The Significance of Omega-3 Foods

Nutritional Perspectives: Journal of the Council on Nutrition of the American Chiropractic Association
January 2016 11
ALAis considered essential because it cannot be synthe-
sized by humans.2 The discussion of the dietary essentiality
of ALA begs the question of whether it is the activity of
ALAitself that is essential or the other fatty acids, EPA, and
DHA, which are derived from ALA. The essentiality of
EPAand DHAremains a matter of debate.3,4,5 The prevail-
ing view is that DHA is the essential omega-3 fatty acid
because its synthesis requires ALA and EPA as substrates.3
Gebauer (2006) identified DHA as an essential omega-3
fatty acid because of the multiple, unique metabolic func-
tions of DHA, which are not replicated by other fatty
acids.3 Spector (1999) proposed DHA is more likely to be
the essential omega-3 constituent because it is necessary for
optimal visual acuity and neural development.5 EPA and
DHA can be synthesized from ALA, but due to the low
conversion efficiency of dietaryALAto EPAand especially
DHA, it is recommended to obtain EPA and DHA from the
diet. Protective tissue levels of EPA and DHA can cur-
rently be achieved only through the direct intake of these
fatty acids.2,6
Omega-3 fatty acids are of special interest to healthcare
professionals and the public, due to their anti-inflammatory,
antithrombotic, and hypolipidemic properties. Omega-3
fatty acids are used in the prevention or treatment of many
chronic diseases, including age-related macular degenera-
tion, arthritis, cancer, coronary heart disease, diabetes, dry
eye disease, mental health, and osteoporosis.7
Nutritional interest in omega-3 fatty acids has increased
dramatically over the past 40 years. Fish are a very rich
source of EPA and DHA, and fish oil dietary supplements
are the primary choice in research designed to study
omega-3 health effects.8 In 2015, the U.S. National Library
of Medicine PubMed® database contained more than
22,000 papers referenced by the keywords “fish oil.” More
than 3600 papers studied the relationship between fish oil
supplementation and disease outcome. The database con-
tained more than 1000 clinical trials involving fish oil
supplementation, and there were nearly 1000 reviews of the
role of fish oil supplementation in human health.9,10
Worldwide, governments and healthcare professional
associations publish recommendations for dietary intake of
omega-3 fatty acids and fish oil, and fish consumption.
Global fish consumption in 2011 was over 70 million tonnes
(metric tons), out of a total world catch of over 90 million
tonnes of fish. Almost 20 percent of the remaining catch
was used to produce fishmeal and fish oil, with nearly three-
fourths of this production used in aquaculture feed for fish
and shrimps. The remainder was used for terrestrial farming
and human dietary supplements.11 The global market for
fish oils and omega-3 supplements is estimated at $3.4 bil-
lion in 2015. The market for supplements is anticipated to
grow 18 percent by the year 2020. Omega-3 supplements
accounted for 87 percent of retail value sales in 2015.12
Consumers are encouraged to eat fish, and to take fish
oil and omega-3 supplements in the form of capsules, gum-
mies, jellies, and fortified foods.11,13,14 Wild oily fish such
as anchovy, bluefish, halibut, herring, lake trout, mackerel,
salmon, sardines, and tuna accumulate high levels of EPA
and DHAin their tissues.15,16 Virtually all fish oil produced
in the world for supplements in 2015 comes from anchovy
and sardine biomass, harvested by Peru and Chile.17
FISH OIL HEALTH BENEFITS
The healing powers of fish and fish oil can be found in
The Book of Tobit (6:4-9) in the Old Testament, and in the
writings of Hippocrates and Pliny.18 Cod liver oil (CLO)
was an important part of Roman and Norse (Viking) nutri-
tion.19 CLO use in England was reported in 1789, and CLO
was used inAmerica by the mid-1800s as a remedy for rick-
ets, arthritis, and inflammatory conditions of the eye. In
1849, speculation existed about the mode of action of CLO
in relation to its chemical make-up, but no significant scien-
tific inquiry into the nature of the fatty acids composition of
fish oils occurred for more than a century.20,21
The complex fatty acids composition of fish oils was
revealed by gas-liquid chromatography and analysis of
nuclear magnetic resonance spectra in the 1950s to early
1960s. Fish oils from all species contain a wide spectrum
Understanding The Significance of Aquatic Omega-3 Food Sources
in the Nutrition Practice
Kimberly Queen, DC, MS, CNS, DACBN
It is a tenant of modern nutrition that the omega-3 long-chain polyunsaturated fatty acids (LC-PUFA)
keep pro-inflammatory and anti-inflammatory responses in balance, and mediate other local control
processes to respond properly to cellular stress.1 The physiologically relevant omega-3 fatty acids are
alpha-linolenic acid (ALA, 18:3n3), eicosapentaenoic acid (EPA, 20:5n3) and docosahexaenoic acid
(DHA, 22:6n3).

12 Vol. 39, No. 1
of saturated and unsaturated long-chain fatty acids and
mixed triglycerides, including myristic acid (14:0), palmitic
acid (16:0), the essential omega-6 LC-PUFA, linoleic acid
(LA, 18:2n6), ALA, EPA, and DHA. Environmental fac-
tors, dietary feed, maturity, and sex of fish influence the
fatty acids composition, which varies not only from species
to species but often to an even greater extent from one fish
to another of the same species.16,22 This is an important
consideration regarding the nutritional benefit of fish raised
in the wild versus fish that are cultured (farmed).23,24,25,26,27
The nutritional significance of fish-oil fatty acids in
humans was marginalized until the 1970s, with research
limited to the development of fishery products. Although
ALA from terrestrial plant sources was known to lower
serum cholesterol, fish oils were deemed unsuitable
because of questions about the stability of the polyunsatu-
rated fatty acids in fish oil, and the potential for undesirable
effects from auto-oxidation and free radical formation. It
was not uncommon in the 1960s to find statements express-
ing surprise that fish oils were useful in lowering serum
cholesterol levels.22
Dyerberg’s pioneering work with Greenlandic Eskimos
in 1970 changed this perception when he revealed a rela-
tionship between the ingestion of omega-3 fatty acids from
aquatic sources with the reduction of plasma cholesterol
and triglycerides.28 Subsequent research on the health
effects of fish oil in diverse populations confirmed Dyer-
berg’s inverse relation hypothesis; that a higher amount of
omega-3 fatty acids (represented by ALA) in the diet,
blood, and tissues moderately decreased the occurrence of
heart disease and its complications.3,6 A 2012 meta-analy-
sis of secondary prevention trials, however, found no
significant effect of omega-3 supplements on all-cause
mortality, cardiac death, sudden death, myocardial infarc-
tion, or stroke.2,29
Current research confirms that all families of LC-PUFA
are important in human nutrition, in terms of the total
amount of fatty acids in the diet, but more importantly, the
ratio of omega-6 to omega-3 fatty acids. The ratio influences
conversion of the precursor molecules, LA, and ALA, to
their higher chain homologs, represented by arachidonic
acid (AA; 20:4n6,) ETA (20:4n-3,) EPA, and DHA. Epi-
demiologic studies have focused on the health effects of
EPA and DHA, notwithstanding the importance of other
LC-PUFA in mediating anti-inflammatory effects and regu-
lating fatty acid desaturase/elongation pathways.3,4,6,7,30
It is not known whether there is a need in the human diet
for supplemental ALA, EPA, and DHA. The requirement
for these omega-3 fatty acids to support neurological func-
tion and that of other tissues may be relatively modest. If
demands for EPA and DHA are modest and primarily serve
to support membrane turnover and renewal in adults, then
it is possible that in healthy individuals consuming a bal-
anced diet limited capacity for synthesis of EPA and DHA
may be sufficient to maintain tissue function.4,29
FISH OIL HEALTH RISKS
The health benefits of whole fish and fish oil supple-
ments may be offset by contaminants that are concentrated
in the food sources. Carcinogen, mutagen, teratogen, and
tumor promoter contaminants in seafood are increasingly
of concern.31,32 Non-carcinogen contaminants such as
methylmercury, heavy metals, the synthetic antioxidant
Ethoxyquin, and antibiotics are commonly the subject of
advisory statements regarding the adverse health effects of
seafood and fish oil consumption.15,33,34,35 The Food and
Drug Administration (FDA) and the Environmental Protec-
tion Agency advise women who may become pregnant,
women who are pregnant, nursing mothers, and young chil-
dren to avoid eating some types of fish and to eat fish and
shellfish that are lower in mercury.3,15
Canthaxanthin is a controversial aquafeed additive used
for the sole purpose of coloring the flesh of farmed salmon
and trout, and various processed fish. Synthetic canthaxan-
thin is associated with retinal damage caused by the
deposition of minute crystals in the eye. Consumer safety
concerns led to a revision of the Acceptable Daily Intake for
canthaxanthin in 1995, but the maximum acceptable level of
canthaxanthin in aquafeed continues to be debated.36,37,38,39
Astaxanthin is another controversial aquafeed additive
and consumer health product. It is a pigmenting carotenoid
that is used for salmon and trout farming to impart desir-
able flesh color and to promote healthy nervous system
development, fish fertility, and growth rate. It is marketed
to consumers as a potent antioxidant supplement that
enhances cardiovascular, cognitive, immune system, and
sexual function.36,40,41,42 The source of astaxanthin may be
natural or synthetic (petrochemical). Natural astaxanthin is
FDA approved for aquafeed, and some natural astaxanthin
sources are approved for human consumption. Synthetic
astaxanthin is not approved for human consumption in food
or supplements. Interestingly, it is approved in the U.S. and
Europe as an aquafeed additive (food dye).40,43
OMEGA-3 FATTY ACID METABOLISM
ALA, EPA, and DHA are important structural compo-
Understanding the Significance of Aquatic Omega-3 Food Sources

January 2016 13
nents of cell membranes that affect membrane fluidity,
flexibility, permeability, and the activity of membrane-
bound enzymes. The fatty acid abundances vary with
dietary supply.2 The low concentration of ALA in cell
membranes and blood lipids in healthy adult humans sug-
gests that ALA has a limited influence on biological
function beyond acting as a substrate for EPA and DHA
synthesis. Some investigators consider this a matter of
debate.4,6 In contrast to ALA, DHA, and to a lesser extent
EPA, are present in substantially greater amounts in cell
membranes and the circulation. In particular, DHA
accounts for about 20–50% of fatty acids in the brain and
the retina.4
ALA can convert to EPA and DHA in the endoplasmic
reticulum (ER) of hepatocytes, but the degree of conver-
sion appears to be unreliable.4,35,44 The conversion
efficiency is very limited in healthy individuals, although
there is a higher conversion in women and non-fish eaters
compared to fish eaters.4,45,46
ALA converts to EPA and DHA in the ER by a combi-
nation of subsequent reactions, involving delta-5
desaturation (D5D), elongation, and delta-6 desaturation
(D6D). Elongation reactions add two carbon atoms to the
substrate fatty acid. D5D and D6D reactions add a double
bond. The conversion of EPA to DHA requires additional
enzymes that are present only in peroxisomes where a -
oxidation sequence removes two carbon atoms from
C24:6n3 (tetracosahexaenoic acid) to produce DHA. An
important question is whether dietary intake of the precur-
sor omega-3,ALA, can provide sufficient amounts of tissue
EPA and DHA by conversion.47,48 There may be a restric-
tion on ALA conversion beyond EPA, and dietary ALA
cannot replace DHA. It is also possible that DHA synthe-
sis can occur independently from this pathway.1,4,30
ALA activity is inversely related to dietary levels of
omega-6 fatty acids (represented by LA). The rate of con-
version of ALA to EPA and DHA is higher when the LA
ratio is low. Since both omega-3 and omega-6 PUFAs are
metabolized by the same pathway, competition exists
betweenALAand LAfor the corresponding elongation and
desaturation enzyme systems.4,49 In studies using human
hepatocytes, when the LA:ALA ratio was 0:1 and 1:1, the
conversion of ALA to EPA and DHA was highest. At 4:1
and 9:1, the levels of conversion for both EPA and DHA
decreased dramatically, and decreased levels of ALA and
EPA were found in cell membranes. A higher ratio of LA to
ALA not only suppresses formation of DHA and EPA but
also strongly depresses transcription levels of genes encod-
ing regulatory proteins of fatty acid metabolism, which are
necessary to fatty acid homeostasis and the regulation of
fatty acid synthesis in the liver. This suggests the impor-
tance of ingesting the appropriate amounts of fatty acids
and the appropriate ratio of omega-6 to omega-3 fatty
acids.4,7,30,50,51
Farmed fish have higher ratios of omega-6 fatty acids to
omega-3 fatty acids than their wild counterparts. This
makes them less favorable for human consumption.26,52
The pathogenesis of many diseases, including cardiovascu-
lar disease (CVD,) cancer, and inflammatory and
autoimmune diseases may be related to a high ratio of
omega-6 to omega-3 fatty acids.7 Accordingly, a balanced
omega-6 to omega-3 fatty acids ratio is important for both
rearing healthy fish and producing a valuable food for
humans.26,36,52
DIETARY GUIDELINES FOR
CARDIOPROTECTIVE EFFECT OF OMEGA-3
FATTY ACIDS
Many of the observational studies and randomized clini-
cal trials of disease outcomes have characterized similar
effects of modest dietary EPAand DHAin reducing the risk
of cardiac death. Some studies indicate that DHA may be
preferentially antiarrhythmic.3,6
Current evidence does not allow strong conclusions
about whether EPAor DHAor a specific ratio of the two, is
the most beneficial. Based on this uncertainty, the daily
recommended intake for both should be between 250 mg
and 500 mg/day to reduce the risk of cardiac death, or up to
1 g/day to treat existing CVD. EPA and DHA should be
consumed in ratios of 1:2 or 2:1.3,6
A dietary strategy for achieving the 500 mg/day recom-
mendation is to consume two fatty (oily) fish meals per
week, EPA/DHA fortified foods or fish oil supplements.
The greatest reduction in risk is associated with fish con-
sumption ranging from one serving per week up to greater
than five servings per week.3,6
The recommendations cannot be easily satisfied with
intake of whole fish and fish oil supplements because the
EPAand DHAcontent in fish vary by species and is depen-
dent on the fish feeding habits, water temperature, and
spawning cycles that influence the proportionate distribu-
tion of omega-3 fatty acids in fish body oils.11 The
omega-3 supplement industry has traditionally relied on
Peruvian fish oil called 18/12 oil, named for the 18 percent
EPA content and 12 percent DHA content it contains (3:2

14 Vol. 39, No. 1
ratio). In recent years, the aim has been to produce oils
with an overall 30 percent PUFAcontent instead of a speci-
fied EPA to DHA ratio.53
DIETARY GUIDELINES FOR GENERAL
POPULATIONS
The nutrition profession lacks clear guidance from gov-
ernmental authorities and researchers to make specific
ALA, EPA, and DHA dietary recommendations for general
populations. The United States has neither a dietary refer-
ence intake (DRI) nor FDA-approved health claim for
ALA, EPA, and DHA.54 The professional literature pro-
vides inconsistent recommendations for dietary ALA, EPA
and DHA, and the consumption of whole fish. This is
probably due to the absence of a standardized calculus for
converting the study findings that measure ALA, EPA and
DHA health benefits to specific dietary guidelines.
This presents a significant dilemma for the practitioner.
We are accustomed to using the DRI-set of nutrient-based
reference values to evaluate an EstimatedAverage Require-
ment (EAR), Recommended Daily Allowance (RDA),
Tolerable Upper Intake Level (UL), or an Adequate Intake
(AI) value for the life stage of the patient. These are impor-
tant tools used in the prevention of nutritional deficiency,
and to prevent the risk of adverse effects from excessive
nutrient intakes.
Our only guidance comes from The Institute of Medi-
cine (IOM) recommendation for the AI for ALA. The AI
for ALA may range from 0.6-1.2 % of energy to prevent
deficiency symptoms, and up to 10% can be provided by
EPA or DHA.3 This recommendation is based on the
median intake of ALA in the United States, according to
NHANES.6
I am interested in the ethical ramifications of prescribing
increased amounts of ALA, EPA, and DHA in the form of
whole fish and fish oil supplements to populations and pop-
ulation subgroups. The risk of excessive omega-3 fatty
acid supplementation has risen along with the awareness of
its health benefits, and it is important to realize the possibil-
ity of excessive use of ALA, EPA, and DHA food sources.1
ALA represents the quantitatively dominant omega-3 fatty
acid in the standard American diet. Daily ALA uptake
averages 1.5 grams.30 Excess ALA, EPA, and DHA con-
sumption can produce a condition known as n-3
dominance.1 Lord (2008) describes this as an imbalance of
fatty acid metabolism that can produce a lowering of class
2 eicosanoid signals such as leukotriene A2 in response to
distress. This may cause the patient difficulty overcoming
infection. Another effect is the increased risk of oxidative
damage and elevated serum lipid peroxides.1
The clinical nutritionist must be as prudent in establish-
ing intake goals for omega-3 LC-PUFA in populations as
in subpopulations. We must be vigilant and urge caution in
the consumption of nutrient supplements that could lead to
excessive nutrient intakes.
The practice of clinical nutrition entails a constant bal-
ancing act, not only between knowledge and wisdom but
also between effect and side-effect, cost and benefit, and
medical, cultural, and political beliefs. The doctor-nutrition-
ist (DACBN) views this through the lens of primum non
nocere; do no harm, and the converse: be of benefit. We
recognize the responsibility to patients first and foremost, as
well as to society, to other health professionals, and to self.55
The reality of nutritional practice has in some ways reduced
the power of the provider because patients are increasingly
consumers of healthcare, exerting their right to self-determi-
nation (autonomy) on the internet to self-diagnose, and in
the nutritional marketplace to self-prescribe. Patient auton-
omy is an important and fundamental reflection of the
dignity of the person.56 Nevertheless, other principles
besides autonomy must be considered to arrive at ethical
guidance for prescribing omega-3 food sources.
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