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Plants as alternative sources of n-3 polyunsaturated fatty acids

May 2018

Authors:

Javier S. Perona

Spanish National Research Council

Jose Maria Castellano

Spanish National Research Council

It is well accepted that the consumption of very long-chain n-3 PUFA of marine origin have beneficial effects on plasma triglyceride concentrations and on systemic inflammation states. α-Linolenic acid (18: 3 n-3, ALA), although also a member of the n-3 PUFA family, is found predominantly in plants and its beneficial effects on health are more controversial. However, it has been suggested that ALA intake may reduce the risk of coronary heart disease when the intake of n-3 PUFA from marine sources is low. It is still unclear whether the effect is per se, or after its bioconversion to eicosapentaenoic (EPA) or docosahexaenoic (DHA) n-3 PUFA. Despite the recommendations of international institutions, including the World Health Organization, to increase fish consumption, in many countries it is difficult to achieve sufficient intake of n-3 PUFA. Access to n-3 PUFA of marine origin may be limited even in those regions with access to the sea. On the other hand, fish stocks are endangered around the world, making aquaculture the only sustainable solution for the future. Thus, the consumption of ALA-rich plant food is postulated as one of the most realistic alternatives to endure the n-3 PUFA intake. Among the different alternatives of plant n-3 PUFA-rich sources, chia (Salvia hispanica), sacha inchi (Plukenetia volubilis) and linseed (Linum usitatissimum), have been considered. Oils obtained from their seeds can provide up to 65% of ALA. In addition, nuts are also appreciated sources of n-3 PUFA. Finally, transgenic plants have also been proposed as sustainable sources of EPA and DHA. We review here the current knowledge on plant n-3 PUFA consumption and the physiological mechanisms, mediated by triglyceride synthesis and the inhibition of inflammatory processes, by which they can exert beneficial effects on human health.

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BIOCHEMISTRY RESEARCH TRENDS

POLYUNSATURATED FATTY

ACIDS (PUFAS)

FOOD SOURCES, HEALTH EFFECTS AND

SIGNIFICANCE IN BIOCHEMISTRY

ANGEL CATALA

EDITOR

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In: Polyunsaturated Fatty Acids (PUFAs) ISBN: 978-1-53613-572-5

Chapter 7

PLANTS AS ALTERNATIVE SOURCES OF N-3

POLYUNSATURATED FATTY ACIDS

Javier S. Perona



, Silvia Garcia-Rodriguez

and Jose M. Castellano

Department of Food and Health,

Instituto de la Grasa-CSIC, Seville, Spain

ABSTRACT

It is well accepted that the consumption of very long-chain n-3

PUFA of marine origin have beneficial effects on plasma triglyceride

concentrations and on systemic inflammation states. -Linolenic acid

(18: 3 n-3, ALA), although also a member of the n-3 PUFA family, is

found predominantly in plants and its beneficial effects on health are

more controversial. However, it has been suggested that ALA intake may

reduce the risk of coronary heart disease when the intake of n-3 PUFA

from marine sources is low. It is still unclear whether the effect is per se,

or after its bioconversion to eicosapentaenoic (EPA) or docosahexaenoic

(DHA) n-3 PUFA. Despite the recommendations of international

institutions, including the World Health Organization, to increase fish

 Corresponding Author: perona@ig.csic.es.

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consumption, in many countries it is difficult to achieve sufficient intake

of n-3 PUFA. Access to n-3 PUFA of marine origin may be limited even

in those regions with access to the sea. On the other hand, fish stocks are

endangered around the world, making aquaculture the only sustainable

solution for the future. Thus, the consumption of ALA-rich plant food is

postulated as one of the most realistic alternatives to endure the n-3

PUFA intake. Among the different alternatives of plant n-3 PUFA-rich

sources, chia (Salvia hispanica), sacha inchi (Plukenetia volubilis) and

linseed (Linum usitatissimum), have been considered. Oils obtained from

their seeds can provide up to 65% of ALA. In addition, nuts are also

appreciated sources of n-3 PUFA. Finally, transgenic plants have also

been proposed as sustainable sources of EPA and DHA. We review here

the current knowledge on plant n-3 PUFA consumption and the

physiological mechanisms, mediated by triglyceride synthesis and the

inhibition of inflammatory processes, by which they can exert beneficial

effects on human health.

1. INTRODUCTION

Few dietary components are so widely recognized as able to improve

the human health as the n-3 PUFA. The shelves of supermarkets and food

stores exhibit many products with labels indicating the presence of these

compounds. The prevalent PUFA found in nature belongs to the n-3 and n-

6 classes, where the double bond that is closest to the methyl terminus of

the acyl chain is located between carbons 3 and 4, and between carbons 6

and 7, respectively. The three main dietary n-3 PUFA are α-linolenic acid

(18:3 n-3, all-cis-octadeca-9,12,15-trienoic acid, ALA), eicosapentaenoic

acid (20:5 n-3, all-cis-eicosa-5,8,11,14,17-pentaenoic acid, EPA), and

docosahexaenoic acid (22:6 n-3, all-cis-docosa-4,7,10,13,16,19-hexaenoic

acid, DHA). Plants can desaturate fatty acids at positions 3, 6 and 9, while

animals, particularly vertebrates (including mammals), can only introduce

unsaturations from carbon 9 towards the carboxyl group. For this reason,

linoleic acid (18:2 n-6, all-cis-octadeca-9,12-dienoic acid, LA) and ALA

can not be synthesized in mammals from precursors of lower unsaturation,

and must be provided by the diet in certain quantities and proportions.

Thus, LA and ALA are recognized as essential fatty acids.

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Although animals cannot synthesize ALA, they can metabolize it to

other longer chain and more unsaturated n-3 PUFA. This occurs by a series

of linked desaturation and elongation reactions that mainly take place in

the liver. Firstly, ALA is converted to stearidonic acid (18:4 n-3) by Δ6-

desaturase, and then elongated to eicosatetraenoic acid (20:4 n-3). Further

desaturation by Δ5-desaturase yields EPA. Conversion of ALA to EPA

competes with the biosynthesis of arachidonic acid (AA; 20:4 n-6) from

LA, since both metabolic pathways use the same microsomal enzyme

system. EPA can be further converted to DHA through a four-step process.

Initially, EPA is elongated to form docosapentaenoic acid (22:5 n-3, DPA),

which is subsequently elongated and unsaturated by Δ6-desaturase to

produce 24:6 n-3. This fatty acid is then transported to the peroxisome,

where it is converted in DHA by partial β-oxidation.

It is assumed that Δ6-desaturase is rate limiting in this pathway. The

activities of Δ6-and Δ5-desaturases are regulated by nutritional status,

hormones, and feedback inhibition by end products, creating a complex

control network for endogenous long-chain PUFA synthesis.

Once consumed in the diet, n-3 PUFA are absorbed from the

gastrointestinal tract and transport to the liver via chylomicron particles.

These fatty acids occupy, preferentially, the sn-2 position in phospholipids

and triglycerides, so they are not released by the intestinal pancreatic lipase

(with specificity for sn-1 and sn-3), being absorbed as lysophospholipids or

monoglycerides. Nor are they released from the circulating chylomicrons

by the vascular lipoprotein lipase. In the liver, n-3 PUFA are used as a

source of triglycerides in lipoprotein particles and phospholipids. From the

liver, n-3 PUFA are released into the blood mainly as phospholipids

associated to plasma albumin, and incorporated into cell membrane

phospholipids throughout the body. In addition, some of them are stored in

the adipose tissue as triglycerides. The conversion of 24:6 n-3 in DHA

would occur, above all, in the astrocytes of the glia. These cells have the

function of providing DHA to the neurons, since this fatty acid is essential

for maintaining the fluidity of the plasma membrane and for the formation

of other bioactive compounds.

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Figure 1. Synthesis of eicosanoids and docosanoids. A) Competition between

arachidonic acid (AA) and eicosapentaenoic acid (EPA) for cyclooxygenases (COX)

and lypoxygenases (LOX). After be released from membrane phospholipids by the

action of phospholipase A2, free AA and EPA are converted by the same enzymes

(COX and LOX) to their oxygenated metabolites prostaglandins (PGs), tromboxanes

(TXs) and leukotrienes (LTs), collectively named eicosanoids. B) Formation of

resolvins and protectins from EPA and docosahexaenoic acid (DPA). (Adapted from

G. Calviello and S. Serini. Dietary Omega-3 Polyunsaturated Fatty Acids and Cancer.

Springer Science + Business Media B. V. 2010. ISBN 978-90-481-3578-3).

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The sn-2 position of membrane glycerophospholipids is devoted to

AA, an n-6 PUFA. AA is released from membrane phospholipids by

phospholipase A2, an enzyme that can be activated by inflammation. The

free AA is then processed by several enzymes belonging to the COX and

LOX families as well as cytochrome P450, to generate potent pro-

inflammatory eicosanoids (Lewis et al., 1990; Tilley et al., 2001; Kroetz

and Zeldin, 2002) (Figure 1).

Since n-3 and n-6 PUFA are metabolized by the same enzymes, COXs

and LOXs, n-3 PUFA compete with n-6 PUFA for these enzymes and

inhibit biosynthesis of n-6 series eicosanoid (Berquin et al., 2008). Several

research groups reported that n-3 PUFA counter-regulate AA-derived

eicosanoids in cells, animals, and humans by inhibiting n-6 PUFA

metabolism and antagonizing them on their oxygenation pathways to

produce mediators (Edwards and O’Flaherty, 2008; Gleissman et al., 2010;

Greene et al., 2011). DHA can downregulate the formation of AA-derived

PGE2. Thus, dietary n-3 PUFA may function as natural COX inhibitors.

EPA and DHA are also released intracellularly from membranes by the

action of phospholipase A2, and subsequently metabolized by the

cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. The action of

COX on EPA produces 3-series thromboxanes (TX3), prostaglandins (PG3)

and prostacyclines (PCI3). Likewise, LOX transforms EPA into 5-series

leukotrienes (LT5). These EPA metabolites have, generally, little biological

activity, but they interfere with the action of analog eicosanoids

synthesized from the AA cascade, generally pro-inflammatory. In addition,

it has been reported that the PCI3 formed in the endothelial cells exert

inhibitory effects on platelet aggregation and are vasodilators. Likewise,

LT5 originated in leukocytes have anti-inflammatory effects and inhibit

chemotaxis and cell adhesion.

1.1. Dietary Sources and Bioavailability of n-3 PUFA

The major dietary source of EPA and DHA are fish, especially those

from cold water. It is well known that fish fat contains compounds of

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dietary and pharmacological interest, and that their physical properties

make them useful as emollients. Two types of fish can be distinguished: a

first category composed of fish such as cod or haddock, whose primary

reserve of lipids is the liver (these fish are often known as white fish or

lean, with <2% fat), and a second category that includes fish whose fat is

distributed in its flesh (muscle), which gives it a whitish tone, which is

sometimes colored by the presence of carotenoids such as astaxanthin.

These fish are known as fatty or blue fish, with >5% fat, and sardines,

anchovies, herring or salmon are typical examples. The content of EPA

and DHA of the different marine species varies depending on the season,

whether they are caught in the open sea or comes from fish farming and the

method of cooking. EPA and DHA may be also artificially added to the

diet as fish oil supplements, in capsule format or as fish oil-enriched food.

In this sense, the fishing industry produces flours and oils from fishing

waste or from species caught for this purpose. Currently, fish oil capsules

are commercialized, which generally contain around 18% of EPA and 12%

of DHA, as well as products based on sardine and anchovy oils, from

particular regions, captured at specific times, presenting an EPA: DHA

ratio of 3-4: 1.

Nowadays, both PUFA n-6 and n-3 constitute a good model for the

development of functional foods and nutraceuticals. Efforts have been

made to incorporate them into milk drinks and derivatives. Margarines,

shortenings and mayonnaises are made enriched in ALA, EPA and DHA,

what is an adequate way to supplement the diet of populations in which

fish consumption is reduced. Bioavailability of n-3 PUFA in humans has

been evaluated by measuring their concentrations in plasma, blood cells

and different tissues. It has been reported that a dietary fish oil

supplementation (3 g/day EPA + DHA) or a daily serving of salmon (1.2

g/day EPA + DHA) may allow an enrichment of EPA and DHA in serum

lipids, ranging from 100 to 130% for EPA, and from 25 to 40% for DHA.

Even higher increases were reported for total phospholipids after dietary

supplementation with EPA and DHA ethyl esters (1.9 and 0.9 g/day,

respectively). It is not definitely established what is the best source for

maximal bioavailability of these fatty acids. However, it has been reported

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that high plasma concentrations of EPA and DHA was better achieved if

their source was fish (containing mainly n-3 PUFA esterified as

acylglycerols), rather than capsules containing the fatty acids ethyl ester

derivatives.

Thus, the latest consensus recommendations and practice guidelines

advice a regular consumption of fish (two or three servings a week),

especially of the small fatty species (sardine, anchovy, mackerel, herring).

Each serving, on average, should provide 200-500 mg of EPA + DHA. The

dietary intake of EPA and DHA has been also recommended during

pregnancy and lactation, since it is well established that these fatty acids

exert crucial effects on growth and neurological development of fetuses

and newborns infants. The maternal plasma phospholipid concentration of

PUFA increases during pregnancy, probably mobilized from maternal

stores. It was suggested that DHA could be stored in the mother’s adipose

tissue, as temporary reservoir. It is recommended that the mother receive

300 mg/day of EPA + DHA, of which, the consumption of DHA should

correspond to 200 mg/day. However, intakes of up to 2.7 g of EPA + DHA

per day (with 1 g/day of DHA) are accepted as the upper limit without

adverse reactions (FAO, 2010). Newborns who receive breastfeeding

adequately meet their n-3 PUFA requirements, since breast milk, on

average, contributes 0.2-0-4% of DHA.

1.2. Beneficial Effects of n-3 PUFA on Human Health

The role of n-3 PUFA as nutritional factors with potential to prevent or

delay the progression of prevalent chronic pathologies has been

established. It is recognized that n-3 PUFA improve dyslipidemia,

especially lowering plasma levels of triglycerides, slightly decrease blood

pressure, inhibit the formation of the atheroma plaque, and reduce the risk

of sudden death, arrhythmia and stroke, in individuals diagnosed of heart

pathologies. Furthermore, these fatty acids can be useful in preventing the

vascular complications of diabetes.

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The importance of an increased dietary intake of n-3 PUFA has been

also recognized for the prevention of neurodegenerative processes.

Epidemiological studies have indicated the possibility that dietary EPA and

DHA may modify the risk and progression of the Alzheimer’s disease.

Similarly, the benefits of EPA and DHA have been demonstrated in

immunity and inflammatory disorders.

1.2.1. Effects of n-3 PUFA in Cardiovascular Diseases

Certain countries, such as those in the Mediterranean basin and Japan,

are known to have a surprisingly low rate of coronary heart disease (CHD)

and cardiac death. This could be partly explained by regional dietary

factors, as suggested by a common feature of the diet of these countries:

the high consumption of fish, the main source of long chain n-3 PUFA.

The number of epidemiological studies and controlled clinical trials that

have evaluated the effects of EPA and DHA (or their food sources) in

relation to cardiovascular risk factors and clinical events, is greater than for

any other food or nutrient.

However, in the last years, a number of meta-analyses of

epidemiological observations and randomized clinical trials focused on n-3

PUFA have not obtained conclusive results with respect to CHD, although

they have detected a consistent protection against cardiac mortality. A

possible explanation of this could be purely methodological, due to the

variability in the selection of the included studies, the variability in the

inclusion/exclusion criteria, the stated objectives, the type and duration of

the interventions, the verification of adherence to the same or the statistical

analysis itself.

The null results could also be explained by other reasons, such as the

substantial improvement in the guidelines for the treatment of ischemic

patients in the last years, or the high basal consumption of fish, EPA and

DHA or fish oil capsules, by patients who are aware of having a high

cardiovascular risk, that are also well informed of the benefits attached to

these PUFA. Under these conditions, the 1 g/day increase in EPA + DHA

consumption could hardly demonstrate efficacy in reducing cardiovascular

risk. n-3 PUFA have pleiotropic effects in addition to lipid modifying

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effects. Both pre-clinical and clinical studies have shown that n-3 PUFA

prevent cardiovascular events by ameliorating endothelial function and

attenuating lipid accumulation, vascular inflammation and macrophage

recruitment.

1.2.2. Effects of n-3 PUFA in Insulin Resistance and Diabetes

There is not a clear consensus from human trials on the systematic use

of n-3 PUFA supplements for people with insulin resistance or type 2

diabetes. Substantial inconsistencies exist between studies of humans

compared to rodent models. While most studies in rodents suggest a

favorable effect of n-3 fatty acids on glucose homeostasis and insulin

sensitivity, human studies are conflicting. Although some report

improvement in insulin sensitivity by fish oil consumption, the majority of

studies do not corroborate the findings.

Most of observational studies reflect a beneficial effect of n-3 PUFA

on insulin action, describing an inverse association between fatty acid level

and the homeostasis model assessment of insulin resistance (HOMA-IR)

index, in populations with a high intake of fish and a low risk for metabolic

syndrome and diabetes type 2, indicating that n-3 PUFA could assist in the

prevention and treatment of insulin resistance in humans (Connor et al.,

2007; Serhan et al., 2008; Gleissman et al., 2010). This association

remained significant even after adjusting for age, gender, BMI, and

ethnicity (Connor et al., 2007). Nevertheless, in a prospective study in

Korean healthy adults, who were followed for three years, the consumption

of fish oil was associated with a lower risk for metabolic syndrome among

men, but not among women (Oh et al., 2010).

In contrast to observational studies, in most of the identified

randomized controlled trials there was no appreciated changes in insulin

sensitivity. A systematic meta-analysis of 11 randomized clinical trials

published until 2010, with 618 participants, concluded that n-3 PUFA

consumption did not affect insulin sensitivity (Teng et al., 2012). Another

systematic review, which examined the effect of EPA and DHA on

metabolic syndrome risk factors, concluded that there are no clear effects

on selected markers, except for an improvement in blood pressure and the

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well-established hypotriglyceridemic effect. Surprisingly, lower doses of

n-3 PUFA were associated with further benefits of reducing pro-

atherogenic low density lipoproteins, whereas greater doses (>3 g/day)

were associated with increases in LDL cholesterol (Hu et al., 2010).

It is well assumed that n-3 PUFA do not provide beneficial effects on

the glycemic control of patients with established type 2 diabetes. Two

meta-analyses, which included 18 and 23 randomized trials, respectively,

involving a large numbers of participants, were concordant in outcomes,

describing that n-3 PUFA supplementation cause a decrease in plasma

triglycerides, a slight increase in LDL, but no effect on the glycemic

control or fasting insulin (Dyerberg et al., 1975; Jatoi et al., 2004).

1.2.3. Effects of n-3 PUFA in Cancer

There is increasing evidence that n-3 PUFA play a key role in cellular

homeostasis. From this idea has arisen the hypothesis that alterations in the

intake and/or metabolism of these fatty acids can alter cellular functions,

thus modifying the progression of tumor cells. In this sense, the n-3 PUFA

have demonstrated antitumor properties both in vitro and in animal models

of cancer (Azrad et al., 2013). However, the evidence in humans is not so

clear and no significant associations have been found between the

paradigmatic cancers of Western society (breast, prostate and colorectal)

and the intake of n-3 PUFA (Gerber, 2012) or the consumption of fish

(Sala-Vila and Calder, 2011). Population-based studies mostly rely on data

from self-reported dietary fat consumption or from assessments based on

national dietary habits, and these evaluations can be poorly correlated to

real fatty acid composition in patient samples by direct measurements. In

addition, the actual amount of n-3 PUFA consumption may be too low to

have a protective effect in some cases. Similarly, the ratio of n-6/n-3 PUFA

could be more important than the absolute amount of n-3 PUFA, as

suggested by animal and human studies (Gu et al., 2013).

Traditional cancer chemotherapy often does not provide satisfactory

long-term clinical results. In most cases, only partial response is achieved,

and cancer cells often continue to proliferate and eventually metastasize.

Combining agents result in superior response rates and increased disease-

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free or even overall survival. However, combinational chemotherapy has

also been associated with increased treatment complexity and toxicity and,

frequently, decreased quality of life (Huober and Thurlimann, 2009). n-3

PUFA are good candidates for chemoprevention or combinational

chemotherapy, as health promoters to increase the quality of life of cancer

patients. It has been reported that plasma n-3 PUFA levels in cancer

patients are up to 50% lower than in healthy individuals, and this is

associated to loss of adipose tissue and skeletal muscle. This suggests that

supplementation with n-3 PUFA may be beneficial. Many studies show

prevention of muscle loss or gain of body mass with n-3 PUFA

supplementation during cancer chemotherapy. n-3 PUFA supplementation

may not only improve the cachexia condition for cancer patients but also

deliver better response to treatment and reduce side effects associated with

cancer chemotherapy (Murphy et al., 2012). Many clinical intervention

trials have been proposed and developed to validate the effectiveness of n-

3 PUFA in cancer prevention and treatment or to provide nutritional

support for cancer patient who suffered weight loss, fatigue, and other

inflammation-related illness (Berquin et al., 2008).

The inflammatory reaction to a local tumor can also trigger a cascade

of systemic inflammation that eventually lead to development of anorexia

and catabolic processes, such as muscle proteolysis and lipolysis, the early

stage of fatigue and cachexia (Gullett et al., 2011). Several clinical trials,

using EPA or marine fish oil (EPA + DHA) in purified form or in the form

of oral supplements, have showed that EPA supplementation (>2 g/day)

can reduce, even stabilize, losses of weight and muscle mass in patients at

advanced stages of cancer (Barberet al., 1999; Fearon et al., 2003; Colomer

et al., 2007; Gullett et al., 2011). However, data from other controlled

randomized trials did not report benefits by the use of EPA (Jatoi et al.,

2004; Fearon et al., 2006). Successful management of cachexia may

require a multimodal approach with nutritional supplementation and

pharmacological treatment. A recent randomized phase III clinical trial

suggested that combination therapy with EPA supplementation, megestrol

acetate, thalidomide, and L-carnitine was significantly more effective in

improving lean body mass and appetite than single agents (Mantovani,

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2010). It is believed that tumor cells can be more easily sensitized to

chemotherapy when membrane lipids contain high level of DHA. A

clinical phase II trial to improve outcome of anthracycline chemotherapy

by using DHA (1.8 g/day) in metastatic breast cancer patients has

demonstrated the delay of tumor progression and a higher overall survival.

The study also found that DHA had no adverse side effects, unlike

chemotherapy (Bougnoux et al., 2009).

2. N-3 PUFA OF VEGETABLE ORIGIN. SEEDS RICH IN

ALPHA-LINOLENIC ACID

As earlier mentioned, ALA is an essential fatty acid that can be

elongated and desaturated to become very long-chain PUFA, such as EPA

and DHA (Morales et al., 2012). Despite the recommendations of the

World Health Organization, the intake of ALA has been reduced in

Western societies. One of the main contributors to the reduction of ALA

consumption was the increase in the intake of grains with a high content of

LA, such as corn. In Western Europe and North America, this has

drastically changed the proportion of n-6:n-3 fatty acids from 8:1 to 20:1,

which is far from what is considered optimal (4:1) (Barceló-Coblijn et al.,

2003).

Unfortunately, it is not an easy goal to increase the intake of n-3 PUFA

due to the scarcity of natural sources and their limited availability. The

natural sources that contain high levels of EPA and DHA are basically

limited to fatty fish and to a number of other types of seafood, which

provides sustainability problems when it comes to encouraging the

population to increase their consumption (Barceló-Coblijn et al., 2009).

Therefore, a suggested alternative would be the vegetable sources of ALA,

particularly in countries with little or no access to fish and seafood.

Variable amounts of ALA are found in plants, zooplankton, phytoplankton

and marine species. In plants, ALA is found in leaves, mainly in

glycolipids, and as triglycerides in certain seed oils, beans and nuts.

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Table 1. Alpha-linolenic acid (ALA) content in ALA-rich

vegetable sources

Common name

Scientific name

g ALA/100g

Flaxseed

Linum usitatissimum

22.8

Flaxseed oil

53.3

Perilla

Perilla frutescens

Perilla oil

Chia seed

Salvia hispanica

17.6

Chia oil

Sclarea seed

Salvia sclarea

Sclarea oil

Sacha inchi oil

Plukenetia volubilis

Camelina oil

Camelina sativa

Rosehip oil

Rosa Rubiginosa

Canola oil / Rapeseed oil

Brassica campestris

Soybean Green raw

Glycine max

0.4

Soybean oil

6.8

Walnuts

Juglans regia

9.1

Cloudberry

Rubus chamaemorus

1.2

Blueberry

Vaccine corymbosum

0.8

Lingonberry/Cowberry

Vaccinium vitis-idaea

0.2

There are few natural sources that have significant amounts of ALA to

meet the consumers demands (Table 1) (Valenzuela et al., 2011; Morales

et al., 2012). Flaxseed oil is widely used industrially in the manufacture of

varnishes and paints for its drying effect but it is used very scarcely as food

due to its high oxidative unstability (Valenzuela et al., 2014).

Recently, other sources of ALA are being proposed experimentally,

like chia (Salvia Hispanica) or sacha inchi (Pluketia volubilis) among

others. These oils, which have Latimamerican origin, together with others

of European and/or Asian origin (camelina, perilla, etc.), are currently

interesting alternatives to provide ALA (Valenzuela et al., 2014). In

particular, perilla oil (approximately 55% ALA), although its consumption

is restricted to Asia, while the consumption of camelina oil (38% ALA) is

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mainly consumed in Nordic countries. (Barceló-Coblijn et al., 2009;

Morales et al., 2012).

3. BIOCONVERSION OF ALA TO EPA AND DHA

In mammals, ALA, after being absorbed at the intestinal level, presents

three possible metabolic pathways: storage in adipose tissue, β-oxidation

and extensive carbon recycling and conversion to EPA and DHA.

β-Oxidation constitutes the main metabolic destination of ALA,

approximately between 60-85%, so that there is little ALA available for

bioconversion in EPA and DHA. However, this high percentage of ALA

used for β-oxidation is not exclusive to ALA, since other PUFA derived

from the diet are β-oxidized in similar percentages. For instance,

approximately 50% of n-6 fatty acids are used for β-oxidation and about

65% of DHA suffer the same fate. Therefore, dietary ALA, similar to other

fatty acids in the diet, undergoes significant utilization by tissues in the

form of energy. Finally, the carbon recycling of ALA is quite efficient,

being used to form saturated fatty acids (Barceló-Coblijn et al., 2009).

ALA is converted to EPA and DHA through a series of chain

desaturation and elongation processes, as stated above. This enzymatic

conversion is quite inefficient, mainly concerning to the production of

DHA. In particular, it is estimated that the conversion efficiency of ALA to

EPA is 0.2%, to DPA n-3 of 0.13% and to DHA of 0.05% (Sanz-París et

al., 2012). As shown in Figure 2, in the endoplasmic reticulum, ALA is

desaturated at 18:4 n-3 by Δ-6 desaturase, then elongated to 20:4 n-3, and

finally converted to EPA by Δ-5-desaturase. EPA can be further elongated

to form 22:5 n-3 and then to 24:5 n-3 followed by a desaturation by Δ-6

desaturase to form 24:6 n-3. Subsequently, in the peroxisome, 24:6 n-3 is

subjected to a β-oxidation to form DHA (Barceló-Coblijn et al., 2009;

Valenzuela et al., 2011).

On the other hand, n-3 and n-6 fatty acids use the same enzymatic

machinery for their elongation and desaturation, and thus, there is a

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competitive relationship between the two routes. The activation of one

route or another will depend on the physiological situation of the

individual. To better understand this competence, it must be taken into

account that the family of n-6 fatty acids has LA as a precursor and one of

its most important derivatives is arachidonic acid (20:4 n-6, AA). ALA

appears to be a much stronger suppressant of the elongation and

desaturation of n-6 fatty acids than the LA of elongation and desaturation

of n-3 PUFA.

Figure 2. Elongation and desaturation pathways for n-3 and n-6 fatty acid families.

Elongation and desaturation of fatty acids is subject to feedback

regulation because both AA and DHA suppress the endogenous conversion

of LA and ALA into longer chain fatty acids, respectively (Barceló-Coblijn

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et al., 2009; Valenzuela et al., 2011). Whereas increasing the level of

dietary ALA provides more substrate for conversion to EPA, high levels of

dietary ALA also have the capacity to inhibit one of the last steps, the

desaturation of 24:5 n-3 (Tu et al., 2010). It should also be considered that

the modulation of fatty acids from these reactions appears to be tissue-

selective, since dietary n-3 fatty acids are more efficiently elongated and

desaturated in the liver, while the brain does not respond to dietary levels

and the heart does not have the ability to elongate and desaturate ALA in

longer chain n-3 fatty acids. (Igarashi et al., 2007; Barceló-Coblijn et al.,

2009)

Several studies carried out in humans have shown that in the

metabolism of ALA there is no dose-dependent relationship for the

biosynthesis of EPA and DHA from this precursor. (Pawlosky et al., 2001;

Schwab et al., 2006; Whelan et al., 2012). But although the conversion of

ALA to DHA occurs in a very low proportion, it is still important, and

much less negligible, given that an even increased accumulation of DHA,

specifically in the brain, is achieved (Morales et al., 2012).

4. HEALTH EFFECTS OF ALA

A number of scientific studies have shown the diverse clinical

applications of n-3, mainly EPA and DHA, highlighting their benefits in

cardiovascular health, dyslipidemias, cancer, diabetes mellitus, rheumatoid

arthritis, psychiatric and neurodegenerative diseases or inflammatory

bowel disease among others. The results of these trials led international

organizations to increase recommendations for the use of EPA and DHA

both for the prevention and treatment of these diseases (Aires et al., 2005;

Morales et al., 2012; Valenzuela et al., 2013; Zarrouk et al., 2017). In

contrast, much less is known about the effects of ALA directly, or after

bioconversion to EPA and DHA. Still, some trials have been carried out

and are summarized below.

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4.1. Preterm and Newborns

ARA and DHA are the most abundant PUFA in the central nervous

system, being particularly concentrated in the synaptic plasma membranes

and photoreceptor cells. For this reason, it is essential that the correct

acquisition of n-3 and n-6 fatty acids occur during embryogenesis and the

early postnatal stages of development. The rapid accumulation of DHA is

directly related to its crucial need for normal neurological and visual

development, in such a way that the fatty acid composition of infant milk is

the main object of study. The composition of breast milk varies according

to diet, but on average it contains DHA (0.3-0.6%), AA (0.4-0.7%), LNA

(8-17%) and ALA (0.5-1%). It should be taken into account that the

Adequate Intake in the FAO/WHO recommendations from 2008 was

between 0.2 and 0.4% of fatty acids (FAO, 2008). Regarding the ratio

between n-6 and n-3 fatty acids, or LNA/ALA, the FAO report concluded

that there was no compelling scientific rationale for recommending a

specific ratio. However, in the global CODEX standards for infant

formula, it is recommended that the LA/ALA ratio be between 5 and 15

(Koletzko et al., 2005). Concerning infant feeding, the evidence provided

by human studies indicates that ALA-enriched milk formula have a modest

impact on DHA levels. Thus, infants taking these formulas have lower

levels of DHA than those breastfed. Therefore, the addition of AA and

DHA to infant formulas has been recommended (Clandinin et al., 1981;

Koletzko et al., 2005).

4.2. Cardiovascular Disease

Some of the potential mechanisms for the cardioprotective effect of

n-3 fatty acids include antiarrhythmic, antiinflammatory, hypotensive, and

hypotriglyceridemic effects. However, it is still unclear if all n-3 fatty acids

could have beneficial effects on CVD or if the benefit is exclusively related

to EPA and DHA. Therefore, there has been great interest in investigating

whether sources enriched with ALA would have similar effects to sources

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enriched with DHA in CVD but the results of these studies are not as

consistent as studies with fish oil diets (Geleijnse et al., 2010).

Studies in humans show that within three hours after its consumption,

ALA is rapidly incorporated into lipoproteins and, consequently, the

plasma concentrations of ALA, EPA and DPA are increased. In a

randomized, double-blind trial, 56 participants received 3g ALA/day in the

form of flaxseed oil capsules or olive oil placebo capsules. After 12 weeks

of treatment, plasma levels of EPA and DPA increased 60% and 25%

respectively, but no changes were observed in the concentrations of

triglycerides, HDL and LDL nor in the particle size of LDL, HDL or IDL

(Layne et al., 1996).

Some authors suggest that the reason for these limited effects may

reflect the limited ability of humans to elongate and desaturate ALA.

However, a recent study individually evaluated the different metabolic

effects of isolated dietary ALA, EPA and DHA in non-obese

normolipidemic volunteers. In this study, volunteers received margarines

for 6 weeks that contained 4.4g/day of ALA, 2.2g/day of EPA or 2.3g/day

of DHA. The results showed not only an increase in the content of ALA

and EPA in LDL, but also a reduction in fasting serum triglycerides in the

ALA group. Importantly, as noted by the authors, this beneficial effect was

observed after the consumption of a relatively low dose of ALA, which

could be perfectly achievable without dietary supplements, through regular

consumption of ALA-rich foods (Egert et al., 2009). In addition, there are

several clinical trials and systematic reviews that attribute beneficial

effects to ALA diets because they reduce the risk of myocardial infarction

and fatal ischemic heart disease in women and men (Djoussé et al., 2001;

Hu et al., 2002).

n-3 PUFA also have antiarrhythmic effects, which probably involve

the modification of ion channel currents by the incorporation of these fatty

acids into the phospholipid membrane of cardiomyocytes. ALA, EPA and

DHA, can block the specific Kv1.5 channels of the atrium at physiological

concentrations, suggesting that ALA could share the antiarrhythmic

properties of marine n-3 PUFA. (Barceló-Coblijn et al., 2009).

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4.3. Inflammatory Diseases

Inflammation is a key feature in a series of clinical conditions, such as

cardiovascular diseases, neurodegenerative diseases, cancer, chronic

intestinal inflammation, rheumatoid arthritis and asthma among many

other pathologies. Inflammation is the cellular physiological response to

exposure to certain substances released, predominantly, by activated

leukocytes. This response usually consists of the reddening and swelling of

the target area and is mediated by at least two different groups of

biomolecules, eicosanoids and cytokines. As we saw in the previous

section, the increase in EPA and DHA levels, reduce the ARA content in

cell membranes and decrease the generation of proinflammatory

eicosanoids derived from n-6 PUFA (Valenzuela et al., 2011). One of the

most common pharmacological approaches to treat inflammation is to

inhibit the biosynthesis of these n-6 eicosanoids, which could be achieved

by providing COX1/2 inhibitors or by increasing the content of n-3 fatty

acids, particularly EPA and DHA through diet.

Diets enriched with n-3 PUFA can also reduce the production of

proinflammatory cytokines, such as interleukin-1, interleukin-6,

interleukin-8 and tumor necrosis factor-α (TNF-α), that are released when

macrophages and monocytes are activated. In such way, both ALA and

DHA can suppress the expression of proinflammatory cytokines by means

of a reduction in gene expression induced by the nuclear factor κB (NF-

κB) and the peroxisomal proliferation factors (PPARs) (Siebenlist et al.,

1994; Zhao et al., 2005). Furthermore, this effect would be related to the

cardioprotective effects of ALA, which would be, at least, partially

mediated by a reduction in the production of inflammatory cytokines (Zhao

et al., 2007).

4.4. Neuroprotective Effect

The protective effects of n-3 PUFA against neurodegenerative

disorders, such as Alzheimer’s disease are very limited, but have gained

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attention due to the fact that DHA is a key component of membrane

phospholipids in the brain. Moreover, observational studies reported lower

incidences of Alzheimer’s disease in populations who consume a high

amount of fish (Gregg et al., 2002; Morris et al., 2003). A prospective

study conducted in participants aged 65–94 y found that ALA intake was

strongly protective in persons with a high risk of Alzheimer’s disease

(Morris et al., 2003).

However, for the moment, most of the available data on the effect of

ALA on neurodegenerative disorders is restricted to experimental animals.

Yamamoto et al. (1987) reported increased learning ability with

supplementation of ALA-rich oil in rats, but most of the effects have been

observed after supplementation of the fatty acid individually and not in the

context of a diet. Administration of ALA to brain and spinal chord

ischemic rats showed significant neuroprotection by reducing neuronal cell

loss, inhibiting of microglia activation and improving functional outcome

(King et al., 2006; Liu et al., 2014).

4.5. Cancer

In studies carried out with cell cultures and experimental animals, it

has been found that diets containing EPA and DHA delay both the growth,

the metastasis of primary tumors and the human carcinoma implants in

mammary cells. In addition, they induce apoptosis and cell differentiation,

as well as the reduction of cell proliferation (Wu et al., 2005). In rats with

colon cancer, n-3 PUFA have been shown to block drug-induced tumor

formation and directly affect the expression of genes related to

tumorigenesis and apoptosis, reducing cellular and DNA damage (Yam et

al., 2001).

Doxorubicin, a conventional chemotherapy agent, has limited clinical

use due to its systemic toxicity to normal healthy tissue. However, a new

conjugate of doxorubicin with ALA showed a good antitumor activity with

lower toxicity than free doxorubicin. In addition, the conjugate exhibited a

more active tumor targeting profile due to the introduction of ALA which

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could be an effective tumor directed remnant for the modification of

chemotherapeutics (Huan et al., 2012).

However, there is also negative evidence regarding ALA. Christensen

et al., (2006) provided support for a deleterious role of ALA in the

development of prostate cancer. In 20 men with prostate cancer, these

authors did not find any beneficial effects of EPA and DHA intake, but

more remarkably, they reported a correlation between the prostate-specific

antigen level and ALA concentrations in prostate tissue. Nevertheless, a

meta-analysis failed to confirm an association between dietary ALA intake

and prostate cancer risk (Carleton et al., 2013). In contrast, there seems to

be more evidence on the influence of ALA on breast cancer (Mason and

Thompson, 2014). In mice, dietary flaxseed oil was shown to reduce

human estrogen receptor-positive breast tumors (MCF-7) growth by 33%

compared to control (Truan et al., 2010). In humans, Thompson et al.,

(2005) demonstrated that a daily intake of 25g flaxseed oil can reduce cell

proliferation and increase cell apoptosis in tumors of postmenopausal

patients with breast cancer.

The mechanisms of the putative protective effect of ALA, but also

EPA and DHA, against cancer can be related to inhibition of tumor

development by eliciting changes in the cell membrane fatty acid

composition, suppression of ARA-derived eicosanoid biosynthesis,

inhibition of cell proliferation and induction of apoptosis (Liu and Ma,

2014).

5. OTHER ALTERNATIVE SOURCES OF N-3 PUFA

The recommended daily intakes of n-3 PUFA are often viewed as

unsustainable and unable to meet future consumer demands (Tocher,

2009). The global demand of wild fish, the most common and effective

source of EPA and DHA, is much larger than the oceans can sustain

(Arthur, 2009). The concern about this demand has moved efforts to

develop alternative sources of n-3 PUFA, including aquaculture, other

marine non-fish products, microalgae and transgenic plants.

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Aquaculture is an increasing food industry, with an annual average of

8.3% increase (Klinger and Naylor, 2012). However, in order to reach high

n-3 PUFA levels in their flesh, seafood and fish grown in aquaculture

require formulated feeds composed of wild caught fish or EPA and DHA

supplementation when being farmed (Adarme-Vega et al., 2014). ALA-

containing plants, like soybean, canola and flaxseed, have also been

suggested as additives for fish food. However, although fish fed plants

present mostly positive effects on growth performance, their meat results

in lower accumulation of n-3 PUFA, so consumers do not gain the same

health benefits. Therefore, aquaculture alone is not sufficient to solve the

problem of n-3 PUFA demand.

Since ALA-rich plants, which as we have reviewed above, are an

unrealistic alternative to meet EPA and DHA demands, krill oil,

microalgae and genetically modified plants have also been suggested as

sources of n-3 PUFA.

5.1. Krill

Krill are small crustaceans particularly abundant in the Arctic and

Antarctic oceans. The oil is extracted from Euphausia superba, the largest

krill species that lives in the Antartic. However, due to their role in marine

ecosystems, Antartic krill harvest is limited to assure for long-term

sustainability (Constable, 2011). Therefore, considerable caution is needed

when increasing the krill catches as it compromises the marine food web.

Krill lipid content is variable (12-50% of dry weight) as it depends on

the season, species and age. However, it is particularly rich in EPA and

DHA, which is attributed to their diet based on microalgae. The overall

fatty acid composition in krill oil is similar to fish oil but the EPA content

is higher, increasing the EPA:DHA ratio from 1:1 in fish oil to 2:1 in krill

oil (Ulven et al., 2011). This might have an important impact on eicosanoid

synthesis and their biological response as stated above.

In contrast to fish, in which EPA and DHA are found in triglycerides,

in krill these fatty acids are mainly found as part of phospholipids (mostly

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in the form of phophatidylcholine) (Ulven et al., 2011). This is of

particular interest, since in has been demonstrated that there is about two-

fold higher DHA accumulation in the brain when this fatty acid is provided

as phospholipids rather than triglycerides (Liu et al., 2014).

Phospholipids have an amphiphilic nature and it has been suggested

that their emulsifying features might contribute to a better absorption in the

intestine (Schuchardt and Hahn, 2013). However, this statement is

controversial and has been questioned by some authors. Köhler et al.,

(2015) carried out a randomized, single-blind, cross-over intervention trial

to compare the bioavailability of EPA and DHA administrated from

Antarctic krill oil, Antarctic krill meal and fish oil. These authors found a

higher bioavailability of EPA and DHA from krill oil but no differences

between krill meal and fish oil, which argues against the interpretation that

phospholipids are better absorbed than triglycerides. Yurko-Mauro et al.,

(2015) performed a double blind, randomized, parallel study in which 66

healthy subjects received a 1.3 g/day dose of EPA + DHA in the form of

fish oil-ethyl esters, fish oil-triglycerides or krill oil for four weeks. They

were unable to find differences in plasma and erythrocyte fatty acid

composition, demonstrating that all forms of EPA + DHA had similar oral

bioavailability.

However, studies on the bioavailability of EPA and DHA from krill oil

are conflicting due to differences in design, including the amounts of EPA

and DHA provided by krill or fish oil. Studies that used the same amount

of EPA and DHA showed that the bioavailability of EPA and DHA from

krill oil seems to be higher compared to fish oil (Ramprasath et al., 2013;

Schuchardt et al., 2011). On the contrary, others found no difference

(Laidlaw et al., 2014). Despite using the same amounts of EPA and DHA,

these studies are difficult to compare because of divergences in duration

but also because fatty acids were analyzed in different plasma matrices:

whole plasma, plasma phospholipids and erythrocytes. Nevertheless,

studies in humans that assessed the biological effect of krill oil and fish oil

did not find significant differences (Ulven et al., 2015). In contrast, studies

in animals show that fish oil intake, unlike krill oil, upregulates the

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cholesterol synthesis pathway. In addition, krill oil seems to regulate also

other glucose and lipid metabolic pathways.

Fish oil and krill oil have also been compared in regard to cognitive

function in senior citizens (61-72 y) (Konagai et al., 2013). Subjects were

asked to take four capsules of each oil and a placebo (medium-chain

triglycerides) twice a day for 12 weeks. Again, no differences were found

between fish and krill oils. Both oils increased oxyhemoglobin

concentrations in the brain, which is associated with enhanced cerebral

function related to circulation. In consequence, the authors concluded that

long-term ingestion of krill or fish oil promotes working memory function

by activating the dorsolateral prefrontal cortex in elderly people,

preventing deterioration in cognitive activity. However, only krill oil had

improving effects in calculation tasks performed by the participants, which

was associated to the presence of EPA and DHA in phospholipids.

Another randomized crossover trial used a combination of krill oil

(88%) and salmon oil (12%), containing contained 46 mg EPA and 31 mg

DHA (Albert et al., 2015). Participants were instructed to take 400 mg n–3

PUFA as capsules per day for eight weeks. Remarkably, the authors found

a decrease in insulin sensitivity compared to the control (canola oil),

increased LDL-cholesterol and apolipoprotein B concentrations and carotid

artery intima-media thickness. This suggested a more atherogenic lipid

profile and higher risk of type-2 diabetes due to krill oil consumption. The

authors were reluctant to attribute the effects to EPA and DHA or to

astaxanthin, an antioxidant carotenoid, contained in the manufactured

capsules, but were unable to provide another explanation.

Krill oil has also been shown to reduce plasma triglycerides large very-

low density lipoprotein (VLDL) and chylomicron particles in healthy

individuals after consumption for 28 days, which was associated to to

increased plasma EPA, DHA and docosapentaenoic acid (DPA)

concentrations and reduced ARA levels (Berge et al., 2014). Plasma EPA

and DHA concentrations were also shown to be increased in overweight

and obese men and women receiving capsules containing 2 g/day of krill

oil for 4 weeks (Maki et al., 2009). In addition, patients treated for three

months with 1 g/day of krill oil showed reduced total cholesterol, LDL,

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and triglycerides, and increased HDL levels, with no difference with fish

oil (Bunea et al., 2004). These studies demonstrated that krill oil can be at

least as effective as fish oil for the management of hyperlipidemia.

5.2. Algae

Algae have been part of the human diet for thousands of years, but

more contemporaneously, in addition to macroalgae, some microalgae are

cultivated for foods and food additives (Chacón-Lee and González-Mariño

2010; FAO, 2016). Today, algae are regarded as important sources of n-3

PUFA, particularly for vegetarians, who may have low intakes of these

fatty acids. Microalgae are the primary sources of DHA and EPA for

zooplankton and fish. Thus, microalgae represent the trophic integration of

DHA-rich flagellates and EPA-rich diatoms in the food web (Viso and

Marty, 1993). Although algae have been proposed as alternatives sources

to fish oil for n-3 PUFA intake because they are easy to cultivate on a large

scale due to their small size, ocean acidification, as a result of increased

atmospheric CO2, can negatively affect the supply of these fatty acids to

higher trophic levels (Rossoll et al., 2012).

Among the ca. 40,000 algal species that have been identified, only a

few hundred have been characterized for their lipid composition (Adarme-

Vega et al., 2012). Despite algae exhibit a great variability regarding their

lipid content, some microalgae can accumulate up to 60% of their dry

weight as triglycerides (Georgianna and Mayfield, 2012). EPA is the

predominant PUFA in many of them, along with DHA and ARA (Norziah

and Ching, 2000). Some strains have demonstrated high accumulation of

EPA and/or DHA. For instance, species of Phaeodactylum and

Nannochloropsis can reach up to 39% of EPA (Yongmanitchai and Ward,

1991; Sukenik, 1991), whereas Thraustochytrium sp. and Schizochytrium

sp. (Burja et al., 2006; Zhu et al., 2007) contain DHA in amounts ranging

30–40% of total fatty acids when grown heterotrophically. The

bioaccessibility for these fatty acids ranges from 50 to 100% (Schuchardt

et al., 2011).

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EPA and DHA content can be modified by changing growing

conditions, such as temperature. For instance, phytoplankton contain more

PUFA when grown at low temperature (Yue and Feng, 2000). In addition,

low nitrogen conditions with high supply of monosodium glutamate can

improve growth and fatty acid synthesis (Lenihan-Geels et al., 2013).

Under stressful low nutrient conditions (but not light), microalgae tend to

accumulate and store photosynthetic products, such as lipids and

carbohydrates (Anderson et al., 2008). Apart for external stresses,

metabolic engineering has been proposed to increase the lipid production

of microalgae, by regulating the expression of desaturases and elongases

that are needed for n-3 PUFA biosynthesis (Adarme-Vega et al., 2012).

Additionally, other options include the modulation of the enzymes

involved in degradation pathways, like β-oxidation.

Figure 3. Microalgae, krill and transgenic plants as n-3 PUFA sources in human

trophic chain.

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As indicated above, algal oil can be particularly interesting for

vegetarians because these individuals are at risk of a lower status of n-3

PUFA, due to the exclusion of fish from their diet (Lee et al., 2000). In

addition, they usually have a high intake of n-6 PUFA from vegetable oils,

mainly LA, which compete with the conversion of ALA to EPA and DHA.

In a randomized controlled trial, postmenopausal vegan and lacto-

vegetarian women received 2.14 g of DHA/day for 6 weeks and no EPA

from algal oil. The study showed that microalgal oil increased the content

of DHA, but also EPA in LDL, in the form of cholesterol esters. Compared

to the control, plasma total cholesterol concentrations were slightly

reduced but no significant changes were observed in LDL and HDL.

Likewise, plasma triglyceride levels were reduced but not significantly.

The authors suggested that this poor effect was related to the low daily

dose of n-3 fatty acids and original favorable lipid profiles in vegetarians.

However, algal DHA can have cardiovascular protective effects by

exerting changes in lipoprotein concentrations when administered at small

doses (Neff et al., 2011). A double-blind, randomized, parallel trial

included algal oil from Schizochytrium sp., fish oil or a corn/soy oil as

control (Maki et al., 2014). The oils were administered in the form of

capsules, providing 443 mg DHA and 164 mg EPA per capsule in the case

of algal oil, and 205 mg DHA and 289 mg EPA for fish oil. Healthy adult

men and women were treated with four capsules per day for 14 weeks.

Ingestion of microalgal oil significantly lowered triglyceride levels

compared with the control, but it was not significantly different from that

produced by fish oil. This lowering effect of microalgal and fish oils is

concomitant to reduced concentrations of VLDL triglycerides as well as

VLDL particle size (Neff et al., 2011). Interestingly, the trial by Maki et al.

(2014) also found that both microalgal and fish oils significantly increased

LDL compared with control. However, this effect was associated with a

shift of lipoprotein particle size toward larger, potentially less atherogenic

subfractions. Nevertheless, the health benefits of DHA-rich algal

supplements are controversial when compared to fish, probably due to

heterogeneity in design of the studies in terms of amounts administered,

duration and sample size, just as we showed above for krill oil.

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5.3. Transgenic Plants

Since terrestrial plants do not produce very long-chain n-3 PUFA

because they lack the necessary genes required to elongate and desaturate

ALA, the only option to obtain EPA and DHA from plants is genetic

modification. Transgenic plants have been proposed as novel terrestrial

sources of n-3 PUFA. It has been argued that these plants represent a less

expensive and more sustainable alternative to microalgae culture and fish

farming, and can avoid well-known concerning issues associated with

ocean fishing, such as contamination with heavy metals, dioxins and

polychlorinated biphenyls (Tocher, 2015). Oils derived from these

transgenic plants could be directed to human consumption, but also as

aquafeed ingredient, as a replacement for fish oils.

The first attempt to generate a plant rich in EPA and DHA was made

in Arabidopsis thaliana, via insertion of microbial desaturases and

elongases enzymes, and achieving the formation of 3% EPA in the leaf

tissues (Barclay et al., 1994). More recently, Petrie et al. (2012) described

the accumulation of DHA up to 15%, also in genetically modified

Arabidopsis thaliana, but the EPA content was even lower (1.8%). Today,

new sources of n-3 PUFA have been developed from Camelina sativa, a

commercially harvested plant that can synthesize EPA and/or DHA when it

is genetically modified (Ruiz-Lopez et al., 2014). Transgenic Camelina is

capable of producing n-3 PUFA in their seeds after the insertion of

cassettes containing a number of fatty acyl desaturase and elongase genes

from algae. Following this procedure, seeds can contain up to 31% EPA or

12% EPA and 14% DHA.

These oils have been evaluated as replacements for fish oil in feeds for

salmon (Salmo salar) (Betancor et al., 2015) and gilthead sea bream

(Sparus aurata) (Betancor et al., 2016). In these trials growth performance

and n-3 PUFA deposition in flesh was comparable to fish fed diets

containing wild-type camelina oil and no adverse effects were observed on

plasma biochemistry or intestinal histology. Although levels of n-3 PUFA

did not reach the concentrations in flesh that were achieved when fish

received diets containing fish oil as lipid source, camelina-derived oils

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doubled the n-3 PUFA content in flesh, in comparison with commercial

feeds (Betancor et al., 2017). This effect was attributed to up-regulation of

hepatic fads2d5 and fads2d6 genes, corresponding to delta-5 and delta-6

fatty acyl desaturases, respectively.

When EPA-rich or EPA+DHA-rich camelina oils were compared,

Betancor et al. (2016) observed reduced performance in fish growth after

the administration of the former that was associated to an imbalance

between EPA and DHA content. In addition, these authors found increased

ARA content in the meals, which is associated to pro-inflammatory effects,

as indicated above. Nevertheless, they observed no significant differences

in flesh fatty acid composition, and no alterations in fish health as shown

by histological and genetic expression analyses.

Fish fed the transgenic oil presented increased lipid deposition in the

liver, which had already been observed in fish fed plant oils, compared to

those fed marine fish oil (Fountoulaki et al., 2009). An explanation for this

observation is that n-3 PUFA have been shown to suppress triglyceride

accumulation in mammalian and fish adipocytes (Kim et al., 2006;

Todorcević et al., 2008). An alternative explanation is related to enhanced

expression in srbep-1, which in turn regulates the expression of hepatic and

lipoprotein lipases. These enzymes are in charge of triglyceride hydrolysis

from lipoproteins and, thus, are involved in the hepatic uptake of fatty

acids.

For the moment, there are no trials in humans consuming dietary fish

farmed using genetically modified plant oils, due to the strict regulations of

transgenic products and low consumer acceptance in the European Union.

Transgenic plants have an enormous potential as source of n-3 PUFA, but,

in the present circumstances, they can not be considered in the short term.

CONCLUSION

n-3-PUFA are recognized as highly beneficial for human health

through their effects on the most prevalent non-communicable chronic

diseases: cardiovascular disease, diabetes, cancer and neurodegenerative

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disorders. International health organizations recommend increasing the

intake of fish and fish oils, the most common and richest sources of EPA

and DHA, which has led to a growing interest in the general population.

Therefore, the market demand for n-3 PUFA has increased in the last years

and it is expected that it will further increase in the future. This not only

implies direct intake by humans in the form of fish or fish oil, but also the

production of nutraceuticals and animal feed. Consequently, it has become

urgent to find new sustainable sources of n-3 PUFA to meet that demand.

This is particularly imperative in certain groups of populations, like

vegetarians, who do not eat n-3 PUFA from animal sources. In addition,

marine fish stocks have declined in the last decades and overfished stocks

have increased. Moreover, the presence of chemical contaminants (e.g.,

mercury) in fish oil are of great concern for most consumers.

Aquaculture was proposed as a solution for the problem but it implies

that farmed fish need to be fed with wild caught fish. Therefore,

aquaculture alone is not sufficient to solve the problem of n-3 PUFA

demand. Plant oils, like flaxseed, chia or sacha inchi oils, but also some

nuts, are rich sources of ALA and have proven to be highly bioavailable as

alternative sources to fish. However, bioconversion of ALA to EPA and

DHA is rather poor, leading scientists to search for other sources of n-3

PUFA, in the form of algae, krill or transgenic plants. Cultivated

microalgae are grown in cost-effective processes and it is likely to be an

expanding industry in the future. However, the industrialized processes

need to be enhanced if these source of n-3 PUFA is to be dedicated to

replace a significant part of fish intake. Krill oil is another proposed source

of n-3 PUFA but it is unlikely that it can be sufficiently sustainable.

Finally, transgenic plants represent a potentially more sustainable source

which also avoid issues associated with marine sources, such as

contamination with heavy metals, dioxins and PCBs. In this case, concerns

are related to social pressure, since genetically modified organisms are not

well accepted by consumers and policy makers. It is likely that it will be

not one, but a combination of the above sources which provide a future

sustainable production of n-3 PUFA.

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REFERENCES

Adarme-Vega, T. C., Thomas-Hall, S. R. and Schenk, P. M. (2014).

Towards sustainable sources for omega-3 fatty acids production.

Current Opinion in Biotechnology, 26: 14–18. https://doi.org/10.1016/

j.copbio.2013.08.003.

Adarme-Vega, T., Lim, D. K. Y., Timmins, M., Vernen, F., Li, Y. and

Schenk, P. M. (2012). Microalgal biofactories: a promising approach

towards sustainable omega-3 fatty acid production. Microbial Cell

Factories, 11(1): 96. https://doi.org/10.1186/1475-2859-11-96.

Aires, D., Capdevila, N. and Segundo, M. J. (2005). Ácidos Grasos

Esenciales. [Essential fatty acids.] www.Nutri-Facts.Org, 24: 96–102.

https://doi.org/10.1590/S1415-790X2003000400003.

Albert, B. B., Derraik, J. G., Brennan, C. M., Biggs, J. B., Garg, M. L.,

Cameron-Smith, D. et al., (2015). Supplementation with a blend of

krill and salmon oil is associated with increased metabolic risk in

overweight men. American Journal of Clinical Nutrition, 102(1): 49–

57. https://doi.org/10.3945/ajcn.114.103028.

Anderson, D. M., Burkholder, J. M., Cochlan, W. P., Glibert, P. M.,

Gobler, C. J., Heil, C. A. et al., (2008). Harmful algal blooms and

eutrophication: Examining linkages from selected coastal regions of

the United States. Harmful Algae, 8(1): 39–53. https://doi.org/

10.1016/j.hal.2008.08.017.

Arthur, R. (2009). Omega-3 sources. Journal of Complementary Medicine,

8: 28.

Azrad, M., Turgeon, C., Demark-Wahnefried, W. (2013). Current evidence

linking polyunsaturated fatty acids with cancer risk and progression.

Front Oncol, 3:224.

Barber, M. D., Ross, J. A., Voss, A. C., Tisdale, M. J., Fearon, K. C.

(1999). The effect of an oral nutritional supplement enriched with fish

oil on weight loss in patients with pancreatic cancer. Br J Cancer.

81:80–6.

Barceló-Coblijn, G., Kitajka, K., Puskás, L. G., Hőgyes, E., Zvara, A.,

Hackler, L. and Farkas, T. (2003). Gene expression and molecular

Complimentary Contributor Copy

J. S. Perona, S. Garcia-Rodriguez and J. M. Castellano

218

composition of phospholipids in rat brain in relation to dietary n−6 to

n−3 fatty acid ratio. Biochimica et Biophysica Acta (BBA) - Molecular

and Cell Biology of Lipids, 1632(1–3): 72–79. https://doi.org/10.1016/

S1388-1981(03)00064-7.

Barceló-Coblijn, G. and Murphy, E. J. (2009). Alpha-linolenic acid and its

conversion to longer chain n−3 fatty acids: Benefits for human health

and a role in maintaining tissue n−3 fatty acid levels. Progress in Lipid

Research, 48(6): 355–374. https://doi.org/10.1016/J.PLIPRES.2009.

07.002.

Barclay, W. R., Meager, K. M. and Abril, J. R. (1994). Heterotrophic

production of long chain omega-3 fatty acids utilizing algae and algae-

like microorganisms. Journal of Applied Phycology, 6(2): 123–129.

https://doi.org/10.1007/BF02186066.

Berge, K., Musa-Veloso, K., Harwood, M., Hoem, N. and Burri, L. (2014).

Krill oil supplementation lowers serum triglycerides without increasing

low-density lipoprotein cholesterol in adults with borderline high or

high triglyceride levels. Nutrition Research, 34(2): 126–133.

https://doi.org/10.1016/j.nutres.2013.12.003.

Berquin, I. M., Edwards, I.J., Chen, Y. Q. (2008). Multi-targeted therapy

of cancer by omega-3 fatty acids. Cancer Lett, 269:363–77.

Betancor, M. B., Li, K., Sprague, M., Bardal, T., Sayanova, O., Usher, S.

et al., (2017). An oil containing EPA and DHA from transgenic

Camelina sativa to replace marine fish oil in feeds for Atlantic salmon

(Salmo salar L.): Effects on intestinal transcriptome, histology, tissue

fatty acid profiles and plasma biochemistry. PLOS ONE, 12(4):

e0175415. https://doi.org/10.1371/journal.pone.0175415.

Betancor, M. B., Sprague, M., Montero, D., Usher, S., Sayanova, O.,

Campbell, P. J. et al., (2016). Replacement of Marine Fish Oil with de

novo Omega-3 Oils from Transgenic Camelina sativa in Feeds for

Gilthead Sea Bream (Sparus aurata L.). Lipids, 51(10): 1171–1191.

https://doi.org/10.1007/s11745-016-4191-4.

Betancor, M. B., Sprague, M., Usher, S., Sayanova, O., Campbell, P. J.,

Napier, J. A. and Tocher, D. R. (2015). A nutritionally-enhanced oil

from transgenic Camelina sativa effectively replaces fish oil as a

Complimentary Contributor Copy

Plants as Alternative Sources of n-3 Polyunsaturated Fatty Acids

219

source of eicosapentaenoic acid for fish. Scientific Reports, 5(1): 8104.

https://doi.org/10.1038/srep08104.

Bougnoux, P., Hajjaji, N., Ferrasson, M. N., Giraudeau, B., Couet, C., et

al., (2009). Improving outcome of chemotherapy of metastatic breast

cancer by docosahexaenoic acid: a phase II trial. Br J Cancer,

101:1978–85.

Bunea, R., El Farrah, K. and Deutsch, L. (2004). Evaluation of the effects

of Neptune Krill Oil on the clinical course of hyperlipidemia.

Alternative Medicine Review : A Journal of Clinical Therapeutic, 9(4):

420–428.

Burja, A. M., Radianingtyas, H., Windust, A. and Barrow, C. J. (2006).

Isolation and characterization of polyunsaturated fatty acid producing

Thraustochytrium species: screening of strains and optimization of

omega-3 production. Applied Microbiology and Biotechnology, 72(6):

1161–1169. https://doi.org/10.1007/s00253-006-0419-1.

Carleton, A. J., Sievenpiper, J. L., de Souza, R., McKeown-Eyssen, G. and

Jenkins, D. J. A. (2013). Case–control and prospective studies of

dietary α-linolenic acid intake and prostate cancer risk: a meta-

analysis. BMJ Open, 3(5): e002280. https://doi.org/10.1136/bmjopen-

2012-002280.

Chacón-Lee, T. L. and González-Mariño, G. E. (2010). Microalgae for

“Healthy” Foods-Possibilities and Challenges. Comprehensive Reviews

in Food Science and Food Safety, 9(6): 655–675. https://doi.org/

10.1111/j.1541-4337.2010.00132.x.

Christensen, J. H., Fabrin, K., Borup, K., Barber, N. and Poulsen, J.

(2006). Prostate tissue and leukocyte levels of n-3 polyunsaturated

fatty acids in men with benign prostate hyperplasia or prostate cancer.

BJU International, 97(2): 270–273. https://doi.org/10.1111/j.1464-

410X.2006.05951.x.

Clandinin, M. T., Chappell, J. E. and Heim, T. (1981). Do low weight

infants require nutrition with chain elongation-desaturation products of

essential fatty acids? Progress in Lipid Research, 20: 901–904.

Complimentary Contributor Copy

J. S. Perona, S. Garcia-Rodriguez and J. M. Castellano

220

Colomer, R., Moreno-Nogueira, J. M., Garcia-Luna, P. P., Garcia-Peris, P.,

Garcia-de-Lorenzo, A., et al., (2007). N-3 fatty acids, cancer and

cachexia: a systematic review of the literature. Br J Nutr, 97:823–31.

Connor, K. M., SanGiovanni, J. P., Lofqvist, C., Aderman, C. M., Chen, J.,

et al., (2007). Increased dietary intake of omega-3-polyunsaturated

fatty acids reduces pathological retinal angiogenesis. Nat Med.13:868–

73.

Constable, A. J. (2011). Lessons from CCAMLR on the implementation of

the ecosystem approach to managing fisheries. Fish and Fisheries, 12:

138–151.

Djoussé, L., Pankow, J. S., Eckfeldt, J. H., Folsom, A. R., Hopkins, P. N.,

Province, M. A. et al., (2001). Relation between dietary linolenic acid

and coronary artery disease in the National Heart, Lung, and Blood

Institute Family Heart Study. The American Journal of Clinical

Nutrition, 74(5): 612–619.

Dyerberg, J., Bang, H. O., Hjorne, N. (1975). Fatty acid composition of the

plasma lipids in Greenland Eskimos. Am J Clin Nutr, 28: 958–66.

Edwards, I. J., O’Flaherty, J. T. (2008). Omega-3 fatty acids and

PPARgamma in cancer. PPAR Res., 2008:358052.

Egert, S., Kannenberg, F., Somoza, V., Erbersdobler, H. F. and Wahrburg,

U. (2009). Dietary α-Linolenic Acid, EPA, and DHA Have Differential

Effects on LDL Fatty Acid Composition but Similar Effects on Serum

Lipid Profiles in Normolipidemic Humans. The Journal of Nutrition,

139(5): 861–868. https://doi.org/10.3945/jn.108.103861.

FAO. (n.d.). The State of World Fisheries and Aquaculture 2016.

FAO. (n.d.). Interim Summary of Conclusions and Dietary

Recommendations on Total Fat; Fatty Acids From the Joint

FAO/WHO Expert Consultation on Fats and Fatty Acids in Human

Nutrition, 10-14 November, 2008, WHO, Geneva Introduction and

Definitions.

Fearon, K. C., Barber, M. D., Moses, A. G., Ahmedzai, S. H., Taylor, G.

S., et al., (2006). Double-blind, placebo-controlled, randomized study

of eicosapentaenoic acid diester in patients with cancer cachexia. J

Clin Oncol, 24:3401–7.

Complimentary Contributor Copy

Plants as Alternative Sources of n-3 Polyunsaturated Fatty Acids

221

Fearon, K. C., VonMeyenfeldt, M. F., Moses, A. G., Van Geenen, R., Roy,

A., et al., (2003). Effect of a protein and energy dense N-3 fatty acid

enriched oral supplement on loss of weight and lean tissue in cancer

cachexia: a randomised double blind trial. Gut., 52: 1479–86.

Fountoulaki, E., Vasilaki, A., Hurtado, R., Grigorakis, K., Karacostas, I.,

Nengas, I. et al., (2009). Fish oil substitution by vegetable oils in

commercial diets for gilthead sea bream (Sparus aurata L.); effects on

growth performance, flesh quality and fillet fatty acid profile:

Recovery of fatty acid profiles by a fish oil finishing diet under

fluctuating water temperatures. Aquaculture, 289(3–4): 317–326.

https://doi.org/10.1016/J.AQUACULTURE.2009.01.023.

Geleijnse, J. M., de Goede, J. and Brouwer, I. A. (2010). Alpha-Linolenic

Acid: Is It Essential to Cardiovascular Health? Current Atherosclerosis

Reports, 12(6): 359–367. https://doi.org/10.1007/s11883-010-0137-0.

Georgianna, D. R. and Mayfield, S. P. (2012). Exploiting diversity and

synthetic biology for the production of algal biofuels. Nature,

488(7411): 329–335. https://doi.org/10.1038/nature11479.

Gerber, M. (2012). Omega-3 fatty acids and cancers: a systematic update

review of epidemiological studies. Br J Nutr, 107:S228–39.

Gleissman, H., Johnsen, J. I., Kogner, P. (2010). Omega-3 fatty acids in

cancer, the protectors of good and the killers of evil? Exp Cell Res,

316:1365–73.

Greene, E. R., Huang, S., Serhan, C. N., Panigrahy, D. (2011). Regulation

of inflammation in cancer by eicosanoids. Prostaglandins Other Lipid

Mediat, 96:27–36.

Gregg, E. W., Engelgau, M. M. and Narayan, V. (2002). Complications of

diabetes in elderly people. BMJ Clinical Research Ed., 325(7370):

916–917.

Gu, Z., Suburu, J., Chen, H., Chen, Y. Q. (2013). Mechanisms of omega-3

polyunsaturated fatty acids in prostate cancer prevention. Biomed Res

Int, 2013:824563.

Gullett, N. P., Mazurak, V. C., Hebbar, G., Ziegler, T. R. (2011).

Nutritional interventions for cancer-induced cachexia. Curr Probl

Cancer. 35:58–90.

Complimentary Contributor Copy

J. S. Perona, S. Garcia-Rodriguez and J. M. Castellano

222

Hu, F. B., Bronner, L., Willett, W. C., Stampfer, M. J., Rexrode, K. M.,

Albert, C. M. et al., (2002). Fish and omega-3 fatty acid intake and risk

of coronary heart disease in women. JAMA, 287(14): 1815–1821.

Hu, Y., Sun, H., Owens, R. T., Gu, Z., Wu, J., et al., (2010). Syndecan-1-

dependent suppression of PDK1/Akt/bad signaling by

docosahexaenoic acid induces apoptosis in prostate cancer. Neoplasia,

12:826–36.

Huan, M., Cui, H., Teng, Z., Zhang, B., Wang, J., Liu, X. et al., (2012). In

Vivo Anti-Tumor Activity of a New Doxorubicin Conjugate via α-

Linolenic Acid. Bioscience, Biotechnology, and Biochemistry, 76(8):

1577–1579. https://doi.org/10.1271/bbb.120256.

Huober, J., Thurlimann, B. (2009). The role of combination chemotherapy

in the treatment of patients with metastatic breast cancer. Breast Care

(Basel), 4:367–72.

Igarashi, M., Ma, K., Chang, L., Bell, J. M. and Rapoport, S. I. (2007).

Dietary n-3 PUFA deprivation for 15 weeks upregulates elongase and

desaturase expression in rat liver but not brain. Journal of Lipid

Research, 48(11): 2463–2470. https://doi.org/10.1194/jlr.M700315-

JLR200.

Jatoi, A., Rowland, K., Loprinzi, C. L., Sloan, J. A., Dakhil, S. R., et al.,

(2004). An eicosapentaenoic acid supplement versus Megestrol acetate

versus both for patients with cancer-associated wasting: a North

Central Cancer Treatment Group and National Cancer Institute of

Canada collaborative effort. J Clin Oncol., 22:2469–76.

Kim, H.-K., Della-Fera, M., Lin, J. and Baile, C. A. (2006).

Docosahexaenoic acid inhibits adipocyte differentiation and induces

apoptosis in 3T3-L1 preadipocytes. The Journal of Nutrition, 136(12):

2965–2969.

King, V. R., Huang, W. L., Dyall, S. C., Curran, O. E., Priestley, J. V and

Michael-Titus, A. T. (2006). Omega-3 Fatty Acids Improve Recovery,

whereas Omega-6 Fatty Acids Worsen Outcome, after Spinal Cord

Injury in the Adult Rat. Journal of Neuroscience, 26(17): 4672–4680.

https://doi.org/10.1523/JNEUROSCI.5539-05.2006.

Complimentary Contributor Copy

Plants as Alternative Sources of n-3 Polyunsaturated Fatty Acids

223

Klinger, D. and Naylor, R. (2012). Searching for Solutions in Aquaculture:

Charting a Sustainable Course. Annual Review of Environment and

Resources, 37(1): 247–276. https://doi.org/10.1146/annurev-environ-

021111-161531.

Köhler, A., Sarkkinen, E., Tapola, N., Niskanen, T. and Bruheim, I.

(2015). Bioavailability of fatty acids from krill oil, krill meal and fish

oil in healthy subjects–a randomized, single-dose, cross-over trial.

Lipids in Health and Disease, 14(1): 19. https://doi.org/10.1186/

s12944-015-0015-4.

Koletzko, B., Baker, S., Cleghorn, G., Neto, U. F., Gopalan, S., Hernell, O.

et al., (2005). Global standard for the composition of infant formula:

recommendations of an ESPGHAN coordinated international expert

group. Journal of Pediatric Gastroenterology and Nutrition, 41(5):

584–599.

Konagai, C., Yanagimoto, K., Hayamizu, K., Li, L., Tsuji, T. and Koga, Y.

(2013). Effects of krill oil containing n-3 polyunsaturated fatty acids in

phospholipid form on human brain function: a randomized controlled

trial in healthy elderly volunteers. Clinical Interventions in Aging, 8:

1247. https://doi.org/10.2147/CIA.S50349.

Kroetz, D. L., Zeldin, D. C. (2002). Cytochrome P450 pathways of

arachidonic acid metabolism. Curr Opin Lipidol., 13:273–83.

Laidlaw, M., Cockerline, C. A. and Rowe, W. J. (2014). A randomized

clinical trial to determine the efficacy of manufacturers’ recommended

doses of omega-3 fatty acids from different sources in facilitating

cardiovascular disease risk reduction. Lipids in Health and Disease,

13(1): 99. https://doi.org/10.1186/1476-511X-13-99.

Layne, K. S., Goh, Y. K., Jumpsen, J. A., Ryan, E. A., Chow, P. and

Clandinin, M. T. (1996). Normal subjects consuming physiological

levels of 18:3(n-3) and 20:5(n-3) from flaxseed or fish oils have

characteristic differences in plasma lipid and lipoprotein fatty acid

levels. The Journal of Nutrition, 126(9): 2130–2140.

Lee, H. Y., Woo, J., Chen, Z. Y., Leung, S. F. and Peng, X. H. (2000).

Serum fatty acid, lipid profile and dietary intake of Hong Kong

Complimentary Contributor Copy

J. S. Perona, S. Garcia-Rodriguez and J. M. Castellano

224

Chinese omnivores and vegetarians. European Journal of Clinical

Nutrition, 54(10): 768–773.

Lenihan-Geels, G., Bishop, K. and Ferguson, L. (2013). Alternative

Sources of Omega-3 Fats: Can We Find a Sustainable Substitute for

Fish? Nutrients, 5(4): 1301–1315. https://doi.org/10.3390/nu5041301.

Lewis, R. A., Austen, K. F., Soberman, R. J. (1990). Leukotrienes and

other products of the 5-lipoxygenase pathway. Biochemistry and

relation to pathobiology in human diseases. N Engl J Med., 323: 645–

55.

Liu, J. and Ma, D. W. L. (2014). The role of n-3 polyunsaturated fatty

acids in the prevention and treatment of breast cancer. Nutrients, 6(11):

5184–5223. https://doi.org/10.3390/nu6115184.

Liu, L., Bartke, N., Van Daele, H., Lawrence, P., Qin, X., Park, H. G. et

al., (2014). Higher efficacy of dietary DHA provided as a phospholipid

than as a triglyceride for brain DHA accretion in neonatal piglets.

Journal of Lipid Research, 55(3): 531–539. https://doi.org/10.1194/jlr.

M045930.

Liu, Y., Sun, Q., Chen, X., Jing, L., Wang, W., Yu, Z. et al., (2014).

Linolenic Acid Provides Multi-cellular Protective Effects After

Photothrombotic Cerebral Ischemia in Rats. Neurochemical Research,

39(9): 1797–1808. https://doi.org/10.1007/s11064-014-1390-3.

Maki, K. C., Reeves, M. S., Farmer, M., Griinari, M., Berge, K., Vik, H. et

al., (2009). Krill oil supplementation increases plasma concentrations

of eicosapentaenoic and docosahexaenoic acids in overweight and

obese men and women. Nutrition Research, 29(9): 609–615.

https://doi.org/10.1016/j.nutres.2009.09.004.

Maki, K. C., Yurko-Mauro, K., Dicklin, M. R., Schild, A. L. and Geohas,

J. G. (2014). A new, microalgal DHA- and EPA-containing oil lowers

triacylglycerols in adults with mild-to-moderate hypertriglyceridemia.

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA),

91(4): 141–148. https://doi.org/10.1016/j.plefa.2014.07.012.

Mantovani, G. (2010). Randomised phase III clinical trial of 5 different

arms of treatment on 332 patients with cancer cachexia. Eur Rev Med

Pharmacol Sci, 14:292–301.

Complimentary Contributor Copy

Plants as Alternative Sources of n-3 Polyunsaturated Fatty Acids

225

Mason, J. K. and Thompson, L. U. (2014). Flaxseed and its lignan and oil

components: can they play a role in reducing the risk of and improving

the treatment of breast cancer? Applied Physiology, Nutrition, and

Metabolism, 39(6): 663–678. https://doi.org/10.1139/apnm-2013-0420.

Morales P, J., Valenzuela B, R., González M, D., González E, M., Tapia O,

G., Sanhueza C, J. and Valenzuela B, A. (2012). Nuevas fuentes

dietarias de acido alfa-linolénico: una visión crítica. [New dietary

sources of alpha-linolenic acid: a critical view.] Revista Chilena de

Nutrición, 39(3): 79–87. https://doi.org/10.4067/S0717-751820120

00300012.

Morris, M. C., Evans, D. A., Bienias, J. L., Tangney, C. C., Bennett, D. A.,

Wilson, R. S. et al., (2003). Consumption of Fish and n-3 Fatty Acids

and Risk of Incident Alzheimer Disease. Archives of Neurology, 60(7):

940. https://doi.org/10.1001/archneur.60.7.940.

Murphy, R. A., Mourtzakis, M., Mazurak, V. C. (2012). n-3

polyunsaturated fatty acids: the potential role for supplementation in

cancer. Curr Opin Clin Nutr Metab Care, 15:246–51.

Neff, L. M., Culiner, J., Cunningham-Rundles, S., Seidman, C., Meehan,

D., Maturi, J. et al., (2011). Algal docosahexaenoic acid affects plasma

lipoprotein particle size distribution in overweight and obese adults.

The Journal of Nutrition, 141(2): 207–213. https://doi.org/10.3945/jn.

110.130021.

Norziah, M. H. and Ching, C. Y. (2000). Nutritional composition of edible

seaweed Gracilaria changgi. Food Chemistry, 68(1): 69–76.

https://doi.org/10.1016/S0308-8146(99)00161-2.

Oh, D. Y., Talukdar, S., Bae, E. J., Imamura, T., Morinaga, H., et al.,

(2010). GPR120 is an omega-3 fatty acid receptor mediating potent

anti-inflammatory and insulin-sensitizing effects. Cell, 142:687–98.

Pawlosky, R. J., Hibbeln, J. R., Novotny, J. A. and Salem, N. (2001).

Physiological compartmental analysis of alpha-linolenic acid

metabolism in adult humans. Journal of Lipid Research, 42(8): 1257–

1265.

Petrie, J. R., Shrestha, P., Zhou, X.-R., Mansour, M. P., Liu, Q., Belide, S.

et al., (2012). Metabolic Engineering Plant Seeds with Fish Oil-Like

Complimentary Contributor Copy

J. S. Perona, S. Garcia-Rodriguez and J. M. Castellano

226

Levels of DHA. PLoS ONE, 7(11): e49165. https://doi.org/10.1371/

journal.pone.0049165.

Ramprasath, V. R., Eyal, I., Zchut, S. and Jones, P. J. H. (2013). Enhanced

increase of omega-3 index in healthy individuals with response to 4-

week n-3 fatty acid supplementation from krill oil versus fish oil.

Lipids in Health and Disease, 12: 178. https://doi.org/10.1186/1476-

511X-12-178.

Rossoll, D., Bermúdez, R., Hauss, H., Schulz, K. G., Riebesell, U.,

Sommer, U. and Winder, M. (2012). Ocean acidification-induced food

quality deterioration constrains trophic transfer. PloS One, 7(4):

e34737. https://doi.org/10.1371/journal.pone.0034737.

Ruiz-Lopez, N., Haslam, R. P., Napier, J. A. and Sayanova, O. (2014).

Successful high-level accumulation of fish oil omega-3 long-chain

polyunsaturated fatty acids in a transgenic oilseed crop. The Plant

Journal, 77(2): 198–208. https://doi.org/10.1111/tpj.12378.

Sala-Vila, A., Calder, P. C. (2011). Update on the relationship of fish

intake with prostate, breast, and colorectal cancers. Crit Rev Food Sci

Nutr, 51:855–71.

Sanz París, A., Sanchis, A. M., Malpartida, K. G. and García Gómez, D. C.

(2012). Propuesta de perfil de ácidos grasos omega 3 en nutrición

enteral. Nutr Hosp. Nutr Hosp, 2727(6). https://doi.org/10.3305/

nh.2012.27.6.6023.

Schuchardt, J. P. and Hahn, A. (2013). Bioavailability of long-chain

omega-3 fatty acids. Prostaglandins, Leukotrienes and Essential Fatty

Acids (PLEFA), 89(1): 1–8. https://doi.org/10.1016/J.PLEFA.2013.

03.010.

Schuchardt, J. P., Schneider, I., Meyer, H., Neubronner, J., von Schacky,

C. and Hahn, A. (2011). Incorporation of EPA and DHA into plasma

phospholipids in response to different omega-3 fatty acid formulations-

-a comparative bioavailability study of fish oil vs. krill oil. Lipids in

Health and Disease, 10: 145. https://doi.org/10.1186/1476-511X-10-

145.

Schwab, U. S., C. Callaway, J., Erkkilä, A. T., Gynther, J., Uusitupa, M. I.

J. and Järvinen, T. (2006). Effects of hempseed and flaxseed oils on

Complimentary Contributor Copy

Plants as Alternative Sources of n-3 Polyunsaturated Fatty Acids

227

the profile of serum lipids, serum total and lipoprotein lipid

concentrations and haemostatic factors. European Journal of Nutrition,

45(8): 470–477. https://doi.org/10.1007/s00394-006-0621-z.

Serhan, C. N., Chiang, N., Van Dyke, T. E. (2008). Resolving

inflammation: dual anti-inflammatory and pro-resolution lipid

mediators. Nat Rev Immunol, 8:349–61.

Siebenlist, U., Franzoso, G. and Brown, K. (1994). Structure, Regulation

and Function of NF-kappaB. Annual Review of Cell Biology, 10(1):

405–455. https://doi.org/10.1146/annurev.cb.10.110194.002201.

Sukenik, A. (1991). Ecophysiological considerations in the optimization of

eicosapentaenoic acid production by Nannochloropsis sp.

(Eustigmatophyceae). Bioresource Technology, 35(3): 263–269.

https://doi.org/10.1016/0960-8524(91)90123-2.

Teng, Y. H., Aquino, R. S., Park, P. W. (2012). Molecular functions of

syndecan-1 in disease. Matrix Biol, 31:3–16.

Thompson, L. U., Chen, J. M., Li, T., Strasser-Weippl, K. and Goss, P. E.

(2005). Dietary Flaxseed Alters Tumor Biological Markers in

Postmenopausal Breast Cancer. Clinical Cancer Research, 11(10):

3828–3835. https://doi.org/10.1158/1078-0432.CCR-04-2326.

Tilley, S. L., Coffman, T. M., Koller, B. H. (2001). Mixed messages:

modulation of inflammation and immune responses by prostaglandins

and thromboxanes. J Clin Invest, 108: 15–23.

Tocher, D. (2009). Issues surrounding fish as a source of omega-3 long-

chain polyunsaturated fatty acids. Lipid Technology, 21(1): 13–16.

https://doi.org/10.1002/lite.200800079.

Tocher, D. R. (2015). Omega-3 long-chain polyunsaturated fatty acids and

aquaculture in perspective. Aquaculture, 449: 94–107. https://doi.org/

10.1016/J.AQUACULTURE.2015.01.010.

Todorcević, M., Vegusdal, A., Gjøen, T., Sundvold, H., Torstensen, B. E.,

Kjaer, M. A. and Ruyter, B. (2008). Changes in fatty acids metabolism

during differentiation of Atlantic salmon preadipocytes; effects of n-3

and n-9 fatty acids. Biochimica et Biophysica Acta, 1781(6–7): 326–

335. https://doi.org/10.1016/j.bbalip.2008.04.014.

Complimentary Contributor Copy

J. S. Perona, S. Garcia-Rodriguez and J. M. Castellano

228

Truan, J. S., Chen, J.-M. and Thompson, L. U. (2010). Flaxseed oil reduces

the growth of human breast tumors (MCF-7) at high levels of

circulating estrogen. Molecular Nutrition & Food Research, 54(10):

1414–1421. https://doi.org/10.1002/mnfr.200900521.

Tu, W. C., Cook-Johnson, R. J., James, M. J., Mühlhäusler, B. S. and

Gibson, R. A. (2010). Omega-3 long chain fatty acid synthesis is

regulated more by substrate levels than gene expression.

Prostaglandins, Leukotrienes and Essential Fatty Acids, 83(2): 61–68.

https://doi.org/10.1016/j.plefa.2010.04.001.

Ulven, S. M. and Holven, K. B. (2015). Comparison of bioavailability of

krill oil versus fish oil and health effect. Vascular Health and Risk

Management, 11: 511. https://doi.org/10.2147/VHRM.S85165.

Ulven, S. M., Kirkhus, B., Lamglait, A., Basu, S., Elind, E., Haider, T. et

al., (2011). Metabolic effects of krill oil are essentially similar to those

of fish oil but at lower dose of EPA and DHA, in healthy volunteers.

Lipids, 46(1): 37–46. https://doi.org/10.1007/s11745-010-3490-4.

Valenzuela, A. and Valenzuela, R. (2014). Acidos grasos omega-3 en la

nutrición ¿como aportarlos? [Omega-3 fatty acids in nutrition, how to

provide them?] Revista Chilena de Nutrición, 41(2): 205–211.

https://doi.org/10.4067/S0717-75182014000200012.

Valenzuela, R., Tapia, G., González, M. and Valenzuela, A. (2011).

Ácidos grasos omega-3 (EPA y DHA) y su aplicación en diversas

situaciones clínicas. [Omega-3 fatty acids (EPA and DHA) and their

application in various clinical situations.] Rev Chil Nutr, 38.

Complimentary Contributor Copy

Towards a productive model for the Sacha Inchi value chain: A scientometric approach

Article

Full-text available

Dec 2023

The diversification of agricultural and livestock production matrixes has the potential to generate value-added products in industrial and promising crops. Specifically, the countries in the Amazon basin have in the Sacha Inchi (Plukenetia volubilis L.) a species oriented toward market niches such as food, oils, cosmetics, pharmaceuticals, and biofuels, whose exploitation and use are aligned with the bioeconomy and circular economy megatrends. The aim of this publication was to identify and analyze the evolution of scientific and technological research in the Sacha Inchi value chain worldwide, based on a methodological design that combines technological intelligence, the analysis of scientific landscapes and bibliometric indicators and content analysis, to establish a baseline for the identification of key elements for the design of an agro-industrial production model. The methodology includes the integration of surveillance and scientific intelligence methods, scientometrics, and critical analysis of key documents selected through bibliometric indicators and expert judgment. The analysis made it possible to identify the research development lines in Sacha Inchi worldwide, and the reference documents that comprise key elements of the activities from cultivation to processing of the product obtained. The basic investigations identified will contribute to the development of productive models of Sacha Inchi in Colombia, where technical aspects must be adapted or validated in suitable agroecological zones or with productive potential to improve the yield and quality of seed for agroindustry. Medium-term research is required to genetically identify the planting material, to facilitate the selection of materials oriented to the production of fruits with the quality required by the agroindustry.

Effect of Extraction Techniques on the Physicochemical Properties, Fatty Acids Composition, and Stability of Purslane Seeds (Portulaca oleracea) Oil Compared to Soybean Seeds (Glycine max) and Sardine Fish (Sardinella maderensis) Oils

Article

Full-text available

Dec 2022

Seed oil and seed oil byproducts of common purslane (Portulaca oleracea L.): A new insight to plant-based sources rich in omega-3 fatty acids

Article

Apr 2020
LWT-FOOD SCI TECHNOL

In the present study, nutritional value, chemical composition and bioactive properties of purslane seeds, seed oils and seedcakes wereexamined. Data were analyzed by a one-way ANOVA, while means were compared with Tukey's HSD test. For seed oil extraction mechanical and ultrasound assisted methods were tested. Cold extraction methods (CE1 and CE2) resulted in higher oil yield (increased by 33.7% and 38.1%, respectively) comparing to hot extraction (HE) method. Seeds contained the highest amount of fats and energy (15.03 ± 0.06 g/100 g dry basis (db) and 459 ± 1 kcal/100 g db, respectively), while seedcakes from CE2 had the highest content in proteins and ash (31.20 ± 0.03 and 4.27 ± 0.06 g/100 g db, respectively). Seeds and seedcakes contained a balanced content of linoleic and α-linolenic acids (33.80-34.74% and 32.83-34.64%, respectively). HE and CE1 oils had slightly higher amounts of α-linolenic (39.67% and 39.57%, respectively) than linoleic acid (35.44% and 35.13%, respectively), whereas CE2 oils contained twice as much linoleic as α-linolenic acid (49.77% and 24.18%, respectively). In conclusion, the tested materials are good sources of omega-6 and omega-3 fatty acids and proteins, while extraction method affected oil yield and fatty acids composition of seed oils.

Food industry by-products

Chapter

Jan 2023

An oil containing EPA and DHA from transgenic Camelina sativa to replace marine fish oil in feeds for Atlantic salmon (Salmo salar L.): Effects on intestinal transcriptome, histology, tissue fatty acid profiles and plasma biochemistry

Article

Full-text available

Apr 2017
PLOS ONE

New de novo sources of omega 3 (n-3) long chain polyunsaturated fatty acids (LC-PUFA) are required as alternatives to fish oil in aquafeeds in order to maintain adequate levels of the beneficial fatty acids, eicosapentaenoic and docosahexaenoic (EPA and DHA, respectively). The present study investigated the use of an EPA+DHA oil derived from transgenic Camelina sativa in Atlantic salmon (Salmo salar) feeds containing low levels of fishmeal (35%) and fish oil (10%), reflecting current commercial formulations, to determine the impacts on tissue fatty acid profile, intestinal transcriptome, and health of farmed salmon. Post-smolt Atlantic salmon were fed for 12-weeks with one of three experimental diets containing either a blend of fish oil/rapeseed oil (FO), wild-type camelina oil (WCO) or transgenic camelina oil (DCO) as added lipid source. The DCO diet did not affect any of the fish performance or health parameters studied. Analyses of the mid and hindgut transcriptomes showed only mild effects on metabolism. Flesh of fish fed the DCO diet accumulated almost double the amount of n-3 LC-PUFA than fish fed the FO or WCO diets, indicating that these oils from transgenic oilseeds offer the opportunity to increase the n-3 LC-PUFA in farmed fish to levels comparable to those found a decade ago.

Comparison of bioavailability of krill oil versus fish oil and health effect

Article

Full-text available

Aug 2015

Background The aim of this review is to summarize the effects of krill oil (KO) or fish oil (FO) on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) incorporation in plasma phospholipids or membrane of red blood cells (RBCs) as shown in human and animal studies. Furthermore, we discuss the findings in relation to the possible different health effects, focusing on lipids, inflammatory markers, cardiovascular disease risk, and biological functions of these two sources of long-chain n-3 polyunsaturated fatty acids (PUFAs). Methods A literature search was conducted in PubMed in January 2015. In total, 113 articles were identified, but based on selection criteria, 14 original papers were included in the review. Results Studies on bioavailability of EPA and DHA from KO and FO in humans and animals are limited and the interpretation is difficult, as different amounts of EPA and DHA have been used, duration of intervention differs, and different study groups have been included. Two human studies – one postprandial study and one intervention study – used the same amount of EPA and DHA from KO or FO, and they both showed that the bioavailability of EPA and DHA from KO seems to be higher than that from FO. Limited effects of KO and FO on lipids and inflammatory markers in human and animal studies were reported. Gene expression data from animal studies showed that FO upregulated the cholesterol synthesis pathway, which was the opposite of the effect mediated by KO. KO also regulated far more metabolic pathways than FO, which may indicate different biological effects of KO and FO. Conclusion There seems to be a difference in bioavailability of EPA and DHA after intake of KO and FO, but more studies are needed before a firm conclusion can be made. It is also necessary to document the beneficial health effects of KO with more human studies and to elucidate if these effects differ from those after regular fish and FO intake.

Supplementation with a blend of krill and salmon oil is associated with increased metabolic risk in overweight men

Article

Full-text available

May 2015
AM J CLIN NUTR

Krill is an increasingly popular source of marine n-3 (ω-3) PUFA that is seen as a premium product. However, to our knowledge, the effect of krill-oil supplementation on insulin sensitivity in humans has not been reported. We assessed whether supplementation with a blend of krill and salmon (KS) oil [which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] affects insulin sensitivity in overweight men. The design was a randomized, double-blind, controlled crossover trial. A total of 47 men with a mean ± SD age of 46.5 ± 5.1 y, who were overweight [body mass index (in kg/m(2)) from 25 to 30] but otherwise healthy, received 5 1-g capsules of KS oil or a control (canola oil) for 8 wk and crossed over to another treatment after a 8-wk washout period. The primary outcome was insulin sensitivity assessed by using the Matsuda method from an oral-glucose-tolerance test. Secondary outcomes included lipid profiles, inflammatory markers, 24-h ambulatory blood pressure, and carotid artery intimamedia thickness. Unexpectedly, insulin sensitivity (per the Matsuda index) was 14% lower with the KS oil than with the control oil (P = 0.049). A mediation analysis showed that, after controlling for the likely positive effects of blood EPA and DHA (i.e., the omega-3 index), the reduction in insulin sensitivity after KS-oil supplementation was more marked [27% lower than with the control oil (P = 0.009)]. Supplementation with a blend of KS oil is associated with decreased insulin sensitivity. Thus, krill-oil supplementation in overweight adults could exacerbate risk of diabetes and cardiovascular disease. This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry as ACTRN12611000602921. © 2015 American Society for Nutrition.

Bioavailability of fatty acids from krill oil, krill meal and fish oil in healthy subjects–a randomized, single-dose, cross-over trial

Article

Full-text available

Dec 2015
LIPIDS HEALTH DIS

Krill contains two marine omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly bound in phospholipids. Typical products from krill are krill oil and krill meal. Fish oils contain EPA and DHA predominantly bound in triglycerides. The difference in the chemical binding of EPA and DHA has been suggested to affect their bioavailability, but little is known on bioavailability of EPA and DHA in krill meal. This study was undertaken to compare the acute bioavailability of two krill products, krill oil and krill meal, with fish oil in healthy subjects. A randomized, single-dose, single-blind, cross-over, active-reference trial was conducted in 15 subjects, who ingested krill oil, krill meal and fish oil, each containing approx. 1 700 mg EPA and DHA. Fatty acid compositions of plasma triglycerides and phospholipids were measured repeatedly for 72 hours. The primary efficacy analysis was based on the 72 hour incremental area under the curve (iAUC) of EPA and DHA in plasma phospholipid fatty acids. A larger iAUC for EPA and DHA in plasma phospholipid fatty acids was detected after krill oil (mean 89.08 ± 33.36% × h) than after krill meal (mean 44.97 ± 18.07% x h, p < 0.001) or after fish oil (mean 59.15 ± 22.22% × h, p=0.003). Mean iAUC’s after krill meal and after fish oil were not different. A large inter-individual variability in response was observed. EPA and DHA in krill oil had a higher 72-hour bioavailability than in krill meal or fish oil. Our finding that bioavailabilities of EPA and DHA in krill meal and fish oil were not different argues against the interpretation that phospholipids are better absorbed than triglycerides. Longer-term studies using a parameter reflecting tissue fatty acid composition, like erythrocyte EPA plus DHA are needed. Trial registration NCT02089165

A nutritionally-enhanced oil from transgenic Camelina sativa effectively replaces fish oil as a source of eicosapentaenoic acid for fish

Article

Full-text available

Jan 2015

For humans a daily intake of up to 500mg omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA) is recommended, amounting to an annual requirement of 1.25 million metric tonnes (mt) for a population of 7 billion people. The annual global supply of n-3 LC-PUFA cannot meet this level of requirement and so there is a large gap between supply and demand. The dietary source of n-3 LC-PUFA, fish and seafood, is increasingly provided by aquaculture but using fish oil in feeds to supply n-3 LC-PUFA is unsustainable. Therefore, new sources of n-3 LC-PUFA are required to supply the demand from aquaculture and direct human consumption. One approach is metabolically engineering oilseed crops to synthesize n-3 LC-PUFA in seeds. Transgenic Camelina sativa expressing algal genes was used to produce an oil containing n-3 LC-PUFA to replace fish oil in salmon feeds. The oil had no detrimental effects on fish performance, metabolic responses or the nutritional quality of the fillets of the farmed fish.

The Role of n-3 Polyunsaturated Fatty Acids in the Prevention and Treatment of Breast Cancer

Article

Full-text available

Nov 2014

Breast cancer (BC) is the most common cancer among women worldwide. Dietary fatty acids, especially n-3 polyunsaturated fatty acids (PUFA), are believed to play a role in reducing BC risk. Evidence has shown that fish consumption or intake of long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for inhibiting mammary carcinogenesis. The evidence regarding α-linolenic acid (ALA), however, remains equivocal. It is essential to clarify the relation between ALA and cancer since ALA is the principal source of n-3 PUFA in the Western diet and the conversion of ALA to EPA and DHA is not efficient in humans. In addition, the specific anticancer roles of individual n-3 PUFA, alone, have not yet been identified. Therefore, the present review evaluates ALA, EPA and DHA consumed individually as well as in n-3 PUFA mixtures. Also, their role in the prevention of BC and potential anticancer mechanisms of action are examined. Overall, this review suggests that each n-3 PUFA has promising anticancer effects and warrants further research.

Replacement of Marine Fish Oil with de novo Omega-3 Oils from Transgenic Camelina sativa in Feeds for Gilthead Sea Bream (Sparus aurata L.)

Article

Sep 2016
LIPIDS

Omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA) are essential components of the diet of all vertebrates. The major dietary source of n-3 LC-PUFA for humans has been fish and seafood but, paradoxically, farmed fish are also reliant on marine fisheries for fish meal and fish oil (FO), traditionally major ingredients of aquafeeds. Currently, the only sustainable alternatives to FO are vegetable oils, which are rich in C18 PUFA, but devoid of the eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) abundant in FO. Two new n-3 LC-PUFA sources obtained from genetically modified (GM) Camelina sativa containing either EPA alone (ECO) or EPA and DHA (DCO) were compared to FO and wild-type camelina oil (WCO) in juvenile sea bream. Neither ECO nor DCO had any detrimental effects on fish performance, although final weight of ECO-fed fish (117 g) was slightly lower than that of FO- and DCO-fed fish (130 and 127 g, respectively). Inclusion of the GM-derived oils enhanced the n-3 LC-PUFA content in fish tissues compared to WCO, although limited biosynthesis was observed indicating accumulation of dietary fatty acids. The expression of genes involved in several lipid metabolic processes, as well as fish health and immune response, in both liver and anterior intestine were altered in fish fed the GM-derived oils. This showed a similar pattern to that observed in WCO-fed fish reflecting the hybrid fatty acid profile of the new oils. Overall the data indicated that the GM-derived oils could be suitable alternatives to dietary FO in sea bream.

Omega-3 Sources

Article

May 2009
J COMPLEMENT MED

Rachel Arthur

• Worldwide, the demand for wild fish is now greater than the ocean can supply and projections suggest complete reliance on aquaculture by 2050 • The nutritional characteristics of farmed fish are largely influenced by the composition of their feed • While net omega-3 content of farmed fish varieties generally appears comparable with or even superior to wild counterparts, other differences in the complete fatty-acid profile may impact on the net health benefits • C onsistent use of vitamin fortificants ensures that some but not all nutrient levels are higher in farmed fish • Limited data on mercury content suggests that there is limited difference between domesticated and wild-harvested fish • There is consistent evidence of significantly higher organohalogen pollutants (OHP) in farmed fish, which may negate some of the health benefits attributed with increased fish consumption • A lternative sources of omega-3s as the basis for aquafeed or for direct human consumption such as microalgae, krill and genetically modified plant crops represent an area of intense research.

Omega-3 long-chain polyunsaturated fatty acids and aquaculture in perspective

Article

Jan 2015
AQUACULTURE

Douglas R Tocher

In the 40 years since the essentiality of polyunsaturated fatty acids (PUFA) in fish was first established by determining quantitative requirements for 18:3n − 3 and 18:2n − 6 in rainbow trout, essential fatty acid (EFA) research has gone through distinct phases. For 20 years the focus was primarily on determining qualitative and quantitative EFA requirements of fish species. Nutritional and biochemical studies showed major differences between fish species based on whether C18 PUFA or long-chain (LC)-PUFA were required to satisfy requirements. In contrast, in the last 20 years, research emphasis shifted to determining “optimal” levels of EFA to support growth of fish fed diets with increased lipid content and where growth expectations were much higher. This required greater knowledge of the roles and functions of EFA in metabolism and physiology, and how these impacted on fish health and disease. Requirement studies were more focused on early life stages, in particular larval marine fish, defining not only levels, but also balances between different EFAs. Finally, a major driver in the last 10–15 years has been the unavoidable replacement of fish oil and fishmeal in feeds and the impacts that this can have on n − 3 LC-PUFA contents of diets and farmed fish, and the human consumer. Thus, dietary n − 3 in fish feeds can be defined by three levels. Firstly, the minimum level required to satisfy EFA requirements and thus prevent nutritional pathologies. This level is relatively small and easy to supply even with today's current high demand for fish oil. The second level is that required to sustain maximum growth and optimum health in fish being fed modern high-energy diets. The balance between different PUFA and LC-PUFA is important and defining them is more challenging, and so ideal levels and balances are still not well understood, particularly in relation to fish health. The third level is currently driving much research; how can we supply sufficient n − 3 LC-PUFA to maintain these nutrients in farmed fish at similar or higher levels than in wild fish? This level far exceeds the biological requirements of the fish itself and to satisfy it we require entirely new sources of n − 3 LC-PUFA. We cannot rely on the finite and limited marine resources that we can sustainably harvest or efficiently recycle. We need to produce n − 3 LC-PUFA de novo and all possible options should be considered.

O.43 A fish oil-enriched nutritional supplementreverses weight-loss in patients with advanced pancreatic cancer

Article

Aug 1998
CLIN NUTR

Plants as alternative sources of n-3 polyunsaturated fatty acids

Abstract

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