Salem 2015
Salem 2015
CURRENT
OPINION Is the world supply of omega-3 fatty acids
adequate for optimal human nutrition?
Norman Salem Jr a and Manfred Eggersdorfer b
Purpose of review
To delineate the available sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for
human consumption and to determine if the available supply is capable of supplying the nutrient levels
recommended by expert bodies.
Recent findings
There are converging opinions among experts, professional organizations and health professionals that a
recommendation for a daily individual consumption of 500 mg of EPA/DHA would provide health benefits,
and this translates to an annual human consumption of 1.3 million metric tons. Current human consumption
of EPA/DHA is estimated to be only a small fraction of this amount and many people may suffer from
suboptimal health as a result of low intake. EPA and DHA originate in the phytoplankton and are made
available in the human food chain mainly through fish and other seafood.
Summary
The fish catch is not elastic and in fact has long since reached a plateau. Aquaculture has grown rapidly,
but most of the fish oil produced is currently being used to support aquaculture feed and so this would
appear to limit aquaculture growth – or at least the growth in availability of fish sources of EPA/DHA.
Vegetable oil-derived alpha-linolenic acid, though relatively plentiful, is converted only at a trace level in
humans to DHA and not very efficiently to EPA, and so cannot fill this gap. Microbial EPA/DHA production
can in the future be increased, although this oil is likely to remain more expensive than fish oil. Plant
sources of EPA and DHA have now been produced in the laboratory via transgenic means and will
eventually clear regulatory hurdles for commercialization, but societal acceptance remains in question. The
purpose of this review is to discuss the various sources of omega-3 fatty acids within the context of the
potential world demand for these nutrients. In summary, it is concluded that fish and vegetable oil sources
will not be adequate to meet future needs, but that algal oil and terrestrial plants modified genetically to
produce EPA and DHA could provide for the increased world demand.
Keywords
fish oil availability, microbial eicosapentaenoic acid/docosahexaenoic acid production, supply of omega-3
fatty acids
1363-1950 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-clinicalnutrition.com
Table 1. Omega-3 PUFA intake recommendations of expert international bodies for adults
American Heart Association 2011 Heart health Two fish meals for primary protection [1]
Heart Foundation Australia 2008 Heart health 500 mg EPA/DHA for primary prevention [2]
FAO/WHO Expert Consultation 2010 General health 250 mg EPA/DHA [3]
European Food Safety Authority 2010 General health 250 mg EPA/DHA [4]
Japanese Ministry of Health 2009 General health >1 g EPA/DHA [5]
Health Council Netherlands 2006 General health 450 mg EPA/DHA from fish [6]
Australia New Zealand National 2006 Chronic disease n-3 LC-PUFAs: 610 mg for men 430 mg for women [7]
Health and Medical Research
Council
Belgian Superior Health Council 2009 Heart health Daily fatty fish or 1 g capsule [8]
Agence Francais de Securite 2014 General health 500 mg EPA/DHA [9]
Sanitaire des Aliments
DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LC, long chain; PUFA, polyunsaturated fatty acid.
FIGURE 2. Major fish species which contribute to EPA/DHA production. Data compiled by the Global Organization for EPA
and DHA Omega-3s (GOED) and based on a calculation of FAO FishStat data [12]. DHA, docosahexaenoic acid; EPA,
eicosapentaenoic acid.
1363-1950 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-clinicalnutrition.com 149
325 205 3
Thousand Thousand
metric tons Thousand
metric tons Reduction fisheries metric tons
Fish and seafood producing fish oil
consumption Algal, yeast, etc.
and wastage microbial sources
500 7.2
× Billion
mg people
EPA/DHA
= 1.3 million EPA/DHA
metric tons per annum
Total supply
GAP
533 thousand
metric tons
1.1 million Human consumption
metric tons 200 thousand
metric tons
FIGURE 3. Summary slide of worldwide EPA/DHA requirement and available supplies for human consumption. Source is
DSM Nutritional Products, Nutrition Science & Advocacy, 2014. DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid.
(2) 9000 metric tons utilized by humans of the ALPHA-LINOLENIC ACID AS A SOURCE OF
200 000 tons derived from seafood industry cut- EPA/DHA
tings The vegetable oil source of omega-3 fatty acids as
(3) 63 000 metric tons utilized by humans of the ALA has been proposed as another possible source of
205 000 metric tons from fish oil extraction EPA and DHA. Vegetable oils are relatively abundant
(4) 197 000 metric tons total human use from fish and Table 2 lists the United States Department of
sources Agriculture (USDA) estimates of major global pro-
(5) 3000 metric tons from nonfish sources includ- duction in 2013–2014 [14]. Soybean and rapeseed
ing algae, yeast, krill, and so on oil are the major sources of ALA, and the total
(6) 200 000 metric tons EPA/DHA grand total use calculated ALA produced this year is estimated to
be over 6100 metric tons. Flax oil (not included in
The total is already likely an overestimate since the USDA estimate) is high in ALA content, with a
it assumes that all of the seafood is consumed, range from about 40 to 60% of fatty acids, and
although food wastage is frequently one-third or worldwide production of flax seed was estimated
more. Very little (less than 5%) of the seafood cut- in 2010 to be about 525 thousand metric tons per
tings total is utilized for human consumption and year [15]. The seed is about 23 wt% ALA and this
would appear to present an opportunity to signifi- then yields an additional 121 thousand metric tons
cantly increase its use. However, such processing is of worldwide ALA production. The total worldwide
done in a decentralized fashion such that there is ALA production from vegetable oils can therefore be
little economic incentive to process the oil appro- estimated to be about 6220 metric tons.
priately for this purpose. In extraction fisheries, Contributions of ALA, however, as a source of
205 000 metric tons of fish oil are produced, and EPA/DHA presupposes that humans can efficiently
most of it goes to supply the aquaculture industry metabolize the ALA to EPA and DHA. The rate of this
with a source of EPA/DHA since salmonids and other conversion may be examined in two ways: by feed-
fish require this nutrient for optimal growth [13]. ing humans ALA and measuring any increases in
Nonfish sources of EPA/DHA come mainly from bloodstream levels of EPA and DHA, or by determin-
fermented algal oils and secondarily from Krill oil, ing endogenous human ALA metabolism in vivo
but at present contribute a very small percentage of through metabolic tracers. Pawlosky and Salem per-
the total available EPA/DHA. The total EPA/DHA formed a tracer experiment wherein deuterated-ALA
available for human consumption (200 000 metric was given to human adults on a controlled Western
tons) represents only about 15% of the above diet and in vivo metabolism monitored via the
calculated human requirement (1.3 million metric bloodstream, reviewed in [16]. These authors, work-
tons). ing at the National Institutes of Health, concluded
Table 2. USDA estimate of global major vegetable oil and calculation of alpha-linolenic acid production in 2013–2014
that only about 0.2% of the absorbed plasma ALA erythrocyte ALA, a nonsignificant increase (0.12%)
was destined for EPA synthesis. Moreover, less than in EPA and a slight decrease in DHA. The EPA-
0.05% of the plasma ALA was destined for DHA supplemented group exhibited only a significant
synthesis. This is consistent with many human increase in EPA, which was much more substantial
supplementation studies in which large doses of (4.41%). DHA supplementation produced signifi-
ALA are given, and the bloodstream shows no cantly increased EPA (1.56%), as well as a large
change in DHA and generally significant but small increase in DHA (7.5%). It thus appears that veg-
increases in EPA [17]. Representatives of the Inter- etable oil ALA can support a small increase in human
national Society for the Study of Fatty Acids and bloodstream EPA, but cannot support DHA and
Lipids – a group of international experts of lipid therefore will not provide a solution to the world-
scientists – have published a position paper con- wide shortage of EPA and DHA.
cerning ALA metabolism, indicating that neither
dietary ALA (see [17] for review, Table 1) nor EPA
(see [17] for review, Table 2) is a good source of DHA STEARIDONIC ACID AS A SOURCE OF
in humans due to the extremely low level of in-vivo EPA/DHA
metabolism [16,17]. ALA can support a higher level Another possible contributor to the EPA/DHA
of bloodstream EPA, but is not nearly as effective as supply for humans is stearidonic acid (SDA,
is preformed EPA in this respect. EPA supplement- 18 : 4n3). Large commercial concerns have devel-
ation is also not able to increase the level of DHA in oped a genetically modified soybean that contains
the human bloodstream [17,18]. a large proportion of this omega-3 fatty acid, and it
A recent study (Table 3) in which ALA, EPA or has been declared safe for human consumption by
DHA was supplemented for 6 weeks to humans the US FDA (http://www.fda.gov/ForConsumers/
confirms these conclusions [18]. The ALA supple- ConsumerUpdates/ucm185688.htm.). The advan-
mentation produced a very small (0.24%) increase in tage of this approach is that it bypasses the delta-6
Table 3. Alpha-linolenic acid vs. eicosapentaenoic acid vs. docosahexaenoic acid supplementation and human bloodstream
content of n-3 fatty acids: Increase in percentage of total erythrocyte n-3 fatty acids after 6 weeks of supplementation
Fatty acid supplemented ALA diet group EPA diet group DHA diet group
Indicates statistically significant difference. ALA, alpha-linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid.
Data taken from [18].
1363-1950 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-clinicalnutrition.com 151
Thraustochytrid algae,
Dinoflagellate, marine, marine or euryhaline,
Zygomycete fungi, soil,
unicellular, flagellated, unicellular, obligate
filamentous, lipid,
obligate heterotroph, heterotroph, high
unique fatty acid
high lipid, unique fatty biomass and high lipid,
profile (ARA)
acid profile (DHA) unique fatty acid
profile (EPA and DHA)
FIGURE 4. Three important commercial organisms used for making long chain polyunsaturated fatty acids for human nutrition.
spread out over the ecosystem, and this represents a and a limited supply of these essential nutrients, the
challenge for the industry so as not to disrupt a genetically modified sources of EPA/DHA will
fragile environment. Krill oil has been marketed become more widely available in the future.
as more efficacious than fish oil purportedly due
to its differing lipid class form. Some species of krill
oils have large proportions of phospholipid forms of CONCLUSION
EPA/DHA [23], although this is variable. However, The major sources of EPA and DHA are from fish and
the claims of greater bioavailability of krill oil are fish oils, and there is not nearly enough of it avail-
not founded on controlled clinical studies and have able to supply commonly recommended levels of
&
been criticized [24 ]. intake for these nutrients in the human population.
Unfortunately, ALA, although relatively abundant,
cannot substitute for its longer chain and more
GENETICALLY MODIFIED VEGETABLE OIL unsaturated n-3 family members since humans have
AS A FUTURE SOURCE OF EPA/DHA only a trace level capacity to perform this conver-
Finally, the potential production of EPA and DHA by sion in vivo. Microbial oil production may theoreti-
land-based plants must be considered. Several cally be expanded in an almost unlimited fashion,
groups have made considerable progress in produc- but at a higher price point. Eventually, lower-priced
ing transgenic oil seed crops that can produce EPA or plant-based DHA oils will become available, but
DHA. Petrie et al. [25] have demonstrated insertion from a genetically modified organism. Economic,
of various desaturase and elongase genes into Ara- social, regulatory and political issues will thus be the
badopsis thaliana in order to produce oils containing main determinants of the availability of EPA and
12–15% of fatty acids as DHA. They state that one DHA in the future.
hectare of a Brassica napus crop employing this
technology producing 12% DHA oilseed would be Acknowledgements
equivalent to that produced from 10 000 fish. Dow The author gratefully acknowledges the input of Adam
Agro Sciences and DSM Inc. have similarly
Ismail and the GOED organization in making available
announced a program to produce DHA in canola
data on fish catch and fish oil production and for
oil [26]. Ruiz-Lopez et al. [27] have recently demon-
Figures 1 and 2.
strated transgenic variants of Camelina sativa that
produce seeds with up to 31% EPA and also one with
up to 12% EPA and 14% DHA. Financial support and sponsorship
Another very interesting development in the Financial support for this review was provided by DSM
genetically modified arena is the introduction of Nutritional Products.
domestic animals that have cloned enzymes such
that their meat is enriched in omega-3 fatty acids. Conflicts of interest
An example of this is given by the transgenic pig rich Norman Salem, Jr and Manfred Eggersdorfer are
in EPA/DHA after introduction of a humanized Cae- employed by DSM, a manufacturer of omega-3 fatty
norhabditis elegans gene, fat-1, which encodes for the acids.
&
omega-3 fatty acid desaturase [28 ]. With this
approach, they were able to increase the content
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