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Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults


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Epidemiological research indicates that long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) improve insulin resistance. The aim of this study was to investigate the effects of seafood consumption on insulin resistance in overweight participants during energy restriction. In this 8 week dietary intervention, 324 participants (20-40 years, BMI 27.5-32.5 kg/m(2), from Iceland, Spain and Ireland) were randomised by computer to one of four energy-restricted diets (-30E%) of identical macronutrient composition but different LC n-3 PUFA content: control (n = 80; no seafood; single-blinded); lean fish (n = 80; 150 g cod, three times/week); fatty fish (n = 84; 150 g salmon, three times/week); (4) fish oil (n = 80; daily docosahexaenoic/eicosapentaenoic acid capsules, no other seafood; single-blinded). Fasting glucose, insulin, adiponectin, plasma triacylglycerol and fatty acids in erythrocyte membrane were measured at baseline and endpoint. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Linear models with fixed effects and covariates were used to investigate the effects of seafood consumption on fasting insulin and HOMA-IR at endpoint in comparison with the control group. Of the participants, 278 (86%) completed the intervention. Fish oil intake was a significant predictor of fasting insulin and insulin resistance after 8 weeks, and this finding remained significant even after including weight loss, triacylglycerol reduction, increased LC n-3 PUFA in membranes or adiponectin changes as covariates in the statistical analysis. Weight loss was also a significant predictor of improvements. LC n-3 PUFA consumption during energy reduction exerts positive effects on insulin resistance in young overweight individuals, independently from changes in body weight, triacylglycerol, erythrocyte membrane or adiponectin. NCT00315770.
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Beneficial effects of long-chain n-3 fatty acids included
in an energy-restricted diet on insulin resistance
in overweight and obese European young adults
A. Ramel & A. Martinéz & M. Kiely & G. Morais &
N. M. Bandarra & I. Thorsdottir
Received: 30 October 2007 / Accepted: 2 April 2008 / Published online: 20 May 2008
Springer-Verlag 2008
Aims/hypothesis Epidemiological research indicates that
long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA)
improve insulin resistance. The aim of this study was to
investigate the effects of seafood consumption on insulin
resistance in overweight participants during energy restriction.
Methods In this 8 week dietary intervention, 324 participants
(2040 years, BMI 27.532.5 kg/m
, from Iceland, Spain and
Ireland) were randomised by computer to one of four energy-
restricted diets (30E%) of identical macronutrient compo-
sition but different LC n-3 PUFA content: control (n=80; no
seafood; single-blinded); lean fish (n=80;150gcod,three
times/week); fatty fish (n=84; 150 g salmon, three times/
week); (4) fish oil (n=80; daily docosahexaenoic/eicosapen-
taenoic acid capsules, no other seafood; single-blinded).
Fasting glucose, insulin, adiponectin, plasma triacylglycerol
and fatty acids in erythrocyte membrane were measured at
baseline and endpoint. Insulin resistance was calculated
using the homeostasis model assessment of insulin resistance
(HOMA-IR). Linear models with fixed effects and covariates
were used to investigate the effects of seafood consumption
on fasting insulin and HOMA-IR at endpoint in comparison
with the control group.
Results Of the partici pants, 278 (86%) completed the
intervention. Fish oil intake was a significant predictor of
fasting insulin and insulin resistance after 8 weeks, and this
finding remained significant even after including weight
loss, triacylglycerol reduction, increased LC n-3 PUFA in
membranes or adiponectin changes as covariates in the
statistical analysis. Weight loss was also a significant pre-
dictor of improvements.
Conclusions/interpretation LC n-3 PUFA consumption
during energy reduction exerts positive effects on insulin
resistance in young overweight individuals, independently
from changes in body weight, triacylglycerol, erythrocyte
membrane or adiponectin.
Trial registration: NCT00315770.
Funding: The YOUNG study is part of the SEAFOODplus
Integrated Project, which is funded by the EC through the 6th
Framework Programme Contract No. FOOD-CT-2004-506359.
Keywords Glucose
Insulin resistance
LC n-3 fatty acids
Weight loss
Diabetologia (2008) 51:12611268
DOI 10.1007/s00125-008-1035-7
Electronic supplementary material The online version of this article
(doi:10.1007/s00125-008-1035-7) contains supplementary material,
which is available to authorised users.
A. Ramel
I. Thorsdottir (*)
Unit for Nutrition Research, Landspitali-University Hospital &
Faculty of Food Science and Nutrition, Eiriksgata 29,
101 Reykjavik, Iceland
A. Martinéz
Department of Physiology and Nutrition, University of Navarra,
Navarra, Spain
M. Kiely
Department of Food and Nutritional Sciences,
University College Cork,
Cork, Ireland
G. Morais
Department of Biochemistry, Faculty of Medical Sciences,
New University of Lisbon,
Lisbon, Portugal
N. M. Bandarra
The National Research Institute on Agriculture
and Fisheries Research,
Lisbon, Portugal
DHA docosahexaenoic acid
EPA eicosapentaenoic acid
FFQ food frequency questionnaire
HOMA-IR homeostasis model assessment of
insulin resistance
LC n-3 PUFA long-chain n-3 polyunsaturated fatty
Obesity and type 2 diabetes mellitus are characterised by
impaired insulin -stimulated glucose disposal in skeleta l
muscle [1]. Fish oil (and its important long-chain n-3
polyunsaturated fatty acids (LC n-3 PUFA) eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA) protect against
insulin resistance and obesity in rodents fed high-fat diets,
and might reduce insulin response to glucose in healthy
humans [24]. According to epidemiological studies, fish
consumption is inversely related to 2 h glucose levels during
follow-up, and is associated with a reduced risk of
developing impaired glucose tolerance in the elderly [5, 6].
An ecological study indicates that the prevalence of type 2
diabetes in men in the Nordic countries is significantly and
inversely associated with both the n-3 PUFA and EPA
content of milk, and positively associated with the ratio of
n-6/n-3 fatty acids in milk [7]. According to a meta-analysis
of published clinical trials, significant doseresponse effects
of EPA on HbA
and triacylglycerol, and of DHA on
fasting blood glucose levels, HbA
and triacylglycerol, have
been demonstrated in individuals with type 2 diabetes [8].
However, several intervention studies concerning LC n-3
PUFA supplementation and insulin resistance have reported
negative outcomes, which require further clarification [9].
The mechanism responsible for the possible fish oil-
induced prevention of insulin resistance is unclear, but
different studies have demonstrated a strong association
between elevated triacylglycerol concentration (plasma and/
or tissues) and insulin resistance [10]. In animal models,
insulin resistance is significantly correlated with hepatic or
plasma triacylglycerol content [11, 12]. Fish oil intake has
been shown to decrease plasma and liver triacylglycerol
levels and VLDL-triacylglycerol secretion, and to suppress
postprandial hypertriacylglycerolaemia [13].
Increasing evidence also suggests that the fatty acid
composition of membrane phospholipids of insulin target
tissues, such as liver, fat pad and skeletal muscle, is a critical
factor that influences both insulin secretion and its biological
actions (e.g. changes in membrane fluidity, diacylglycerol
second messenger function) [14, 15]. The fatty acid profile of
muscle membrane phospholipids has been associated with
insulin sensitivity in rodents [16, 17] and humans [1821].
These studies demonstrated a positive correlation between a
high content of LC n-3 PUFA and insulin sensitivity.
Adiponectin is an adipocyte-derived hormone that
stimulates glucose utilisation and fatty acid oxidation in
muscle and decreases hepatic gluconeogenesis, and a low
plasma level of this protein is an independent risk factor for
the future development of type 2 diabetes [22]. Moreover,
an association between circulating adiponectin and plasma
n-3 PUFA was recently found in healthy humans [23].
Based o n this evidence, it has been hypothesised that
possible protective effects of EPA and DHA may involve
induction of adiponectin. In animal research, the intake of
diets rich in EPA and DHA (5.3% of total energy intake)
leads to elevated systemic concentrations of adiponectin,
largely independent of food intake or adiposity [24].
To investigate the effects of the consumption of seafood
containing different amounts of LC n-3 PUFA on insulin
resistance, we conducted a randomise d controlled dietary
intervention trial in overweight and obese young adults
from three European countries. The goals of the present
study were to investigate whether seafoo d intake during
energy restriction impro ves fasting insulin and insulin
resistance (homeostasis model assessment of insulin resis-
tance [HOMA-IR]). We also paid particular attention to
plasma triacylglycerol, fatty acid composition of membrane
phospholipids, and plasma adiponectin levels, to estimate
their combined or independent contribution to changes in
insulin sensitivity during this 8 week trial.
Participants A total of 324 overweight individuals (138
men, 18 6 women) were recruited to our study SEAFOOD-
plus YOU NG (, accessed 4
April 2008) through advertisements on hospital and univer-
sity noticeboards, 140 from Iceland, 120 from Spain and 64
from Ireland. All subjects were screened for inclusion and
exclusion criteria. The inclusion criteria were a BMI in the
range of 27.532.5 kg/m
, age 2040 years and a waist
circumference of 94 cm and 80 cm for men and women,
respectively. Exclusion criteria were weight change (±3 kg)
in response to a weight loss diet within 3 months before the
start of the study, use of supplements containing n-3 fatty
acids, calcium or vitamin D during the last 3 months, allergy
to fish, pregnancy or lactation, drug treatment for hyperten-
sion, hyperlipidaemia and diabetes mellitus. None of the
participants was diagnosed with type 2 diabetes, but 12
participants had impaired fasting glycaemia (>5. 6 and
<6.9 mmol/l). About 86% (n=278) of the participants
completed the intervention. The study was approved by
the National Bioethical Committee in Iceland (04031), the
1262 Diabetologia (2008) 51:12611268
Ethical Committee of the University of Navarra in Spain
(24/2004) and the Clinical Research Ethics Committee of
the Cork University Hospital in Ireland. The study followed
the Helsinki guidelines (as revised in 2000), and all
participants gave their written consent. Power calculations
for the study were based on weight loss, the primary
endpoint of the study. It was estimated that a participation
rate of 7080% allowed the detection of approximately 1 kg
difference in weight loss between the four diet groups,
assuming an sSD of 3 kg, a p value for significance of <0.05
and a statistical power of >0.8.
Study design This study was a randomised controlled
dietary intervention trial. It was conducted at the Land-
spitali-University Hospital in Reykjavik, Iceland, the
University College of Cork, Ireland, and the University of
Navarra in Pamplona, Spain, and took place during the
period from April 2004 to November 2005. The interven-
tion lasted for 8 consecutive weeks, during which time the
participants were instructed to follow a diet restricted in
terms of energy to 70% of their normal intake, which was
determined by calculating energy expenditure by Harris
Benedict equations [25], using a correction factor to take
into account the overweight status of the subjects [26] and
an adjustment for physical activity level [27].
The participants were random ly assigned to one of the
following four diets, which varied with respect to the
amount of LC n-3 PUFA:
Diet 1: no seafood (control; 6×500 mg sunflower oil
capsules/day, Loders Croklaan [Lipid Nutrition],
Wormerveer, the Netherlands; encapsulated by
Banner Pharmacaps, Tilburg, the Netherlands);
Diet 2: lean fish (150 g cod, three times/week);
Diet 3: fatty fish (150 g salmon, three times/week); or
Diet 4: fish oil capsules (6×500 mg capsules/day, Loders
Croklaan, encapsulated by Banner Pharmacaps).
A chart of participant flow through the study is presented
in Electronic supplementary material Fig. 1.
Diet group 1 and 4 were single-blinded. For compara-
bility, the diets prescribed were of identical macronutrient
composition: total fat (~30% of total energy), carbohydrate
(~50% of total energy), protein (~20% of total energy) and
dietary fibre (~2025 g). Each diet provided different
amounts of LC n-3 PUFA: the placeb o capsules in diet
group 1 provided 0 g/day, cod in diet 2 provided 0.26 g/
day, salmon in diet group 3 provided 2.1 g/day, and fish oil
capsules p rovided 1.3 g/da y. Each subject re ceive d a
detailed meal plan to follow, as well as recipe booklets
and instructions, so as to minimise differences between
diets in terms of sources of fat (other than LC n-3 PUFA),
fruit and vegetable consumption and meal frequency. The
physical activity level of the participants remained un-
changed during the intervention. (For more information on
the intervention see Thorsdottir et al. [28].) To measure
compliance, seafood intake was assessed by a validated
food frequency questionnaire (FFQ) and dietary intake was
assessed by 2 day weighed food records before baseline
(habitual diet) and in week 6 or later of the intervent ion trial
[29]. Compliance was also assessed by analysing n-3 and n-
6 fatty acids in erythrocyte phospholipids in fasting blood
samples, as previously reported [28]. Results showed good
compliance with the intervention diets.
Anthropometric measurements All measurements were
done using standard procedu res, as outlined in a research
protocol approved and used by all centres participating in
the study. Anthropometrical measurements were performed
at baseline and endpoi nt of the study. Body weight was
measured in light underwear on a calibrated scale (model
no. 708; Seca, Hamburg, Germany). The height of the
subjects was measured with a calibrated stadiometer. Fat
mass and fat-free mass were assessed by bioelectrical
impedance analysis (BIA; Bodystat 1500; Bodystat, Doug-
las, Isle of Man, British Isles).
Biochemical measurements Participants were instructed to
avoid strenuous exercise and alcohol consumption the day
before the drawing of blood samples at baseline and
endpoint, which were analysed for fasting concentrations
of blood glucose (mmol/l), insulin (pmol/l), plasma triacyl-
glycerol (mmol/l) and adiponectin (
μg/ml). All the blood
analyses were performed centrally. Insulin was measured
with electrochemiluminescence immunoassay (ECLIA) on
a Modular Analytics E170 system from Roche Diagnostics
(Manheim, Germany). Plasma triacylglycerol and glucose
were analys ed using an enzymatic colorimetric assay and
an automated analyzer (Hitachi 911; Roche Diagnostics).
Adiponectin was measured with a radioimmunoassay kit
developed by Linco Research (St Charles, MO, USA).
Fatty acid composition in extracted erythrocyte membrane
phospholipids was analysed by gas chromatography under
the conditions described previously [30].
Insulin resis tance In the present study we used the update d
HOMA model (known as HOMA2, computer model) to
calculate insulin resistance (referred to as HOMA-IR), as
described previously [31], which can be downloaded as a
calculator or Excel spread sheet from the homepage of the
Diabetes Trials Unit, University of Oxford, UK (http://, accessed 4 April 2008).
Statistical analysis The data were entered into the SPSS
statistical package, version 11.0 (SPSS, Chicago, IL, USA).
Wilcoxon test was used to calculate whether there were
significant changes in the variables between baseline and
Diabetologia (2008) 51:12611268 1263
endpoint. The baseline characteristics of the groups were
compared using linear models with fixed effects (country, sex,
diet group) and covariate (age). To find out whether diet groups
predict endpoint fasting insulin and HOMA-IR after 8 weeks,
linear models with fixed effects (country, sex, diet group) and
covariates (age, baseline value of the relevant outcome
variable) were constructed. To find out whether changes in
body weight, triacylglycerol, membrane lipid fatty acids or
adiponectin can explain possible effects of diet groups on
outcomes, the blood biochemical and anthropometrical varia-
bles were entered as additional covariates in separate linear
models. Insulin and HOMA-IR values were log-transformed
for this analysis. Results from the linear models are shown as
parameter estimates where the cod, salmon and fish oil groups
were compared separately with the control group. The
numbers in the parameter estimates (B, lower confidence limit,
higher confidence limit) were back-transformed and are shown
as 1 B,1 lower confidence limit, 1 higher confidence
limit, respectively, thus giving percentage differences between
groups with respect to endpoint variables. A p value of less
than 0.05 was regarded as statistically significant.
Baseline anthropometric variables, hormones, HOMA-IR
and fatty acid values are reported in Table 1. Despite
randomisation, the cod group had higher triacylglycerol
levels at baseline than the control group (p=0.017), and all
intervention groups had lower EPA values at baseline than
the control group ( p=0.0040.026). Other baseline param-
eters did not significantly differ between groups. During the
intervention, the body weight of participants decreased
(5.2±3.2 kg, p<0.001, n=278), as did fasting insulin,
glucose, triacylglycerol and adiponectin levels and HOMA-
IR, whereas LC n -3 PUFA content in membrane lipids
significantly increased (all p<0.001; Table 2).
Linear models
The following variables were entered into the linear models
to find out whether diet groups can predict endpoint fasting
insulin (Table 3) and HOMA IR (Table 4 ): sex, country, diet
groups, age and baseline value of the dependent variable.
Fasting insulin and HOMA-IR were significantly lower in the
fish oil group than in the control group at endpoint (16.4%, p=
0.025 and 17.2%, p=0.022, respectively). To find out
whether the effects of diet groups on endpoint fasting insulin
and HOMA-IR can be explained by changes in weight loss,
triacylglycerol reduction, increased EPA/DHA content in
membrane lipids or adiponectin, these anthropometric and
blood chemical variables were entered as additional cova-
Table 1 Baseline data of the participants
Parameter Control Cod Salmon Fish oil
Body weight (kg)
min. 70.1 70.5 67.3 66.7
25 79.9 83.5 82.7 79.2
50 86.7 88.6 88.3 84.8
75 95.4 95.9 98.0 91.6
max. 120.2 117.8 122.3 109.7
Fasting glucose (mmol/l)
min. 3.94 3.67 3.83 4.00
25 4.68 4.61 4.72 4.61
50 4.97 4.83 5.17 4.89
75 5.26 5.28 5.44 5.22
max. 6.06 6.72 5.89 6.94
Fasting insulin (pmol/l)
min. 27.1 20.8 26.4 18.1
25 47.9 47.2 50.7 48.6
50 66.0 61.1 68.8 62.5
75 86.8 87.5 93.8 84.0
max. 279.2 154.2 254.2 184.7
min. 0.50 0.37 0.49 0.33
25 0.89 0.88 0.95 0.91
50 1.18 1.15 1.30 1.17
75 1.56 1.64 1.74 1.58
max. 5.10 2.82 4.63 3.47
Adiponectin (μg/ml)
min. 3.2 3.4 2.9 4.6
25 8.2 7.8 8.0 8.7
50 12.4 10.7 10.3 10.8
75 17.1 15.7 15.6 15.4
max. 34.8 26.8 38.4 30.4
EPA (%)
min. 0.29 0.22 0.37 0.22
25 0.78 0.75 0.74 0.79
50 1.23 0.95 0.93 1.08
75 1.83 1.34 1.24 1.33
max. 5.90 2.80 3.17 4.86
DHA (%)
min. 0.99 2.32 2.65 2.37
25 4.98 4.67 4.88 5.22
50 5.92 5.61 5.88 5.90
75 6.48 6.53 6.49 6.68
max. 11.3 7.8 9.1 11.4
Triacylglycerol (mmol/l)
min. 0.32 0.50 0.44 0.33
25 0.71 0.84 0.86 0.67
50 0.91 1.11 1.07 0.97
75 1.27 1.61 1.54 1.41
max. 4.40 4.34 3.25 4.51
Values are shown as minimum (min.), maximum (max.) and the
quartile cut-off values
Fasting values
In erythrocyte membrane phospholipids
All intervention groups had lower EPA values at baseline than the control
group (p= 0.0040.026) when corrected for country , sex and age)
Significant difference between cod and control group, p=0.017,
when corrected for country, sex and age)
1264 Diabetologia (2008) 51:12611268
riates. The differences between the fish oil group and control
remained significant (values 15.8% and 16.1% lower than
control, respectively), and weight loss was revealed to be an
additional significant predictor of both outcomes each kg
weight loss predicted a 3.4% and 3.5% reduction, respec-
tively). Triacylglycerol reduction, EPA changes and adipo-
nectin changes did not contribute significantly in the linear
models. The results of the linear models show estimated
changes in endpoint insulin (Table 3) and HOMA-IR
(Table 4)inresponsetoanincreaseinEPA;theuseof
DHA instead did not change the results.
In this randomised dietary intervention trial we investigated
the effects of seafood intake and weight loss on fasting insulin
and HOMA-IR in young overweight and obese European
adults from three different countries following an energy-
restricted diet. Participants consumed cod (150 g, three times/
week), salmon (150 g, three times/week), fish oil (6×500 mg
capsules/day) or placebo capsules (6×500 mg capsules/day),
but otherwise consumed diets of identical macronutrient
composition and percentage energy restriction [28]. During
these 8 weeks, average fasting insulin decrea sed and
HOMA-IR improved in the participants.
The most important finding of our study is that the fish oil
diet reduces fasting insulin and improves HOMA-IR to a
significantly greater extent than the control diet (between
15.8% and 17.2%, depending on the statistical model) and to
an extent similar to that observed with a weight loss of 4.7 kg
(calculated by dividing the B coefficients of the fish oil group
and weight loss from the linear models). Animal research,
ecological and epidemiological studies have shown associ-
ations between LC n-3 PUFA intake and insulin sensitivity
[2, 5, 6, 7], but, according to reviews [9, 32], there is
relatively little evidence from interventions that n-3 PUFA
supplementation has positive effects on insulin sensitivity in
humans. An early experimental study reported positive
effects of 3 g/day (in total) of EPA and DHA on insulin
sensitivity (measured by in vivo insulin-stimulated glucose
uptake by simultaneous infusions of glucose and insulin) in
six individuals with type 2 diabetes [33]. Another study [34],
which investigated the combined effects of fish consumption
and weight loss on cardio vascul ar risk factors in 69
overweight patients, found that the greatest decreases in
fasting insulin and glucose occurred in the fish+weight-loss
group. However, there were no independent effects of fish
on glucose or insulin. A similar intervention study involving
116 overweight insulin-resistant women showed independent
(from weight loss) effects of LC n-3 PUFA supplementation
on triacylglycerol and adiponectin levels, but not insulin
sensitivity [35]. The Kuopio, Aarhus, Naples, Wollongong
Table 2 Changes in weight and hormone and fatty acid levels during
the 8 week intervention
Parameter Control Cod Salmon Fish oil
Body weight (kg)
min. 2.2 1.4 0.7 0.7
25 2.6 3.5 3.1 2.9
50 4.5 5.4 5.6 5.2
75 5.9 7.2 7.4 7.8
max. 11.6 12 15.3 12.7
Fasting glucose (mmol/l)
min. 0.94 1.50 1.06 0.67
25 0.11 0.17 0.11 0.17
50 0.00 0.11 0.11 0.17
75 0.28 0.28 0.50 0.29
max. 0.89 1.67 1.06 2.06
Fasting insulin (pmol/l)
min. 51.4 99.3 51.4 63.2
25 9.7 3.5 4.2 5.6
50 9.7 9.7 17.4 16.0
75 31.3 22.9 32.6 27.8
112.5 70.1 123.6 94.5
min. 0.99 1.91 0.95 1.17
25 0.15 0.08 0.04 0.08
50 0.15 0.18 0.32 0.30
75 0.56 0.46 0.61 0.50
max. 2.07 1.29 2.29 1.80
Adiponectin (μg/ml)
min. 6.7 6.4 8.0 5.2
25 0.9 1.2 0.7 1.0
50 0.5 0.2 0.9 0.5
75 2.2 1.9 2.1 2.1
max. 7.3 7.8 7.7 7.2
EPA (%)
min. 5.1 1.8 1.4 3.4
25 0.6 0.3 0.2 0.3
50 0.2 0.1 0.7 0.6
75 0.0 0.1 1.2 1.0
max. 4.5 1.9 2.7 4.8
DHA (%)
min. 6.7 5.3 3.0 4.9
25 1.0 0.2 0.4 0.0
50 0.2 0.7 1.5 0.7
75 0.4 1.4 2.3 1.4
max. 5.9 3.4 6.2 4.5
Triacylglycerol (mmol/l)
min. 0.92 0.76 0.65 1.05
25 0.22 0.03 0.05 0.13
50 0.02 0.14 0.21 0.10
75 0.21 0.43 0.52 0.34
max. 2.21 1.97 1.80 2.98
Values are shown as minimum (min.), maximum (max.) and the
quartile cut-off values
Fasting values
In erythrocyte membrane phospholipids
Diabetologia (2008) 51:12611268 1265
and Uppsala (KANWU) study, a controlled multi-centre
isoenergetic dietary intervention study focusing on dietary fat
composition but not weight loss in 162 individuals, showed
that decrea sin g die tar y s atura ted fatty acid intak e an d
increasing monounsaturated fatty acid intake improves insulin
sensitivity, but no effect of fish oil supplementation on insulin
sensitivity was found, despite reduced plasma triacylglycerol
concentrations [36]. Similarly, a recent study investigating 29
India n Asians, a group particularly suscep tible to the
metabolic syndrome and type 2 diabetes, did not find an
effect of LC n-3 PUFA supplementation on insulin resistance,
even though supplementation was associated with improved
fasting and postprandial plasma triacylglycerol metabolism
[37]. In comparison with the above-mentioned studies, the
present study investigated a greater number of subjects. The
higher statistical power can explain our significant findings.
Significant weight loss was achieved in our study, and it can
be speculated that LC n-3 PUFA exert their positive health
effects on insulin sensitivity best during weight loss;
however, similar or greater amounts of weight loss were
achieved in similar studies [34, 35] that did not report
significant effects of LC n-3 PUFA on insulin sensitivity.
We cannot explain why endpoint fasting insulin and
HOMA-IR values for the salmon group were not significantly
different from those for the control group, despite the fact that
salmon provided the highest dose of LC n-3 PUFA in our
Table 3 Estimated changes
in endpoint insulin
relative to the control group
Model B
95% CI
p value
Unadjusted model
Cod group
0.014 1.007 1.208 0.978
Salmon group
0.535 1.493 0.583 0.327
Fish oil group
1.139 1.986 0.160 0.025
Adjusted model
Cod group
0.069 0.951 1.271 0.901
Salmon group
0.632 1.625 0.549 0.276
Fish oil group
1.097 1.972 0.076 0.037
Weight loss (kg) 0.236 0.340 0.125 <0.001
Triacylglycerol change (mmol/l) 0.021 0.569 0.667 0.948
Increase in EPA
0.056 0.243 0.375 0.715
Adiponectin decrease (μg/ml) 0.063 0.181 0.049 0.276
All models are corrected for baseline values of insulin, age, sex and country
Compared with control group
In erythrocyte membrane phospholipids
B Coefficients are presented as 1 back-transformed B, e.g. endpoint insulin and is 16.4% lower in the fish oil group than in the control group,
and each kg weight loss results in a 3.4% lower endpoint insulin (for all groups)
Table 4 Estimated changes
in endpoint HOMA-IR
to the control group
Model B
95% CI
p value
Unadjusted model
Cod group
0.004 0.152 0.172 0.966
Salmon group
0.075 0.217 0.093 0.359
Fish oil group
0.172 0.295 0.027 0.022
Adjusted model
Cod group
0.012 0.137 0.187 0.886
Salmon group
0.089 0.234 0.083 0.290
Fish oil group
0.161 0.289 0.011 0.036
Weight loss (kg) 0.035 0.050 0.019 <0.001
Triacylglycerol change (mmol/l) 0.001 0.086 0.095 0.990
Increase in EPA
0.010 0.034 0.056 0.668
Adiponectin decrease (μg/ml) 0.009 0.026 0.008 0.296
All models are corrected for baseline values of HOMA-IR, age, sex and country
Compared with control group
In erythrocyte membrane phospholipids
B coefficients are presented as 1 back-transformed B, e.g. endpoint HOMA-IR 17.2% lower in the fish oil group than in the control group, and
each kg weight loss results in a 3.5% lower HOMA-IR (for all groups)
1266 Diabetologia (2008) 51:12611268
study. The estimated improvements for the salmon group
were lower than those for the fish oil group (7.510.5%), but
were not significantly different (p=0.1910.334, analyses
not shown). The LC n-3 PUFA from salmon were
bioavailable, as indicated by increases in DHA and EPA in
erythrocyte membrane. It can be speculated that other con-
stituents in salmon could counteract the effects of LC n-3
PUFA. However, it should be mentioned that predicted
changes in the salmon group were the same direction as
those in the fish oil group, but they did not reach statistical
significance. This is in contrast to the cod group, which did
not show any effects compared with the control group.
Unexpectedly, the positive effects of LC n-3 PUFA on the
outcome variables during the 8 week intervention cannot be
explained by reductions in weight loss or triacylglycerol, or
changes in membrane fatty acids or adiponectin. It has long
been recognised that fish oil can decrease plasma and liver
triacylglycerol levels and VLDL-triacylglycerol secretion,
and suppress postprandial hypertriacylglycerolaemia [13].
However, the inclusion of plasma triacylglycerol in our
linear models did not alter the strength of fish oil as a
significant predictor of insulin sensitivity.
In several cross-sectional studies, measures of insulin
sensitivity are negatively correlated with the percentage of
individual long-chain polyunsaturated fatty acids in the
phospholipid fraction of muscle in patients or healthy subjects
[18, 19]. An animal study investigated the effects of fish oil
intake on membrane composition and insulin sensitivity in
rats and showed that incorporation of n-3 fatty acids into
adipocyte membrane phospholipids was higher in rats fed fish
oil than in the control group, and insulin action was positively
correlated with the fatty acid unsaturation index in membrane
phospholipids [38]. Furthermore, a recent human intervention
study showed that increased incorporation of LC n-3 PUFA
and reduced saturated fatty acids in skeletal muscle mem-
brane phospholipids is associated with better insulin sensitiv-
ity [21]. According to our linear models, changes in membrane
fatty acid composition do not play an independent role in the
improvements in insulin sensitivity in our participants. It is
possible that phospholipid composition in erythrocytes does
not reflect phospholipid composition in muscle [39]and/orthe
study duration of 8 weeks was too short to allow a full steady
state to be achieved with respect to phospholipid fatty acid
composition of skeletal muscle, liver and depot fat.
Adiponectin is a hormone secreted by the adipose tissue,
and its administration enhances insulin action in animals [40].
Cross-sectional studies have shown adiponectin levels to be
associated with insulin sensitivity [41, 42]. When we use our
baseline data to calculate correlations between insulin
sensitivity and adiponectin (results not shown), we see the
same associations as in the aforementioned cross-sectional
studies. However, according to the fitted statistical models,
changes in adiponectin did not predict changes in insulin
sensitivity. It could be that during the intervention, other
factors, namely fish oil intake and weight loss, had a much
stronger effect on insulin sensitivity then the small changes
in adiponectin, such that effects of adiponectin were not
visible in our analysis.
Limitations A common limitation of a dietary intervention
trial is blinding. In our study the fish oil and control groups
were single-blinded, whereas the cod and salmon groups were
not (fish was received as a fillet). Another limitation is the
uncertainty of whether the dietary intakes during the study
period were as prescribed. This risk was minimised by the
intense support provided by the staff and frequent contact with
the participants via phone and personal visits. Compliance
was tested during the intervention trial using an FFQ,
validated for assessing frequency of seafood consumption
[29], at the endpoint of the study, and measuring erythrocyte
fatty acid composition at the end of the intervention.
Changes in n-3 fatty acids in erythrocyte membrane were
in accordance with fatty acid composition of the diets, and
results from the FFQ confirmed good compliance.
Conclusion Fish oil consumption during an 8 week energy-
restricted diet exerts positive effects on fasting insulin and on
a measure of insulin resistance in young overweight or obese
individuals. These effects are independent from weight loss,
changes in plasma triacylglycerol, erythrocyte membrane
EPA/DHA or adiponectin concentrations. Weight loss is an
additional independent predictor of improvements in individ-
uals who consume fish oils. The present randomised dietary
intervention trial supports previous epidemiological evidence,
and demonstrates the importance of LC n-3 PUFA consump-
tion for improvement of insulin resistance and, possibly, for
the prevention of type 2 diabetes in addition to weight-
lowering strategies. Future intervention studies are required
to confirm the results of this study.
Acknowledgements This work is included in the SEAFOODplus
YOUNG, co-ordinated by Prof. Inga Thorsdottir, being part of the
SEAFOODplus Integrated Project, which is funded by the European
Commission through the 6th Framework Programme Contract with Ref.
FOOD-CT-2004506359. Thanks are given to the EU Commission for
financial support, and to the volunteers who participated in the study.
Duality of interest The authors declare that there is no duality of
interest associated with this manuscript.
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... Noteworthy, modifications in insulin clearance occurred in the absence of weight loss, but were related to changes in insulin sensitivity. This finding confirms the evidence that insulin extraction is more closely associated with insulin resistance than body weight per se 2,8,36 and proves the ability to achieve important metabolic benefits without the need for caloric restriction in this population at high risk for type 2 diabetes. ...
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Aim: A low n-6 to n-3 polyunsaturated fatty acid (PUFA) ratio diet reduces hyperinsulinemia in insulin-resistant adolescents even in the absence of change in body weight and glucose metabolism. The aim of this study was to examine the determinants and metabolic impact of the dietary-induced reduction in fasting and post-load insulin levels in obese youths. Materials and methods: Insulin secretion and clearance were assessed by measuring and modeling plasma insulin and C-peptide in 17 obese youth who underwent a 9-point, 180-min oral glucose tolerance test (OGTT) before and after a 12-week, eucaloric low n-6:n-3 PUFA ratio diet. Hepatic fat content was assessed by repeated abdominal magnetic resonance imaging (MRI). Results: Insulin clearance at fasting and during the OGTT was significantly increased after the diet, while absolute and glucose-dependent insulin secretion and model-derived parameters of β cell function were not affected. Dietary-induced changes in insulin clearance positively correlated with changes in whole-body insulin sensitivity and β cell glucose sensitivity, but not with changes in hepatic fat. Subjects with greater increases in insulin clearance showed a worse metabolic profile at enrollment, characterized by impaired insulin clearance, β cell glucose sensitivity, and glucose tolerance, and benefited the most from the diet, achieving greater improvements in glucose-stimulated hyperinsulinemia, insulin resistance, and β cell function. Conclusions: We demonstrated that a 12-week low n-6:n-3 PUFA ratio diet improves hyperinsulinemia by increasing fasting and post-load insulin clearance in obese youth, independently of weight loss, glucose concentrations and insulin secretion. This article is protected by copyright. All rights reserved.
... Individual differences in energy metabolism affect patterns of adipose gain, muscle mass, other aspects of body composition, and cardiometabolic disease risk. Some, but not all, studies have shown that supplementation with FO affects energy metabolism (18,(38)(39)(40). Although there was no relation between erythrocyte concentrations of LCn-3PUFAs and energy metabolism at baseline (before a meal challenge), a higher ω-3 index and DHA were associated with a less steep rise in fat oxidation after the initial decline. ...
Background Sarcopenia may hasten the risk of mortality in women with breast cancer. Long-chain omega-3 (n–3) polyunsaturated fatty acids (LCn–3PUFAs) may favor muscle mass which, in turn, could enhance resilience of cancer patients toward cancer treatment. Objectives The objective of this study was to measure the relation of erythrocyte LCn–3PUFA concentrations with lean mass, grip strength, and postprandial energy metabolism in women with newly diagnosed breast cancer. Methods This cross-sectional analysis evaluated women (n = 150) ages 65 y and younger who were recently diagnosed with breast cancer (stages I–III). Erythrocyte LCn–3PUFA composition was measured using GC. Body composition was measured by DXA. Grip strength was assessed at the same visit. Postprandial energy metabolism was measured for 7.5 h after the consumption of a high-calorie, high-saturated-fat test meal using indirect calorimetry. Associations of fatty acids with outcomes were analyzed using multiple linear regression models and linear mixed-effects models. Results The ω-3 index, a measurement of LCn–3PUFA status, was positively associated with appendicular lean mass (ALM)/BMI (β = 0.015, P = 0.01) and grip strength (β = 0.757, P = 0.04) after adjusting data for age and cancer stage. However, when cardiorespiratory fitness was also included in the analyses, these relations were no longer significant (P > 0.08). After a test meal, a higher ω-3 index was associated with a less steep rise in fat oxidation (P = 0.02) and a steeper decline in glucose (P = 0.01) when adjusting for age, BMI, cancer stage, and cardiorespiratory fitness. Conclusions The ω-3 index was positively associated with ALM/BMI and grip strength in women newly diagnosed with breast cancer and was associated with altered postprandial substrate metabolism. These findings warrant further studies to determine whether enriching the diet with LCn–3PUFAs during and after cancer treatments is causally linked with better muscle health and metabolic outcomes in breast cancer survivors.
... Moreover, it has been reported that BAT is activated by food ingredients such as capsinoids, thereby contributing to a reduction in body fat [15,16]. Fish oil (FO) also has anti-obesity effects in humans [17][18][19]. FO contains a high content of n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which must be obtained from the diet or synthesized from alpha-linolenic acid in the body [20][21][22]. DHA and EPA bind to peroxisome proliferator-activated receptor (PPAR) α and thereby activate PPARα [23,24], which is highly expressed in BAT [25]. ...
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Increasing energy expenditure (EE) is beneficial for preventing obesity. Diet-induced thermogenesis (DIT) is one of the components of total EE. Therefore, increasing DIT is effective against obesity. We examined how much fish oil (FO) increased DIT by measuring absolute values of DIT in mice. C57BL/6J male mice were given diets of 30 energy% fat consisting of FO or safflower oil plus butter as control oil (Con). After administration for 9 days, respiration in mice was monitored, and then the data were used to calculate DIT and EE. DIT increased significantly by 1.2-fold in the FO-fed mice compared with the Con-fed mice. Body weight gain was significantly lower in the FO-fed mice. FO increased the levels of uncoupling protein 1 (Ucp1) mRNA and UCP1 protein in brown adipose tissue (BAT) by 1.5- and 1.2-fold, respectively. In subcutaneous white adipose tissue (subWAT), the levels of Ucp1 mRNA and UCP1 protein were increased by 6.3- and 2.7-fold, respectively, by FO administration. FO also significantly increased the expression of markers of browning in subWAT such as fibroblast growth factor 21 and cell death-inducing DNA fragmentation factor α-like effector a. Thus, dietary FO seems to increase DIT in mice via the increased expressions of Ucp1 in BAT and induced browning of subWAT. FO might be a promising dietary fat in the prevention of obesity by upregulation of energy metabolism.
... Adiponectin has a role in the modulation of lipid and glucose metabolism together with insulin-sensitive tissues. 27 In humans, levels of adiponectin are lower in IR states, as well as in T2DM. Experimental studies revealed supplementation with O-3 PUFA improved insulin sensitization, thru increased levels of adiponectin and reduced inflammation. ...
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Despite advances in medical management diabetes mellitus (DM), it remains on the rise and it is the major cause of morbidity and mortality. Its etiology is multifactorial involving environmental, genetic and behavioral origins. It is closely linked to sedentary life and inappropriate food intake. Patients with DM should know about the uses of correct nutritional habits, which is the key in the regulation of blood glucose. Despite the promising experimental investigations, currently, the clinical evidence for the usage of omega-3 sup-plementation for the management of DM and its complications is both conflicting and limited. In this narrative review, I will summarize recent findings about dietary sources, the potential mechanisms, benefits, and practical considerations on omega-3 polyunsaturated fatty acid supplementation for the management of DM. The search of literature for this narrative review was done comprehensively by using appropriate search terms and different electronic databases.
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Insulin resistance is an important feature of metabolic syndrome and a precursor of type 2 diabetes mellitus (T2DM). Overnutrition-induced obesity is a major risk factor for the development of insulin resistance and T2DM. The intake of macronutrients plays a key role in maintaining energy balance. The components of macronutrients distinctly regulate insulin sensitivity and glucose homeostasis. Precisely adjusting the beneficial food compound intake is important for the prevention of insulin resistance and T2DM. Here, we reviewed the effects of different components of macronutrients on insulin sensitivity and their underlying mechanisms, including fructose, dietary fiber, saturated and unsaturated fatty acids, and amino acids. Understanding the diet-gene interaction will help us to better uncover the molecular mechanisms of T2DM and promote the application of precision nutrition in practice by integrating multi-omics analysis.
Peroxisome proliferator activated receptor gamma (PPARγ) activation has been shown to protect against intestinal injury induced by different stimuli. PPARγ is known to regulate tight junction proteins (TJP) in epithelial cells. Both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are natural PPARγ agonists, but the implication of PPARγ in their physiological effects on the gut is poorly understood. Therefore, this study was conducted to investigate the mechanism of EPA and DHA effects on intestinal epithelial cell barrier function in IPEC-J2 cells exposed to deoxynivalenol (DON), a known food mycotoxin that is toxic to both humans and animals. Exposure of cells to EPA and DHA significantly increased mRNA expression of a PPARγ target gene, AP2, and concomitantly increased the protein expression of claudin-4. Treatment with EPA and DHA also reversed the endocytosis and degradation of claudin-4 caused by DON exposure. EPA and DHA also restored the membrane presence of claudin-4 and ZO-1 that was disrupted by DON. However, the protective effects of EPA and DHA against DON exposure was abolished by a specific PPARγ antagonist (T0070907), confirming the importance of PPARγ in regulating TJP expression by the fatty acids. Effect of PPARγ activation by EPA and DHA also included the restoration of transepithelial electrical resistance (TEER) and reduction of fluorescein isothiocyanate-labeled dextran (FITC-dextran) permeability that have been perturbed by DON. However, the effectiveness of EPA and DHA in opposing DON-induced decrease in TEER and the increase in FITC-dextran permeability was not affected by PPARγ inhibition, potentially suggesting the involvement of other PPARγ-independent mechanisms in the observed benefits from EPA and DHA. Collectively, this study shows that the protective effects of EPA and DHA against DON-induced intestinal barrier disruption are through both PPARγ-dependent and-independent pathways. Therefore, EPA and DHA containing ingredients could be used to prevent the DON-induced gut barrier dysfunction in humans and animals.
Context: Current recommendations for counteracting the action of obesity advocate the consumption of a healthy diet and participation in regular physical activity. Studies have indicated towards a potential role of long-chain omega-3 polyunsaturated fatty acids (LC N-3 PUFA) in a number of effects which ameliorate the condition of obesity. Objective: To assess the effect of LC N-3 PUFA (Docosahexaenoic acid and Ecosapentaenoic acid) on obese individuals. Data sources: Using Cochrane guidelines, electronic databases-Google Scholar and PubMed-NCBI were searched for evidence from the last 10 years (March 2007-17). Study selection: Randomized Controlled Trials (RCT) based on LC N-3 PUFA supplementation involving obese adult were included. Result: The association between change in body weight/ body mass index (BMI)/ waist circumference and fish oil supplementation in 31 RCTs involving overweight or obese adults was investigated. Of the 31 studies, 9 did not provide any evidence for the biomarkers of LC N-3 PUFA intake like EPA/DHA fatty acids plasma concentration and N-3 FA percentage in serum phospholipids. The preliminary evidence suggested that LC N-3 PUFA supplementation combined with energy-restricted diets or exercises prevents weight regain. Treatment groups showed a higher drop in BMI and body fat percentage (0.24kg/m2; 0.49%) than controls. Conclusion: While there is growing evidence that LC N-3 PUFA can improve body composition, contradictory findings have also been reported. There is an urgent need for long-term studies and meta-analysis in this area of research to generate conclusive evidence on the effects of LC n-3 PUFA supplementation on obesity.
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The province of Newfoundland and Labrador, Canada, generates tons of shrimp processing by-product every year. Shrimp contains omega (n)-3 polyunsaturated fatty acids (PUFA) and astaxanthin (Astx), a potent antioxidant that exists in either free or esterified form (Astx-E). In this study, shrimp oil (SO) was extracted from the shrimp processing by-product using the Soxhlet method (hexane:acetone 2:3). The extracted SO was rich in phospholipids, n-3 PUFA, and Astx-E. The 3T3-L1 preadipocytes were differentiated to mature adipocytes in the presence or absence of various treatments for 8 days. The effects of SO were then investigated on fat accumulation, and the mRNA expression of genes involved in adipogenesis and lipogenesis in 3T3-L1 cells. The effects of fish oil (FO), in combination with Astx-E, on fat accumulation, and the mRNA expression of genes involved in adipogenesis and lipogenesis were also investigated. The SO decreased fat accumulation, compared to untreated cells, which coincided with lower mRNA expression of adipogenic and lipogenic genes. However, FO and FO + Astx-E increased fat accumulation, along with increased mRNA expression of adipogenic and lipogenic genes, and glucose transporter type 4 (Glut-4), compared to untreated cells. These findings have demonstrated that the SO is a rich source of n-3 PUFA and Astx-E, and has the potential to elicit anti-adipogenic effects. Moreover, the SO and FO appear to regulate adipogenesis and lipogenesis via independent pathways in 3T3-L1 cells.
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Insulin resistance (IR) is apparent when tissues responsible for clearing glucose from the blood, such as adipose and muscle, do not respond properly to appropriate signals. IR is estimated based on fasting blood glucose and insulin, but some measures also incorporate an oral glucose challenge. Certain (poly)phenols, as supplements or in foods, can improve insulin resistance by several mechanisms including lowering postprandial glucose, modulating glucose transport, affecting insulin signalling pathways, and by protecting against damage to insulin-secreting pancreatic β-cells. As shown by intervention studies on volunteers, the most promising candidates for improving insulin resistance are (−)-epicatechin, (−)-epicatechin-containing foods and anthocyanins. It is possible that quercetin and phenolic acids may also be active, but data from intervention studies are mixed. Longer term and especially dose-response studies on mildly insulin resistant participants are required to establish the extent to which (poly)phenols and (poly)phenol-rich foods may improve insulin resistance in compromised groups.
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The 4th edition of the Nordic Nutrition Recommendations, NNR 2004, gives the proportions between energy yielding nutrients, recommended daily intakes (RI) of certain vitamins and minerals, and reference values for energy intakes in different age and sex groups. Recommendations are also given for dietary fibre, salt and alcohol. Recommendations on daily physical activity are now included and interaction with physical activity has been taken into account for the individual nutrient recommendations wherever appropriate. For adults 30 minutes of daily physical activity of at least moderate intensity is recommended. More physical activity (about 60 minutes daily) with a moderate and/or vigorous intensity may be needed for prevention of weight gain. For children a minimum of 60 minutes of physical activity every day is recommended. As in the 3rd edition, the recommendation is to limit of the intake of saturated plus trans fatty acids to about 10% of the total energy intake (E%) and of the total fat intake to 30 E%. The intake of carbohydrate and dietary fibres should increase, while the intake of refined sugars should not exceed 10 E%. The RI for vitamin A (women) has been lowered, while it has been increased for vitamin D (children and adults up to 60 y), vitamin C (adults) and folate (women of reproductive age; pregnant and lactating women). NNR is to be used for planning and evaluation of diets, and as a basis for food and nutrition policy, teaching and dietary information.
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To study the effects of dietary fish oil on insulin-stimulated glucose metabolism in adipocytes of insulin-resistant rats (rats fed 50% sucrose and 30% fat), eighteen 5-wk-old Sprague-Dawley rats were fed, for 6 wk, a diet containing 30% fat as either fish oil (FO) or a mixture of vegetable and animal oils (control oils (CO)). A third reference group was fed a standard diet (62% corn starch and 13% fat). At the end of the 6- wk period, the two experimental groups had comparable plasma glucose concentrations that were higher than that found in the reference group. FO feeding corrected the hyperinsulinemia of the experimental rats (P < 0.05) to reach values in the reference group. Plasma triacylglycerol (P < 0.01) and cholesterol (P < 0.001) concentrations were also lower in rats fed FO than in those fed CO. The body weights of FO-fed rats were similar to that of CO-fed rats, but epididymal adipose tissue weight was lower (P < 0.01). Adipocytes of FO- fed rats, compared with those of CO-fed rats, had high insulin-stimulated glucose transport (P < 0.05), oxida tion (P < 0.001) and incorporation into total lipids (P < 0.05). The incorporation of (n-3) polyunsaturated fatty acids in adipocyte membrane phospholipids was higher in FO-fed rats than in those fed CO (P < 0.0001). Insulin action was positively correlated with the fatty acid unsaturation index in membrane phospho lipids. Thus dietary fish oil has beneficial effects on insu- linemia, plasma lipids and insulin-stimulated glucose metabolism in insulin-resistant slightly diabetic rats. J. Nutr. 126: 1951-1958, 1996.
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Over the past 20 years many studies and clinical investigations have addressed the beneficial effects of polyunsaturated fatty acids in general and ω3 fatty acids in particular. It is currently known that ω3 fatty acids play important role in the prevention of several pathologies like the coronary heart disease, hypertension, diabetes and other. The protection played by ω3 fatty acids against coronary heart disease may be related to antiatherogenic effects and/or to the modification of risk factors through mechanisms related to lipid metabolism. The objective of this work was to evaluate, in healthy volunteers, the effect of a diet supplementation with canned sardine, which is rich in co3 fatty acids on the profile of plasma and erythrocytes, lipids, phospholipids and fatty acids.The serum levels of total cholesterol and high density lipoproteins (HDL) did not change during the period of the supplementation, tri-acylglycerol levels showed a trend for a decrease and low density lipoproteins (LDL)-derived thiobarbituric acid-reactive substances (LDL TBARS) levels showed a decrease. Incorporation of eicosapentaenoic and docosahexaenoic fatty acids (EPA and DHA, respectively) into plasma and erythrocyte phospholipids was observed. The results suggest that the undergone dietary supplementation may have allowed the incorporation of co3 polyunsaturated fatty acids into cell membranes and has increased the resistance of LDL to oxidative stress. This may represent protection factors against atherosclerosis and cardiovascular disease.
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Insulin action was assessed by using the hyperinsulinemic (approximately 800 pmol/L) euglycemic clamp in rats fed equal amounts of glucose or fructose (35% of calories) for 4 wk. The glucose infusion rate required to maintain euglycemia was decreased in fructose-fed animals (14.6 +/- 1.4 vs 21.8 +/- 1.1 for glucose-fed rats, p less than 0.001) with this whole-body effect contributed to equally by an impairment in hepatic insulin action and a reduction in peripheral glucose disposal in a range of tissues. There was no difference in basal glucose turnover, energy expenditure, or postprandial blood glucose and insulin responses to the diets. In the fructose-fed rats there was an increase in fasting triglyceride levels by 2 wk. Euglycemic clamp glucose disposal correlated positively and clamp hepatic glucose output correlated negatively with fasting triglyceride levels. In summary, fructose but not glucose feeding led to impaired insulin action in both the liver and peripheral tissues, effects that may depend on antecedent circulating triglyceride levels.
The effects of three dietary fats, corn oil (CO), tallow (T) and marine oil (MO), on serum triglyc érides, hepatic lipogenic enzyme activity and lipogenesis in vivo using 3H2O were measured in fed and fasted rats that had been consuming diets in which the carbohydrate was either glucose or fructose. Hepatic triglycéride secretion was also measured in fasted rats fed the same diets. In both the fed and fasted state, hepatic enzyme activity and lipogenesis in vivo were greater in fructose-fed rats than in glucose-fed rats and less in both CO- and MO-fed rats than in T-fed rats. In rats fed glucose, serum triglycérides were lower in fasted rats fed MO than in fasted rats fed CO. In rats fed glucose or fructose, hepatic triglycéride secretion was lower in rats fed MO than in those fed CO or T. J. Nutr. 118: 1061-1067, 1988. lipogenesis
The UK dietary guidelines for cardiovascular disease acknowledge the importance of long-chain omega-3 polyunsaturated fatty acids (PUFA) – a component of fish oils – in reducing heart disease risk. At the time, it was recommended that the average n-3 PUFA intake should be increased from 0.1 to 0.2 g day−1. However, since the publication of these guidelines, a plethora of evidence relating to the beneficial effects of n-3 PUFAs, in areas other than heart disease, has emerged. The majority of intervention studies, which found associations between various conditions and the intake of fish oils or their derivatives, used n-3 intakes well above the 0.2 g day−1 recommended by Committee on Medical Aspects of Food Policy (COMA). Furthermore, in 2004, the Food Standards Agency changed its advice on oil-rich fish creating a discrepancy between the levels of n-3 PUFA implied by the new advice and the 1994 COMA guideline. This review will examine published evidence from observational and intervention studies relating to the health effects of n-3 PUFAs, and discuss whether the current UK recommendation for long-chain n-3 PUFA needs to be revisited.
The aim of the study was to validate a food frequency questionnaire (FFQ) measuring seafood intake among young adults in Europe. Participants from Iceland, Spain and Ireland (n = 56), aged 20–40, filled out a pre-coded FFQ on seafood. One week after filling out the questionnaire, the participants started a 7–14-day food record (FR). The FFQ was found suitable to rank young adults according to their customary intake of fish and fish oil, but it overestimated the amount consumed. The FFQ could be used as a tool to identify high- and low-fish consumers.
To examine the association of fish intake with the subsequent risk of impaired glucose tolerance and diabetes mellitus (glucose intolerance). In 1971, information about food intake was obtained by the cross-check dietary history method on 175 men and women aged 64-87 yr who were normoglycemic and free of clinical diabetes. During the follow-up period from 1972 to 1975, an oral glucose tolerance test was performed annually, and in 59 of 175 elderly people a diagnosis of glucose intolerance was made at least once. In 1971, approximately 60% of the subjects usually ate fish, with a mean daily intake of 24.2 g. In fish eaters, the incidence of glucose intolerance was significantly lower compared with nonfish eaters (odds ratio [OR] 0.40, 95% confidence interval [CI] 0.21-0.77). With logistic regression analysis, this inverse association could not be explained by taking into account age and sex or possible confounding baseline characteristics, such as the prevalence of myocardial infarction, body mass index, energy intake per kilogram body weight, or intake of carbohydrates (OR 0.47, 95% CI 0.23-0.93). Baseline characteristics of the oral glucose tolerance test and serum triglyceride levels could also not account for this result. These results suggest that, in an elderly population, the habitual consumption of a small amount of fish may protect against the development of impaired glucose tolerance and diabetes mellitus.
High levels of some but not all dietary fats lead to insulin resistance in rats. The aim of this study was to investigate the important determinants underlying this observation. Insulin action was assessed with the euglycemic clamp. Diets high in saturated, monounsaturated (omega-9), or polyunsaturated (omega-6) fatty acids led to severe insulin resistance; glucose infusion rates [GIR] to maintain euglycemia at approximately 1000 pM insulin were 6.2 +/- 0.9, 8.9 +/- 0.9, and 9.7 +/- 0.4 min-1, respectively, versus 16.1 +/- 1.0 in chow-fed controls. Substituting 11% of fatty acids in the polyunsaturated fat diet with long-chain omega-3 fatty acids from fish oils normalized insulin action (GIR 15.0 +/- 1.3 Similar replacement with short-chain omega-3 (alpha-linolenic acid, 18:3 omega 3) was ineffective in the polyunsaturated diet (GIR 9.9 +/- 0.5 but completely prevented the insulin resistance induced by a saturated-fat diet (GIR 16.0 +/- 1.5 and did so in both the liver and peripheral tissues. Insulin sensitivity in skeletal muscle was inversely correlated with mean muscle triglyceride accumulation (r = 0.95 and 0.86 for soleus and red quadriceps, respectively; both P less than 0.01). Furthermore, percentage of long-chain omega-3 fatty acid in phospholipid measured in red quadriceps correlated highly with insulin action in that muscle (r = 0.97). We conclude that 1) the particular fatty acids and the lipid environment in which they are presented in high-fat diets determine insulin sensitivity in rats; 2) impaired insulin action in skeletal muscle relates to triglyceride accumulation, suggesting intracellular glucose-fatty acid cycle involvement; and 3) long-chain omega-3 fatty acids in phospholipid of skeletal muscle may be important for efficient insulin action.