that the deleterious

effect of SFA on CHD in epidemiological studies is

explained by the hypercholesterolemic effects of myr-

istic, palmitic, and perhaps also lauric acid. There are

less data to support a hypercholesterolemic effect of

consuming stearic acid. Recently, research has sug-

gested that the cholesterol-raising properties of myr-

istic and palmitic acid may be related to the intake of

PUFA, such that, when PUFA falls below a threshold

intake (around 5% of energy), the cholesterol-raising

properties of these SFA are greatly augmented.

0017MUFA Generally, studies have found that popula-

tions that consume high MUFA diets have a lower

risk of CHD. Clinical and animal studies have con-

firmed that consumption of MUFA (i.e., oleic acid) is

associated with lower total- and LDL-cholesterol

levels and higher high-density lipoprotein (HDL)-

cholesterol levels. Consumption of MUFA has also

been reported to increase LDL-receptor activity.

0018n-6 PUFA Epidemiological studies report that

populations that consume 10% of their fats as linoleic

acid have a lower risk of developing CHD. A lower

dietary ratio of PUFA/SFA is associated with higher

plasma cholesterol concentrations and a higher popu-

lation risk of CHD. In clinical studies, it has been

shown that consumption of linoleic acid decreases

the synthesis of cholesterol in the body and increases

LDL-receptor activity, resulting in lower total- and

LDL-cholesterol levels. Most countries’ dietary

recommendations have attempted to promote an

increase in the intake of n-6 PUFA for its beneficial

effects on reducing the risk of CHD. However,

some studies have also indicated that a high intake

of n-6 fatty acids (much higher than the current rec-

ommendation of 10% of energy) may reduce HDL-

cholesterol levels and shift the physiologic state to one

that is prothrombotic and proaggregatory, changes

that are associated with an increased risk of CHD.

0019n-3 PUFA Epidemiological studies conclude that the

incidences of CHD and atherosclerosis are inversely

associated with consumption of n-3 PUFA, particu-

larly EPA. The antiatherosclerotic actions of n-3

PUFA have been supported in animal and human

clinical trials. Experimentally, it has been demon-

strated that consumption of n-3 fatty acids (a-lino-

lenic, DHA, or EPA) reduced plasma triacylglycerol

levels (very-low-density lipoprotein-triacylglycerols),

a risk factor for heart disease (especially in women).

Evidence for the beneficial effects of consuming n-3

PUFA on blood triacylglycerols, blood pressure, car-

diac and vascular function, eicosanoids, coagulation,

and immunological responses has prompted many

health agencies to recommend increasing the intake

of these fatty acids to reduce the risk of CHD. There is

still, however, a high degree of uncertainty in defining

both the type and amount of n-3 PUFA that is

considered preventative. In a recent metaanalysis of

studies examining the relationship between fish con-

sumption and CHD, it was concluded that consump-

tion of 40–60 g of fish each day was associated with a

markedly reduced CHD mortality in high-risk popu-

lations but not in low-risk populations. In cardiac

patients, there are reports of beneficial effects of

ingesting oily fish on the incidence of bypass graft

2322 FATTY ACIDS/Dietary Importance

occlusions, forearm vasodilation, arrhythmias, non-

fatal stroke, nonfatal myocardial infarction, and

cardiac death. There is also increasing evidence for

an antiarrhythmic action of n-3 PUFA in humans.

Most of the studies in high-risk populations have

been carried out by feeding fish oils (EPA and

DHA), and less is known about the effects of their

plant-derived precursor, a-linolenic acid.

0020 Trans-fatty acids A high consumption of trans-

fatty acids is associated with an increase in LDL-

cholesterol and a decrease in HDL-cholesterol, two

changes that would increase the risk of CHD. Trans-

fats account for about 2–8% of the calories in our

diets, compared with 12–14% for saturated fats. Cur-

rently, most nutritionists and researchers recommend

that hydrogenated fats containing trans-fatty acids be

limited or reduced in the diet.

0021 Cancer Human epidemiological and experimen-

tal studies have established a positive relationship

between high (mainly SFA) intake and cancer. How-

ever, high intakes of SFA or n-6 PUFA increase the

growth of tumors in several animal models, while

decreasing the n-6/n-3 ratio (by increasing the intake

of n-3 fatty acids) has been shown to inhibit the

growth and metastasis of rodent tumors. There is

convincing evidence that both DHA and EPA can

inhibit the growth of cancer cells (breast and colon)

both in vitro and in explants. It has been suggested

that the n-6/n-3 ratio of the diet, rather than the

absolute intakes of these PUFA, may define cancer

risk. Possible mechanisms include both direct effects

on tumor growth and indirect effects on anticancer

immune defenses. Although many studies support a

recommendation to decrease the n-6/n-3 ratio in the

diet, most cancer agencies do not yet feel that there

are sufficient human data to make recommendations

to the population. Current recommendations to pre-

vent cancer have been aimed at promoting a decrease

in dietary fat intake, focusing on reducing the intake

of SFA. There are currently no specific fatty acid

recommendations for those with, or recovering from,

cancer. There are data to support beneficial effects of

supplementing individuals with DHA/EPA. These

benefits include reducing tumor growth, improving

anticancer immune defenses, improving the response

to surgery, chemotherapy, and radiation treatments,

and decreasing cachexia-mediated weight loss.

Estimated Intakes and Recommendations

for Fatty Acids in the Diet

0022Quantitative dietary guidelines for fats were first

issued in the late 1970s and have changed relatively

little since that time. Current recommendations for

total fat in the diet of adults by most Western coun-

tries is less than or equal to 30% of energy. The lower

limit of fat intake to meet the energy needs of adults is

assumed to be between 10 and 15% of dietary energy,

provided that enough carbohydrates are available.

This minimum level depends on the fat requirement

to meet energy needs, the need for essential fatty

acids, and the amount of fat in the diet that is neces-

sary to absorb fat-soluble vitamins (particularly vita-

mins A and E). Most countries recommend that the

intake of SFA should not exceed 10% of the energy

intake, PUFA should comprise about 10% of energy

and the remainder of the intake of fat be comprised of

MUFA. A comparison of dietary fat and fatty acid

recommendations between several countries is shown

in Table 2.

SFA and MUFA

0023In the past 30 years, the absolute consumption of

SFA in Western diets has declined. For example, in

the UK, SFA intake has declined by 40%. Based on

the lower risk of some chronic diseases in Mediterra-

nean countries, where the population consumes

diets high in MUFA, it is generally recommended

that the population replace SFA with MUFA. How-

ever, since 1970, the intake of MUFA in the UK has

declined by 30%.

tbl0002 Table 2 Dietary fat recommendations from selective countries around the world

Country Total fat (percentage of energy) SFA (percentage of energy) MUFA (percentage of energy) PUFA (percentage of energy)

UK 33 10 None stated 6–10

Canada <30 10 None stated >3.5

USA 30 10 None stated None stated

Japan 20–25 6–8 8–10 6–8

New Zealand 30–35 12 20 8

Iceland 25–30 15 None stated None stated

Malaysia 20–30 10 10 10

Singapore 20–30 10 10 10

Source: Inform (2001) International News of Fats, Oils and Related Materials 12(2): 132–140, published by the AOCS Press.

FATTY ACIDS/Dietary Importance 2323

PUFA

0024 For adults, the recommended intake for essential

fatty acids is in the range of 3–5% of dietary energy

for linoleic acid, and 0.5–1.0% of dietary energy for

linolenic acid (about 1–4 g day

1

). During the past 60

years, in the UK, the consumption of PUFA has in-

creased by 25%, despite a decrease in total fat intake.

This was likely contributed to by the increased con-

sumption of linoleic acid in margarines and various

plant oils (sunflower, safflower, cottonseed, soybean,

canola). Estimated intakes of PUFA are similar in

North America, with the exception that the intake

of n-3 fatty acids may be lower than in the diet of

those in the UK. This increased intake of linoleic acid

(approximately 10–14 g day

1

) over the past decades

has changed the balance between n-6 and n-3 fatty

acids in the diet. Dietary intake studies, in developed

countries, estimate that the dietary n-6/n-3 fatty acid

ratio approaches 14:1–20:1. However, most studies

suggest that a ratio between 4:1 and 10:1 is needed to

achieve the health benefits associated with consump-

tion of n-3 fatty acids.

0025 Despite the health benefits of n-3 PUFA, the mean

daily intake falls far short of any current recommen-

dation. The intake of DHA and EPA in most de-

veloped countries is small and related to the intake

of fatty fish, and so promoting fish consumption is the

most obvious way to increase n-3 PUFA intake. In

North America, it is recommended that people should

have at least two servings of fish per week. On a

cautionary note, PUFA are oxidized more readily

than SFA and MUFA and may increase the suscepti-

bility of cellular membranes to lipid peroxidation.

Indeed, increased free-radical production has been

demonstrated in animals fed diets rich in n-3 PUFA.

Consuming additional antioxidants such as vitamin E

can minimize oxidation risk.

Conclusions and Summary

0026 Fat contributes more than a third of the energy in the

diet of most people. Fat comprises a number of differ-

ent fatty acids varying in carbon chain length and

degree of saturation. Specific dietary fatty acids have

many essential roles in the body in addition to pro-

viding an energy-efficient fuel. Changing the types or

fatty acids in the diet changes the composition and

function of membranes, eicosanoid synthesis, regu-

lates gene expression, controls neurological and retinal

development, and modulates immune function in

health and disease. There is considerable research

demonstrating the importance of n-3 PUFA or the

n-6/n-3 PUFA ratio in the prevention and treatment

of CHD and cancer. Onthe basis of current knowledge,

an increase in the consumption of long-chain n-3 fatty

acids seems a prudent recommendation. In summary,

dietary fatty intake represents a major environmental

factor affecting optimal growth, development, re-

sponse to injury, and overall health in the population.

See also: Cancer: Diet in Cancer Prevention; Diet in

Cancer Treatment; Fats: Requirements; Fatty Acids:

Properties; Metabolism; Gamma-linolenic Acid; Fats:

Classification

Further Reading

Calder PC (1999) Dietary fatty acids and the immune

system. Lipids 34 (Supplement): S137–S140.

Calder PC and Deckelbaum RJ (1999) Dietary lipids: more

than just a source of calories. Current Opinion in

Clinical Nutrition & Metabolic Care 2: 105–107.

Gibney MJ (1999) Strategies for altering population intakes

of fats and fatty acids. Proceedings of the Nutrition

Society 58: 189–191.

Hamosh M and Salem N, Jr. (1998) Long-chain polyunsat-

urated fatty acids. Biology of the Neonate 74: 106–120.

Innis SM (2000) The role of dietary n-6 and n-3 fatty acids

in the developing brain. Developmental Neuroscience

22: 474–480.

Marckmann P and Gronbaek M (1999) Fish consumption

and coronary heart disease mortality. A systematic

review of prospective cohort studies. European Journal

of Clinical Nutrition 53: 585–590.

Milner JA and Allison RG (1999) The role of dietary fat in

child nutrition and development: summary of an ASNS

workshop. American Society for Nutritional Sciences.

Journal of Nutrition 129: 2094–2105.

Mori TA and Beilin LJ (2001) Long-chain omega 3 fatty

acids, blood lipids and cardiovascular risk reduction.

Current Opinion in Lipidology 12: 11–17.

Roche HM (1999) Unsaturated fatty acids. Proceedings of

the Nutrition Society 58: 397–401.

Simopoulos AP (1999) Essential fatty acids in health and

chronic disease. American Journal of Clinical Nutrition

70: 560S–569S.

Uauy R and Valenzuela A (2000) Marine oils: the health

benefits of n-3 fatty acids. Nutrition 16: 680–684.

Trans

-fatty Acids: Health

Effects

A Aro, National Public Health Institute (KTL), Helsinki,

Finland

Effects on Serum Lipoproteins

0001Early studies on the effects of trans-fatty acids on

serum total cholesterol levels in human subjects gave

conflicting results. Studies in experimental animals

2324 FATTY ACIDS/

Trans

-fatty Acids: Health Effects

like rats, mice, and pigs did not show any appreciable

difference between the effects on serum cholesterol of

partially hydrogenated vegetable oils and nonhydro-

genated oils. Therefore, the common impression was

that trans-fatty acids were not hypercholesterolemic

or that their effect on serum cholesterol concentration

was weak and clinically not important. This impres-

sion was not changed until studies focusing attention

separately on low-density lipoprotein (LDL) and

high-density lipoprotein (HDL) became available in

the 1990s.

0002 Since 1990, several dietary intervention trials have

indicated that, when compared with oleic acid, trans-

fatty acids from partially hydrogenated vegetable oils

or fish oils increase serum LDL-cholesterol and tend

to reduce HDL-cholesterol in a dose-dependent

manner (Figure 1). The increase in LDL-cholesterol

has been apparent in all studies, but without a clear

dose-effect. The HDL-cholesterol concentration has

showed little change by small doses of trans-fatty

acids, but higher amounts, in the order of 6–11% of

energy, have clearly reduced HDL-cholesterol con-

centrations in a dose-dependent manner. In most

studies, the LDL-cholesterol-raising effect has been

somewhat weaker than that of equal amounts of

C12–16 saturated fatty acids, but this may partly

depend on short study periods. Corresponding effects

on serum apoproteins, an increase in apoprotein B

and a decrease in apoprotein A-I concentration,

have been found in those studies where apoprotein

concentrations have been measured. In some studies,

an increase in serum triglycerides has been observed

but the effect has been weak and generally statistic-

ally nonsignificant.

0003Partially hydrogenated fish oils that are used in

some countries like Iceland and Norway and were

previously also consumed in other north-western

European countries seem to have a more powerful

effect on serum lipoproteins than trans-fatty acids of

vegetable origin (Figure 2). The isomeric composition

of C18:1 trans-fatty acids is rather similar in partially

hydrogenated vegetable and fish oils, but the various

long-chain C20–22 trans-isomers that are formed

when fish oils are chemically hydrogenated may

have an exceptionally strong LDL-cholesterol-raising

effect. The effect on lipoproteins of the delta-11

isomer trans-vaccenic acid, the main trans-isomer of

animal fats, has not been studied separately from

other fatty acids, because pure preparations have

not been available for this purpose. The effects of

different C18:1 trans-isomers may vary, because the

isomers are metabolized by different routes. Trans-

vaccenic acid is desaturated to conjugated linoleic

acid (CLA) by the delta-9-desaturase, whereas the

main isomers of partially hydrogenated vegetable

and fish oils, the delta-9-(elaidic acid) and delta-

10-isomers, cannot be metabolized by this pathway.

The effects of CLA on the risk of coronary heart

disease (CHD) are poorly known, but some CLA-

isomers may have antiatherogenic properties

according to experimental studies in animals. Infor-

mation on the metabolism of trans-fatty acid isomers

is limited. Generally, the trans-isomers seem to be

metabolized by the same pathways as the correspond-

ing cis-isomers.

−0.3

−0.2

−0.1

0.1

0.2

0.3

0.4

0510

Cholesterol (mmol l

−1

)

Trans - C18:1 (% of energy)

LDL

HDL

fig0001 Figure 1 Effects on serum low-density lipoprotein (LDL)-

cholesterol (closed symbols) and high-density lipoprotein

(HDL)-cholesterol concentrations (open symbols) of trans-fatty

acids from partially hydrogenated vegetable oils as compared

with oleic acid in six controlled dietary trials. Data from Katan

MB, Zock PL and Mensink RP (1995) Tr a n s fatty acids and their

effects on lipoproteins in humans. Annual Review of Nutrition 15:

473–493.

−0.5

−0.4

−0.3

−0.2

−0.1

0.1

0.2

0.3

0.4

0.5

Cholesterol LDL-chol HDL-chol Triglycerides

mmol l

−1

fig0002Figure 2 Effects on serum and lipoprotein lipids by 3-week

feeding of partially hydrogenated fish oil (dark columns), partially

hydrogenated vegetable oil (gray columns), and butter (light

columns). The columns indicate changes from a customary Nor-

wegian background diet. LDL-chol, low-density-lipoprotein chol-

esterol; HDL-chol, high-density lipoprotein cholesterol. Data from

Almendingen K, Jordal O, Kierulf P, Sandstad B and Pedersen JI

(1995) Effects of partially hydrogenated fish oil, partially hydro-

genated soybean oil, and butter on serum lipoproteins and Lp[a]

in men. Journal of Lipid Research 36: 1370–1384.

FATTY ACIDS/

Trans

-fatty Acids: Health Effects 2325

0004 In the clinical trials with partially hydrogenated

vegetable oils and fish oils, amounts of trans-fatty

acids (3–10% of energy) have been used that are

higher than the habitual consumption in most coun-

tries. The trans-fatty acids have been derived from

specially designed products high in trans-fatty acids

and not from commonly available foods. Therefore it

is difficult to estimate the effects of the amounts that

are habitually consumed by people in western coun-

tries as part of their diets. Studies on the composition

of foods have revealed that processed foods that

contain trans-fatty acids often contain more cis-

unsaturated fatty acids than the corresponding foods

that are based on saturated animal fats. As an

example, icecream that is manufactured from par-

tially hydrogenated vegetable oil contains more cis-

unsaturated fatty acids than icecream based on milk

fat or coconut oil. Thus the effects of moderate

amounts of trans-fatty acids may be balanced by the

neutral or LDL-cholesterol-reducing effects of the

concomitant cis-unsaturated fatty acids of the same

foods.

Trans

-Fatty Acids and Risk of Coronary

Heart Disease

0005 The observed effects of dietary trans-fatty acids on

serum lipoproteins, an increase in LDL-cholesterol

concentration combined with a reduction in HDL-

cholesterol, are expected to increase the risk of

CHD. The associations between trans-fatty acid

intake and risk of CHD have been studied in several

case-control studies and cohort studies. Some studies

have supported the concept of increased risk of CHD

by high consumption of trans-fatty acids, but the

results have been somewhat controversial.

0006In most case-control studies the fatty acid compos-

ition of adipose tissue or serum has been used as an

indicator of trans-fatty acid intake. In three studies,

C16:1 trans-fatty acids that are mainly derived

from fats of animal origin were higher in cases

than in control subjects, but in other studies the

C16:1 trans-isomers did not show significant associ-

ations with the risk of CHD. In six of the studies, no

significant case-control difference was found in

C18:1 trans-fatty acids. One study showed a direct

association between C18:1 trans-fatty acids in plate-

let phospholipids and risk of CHD, and one study

showed an inverse association between C18:1 trans-

fatty acids in adipose tissue and risk of sudden cardiac

death. One study from the USA, based on food intake

data, showed an increased relative risk of CHD in the

highest quintile of trans-fatty acid intake but a de-

creased risk in the third quintile, representing moder-

ate intake. In the largest of the case-control studies,

the multicenter EURAMIC study, adipose tissue

samples from 671 male survivors of a first acute

myocardial infarction and from 717 reference men

were studied. No overall case-control difference was

found in C18:1 trans-fatty acids (Figure 3). The

0 0.5 1 1.5 2 2.5 3

All countries

Spain (Granada)

Spain (Malaga)

Germany

Finland

Russia

Switzerland

Israel

Norway

Scotland

Netherlands

Cases

Controls

Adipose tissue C18:1 trans-fatty acids (%)

fig0003 Figure 3 Mean proportions of adipose tissue C18:1 trans-fatty acids in male survivors of a first myocardial infarction (cases) and

male control subjects without coronary heart disease (controls) in the nine countries of the European multicenter, case-control

EURAMIC study conducted in 1991–92. Data from Aro A, Kardinaal AFM, Salminen I et al. (1995) Adipose tissue isomeric trans fatty

acids and risk of myocardial infarction in nine countries: the EURAMIC study. Lancet 345: 273–278.

2326 FATTY ACIDS/

Trans

-fatty Acids: Health Effects

case-control differences differed between the coun-

tries. In Norway and Finland, cases with acute myo-

cardial infarction had significantly higher

proportions of trans-fatty acids in the adipose tissue

than control subjects. In Russia and one of the Span-

ish centers, a significant difference in the other direc-

tion was found. The results showed up to sixfold

differences between the countries in adipose tissue

trans-fatty acids, suggesting large differences in the

average dietary intakes of trans-fatty acids between

the nine participating countries.

0007 The differences in dietary intakes were subse-

quently confirmed by the TRANSFAIR study in 14

European countries. When the two Spanish centers of

the EURAMIC study that showed very low propor-

tions of C18:1 trans-fatty acids in the adipose tissue

were excluded, the results suggested a borderline sig-

nificant increase in the relative risk of CHD in the

two highest quartiles of adipose tissue C18:1 trans-

fatty acids compared with the lowest quartile. The

C18:1 trans-fatty acids are the largest and clinically

most important cluster of trans-fatty acids. The C16:1

trans-fatty acids are a minor component mainly

derived from ruminant animal fats. Different cis/

trans-isomers of C18:2 are derived in relatively

small quantities from both partially hydrogenated

vegetable oils and ruminant animal fats. Epidemi-

ological studies do not suggest any major impact on

the risk of CHD by these small trans-fatty acid

clusters.

0008 The discordant results of the case-control studies

seem to reflect more analytical problems, problems in

interpreting the fatty acid composition of tissues, and

difficulties in distinguishing between the causes and

effects of the disease in subjects with diagnosed CHD

than real effects on the risk of CHD. The differing

results may also indicate that trans-fatty acids in

tissues are markers of some other associated factors

that have more impact on CHD risk than the small

amounts of trans-fatty acids in the diet. Overall, the

results seem to agree with the concept that the current

average intakes of trans-fatty acids are too low to

have a significant effect on CHD risk.

0009Four cohort studies have addressed the association

between the intake of trans-fatty acids measured

either with semiquantitative food-frequency ques-

tionnaires or modified dietary history methods.

All these studies showed a significantly increased

relative risk of CHD in the highest quintile or tertile

of trans-fatty acid intake compared with the lowest

(Table 1). The increased risk was associated with

high intakes of C18:1 trans-fatty acids only, whereas

moderate intakes were not significantly associated

with the risk of CHD. In the female and male

cohorts from the USA and in the male ATBC study

cohort from Finland, the mean intake of trans-fatty

acids in the highest quintile was between 1.6 and

2.9% of energy intake. In the Dutch Zutphen elderly

study, the median intake of the highest tertile was

much higher – 6.4% of energy intake. The results of

the two US studies suggested that the increased risk

of CHD was due to trans-fatty acids from partially

hydrogenated vegetable oils only, whereas in the

Dutch study, no difference between the risk effects

tbl0001 Table 1 Multivariate

relative risk (RR) and 95% confidence intervals (CI) of coronary heart disease in cohort studies in relation to

trans-fatty acid intake

Intake of trans-fattyacids

Quintile 1 (low) Quintile 2 Quintile 3 Quintile 4 Quintile 5 (high)

Nurses’ Health Study (Hu et al., 1997)

No. of cases 939

RR (95% CI) 1.0 1.07 (0.86–1.33) 1.10 (0.89–1.37) 1.13 (0.91–1.39) 1.27 (1.03–1.56)

Health Professionals

Follow-upStudy(Ascherioetal.,1996)

No. of cases 112 140 147 154 181

RR (95% CI) 1.0 1.12 (0.86–1.44) 1.12 (0.87–1.44) 1.12 (0.86–1.46) 1.21 (0.93–1.58)

ATBCstudy(Pietinenetal.,1997)

No. of cases 244 288 268 297 302

RR (95% CI) 1.0 1.10 (0.93–1.31) 0.97 (0.82–1.16) 1.07 (0.90–1.28) 1.14 (0.95–1.35)

Tertile 1 (low) Tertile 2 Tertile 3 (high)

Zutphen elderly study (Oomen et al., 2001)

No. of cases 24 30 44

RR (95 CI) 1.0 1.34 (0.76–2.37) 2.00 (1.07–3.75)

Adjusted for various risk factors of coronary heart disease.

Oomen CM, Ocke

MC, Feskens EJM et al. (2001) Tr a n s fatty acid intake is associated with an increased 10-year risk of coronary heart disease in the

Zutphen Elderly Study. Lancet 357: 746–751.

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Trans

-fatty Acids: Health Effects 2327