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

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As much as a 10% variation in oil content among

individual fish of the same species may be found.

Fatty acid analyses of commercial fish oils given as

ranges of values are more predictive of actual content

than data from analysis of oil extracted from a small

number of specimens of fish or fish tissues. Addition-

ally, oil as a byproduct of fish meal production will

have a different fatty acid content than oil from the

same species that has been solvent extracted, perhaps

owing to phospholipid fatty acids remaining in the

fish meal. HUFAs are particularly susceptible to this

phenomenon. (See Fish: Fish as Food.)

Liver Oils

0010 Fish liver oils contain slightly different proportions of

triglyceride and phospholipid fatty acids, as well as

minor components, than body oils. The DHA concen-

tration is apt to be higher than in herring or men-

haden body oils. Shark liver oils may have amounts

of diacylglyceryl ethers approaching those of trigly-

cerides. These glyceryl ethers are also found, to a

far lesser degree, in certain shark body oils and a

few other species of fish. The fatty acids of these

alkoxydiglycerides are predominantly saturated, and

monoenoic in the etherlinked portion, and the ester-

linked fatty acids are about 25% HUFAs.

Minor Components

0011 Phospholipids, approximately 50% lecithin and 25%

cephalin, contribute to the total fatty acid, especially

HUFA, content. Phospholipids are associated with

cell membranes and, therefore, are scarce in oil pro-

duced as a byproduct of meal production. Hydrocar-

bons are present at very low levels in most fish oils,

but the liver oil of several species of shark may be up

to 90% squalene (Figure 1) with small amounts of

pristine and zamene. Hydrocarbons are usually found

in those fish oils containing alkoxydiglycerides. (See

Phospholipids: Properties and Occurrence.)

0012 Sterols, almost all being cholesterol (Figure 1), are

always present in crude fish oils, with concentrations

between 5 and 8 mg per gram of oil. Processing, how-

ever, can remove much free cholesterol and some

cholesterol esters.

0013 Wax esters, while present in certain species of fish

(e.g., orange roughy), are not found in liver oils or in

marketed fillets as the esters occur just under the skin

and are removed by deep cutting during fillet pre-

paration. The fat-soluble vitamins A, D and E are

always found as minor components, although levels

present are subject to the variables previously men-

tioned. While body oils contain relatively low

amounts of A and D, liver oils are considerably

higher. Menhaden oil contains 60–150 RE/g of vita-

min A and 1.25–2.50 mg/g of vitamin D. Vitamin A in

halibut, shark and tuna liver oils is of high potency

(up to 210 000 RE/g) while cod liver oil has a lower

content (up to 1800 RE/g). Vitamin D in cod liver oil

is usually less than 2.5 mg/g while some tuna liver oils

reach 1250 mg/g. Vitamin A in halibut, shark and tuna

liver oils is of high potency (up to 700 000 IU g

1

while cod liver oil has a lower content (up to

6000 IU g

1

). Vitamin D in cod liver oil is usually

less than 100 IU g

1

, while some tuna liver oils reach

250 000 IU g

1

.(See Cholecalciferol: Physiology;

Retinol: Physiology; Tocopherols: Physiology.)

0014The vitamin E (tocopherol) content of fish oils is

similar to that of vegetable oils. Typical published

values range between 40 and 630 mgg

1

, with cod

liver oil about 560 mgg

1

and herring oil about

100 mgg

1

0015Carotenoid pigments such as astaxanthine may be

present as a result of dietary components. These pig-

ments give an orange–red tint to the oil. (See Caro-

tenoids: Physiology.)

0016Oxidation and hydrolytic products, free fatty acids

and amines, peroxides, carbonyls, and volatile com-

pounds will be present to various degrees, reflecting

the stability of the oil. Spoilage impurities from fish

can contribute objectionable off-odors and off-

flavors to their extracted oils. Insoluble matter, such

as moisture, dirt, protein, and rust is removed or

reduced to < 5%. Soluble impurities include pig-

ments, trace metals, oxidation and decomposition

products (e.g., sulfur and phosphorus), mono- and

diglycerides and unsaponifiables. Contaminants that

occasionally may be found, depending on the source

of crude oil, are pesticide residues and chlorinated

biphenyls. The processing steps of hydrogenation

and deodorization remove or reduce these com-

pounds to nondetectable levels.

Stability

0017Deterioration of fish oils is associated with oxygen

and/or heat. Free fatty acids are hydrolytic products

of triglycerides, and levels above 3% are indicative of

poor oil quality. Most changes, however, are the

result of oxidation of fatty acid portions of triglycer-

ides. The ethylene bonds of fatty acids are very react-

ive and combine with oxygen and peroxides. Because

fish oils are highly unsaturated, they are more vulner-

able to exposure to air than vegetable oils, even

though the oxidative mechanisms operate in the

same manner, albeit at an increased rate. An induc-

tion period during which changes are not readily

detected is followed by autoxidation involving for-

mation of free radicals and free radical chain

propagation (Figure 2). During this time, free radicals

react with oxygen to form hydroperoxides. Terminal

2498 FISH OILS/Composition and Properties

Initiation step:

Propagation steps:

HH H

(Hydrocarbon

chain radical)

HHH

OOH

(Hydroperoxy

radical)

Decomposition of the hydroperoxide forms additional radicals:

LIPID OXIDATION

AH represents the antioxidant:

(Terminates)

(Does not react)

ANTIOXIDANT ACTION

fig0002 Figure 2 Oxidation and free radical chain propagation leading to rancidity. Antioxidants inhibit and interrupt free radical propaga-

tion. Reproduced from Fish Oils: Composition and Properties, Encyclopaedia of Food Science, Food Technology and Nutrition, Macrae R,

Robinson RK and Sadler MJ (eds), 1993, Academic Press.

FISH OILS/Composition and Properties 2499

oxidation products include peroxides, carbonyls such

as malonaldehyde, and objectional flavor and odor

compounds created by the decomposition of perox-

ides and oxidation of breakdown products. Plots

of storage time versus degree of oxidation give a

typical induction curve, indicating an accelerating

oxidation rate. The increase in carbonyls and hydro-

peroxides is roughly equivalent to oxygen uptake.

Compared with most other oils, fish oils increase in

peroxide value (PV) earlier and the break in the in-

duction curve is less sharp. (See Oxidation of Food

Components.)

Flavors and Odors

0018 ‘Fishy’ flavors and odors occur early in oxidation and

will continue if the oil is stored with limited access to

air. Even when the PV is low, reversion flavors, char-

acterized as ‘beany’ or ‘grassy,’ can be present. Rever-

sion is characterized by a return to preprocessing

flavors after storage and occurs before the onset of

rancidity. The rancid odors and flavors developing

later are typical of all rancid fats and oils. Capillary

gas-chromatographic methods for analysis of volatile

products have made possible the chemical identifica-

tion of specific odours. Fish oil stability is best main-

tained by low-temperature storage and exclusion of

oxygen. (See Flavor (Flavour) Compounds: Structures

and Characteristics; Sensory Evaluation: Aroma.)

0019 Sometimes fish oils are produced from fish that

have not been properly refrigerated, and considerable

bacterial or enzymatic spoilage may have occurred.

Volatile products of spoilage will be partially trans-

ferred to the oil. Initially, spoilage products that

predominate are nitrogenous, especially trimethyla-

mine. Later, sulfur compounds may contribute to

the more obnoxious odors as well as act as catalyst

inhibitors.

0020 The presence of prooxidants, such as free fatty acids

and other natural impurities, hematin compounds,

metal ions, peroxides, heat, air, and light as well as

antioxidants and the levels of o-3 fatty acids, deter-

mine the length of the induction period. With o-3

fatty acids, there is a less distinct break in the induc-

tion curve, and antioxidants are less effective during

this period. Since chemical tests do not give values

that consistently correspond to a specific degree of

rancidity, additional sensory evaluation by trained

test panels is necessary for satisfactory stability deter-

mination. Different degrees of rancidity are readily

detectable.

Antioxidants

0021 Antioxidants are substances that, at relatively low

concentrations, inhibit the rate of reaction of an

oxidizable substrate with oxygen by reacting with

a free radical early in the oxidation process. The

intermediate compound formed is unable to continue

the free radical chain reaction. Synthetic antioxidants

– polyphenolic compounds – are added to fish oils to

increase induction periods, as they are more effective

than the naturally occurring antioxidants that are

present in oils of both fish and plants. The toco-

pherols, eight or more, but mostly a-tocopherol,

occur over a range of concentrations in fish oils

from 40 to 630 mg per gram of oil. While the vitamin

E activity is highest in a-tocopherol, antioxidant ac-

tivity is less than in some of the other tocopherols.

The tocopherols are readily oxidized and are des-

troyed by heat. Among compounds that exert syner-

gistic antioxidant activity are lecithin, squalene, and

metal sequestrants such as ascorbic, citric, and

phosphoric acids. (See Antioxidants: Natural Anti-

oxidants; Synthetic Antioxidants.)

Determination of Fatty Acids and

Triglycerides

0022Gas–liquid chromatography (GLC) is a commonly

used method for lipid analysis. Although marine

fatty acids are generally derivatized by transesterifi-

cation, saponification and extraction followed by

derivatization to fatty acid methyl esters (FAMEs)

may be used. Separation of lipid classes and purifica-

tion of FAMEs before GC, mass spectroscopy, and

Fourier transform infrared spectroscopy, which

enable analysis of individual fatty acid derivatives

separated by GLC, is followed by computer predic-

tion of identities. High performance liquid chroma-

tography (HPLC) provides higher resolution and

greater accuracy, but is more expensive and not uni-

versally available. HPLC can identify individual tri-

glycerides (acylglycerides) while mono and

diglycerides may be determined, after HPLC separ-

ation, with an evaporative light scattering detector.

(See Chromatography: Thin-layer Chromatography;

Gas Chromatography; Fatty Acids: Analysis; Mass

Spectrometry: Principles and Instrumentation; Trigly-

cerides: Characterization and Determination.)

0023Chain length can be determined by the linear rela-

tion between the logarithm of retention time and the

number of carbon atoms. Tables of calculations of

equivalent chain length (ECL) may be used to identify

FAMEs separated by GC.

0024Further refinement of GC and related technology

culminated in a collaborative study to develop

an Association of Official Analytical Chemists

(AOAC)-approved method to analyze fish oils and

fish oil ethyl esters of PUFAs. This method, utilizing

wall-coated open tubular GC (WCOT-GC) and flame

ionization is especially suitable for analysis of

2500 FISH OILS/Composition and Properties

encapsulated fish oil and concentrated o-3 compon-

ents obtained by fractionation from triglycerides.

0025 When such instruments are not available, GC may

be used with several other AOAC, American Oil

Chemist’s Society or International Association of

Fish Meal Manufacturers methods such as bromina-

tion, hydrogenation, argentation TLC, urea adduc-

tion, ozonolysis and/or hydrazine reduction.

Bromination distinguishes between saturated and

unsaturated FAMEs, as does hydrogenation with re-

analysis. Argentation TLC involves separation of

FAMEs on silver nitrate-impregnated silica gel-coated

TLC plates followed by GC analysis of the fractions.

Urea crystallization concentrates branched-chain,

cyclic, and unsaturated FAMEs or nonesterified

acids. Ozonolysis has long been used to determine

the structure of unsaturated fatty acids and esters.

The resulting ozonides are then fragmented by chem-

ical reduction or oxidation. Partial hydrazine reduc-

tion can locate ethylene bonds.

Determination of Minor Components

0026 Lipids that are present in relatively small amounts or

are present in oil from very few species include phos-

pholipids, cholesterol, hydrocarbons, and diacylgly-

ceryl esters. Triglycerides are extracted with diethyl

ether, whereas chloroform–methanol extracts phos-

pholipids. Cholesterol is determined by WCOT-GC.

0027 Commercial fish oils are routinely analyzed for free

fatty acids, iodine value (IV), moisture, impurities,

and color. Free fatty acids are measured by titrating

with alkali. The IV measures unsaturation and, there-

fore, the oxidation potential of the oil. Iodine com-

bines with fatty acids at ethylene bonds and thereby

enables a measurement of unsaturation. As oxygen or

peroxides react at these bonds, the IV increases. By

the Wijs method, oil is combined with potassium

iodide, and values are expressed as grams of iodine

absorbed per 100 g of sample. Moisture is determined

by distillation with an immiscible solvent. The per-

centage of unsaponifiable matter is gravimetrically

determined after several alkali extractions of saponi-

fiables. Color is designated by Gardner numbers after

comparison with consecutively numbered standards.

0028 Determination of stability in fish oils involves ana-

lyzing for hydrolytic and oxidative degradation prod-

ucts. Chemical tests most often used are to determine

free fatty acid, the IV, the thiobarbituric acid (TBA)

value, the anisidine value and the gain in weight of the

sample during the course of oxidation. Since these

tests do not give values that consistently correspond

to a specific degree of rancidity, additional sensory

evaluation by trained test panels is necessary for sat-

isfactory stability determination.

0029The hydroperoxide decomposition product, malo-

naldehyde, reacts with TBA to give a pink color. PV

indicates the content of hydroperoxide, an initial

chemical oxidation product. The hydroperoxides oxi-

dize potassium iodide and the liberated iodine is ti-

trated with thiosulfate. The anisidine value is related

to the level of breakdown products of hydroperoxides

present and measures unsaturated aldehydes. Vita-

mins and contaminants may be detected by several

AOAC methods. Heavy metals are best detected with

cyclic instrumental neutron activation, although

atomic absorption spectrometry is adequate where

only a few selected (known) metals are to be deter-

mined. Chlorinated biphenyls are best indicated by

WCOT-GC. Refined fish oil ready for further pro-

cessing has minimal identifiable impurities and is,

essentially, all triglyceride. (See Contamination of

Food; Heavy Metal Toxicology.)

See also: Carotenoids: Physiology; Cholecalciferol:

Physiology; Chromatography: Thin-layer

Chromatography; Fats: Classification; Fatty Acids:

Properties; Metabolism; Analysis; Fish: Fish as Food;

Mass Spectrometry: Principles and Instrumentation;

Phospholipids: Properties and Occurrence; Retinol:

Physiology; Tocopherols: Physiology; Triglycerides:

Structures and Properties; Characterization and

Determination; Vegetable Oils: Dietary Importance

Further Reading

Ackman RG (1982) Fatty acid composition of fish oils. In:

Barlow SM and Stansby ME (eds) Nutritional Evalu-

ation of Long-chain Fatty Acids in Fish Oil, pp. 25–88.

London: Academic Press.

AOAC (1990) Official Methods of Analysis of the AO AC,

15th edn. Washington, DC: Association of Official Ana-

lytical Chemists.

AOCS (1998) Official Methods and Recommended Prac-

tices of the AOCS, 5th edn. Champagne, IL: American

Oil Chemists’ Society.

Hamilton RJ and Rice RD (eds) (1995) Fish Oil: Technol-

ogy, Nutrition and Marketing. London: PJ Barnes and

Associates.

Nollet LM (ed.) (1996) Handbook of Food Analysis, vol. 1.

New York: Marcel Dekker.

Pigott GM and Tucker BW (1990) Seafood: Effects of Tech-

nology on Nutrition. New York: Marcel Dekker.

Stansby ME (ed.) (1967) Fish Oils. Westport, CT: AVI.

Stansby ME (1981) Reliability of fatty acid values purport-

ing to represent composition of oil from different species

of fish. Journal of the American Oil Chemist’s Society

58: 13–16.

Stansby ME (ed.) (1990) Fish Oils in Nutrition. New York:

AVI, Van Nostrand Reinhold.

Windsor M and Barlow S (1981) Introduction to Fishery

By-products. Farnham: Fishing News Books.

FISH OILS/Composition and Properties 2501

Dietary Importance

R Rice, The Fish Foundation, Tiverton, UK

Fish Oils

0001 The oils from cold-water fish are unique among all

of the edible oils and fats. They are the only nutrition-

ally significant source of the long-chain omega-3

(o-3 or n-3) polyunsaturates. The liver oils from

fish such as cod and halibut have an added feature

in that they are the major natural sources of vitamins

A and D.

0002 Changes in eating habits over the last 100 years

have resulted in marked changes in fat intake, and in

particular in the intake of the polyunsaturates con-

sidered essential for human health. Two families of

polyunsaturates are considered essential, and they are

known as o-3 (or n-3) and o-6 (or n-6). Average

intakes of the o-3 family have fallen considerably,

while at the same time, intakes of the o-6 family

have increased dramatically. For reasons that will be

explained, this change has placed more emphasis on

the need to insure an adequate intake of preformed

long-chain o-3 polyunsaturates from fish. The causes

and consequences of this change will be explored in

what follows. In particular, attention will focus on the

dietary role of the polyunsaturates, on the way in

which dietary intake of polyunsaturates has changed

over the years, and on the health impact of these

dietary changes, in areas such as heart disease, inflam-

matory disease, skin, lung and kidney diseases, and

mental health.

0003 A summary of current suggestions for recom-

mended intakes will complete this overview.

Dietary Polyunsaturates

Essential Fatty Acids

0004 The world is now generally familiar with the concept

that certain food components are vital to continued

good health. Vitamins, minerals, and the essential

amino acids are well studied and documented. What

is less well known is that there are also certain types

of fat that are essential to good health, fats which

cannot be manufactured by the human body, and

thus must be supplied preformed in the diet. The

concept of ‘essential’ fats was originated by George

and Mildred Burr and colleagues, working in the USA

in the late 1920s. They found that rats fed on syn-

thetic diets devoid of any fat developed scaly tails and

skin problems that could be corrected by adding some

corn oil. Their work started the thinking that there

might be some factor or factors in fats that were

essential to health. This work, and that of other

pioneers such as Ralph Holman and Hugh Sinclair

led to the realization that there were two distinct

factors, originally termed vitamins F

and F

. It was

soon discovered that these factors were not vitamins

as such, but nevertheless had significant health

impacts if they were excluded from the diet. They

were therefore called ‘essential fatty acids,’ and

further work identified the two substances as polyun-

saturated fatty acids, linoleic acid (18:2, w-6) and

a-linolenic acid (18:3, w-3). Though this work was

of necessity carried out on laboratory animals,

such as rats, current nutrition thinking is that

humans are equally in need of the essential poly-

unsaturates. The impact of a lack of dietary polyun-

saturates is a long-term impact, with effects taking

many weeks or months to become apparent. In such

circumstances, it is difficult to see how ethical experi-

ments could be designed to prove the need for the

essential polyunsaturates in humans, though some

data from human accident victims, and parenteral

feeding studies do provide limited direct proof of

their essentiality for humans.

Metabolism of Polyunsaturates

0005The dietary 18 carbon fatty acids linoleic and

a-linolenic are converted, by a common enzyme

system, into 20 and 22 carbon derivatives (see Figure

1). Since the conversion enzymes are the same for

both o-3 and o-6 polyunsaturates, the phenomenon

of competitive inhibition occurs. This means that

if there is a predominance of one family over the

other, the subordinate family gets crowded out of

enzyme sites, and the conversion process favors the

dominant family. The result is that an excess of the

dietary o-6 polyunsaturate linoleic acid inhibits con-

version of the o-3 polyunsaturate a-linolenic acid to

the 20 and 22 carbon forms eicosapentaenoic acid

and docosahexaenoic acid. Fish are the only nutri-

tionally significant source of preformed long-chain

o-3 polyunsaturates, so consumption of fish can in

principle compensate for the inhibition of the conver-

sion process. However, in many Western countries,

fish consumption is low and falling. The long-chain

polyunsaturates (of both families) have most of the

true biological functions of the essential polyunsatur-

ates. These can be broadly categorized as:

0006Components of cell membranes, conferring crit-

ical properties on the membrane.

0007Precursors of short-lived, powerful biological

regulators known collectively as eicosanoids.

0008Components in the regulation of gene-expression.

2502 FISH OILS/Dietary Importance

Membrane Composition

0009 All cells in the human body consist of a membrane

surrounding the cell contents. These contents vary,

depending on whether the cell is a skin cell, a bone

cell, or indeed a nerve cell. Whatever job the cell does,

the membrane surrounding it will be structurally

similar, and an important feature is that it contains

significant amounts of polyunsaturates. The exact

structure and composition of the membrane in differ-

ent cells within the body are determined by various

factors including genetics, location, function, and

diet. Diet affects membrane properties and function,

by means of the amount and make-up of the polyun-

saturates supplied in the diet and thus available for

incorporation. Every cell in the human body has a

need for both o-6 and o-3 polyunsaturates. Both are

needed for optimal health, and if one or the other

dominates, health can be compromised, as will be

made clear in later sections.

Eicosanoid Precursors

0010 The concept of endocrine hormones (such as insulin)

is well established: these are chemical substances se-

creted into the bloodstream and carried by the circu-

latory system to any and every cell in the body, and

which have specific receptors in target cells that react

to the presence of the hormone, bringing about a

change.

0011 There is another system of regulators found within

the body, known collectively as ‘eicosanoids,’ named

after the 20 carbon fatty acids (Greek eicos¼20) from

which they are formed. These substances are much

more powerful in their actions than the endocrine

hormones, so much so that they cannot be centrally

produced and distributed, but must be produced

locally, in the cells where they are needed, and then

destroyed soon afterwards. So far, two families of

eicosanoids are well known and understood: the pros-

taglandins, and the leukotrienes. A third subgroup,

known collectively as lipoxins, may also be a part of

this wider group, though lipoxins are less well studied

or understood at present.

0012The dietary 18 carbon polyunsaturates are metab-

olized to 20 carbon forms, which are then available

for further metabolism by oxidative enzymes such

as cyclooxygenase, or lipoxygenase. The oxidation

products of the cyclooxygenase enzyme are available

for further metabolism to prostaglandins, whereas

the oxidation products of the lipoxygenases are fur-

ther metabolized to form leukotrienes. Both o-3 and

o-6 polyunsaturates are capable of being metabolized

by these enzyme systems, and the resultant end

products, though structurally similar, have functional

properties that are slightly but significantly different.

The point can be illustrated by reference to the circu-

latory system.

0013The clotting power of blood is obviously a valuable

self-repair mechanism, but one that can sometimes be

triggered when clotting is not needed, and this can

lead to formation of a clot, or thrombus, within the

intact circulatory system, resulting in a blockage of

the flow of blood through a blood vessel. If this

happens in an artery supplying blood to heart muscle,

a heart attack can be triggered. If it happens in an

artery supplying blood to the brain, a stroke can

result. The circulatory system has an elaborate system

of checks and balances to control this process. The

cells that line the interior surfaces of blood vessels are

known as endothelial cells, and they are equipped

with an enzyme system that makes a substance called

prostacyclin from the C20 polyunsaturates contained

% fat cals

(−4 10)

(−10

000) 1800

Time (years)

Saturated

Hunter−Gatherer Agricultural Industrial

Total fat

1900 2000

CAD

ω-6

ω-3

fig0001 Figure 1 Dietary fat and polyunsaturate changes during man’s evolution. CAD, incidence of coronary artery disease. From Leaf A

and Weber PA (1987) A new era for science in nutrition. American Journal of Clinical Nutrition 45:1053 with permission.

FISH OILS/Dietary Importance 2503

within the endothelial cell membrane. Prostacyclin

acts as an inhibitor of clot formation, so that if a

blood clot comes into contact with endothelial cells,

it is dissolved. If there is massive physical damage to

the blood vessels, in circumstances where the clotting

ability of blood is clearly required to prevent major

blood loss, the endothelial tissue being destroyed by

the trauma cannot make prostacyclin, and thus clot-

ting is enabled. The proclotting system is based on a

prostaglandin called thromboxane, and this is pro-

duced in the blood platelets circulating in the blood-

stream. Enzymes within the platelet cell convert the

C20 polyunsaturates in the platelet membrane to

thromboxane. Both o-3 and o-6 polyunsaturates

can be converted to prostacyclins and thromboxanes.

However, and herein lies the significance, the throm-

boxane produced from conversion of the o-3 20

carbon polyunsaturate eicosapentaenoic acid (EPA,

20:5, o-3) is a weak promoter of clotting, whereas

its counterpart produced from the o-6 20 carbon

polyunsaturate, arachidonic acid (AA, 20:4, o-6) is

strongly proclotting. The prostacyclin produced from

the o-3 family and the prostacyclin produced from the

o-6 family appear to have comparable levels of anti-

clotting power, so that the net effect of increasing the

level of o-3 polyunsaturates in cell membranes is to

make clotting less likely. Of course, this can be carried

to extremes, and if the o-3 family dominates, clotting

can be inhibited to such an extent that uncontrolled

bleeding and subsequent blood loss can threaten life.

Inuits eating their traditional diets have found them-

selves in this situation, and there are many reports of

Inuits dying from blood loss after wounds and acci-

dents. This imbalance is as much a problem as having

too much o-6, which predisposes to thrombotic

diseases such as heart attacks and strokes.

Gene Expression

0014 The way in which the information that is contained

within the genetic code is actually put into physical

form is called ‘gene expression.’ Though the mechan-

isms that are used to achieve this are known, there is

still much to learn. At present, there is evidence to

show that dietary polyunsaturates do have an influ-

ence over this process, but the precise way in which

this influence is exercised is not understood.

Time Trends in Dietary Polyunsaturate

Intake

0015 In view of the fact that our ability to accurately

measure small amounts of polyunsaturates has only

existed since the mid-1950s, it is difficult to research

the levels of dietary polyunsaturates much before this

date. Estimates can be made, knowing the levels of

polyunsaturates in certain foods (from modern-day

measurements) and knowing what foods would have

been available to eat at certain times. Using this ap-

proach, experts in the area have estimated that during

the times prior to and during the period in which

modern man evolved, the balance of the two families

of dietary polyunsaturates would have been close to

1:1. Though many thousands of years may have

passed since those times, evolution is such a slow

process, that in evolutionary terms, the human race

is still in the ‘Stone Age’ stage of physical develop-

ment. It is therefore reasonable to assume that the

biological systems that control human health today

will be similar to those that evolved all those eons

ago. Those systems evolved on a mix of the two

families that was close to 1:1. Today, in the West,

we have a diet that supplies around 10 times more

of the o-6 polyunsaturates than the o-3s. This has

come about because o-6 intakes have increased

while o-3 intakes have declined, and much of this

change has taken place within the past 50 years (see

Figure 2).

0016Since the mid-1950s, data from the UK show that

national intakes of the o-6 family have more than

doubled in response to advertisements promoting

the cholesterol-lowering benefits of vegetable oils

and margarines (such as sunflower, sesame, corn,

etc.) in an attempt to increase protection against

heart disease. At the same time, our national intake

of o-3 polyunsaturates has dropped, mainly as a

result of reduced fish consumption and a preference

for white fish like cod or haddock that have relatively

low oil (and so low o-3) content. A further compli-

cating factor is that our ability to elongate the 18

carbon o-3 polyunsaturate, a-linolenic acid to the

20 and 22 carbon forms is compromised by the cur-

rent high intake of the o-6 polyunsaturate linoleic

acid (see Figure 1). Thus, not only is the dietary intake

of the 20 and 22 carbon o-3 polyunsaturates reduced,

but our ability to make our own from the 18 carbon

form is also reduced.

0017The overall consequence of these long-term dietary

changes is that the cells in our bodies are increasingly

being primed with the wrong mixture – too much o-6

and not enough o-3 – with variable effects depending

on which part of the body is being considered.

Health Impact of a Change in Dietary

Polyunsaturates

0018The exact impact of a change in the dietary balance

between the two families of polyunsaturates will

depend on which area of the body is under consider-

ation. The following sections will examine the impact

on the health of heart, brain, skin, lung, and kidney.

2504 FISH OILS/Dietary Importance

Heart Health

0019 Since the mid-1970s, when interest in this field was

sparked by observations that native-dwelling Green-

land Inuits had high fat/high cholesterol diets yet no

heart disease, much research has focused on the role

of the o-3 polyunsaturates in heart disease. As a result

of this work, it is now widely acknowledged that the

long-chain o-3 polyunsaturates have a beneficial

impact on several established risk factors for heart

disease. The blood lipid profile is improved, blood

pressure and viscosity are lowered somewhat, blood

clotting is made less likely, and the risk of develop-

ment of abnormally rapid heart rhythm is reduced.

0020 Cholesterol The initial investigations focused on the

effect of the long-chain o-3 polyunsaturates on blood

lipids. Early work suggested that the o-3s might have

a cholesterol-lowering effect. The apparent lowering

of cholesterol was in fact subsequently shown to be

due to a reduction in the level of very-low-density

lipoprotein cholesterol (VLDL) particles in individ-

uals with abnormally high levels of such particles.

The VLDL particles were cleared from the blood of

these patients, as a result of the ability of long-chain

o-3 polyunsaturates to lower serum levels of triacyl-

glycerides (triglycerides), the major component of

VLDL particles. This observation resulted in a

lowering of total serum cholesterol, as a consequence

of the removal of the small amount of cholesterol

present in the large amounts of VLDL particles. This

led to the erroneous impression that low-density lipo-

protein (LDL) cholesterol was being lowered, some-

thing that was later shown to be incorrect. An

elevated serum LDL level is a major risk factor for

heart disease, and this mechanism was for a time

thought to reflect the way in which the o-3s offered

their heart protection. The consensus of opinion now

is that the long-chain o-3 polyunsaturates do not

have any marked impact on serum LDL cholesterol

levels, and that the protective form of cholesterol,

high-density lipoprotein (HDL) cholesterol, is

elevated by around 10% in most people. The early

studies on the ability of the long-chain o-3 polyunsat-

urates to reduce blood levels of triacylglycerides were

carried out largely in the UK. Though, at the time, an

elevated serum triacylglyceride level was not con-

sidered to be an independent risk factor for heart

disease, that view is now changing, particularly

since the inverse relationship between serum triacyl-

glyceride levels and high-density lipoprotein choles-

terol levels has been better understood.

0021The long-chain o-3s have also been shown to have

a moderate but clinically significant blood pressure-

lowering effect, especially in subjects with above-

normal starting levels. Blood viscosity is also mildly

but significantly lowered by the long-chain o-3s. The

impact of the long-chain o-3 polyunsaturates on the

balance of proclotting and anticlotting forces within

the blood clotting process also contributes to protec-

tion against a heart attack, though this effect is not

easy to demonstrate in a clinically meaningful way.

0022Though a heart attack is triggered by a blood clot

formed within the circulation, the real damage occurs

when the rhythm control system of the heart causes

it to beat very rapidly in an attempt to pump more

blood to the brain. This leads to the heart pumping so

rapidly that its effectiveness as a pump is lost (ven-

tricular arrhythmia), and death from brain oxygen

w-6 polyunsaturates w-3 polyunsaturates

Linoleic acid (18:2)

Alpha-linolenic acid (18:3)

From vegetable oils such as sunflower,

sesame, safflower, etc.

From linseed and rapeseed oils

Dietary 18 carbon polyunsaturates are

converted in the body to 20 and 22 carbon forms

An excess of ω-6 inhibits

conversion of the ω-3 family

(and vice versa)

Arachidonic acid (20:4)

Found in small amounts in meat, eggs

Eicosapentaenoic acid (20:5)

Major source is oil-rich fish

Docosahexaenoic acid (22:6)

Major source is oil-rich fish;

small amounts in meats and eggs

fig0002 Figure 2 Importance of dietary balance with respect to the polyunsaturates. The figures after the name of a polyunsaturate denote

the number of carbon atoms in the molecule, with the figure after the colon indicating the number of double bonds.

FISH OILS/Dietary Importance 2505

starvation follows rapidly. Myocytes are the cells

within the heart tissue that generate the tiny electrical

impulses that cause heart muscle cells to contract, and

the heart to ‘beat.’ When myocytes are given extra

o-3 polyunsaturates in their make-up, they are much

less prone to develop rhythm irregularities when

some sort of adverse condition, such as a heart attack,

occurs. Work carried out by Harvard Professor Alex

Leaf has established that the type and level of poly-

unsaturate present in myocyte membranes have a

major impact on the cell’s susceptibility to the devel-

opment of abnormally rapid rhythms. What this

means in terms of human health is not easy to re-

search, because of the practical and ethical problems

involved. The nearest approach is the use of labora-

tory investigations with animals. Work by Dr John

Charnock, at the CSIRO in Australia, has shown that

giving more of the long-chain 20 and 22 carbon o-3

polyunsaturates (e.g., EPA and DHA) to rats at high

risk of developing cardiac rhythm disturbances

completely prevented the appearance of the rhythm

irregularities.

0023 Studies with Heart Patients The key question is

whether eating more long-chain o-3 polyunsaturates

(either from fish or from fish oil supplements) is

useful in helping people at high risk of dying from a

heart attack to live longer. Now, there are three sep-

arate, independent, controlled studies from different

parts of the world demonstrating that this is indeed

the case.

0024 The first such study was carried out by a team from

the Medical Research Council in the UK. One thou-

sand heart attack survivors were advised to eat more

fish, or take more long-chain o-3 polyunsaturates in

the form of fish oil. When they looked at the death

rate over the following 2 years, the researchers found

that, compared with a similar group of patients ad-

vised to eat more dietary fiber, or to eat less fat, the

fish group had about 30% fewer deaths. A subsidiary

investigation of these patients revealed that the effect

was due to the o-3 polyunsaturates in the fish, rather

than some other component.

0025 An Indian study also looked at the impact of rec-

ommending more o-3 polyunsaturates to heart attack

victims, and found a striking protective effect of the

o-3 polyunsaturates compared with patients given

placebo.

0026 The most recent, and by far the most important,

study scientifically was reported from Italy in 1999.

There, doctors studied more than 11 000 heart attack

victims. Half were given an o-3 supplement derived

from fish oil, and the other half a placebo. After more

than 3 years of follow-up, analysis revealed that the

total mortality in the patients given o-3 fatty acids

was 20% lower than in those patients not so treated,

and the incidence of sudden cardiac death was

reduced by 45%.

0027Though the early studies used relatively large

amounts of o-3 (3000–6000 mg per day), more recent

clinical studies have used smaller amounts (1000–

2000 mg per day) and shown them to be effective at

reducing death rates after a heart attack. These stud-

ies clearly show that if heart attack survivors were to

be recommended to eat oil-rich fish, or take a fish oil

supplement immediately after their attack, their

chances of falling victim to a second attack would

be greatly reduced.

Brain Health

0028Brain cells are different in many ways from other

body cells. In contrast to most other body cells, they

are formed at or around birth, and after the first year

or so of life, few further brain cells are formed. The

cells do, however, increase in size and form synapses,

or connections, with other brain cells. There is also a

high proportion of membrane in brain cells compared

with content. As in heart cells, the mix of polyunsat-

urates in the brain cell membrane has a marked

impact on how it works and, of course, on brain

function.

0029Studies completed within the past few years have

demonstrated that the level and amount of poly-

unsaturates in the diet can alter the composition of

brain membrane polyunsaturates. Other recent

studies have shown that adding o-3 polyunsaturates

to the diet can alter the way the brain functions.

Increasing the dietary intake of o -3 polyunsaturates

has been shown to:

reduce severe manic depression; ameliorate the worst

effects of schizophrenia; reduce aggression under stress;

improve the behavior and reading skills of children with

attention deficit hyperactivity disorder (ADHD); and

improve problem-solving ability in very young children.

0030An inadequate intake of o-3 has also been implicated

in postnatal depression and may be associated with

dyspraxia in children. The 3–4 point IQ advantage

found in breastfed infants compared with bottle-fed

infants is also probably related to the natural o-3

content of breast milk. Only recently have some

infant formula milks been fortified with long-chain

o-3s, a trend that seems certain to continue.

Skin

0031The membranes of skin cells are perhaps some of the

most important in the human body since they repre-

sent the ultimate barrier between our inner selves and

the outside world. The part that polyunsaturates play

in skin health has been extensively investigated, and

2506 FISH OILS/Dietary Importance

their role is relatively well understood. The moisture

barrier properties of the skin are of key importance,

and without a good level and balance of polyunsatur-

ates in skin cell membranes, moisture loss would be

severe. The sensitivity of skin cells to problems like

psoriasis and dermatitis is related to the level of o-3

polyunsaturates present. Recent research has sug-

gested that there may be a link between the level

and type of polyunsaturate in skin cell membranes

and the recent upsurge in prevalence of asthma and

allergic conditions.

003 2 One of the adverse conditions that skin cells have

to face is sunlight. Studies have shown that sensitivity

to ultraviolet radiation is reduced in skin cells that

have a good level of o-3, implying some protection

against sunburn. The same research suggests that this

could ultimately lead to a degree of protection from

skin cancer.

Lungs

0033 The cells that line the airways in the lungs are in effect

modified skin cells. Lung cells containing higher

levels of o-3 are less prone to damage by cigarette

smoke, and probably by other environmental pollu-

tants. When smoke contacts the lungs, an inflamma-

tory reaction is set up leading to congestion in the

lungs and ultimately to a condition known as chronic

obstructive pulmonary disease (COPD), or emphy-

sema. Higher than average levels of o-3 in the diet

lead to a reduction in COPD, probably because the

lungs are less sensitized and do not react in the same

hyperresponsive way as lungs with low o-3 levels.

Cigarette smoking is none the less very damaging to

health.

Kidneys

0034 The role of the o-3 polyunsaturates in healthy kidney

function is well documented, although the research

is taking a long time to penetrate renal units in

hospitals. Work carried out over many years by Dr

Jim Donadio at the Hormel Institute in the USA has

shown consistently that o-3 supplementation in

patients with failing kidneys restores much of their

kidney function and often eliminates the need for a

transplant. This effect is thought to be due to a

reduced inflammatory response following a greater

intake of fish oil.

0035Associated work has also shown that the presence

of o-3 polyunsaturates when administering the

immune suppressing drug, cyclosporin A, can reduce

some of the drug’s damaging side-effects.

Intake Recommendations

0036Various bodies have attempted to make recommenda-

tions on the amounts of the o-3 polyunsaturates

that should be consumed both by adults and, more

recently, by infants. Table 1 summarizes the major

recommendations made to date. Some of the

earlier recommendations are not specific as to

whether the recommendations relate to short-chain

or long-chain o-3 polyunsaturates, so have limited

value. Generally, as research has led to a greater

understanding of the issues involved, the recommen-

dations have become more specific, and discussions

are under way to further refine the existing recom-

mendations. The most recent was an ad-hoc Expert

Workshop held in the USA in April 2000. The make-

up of the group, and their detailed recommendations,

can be seen by visiting the ISSFAL website at

www.issfal.org.uk. A summary of their recommenda-

tions can be seen in Table 2 for adults, and Table 3 for

infant feeding. A consensus is emerging that intake of

long-chain o-3 polyunsaturates should be around

0.2–0.3% of energy intake, which, for a 2000-kcal

intake, means a total long-chain o-3 intake of about

400–600 mg per day, or 3–4 g per week.

0037Recommendations on polyunsaturated fatty acid

composition of infant feeding formulae have not yet

tbl0001 Table 1 Summary of recommendations for intake of o-3 polyunsaturates

Source Specific o-6:o-3ratio

recommended

Other specific recommendations

National Nutrition Council (Norway) (1989) None o-3 0.5%en (1–2 g per day)

Nordic Nutrition Committee (1989) None o-3 0.5%en (1–2 g per day)

NATO Workshop on o-3/o-6 (1989) None 0.8 g per day EPA/DHA (0.27%en)

Scientific Review Committee of Canada (1990) 5:1–6:1 o-3 at least 0.5%en

British Nutrition Task Force (1992) 6:1 EPA 0.2–0.5%en; DHA 0.5%en

Scientific Committee for Food of the European

Community (1993)

4.5:1–6:1.5 o-3 as 0.5% of total calories

FAO/WHO Expert Committee on Fats & Oils in

Human Nutrition (1994)

5:1–10:1 Consider preformed DHA in pregnancy

Committee on Medical Aspects of Food Policy (1994) None EPA/DHA 0.1–0.2 g per day (1.5 g per week); at least

two portions of fish/week

FISH OILS/Dietary Importance 2507