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CHAPTER
27
Fish and Fish Oil in Health and Disease Prevention. http://dx.doi.org/10.1016/B978-0-12-802844-5.00003-8
Copyright © 2016 Elsevier Inc. All rights reserved.
3
Recommended Intake of Fish and Fish
Oils Worldwide
C.K. Richter*, A.C. Skulas-Ray**, P.M. Kris-Etherton**
*Department of Nutritional Sciences, The University of Arizona, Tucson, Arizona,
United States; **Department of Nutritional Sciences, The Pennsylvania State University,
University Park, Pennsylvania, United States
INTRODUCTION
The relationship between long-chain (LC) omega-3 (n–3) polyunsaturated fatty acid (PUFA) intake and reduced
cardiovascular disease (CVD) mortality was rst discovered decades ago and the cardiovascular health benets of the
LC n–3 PUFAs, eicosapentaenoic acid (EPA, 20:5n3) and docosahexaenoic acid (DHA, 22:6n3), have been extensively
studied (Mozaffarian and Wu, 2012; Mozaffarian and Wu, 2011; Mozaffarian and Rimm, 2006). In a pooled analysis of
prospective studies and randomized clinical trials, modest consumption of sh or sh oil (eg, 1–2 servings/week pro-
viding ∼250 mg/day of EPA + DHA) lowered the relative risk of CHD mortality by 36% when compared to little or
no intake (Mozaffarian and Rimm, 2006). EPA and DHA also lower plasma triglycerides, resting heart rate, and blood
pressure, and may improve endothelial function (Mozaffarian and Wu, 2011); however, the effect of these changes on
clinical events (ie, CHD death) tend to have varying time courses and depend on the dose of EPA + DHA (Mozaffar-
ian and Rimm, 2006). For instance, at intakes <750 mg/day, antiarrhythmic effects predominate and can reduce clini-
cal events within weeks. Conversely, a reduction in triglycerides is hypothesized to require a longer period of time to
reduce clinical events (ie, months or years) and has a stronger effect at higher doses of EPA + DHA (Mozaffarian and
Rimm, 2006). Oily sh are the primary dietary source of EPA and DHA, and LC n–3 PUFA supplements (eg, sh oil)
are also widely available. Based on the evidence for their role in cardiovascular health and other disease outcomes,
multiple authoritative organizations worldwide have issued recommendations for sh and/or LC n–3 PUFA intake.
Despite appreciation for the health-promoting effects of LC n–3 PUFAs, there is wide variation in global in-
take and many populations consume well below the amounts associated with benecial health outcomes. For
instance, the diet of Greenland Eskimos is much higher in LC n–3 PUFAs than the typical Danish diet because of
their reliance on whale, seal, and sh meat (Bang et al., 1976; 1980). Similarly, daily sh and shellsh consump-
tion in Japan is also relatively high and was estimated to be ≈ 80 g/day in 2000 (Sugano and Hirahara, 2000).
Conversely, sh and LC n–3 PUFA intake is generally very low in the United States. The most recent analysis of
National Health and Nutrition Examination Survey (NHANES) data (2003–08) found that the mean intake of total
sh and sh high in omega-3 fatty acids was 0.61 and 0.15 oz/day, respectively (Papanikolaou et al., 2014). Since
the data are skewed by a very small percentage of high sh consumers, median intakes were even lower at 0.43 and
0.07 oz/day, respectively (Papanikolaou et al., 2014). With respect to EPA and DHA, average intake from dietary
sources (18 and 50 mg/day, respectively) and foods plus supplements (41 and 72 mg/day, respectively) were also
far below recommended amounts (Papanikolaou et al., 2014). This is similar to previously reported averages for
EPA and DHA intake from 1999–2000 NHANES data (30 and 70 mg/day, respectively, Ervin et al., 2004), as well as
the 1994–96 and 1998 Continuing Survey of Food Intakes by Individuals (28 and 57 mg/day, respectively; Institute
of Medicine, 2005). Other countries with relatively low LC n–3 PUFA intake include Australia (Howe et al., 2006),
Belgium (Sioen et al., 2006), Germany (Linseisen et al., 2003), the United Kingdom (Givens and Gibbs, 2006), and
Canada (Dewailly et al., 2001).
28 3. RECOMMENDED INTAKE OF FISH AND FISH OILS WORLDWIDE
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
This chapter will discuss the recommendations for sh and/or LC n–3 PUFA intake issued by organizations
worldwide. The omega-3 content of common sh and seafood varieties will be provided to demonstrate the number
of servings that need to be consumed per week to meet recommendations for LC n–3 PUFA. With respect to sh
consumption, concerns about potential contaminants and differences between wild-caught versus farmed species
will be discussed. Fish oil and other types of supplements are also available. The potential benets and drawbacks
of using supplements as a source of LC n–3 PUFA will be discussed, including considerations about the amount and
type of LC n–3 PUFA provided per capsule, as well as possible side effects. Although sh and sh oil are the primary
sources of LC n–3 PUFA, other dietary sources and supplements are likely to become increasingly important con-
tributors to LC n–3 PUFA intake and will be discussed in the chapter. Special attention should also be given to the
LC n–3 PUFA needs of specic life stages (ie, pregnant and/or lactating women) and populations (ie, vegetarians).
Emerging evidence has indicated that a third LC n–3 PUFA species—docosapentaenoic acid (DPA, 22:5n3)—may
contribute to the benecial health effects previously attributed solely to EPA and DHA. The sustainability of sh and
sh oil is also a primary concern and the chapter will conclude with a brief discussion about this and the potential
alternatives for meeting LC n–3 PUFA needs in the future.
INTAKE RECOMMENDATIONS
Recommendations Issued by Worldwide Authorities
LC n–3 PUFA were rst considered for inclusion in nutrition recommendations by a North Atlantic Treaty Organi-
zation (NATO) workshop that was convened in 1988, based on earlier pioneering research with Greenland Eskimos.
Although the members could not agree on a recommendation for n–3 fatty acid intake, it was recognized that 300–
400 mg/day of LC n–3 PUFA was likely needed to prevent a deciency in adults (Simopoulos, 1989). In 2002, the
Institute of Medicine (IoM) concluded that there was insufcient data to determine dietary reference intakes for EPA
and/or DHA. However, an Adequate Intake (AI), which is a recommended daily intake based on the nutrient intake
of apparently healthy people that is assumed to be adequate, was established for alpha-linolenic acid (ALA) as 1.6 g/
day for men and 1.1 g/day for women. It was recommended that up to 10% of this AI for ALA could be provided
by EPA and/or DHA (Institute of Medicine, 2005). Since then, substantial evidence has accumulated demonstrat-
ing a clear, inverse relationship between EPA + DHA intake and the risk of fatal CHD and possibly other disease
states (Harris et al., 2009). Recommendations have evolved to reect this growing evidence-base, and numerous
authorities have issued recommendations that now incorporate more specic guidelines for sh consumption and/
or EPA + DHA intake to promote health and reduce the risk of CVD and other chronic diseases.
The most up-to-date recommendations for sh and/or specic LC n–3 PUFA intake issued by selected dietary
and health authorities are provided in Table 3.1. A range of EPA + DHA intakes are recommended by different
authorities. For instance, whereas the European Food Safety Authority (EFSA) and Food and Agriculture Orga-
nization (FAO) recommend 250 mg/day, the Japanese Ministry of Health recommends a minimum consumption
of 1000 mg/day (Table 3.1; EFSA Panel on Dietetic Products, 2010; Joint FAO/WHO Expert Consulation, 2010a;
Ezaki et al., 2012). However, there is general consensus among the majority of expert bodies for 250–500 mg of
EPA + DHA per day, which can be provided by 2–3 servings of oily sh per week. Of the health organizations
listed in Table 3.1, only the Australia & New Zealand National Health and Medical Research Council specically
refer to the LC n–3 PUFA docosapentaenoic acid (DPA, 22:5 n3). Comparatively, little is known about DPA, but
current evidence indicates that it may provide a signicant amount of LC n–3 PUFA intake in populations that
consume meat from grass-fed ruminants and may provide similar health benets (further discussion of DPA is
provided later in the chapter). Further research on the role of DPA is warranted and future recommendations
may need to consider including specic reference to DPA.
The recommendations issued by many organizations are intended to reduce the risk of chronic diseases
(especially CHD) and promote the general health of the adult population as a whole. However, the optimal intake
of LC n–3 PUFAs and/or sh may depend on the specic population and outcome of interest; thus, some organiza-
tions also provide recommendations to reduce the risk of specic chronic conditions/diseases, such as, secondary
prevention of CHD and treatment of hypertriglyceridemia. For instance, the American Heart Association (AHA)
recommends the equivalent of 500 mg EPA + DHA per day (provided by two servings/week of preferably oily sh)
for primary prevention, 1 g/day for secondary prevention in individuals with established CHD (preferably from
oily sh, or using EPA+DHA supplements in consultation with a physician), and 2–4 g/day for the treatment of
high triglycerides.
INTAKE RECOMMENDATIONS 29
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
TABLE 3.1 Current Fish and/or LC n-3 PUFA Intake Recommendations for Adults from Selected National and International Authorities
Country/
region Authority (year) Target Recommendation
Global FAO/WHO Expert Consultation
(2010) (Joint FAO/WHO Expert
Consulation, 2010a)
Healthy adults 250 mg EPA + DHA per day
Pregnant/lactating women 300 mg EPA + DHA per day with at least 200 mg from
DHA
International Society for the Study
of Fatty Acids and Lipids (Cunnane
et al., 2004)
Reduce CHD risk in
healthy adults
Minimum of 500 mg EPA + DHA per day
Perinatal Lipid Intake Working
Group (2008) (Koletzko et al., 2007)
Pregnant and lactating
women
At least 200 mg per day of DHA
Consume 1–2 portions of sea sh, including oily sh,
per week
Europe European Food Safety Authority
(EFSA Panel on Dietetic
Products, 2010)
Healthy adults 250 mg EPA + DHA per day
1–2 fatty sh meals per week
Pregnancy and lactation General 250 mg per day of EPA + DHA
recommendation plus additional 100 mg per day
of DHA
United
States
American Heart Association (Kris-
Etherton et al., 2002; Lloyd-Jones
et al., 2010)
Healthy adults 500 mg EPA + DHA per day
At least two 3.5 ounce servings of (preferably oily) sh
per week
Secondary CHD
prevention
1 g EPA + DHA per day
Treatment of
hypertriglyceridemia
2–4 g EPA + DHA per day
Pregnant/lactating women Up to 12 ounces per week of a variety of sh that are low
in mercury (avoid shark, swordsh, king mackerel, and
tilesh; limit consumption of albacore “white” tuna to six
ounces per week)
Dietary Guidelines for Americans
U.S. Department of Health
and Human Services and U.S.
Department of Agriculture.
2015–2020 Dietary Guidelines for
Americans. 8th ed, 2015.
General health of adults Consume at least 8 ounces of seafood per week, which
provides on average 250 mg/day EPA+DHA
Pregnant/lactating women Consume at least 8 and up to 12 ounces of seafood per
week from a variety of seafood types that are lower
mercury
New 2015 Dietary Guidelines for
Americans have been issued, which
supplants the Dietary Guidelines
Advisory Committee Report
Academy of Nutrition and Dietetics
(Vannice and Rasmussen, 2014)
General adult population Consume two or more servings of fatty sh per week to
provide at least 500 mg EPA + DHA per day
National Lipid Association (2014) Treatment of
hypertriglyceridemia
2–4 g/d LC n-3 fatty acids
Jacobson T.A., et al., 2014. National Lipid Association
recommendations for patient-centered management
of dyslipidemia: Part 1 - executive summary. J. Clin.
Lipidol. 8 (5), 473–88.
United
Kingdom
NICE (National Institute for Health
and Care Excellence, 2014)
Secondary prevention
and/or people at high risk
of CVD
Eat at least two portions of sh per week, including a
portion of oily sh
(Continued)
30 3. RECOMMENDED INTAKE OF FISH AND FISH OILS WORLDWIDE
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
Although these recommendations have existed for many years, only select populations consistently consume the
recommended amount of sh and/or EPA + DHA. Therefore, strategies to increase consumption need to be devised
and implemented. One such strategy may be improving messages to the public and increasing awareness of how
these recommendations can be met by either dietary sources or supplements.
DIETARY SOURCES
Meeting Recommendations with Fish and/or Other Dietary Sources
Seafood, particularly oily sh, is the primary dietary source of LC n–3 PUFA. However, the LC n–3 PUFA content
of sh varies by species and can also be inuenced by how the sh were raised (ie, wild-caught or farm-raised). The
EPA, DPA, and DHA content of common sh/seafood varieties is presented in Table 3.2 along with the number of
servings needed per week to meet the daily EPA + DHA recommendation. Compared to oily sh, white sh, or non–
oily sh tends to provide much less LC n–3 PUFA. For instance, whereas the recommended daily intake of 500 mg
of EPA + DHA can be met by consuming approximately 2 servings of salmon or herring over the course of a week, it
would require over 10 servings of canned light tuna and ∼30 servings of tilapia to provide a similar amount of EPA
and DHA (Table 3.2). In general, the best sources of LC n–3 PUFA include Atlantic, Chinook, Coho, or Sockeye variet-
ies of salmon; Pacic or Atlantic herring; anchovies; sardines; and rainbow trout (Table 3.2).
Although all seafood provides EPA and DHA, it is important for consumers to recognize that not all varieties
are rich sources of LC n–3 PUFA (Weaver et al., 2008; Harris, 2008). Large differences in the fatty acid prole within
species can also occur due to many factors, including diet (Hardy and Lee, 2010; Theophilus Olayiwola et al., 2011)
and the location or time of year that wild sh are harvested (Jobling and Bendiksen, 2003; Gallagher et al., 1989;
Zlatanos and Laskaridis, 2007). In 2013, the most commonly consumed sh/seafood varieties in the United States
were shrimp, salmon, canned tuna, tilapia, pollock, pangasius, cod, catsh, crab, and clams (National Fisheries
Institute, 2013). Unfortunately, the majority of these species are very low in fat and therefore contain little LC n–3
PUFAs. Without a clear understanding of which types of sh provide the most LC n–3 PUFA content, consumers
are likely to base their seafood choices on availability and cost—which in many cases will result in the consump-
tion of predominantly low LC n–3 PUFA varieties, such as, farmed tilapia. However, sh are also a good source of
Country/
region Authority (year) Target Recommendation
Australia
and New
Zealand
National Heart Foundation of
Australia (2008; updated in 2015)
(Sugano and Hirahara, 2000;
Papanikolaou et al., 2014)
Adults 2–3 servings of sh (including oily sh) per week to
provide 250–500 mg EPA + DHA per day
Secondary CHD
prevention
1000 mg EPA + DHA per day
Treatment of
hypertriglyceridemia
Starting dose of 1200 mg EPA + DHA per day,
increasing to 4000 mg per day until TG target is reached
Australia & New Zealand National
Health and Medical Research
Council (Australian National Health
and Medical Research Council, 2006)
Reduce chronic disease
risk
Combined EPA + DPA + DHA intake of 610 mg per day
for men and 430 mg per day for women
Netherlands Health Council of the Netherlands
(Health Council of the
Netherlands, 2001)
General health of adults 200 mg per day of n–3 fatty acids in sh
France French Food Safety Agency
(ANSES, 2010)
General health of adults 250 mg per day of DHA and 250 mg per day of EPA for
a combined intake of 500 mg per day of EPA + DHA
Canada Dietitians of Canada (Kris-Etherton
et al., 2007)
General health of adults Two servings of sh per week, preferably fatty sh
∼8 ounces of cooked sh per week provides ∼500 mg
per day EPA and DHA
Japan Japanese Ministry of Health (2010)
(Ezaki et al., 2012)
Preventing lifestyle-related
disease
More than 1 g per day of EPA and DHA (lower
boundary; no upper boundary set)
TABLE 3.1 Current Fish and/or LC n-3 PUFA Intake Recommendations for Adults from Selected National and International
Authorities (cont.)
DIETARY SOURCES 31
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
TABLE 3.2 Omega-3 Content (Milligrams per 3 Ounce Serving) Provided by Common Fish/Seafood Varieties and the Number of
Servings Required per Week to Meet the 500 mg/day Recommendation for EPA + DHAa
EPA D PA DHA EPA+DHA
Servings/week to meet
500 mg/day recommendationb
SALMON
Atlantic, farmed 586 NA 1238 1824 2
Atlantic, wild 349 313 1215 1564 2
Chinook 858 252 618 1476 2.5
Coho 462 250 706 1168 3
Sockeye 353 145 690 1043 3.5
Chum 254 86 429 683 5
Pink 185 48 339 524 6.5
HERRING
Pacic 1056 187 751 1807 2
Atlantic 773 60 939 1712 2
Anchovies (raw) 457 25 774 1231 3
Sardinesc402 0 433 835 4
TROUT (RAINBOW)
Wild 398 NA 442 840 4
Farmed 220 93 524 744 4.5
BASS
Striped 184 NA 638 822 4.5
Sea 175 82 473 648 5.5
Freshwater 259 92 389 648 5.5
POLLOCK
Atlantic 77 24 383 460 7.5
Alaska 73 23 360 433 8
TUNA
Bluen 309 136 970 1279 3
White, cannedd198 15 535 733 5
Skipjack 77 14 201 278 12.5
Light, cannedd40 8 190 230 15
Yellown 13 4 89 102 34
MACKEREL
Atlantic 428 90 594 1022 3.5
Kinge148 19 193 341 10
OYSTER (RAW)
Pacic 372 17 212 584 6
Farmed 160 NA 173 333 10.5
Eastern 149 8 114 263 13.5
(Continued)
32 3. RECOMMENDED INTAKE OF FISH AND FISH OILS WORLDWIDE
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
high-quality protein, are low in total and saturated fat, and are a good source of other nutrients, including iodine,
vitamin D, zinc, magnesium, phosphorus, selenium, and potassium (Ruxton, 2011). Thus, although they contribute
very little to LC n–3 PUFA intake, these types of seafood can remain healthful choices if they are baked or broiled
(not breaded or fried; Harris, 2008).
Aquaculture production has risen dramatically since the early 1990s in response to declining wild sh stocks
(FAO, 2014). Salmon, tilapia, catsh, and trout are the most commonly consumed farm-raised sh (Weaver
EPA D PA DHA EPA+DHA
Servings/week to meet
500 mg/day recommendationb
CRAB
Alaska king 251 26 100 351 10
Dungeness 239 11 96 335 10.5
Blue 86 8 57 143 24.5
HALIBUT
Greenland 573 97 428 1001 3.5
Atlantic and Pacic 68 17 132 200 17.5
COD
Pacic 36 4 100 136 25.5
Atlantic 3 11 131 134 26
CATFISH
Wild 85 NA 116 201 27.5
Farmed 17 15 59 76 46
OTHER
Swordshe108 143 656 764 4.5
Tileshe146 122 623 769 4.5
Shark (mixed species; raw)e269 93 448 717 5
Walleye (pink) 94 42 245 339 10.5
Flounder/Sole 143 29 112 255 13.5
Clam 117 88 124 241 14.5
Shrimp 115 10 120 235 15
Grouper 30 14 181 211 16.5
Lobster 99 566 165 21
Scallop 61 4 88 149 23.5
Haddock 43 593 136 25.5
Mahi mahi (dolphinsh) 22 10 96 118 29.5
Tilapia 4 52 113 117 30
Orange roughy 5 1 21 26 134.5
NA, not available.
a Data from USDA National Nutrient Database for Standard Reference Release 27. All values are based on cooked varieties unless otherwise specified.
b Servings rounded to nearest 0.5 value.
c Atlantic, canned in oil, drained solids with bone.
d Canned in water, without salt, drained solids.
e Species with highest mercury content (≈1 ppm).
TABLE 3.2 Omega-3 Content (Milligrams per 3 Ounce Serving) Provided by Common Fish/Seafood Varieties and the Number of
Servings Required per Week to Meet the 500 mg/day Recommendation for EPA + DHAa (cont.)
DIETARY SOURCES 33
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
et al., 2008). For some species, it is important to distinguish between wild caught and farmed varieties due to dif-
ferences in LC n–3 PUFA content and concerns about environmental sustainability (discussed in the following
sections). For instance, farmed versus wild Atlantic salmon typically has higher EPA + DHA content, whereas wild
rainbow trout may contain more EPA + DHA than its farmed counterparts (Table 3.2). A recent analysis of the fatty
acid composition of farmed and wild species concluded that, in general, farmed species have equivalent or greater
amounts of EPA and DHA compared to their wild-caught comparators (Cladis et al., 2014). However, farm-raised
sh also tend to be higher in total fat, largely due to saturated fatty acids (SFA), monounsaturated fatty acids
(MUFA), and n–6 fatty acids (Weaver et al., 2008; Cladis et al., 2014; Gebauer et al., 2006). These differences in the
fatty acid prole are likely inuenced by the composition of the diet consumed by farmed sh. Diets high in SFA,
MUFA, and n–6 obtained from plant or animal sources are inexpensive, readily available, and thus are often used
to reduce costs. Certain species, such as tilapia, can also be cultured intensively with feeds that contain less protein,
more carbohydrates, and a wide range of fat sources, which inuences tissue fatty acid concentrations (Weaver
et al., 2008).
Concerns have also been raised about environmental toxins in sh, such as, methylmercury, polychlorinated bi-
phenyls (PCBs), and dioxins. Most sh contain trace amounts of methylmercury from natural sources (eg, erosion of
geologic deposits and volcanic emissions), but this can be exacerbated by environmental contamination from indus-
trial practices. Methylmercury is readily absorbed by tissues and thus tends to bioaccumulate. Therefore, larger, old-
er, and higher-trophic-level species generally have higher methylmercury content. However, methylmercury content
can vary greatly between and within species because it reects the concentration of methylmercury in their prey spe-
cies, the level of contamination in their environment, and species-specic physiological factors related to metabolism
and growth rate (Mahaffey et al., 2011). In general, shark, tilesh, swordsh, and king mackerel contain the highest
methylmercury content. At-risk population groups (ie, women who are pregnant, could become pregnant, or are
lactating, and infants and young children) should avoid consuming these species (US Food and Drug Administration
and Environment Protection Agency, 2004). The health effects of low-level methylmercury exposure in adults who
are not considered at-risk are not well established. However, methylmercury may modestly decrease the benets of
sh intake (Mozaffarian and Rimm, 2006). Although regulatory efforts have effectively reduced the use and emission
of PCBs and dioxins, both compounds persist in the environment and remain present in low concentrations in many
foods. However, commercially sold sh—whether wild-caught or farm-raised—contain very little PCBs and dioxins
and are responsible for only ≈ 9% of total dietary exposure in the United States (Mozaffarian and Wu, 2011; Joint
FAO/WHO Expert Consulation, 2010b). Cooking as well as removing the skin and fat of sh can also substantially
reduce PCB and dioxin concentrations. Unfortunately, preparation methods have little impact on methylmercury
content. Overall, the health benets of sh intake outweigh the potential risks and consuming a variety of seafood
will minimize exposure to environmental toxins while still maximizing the health benets of consuming sh (Mozaf-
farian and Rimm, 2006).
Although oily sh are the most concentrated source of LC n–3 PUFA, many non–sh sources of EPA and
DHA are now available and can be used to fortify foods. Numerous food products have been enriched with LC
n–3 PUFAs from sh or microalgae (Mahaffey et al., 2011; Whelan and Rust, 2006). Enriching chocolates, instant
oats, milk, dips, salad dressings, breads, and other products with ≈ 125 mg EPA + DHA per serving (to provide ≈
1 g/day) has been shown to increase LC n–3 PUFA status (Murphy et al., 2007). Eggs can also provide a substan-
tial source of LC n–3 PUFA if laying hens are fed supplemental sh oil or algae oil because the fatty acid composi-
tion of the egg yolk reects the lipid content of the hen’s diet(Leskanich and Noble, 1997). For instance, eggs con-
taining 56 mg EPA and 211 mg DHA have been produced from hens supplemented with sh oil (Elkin et al., 2015).
Algae oil supplementation has resulted in similar increases in the total n–3 fatty acid and DHA content of egg
yolks (Herber and Van Elswyk, 1996). Supplementing animal feeds with sh oil or shmeal can similarly in-
crease the LC n–3 PUFA content of poultry and pork products, although this requires the development of feeding
strategies that maximize LC n–3 PUFA enrichment without compromising consumer palatability (Leskanich and
Noble, 1997; Howe et al., 2002). For instance, a tuna shmeal supplement has been used to increase the total LC
n–3 PUFA content of pork and chicken products to ≈ 60–200 mg per 100 g serving, while maintaining consumer
acceptance (Howe et al., 2002). However, this strategy has proven less promising in ruminant species that typi-
cally consume a smaller amount of dietary fat and usually biohydrogenate unsaturated fatty acids unless they
are protected (ie, with an enteric coating) (Wachira et al., 2002; Ashes et al., 1992; Mandell et al., 1997). Producing
plant and animal products enriched with LC n–3 PUFA by genetic engineering may also provide an alternative
(Whelan, 2009; Kang et al., 2004; Lai et al., 2006). Based on the historic reluctance of Western populations to in-
crease fatty sh intake, fortication of commonly consumed foods with LC n–3 PUFA may offer a feasible solution
(Harris, 2007a).
34 3. RECOMMENDED INTAKE OF FISH AND FISH OILS WORLDWIDE
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
SUPPLEMENTAL SOURCES
Meeting Recommendations with Fish Oil or Other Supplements
LC n–3 PUFA can also be obtained from a variety of supplements, including sh oil and non sh-based products.
Some individuals may prefer supplements due to personal preferences, such as, ethical or environmental concerns,
disliking the taste of sh, unfamiliarity with seafood preparation and cooking methods, cost, food allergies, and a
perceived risk of pollutants. Others may require a supplement to achieve higher recommended LC n–3 PUFA intakes
that are not attainable by dietary means alone (ie, those with established CHD or elevated triglycerides). The EPA
and DHA content of prescription products and dietary supplements is provided in Table 3.3. The EPA + DHA content
provided by a 1 g capsule is typically 200–800 mg (Chee et al., 1990; Tatarczyk et al., 2007). Supplements are not sub-
ject to the same regulatory standards as pharmaceutical preparations (ie, Lovaza, Vascepa, and Epanova) and thus
may have more variation in their LC n–3 PUFA content. However, multiple quality assessments of common brands
have conrmed that the actual LC n–3 PUFA content of sh oil supplements is generally consistent with that reported
on the manufacturers’ label (Chee et al., 1990; Tatarczyk et al., 2007; ConsumerLab.com, 2014). Additionally, sh
oil supplements contain little to no mercury (Foran et al., 2003) and low absolute quantities of other contaminants
(ie, dioxins and PCBs; Mozaffarian and Wu, 2011; Food Safety Authority of Ireland, 2002; Jacobs et al., 2002).
LC n–3 PUFA supplements are available in a variety of formulations [ie, natural triglycerides (TG), ethyl esters
(EE), free fatty acids (FFA), and reesteried triglycerides (rTG)]. In foods and standard sh body oils (ie, menhaden
or cod liver oils), LC n–3 PUFAs are naturally found in the TG form (Rubio-Rodríguez et al., 2010). However, crude
sh body oil supplements contain only ≈ 18% EPA and ≈ 12% DHA (Schuchardt and Hahn, 2013). This requires
that a relatively large number of capsules be taken to meet recommended LC n–3 PUFA intake, creating signicant
challenges for compliance (Dyerberg et al., 2010). Rening processes—referred to as molecular distillation—have
been developed to deodorize and concentrate sh oils, resulting in products with 50%–85% EPA + DHA content
(Rubio-Rodríguez et al., 2010). This manufacturing process involves hydrolysis of the TG-bound LC n–3 PUFA from
the glycerol backbone, releasing FFAs that are then bound to ethanol, creating an EE fatty acid. This concentrates the
TABLE 3.3 EPA and DHA Content of Common Supplements and the Number of Capsules Required to Meet the 1 g/day
Recommendation.
Prescription omega-3 productsaFormulation EPA DHA EPA + DHA
Capsules required to meet ≈ 1 g/day
EPA + DHA recommendation
VascEPAb (Bays et al., 2011) Ethyl esters ≥960 0≥960 1 (960 mg/day EPA only)
EPAnova (Kastelein et al., 2014) Free fatty acids 550 200 750 1 (750 mg/day)
Lovazac (Bays, 2006) Ethyl esters 465 375 840 1 (840 mg/day)
Dietary Supplements
Standard menhaden sh body oild
(Kris-Etherton et al., 2002)
Triglycerides 180 120 300 3 (900 mg/day)
Omega-3 fatty acid concentrated
(Kris-Etherton et al., 2002)
Triglycerides 300 200 500 2 (1000 mg/day)
Cod liver oileTriglycerides 80 100 180 5 (900 mg/day)
Microalgae oilfTriglycerides 90 160 250 4 (1000 mg/day)
Krill oilgPhospholipids, free fatty
acids, and triglycerides
128 60 ∼190 5 (950 mg/day)
a Approved by the FDA for the treatment of hypertriglyceridemia (fasting serum triglycerides ≥500 mg/dL).
b Also referred to as AMR101 (Amarin) or Icosapent ethyl, and is marketed as Epadel in Japan.
c Previously known as Omacor.
d The United States Pharmacopeial Convention (USP) has verified supplements made by Berkley & Jensen, Equaline, Kirkland Signature, and Nature Made. ConsumerLab.com
has also performed quality testing on 53 supplements containing omega-3 fatty acids and verified their contents of EPA and DHA, as well as freshness, purity, and cost
(ConsumerLab.com, 2014).
e EPA and DHA content may vary by brand. Values in table represent labeled EPA and DHA content of Carlson cod liver oil gems super 1000 mg (http://www.carlsonlabs.com/p-109-
cod-liver-oil-gems-super-1000-mg.aspx).
f EPA and DHA content may vary by brand. Values in table represent labeled EPA and DHA content of Nordic Naturals Algae Omega 650 mg softgels (http://www.nordicnaturals.
com/en/Products/Product_Details/514/?ProdID = 1654).
g EPA and DHA content may vary by brand. Values in table represent labeled EPA and DHA content of Schiff MegaRed Ultra Strength Omega-3 Krill Oil 1000 mg softgels
(http://www.megared.com/our-products/megared-ultra-strength-1000-mg-omega-3-krill-oil/).
SUPPLEMENTAL SOURCES 35
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
fatty acids and removes any contaminants. Once the desired concentration is achieved, EEs can be chemically con-
verted back to triglycerides, forming rTG. Since the production of EEs is less costly, the majority of sh oil concentrate
supplements and the two of the three FDA-approved pharmaceutical preparations (ie, Lovaza and Vascepa) are in
the EE form. FFAs, which are susceptible to autooxidation and more likely to cause gastrointestinal side effects when
administered orally (Lawson and Hughes, 1988), were traditionally removed during the rening process (Schuchardt
and Hahn, 2013). However, these effects can be reduced by encapsulation (Lawson and Hughes, 1988) and coating
with a polyacrylate material that facilitates a delayed release in the small intestine rather than the stomach (Davidson
et al., 2012). FFA formulations using these technologies have become commercially available (ie, Epanova).
There is much debate regarding potential differences in the bioavailability of these different LC n–3 PUFA for-
mulations and how different factors, such as taking capsules with a fat-containing meal, may affect digestion and
absorption. In general, there seems to be some indication that bioavailability is highest for the FFA form (Ghasemifard
et al., 2014), with TG-bound and rTG-bound forms being more bioavailable than the EE form (Schuchardt and
Hahn, 2013; Ghasemifard et al., 2014). However, these conclusions are limited by differences in sample size, length of
supplementation, and the outcome measure used to assess bioavailability (ie, red blood cell [RBC] or plasma/serum
fatty acid concentrations; Schuchardt and Hahn, 2013; Ghasemifard et al., 2014). Most importantly, equal amounts of
LC n–3 PUFA were not provided by the different formulations in many studies (Ghasemifard et al., 2014). Other stud-
ies have also found no differences in bioavailability among the different formulations (Nordoy et al., 1991; Krokan
et al., 1993). Thus, at this time, there is not scientic consensus about the bioavailability of different preparations of LC
n–3 fatty acids. It is generally recommended that sh oil supplements be taken with a meal; however, the fat content of
the meal can substantially alter bioavailability, particularly for EE preparations. Thus, whether a lipid-rich meal was
incorporated into the supplementation design may have substantially inuenced bioavailability results (Schuchardt
and Hahn, 2013; Dyerberg et al., 2010; Ghasemifard et al., 2014). It is also unclear whether potential differences in
bioavailability translate into signicant differences in physiological effects. Although current evidence indicates that
EE preparations may have the lowest bioavailability, the key randomized trials demonstrating the cardioprotective
effects of EPA and DHA used EE preparations (GISSI-Prevenzione Investigators, 1999; Tavazzi et al., 2008; Yokoyama
et al., 2007). EE-based supplements also consistently increase the n–3 index, a robust marker of EPA and DHA intake
(Skulas-Ray et al., 2011; Neubronner et al., 2011; Harris, 2007b). In addition, there is extensive evidence for the triglyc-
eride-lowering effect of each form of supplement (Skulas-Ray et al., 2008; Bays, 2006; Kastelein et al., 2014; Ballantyne
et al., 2012). Thus, bioavailability is not typically an important consideration for selecting a LC n–3 PUFA supplement.
Other types of LC n–3 PUFA supplements are also available, including EPA- or DHA-only supplements, cod liver
oil, krill oil, and microalgae oil. Puried EPA-only and DHA-only supplements have been used to investigate po-
tential differential effects of the two fatty acids on CVD risk factors. It is beyond the scope of this chapter to provide
an in–depth discussion of these ndings; however, reviews have concluded that EPA and DHA have shared and
complementary effects, although further investigation is warranted as studies of individual fatty acids are relatively
limited (Mori and Woodman, 2006; Wei and Jacobson, 2011; Jacobson et al., 2012). However, it may be more practical
to continue focusing on their combined consumption as this is how LC n–3 PUFA are consumed in dietary sourc-
es, evidence for their individual effects remains limited, and increasing consumption of either would be benecial
(Mozaffarian and Wu, 2012). Cod liver oil is a less concentrated source of EPA and DHA but also provides substantial
amounts of vitamins A, D, and E (Lentjes et al., 2014). Although cod-liver oil supplementation is more often associ-
ated with traditional “folk” medicine approaches (ie, prevention of rickets), it has been shown to reduce total cho-
lesterol (Kingsbury et al., 1961), as well as triglycerides, while increasing HDL-C (Sanders et al., 1981). Oil can also
be extracted from cultivated microalgae (Adarme-Vega et al., 2012), with different varieties producing varying con-
centrations of EPA, DHA, and other LC n–3 PUFA (Doughman et al., 2007; Ward and Singh, 2005; Patil et al., 2007);
however, the microalgae strains that have been developed for commercial use (ie, Crypthecodinium cohnii, Schizo-
chytrium species, and Ulkenia species) produce DHA-rich oil (≈ 40% DHA w/ ≤ 2.5% EPA; Doughman et al., 2007;
Bernstein et al., 2012). Microalgae oil is very low in contaminants (Doughman et al., 2007), can be a nutritionally
equivalent source of DHA as cooked salmon (Arterburn et al., 2008), and lowers triglycerides to a similar extent as
sh oil supplementation (Bernstein et al., 2012). Krill oil has recently gained a great deal of attention as an alterna-
tive to sh oil. It is processed from Antarctic krill (Euphausia superba) and also provides astaxanthin—an antioxidant
responsible for the pink coloration of krill, salmon, trout, shrimp, and other crustaceans. Compared to sh oil, krill
oil has a much lower concentration of LC n–3 PUFA (Tou et al., 2007; Ulven et al., 2011) with a higher EPA to DHA
ratio (2:1 versus 1.5:1; Berge et al., 2014) [99]. Krill oil also provides EPA and DHA in the phospholipid rather than TG
form (Berge et al., 2014) and many claims have been made about greater bioavailability due to the provision of fatty
acids in this form. However, this has yet to be conclusively demonstrated as no direct comparisons of krill oil and
sh oil supplements have been conducted (Salem and Kuratko, 2014). Commercial krill oil products can also vary in
36 3. RECOMMENDED INTAKE OF FISH AND FISH OILS WORLDWIDE
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
phospholipid content (19–81%) and contain di- and triglycerides (13–34%), as well as free fatty acids (3.5–36%; Salem
and Kuratko, 2014; Araujo et al., 2014). Limited evidence demonstrates that krill oil supplementation has been shown
to lower serum triglycerides (Ulven et al., 2011; Berge et al., 2014; Bunea et al., 2004). Compared to standard sh oil
supplements, microalgae and krill oil supplements are more expensive.
Although sh oil supplements offer a viable alternative to consuming sh and effectively increase LC n–3 PUFA
intake, there is some risk of mild, predominately gastrointestinal, side effects. With respect to prescription LC n–3
PUFAs, the most commonly reported side effects are: (1) diarrhea, nausea, abdominal pain or discomfort, and burp-
ing with Epanova (AstraZeneca, 2014); (2) burping, upset stomach, and a change in the sense of taste with Lovaza
(GlaxoSmithKline, 2014); and (3) joint pain with Vascepa (Amarin Corporation, 2015). Like other lipid-lowering
medications, both Lovaza and Epanova can also transiently increase liver function enzymes in some individu-
als and should be periodically monitored by a medical practitioner (AstraZeneca, 2014; GlaxoSmithKline, 2014).
Gastrointestinal side effects can often be resolved by switching to a different formulation or taking the capsule with
meals or at a different time of day (Mozaffarian and Wu, 2011). EE preparations should not be frozen but for other
formulations, taking the capsule frozen may help to reduce gastrointestinal side effects. Some supplements are pro-
vided as enteric-coated capsules designed to release the oils in the intestine rather than the stomach to prevent a shy
aftertaste or shy burps. Both prescription and dietary supplement formulations containing DHA have been shown
to increase LDL-C (Mozaffarian and Wu, 2012; Mori and Woodman, 2006; Bernstein et al., 2012). However, increases
in LDL-C were typically associated with greater reductions in TG (Wei and Jacobson, 2011; Jacobson et al., 2012) and
were primarily due to an increase in LDL particle size, thereby resulting in a less atherogenic lipid/lipoprotein prole
(Mozaffarian and Wu, 2012; Mori and Woodman, 2006). The magnitude of this response also typically depends on the
TG and LDL-C concentrations of individuals prior to supplementation (Wei and Jacobson, 2011; Jacobson et al., 2012).
Additional Considerations Regarding LC n–3 PUFA
Special attention should also be given to the LC n–3 PUFA needs of specic life stages and population groups, the
emerging role of docosapentaenoic acid (DPA, 22:5n3), and the sustainability of sh and sh oil supplements as the
primary source of LC n–3 PUFA.
SPECIFIC LIFE STAGES AND POPULATION GROUPS
Pregnant or Lactating Women
DHA is an essential nutrient required for proper growth and development of the brain and retina (Innis, 2004;
Koletzko and Rodriguez-Palmero, 1999). Both observational studies and intervention trials have demonstrated that
greater maternal LC n–3 PUFA consumption during pregnancy is associated with better visual and neural devel-
opment (Mahaffey et al., 2011; Innis, 2007), whereas reduced DHA in these brain and retinal tissues can result in
decreased visual and psychomotor development (Innis, 2004). The DHA content of the maternal diet is the primary
determinant of the amount of DHA transferred to the fetus via the placenta and the amount of DHA secreted in
breastmilk (Innis, 2004; Innis, 2008). Uptake of DHA into these tissues is greatest during the third trimester and the
rst 2 years of life, making the pre- and postnatal periods of critical importance for maternal DHA consumption
(Mahaffey et al., 2011; Koletzko and Rodriguez-Palmero, 1999). Therefore, women should consume adequate quanti-
ties of seafood high in LC n–3 PUFA or supplement their diet during pregnancy and lactation to ensure that they can
meet the needs of the fetus in addition to their own physiological needs. Recommendations for LC n–3 PUFA intake
have been issued specically for women who are pregnant, may become pregnant, or are lactating (Table 3.1). In
many cases, these recommendations specify the amount of DHA that should make up the total LC n–3 PUFA intake
(Joint FAO/WHO Expert Consulation, 2010a) or advocate additional DHA intake beyond that suggested for the gen-
eral population (EFSA Panel on Dietetic Products, 2010).
Awareness of the benets of DHA intake for fetal development coexists with concerns about environmental toxins in
sh/seafood. Women who are pregnant, women who may become pregnant, lactating women, and children are consid-
ered at-risk groups due to the potential for detrimental neurodevelopmental effects of pre- and postnatal methylmercury
exposure. Three long-term studies have been conducted in populations with frequent maternal sh consumption (New
Zealand, the Faroe Islands, and the Seychelles) to evaluate the effects of prenatal methylmercury exposure (Crump
et al., 1998; Grandjean et al., 1997; Myers et al., 2003). In some cases, higher maternal methylmercury exposure was
associated with poorer scores on subsets of neurodevelopmental assessments in children (Crump et al., 1998; Grandjean
SPECIFIC LIFE STAGES AND POPULATION GROUPS 37
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
et al., 1997). These studies provided the basis for the Environmental Protection Agency’s (EPA) methylmercury refer-
ence dose (RfD), which is dened as the amount that can be consumed daily over the course of the lifetime without any
expectation of adverse effects, and is set at 0.1 µg of mercury per kg of body weight per day. The mercury content in
selected sh/seafood species is provided in Table 3.4. In June 2004, the United States Food and Drug Administration
(FDA) and EPA jointly issued an advisory on seafood consumption for pregnant and nursing women (US Food and
TABLE 3.4 Average Mercury Content of Selected Species of Fish/Seafood Compared to the EPA + DHA Content of These
Species (per Three Ounce Serving)a
Species Mercury (µg) EPA + DHA (mg)
Varieties with highest mercury contentb
Tilesh (Gulf of Mexico) 123 770
Swordsh 84.6 760
Shark 83.2 720
King mackerel 62.1 340
Commonly consumed varieties
Salmon 1.87 520–1820
Herring 7.14 1710–1810
Anchovies 1.45 1230
Atlantic mackerel 4.25 1020
Sardines 1.11 840
Trout (freshwater) 6.04 740–840
Bass (saltwater, black, striped) 12.9 650–820
Pollock 2.64 430–460
Tuna, canned, light 10.9 230
Tuna, canned, white 29.8 730
Tuna, yellown 30.1 100
Tuna, Skipjack 12.2 280
Oyster 1.02 260–580
Crab 5.53 140–350
Halibut 20.5 200–1000
Cod 9.44 130–140
Catsh 2.13 80–200
Flatsh (includes ounder, plaice, sole) 4.76 260
Clam 0.77 240
Shrimp 0.77 240
Grouper 38.1 210
Lobster (Northern/American) 9.1 170
Scallop 0.26 150
Haddock 4.68 140
Tilapia 1.11 120
Orange roughy 48.5 30
a Data from United States Food and Drug Administration, “Mercury Levels in Commercial Fish and Shellfish (1990–2010)” (available at: http://www.fda.gov/food/
foodborneillnesscontaminants/metals/ucm115644.htm) and USDA National Nutrient Database for Standard Reference Release 27.
b Should be avoided by at-risk population groups (ie, pregnant or lactating women, women of child-bearing potential, and children).
38 3. RECOMMENDED INTAKE OF FISH AND FISH OILS WORLDWIDE
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
Drug Administration and Environment Protection Agency, 2004). It recommended that species with the highest meth-
ylmercury content (ie, shark, swordsh, king mackerel, and tilesh) be avoided entirely by at-risk groups. Women and
young children were advised to “eat up to 12 ounces or 2 average meals a week of a variety of sh and shellsh that are
lower in mercury,”, such as, shrimp, canned light tuna, salmon, pollock, and catsh (US Food and Drug Administration
and Environment Protection Agency, 2004). Although the advisory acknowledges the nutritional benets of consuming
a variety of sh/shellsh, of the examples of commonly consumed low-mercury species given in the advisory, salmon
is the only option that would provide the recommended EPA + DHA intake within the 12 ounce per week restriction
(Table 3.2). The advisory additionally restricts consumption of albacore (“white”) tuna to 6 ounces per week due to its
higher methylmercury content. Conversely, canned light tuna does not need to be restricted in this way, although it con-
tains lesser amounts of EPA and DHA. Unfortunately, many pregnant women and their health-care providers likely do
not make this distinction, resulting in complete avoidance of tuna (and likely other seafood, as well).
While the neurodevelopmental harm associated with excessive methylmercury consumption should not be ig-
nored, most authorities agree that the benets of sh consumption far outweigh the potential risk from consum-
ing small amounts of contaminants (Mozaffarian and Rimm, 2006; Joint FAO/WHO Expert Consulation, 2010b).
Unfortunately, this message has not always been effectively conveyed to the public (Verbeke et al., 2005). Messages
about risk often predominate in the news media (Greiner et al., 2010) and concerns about prenatal methylmer-
cury exposure and developmental impairments can quickly overtake the message that greater sh consumption is
benecial for fetal development (Bloomingdale et al., 2010). This may create an unnecessarily negative perception
of sh and cause pregnant women to further reduce their already insufcient sh intake. For instance, following
well-publicized national advisories about the risks of mercury in sh in 2001, total sh consumption decreased in a
cohort of pregnant Massachusetts women (Oken et al., 2003). A risk assessment of the effects of the 2001 advisory also
demonstrated that consumers tend to reduce consumption of all types of sh species, resulting in reduced intake of
LC n–3 PUFA as well as methylmercury (Shimshack and Ward, 2010). Additionally, although the FDA/EPA advisory
is intended for at-risk groups (ie, women of child-bearing age and children), there are likely spill-over effects in low-
risk groups and reduced consumption in the general population (Shimshack et al., 2007).
The FDA and EPA have issued a 2014 draft revision of their 2004 advisory, although it has yet to be nalized (US
Food and Drug Administration, 2014). The new advisory is intended to encourage women to eat the recommended
amount and types of sh and now includes a minimum of 8 ounces per week (US Food and Drug Administra-
tion, 2014), in accordance with the DGA2015 recommendation that “women who are pregnant or breastfeeding con-
sume at least 8 ounces and up to 12 ounces of a variety of seafood per week, from choices lower in methyl mercury”
(USDA, HSS, 2010). Other countries, such as Japan, offer less restrictive guidance and highlight the nutritional value
of sh consumption. For instance, the Japanese Ministry of Health urges pregnant women not to stop eating sh or
reduce their intake but to pay attention to which species may contain high mercury levels (Ser and Watanabe, 2012).
Fish consumption advisories require careful formulation to ensure that the benets and risks of sh consump-
tion are communicated effectively and are accessible to both high- and low-risk groups (Mahaffey et al., 2011; Oken
et al., 2012). It is possible to select species that will minimize methylmercury exposure while providing the benets
associated with sh consumption (Bellinger, 2014; Del Gobbo et al., 2010; Dewailly et al., 2008); for instance, Atlantic
mackerel, salmon, and sardines contain substantial LC n–3 PUFA content with low-to-moderate methylmercury
(Mahaffey et al., 2011). However, there are currently no clear guidelines for consumers to select an appropriate
combination of sh to obtain the recommended amount of LC n–3 PUFA without exceeding the methylmercury
reference dose. Many consumers may also be overwhelmed by the number and complexity of factors that must be
considered (Oken et al., 2012). The difculty of conveying this message is likely somewhat responsible for pregnant
and lactating women in Canada, Australia, Europe, and the United States consuming far below the recommended
amount of sh and/or DHA (Cosatto et al., 2010; Sioen et al., 2010; Denomme et al., 2005; Innis and Elias, 2003; Jia
et al., 2015). Ultimately, the best long-term solution for reducing methylmercury concentrations in sh is controlling
global mercury sources. Unfortunately, despite the progress that has been made in this regard, it will take many
years for these changes to become apparent in the food system. In the interim, clearer and more effective messages
are needed to ensure that pregnant and lactating women consume adequate amounts of sh and LC n–3 PUFA while
remaining protected from undue methylmercury exposure.
Vegetarian and Vegan Populations
As LC n–3 PUFA are primarily obtained from the consumption of sh and/or sh oil, vegetarian and vegan popu-
lations tend to have very low or no LC n–3 PUFA intake and may benet from alternative dietary and/or supplement
options. Vegetarians consume minimal EPA (<5 mg/day) and varying amounts of DHA (typically ≈20 mg/day),
SPECIFIC LIFE STAGES AND POPULATION GROUPS 39
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
depending on dairy and egg consumption (Davis and Kris-Etherton, 2003; Sanders, 2009; Geppert et al., 2005). Vegans
consume negligible amounts of both EPA and DHA (Davis and Kris-Etherton, 2003). Even if vegetarians/vegans con-
sume adequate amounts of ALA—the precursor of LC n–3 PUFA—this is not a viable substitute for preformed EPA
and DHA due to poor conversion. Conversion of ALA to LC n–3 PUFA requires a series of alternating desaturation
and elongation reactions, and conversion efciency tends to vary considerably among individuals. General consensus
is that conversion to EPA is limited (≈8% in adult men; Burdge and Calder, 2005). Further conversion to DHA is esti-
mated to be even lower, with the majority of studies reporting estimates of less than 0.05% in adult men (Burdge and
Calder, 2005). Premenopausal women tend to exhibit higher conversion rates, particularly for the production of DHA
(≈2.5-fold greater conversion rates for EPA and >200-fold greater for DHA; Burdge and Calder, 2005), possibly as a
means of ensuring that the DHA needs of the fetus/neonate can be met (Burdge and Calder, 2005; Burdge et al., 2002).
However, greater dietary intake of n–6 fatty acids and/or LC n–3 PUFA may inhibit ALA conversion (Burdge and
Calder, 2005). In general, vegetarians and vegans tend to have substantially lower plasma, blood cell, tissue, and
breastmilk concentrations of EPA and DHA compared to omnivores (Sanders, 2009; Harris, 2014), indicating that in
vivo ALA conversion rates may be insufcient to achieve EPA and DHA concentrations equivalent to those achieved
by consuming sh. Therefore, vegetarian/vegan dietary sources and/or supplements are needed to ensure that this
portion of the population has the means to meet LC n–3 PUFA recommendations.
A limited number of vegetarian dietary sources and supplements are now available and are likely to become in-
creasingly accessible in the future as demand for these products grows. Individuals who consume eggs can obtain
a reasonable amount of DHA (up to 100–150 mg DHA/egg from chicken fed microalgae), but very little EPA (Davis
and Kris-Etherton, 2003). Seaweed, or macroalgae, is even lower in fat than most vegetables, but does contain small
amounts of LC n–3 PUFA (≈100 mg EPA per 100 g serving; Davis and Kris-Etherton, 2003). As previously noted, mi-
croalgae oil is a viable supplement option but still remains more expensive compared to sh body oil supplements.
Supplementation with microalgae has been shown to signicantly increase the n–3 index, an established marker of
LC n–3 PUFA intake, to concentrations associated with the lowest cardiovascular risk (Geppert et al., 2005). However,
the algae oils currently commercially available are DHA-rich and provide much less EPA (Doughman et al., 2007).
There is some evidence to suggest that retroconversion of supplemental DHA occurs at physiologically meaningful
rates (Conquer and Holub, 1997), but additional sources of EPA may also be required.
Stearidonic acid (SDA; 18:4 n–3), the metabolic intermediate of ALA and EPA, may provide a viable plant-based
alternative for obtaining EPA (Whelan, 2009). Although SDA is not a major component of the diet, it is a minor
constituent in sh/seafood and is found in relatively high amounts in seeds from the Boraginaceae family, such
as, echium oil (12–14% SDA; Walker et al., 2013; Surette, 2013; Guil-Guerrero et al., 2001; Kuhnt et al., 2012). Few
SDA-containing seed oils are commercially available, but growing interest in alternative LC n–3 PUFA sources has
led to development of genetically modied varieties of canola and soybean enriched in SDA (SDA soybean, 20–30%
SDA; Lemke et al., 2010; Ursin, 2003). SDA-enriched soybean oil is also relatively oxidatively stable, increasing its
potential integration into a wide range of food products (Decker et al., 2012), and has been predicted to be a less
costly source of EPA than seafood or sh oil supplements (Kennedy et al., 2012). Interest in SDA is largely due to
the fact that it is more efciently converted to EPA than ALA. SDA does not appear to accumulate in tissues; when
preformed SDA is consumed it is rapidly converted to EPA resulting in signicant increases in tissue EPA and the
n–3 index (Lemke et al., 2010; Harris et al., 2008; Krul et al., 2012; James et al., 2003). However, compared to dietary
EPA, dietary SDA is ≈ 17% as effective at raising EPA concentrations in plasma phospholipids and RBC membranes
and has no effect on DHA concentrations (Harris et al., 2008). Despite the evidence that SDA can increase tissue
EPA concentrations, it remains unclear whether SDA can impart health benets for CVD risk factors or outcomes.
Randomized controlled trials have found no effect of SDA supplementation on lipid biomarkers (ie, TG, TC, LDL-C,
and HDL-C; Whelan et al., 2012) in healthy (Krul et al., 2012), overweight, or obese populations (Lemke et al., 2010;
Harris et al., 2008; Pieters and Mensink, 2015). However, the lack of effect in these trials may be due to the wide
range of BMI and lipid levels of participants as the EPA-supplementation comparator group employed by many
of these studies also did not experience reductions in TG (Walker et al., 2013; Lemke et al., 2010; Harris et al., 2008;
Krul et al., 2012). Additionally, the duration of these trials may have been too short, they may have been underpow-
ered with too few participants, or used doses of SDA that were too low as an SDA dose of 9 g/day may be required
to detect health effects (Walker et al., 2013). Thus, further investigation into the potential health effects of SDA is
warranted. Although they remain many years away from commercial production, transgenic varieties of canola,
soybean, and safower have also been developed to produce seed oils enriched in EPA and/or DHA (Surette, 2013;
Truksa et al., 2006; Sayanova and Napier, 2011; Napier et al., 2015; Petrie et al., 2014; Damude and Kinney, 2007).
However, any genetically modied crops are likely to face some degree of consumer resistance due to the negative
perception of transgenic products.
40 3. RECOMMENDED INTAKE OF FISH AND FISH OILS WORLDWIDE
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
Additional research is needed to clarify the benets of LC n–3 PUFA supplementation in vegetarian and vegan
populations. Vegetarian and vegan dietary patterns tend to be associated with better health (Harris, 2014), and it
remains unclear whether LC n–3 PUFA supplementation can further reduce the risk of chronic disease in these popu-
lations (Sanders, 2009; Harris, 2014). However, the EPA and DHA status of vegetarians and vegans is generally well
below that considered to be cardioprotective (Harris, 2014). At this point in time, increasing ALA and SDA consump-
tion, combined with supplementation of preformed DHA from algae oil, offers the best means of increasing EPA and
DHA in people who do not consume any animal products.
Docosapentaenoic Acid (DPA, 22:5n3)
Emerging evidence suggests that docosapentaenoic acid (DPA, 22:5n3), the intermediate fatty acid species be-
tween EPA and DHA, may also play a role in imparting the health benets previously attributed solely to EPA and
DHA. Although evidence remains limited, a lower serum concentration of n–3 DPA has been associated with greater
risk of myocardial infarction (Oda et al., 2005). Furthermore, plasma n–3 DPA has been inversely associated with
total mortality (particularly from stroke-related deaths; Mozaffarian et al., 2013), nonfatal myocardial infarction (Sun
et al., 2008), and incident CVD in some ethnic groups (de Oliveira Otto et al., 2013). An inverse relationship between
RBC n–3 DPA and triglycerides has been documented in two studies (Dai et al., 2016; Skulas-Ray et al., 2015), and this
may have important implications for the management of atherogenic dyslipidemia. An inverse association with the
inammatory marker C-reactive protein (CRP) has also consistently been reported for plasma, serum, and RBC n–3
DPA concentrations (de Oliveira Otto et al., 2013; Skulas-Ray et al., 2015; Reinders et al., 2012; Mozaffarian et al., 2011;
Micallef et al., 2009; Labonte et al., 2014) whereas no association between CRP and RBC EPA or DHA content has been
found in many of these same study populations (Skulas-Ray et al., 2011; Labonte et al., 2014; Flock et al., 2014). Like
EPA and DHA, n–3 DPA is also converted into unique specialized pro-resolving mediators (ie, resolvins, protectins,
and maresins) that promote the resolution of inammation (Dangi et al., 2009; Dalli et al., 2013). Based on their dif-
fering associations with inammatory markers and the structural differences among n–3 DPA, EPA, DHA, and their
metabolites, it is possible that they may inuence different aspects of the innate immune system.
A better understanding of how n–3 DPA stores respond to LC n–3 PUFA supplementation is needed to clarify
the role of n–3 DPA in health outcomes. Cell-based studies have demonstrated that interconversion of EPA and n–3
DPA occurs readily (Benistant et al., 1996; Kaur et al., 2011; Norris and Dennis, 2012), while conversion of n–3 DPA to
DHA is limited (Kaur et al., 2010). In clinical trials, supplementation with EPA + DHA (Skulas-Ray et al., 2015; Cao
et al., 2006; Meyer et al., 2009; Katan et al., 1997) and puried EPA (Krul et al., 2012; Mori et al., 2000; von Schacky
and Weber, 1985) has also been shown to increase RBC and plasma n–3 DPA. Prior to supplementation, EPA and n–3
DPA levels in the body are also commonly associated whereas there is no relationship between n–3 DPA and DHA
concentrations (Mozaffarian et al., 2013; Sun et al., 2008; Skulas-Ray et al., 2015; Mozaffarian et al., 2011). Therefore,
endogenous production from EPA may be an important means of increasing tissue n–3 DPA reserves.
Endogenous n–3 DPA stores may also serve as a source of EPA, which could have important implications for
disease states related to LC n–3 PUFA intake. EPA and n–3 DPA are highly interconvertible and EPA concentrations
have been increased by DPA supplementation in both cell-based (Benistant et al., 1996) and clinical studies (Miller
et al., 2013). LC n–3 PUFA also tend to exhibit cell/tissue specicity. Plasma EPA appears to serve as a more dynamic
and readily available pool of LC n–3 fatty acids that increases and decreases more quickly than DHA (Sun et al., 2008;
Katan et al., 1997; Brown et al., 1991). Furthermore, DHA is enriched in myocardial and neuronal membranes (Harris
et al., 2004), and the EPA content of RBCs is lower than that of n–3 DPA and DHA (Dai et al., 2016; Cao et al., 2006;
Katan et al., 1997; Miller et al., 2013). Thus, 22-carbon fatty acids may be preferentially stored in specic tissue com-
partments, and in the case of n–3 DPA, may serve to replenish plasma EPA that has been utilized.
Less research has been conducted on n–3 DPA compared to EPA and DHA, and consequently the contribution
of n–3 DPA to total LC n–3 PUFA intake has not been a focus of nutrition information messaging. Supplement la-
bels typically do not quantify the amount of n–3 DPA provided and intervention studies rarely report the n–3 DPA
content of supplements. Nutrient databases may also be similarly limited and inaccuracies in the DPA content of
foods have been found in both Canadian and Australian nutrient databases, resulting in substantial underestima-
tions of intake (Howe et al., 2006; Jia et al., 2015). For example, when the 1995 Australian National Nutrition Sur-
vey was reanalyzed using a database with updated fatty acid composition data, 30% greater estimates for LC n–3
PUFA intake were found, largely due to inaccuracies in preexisting data regarding the DPA content of meats (Howe
et al., 2006). Whereas DPA is a much smaller component of most sh and sh oil supplements compared to EPA
and DHA (Howe et al., 2007), grass-fed red meat (particularly beef and lamb) is a modest source of n–3 DPA (and
to a lesser extent, EPA; Howe et al., 2006). In Australians, the category of meat, poultry, and game is often the 2nd
SUSTAINABILITY 41
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
largest contributor to LC n–3 PUFA intake (following sh and seafood) due to its DPA content (Howe et al., 2006;
Rahmawaty et al., 2013). Conversely, United States nutrient databases typically report very little, if any, LC n–3 PUFA
content in meat. This may reect lack of available fatty acid composition data or differences in the PUFA composi-
tion of meat from pasture-fed versus grain-fed livestock. Studies comparing the effect of different feeding systems
on the fatty acid composition of beef have demonstrated that grass-based feeding can signicantly increase EPA,
DPA, and DHA content, although the increase in these fatty acids is modest (Ponnampalam et al., 2006; Nuernberg
et al., 2005; Scollan et al., 2006; Turner et al., 2015). Therefore, Australian cattle, which are predominantly pasture-fed,
tend to have higher LC n–3 PUFA concentrations than grain-fed cattle, which is a common feeding system in the
United States (Howe et al., 2007; Ponnampalam et al., 2006). Thus, additional research is needed to better quantify the
amount of n–3 DPA in supplements and foods, and identify factors that may inuence n–3 DPA concentrations (ie,
farming practices). However, current evidence indicates that n–3 DPA is a physiologically important LC n–3 PUFA
and should be included in future investigations of the health benets of individual n–3 fatty acid species, analyses of
LC n–3 PUFA intakes, and dietary recommendations.
SUSTAINABILITY
Even at current levels of sh and sh oil consumption—which are far below recommendations—the sustainabil-
ity of sh production is uncertain (Jenkins et al., 2009). In the 1950s and 1960s, global production from wild sheries
increased ∼6% per year but average rates of increase had declined to ≈2% by the 1970s and 1980s (FAO, 2000). By
the 1990s, despite increasing shing effort, global catches had plateaued and the majority of sh stocks were fully
exploited or had already collapsed (Jenkins et al., 2009; FAO, 2000). The proportion of sh stocks being harvested
at a biologically sustainable amount has declined from 90% in 1974 to 71.2% in 2011 (FAO, 2014). Furthermore, in
2011, 28.8% of sh stocks were considered overshed (FAO, 2014). Global marine capture has remained relatively
stable at ≈80–90 million tons from 1990–2014 (FAO, 2014, 2012, 2012). To meet the growing demand for seafood,
which could no longer be met by increasing wild catches, aquaculture production has steadily risen since the 1970s.
In 2014, aquaculture production contributed a record 42.2% of total sh production, compared to just 25.7% in 2000
(FAO, 2014). However, annual growth rates have declined from 10.8% over 1990–2000 to 6.2% during the 2000–12
period (FAO, 2014). Per capita sh consumption has increased from 10 kg in the 1960s to over 19 kg in 2012 and is
projected to continue increasing (FAO, 2014). If the global population were to begin following intake recommenda-
tions, for each individual, the 500 mg EPA + DHA per day recommendation would translate to 182.5 g/year (Salem
and Eggersdorfer, 2015); assuming a worldwide population of 7.2 billion, total global intake requirements would
be ≈1.3 billion kg/year (Salem and Eggersdorfer, 2015). In terms of sh servings, this would require over 100 three-
ounce servings of wild Atlantic salmon per person per year—and even greater quantities for species with less LC n–3
PUFA (Table 3.2). Thus, pressures on both wild sh stocks and aquaculture systems is unlikely to subside and the
development of more sustainable harvesting practices or alternative sources of LC n–3 PUFA will likely be required.
Although aquaculture is often perceived as a potential solution to reduce pressure on wild sh stocks, cer-
tain types of aquaculture may actually contribute to the collapse of global sheries (Naylor et al., 2000). Farm-
ing carnivorous sh (eg, salmon, Bluen tuna, and sea bass) and marine shrimp can further deplete wild shery
stocks through habitat destruction, pollution from waste disposal, exotic species and pathogen invasions (Krkosek
et al., 2007), and requirements for high-protein diets that contain substantial amounts of sh meal from wild-caught
sh (Jenkins et al., 2009; Naylor et al., 2000; Naylor et al., 1998). Many intensive aquaculture systems rely heavily on
added feeds because sh are stocked at a density beyond the capacity of natural food sources (Naylor et al., 2000).
In these systems, carnivorous sh require 2.5–5 times more sh protein in sh meal than is ultimately produced by
the farmed product (Tacon, 1997). Many of the species typically used for sh meal are already over-shed, which
may have ramications throughout the food web for their larger predator species (Pauly et al., 2005). Conversely,
farming herbivorous species or lter feeders (ie, carp and mollusks) reduces the need for sh meal/oil in feed and
thus is a greater contributor to the net global sh supplies (Naylor et al., 2000). By integrating the production of
multiple trophic levels, polyculture systems utilize resources more efciently and reduce environmental contami-
nation compared to typical intensive monoculture methods, and may offer a practical solution for continued, sus-
tainable expansion of the industry (Naylor et al., 2000; Neori et al., 2004; Chopin et al., 2001; Granada et al., 2015).
For instance, seaweed (Neori et al., 1996; Troell et al., 1999) (Troell et al., 1999; Samocha et al., 2015), oysters (Jones
and Iwama, 1991), and mussels (Soto and Mena, 1999; Handå et al., 2012) can be grown in wastewater from salmon
and/or shrimp farming, using efuent output from one system as a resource for others. Ultimately, aquaculture
sustainability will likely require greater regulation and enforcement of management techniques to reduce habitat
42 3. RECOMMENDED INTAKE OF FISH AND FISH OILS WORLDWIDE
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
destruction, prevent the escape of pathogens or farmed sh, and ensure proper treatment of wastewater (Naylor
et al., 2000).
Identifying and developing alternative LC n–3 PUFA sources will also help to alleviate pressures on wild sheries
and allow aquaculture systems to grow sustainably. Microalgae oil, krill oil, and genetically modied plants and/or
animals are currently the most promising alternatives but still encounter some limitations. Algae oil has been com-
mercially produced since the 1990s to fortify infant formula with DHA (to achieve amounts similar to those found in
human breastmilk; Kuratko and Salem, 2013; Spolaore et al., 2006). There is likely considerable room for growth and
marketing to consumer niches as algae oil is considered environmentally friendly, free of ocean-borne contaminants,
vegetarian, and can be manufactured under kosher and halal conditions (Salem and Eggersdorfer, 2015); however,
algae oil remains more expensive than sh oil supplements and the development of new production facilities contin-
ues to be capital-intensive. Supplementation with algae oil may increase LDL-C (Bernstein et al., 2012), an effect that
can also be caused by sh oil supplementation, and which may be due to the DHA and/or saturated fat content of
commercially available algae oil (Geppert et al., 2005). Despite krill oil recently becoming a larger contributor to the
supplement market, the present krill oil harvest is estimated to be below 0.1% of the over 300 million tons of available
biomass in the Antarctic Ocean (Kwantes and Grundmann, 2015). The Commission for the Conservation of Antarctic
Living Resources has estimated sustainable harvest rates (Kwantes and Grundmann, 2015; Nicol et al., 2012), but
concerns have been raised about the fragility of the Antarctic ecosystem (Kwantes and Grundmann, 2015), nega-
tive effects of climate change in krill populations (Nicol et al., 2012; Flores et al., 2012), possible declines in krill
stocks (Atkinson et al., 2004), and potential ramications for species higher on the food chain (Atkinson et al., 2004;
Trivelpiece et al., 2011). Krill oil is much more expensive than sh oil and contains a lower concentration of LC
n–3 PUFA, requiring that more krill oil be consumed to achieve the same dose of LC n–3 PUFA (Kwantes and
Grundmann, 2015). Genetically modied plants and/or animals capable of producing LC n–3 PUFA may offer a
more efcient alternative, but are likely to face consumer resistance in some markets. Soybeans that have been ge-
netically modied to produce SDA may offer an alternative to preformed EPA, but additional research is needed to
determine if SDA can impart health benets similar to those of EPA and DHA. Progress has been made in develop-
ing transgenic crops enriched in EPA and/or DHA, but they are not yet commercially available. Transgenic pigs that
can endogenously synthesize LC n–3 PUFA have also been successfully produced (Lai et al., 2006) but likely face
the greatest degree of consumer resistance and regulatory hurdles. Although these alternatives are likely to remain
relatively minor contributors to LC n–3 PUFA intake for the immediate future, the increasingly limited supply of sh
and sh oil may ultimately require that these barriers be overcome.
CONCLUSION
Despite substantial evidence that health benets are associated with higher intake of sh and/or LC n–3 PUFA,
many populations consume very little. Numerous expert authorities have issued recommendations for amounts
of sh and/or LC n–3 PUFA intake to promote health and reduce CVD risk, with the general consensus specify-
ing intake of 250–500 mg of EPA + DHA per day or 2–3 servings of oily sh per week. These recommendations
can be met by consuming a variety of different sh species. However, many commonly consumed sh contain
relatively low concentrations of LC n–3 PUFA and some are a source of environmental toxins. For individuals
who cannot or prefer not to eat sh and those who require a higher intake of LC n–3 PUFA, supplementation may
offer a viable alternative. Many varieties of sh and nonsh-based supplements are now available. Important
considerations regarding supplements include: the amount of EPA + DHA provided in each capsule, the supple-
ment formulation, potential side effects, cost, and sustainability. Although sh oils are the predominant source
of LC n–3 PUFA, alternative supplement options include krill oil, algae oil, and SDA-enriched oils that can be
converted to EPA. In addition to recommendations for the general population, special consideration should be
given to the DHA needs of pregnant/lactating women and the LC n–3 PUFA needs of vegetarian/vegan popula-
tions. Emerging evidence also indicates that in addition to EPA and DHA, a third LC n–3 PUFA, DPA, may confer
health benets. Therefore, the amount of DPA in foods and supplements should be better quantied and addi-
tional research is needed to determine the effect of DPA supplementation and better characterize how DPA stores
respond to n–3 supplementation. Although global LC n–3 PUFA intake remains well below recommendations,
the sustainability of worldwide sh production is a signicant concern. Careful management of wild-capture
sheries, implementation of more sustainable aquaculture systems, as well as identication and development of
alternative LC n–3 PUFA sources, will be essential to ensuring the continued availability of LC n–3 PUFA to meet
global recommended intakes.
I. FISH AND FISH OIL INTAKE AND RECOMMENDATIONS
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