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Omega-3 fatty acids EPA and DHA: Health benefits throughout life


Abstract and Figures

Omega-3 [(n-3)] fatty acids have been linked to healthy aging throughout life. Recently, fish-derived omega-3 fatty acids EPA and DHA have been associated with fetal development, cardiovascular function, and Alzheimer's disease. However, because our bodies do not efficiently produce some omega-3 fatty acids from marine sources, it is necessary to obtain adequate amounts through fish and fish-oil products. Studies have shown that EPA and DHA are important for proper fetal development, including neuronal, retinal, and immune function. EPA and DHA may affect many aspects of cardiovascular function including inflammation, peripheral artery disease, major coronary events, and anticoagulation. EPA and DHA have been linked to promising results in prevention, weight management, and cognitive function in those with very mild Alzheimer's disease.
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Omega-3 Fatty Acids EPA and DHA: Health
Benefits Throughout Life
Danielle Swanson,
Robert Block,
and Shaker A. Mousa
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY;
Department of Community and
Preventive Medicine, and Division of Cardiology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY;
College of Medicine, King Saud University, Riyadh, Saudi Arabia
Omega-3 [(n-3)] fatty acids have been linked to healthy aging throughout life. Recently, sh-derived omega-3 fatty acids EPA and DHA have been
associated with fetal development, cardiovascular function, and Alzheimers disease. However, because our bodies do not efficiently produce
some omega-3 fatty acids from marine sources, it is necessary to obtain adequate amounts through fish and fish-oil products. Studies have
shown that EPA and DHA are important for proper fetal development, including neuronal, retinal, and immune function. EPA and DHA may affect
many aspects of cardiovascular function including inflammation, peripheral artery disease, major coronary events, and anticoagulation. EPA and
DHA have been linked to promising results in prevention, weight management, and cognitive function in those with very mild Alzheimers
disease. Adv. Nutr. 3: 17, 2012.
Omega-3 [(n-3)] long-chain PUFA, including EPA and
DHA, are dietary fats with an array of health benets (1).
They are incorporated in many parts of the body including
cell membranes (2) and play a role in antiinammatory pro-
cesses and in the viscosity of cell membranes (3,4). EPA and
DHA are essential for proper fetal development and healthy
aging (5). DHA is a key component of all cell membranes
and is found in abundance in the brain and retina (6).
EPA and DHA are also the precursors of several metabolites
that are potent lipid mediators, considered by many investi-
gators to be benecial in the prevention or treatment of sev-
eral diseases (7).
It can be challenging to get the appropriate intake of EPA
and DHA through diet alone, even though EPA and DHA
are produced by water plants such as algae and are prevalent
in marine animals. A shorter chain omega-3 fatty acid, a-li-
nolenic acid (ALA),
is a prominent component of our diet
as it is found in many land plants that are commonly eaten,
but it does not provide the health benefits seen with EPA and
DHA. Although it is possible for the body to convert ALA to
EPA and DHA by enlongase and desaturase enzymes, re-
search suggests that only a small amount can be synthesized
in the body from this process (8). For example, 1 study sug-
gested that only w2 to 10% of ALA is converted to EPA or
DHA (9), and other studies found even less: Goyens et al.
(10) found an ALA conversion of w7% for EPA, but only
0.013% for DHA; Hussein et al. (11) found an ALA conver-
sion of only 0.3% for EPA and <0.01% for DHA.
The current American diet has changed over time to be
high in SFA and low in omega-3 fatty acids (12). This change
in eating habits is centered on fast food containing high
amounts of saturated fat, which has small amounts of essen-
tial omega-3 PUFA compared with food prepared in the
home (13). Seafood sources such as sh and sh-oil supple-
ments are the primary contributors of the 2 biologically im-
portant dietary omega-3 fatty acids, EPA and DHA (1416).
This low intake of dietary EPA and DHA is thought to be as-
sociated with increased inflammatory processes as well as
poor fetal development, general cardiovascular health, and
risk of the development of Alzheimers disease (AD).
This review focuses on the many benets of EPA and
DHA supplementation throughout life, including use during
pregnancy for proper fetal development and full-term gesta-
tion, to reduce many cardiovascular issues, and potential
uses in AD.
Supported by the Pharmaceutical Research Institute and in part by grant 10-NAN1034-02
from the Long-Term Comprehensive National Plan for Science, Technology and Innovation,
King Saud University, Kingdom of Saudi Arabia.
Author disclosures: D. Swanson, R. Block, and S.A. Mousa, no conflicts of interest.
* To whom correspondence should be addressed: E-mail:
Abbreviations used: AD, Alzheimer’s disease; ALA, a-linolenic acid; CRP, C-reactive protein;
MMSE, Mini-Mental State Examination; PAD, peripheral arterial disease.
ã2012 American Society for Nutrition. Adv. Nutr. 3: 1–7, 2012; doi:10.3945/an.111.000893. 1
Omega-3 fatty acids and fetal development
Maternal nutrition guidelines have always stressed a diet in-
cluding sufcient caloric and protein requirements, but re-
cently fatty acids have also been deemed important (17).
This is partially due to the fact that EPA and DHA supple-
mentation during pregnancy has been associated with mul-
tiple benets for the infant (Table 1). During pregnancy, the
placenta transfers nutrients, including DHA, from the
mother to the fetus (18). The amount of omega-3 fatty
acid in the fetus is correlated with the amount ingested by
the mother, so it is essential that the mother has adequate
nutrition (19). The 2010 U.S. Department of Health and
Human Services dietary guidelines recommend that women
who are pregnant or breastfeeding should consume 8 to 12
ounces of seafood per week from a variety of seafood types
(12). Ingesting 812 oz of seafood per week, depending on
the type of fish, is equivalent to w300900 mg EPA+DHA
per day. Unfortunately, this amount is not being met by
most mothers in the United States and Canada, which
means that infants many not be receiving adequate amounts
of these vital nutrients in the womb (20).
Several studies conrmed the benet of omega-3 supple-
mentation during pregnancy in terms of proper develop-
ment of the brain and retina. Of the 2 most important
long-chain omega-3 fatty acids, EPA and DHA, DHA is
the more important for proper cell membrane function
and is vital to the development of the fetal brain and retina
(17). During the third trimester, vast amounts of DHA accu-
mulate in fetal tissue (20). The 2 most inltrated fetal areas
include the retina and brain, which may correlate with nor-
mal eyesight and brain function (19). A study by Judge et al.
(20) found that children whose mothers had taken DHA
supplementation during pregnancy (n= 29) had signifi-
cantly better problem-solving skills at 9 mo old (P=
0.017) than those whose mothers had not taken DHA sup-
plementation during pregnancy (n= 15). Another study
provided a cognitive assessment of children 2.5 y after
maternal EPA+DHA supplementation during pregnancy
from 20 wk of gestation until delivery (n= 33) compared
with children in a placebo group (n= 39). Children in the
EPA + DHAsupplemented group attained significantly higher
scores for eye and hand coordination [mean score, 114
TABLE 1. Studies involving omega-3 fatty acid supplementation and pregnancy
Study Design
No. of pregnant
patients who
completed trial
Omega-3 fatty acids
assessed and amounts
Judge et al. (20) Double-blind,
29 DHA (average
consumption 1500 mg/wk
DHA (n= 14, gestation
week 24 until birth)
vs. placebo (n= 15)
Maternal DHA intake was associated
with enhanced infant problem-solving
skills but not recognition skills
at 9 mo old
Dunstan et al. (19) Double-blind,
98 DHA (2.2 g/d) and EPA
(1.1 g/d) (gestation
week 20 until birth)
vs. placebo (n= 39)
At 2.5 y old, children (n= 32) whose
mothers were supplemented had
significantly better scores of hand
and eye coordination
Olsen et al. (23) Randomized clinical
n= 435 supplemented,
n= 463 placebo
DHA+EPA (sh-oil
capsules with 2.7 g/d
Supplementation delayed onset of
delivery in subjects who had
experienced preterm delivery in
previous pregnancies and were
classified as low and medium fish
Olsen et al. (21) Placebo-controlled,
Supplemented (n= 263)
vs. placebo (n= 136)
DHA+EPA (sh-oil
capsules daily, 2.7 g/d
Supplementation during pregnancy
was associated with a decreased
incidence of asthma in the children
at 16 y old
Makrides et al. (25) Double-blind,
2399 (n= 1197
n= 1202 placebo;
726 children were
followed up with)
DHA (sh-oil capsules
providing 800 mg/d DHA)
Supplementation did not result
in lower levels of postpartum
depression in mothers or
improved cognitive and language
development in offspring during
early childhood
Krauss-Etschmann et al. (26) Double-blind,
311 DHA+EPA daily with either
fish oil with DHA (0.5 g)
and EPA (0.15 g) or with
methyltetrahydrofolic acid
(400 mg), both, or placebo,
from gestation week 22
Fish-oil supplementation was
associated with decreased levels
of maternal inflammatory/T
cytokines and a decrease of fetal
Th2-related cytokines
Furuhjelm et al. (27) Placebo-controlled,
145 DHA+EPA daily with
either DHA (1.1 g) and
EPA (1.6 g), or placebo,
given from gestation
week 25 to an average
34 mo of breastfeeding
At 1 y old, infants whose mothers
were supplemented had a
decreased risk of food allergy
and IgE-associated eczema
2 Swanson et al.
(SD 10.2] than those in the placebo group [mean score, 108
(SD 11.3)] (P= 0.021, adjusted P= 0.008) (19).
Of great clinical importance, EPA and DHA supplemen-
tation during pregnancy has been associated with longer
gestation and increased concentrations of EPA and DHA
in fetal tissues (21). In 2005, preterm births accounted for
12.7% of all births in the United States, increasing the like-
lihood of health complications (22). Carrying a baby to term
is very important because prematurity is the cause of various
infant diseases and can lead to death; preterm delivery is an
underlying factor for 85% of the deaths of normally formed
infants (23). One mechanism by which EPA and DHA may
decrease the incidence of preterm birth is by decreasing
prostaglandin E
and prostaglandin F
production, there-
fore reducing inflammation within the uterus, which could
be associated with preterm labor (21,24). Several studies in-
vestigated EPA and DHA intake during pregnancy and its
correlation with longer gestation. Conclusions were that
EPA+DHA supplementation during pregnancy delayed the
onset of delivery to term or closer to term; however, supple-
mentation did not delay delivery to the point of being post-
term (20,23,25). This supports the evidence that EPA+DHA
ingestion leads to optimal pregnancy length. EPA+DHA
supplementation reduced the HR of preterm delivery by
44% (95% CI: 1464%) in those who consumed relatively
low amounts of fish and 39% (95% CI: 1656%) in those
who consumed medium amounts of fish; however, a level
of statistical significance was not met (P= 0.10) (23). The
Judge et al. (20) study found that women who had DHA
supplementation from gestation week 24 until full-term de-
livery carried their infants significantly (P= 0.019) longer
than did the women in the placebo group. One study found
that DHA supplementation after gestation week 21 led to
fewer preterm births (<34 wk of gestation) in the DHA
group compared with the control group (1.09% vs. 2.25%;
adjusted RR, 0.49; 95% CI: 0.250.94; P= 0.03). Also, mean
birth weight was 68 g heavier (95% CI: 23114 g; P=
0.003) and fewer infants were of low birth weight in the
DHA group compared with the control group (3.41% vs.
5.27%; adjusted RR, 0.65; 95% CI: 0.440.96; P= 0.03) (25).
There is also evidence that mothers who use EPA and
DHA supplementation during pregnancy and breastfeeding
may protect their children against allergies. This may be due
to the fact that sh-oil supplementation has been associated
with decreased levels of body cells associated with inamma-
tion and immune response (26). In a study about food al-
lergy and IgE-associated eczema, the period prevalence of
food allergy was lower in the maternal EPA+DHA supple-
mentation group compared to placebo (P< 0.05), and the
incidence of IgE-associated eczema was also lower in the
maternal EPA+DHA supplementation group compared to
placebo (P< 0.05) (27).
Omega-3 fatty acids and cardiovascular disease
Cardiovascular disease is the cause of 38% of all deaths in
the United States, many of which are preventable (28).
Chronic inammation is thought to be the cause of many
chronic diseases, including cardiovascular disease (29).
EPA and DHA are thought to have antiinammatory effects
and a role in oxidative stress (30) and to improve cellular
function through changes in gene expression (31). In a study
that used human blood samples, EPA+DHA intake changed
the expression of 1040 genes and resulted in a decreased ex-
pression of genes involved in inammatory and atherogen-
esis-related pathways, such as nuclear transcription factor
kB signaling, eicosanoid synthesis, scavenger receptor activ-
ity, adipogenesis, and hypoxia signaling (31). Circulating
markers of inflammation, such as C-reactive protein
(CRP), TNF a, and some ILs (IL-6, IL-1), correlate with
an increased probability of experiencing a cardiovascular
event (32). Inflammatory markers such as IL-6 trigger
CRP to be synthesized by the liver, and elevated levels of
CRP are associated with an increased risk of the develop-
ment of cardiovascular disease (33). A study of 89 patients
showed that those treated with EPA+DHA had a significant
reduction in high-sensitivity CRP (66.7%, P< 0.01) (33).
The same study also showed a significant reduction in
heat shock protein 27 antibody titers (57.69%, P< 0.05),
which have been shown to be overexpressed in heart muscle
cells after a return of blood flow after a period of ischemia
(ischemia-reperfusion injury) and may potentially have a
cardioprotective effect (33).
Therehavebeenconicting results reported about EPA
and DHA and their use with regard to major coronary events
and their use after myocardial infarction. EPA+DHA has been
associated with a reduced risk of recurrent coronary artery
events and sudden cardiac death after an acute myocardial in-
farction (RR, 0.47; 95% CI: 0.2190.995) and a reduction in
heart failure events (adjusted HR: 0.92; 99% CI: 0.8490.999)
(3436). A study using EPA supplementation in combination
with a statin, compared with statin therapy alone, found that,
after 5 y, the patients in the EPA group (n=262)whohada
history of coronary artery disease had a 19% relative reduc-
tion in major coronary events (P= 0.011). However, in pa-
tients with no history of coronary artery disease (n=104),
major coronary events were reduced by 18%, but this finding
was not significant (37). This Japanese population already has
a high relative intake of fish compared with other nations,
and, thus, these data suggest that supplementation has cardi-
ovascular benefits in those who already have sufficient base-
line EPA+DHA levels. Another study compared patients
with impaired glucose metabolism (n= 4565) with normo-
glycemic patients (n= 14,080). Impaired glucose metabolism
patients had a significantly higher coronary artery disease HR
(1.71 in the non-EPA group and 1.63 in the EPA group). The
primary endpoint was any major coronary event including
sudden cardiac death, myocardial infarction, and other non-
fatal events. Treatment of impaired glucose metabolism
patients with EPA showed a significantly lower major coro-
nary event HR of 0.78 compared with the nonEPA-treated
impaired glucose metabolism patients (95% CI: 0.600.998;
P= 0.048), which demonstrates that EPA significantly sup-
presses major coronary events (38). When looking at the
use of EPA+DHA and cardiovascular events after myocardial
Health benets of omega-3 fatty acids 3
infarction, of 4837 patients, a major cardiovascular event oc-
curred in 671 patients (13.9%) (39). A post hoc analysis of the
data from these diabetic patients showed that rates of fatal
coronary heart disease and arrhythmia-related events were
lower among patients in the EPA+DHA group than among
the placebo group (HR for fatal coronary heart disease:
0.51; 95% CI: 0.270.97; HR for arrhythmia-related events:
0.51; 95% CI: 0.241.11, not statistically significant) (39). An-
other study found that there was no significant difference in
sudden cardiac death or total mortality between an EPA
+DHA supplementation group and a control group in those
patients treated after myocardial infarction (40). Although
these last 2 studies appear to be negative in their results, it
is possible that the more aggressive treatment with medica-
tions in these more recent studies could attribute to this.
Omega-3 fatty acids have been found to play a role in ath-
erosclerosis and peripheral arterial disease (PAD). It is
thought that both EPA and DHA improve plaque stability,
decrease endothelial activation, and improve vascular per-
meability, thereby decreasing the chance of experiencing a
cardiovascular event (41). It was found that EPA supplemen-
tation is associated with signicantly higher amounts of EPA
in the carotid plaque than placebo (P< 0.0001), which may
lead to decreased plaque inflammation and increased stabil-
ity (42). PAD, a manifestation of atherosclerosis, is charac-
terized by buildup of plaque in the arteries of the leg and
can eventually lead to complete blockage of the arteries.
EPA+DHA supplementation has been shown to improve en-
dothelial function in patients with PAD by decreasing
plasma levels of soluble thrombomodulin from a median
value of 33.0 mg/L to 17.0 mg/L (P= 0.04) and improve
brachial artery flowmediated dilation from 6.7% to
10.0% (P= 0.02) (43). Patients who had PAD and were sup-
plemented with EPA experienced a significantly lower major
coronary event HR than those who did not take EPA (HR:
0.44; 95% CI: 0.190.97; P= 0.041) (44).
Omega-3 fatty acids have been shown to increase platelet
responsiveness to subtherapeutic anticoagulation therapies,
including aspirin. Recently, it was noted that patient re-
sponse to aspirin for anticoagulation therapy is widely vari-
able (45), and, thus, the number of patients with a low
response to aspirin or aspirin resistance is estimated to range
from <1% to 45%, depending on many variables. However,
in patients with stable coronary artery disease taking low-
dose aspirin, EPA+DHA supplementation has been proven
to be as effective as aspirin dose escalation to 325 mg/d
for anticoagulation benefits (45). The antiplatelet drug clo-
pidogrel has also been associated with hyporesponsiveness
in some patients. This could be attributed to poor patient
compliance, differences in genes and platelet reactivity, var-
iability of drug metabolism, and drug interactions. More im-
portantly, in 1 study, patients receiving standard dual
antiplatelet therapy (aspirin 75 mg/d and clopidogrel 600-mg
loading dose followed by 75 mg/d) were assigned to either
EPA+DHA supplementation or placebo. After 1 mo of treat-
ment, the P2Y
receptor reactivity index (an indicator of
clopidogrel resistance) was significantly lower, by 22%, for
patients taking EPA+DHA compared with patients taking
placebo (P= 0.020) (46).
Omega-3 fatty acids and AD
AD is a devastating disease for which there are limited treat-
ment options and no cure. Memory loss is an early indicator
of the disease, which is progressive, and leads to the inability
of the patient to care for him- or herself and eventually to
death (47). Currently, the number of individuals with AD
is estimated to be 26.6 million and is expected to increase
to 106.2 million by 2050 (48). There have been many studies
conducted regarding the use of omega-3 fatty acid supple-
mentation and AD (Table 2). DHA is present in large
amounts in neuron membrane phospholipids, where it is in-
volved in proper function of the nervous system, which is
why it is thought to play a role in AD (49). A case-control
study consisting of 148 patients with cognitive impairment
[Mini-Mental State Examination (MMSE) score <24] and
45 control patients (MMSE score $24) showed that serum
cholesteryl ester-EPA and -DHA levels were significantly
lower (P< 0.05 and P< 0.001, respectively) in all MMSE
score quartiles of patients with AD compared with control
values (49). Another study found that a diet characterized
by higher intakes of foods high in omega-3 fatty acids (salad
dressing, nuts, fish, tomatoes, poultry, cruciferous vegeta-
bles, fruits, dark and green leafy vegetables), and a lower in-
take of foods low in omega-3 fatty acids (high-fat dairy
products, red meat, organ meat, butter) was strongly associ-
ated with a lower AD risk (50). Image analysis of brain sec-
tions of an aged AD mouse model showed that overall
plaque burden was significantly reduced by 40.3% in mice
with a diet enriched with DHA (P< 0.05) compared with
placebo. The largest reductions (4050%) were seen in brain
regions that are thought to be involved with AD, the hippo-
campus and parietal cortex (51). A central event in AD is
thought to be the activation of multiple inflammatory cells
in the brain. Release of IL-1B, IL-6, and TNF afrom mi-
croglia cells may lead to dysfunction of the neurons in the
brain (52). In 1 study, AD patients treated with EPA
+DHA supplementation increased their plasma concentra-
tions of EPA and DHA, which were associated with reduced
release of inflammatory factors IL-1B, IL-6, and granulocyte
colonystimulating factor from peripheral blood mononu-
clear cells (53).
Unintended weight loss is a problem that many patients
with AD may face, and EPA+DHA supplementation has
had a positive effect on weight gain in patients with AD.
In a study using EPA+DHA supplementation, patients
weight significantly increased by 0.7 kg in the EPA+DHA
treatment group at 6 mo (P= 0.02) and by 1.4 kg at 12
mo (P< 0.001) and was observed mainly in patients with
a BMI <23 at the study start (54). This means that those pa-
tients with a lower BMI preferentially gained weight com-
pared with those patients already with a higher BMI.
Although results from studies regarding the disease pro-
cesses of AD seem to be promising, there are conicting data
regarding the use of omega-3 fatty acids in terms of cognitive
4 Swanson et al.
function. Neuropsychiatric symptoms accompany AD from
early stages and tend to increase with the progression of the
disease (55). An analysis of 174 patients randomized to a
placebo group or to a group with mild to moderate AD
(MMSE score $15) treated with daily DHA (1.7 g) and
EPA (0.6 g) found that at 6 mo, the decline in cognitive func-
tion did not differ between the groups. Yet, in a subgroup
with very mild cognitive dysfunction (n= 32, MMSE score
>27), they observed a significant reduction in the MMSE de-
cline rate in the DHA+EPA-supplemented group compared
with the placebo group (47). Another study that looked at
DHA supplementation in individuals with mild to moderate
AD used the Alzheimers Disease Assessment ScaleCognitive
subscale, which evaluates cognitive function on a 70-point
scale in terms of memory, attention, language, orientation,
and praxis. This study found that DHA supplementation
had no beneficial effect on cognition during the 18-mo trial
period for the DHA group vs. placebo (56).
The omega-3 PUFA EPA and DHA are important through-
out life and are a dietary necessity found predominantly in
sh and sh-oil supplements. The omega-3 fatty acids
EPA and DHA are essential for proper fetal development,
and supplementation during pregnancy has also been linked
to decreased immune responses in infants including de-
creased incidence of allergies in infants. Omega-3 fatty
acid consumption has been associated with improved cardi-
ovascular function in terms of antiinammatory properties,
PAD, reduced major coronary events, and improved anti-
platelet effects in the face of aspirin resistance or clopidogrel
hyporesponsiveness. Patients with AD have been shown to
be decient in DHA, and supplementing them with EPA
+DHA not only reverses this deciency, but may also im-
prove cognitive functioning in patients with very mild AD.
With increasing rates of pediatric allergies, cardiovascular
disease, and AD in the United States, EPA and DHA may
be a safe and inexpensive link to a healthier life. Further re-
search should be conducted in humans to assess a variety of
clinical outcomes including quality of life and mental status.
In addition, because potent lipid mediator metabolites of
EPA and DHA are of great interest currently, their inuence
on these important outcomes should be assessed because
current evidence suggests that their antiinammatory and
tissue-protective effects are nearly 1000 times greater than
those of EPA and DHA (7).
Thanks to Dr. Kelly A. Keating (Pharmaceutical Research In-
stitute at Albany College of Pharmacy and Health Sciences)
for her outstanding editorial support. All authors have read
and approved the nal version of this manuscript.
Literature Cited
1. Su KP, Huang SY, Chiu TH, Huang KC, Huang CL, Chang HC, Pariante
CM. Omega-3 fatty acids for major depressive disorder during preg-
nancy: results from a randomized, double-blind, placebo-controlled
trial. J Clin Psychiatry. 2008;69:64451.
2. Lazzarin N, Vaquero E, Exacoustos C, Bertonotti E, Romanini ME,
Arduini D. Low-dose aspirin and omega-3 fatty acids improve uterine
artery blood flow velocity in women with recurrent miscarriage due to
impaired uterine perfusion. Fertil Steril. 2009;92:296300.
3. Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie
MJ, Mittendorfer B. Dietary omega-3 fatty acid supplementation
TABLE 2. Studies involving omega-3 fatty acid supplementation and Alzheimers disease
Study Design No. of patients
Omega-3 fatty acids
assessed and amounts Major nding
Omega AD study,
Freund-Levi et al. (47)
DHA (1.7 g/d) and
EPA (0.6 g/d)
Decline in cognitive function did
not differ between supplemented
group and placebo group at 6 mo.
However, patients with very mild
cognitive dysfunction (n= 32, MMSE
score .27) in the EPA+DHA-supplemented
group had a significant reduction in MMSE
score decline rate at 6 mo
Omega AD study,
Vedin et al. (53)
first subjects to be
randomized in the
Omega AD Study
DHA (1.7 g/d) and
EPA (0.6 g/d)
Supplementation was associated with
decreased levels of IL-1b, IL-6, and granulocyte
colonystimulating factor from peripheral
blood mononuclear cells at 6 mo
Omega AD study,
Irving et al. (54)
DHA (1.7 g/d) and
EPA (0.6 g/d) for 6 mo,
then for all subjects
group and placebo
Supplementation was associated with positive
weight gain and appetite in supplementation
group at 6 mo, but not in the placebo group,
and for both groups at 12 mo
Omega AD study,
Quinn et al. (56)
295; mild to moderate
AD (MMSE score 1426)
supplementation group
(n= 171), placebo group
(n= 124)
DHA (2 g/d for
18 mo)
DHA supplementation led to no benecial
effect on rate of cognitive and functional
Subjects in the Omega AD study were patients with mild to moderate AD (n= 89) with acetylcholine esterase inhibitor use and an MMSE score between 15 and 30 and a
placebo group (n= 85). Supplementation was for 12 mo; the placebo group was started on supplementation after 6 mo. AD, Alzheimers disease; MMSE, Mini-Mental State
Health benets of omega-3 fatty acids 5
increases the rate of muscle protein synthesis in older adults: a random-
ized controlled trial. Am J Clin Nutr. 2011;93:40212.
4. Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Fatty acid
analysis of blood plasma of patients with Alzheimers disease, other
types of dementia, and cognitive impairment. Lipids. 2000;35:130512.
5. Dunstan JA, Mitoulas LR, Dixon G, Doherty DA, Hartmann PE, Simmer
K, Prescott SL. The effects of fish oil supplementation in pregnancy on
breast milk fatty acid composition over the course of lactation: a ran-
domized controlled trial. Pediatr Res. 2007;62:68994.
6. Krauss-Etschmann S, Shadid R, Campoy C, Hoster E, Demmelmair H,
Jimenez M, Gil A, Rivero M, Veszpremi B, Decsi T, et al. Effects of fish-
oil and folate supplementation of pregnant women on maternal and
fetal plasma concentrations of docosahexaenoic acid and eicosapentae-
noic acid: a European randomized multicenter trial. Am J Clin Nutr.
7. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual
anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immu-
nol. 2008;8:34961.
8. Neff LM, Culiner J, Cunningham-Rundles S, Seidman C, Meehan D,
Maturi J, Wittkowski KM, Levine B, Breslow JL. Algal docosahexaenoic
acid affects plasma lipoprotein particle size distribution in overweight
and obese adults. J Nutr. 2011;141:20713.
Huang SY. The effects of omega-3 fatty acids monotherapy in Alzheimers
disease and mild cognitive impairment: a preliminary randomized double-
blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychi-
atry. 2008;32:153844.
10. Goyens PL, Spilker ME, Zock PL, Katan MB, Mensink RP. Compartmen-
tal modeling to quantify alpha-linolenic acid conversion after longer term
intake of multiple tracer boluses. J Lipid Res. 2005;46:147483.
11. Hussein N, Ah-Sing E, Wilkinson P, Leach C, Griffin BA, Millward DJ.
Long-chain conversion of [13C]linoleic acid and alpha-linolenic acid in
response to marked changes in their dietary intake in men. J Lipid Res.
12. Dietary Guidelines for Americans. 2010. Washington, DC: U.S. Gov-
ernment Printing Office.
13. Dangardt F, Osika W, Chen Y, Nilsson U, Gan LM, Gronowitz E,
Strandvik B, Friberg P. Omega-3 fatty acid supplementation improves
vascular function and reduces inflammation in obese adolescents. Ath-
erosclerosis. 2010;212:5805.
14. Leaf DA, Hatcher L. The effect of lean fish consumption on triglyceride
levels. Phys Sportsmed. 2009;37:3743.
15. Mann NJ, OConnell SL, Baldwin KM, Singh I, Meyer BJ. Effects of seal
oil and tuna-fish oil on platelet parameters and plasma lipid levels in
healthy subjects. Lipids. 2010;45:66981.
16. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa
Y, Oikawa S, Sasaki J, Hishida H, Itakura H, et al. Effects of EPA on cor-
onary artery disease in hypercholesterolemic patients with multiple risk
factors: sub-analysis of primary prevention cases from the Japan EPA
Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200:13540.
17. Ramakrishnan U, Stein AD, Parra-Cabrera S, Wang M, Imhoff-Kunsch
B, Juarez-Marquez S, Rivera J, Martorell R. Effects of docosahexaenoic
acid supplementation during pregnancy on gestational age and size at
birth: randomized, double-blind, placebo-controlled trial in Mexico.
Food Nutr Bull. 2010;31:S10816.
18. Helland IB, Smith L, Blomen B, Saarem K, Saugstad OD, Drevon CA.
Effect of supplementing pregnant and lactating mothers with n-3 very-
long-chain fatty acids on childrens IQ and body mass index at 7 years
of age. Pediatrics. 2008;122:e4729.
19. Dunstan JA, Simmer K, Dixon G, Prescott SL. Cognitive assessment of
children at age 2(1/2) years after maternal fish oil supplementation in
pregnancy: a randomised controlled trial. Arch Dis Child Fetal Neona-
tal Ed. 2008;93:F4550.
20. Judge MP, Harel O, Lammi-Keefe CJ. Maternal consumption of a do-
cosahexaenoic acid-containing functional food during pregnancy: ben-
efit for infant performance on problem-solving but not on recognition
memory tasks at age 9 mo. Am J Clin Nutr. 2007;85:15727.
21. Olsen SF, Osterdal ML, Salvig JD, Mortensen LM, Rytter D, Secher NJ,
Henriksen TB. Fish oil intake compared with olive oil intake in late preg-
nancy and asthma in the offspring: 16 y of registry-based follow-up from
a randomized controlled trial. Am J Clin Nutr. 2008;88:16775.
22. Harper M, Thom E, Klebanoff MA, Thorp J, Jr., Sorokin Y, Varner MW,
Wapner RJ, Caritis SN, Iams JD, Carpenter MW, et al. Omega-3 fatty
acid supplementation to prevent recurrent preterm birth: a randomized
controlled trial. Obstet Gynecol. 2010;115:23442.
23. Olsen SF, Osterdal ML, Salvig JD, Weber T, Tabor A, Secher NJ. Dura-
tion of pregnancy in relation to fish oil supplementation and habitual
fish intake: a randomised clinical trial with fish oil. Eur J Clin Nutr.
24. Roman AS, Schreher J, Mackenzie AP, Nathanielsz PW. Omega-3 fatty
acids and decidual cell prostaglandin production in response to the in-
flammatory cytokine IL-1beta. Am J Obstet Gynecol. 2006;195:16939.
25. Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, Ryan P.
Effect of DHA supplementation during pregnancy on maternal depres-
sion and neurodevelopment of young children: a randomized con-
trolled trial. JAMA. 2010;304:167583.
26. Krauss-Etschmann S, Hartl D, Rzehak P, Heinrich J, Shadid R, Del
Carmen Ramirez-Tortosa M, Campoy C, Pardillo S, Schendel DJ, Decsi
T, et al. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-
beta levels after fish oil supplementation of pregnant women. J Allergy
Clin Immunol. 2008;121:46470 e6.
27. Furuhjelm C, Warstedt K, Larsson J, Fredriksson M, Bottcher MF,
Falth-Magnusson K, Duchen K. Fish oil supplementation in pregnancy
and lactation may decrease the risk of infant allergy. Acta Paediatr.
28. Kelley DS, Siegel D, Fedor DM, Adkins Y, Mackey BE. DHA supple-
mentation decreases serum C-reactive protein and other markers of in-
flammation in hypertriglyceridemic men. J Nutr. 2009;139:495501.
29. Schubert R, Kitz R, Beermann C, Rose MA, Baer PC, Zielen S, Boehles
H. Influence of low-dose polyunsaturated fatty acids supplementation
on the inflammatory response of healthy adults. Nutrition. 2007;23:
30. Bloomer RJ, Larson DE, Fisher-Wellman KH, Galpin AJ, Schilling BK.
Effect of eicosapentaenoic and docosahexaenoic acid on resting and
exercise-induced inflammatory and oxidative stress biomarkers: a ran-
domized, placebo controlled, cross-over study. Lipids Health Dis. 2009;
31. Bouwens M, van de Rest O, Dellschaft N, Bromhaar MG, de Groot LC,
Geleijnse JM, Muller M, Afman LA. Fish-oil supplementation induces
antiinflammatory gene expression profiles in human blood mononu-
clear cells. Am J Clin Nutr. 2009;90:41524.
32. Micallef MA, Garg ML. Anti-inflammatory and cardioprotective effects
of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic
individuals. Atherosclerosis. 2009;204:47682.
33. Ebrahimi M, Ghayour-Mobarhan M, Rezaiean S, Hoseini M, Parizade
SM, Farhoudi F, Hosseininezhad SJ, Tavallaei S, Vejdani A, Azimi-
Nezhad M, et al. Omega-3 fatty acid supplements improve the cardio-
vascular risk profile of subjects with metabolic syndrome, including
markers of inflammation and auto-immunity. Acta Cardiol. 2009;64:
34. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil,
omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;
35. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R,
Lucci D, Nicolosi GL, Porcu M, Tognoni G. Effect of n-3 polyunsatu-
rated fatty acids in patients with chronic heart failure (the GISSI-HF
trial): a randomised, double-blind, placebo-controlled trial. Lancet.
36. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R,
Franzosi MG, Geraci E, Levantesi G, Maggioni AP, et al. Early protec-
tion against sudden death by n-3 polyunsaturated fatty acids after my-
ocardial infarction: time-course analysis of the results of the Gruppo
Italiano per lo Studio della Sopravvivenza nellInfarto Miocardico (GIS-
SI)-Prevenzione. Circulation. 2002;105:1897903.
6 Swanson et al.
37. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa
Y, Oikawa S, Sasaki J, Hishida H, Itakura H, et al. Effects of eicosapen-
taenoic acid on major coronary events in hypercholesterolaemic pa-
tients (JELIS): a randomised open-label, blinded endpoint analysis.
Lancet. 2007;369:10908.
38. Oikawa S, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito
Y, Ishikawa Y, Sasaki J, Hishida H, Itakura H, et al. Suppressive effect of
EPA on the incidence of coronary events in hypercholesterolemia with
impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid In-
tervention Study (JELIS). Atherosclerosis. 2009;206:5359.
39. Kromhout D, Giltay EJ, Geleijnse JM. n-3 fatty acids and cardiovascular
events after myocardial infarction. N Engl J Med. 2010;363:201526.
40. Rauch B, Schiele R, Schneider S, Diller F, Victor N, Gohlke H, Gottwik
M, Steinbeck G, Del Castillo U, Sack R, et al. OMEGA, a randomized,
placebo-controlled trial to test the effect of highly purified omega-3
fatty acids on top of modern guideline-adjusted therapy after myocar-
dial infarction. Circulation. 2010;122:21529.
41. Dawczynski C, Martin L, Wagner A, Jahreis G. n-3 LC-PUFA-enriched
dairy products are able to reduce cardiovascular risk factors: a double-
blind, cross-over study. Clin Nutr. 2010;29:5929.
42. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ,
Gudmundsen O, Vige R, Payne SP, Ye S, et al. Eicosapentaenoic acid
(EPA) from highly concentrated n-3 fatty acid ethyl esters is incorpo-
rated into advanced atherosclerotic plaques and higher plaque EPA is
associated with decreased plaque inflammation and increased stability.
Atherosclerosis. 2010;212:2529.
43. Schiano V, Laurenzano E, Brevetti G, De Maio JI, Lanero S, Scopacasa
F, Chiariello M. Omega-3 polyunsaturated fatty acid in peripheral arte-
rial disease: effect on lipid pattern, disease severity, inflammation pro-
file, and endothelial function. Clin Nutr. 2008;27:2417.
44. Ishikawa Y, Yokoyama M, Saito Y, Matsuzaki M, Origasa H, Oikawa S,
Sasaki J, Hishida H, Itakura H, Kita T, et al. Preventive effects of eico-
sapentaenoic acid on coronary artery disease in patients with peripheral
artery disease. Circ J. 2010;74:14517.
45. Lev EI, Solodky A, Harel N, Mager A, Brosh D, Assali A, Roller M,
Battler A, Kleiman NS, Kornowski R. Treatment of aspirin-resistant pa-
tients with omega-3 fatty acids versus aspirin dose escalation. J Am Coll
Cardiol. 2010;55:11421.
46. Gajos G, Rostoff P, Undas A, Piwowarska W. Effects of polyunsaturated
omega-3 fatty acids on responsiveness to dual antiplatelet therapy in pa-
tients undergoing percutaneous coronary intervention: the OMEGA-PCI
(OMEGA-3 fatty acids after pci to modify responsiveness to dual anti-
platelet therapy) study. J Am Coll Cardiol. 2010;55:16718.
47. Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-
Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J.
Omega-3 fatty acid treatment in 174 patients with mild to moderate
Alzheimer disease: OmegAD study: a randomized double-blind trial.
Arch Neurol. 2006;63:14028.
48. Gillette-Guyonnet S, Andrieu S, Dantoine T, Dartigues JF, Touchon J,
Vellas B. Commentary on "A roadmap for the prevention of dementia
II. Leon Thal Symposium 2008." The Multidomain Alzheimer Preven-
tive Trial (MAPT): a new approach to the prevention of Alzheimers
disease. Alzheimers Dement. 2009;5:11421.
49. Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, Coakley D,
Gibney MJ. Low serum cholesteryl ester-docosahexaenoic acid levels in
Alzheimers disease: a case-control study. Br J Nutr. 2003;89:4839.
50. Gu Y, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N. Food combina-
tion and Alzheimer disease risk: a protective diet. Arch Neurol. 2010;
51. Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N, Jr.,
Frautschy SA, Cole GM. A diet enriched with the omega-3 fatty acid
docosahexaenoic acid reduces amyloid burden in an aged Alzheimer
mouse model. J Neurosci. 2005;25:303240.
52. Freund-Levi Y, Hjorth E, Lindberg C, Cederholm T, Faxen-Irving G,
Vedin I, Palmblad J, Wahlund LO, Schultzberg M, Basun H, et al. Ef-
fects of omega-3 fatty acids on inflammatory markers in cerebrospinal
fluid and plasma in Alzheimers disease: the OmegAD study. Dement
Geriatr Cogn Disord. 2009;27:48190.
53. Vedin I, Cederholm T, Freund Levi Y, Basun H, Garlind A, Faxen Irving
G, Jonhagen ME, Vessby B, Wahlund LO, Palmblad J. Effects of doco-
sahexaenoic acid-rich n-3 fatty acid supplementation on cytokine re-
lease from blood mononuclear leukocytes: the OmegAD study. Am J
Clin Nutr. 2008;87:161622.
54. Irving GF, Freund-Levi Y, Eriksdotter-Jonhagen M, Basun H, Brismar
K, Hjorth E, Palmblad J, Vessby B, Vedin I, Wahlund LO, et al.
Omega-3 fatty acid supplementation effects on weight and appetite
in patients with Alzheimers disease: the omega-3 Alzheimers disease
study. J Am Geriatr Soc. 2009;57:117.
55. Freund-Levi Y, Basun H, Cederholm T, Faxen-Irving G, Garlind A, Grut
M, Vedin I, Palmblad J, Wahlund LO, Eriksdotter-Jonhagen M. Omega-3
supplementation in mild to moderate Alzheimers disease: effects on neu-
ropsychiatric symptoms. Int J Geriatr Psychiatry. 2008;23:1619.
56. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van
Dyck C, Galvin JE, Emond J, Jack CR, Jr., Weiner M, et al. Docosahex-
aenoic acid supplementation and cognitive decline in Alzheimer dis-
ease: a randomized trial. JAMA. 2010;304:190311.
Health benets of omega-3 fatty acids 7
... DHA is transported across the maternal placenta to the fetus, and the amount depends on the content of this acid in the pregnant woman's diet, which is why meeting the requirement for this EFA plays such an important role in the nutrition of mothers-to-be [10,12,13]. Adequate intake or supplementation of DHA during pregnancy results in a high content of this acid in the brain and retina, which in turn influences the adequate maturation of the nervous system, the development of behavioral, cognitive, and speech functions, and higher ocular coordination scores in infants and young children [14]. DHA, together with EPA, influences adequate surfactant synthesis, which, when deficient, can lead to acute respiratory failure in preterm infants [13]. ...
... Ensuring an optimal supply and availability of DHA in the mother-to-be's diet has a great impact on prolonging the duration of pregnancy, which is protective against the occurrence of preterm birth, and on increasing the birth weight of the newborn, without increasing the risk of macrosomia [12,14,16]. A study in which 800 mg of DHA per day was given to pregnant women showed a significant increase in the duration of pregnancy and the birth weight of the baby [17], while the same effect was already achieved with lower doses of this acid [18]. ...
... Meeting the need for adequate amounts of DHA is extremely important during pregnancy. Sufficient accumulation of this acid in the brain and retina influences the normal development of the nervous system,and behavioural functions, enhances fetal immunity, as well as protects against the occurrence of preterm birth and increases the birth weight of the newborn [13,14,15,16,51] Given the great importance of DHA and EPA during pregnancy, according to the National Centre for Nutrition Education [4], pregnant women should take 250 mg/day of DHA + EPA, as recommended for adults + an additional 100-200 mg/day of DHA to ensure adequate concentration of these acids in the mother's body and optimal distribution to the foetus. According to the position of the Polish Group of Experts [6], pregnant women should supplement DHA in the amount of at least 200 mg per day, and in the case of low fish consumption, provide a supplementation dose of 400-600 mg DHA/day. ...
Full-text available
Background: Polyunsaturated fatty acids, essential for the human body, have several positive functions that affect human health. Pregnancy is a time of particular demand for these acids, especially DHA and EPA, whose sources are mainly oily marine fish. The supply of adequate amounts of these acids conditions the proper development of the fetus, influencing, among other things, the formation of the central nervous system and the development of the child's retina, as well as protecting against premature birth and increasing the child's birth weight. The aim of the study was to assess the frequency of consumption of fish, vegetable oils, and products rich in polyunsaturated fatty acids and evaluate DHA supplementation by pregnant women, as well as to assess knowledge of PFAs, especially DHA and EPA. Material and methods: 210 pregnant women were included in the study. A self-administered and online survey questionnaires were used as the research tool. A database was created using Microsoft Excel. Results: According to the recommended amounts, 2-3 times a week, Marine fish was consumed by only 12.86% of the women surveyed. Regular consumption of ALA-rich products, such as flaxseed, was declared by 10 respondents, while 59.05% of the surveyed women did not consume it at all. The use of DHA acid supplementation during pregnancy was unequivocally declared by 58 women surveyed, representing only ¼ of the women surveyed. Conclusions: The dietary behavior of pregnant women related to fish consumption is not correct, the overall proportion of fish in the diet of the subjects does not cover the recommended amounts. Vegetable oils and products rich in PFAs are not consumed with adequate frequency by pregnant women. DHA supplementation by pregnant women, despite low fish consumption, is underestimated and at a very low level.
... All three studies did quantify eicosapentaenoic acid (EPA) at proportions ranging from 17 to 52%, with the wide variation due to the type of sample evaluated; the lowest EPA proportion was found in the sample consisting of only viscera. As an omega-3 FA, EPA is well-known for its role in prevention of cardiovascular disease [14], while 12-MTA has been shown to have anti-inflammatory, anti-cancer and wound healing activity [15]. Thus, C. frondosa viscera lipids may contain a number of important bioactive components. ...
The sea cucumber, Cucumaria frondosa, is harvested primarily for its muscular bands and body wall. Development of a nutraceutical product based on lipid recovered from its viscera would give commercial value to the entire organism; however, such development requires knowledge of the lipid and fatty acid (FA) profiles of the viscera. Here, we describe the lipid and FA composition of viscera recovered from C. frondosa harvested in coastal waters in the northwest Atlantic, taking into account variation due to harvest season. We found highest lipid content at ~29% in winter, with diacylglyceryl ethers (DAGE) comprising ~55% of the total lipid mass and triacylglycerols (TAG), phospholipids (PL) and monoacylglycerol ethers (MAGE) at 5-25% each. The branched chain FA, 12-methyltetradecanoic acid (12-MTA), represented 42% of total FA mass in DAGE. In summer, lipid content was lower at 24% and TAG was the dominate lipid, with proportions more than double that found in winter (45% vs. 20%); DAGE in summer dropped to ~30% of total lipids. In TAG, 12-MTA was much lower than found in DAGE in winter, at only 10% but eicosapentaenoic acid (EPA) content was ~20%, which brought the total EPA% to 28% of total FA-the highest among all three seasons. There was little effect of season on MAGE or PL proportions. These data can help harvesters maximize catch efforts in terms of lipid yield and profile.
... Among the ω3 PUFAs, great attention has been accorded to DHA and EPA values in view of their beneficial health effects. Thus, clinical and epidemiological studies have associated EPA consumption with low prevalence of coronary, circulatory, and inflammatory diseases [48], whereas DHA has been related to foetal development, prevention of neurodegenerative diseases, and correct functioning of the nervous system and visual organs in the foetus [49]. In the present study, a comparison between traditional lipid extracts of initial by-products and lyophilised by-products showed that the lyophilisation process led to an average value increase for both PUFA compounds; such increase was found significant (p < 0.05) for DHA (Table 2). ...
Full-text available
A novel approach of bioactive lipid extraction by different green solvents was carried out on squid (Doryteuthis gahi) by-products. By-products (viscera, heads, skin, tails, etc.), considered as a single product, were subjected to the following solvent systems: ethanol, acetone, ethyl acetate, 1/1 ethanol/acetone, 1/1 ethanol/ethyl acetate, and 1/1 acetone/ethyl acetate. Analyses carried out included lipid yield, lipid class content, and fatty acid (FA) composition. Results were compared to the lipid extract obtained by the traditional procedure (1/1 chloroform/methanol). Lipid yields obtained by green solvents led to a 33.4–73.2% recovery compared to traditional extraction; the highest values (p < 0.05) were obtained by ethanol-containing systems. Compared to the traditional procedure, ethanol systems showed an 85.8–90.3% recovery of phospholipid compounds and no differences (p > 0.05) in the ω3/ω6 ratio. Green-extracting systems led to higher average values for eicosapentaenoic acid content (15.66–18.56 g·100 g−1 total FAs) and polyene index (1.93–3.29) than chloroform/methanol extraction; differences were significant (p < 0.05) for systems including acetone and ethyl acetate. No differences (p > 0.05) were detected for docosahexaenoic acid content between the traditional procedure and green systems, with all values being included in the 31.12–32.61 g·100 g−1 total FA range. The suitability of EtOH-containing green systems for extraction of bioactive lipid compounds from squid by-products was concluded.
... Their anti-inflammatory properties are associated with improvement of cardiovascular functions, which alters lipid metabolism, induces hemodynamic changes, decreases arrhythmias, improves endothelial function, and modulates platelet function [43,44]. EPA and DHA have also been studied in regard to Alzheimer's disease (AD), and they were shown to improve cognitive functioning in mild AD patients [45]. According to previous reports that fish oil containing omega-3 PUFAs exhibits UVB-protective effects [8,9], the extracts of different organs of N. rossii and C. gunnari were evaluated for their MMP-1-inhibitory activity, where all extracts showed inhibition against UVB-induced NHDF cells, with extracts of N. rossii skin and liver exhibiting the most significant inhibitory activity against MMP-1 compared to both the UVB-irradiated group and the normal group. ...
Full-text available
Total fatty-acid (FA) contents of different organs (stomach, liver, brain, and skin) of two Antarctic fish, marbled rockcod (Notothenia rossii) and mackerel icefish (Champsocephalus gunnari), were examined using gas chromatography–mass spectrometry (GC–MS). N. rossii possessed higher contents of total omega-3, where eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the most represented omega-3 FAs, were distributed throughout all parts of the fish. The highest level of EPA was observed in the skin and that of DHA was observed in the brain of N. rossii. C. gunnari showed organ peculiarity in that most of the omega-3 FAs were found in stomach and skin. Specifically, the highest levels of EPA and DHA were both observed in the stomach. Although N. rossii and C. gunnari both inhabit the Antarctic Southern Oceans, their characteristics in terms of the composition of fatty acids were shown to vary. The extracts were also evaluated for matrix metalloproteinase-1 (MMP-1)-inhibitory activities in UVB-induced human dermal fibroblasts, where extracts of the skin and liver of N. rossii showed the most significant inhibition upon MMP-1 production. These findings provide experimental evidence that the extracts of the Antarctic fish could be utilized as bioactive nutrients, particularly in the enhancement of skin health.
... Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are important components of ω-3 PUFAs, and they are also the most studied ω-3 PUFAs. ω-3 PUFAs have a certain role in preventing cardiovascular disease, adjusting inflammation, and improving nutritional status [4]. Mocellin et al.'s study showed that ω-3 PUFAs increased plasma albumin and prealbumin levels in gastric cancer patients [5]. ...
Full-text available
Background: Radiotherapy and chemotherapy in patients with lung cancer can lead to a series of problems such as malnutrition and inflammatory reaction. Some studies have shown that ω-3 polyunsaturated fatty acids (PUFAs) could improve malnutrition and regulate inflammatory reaction in these patients, but no relevant meta-analysis exists. Methods: We systematically searched randomized controlled trials of ω-3 PUFAs in the adjuvant treatment of lung cancer in the PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang databases. Relevant outcomes were extracted, and we pooled standardized mean differences (SMDs) using a random or fixed-effects model. The risk of bias was evaluated according to the Cochrane Handbook (version 15.1). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: A total of 7 studies were included. The SMDs (95% CI) of body weight change, albumin change, energy intake, and protein intake at the end of intervention were 1.15 (0.50, 1.80), 0.60 (0.11, 1.09), 0.39 (-0.10, 0.89), and 0.27 (-0.04, 0.58), respectively. The SMDs (95% CI) of CRP change and TNF-α change were -3.44 (-6.15, -0.73) and -1.63 (-2.53, -0.73), respectively. Conclusions: ω-3 PUFAs can improve nutritional status and regulate indicators of inflammation in patients with lung cancer undergoing radiotherapy and chemotherapy. This study was registered in the PROSPERO (registration number: CRD42022307699).
... PUFAs such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have numerous health benefits to humans and animals. DHA improves brain function by assisting neurons, promoting both short-and long-term memory, and facilitating the treatment of brain-related disorders, whereas EPA and DHA together aid in fetal development, inflammation prevention, and the treatment of cardiovascular illnesses [47]. Nowadays, marine fish such as salmon and cod are the foremost source of these bioactive compounds for human utilization. ...
Full-text available
Whole-cell microalgae biomass and their specific metabolites are excellent sources of renewable and alternative feedstock for various products. In most cases, the content and quality of whole-cell biomass or specific microalgal metabolites could be produced by both fresh and marine microalgae strains. However, a large water footprint for freshwater microalgae strain is a big concern, especially if the biomass is intended for non-food applications. Therefore, if any marine microalgae could produce biomass of desired quality, it would have a competitive edge over freshwater microalgae. Apart from biofuels, recently, microalgal biomass has gained considerable attention as food ingredients for both humans and animals and feedstock for different bulk chemicals. In this regard, several technologies are being developed to utilize marine microalgae in the production of food, feed, and biofuels. Nevertheless, the production of suitable and cheap biomass feedstock using marine microalgae has faced several challenges associated with cultivation and downstream processing. This review will explore the potential pathways, associated challenges, and future directions of developing marine microalgae biomass-based food, feed, and fuels (3F).
... Moreover, aquatic products, especially fish, are potential sources of nutritional components, polyunsaturated fatty acids, minerals, bioactive peptides, and vitamins (Prester, 2011;Strobel et al., 2012;Swanson et al., 2012). In addition, the fermented fish and aquatic products prepared via indigenous solid substrate fermentation process, which is either by native microflora or by addition of starter cultures, have been proven to demonstrate beneficial effect against metabolic disorders and diet-related risks. ...
Fermented fish and other aquatic fermented products are unique in terms of nutritional value and sensory attributes, thereby holding a high demand around the globe. Based on the geological significance, Southeast Asia dominates various traditional fermented fish products compared to European countries owing to the availability of a wide range of raw materials. Generally, fermentation is known to have an important role in preserving nutrients, improving textural and flavor properties of fish. Primarily, this could depend on the types of fermentation methods (spontaneous and non-spontaneous) and quality of raw material employed. During fermentation, the enzyme activity influenced by the interaction of various native or selective microflora has been correlated to generate diversified bioactive compounds. Some of these compounds are known to exhibit numerous health benefits and are termed “bioactive compounds.” In addition, these bioactive compounds are known to show a protective or preventive role against various diseases. Concerning this, the present chapter aims to provide information on fermented fish and other aquatic fermented products based on the geographic distribution, their traditional significance and types of fermentation processes, microbiome involved, bioactive compounds pertaining fermentation process, and various health benefits such as antioxidant, antidiabetic, anticancer properties, etc.
Obesity is a main risk factor for the onset and the precipitation of many non-communicable diseases. This condition, which is associated with low-grade chronic systemic inflammation, is of main concern during pregnancy leading to very serious consequences for the new generations. In addition to the prominent role played by the adipose tissue, dysbiosis of the maternal gut may also sustain the obesity-related inflammatory milieu contributing to create an overall suboptimal intrauterine environment. Such a condition here generically defined as “inflamed womb” may hold long-term detrimental effects on fetal brain development, increasing the vulnerability to mental disorders. In this review, we will examine the hypothesis that maternal obesity-related gut dysbiosis and the associated inflammation might specifically target fetal brain microglia, the resident brain immune macrophages, altering neurodevelopmental trajectories in a sex-dependent fashion. We will also review some of the most promising nutritional strategies capable to prevent or counteract the effects of maternal obesity through the modulation of inflammation and oxidative stress or by targeting the maternal microbiota.
Full-text available
Today, the world population is aging at a fast rate. This scenario of the accelerated aging of human populations entails increased concern for healthy aging that is associated with a rise in scientific production related to the topic. In this study, the Scopus database from Elsevier was used, with a final search carried out on 5 January 2022, and various bibliometric indicators were obtained from SciVal. The study was fundamentally intended to characterize, determine trends, and understand the evolution and current state of research on the concept of “healthy aging” in the last decade. We found that there has been proportionally greater and more accelerated growth in the subject with respect to the general productivity of the world and that countries with high life expectancies tend to have made more effort to investigate this topic. The “hottest” research areas were found to be related to the cognitive aspect and the biological mechanisms involved in aging.
In this study, five plant matrices (pea, mung bean, lentils, soy and sunflower) were fermented using Bacillus subtilis var. natto. Then the process influence on the content of fatty acids and proteins was evaluated, depending on the fermentation length. Fermentation was conducted for 144 hours in controlled conditions of temperature and relative humidity (37°C, 75%). Samples for tests were collected every 24 hours. Gas chromatography coupled with triple quadrupole tandem mass spectrometry (GC-MS/MS) was used to evaluate fatty acids content in fermented seeds. Their composition was expressed as a percentage of the total quantity of fatty acids. The protein content in plant matrices was analysed with the modified Bradford protein assay, using the TECAN apparatus with the i-Control software, of the wave length of ʎ=595 nm. Studies showed that the prolonged fermentation time influenced an increase of polyunsaturated fatty acids (PUFA) content in all studied seeds. Promising results were obtained for soy, sunflower, and lentil seeds, amounting to 3.6%; 68.7% and 67.7%, respectively. This proves that the process of seed fermentation can be effectively used to increase their nutritional value.
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Fish are a rich source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two long-chain polyunsaturated n-3 fatty acids (LC n-3 PUFA) with cardiovascular benefits. A related but less-investigated LC n-3 PUFA, docosapentaenoic acid (DPA), is more common in seal oil and pasture-fed red meats. This study compared indicators of platelet function and plasma lipids in healthy volunteers given supplements containing these different fatty acids (FA) for 14days. Subjects, randomised into three groups of ten, consumed capsules of tuna oil (210mg EPA, 30mg DPA, 810mg DHA), seal oil (340mg EPA, 230mg DPA, 450mg DHA) or placebo (sunola) oil. Supplementary LC n-3 PUFA levels were approximately 1g/day in both fish and seal oil groups. Baseline dietary FA and other nutrient intakes were similar in all groups. Both fish and seal oil elevated platelet DHA levels (P<0.01). Seal oil also raised platelet DPA and EPA levels (P<0.01), and decreased p-selectin (P=0.01), a platelet activation marker negatively associated with DPA (P=0.03) and EPA (P<0.01) but not DHA. Plasma triacylglycerol decreased (P=0.03) and HDL-cholesterol levels increased (P=0.01) with seal oil only. Hence, seal oil may be more efficient than fish oil at promoting healthy plasma lipid profiles and lowering thrombotic risk, possibly due to its high DPA as well as EPA content. KeywordsDocosapentaenoic acid-Omega-3 polyunsaturated fatty acids-Cardiovascular disease-Triacylglycerols-Platelet activation-P-selectin
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Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease. We aimed to test the hypothesis that long-term use of eicosapentaenoic acid (EPA) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish. 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999. Patients were randomly assigned to receive either 1800 mg of EPA daily with statin (EPA group; n=9326) or statin only (controls; n=9319) with a 5-year follow-up. The primary endpoint was any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. Analysis was by intention-to-treat. The study was registered at, number NCT00231738. At mean follow-up of 4.6 years, we detected the primary endpoint in 262 (2.8%) patients in the EPA group and 324 (3.5%) in controls-a 19% relative reduction in major coronary events (p=0.011). Post-treatment LDL cholesterol concentrations decreased 25%, from 4.7 mmol/L in both groups. Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events. Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group. Sudden cardiac death and coronary death did not differ between groups. In patients with a history of coronary artery disease who were given EPA treatment, major coronary events were reduced by 19% (secondary prevention subgroup: 158 [8.7%] in the EPA group vs 197 [10.7%] in the control group; p=0.048). In patients with no history of coronary artery disease, EPA treatment reduced major coronary events by 18%, but this finding was not significant (104 [1.4%] in the EPA group vs 127 [1.7%] in the control group; p=0.132). EPA is a promising treatment for prevention of major coronary events, and especially non-fatal coronary events, in Japanese hypercholesterolaemic patients.
Although several epidemiological studies have reported that higher intake of n-3 long-chain polyunsaturated fatty acids during pregnancy is associated with both a reduced risk of postpartum depression and improved neurodevelopmental outcomes in offspring, the results of other intervention trials have been inconsistent. Despite the uncertainty of benefit, there are now international recommendations for pregnant women to increase their intake of docosahexaenoic acid (DHA), the n-3 long-chain polyunsaturated fatty acids believed to be responsible for the improved outcomes. The DHA to Optimize Mother Infant Outcome (DOMINO) study was a double-blind, multicenter, randomized controlled trial designed primarily to determine whether DHA supplementation during the last half of pregnancy would reduce the risk of maternal postpartum depression and improve early neurodevelopmental outcome of offspring. The study subjects were 2399 women with singleton pregnancies <21 weeks' gestation who were enrolled in 5 Australian maternity hospitals between 2005 and 2008, and 726 offspring who were followed up until 18 months of age. The women were randomly assigned to receive fish oil capsules providing 800 mg/d of DHA (n = 1197) or identical capsules without DHA (n = 1202). The level of postpartum depression was evaluated using a self-reported Edinburgh Postnatal Depression Scale (EPDS). A score >12 on the EPDS at 6 weeks or 6 months postpartum indicated a high level of depression. In the offspring, neurodevelopmental outcomes were compared at 18 months of age in the DHA group (n = 351) and the control group (n = 375) using the Cognitive and Language Composite Scales of the Bayley Scales of Infant and Toddler Development, Third Edition. More than 96% of the 2399 enrolled women completed the trial. There was no significant difference between the DHA and control groups in the percentage of women reporting high levels of depressive symptoms (EPDS score >12) at 6 weeks (DHA group: 9.6% vs. control group: 10.9%) or 6 months postpartum (9.7% vs. 11.5%); the adjusted relative risks were 0.87 (95% confidence interval [CI], 0.68–1.10; P = 0.24) and 0.83 (95% CI, 0.66–1.05; P = 0.11). Similarly, there was no significant difference between children in the DHA group and those in the control group with respect to mean cognitive scores (adjusted mean difference, 0.01; 95% CI, −1.36 to 1.37; P = 0.99) and mean language composite scores (adjusted mean difference, −1.42; 95% CI, −3.07 to 0.22; P = 0.09). These findings provide no support for routine supplementation with DHA in pregnant women, either to reduce symptoms of postpartum depression or to improve neurodevelopmental cognitive or language outcomes in early childhood.
Background-Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction. Methods and Results-In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths. Conclusions-The early effect of low-dose ( I g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.
Background Several epidemiological and experimental studies suggest that n-3 polyunsaturated fatty acids (PUFA) can exert favourable effects on atherothrombotic cardiovascular disease, including arrhythmias. We investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause. Methods We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients with chronic heart failure of New York Heart Association class II–IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to n-3 PUFA 1 g daily (n=3494) or placebo (n=3481) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3·9 years (IQR 3·0–4·5). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. This study is registered with, number NCT00336336. Findings We analysed all randomised patients. 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (adjusted hazard ratio [HR] 0·91 [95·5% CI 0·833–0·998], p=0·041). 1981 (57%) patients in the n-3 PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 0·92 [99% CI 0·849–0·999], p=0·009). In absolute terms, 56 patients needed to be treated for a median duration of 3·9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In both groups, gastrointestinal disorders were the most frequent adverse reaction (96 [3%] n-3 PUFA group vs 92 [3%] placebo group). Interpretation A simple and safe treatment with n-3 PUFA can provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure in a context of usual care. Funding Società Prodotti Antibiotici (SPA; Italy), Pfizer, Sigma Tau, and AstraZeneca.
Background: Perinatal depression is common, and treatment remains challenging. Depression has been reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs). A pro- found decrease of omega-3 PUFAs in the mother during pregnancy is associated with the higher demand of fetal development and might precipitate the occurrence of depression. In this study, we examined the efficacy of omega-3 PUFA monotherapy for the treatment of depression during pregnancy.
Since the first AHA Science Advisory “Fish Consumption, Fish Oil, Lipids, and Coronary Heart Disease,”1 important new findings, including evidence from randomized controlled trials (RCTs), have been reported about the beneficial effects of omega-3 (or n-3) fatty acids on cardiovascular disease (CVD) in patients with preexisting CVD as well as in healthy individuals.2 New information about how omega-3 fatty acids affect cardiac function (including antiarrhythmic effects), hemodynamics (cardiac mechanics), and arterial endothelial function have helped clarify potential mechanisms of action. The present Statement will address distinctions between plant-derived (α-linolenic acid, C18:3n-3) and marine-derived (eicosapentaenoic acid, C20:5n-3 [EPA] and docosahexaenoic acid, C22:6n-3 [DHA]) omega-3 fatty acids. (Unless otherwise noted, the term omega-3 fatty acids will refer to the latter.) Evidence from epidemiological studies and RCTs will be reviewed, and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid (plant- and marine-derived) supplementation. This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration (FDA) about the presence of environmental contaminants in certain species of fish. ### Coronary Heart Disease As reviewed by Stone,1 three prospective epidemiological studies within populations reported that men who ate at least some fish weekly had a lower coronary heart disease (CHD) mortality rate than that of men who ate none.3–6⇓⇓⇓ More recent evidence that fish consumption favorably affects CHD mortality, especially nonsudden death from myocardial infarction (MI), has been reported in a 30-year follow-up of the Chicago Western Electric Study.7 Men who consumed 35 g or more of fish daily compared with those who consumed none had a relative risk of death from CHD of 0.62 and a relative risk of nonsudden death from MI of 0.33. In an …