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Metabolic Effects of Krill Oil are Essentially Similar to Those of Fish Oil but at Lower Dose of EPA and DHA, in Healthy Volunteers

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The purpose of the present study is to investigate the effects of krill oil and fish oil on serum lipids and markers of oxidative stress and inflammation and to evaluate if different molecular forms, triacylglycerol and phospholipids, of omega-3 polyunsaturated fatty acids (PUFAs) influence the plasma level of EPA and DHA differently. One hundred thirteen subjects with normal or slightly elevated total blood cholesterol and/or triglyceride levels were randomized into three groups and given either six capsules of krill oil (N = 36; 3.0 g/day, EPA + DHA = 543 mg) or three capsules of fish oil (N = 40; 1.8 g/day, EPA + DHA = 864 mg) daily for 7 weeks. A third group did not receive any supplementation and served as controls (N = 37). A significant increase in plasma EPA, DHA, and DPA was observed in the subjects supplemented with n-3 PUFAs as compared with the controls, but there were no significant differences in the changes in any of the n-3 PUFAs between the fish oil and the krill oil groups. No statistically significant differences in changes in any of the serum lipids or the markers of oxidative stress and inflammation between the study groups were observed. Krill oil and fish oil thus represent comparable dietary sources of n-3 PUFAs, even if the EPA + DHA dose in the krill oil was 62.8% of that in the fish oil. Electronic supplementary material The online version of this article (doi:10.1007/s11745-010-3490-4) contains supplementary material, which is available to authorized users.
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ORIGINAL ARTICLE
Metabolic Effects of Krill Oil are Essentially Similar to Those
of Fish Oil but at Lower Dose of EPA and DHA, in Healthy
Volunteers
Stine M. Ulven Bente Kirkhus Amandine Lamglait
Samar Basu Elisabeth Elind Trond Haider
Kjetil Berge Hogne Vik Jan I. Pedersen
Received: 7 July 2010 / Accepted: 9 October 2010 / Published online: 2 November 2010
ÓThe Author(s) 2010. This article is published with open access at Springerlink.com
Abstract The purpose of the present study is to investi-
gate the effects of krill oil and fish oil on serum lipids and
markers of oxidative stress and inflammation and to eval-
uate if different molecular forms, triacylglycerol and
phospholipids, of omega-3 polyunsaturated fatty acids
(PUFAs) influence the plasma level of EPA and DHA
differently. One hundred thirteen subjects with normal or
slightly elevated total blood cholesterol and/or triglyceride
levels were randomized into three groups and given
either six capsules of krill oil (N=36; 3.0 g/day, EPA ?
DHA =543 mg) or three capsules of fish oil (N=40;
1.8 g/day, EPA ?DHA =864 mg) daily for 7 weeks. A
third group did not receive any supplementation and served
as controls (N=37). A significant increase in plasma
EPA, DHA, and DPA was observed in the subjects sup-
plemented with n-3 PUFAs as compared with the controls,
but there were no significant differences in the changes in
any of the n-3 PUFAs between the fish oil and the krill oil
groups. No statistically significant differences in changes in
any of the serum lipids or the markers of oxidative stress
and inflammation between the study groups were observed.
Krill oil and fish oil thus represent comparable dietary
sources of n-3 PUFAs, even if the EPA ?DHA dose in the
krill oil was 62.8% of that in the fish oil.
Keywords Plasma lipoproteins Plasma lipids Dietary
fat Nutrition, n-3 fatty acids Lipid absorption
Phospholipids
Abbreviations
EPA Eicosapentaenoic acid
DHA Docosahexaenoic acid
FA Fatty acid
PL Phospholipids
PUFA Polyunsaturated fatty acid
TG Triglycerides
Introduction
An association between consumption of fish and seafood
and beneficial effects on a variety of health outcomes has
been reported in epidemiologic studies and clinical trials
[15]. These effects are mainly attributed to the omega-3
Electronic supplementary material The online version of this
article (doi:10.1007/s11745-010-3490-4) contains supplementary
material, which is available to authorized users.
S. M. Ulven (&)E. Elind
Faculty of Health, Nutrition, and Management,
Akershus University College, 2001 Lillestrøm, Norway
e-mail: stinemarie.ulven@hiak.no
B. Kirkhus
Nofima Mat, A
˚s, Norway
A. Lamglait
Mills DA, Oslo, Norway
S. Basu
Department of Public Health and Caring Sciences,
Uppsala University, Uppsala, Sweden
T. Haider
Link Medical Research AS, Oslo, Norway
K. Berge H. Vik
Aker BioMarine ASA, Oslo, Norway
J. I. Pedersen
Department of Nutrition, Institute of Basic Medical Sciences,
University of Oslo, Oslo, Norway
123
Lipids (2011) 46:37–46
DOI 10.1007/s11745-010-3490-4
long-chain polyunsaturated fatty acids (n-3 PUFAs) abun-
dant in fish and seafood, and in particular to eicosapenta-
enoic acid (EPA) and docosahexaenoic acid (DHA). The
effects of marine n-3 PUFAs on various risk factors of
cardiovascular disease (CVD) are in particular well docu-
mented. In large systematic reviews of the available liter-
ature, consistent reductions in triglyceride (TG) levels
following consumption of n-3 PUFAs have been demon-
strated as well as increases in levels of high-density lipo-
protein (HDL) cholesterol [6,7]. The net beneficial
effects of these changes have been disputed, although
several large intervention studies indicate that n-3 PUFAs
reduce mortality in patients with high risk of developing
coronary heart disease (CHD) [8]. Moreover, guidelines
published by the American Heart Association for reduc-
ing CVD risk recommend fish consumption and fish oil
supplementation based on the acknowledgement that EPA
and DHA may decrease the risk of CHD, decrease sudden
deaths, decrease arrhythmias, and slightly lower blood
pressure [9].
Reports on health benefits have led to increased demand
for products containing marine n-3 PUFAs. Since fish is a
restricted resource, there is growing interest in exploiting
alternative sources of marine n-3 PUFAs. Antarctic krill
(Euphausia superba) is a rich source of n-3 PUFAs. Krill is
by far the most dominant member of the Antarctic zoo-
plankton community in terms of biomass, which is esti-
mated to be between 125 and 750 million metric tons
(according to the Food and Agriculture Organization of the
United Nations; http://www.fao.org/fishery/species/3393/
en), and thus attractive for commercial harvest. The DHA
content of krill oil is similar to that of oily fish, but the EPA
content is higher [10]. The overall fatty acid composition
resembles that of fish. In fish, the fatty acids are mainly
stored as TG, whereas in krill 30–65% of the fatty acids are
incorporated into phospholipids (PL) [10]. Whether being
esterified in TG or in PL impacts on the absorption effi-
ciency of FAs into the blood and on effects on serum lipid
levels are issues for discussion. In a study by Maki et al.
[11] comparing the absorption efficacy of n-3 PUFAs from
different sources it was shown that EPA and DHA from
krill oil were absorbed at least as efficiently as EPA and
DHA from menhaden oil (TG) [11], and studies in newborn
infants have indicated that fatty acids in dietary PL may be
better absorbed than those from TG [1214]. Studies
addressing the compartmental metabolism of dietary DHA
have indicated that the metabolic fate of DHA differs
substantially when ingested as TG compared with phos-
phatidylcholine, in terms of both bioavailability of DHA in
plasma and accumulation in target tissues [15]. Only a
limited number of studies addressing health outcomes
following ingestion of krill oil as compared with fish oil are
currently available, but some of these have shown
promising effects of krill oil on serum lipids and on
markers of inflammation and oxidative stress (reviewed in
[10]).
The aim of this study is to investigate the plasma levels
of EPA and DHA, and the effects on serum lipids and on
some biomarkers of inflammation, oxidative stress, and
hemostasis, after krill oil and fish oil administration
in healthy subjects after a 7-week intervention period.
Safety was evaluated based on assessment of hematology
and biochemistry parameters, and registration of adverse
events.
Experimental Procedures
Study Subjects
The 129 subjects included in the study were healthy vol-
unteers of both genders with normal or slightly elevated
total blood cholesterol (\7.5 mmol/L) and normal or
slightly elevated blood triglyceride level (\4.0 mmol/L).
Subjects with body mass index (BMI) [30 kg/m
2
, hyper-
lipidemia, hypertension, coronary, peripheral or cerebral
vascular disease were excluded from participating in the
study. No concomitant medication intended to influence
serum lipid level was permitted. All study subjects were
informed verbally and in writing, and all subjects signed an
informed consent form before entering the study. The study
was approved by the Regional Ethics Committee.
Study Design
The study was an open single-center, randomized, parallel
group designed study. Screening of subjects (N=149) was
performed at the first visit to include subjects that satisfied
the eligibility criteria (N=129). These were randomized
into three study groups. Seven participants were lost before
the baseline visit. The remaining 122 participants were
given either 3 g krill oil daily (N=41), 1.8 g fish oil daily
(N=40) or no supplementation (N=41) for a period of
7 weeks. A total of 115 participants finished the study. The
disposition of the subjects is illustrated in Fig. 1. None of
the subjects regularly ate fatty fish more than once a week
prior to inclusion or during the 7-week intervention period.
None were using cod liver oil or other marine n-3 sup-
plements during the study or at least 2 months prior to
inclusion. All the participants were instructed by a nutri-
tionist to keep their regular food habits during the study.
Study Products
The krill oil capsules contained processed krill oil extracted
from Antarctic krill (Euphausia superba). The product was
38 Lipids (2011) 46:37–46
123
manufactured by Aker BioMarine ASA. Each capsule
contained 500 mg oil that provided 90.5 mg EPA and
DHA, and a total of 103.5 mg n-3 PUFAs. The capsules
were made of gelatin softened with glycerol. The daily
study dosage was six capsules (each of 500 mg oil). The
comparator omega-3 fish oil product was manufactured by
Peter Mo
¨ller AS, Oslo, Norway. The daily study dosage
was three capsules each containing 600 mg fish oil that
provided 288 mg EPA and DHA, and a total of 330 mg n-3
PUFAs. The capsules were made of gelatin softened with
glycerol. The fatty acid profile of the study products is
presented in Table 1. The daily dose of EPA, DHA, and
total n-3 PUFAs in the krill oil and fish oil groups is pre-
sented in Table 2. The daily EPA ?DHA dose in the krill
oil group was 62.8% of the dosage given in the fish oil
group. DL-a-tocopheryl acetate (vitamin E), retinyl palmi-
tate (vitamin A), and cholecalciferol (vitamin D) were
added to the product.
Clinical Assessment
Demographic characteristics (gender, age, height, and
weight), concomitant medication, and medical history were
recorded at the screening visit. In addition, all subjects
went through a physical examination to confirm satisfac-
tion of the eligibility criteria.
Changes in concomitant medication from screening,
smoking and alcohol habits, and clinical symptoms before
intake of the study products were also registered.
Serum Lipids and Blood Safety Parameters
Blood from venipuncture was collected after an overnight
fast (C12 h) at baseline and at final visit. The subjects were
instructed to refrain from alcohol consumption and from
vigorous physical activity the day before the blood sam-
pling. Serum was obtained from silica gel tubes (BD
Vacutainer), kept at room temperature for at least 30 min
until centrifugation at 1,300 9gfor 12 min at room tem-
perature. Serum analysis of total, low-density lipoprotein
Assessed for eligibility (n=149)
Randomized (n=129)
Allocated to control (n=42)
Received allocated
intervention (n=41)
Allocated to krill oil (n=44)
Received allocated
intervention (n=41)
Completed the study (n=37)
Analyzed (n=37)
Excluded from analysis (n=0)
Analyzed (n=36)
Excluded from analysis (n=2)
Analyzed (n=40)
Excluded from analysis (n=0)
Completed the study (n=40)
Allocated to fish oil (n=43)
Received allocated
intervention (n=40)
Completed the study (n=38)
Fig. 1 Disposition of subjects
Table 1 Relative content of fatty acids in the study products
Fatty acid Fish oil (area %) Krill oil (area %)
14:0 3.2 7.4
16:0 7.8 21.8
18:0 2.6 1.3
20:0 0.6 \0.1
22:0 0.4 0.2
16:1n-7 3.9 5.4
18:1n-9, -7, -5 6.1 18.3
20:1n-9, -7 2.0 1.2
22:1n-11, -9, -7 2.5 0.8
24:1n-9 \0.2 0.2
16:2n-4 0.7 0.5
18:2n-6 0.8 1.8
18:3n-6 \0.2 0.2
20:2n-6 0.3 \0.1
20:3n-6 0.2 \0.1
20:4n-6 1.5 0.5
22:4n-6 0.5 \0.1
18:3n-3 0.5 1.0
18:4n-3 1.9 1.6
20:3n-3 \0.2 \0.1
20:4n-3 \0.2 0.7
20:5n-3 27.0 19.0
21:5n-3 1.5 0.5
22:5n-3 4.8 0.5
22:6n-3 24.0 10.9
Other FA 7.2 6.4
Saturated FA 16.0 30.7
Monounsaturated FA 18.0 25.9
n-3 59.0 34.1
n-6 2.9 2.5
Lipids (2011) 46:37–46 39
123
(LDL), and HDL-cholesterol, TG, apolipoprotein A1, and
apolipoprotein B was performed at the routine laboratory
at Department of Medical Biochemistry at the National
Hospital, Norway using standard methods. Blood samples
for analysis of hematology and serum biochemistry
parameters including hemoglobin, leukocytes, erythro-
cytes, thrombocytes, hematocrit, glucose, calcium, sodium,
potassium, urea, creatinine, alkaline phosphatase, alanine
aminotransferase, bilirubin, albumin, and total protein were
collected and analyzed at the routine laboratory at
Department of Medical Biochemistry at the National
Hospital, Norway using standard methods.
Plasma Fatty Acid Composition
Plasma was obtained from ethylenediamine tetraacetic acid
(EDTA) tubes (BD Vacutainer) kept on ice immediately
and within 12 min centrifuged at 1,300 9gfor 10 min at
10°C. Plasma samples were kept frozen at -80°C until
analysis. Plasma fatty acid composition was analyzed by
Jurilab Ltd., Finland using a slight modification of the
method of Nyyssonen et al. [16]. Plasma (250 lL), fatty
acids, and 25 lL internal standard (eicosane 1 mg/mL in
isopropanol) were extracted with 6 mL methanol–chloro-
form (1:2), and 1.5 mL water was added. The two phases
were separated by centrifugation, and the upper phase was
discarded. To the chloroform phase, 1 mL methanol–water
(1:1) was added, and this extraction was repeated twice.
The chloroform phase was evaporated under nitrogen. For
methylation, the remainder was treated with 1.5 mL sul-
furic acid–methanol (1:50) at 85°C for 2 h. The mixture
was diluted with 1.5 mL water and extracted with light
petroleum ether. The fatty acids from the ether phase were
determined using a gas chromatograph (Agilent Technol-
ogies 6890)/mass spectrometer (Agilent Technologies
5973) with electron impact ionization and a HP-5ms cap-
illary column (Hewlett Packard). For retention time and
quantitative standardization, fatty acids purchased from
Nu-Chek-Prep (Elysian, MN, USA) were used. All work
was carried out under a certified ISO 9001/2000 quality
system.
Plasma a-Tocopherol
Human plasma (100 lL) was diluted with 300 lL 2-pro-
panol containing the internal standard tocol and butylated
hydroxytoluene (BHT) as an antioxidant. After thorough
mixing (15 min) and centrifugation (10 min, 4,000 9gat
10°C), an aliquot of 1 lL was injected from the supernatant
into the high-performance liquid chromatography (HPLC)
system. HPLC was performed with a HP 1100 liquid
chromatograph (Agilent Technologies, Palo Alta, CA,
USA) with a HP 1100 fluorescence detector (emission
295 nm, excitation 330 nm). Tocopherol isomers were
separated on a 2.1 9250 mm reversed-phase column. The
column temperature was 40°C. A two-point calibration
curve was made from analysis of a 3% albumin solution
enriched with known concentration of tocopherols.
Recovery is [95%, the method is linear from 1 to 200 lM
at least, and the limit of detection is 0.01 lM. Relative
standard deviation (RSD) is 2.8% (17.0 lM) and 4.6%
(25.1 lM).
Urinary F2 Isoprostanes
Fasting urine samples were analyzed for 8-iso-prostaglan-
din F
2a
(8-iso-PGF
2a
) by a highly specific and validated
radioimmunoassay as described by Basu [17]. Urinary
levels of 8-iso-PGF
2a
were adjusted by dividing the 8-iso-
PGF
2a
concentration by that of creatinine.
Markers of Inflammation and Hemostasis
Plasma interleukin-6 (IL-6), tumour necrosis factor-alpha
(TNFa), monocyte chemotactic protein-1 (MCP-1),
thromboxane B
2
(TxB
2
), interferon-gamma (INFc), soluble
E-selectin and P-selectin, soluble intracellular adhesion
molecule-1 (ICAM-1), and vascular cell adhesion mole-
cule-1 (VCAM-1) were determined by Fluorokine
Ò
MAP
kits (R&D Systems, Inc., Minneapolis, MN, USA). Plasma
leukotriene B
4
(LTB
4
) and thromboxane B
2
(TxB
2
) were
assessed as described by Elvevoll et al. [18]. High-sensi-
tivity C-reactive protein (hsCRP) evaluation was per-
formed at the routine laboratory at Department of Medical
Biochemistry at the National Hospital, Norway using
standard method.
Statistics
All continuous variables were summarized by product
group and visit number and described using standard
statistical measures, i.e., number of observations, mean,
Table 2 n-3 fatty acid contents
of the study products Study product Daily study dose Daily dose
EPA
Daily dose
DHA
Daily dose
EPA ?DHA
Daily dose
n-3 PUFAs
Fish oil 3 capsules (1.8 g oil) 450 mg 414 mg 864 mg 990 mg
Krill oil 6 capsules (3.0 g oil) 348 mg 195 mg 543 mg 621 mg
40 Lipids (2011) 46:37–46
123
standard deviation (SD), median, minimum, and maxi-
mum. Absolute and percentagechangefrombaselineto
the week-7 visit are presented as summary statistics. All
categorical (discrete, including ordinal) variables are
presented in contingency tables showing counts and
percentages for each treatment group at all time points.
Continuously distributed efficacy laboratory parameters
(lipids, EPA, DHA, and docosapentaenoic acid (DPA))
were analyzed by analysis of covariance (ANCOVA)
using the following model: change in parameter value =
baseline value ?treatment ?gender ?age ?error.
Change from baseline to week 7 was used as a depen-
dent variable in the model. A linear model using SAS GLM
with gender as fixed effect, subject as random effect, and
baseline value and age as covariates was applied. A
reduced ANCOVA model with baseline value and treat-
ment was used for the secondary efficacy parameters.
Significant treatment effects were analyzed by pairwise
tests. Changes from baseline to end of intervention were
tested by paired t-test.
Results
Subject Characteristics at Baseline
Figure 1shows the disposition of all subjects. One hundred
fifteen of 129 randomized subjects completed the study.
Withdrawal rates were similar in all three groups (three
withdrawals in the fish oil group, six withdrawals in the
krill oil group, and five withdrawals in the control group).
Three subjects discontinued the study due to clinical
symptoms (all in the krill group), three subjects violated
the exclusion criteria (two in the fish oil group and one in
the krill oil group), and one subject in each group was lost
to follow-up. Two subjects in the control group were
withdrawn due to concomitant treatments, and three sub-
jects withdrew their consent (one subject in the krill oil
group and two subjects in the control group). Clinical
symptoms included symptoms of common cold or gastro-
intestinal symptoms. During database clean-up, it was
detected that two subjects (in the krill oil group) had been
allowed to enter the study although they violated the entry
criteria. They where therefore excluded from the per pro-
tocol subjects. The statistical analyses of efficacy were
performed on the data collected from 113 per protocol
subjects (Fig. 1).
The study groups were comparable in terms of weight,
height, BMI, gender, and age at baseline (Table 3). Vital
signs including systolic and diastolic blood pressure and
heart rate were within normal ranges. More females than
males were included in all study groups.
Fatty Acid Composition in Plasma
Plasma levels of EPA, DHA, and DPA increased signifi-
cantly from baseline to the end of the intervention phase in
the groups receiving fish oil and krill oil, but not in the
control group. The changes in EPA, DHA, and DPA dif-
fered significantly between the subjects supplemented with
n-3 PUFAs and the subjects in the control group, but there was
no significant difference in the change in any of the n-3 PUFAs
between the fish oil and the krill oil groups (Table 4).
There were significant within-group changes in indi-
vidual FAs from start to end of intervention, but no clear
trends in changes in the plasma FA composition were
apparent in any of the study groups (Table 4).
The level of arachidonic acid (C20:4n-6) increased from
baseline in the krill group, whereas a decrease was
observed in the fish oil group. The changes in arachidonic
acid between the fish oil and the krill oil groups, and the
control group differed significantly (p=0.001). Pairwise
comparisons showed that the mean increase in arachidonic
acid in the krill oil group was significantly different from
the mean decreases in the fish oil and control groups, but
there was no significant difference between the mean
changes in arachidonic acid level between the fish oil and
control groups.
Serum Lipids
Small changes in the levels of HDL-cholesterol, LDL-
cholesterol, and TG were observed in all study groups from
start to end of the intervention phase, but only the within-
group increase in LDL-cholesterol seen in the fish oil
group (p=0.039) was statistically significant. The tests
comparing the differences between the study groups gave
no statistically significant results (Table 5). The HDL-
cholesterol/TG ratio and the change from start to end of the
intervention were calculated for all study groups. No sig-
nificant changes in the HDL-cholesterol/TG ratio from start
to end of the interventions were detected in the fish oil or
Table 3 Demographic information and body measurements
Parameter, mean (SD) Study groups
Fish oil
(N=43)
Krill oil
(N=44)
Control
(N=42)
Age (years) 38.7 (11.1) 40.3 (14.8) 40.5 (12.1)
Height (cm) 171.2 (7.8) 171.3 (8.6) 172.2 (9.4)
Weight (kg) 71.7 (12.0) 69.8 (13.7) 71.7 (12.0)
BMI (kg/m
2
) 24.4 (3.0) 23.6 (3.3) 23.9 (3.0)
Gender
Female (n) 34 (79.1%) 31 (70.5%) 28 (66.7%)
Male (n) 9 (20.9%) 13 (29.5%) 14 (33.3%)
Lipids (2011) 46:37–46 41
123
Table 4 Fatty acid composition in plasma
Parameter (lmol/L) Treatment NBaseline End of study Change p-Value
a
for
change
p-Value
b
between
groups
C14:0 myristic acid Fish oil 40 67.4 ±57.07 69.4 ±62.32 2.0 ±44.05 0.77
Krill oil 36 55.5 ±32.43 57.8 ±26.15 2.3 ±30.93 0.65 0.71
Control 37 60.5 ±29.25 58.1 ±38.01 -2.4 ±35.46 0.69
C15:0 pentadecanoic acid Fish oil 40 18.2 ±14.42 16.2 ±8.22 -2.1 ±12.01 0.28
Krill oil 36 14.7 ±5.03 15.5 ±3.69 0.8 ±4.44 0.30 0.27
Control 37 15.0 ±5.02 15.0 ±5.26 0.1 ±4.32 0.94
C16:0 palmitic acid Fish oil 40 1,661.0 ±496.5 1,522. ±339.3 -139.0 ±409.5 0.038
Krill oil 36 1,548.9 ±477.9 1,547. ±260.0 -2.3 ±414.9 0.97 0.35
Control 37 1,652.7 ±374.2 1,578. ±315.6 -74.6 ±327.7 0.17
C16:1n-7 palmitoleic acid Fish oil 40 67.7 ±35.41 63.0 ±33.54 -4.7 ±27.91 0.29
Krill oil 36 66.1 ±49.18 61.8 ±26.56 -4.4 ±35.91 0.47 0.62
Control 37 68.7 ±32.98 63.9 ±35.07 -4.8 ±28.62 0.31
C17:0 margaric acid Fish oil 40 24.2 ±8.38 23.9 ±8.44 -0.3 ±6.09 0.76
Krill oil 36 22.6 ±5.85 24.0 ±5.84 1.4 ±5.49 0.14 0.089
Control 37 23.3 ±5.46 21.7 ±5.84 -1.6 ±4.85 0.048
C18:0 stearic acid Fish oil 40 580.6 ±136.6 578.5 ±130.2 -2.2 ±133.2 0.92
Krill oil 36 548.5 ±116.7 568.9 ±112.6 20.4 ±91.7 0.19 0.17
Control 37 594.8 ±103.5 562.4 ±147.2 -32.4 ±125.4 0.12
C18:1n-9 oleic acid Fish oil 40 558.9 ±166.1 516.2 ±146.8 -42.7 ±154.0 0.087
Krill oil 36 532.8 ±198.5 521.8 ±109.1 -11.0 ±191.0 0.73 0.71
Control 37 570.2 ±146.8 547.2 ±156.1 -23.0 ±151.9 0.36
C18:2n-6 linoleic acid Fish oil 40 829.3 ±349.8 779.8 ±254.5 -49.6 ±251.3 0.22
Krill oil 36 742.0 ±214.0 744.2 ±187.9 2.2 ±215.8 0.95 0.44
Control 37 812.0 ±219.6 735.7 ±212.4 -76.3 ±167.5 0.0088
C18:3n-3 alpha-linoleic acid Fish oil 40 61.7 ±17.89 61.9 ±20.22 0.2 ±20.95 0.95
Krill oil 36 67.3 ±25.24 68.4 ±21.88 1.1 ±20.08 0.73 0.15
Control 37 68.3 ±20.40 62.8 ±22.07 -5.5 ±19.55 0.094
C20:3n-3 eicosatrienoic acid Fish oil 40 39.6 ±18.08 33.5 ±17.97 -6.0 ±10.00 0.0005
Krill oil 36 39.3 ±19.20 34.9 ±13.20 -4.4 ±13.23 0.054 0.22
Control 37 39.8 ±18.24 37.7 ±18.28 -2.1 ±8.65 0.16
C20:4n-6 arachidonic acid Fish oil 40 192.6 ±50.0 178.5 ±45.3 -14.1 ±29.6 0.0046
Krill oil 36 180.1 ±52.4 192.1 ±40.2 12.0 ±32.8 0.035 0.0010
Control 37 189.8 ±44.2 182.8 ±38.0 -7.0 ±32.3 0.20
C22:0 behenic acid Fish oil 40 21.5 ±6.05 21.8 ±6.36 0.4 ±3.30 0.49
Krill oil 36 20.2 ±5.29 22.0 ±6.25 1.9 ±3.51 0.003 0.040
Control 37 18.9 ±6.02 18.3 ±4.83 -0.6 ±4.07 0.36
C24:0 lignoceric acid Fish oil 40 10.0 ±4.07 10.3 ±4.19 0.3 ±1.71 0.22
Krill oil 36 9.7 ±2.86 10.4 ±3.15 0.7 ±2.04 0.040 0.26
Control 37 8.9 ±3.37 8.5 ±3.05 -0.4 ±2.57 0.40
C24:1n-9 neuronic acid Fish oil 40 18.2 ±6.88 18.9 ±6.15 0.6 ±3.75 0.29
Krill oil 36 16.7 ±5.99 17.3 ±5.87 0.6 ±5.00 0.48 0.17
Control 37 15.7 ±5.39 16.7 ±5.70 1.0 ±5.67 0.30
C20:5n-3 EPA Fish oil 40 31.2 ±23.11 76.3 ±36.02 45.2 ±29.65 \0.0001
Krill oil 36 30.4 ±21.57 74.9 ±38.66 44.5 ±35.21 \0.0001 \0.0001
Control 37 43.9 ±40.74 37.2 ±28.64 -6.6 ±28.58 0.17
42 Lipids (2011) 46:37–46
123
control groups. In the krill oil group, however, there was a
significant increase in the HDL-cholesterol/TG ratio. The
test for differences between the study groups gave no
significant results (Table 5).
Although the interventions did not significantly change
TG levels a reduction was seen in those subjects in the krill
oil group having the highest baseline values (Fig. 2).
The changes in levels of Apo B-100 from baseline to
end of study were minor in all study groups. Moreover,
the test for differences between the study groups in
changes in Apo A1 was not significant. However, the
within-group changes of Apo A1 levels from start to end
of the interventions were statistically significant in the
krill oil group.
Table 5 Serum lipids and lipoproteins
Parameter Treatment NBaseline End of study Change p-Value
a
for
change
p-Value
b
between
groups
HDL-cholesterol (mmol/L) Fish oil 40 1.56 ±0.384 1.61 ±0.396 0.05 ±0.157 0.063
Krill oil 36 1.50 ±0.368 1.63 ±0.517 0.13 ±0.404 0.061 0.50
Control 37 1.59 ±0.354 1.63 ±0.395 0.04 ±0.228 0.29
LDL-cholesterol (mmol/L) Fish oil 40 2.96 ±0.747 3.09 ±0.827 0.13 ±0.377 0.039
Krill oil 36 3.07 ±0.724 3.16 ±0.796 0.09 ±0.390 0.18 0.45
Control 37 2.98 ±0.824 3.03 ±0.802 0.05 ±0.361 0.44
Triglycerides (mmol/L) Fish oil 40 0.95 ±0.541 0.94 ±0.542 -0.01 ±0.462 0.84
Krill oil 36 1.10 ±0.638 1.01 ±0.649 -0.09 ±0.417 0.21 0.65
Control 37 0.92 ±0.414 0.93 ±0.523 0.02 ±0.429 0.82
HDL/triglycerides (%) Fish oil 40 225.8 ±151.08 216.8 ±119.33 109.5 ±44.62 0.19
Krill oil 36 196.9 ±134.24 228.3 ±146.62 129.2 ±68.99 0.016 0.41
Control 37 217.7 ±138.65 234.4 ±148.20 113.0 ±49.28 0.12
Total-cholesterol (mmol/L) Fish oil 40 4.93 ±0.778 5.13 ±0.809 0.20 ±0.424 0.0049
Krill oil 36 4.99 ±0.815 5.20 ±0.917 0.21 ±0.496 0.014 0.78
Control 37 4.95 ±0.925 5.07 ±0.861 0.12 ±0.524 0.18
Apo A1 (mmol/L) Fish oil 40 1.64 ±0.269 1.68 ±0.250 0.04 ±0.130 0.058
Krill oil 36 1.64 ±0.241 1.73 ±0.376 0.09 ±0.267 0.047 0.70
Control 37 1.68 ±0.272 1.75 ±0.272 0.07 ±0.173 0.023
Apo B-100 (mmol/L) Fish oil 40 0.81 ±0.184 0.80 ±0.199 -0.01 ±0.100 0.64
Krill oil 36 0.83 ±0.208 0.81 ±0.226 -0.02 ±0.126 0.35 0.80
Control 37 0.79 ±0.197 0.78 ±0.198 -0.01 ±0.098 0.41
a
Test of within-group changes
b
Test comparing change from start to end of intervention between the fish oil, krill oil, and control groups
Table 4 continued
Parameter (lmol/L) Treatment NBaseline End of study Change p-Value
a
for
change
p-Value
b
between
groups
C22:6n-3 DHA Fish oil 40 47.0 ±22.08 70.4 ±25.70 23.4 ±16.55 \0.0001
Krill oil 36 44.8 ±21.36 64.2 ±26.15 19.4 ±23.75 \0.0001 \0.0001
Control 37 57.4 ±30.94 51.3 ±23.70 -6.1 ±21.25 0.088
C22:5n-3 DPA Fish oil 40 8.8 ±3.98 12.7 ±5.06 3.9 ±3.24 \0.0001
Krill oil 36 8.2 ±3.33 11.9 ±3.56 3.6 ±3.68 \0.0001 \0.0001
Control 37 9.6 ±5.09 8.6 ±3.84 -1.0 ±3.56 0.090
Total fatty acids Fish oil 40 4,250.7 ±1,148.1 4,064.6 ±890.8 -186.0 ±921.8 0.21
Krill oil 36 3,958.1 ±983.7 4,045.5 ±662.5 87.4 ±810.7 0.52 0.15
Control 37 4,261.3 ±804.2 4,016.8 ±774.4 -244.5 ±685.5 0.037
a
Test of within-group changes
b
Test comparing change from start to end of intervention between the fish oil, krill oil, and control groups
Lipids (2011) 46:37–46 43
123
Oxidative Stress, Markers of Inflammation,
and Hemostasis
a-Tocopherol is considered an antioxidant, and an increase
in PUFAs may lead to increased oxidative stress. Although
a-tocopherol was added to both supplements, no significant
change in levels of a-tocopherol was detected (Supple-
mentary Table). A tendency towards a reduced level of
a-tocopherol was observed in all study groups. F2-iso-
prostanes, formed from free-radical-induced peroxidation
of membrane-bound arachidonic acid, are considered a
reliable biomarker of oxidative stress. However no differ-
ences were observed in urine F2-isoprostane, suggesting
that there was not an increase in oxidative stress. No sig-
nificant changes were observed in levels of hsCRP, markers
of inflammation or hemostasis (Supplementary Table).
Discussion
The primary finding of the present study was that plasma
concentrations of EPA, DPA, and DHA increased signifi-
cantly in both the krill oil and fish oil groups compared
with the control group following daily supplementation for
7 weeks. There was no statistically significant difference
between these two groups in the levels of the increases in
EPA and DHA. Since the subjects in the krill oil group
received 62.8% of the total amount of n-3 PUFAs received
by the subjects in the fish oil group, these findings indicate
that the bioavailability of n-3 PUFAs from krill oil (mainly
PL) is as, or possibly more, efficient as n-3 PUFA from fish
oil (TG). This supports the results of a previous study with
krill oil and menhaden oil in humans [11]. In the study
performed by Maki et al., plasma EPA increased 90% and
DHA increased 51% from baseline levels. In the current
study EPA increased 146% and DHA increased 43% from
baseline levels. The small discrepancy between these two
studies might be related to different levels of EPA and
DHA in the oils used, different treatment time (7 versus
4 weeks), and different dose used (3 g oil versus 2 g). It
has been hypothesized that PL improve the bioavailability
of lipids, which may facilitate absorption of EPA and DHA
from marine PL compared with TG, but the extent to which
this contributes to the efficient absorption observed in the
krill oil group is unknown.
AHA dietary guidelines for long-chain n-3 PUFAs and
fish for primary prevention of coronary diseases are two
servings of fatty fish per week [9]. This recommendation
will provide the order of 250–500 mg EPA ?DHA per
day [19]. In the present study we have shown that daily
intake of 3 g krill oil containing 543 mg EPA ?DHA
increases the plasma level of EPA and DHA to the same
extent as intake of fish oil containing 864 mg EPA ?DHA.
A food-based approach for achieving adequate intake of
n-3 PUFAs is recommended [20]. However, for some
individuals nutritional supplements may be needed, such as
those who do not like fish or for other reasons choose not to
include fish in their diet. This study demonstrates that
supplementation with krill oil will be a good source of EPA
and DHA in their daily diet.
Serum TG and HDL-cholesterol have been observed to
be inversely related [21]. Although the metabolic relation
that exists between HDL-cholesterol and TG is not fully
understood, the ratio between TG and HDL-cholesterol has
been shown to be a powerful risk predictor for CHD [22,
23]. In the present study, no statistically significant dif-
ferences in HDL-cholesterol, TG or HDL-cholesterol/TG
ratio were observed between the study groups. However,
the change in the HDL-cholesterol/TG ratio in the krill oil
group was statistically significant (Table 5). This obser-
vation supports the impression of a more pronounced effect
of krill oil supplementation on HDL-cholesterol and TG
compared with other n-3 PUFA supplements. However, to
verify these effects of krill oil, they should be studied in a
population with elevated blood TG levels and lowered
HDL-cholesterol, i.e., in a population with markers of
metabolic syndrome. The increase in HDL-cholesterol was
slightly higher in the krill oil group than in the fish oil
group (8.7% versus 3.2%), although not significantly so
(p=0.061). Compared with fish oil, krill oil contains a
high amount of astaxanthin, which has been indicated to
Fig. 2 Correlation between baseline TG levels and change in TG
levels after 7 weeks of intervention with krill oil or fish oil
44 Lipids (2011) 46:37–46
123
increase HDL-cholesterol as well as decrease TG in
humans [24]. Moreover, intake of PL may increase HDL-
cholesterol [25]. The small increase in LDL-cholesterol,
but no effect on HDL-cholesterol, in the fish oil group is in
accordance with previous findings [7].
The analysis of the changes in the plasma fatty acid
composition following 7 weeks of intervention with n-3
PUFAs showed that the levels of arachidonic acid and
behenic acid significantly increased from baseline in the
krill oil group as compared with the fish oil and control
groups. Moreover, arachidonic acid was significantly
decreased in the fish oil group. Intake of n-3 PUFAs from
fish oil can be incorporated in cell PL in a time- and dose-
dependent manner at the expense of arachidonic acid [26].
The explanation and importance of this finding are not
clear. However, one possible explanation might be that
arachidonic acid is mobilized from the cell membranes to
the blood by EPA and DHA linked to the PL in the krill oil.
However, the changes in plasma arachidonic acid were
small compared with the changes in EPA and DHA, and
there was no significant difference in the increase in EPA/
arachidonic acid ratio between the two intervention groups.
The CRP leveldid not changeduring the study in any of the
study groups, and no significant changes were observed in the
other markers of inflammation and hemostasis (data not
shown). This is in accordance with others who have examined
the effect of fish oil among apparently healthy individuals
[2731]. Moreover, no statistically significant differences
were found in a-tocopherol levels and F2-isoprostanes in
urine, suggesting that no oxidative stress occurred.
Thesafetyanalysisrevealednoclearpatternsinthechanges
in any of the hematological or serum biochemical variables,
vital signs or weight that might indicate a relation with
administration of any of the studied products. Clinical symp-
toms registered during the study included mainly symptoms of
common cold or gastrointestinal symptoms. However, one
subject in the fish oil group experienced moderate bruises, and
one subject in the krill oil group withdrew from the study
because of an outbreak of rash that was possibly related to
intake of the study products. Safety laboratory parameters and
other safety observations such as occurrence of adverse events
indicate that krill oil is well tolerated. There were no apparent
differences in the rate of adverse events or blood safety
parameters between the krill oil, fish oil or control groups.
In conclusion, the present study shows that n-3 PUFAs
from krill oil in the form of PL are readily and effectively
absorbed after ingestion and subsequently distributed in the
blood. The krill oil supplement is safe and well tolerated.
Krill oil thus represents a valuable source of n-3 PUFAs.
Acknowledgments The authors would like to thank the volunteers
who participated in this study. This work was partially funded by
Aker BioMarine ASA.
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
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Thesis
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La prévention primaire et secondaire des pathologies inflammatoires chroniques telles que l’obésité et la maladie de Crohn (MC) reposent majoritairement sur des mesures hygiéno-diététiques incluant l’activité physique et la nutrition. Dans le cadre de ce travail de thèse, l’objectif principal était d’étudier l’influence de modalités d’exercice - exercice imposé de type intermittent de haute intensité (HIIT) ou activité de roue spontanée - associé à un apport en lin, riche en acides gras polyinsaturés (AGPI) n-3, sur les interrelations « composition corporelle – inflammation – microbiote intestinal » dans un contexte de pathologies inflammatoires chroniques (obésité, MC) sur modèles murins. Le deuxième objectif était d’étudier spécifiquement deux formes de lin, à travers la graine ou l’huile, afin de déterminer si la matrice de la graine de lin extrudée pouvait avoir des effets qui lui sont propres. Nos résultats indiquent qu’un programme de type HIIT est efficace pour prévenir la prise de poids et de masse grasse, et que le lin, indépendamment de sa forme, diminue l’inflammation. Nos travaux ont également montré un effet majeur du HIIT et de la graine de lin extrudée (TRADILIN, Valorex®) sur la modulation de la composition du microbiote intestinal associé à la muqueuse. Certaines de ces variations étaient corrélées aux modulations de la composition corporelle mais non à l’inflammation. Nos travaux ont montré spécifiquement un effet synergique du HIIT et de l’huile de lin sur l’abondance d’Oscillospira spp. et sur la conversion de l’acide α-linolénique en acide docosahexaénoïque. En conclusion, nos résultats montrent qu’un apport en lin, et particulièrement sous forme de graines extrudées, associé à une activité physique imposée et suffisamment intense, pourraient être efficace dans la prévention et/ou la prise en charge des pathologies inflammatoires chroniques telles que l’obésité et la MC. Les interrelations « composition corporelle – inflammation – microbiote intestinal », restent toutefois à approfondir et les mécanismes sous-jacents à explorer.
... Although modulating the FA content in brain still represents a challenge comparatively to other tissues, dietary interventions may be effective in targeting serum lipid pools important for brain DHA uptake (8). Thereby, several works have shown a higher (9)(10)(11) or equal (12)(13)(14) bioavailability of DHA esterified to phospholipids (PL) in comparison to DHA esterified to triacylglycerols (TAG). Other works are more controversial (15,16), insomuch as a higher concentration of circulating DHA would not predict brain accretion of DHA (17)(18)(19). ...
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The effects of different extraction solvents on the extraction yield and chemical composition of oils from by‐products of marine shrimp Penaeus vannamei (Pv) and freshwater shrimp Procambarus clarkia (Pc) were investigated. Our results indicated that the ethanol and n‐hexane mixture (4:1, v/v) was suitable solvent for simultaneous extraction of phospholipid and non‐polar lipids. By contrast, the ethanol and n‐hexane mixture (4:1, v/v) and single ethanol were suitable solvents for the extraction of polyunsaturated fatty acids‐rich (36.10‐42.78% of total fatty acids for Pv and 23.57‐25.58% of total fatty acids for Pc) and phosphatidylcholine‐rich (66.22‐67.09 mol% of total phospholipids for Pv and 55.01‐58.68 mol% of total phospholipids for Pc) oils, but acetone was suitable solvent for the extraction of astaxanthin‐rich oil (436.19 μg/g oil for Pv and 799.27 μg/g oil for Pc). The findings will provide relevant information that can be used to improve the production of nutritional oils from shrimp by‐products.
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The marine crustacean krill (order Euphausiacea) has not been a traditional food in the human diet. Public acceptance of krill for human consumption will depend partly on its nutritive value. The aim of this article is to assess the nutritive value and potential health benefits of krill, an abundant food source with high nutritional value and a variety of compounds relevant to human health. Krill is a rich source of high-quality protein, with the advantage over other animal proteins of being low in fat and a rich source of omega-3 fatty acids. Antioxidant levels in krill are higher than in fish, suggesting benefits against oxidative damage. Finally, the waste generated by the processing of krill into edible products can be developed into value-added products.