Prevention of Type 2 Diabetes through Sardines Consumption: An Integrative Review

Abstract

There are many studies regarding stop the progression to type 2 diabetes (T2D) through dietary control but there is no global recommendation for a specific diet. The strongest evidence is weight control through nutritional education but it does not include elderly people because of the risk of malnutrition that would entail. Therefore, the search for specific foods that can help slow down the progress towards T2D are of great interest. Although the controversy between fish consumption and the risk of developing T2D, it has been observed that oily fish could play a protective role. This type of fish may contain large amounts of persistent organic pollutants (POPs) but, on the contrary, contain omega-3 with effects on the cardiovascular system. In addition, the presence of taurine, a semi-essential amino acid very present in oily fish and which has been studied its antidiabetogenic effect, could play an essential role in the protective effect of this type of fish against T2D. Among them, the one with the highest concentrations of omega-3 and taurine as well as low concentration of POPs is sardine. An integrative review of observational studies and clinical trials was performed to investigate the association between sardine consumption and T2D prevention.

Full text

Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=lfri20
Food Reviews International
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/lfri20
Prevention of Type 2 Diabetes through Sardines
Consumption: An Integrative Review
Diana A. Díaz-Rizzolo , Anna Miro & Ramon Gomis
To cite this article: Diana A. Díaz-Rizzolo , Anna Miro & Ramon Gomis (2021): Prevention of Type
2 Diabetes through Sardines Consumption: An Integrative Review, Food Reviews International,
DOI: 10.1080/87559129.2020.1867565
To link to this article: https://doi.org/10.1080/87559129.2020.1867565
© 2021 The Author(s). Published with
license by Taylor & Francis Group, LLC.
View supplementary material
Published online: 06 Jan 2021.
Submit your article to this journal
Article views: 386
View related articles
View Crossmark data

REVIEW
Prevention of Type 2 Diabetes through Sardines Consumption: An
Integrative Review
Diana A. Díaz-Rizzolo
a,b,c
, Anna Miro
b
, and Ramon Gomis
a,b,d,e,f
a
Faculty of Health Science, Universitat Oberta De Catalunya, Barcelona, Spain;
b
Diabetes and Obesity Research
Laboratory, Institut dInvestigacions Biomèdiques August Pi I Sunyer (IDIBAPS) – Hospital Clinic of Barcelona,
Barcelona, Spain;
c
Primary Healthcare Transversal Research Group, IDIBAPS, Barcelona, Spain;
d
Department of
Medicine, University of Barcelona, Barcelona, Spain;
e
Department of Medicine, Centro De Investigación Biomédica En
Red De Diabetes Y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain;
f
Department of Endocrinology and
Nutrition, Hospital Clinic of Barcelona, Barcelona, Spain
ABSTRACT
There are many studies regarding stop the progression to type 2 diabetes
(T2D) through dietary control but there is no global recommendation for
a specic diet. The strongest evidence is weight control through nutritional
education but it does not include elderly people because of the risk of
malnutrition that would entail. Therefore, the search for specic foods that
can help slow down the progress towards T2D are of great interest. Although
the controversy between sh consumption and the risk of developing T2D, it
has been observed that oily sh could play a protective role. This type of sh
may contain large amounts of persistent organic pollutants (POPs) but, on
the contrary, contain omega-3 with eects on the cardiovascular system. In
addition, the presence of taurine, a semi-essential amino acid very present in
oily sh and which has been studied its antidiabetogenic eect, could play an
essential role in the protective eect of this type of sh against T2D. Among
them, the one with the highest concentrations of omega-3 and taurine as
well as low concentration of POPs is sardine. An integrative review of
observational studies and clinical trials was performed to investigate the
association between sardine consumption and T2D prevention.
KEYWORDS
Type 2 diabetes; prediabetes;
prevention; fish; oily fish;
sardine; taurine; omega-3
T2D risk
Diabetes mellitus (DM) has become a worldwide health problem and its prevalence is continuously
increasing. Type 2 diabetes (T2D) is the most common form of DM, covering between 90 and 95% of
the total cases, and it is, together with its complications, a major cause of early death particularly in low
and middle-income countries .
[1]
T2D is led by a first state named prediabetes (preDM) which is characterized by high circulating
glucose levels above normal but without reaching diabetes levels. According to the American Diabetes
Association (ADA), preDM may be diagnosed based on plasma glucose criteria, by the presence of
impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and/or high values of glycated
hemoglobin (HbA1c) .
[2]
The natural history of preDM predicts that up to 70% of individuals with this condition will
develop T2D and the annual conversion ratio in general population is around 5–10% .
[3,4]
But,
both prevalence of T2D and preDM increase significantly with age
[5]
and it is considered that the
number of new-onset T2D in ≥65 years old is increasing 4.5-fold compared to 3-fold in total
CONTACT Diana A. Díaz-Rizzolo Email dadiaz@clinic.cat Faculty of Health Science, Universitat Oberta De Catalunya,
Barcelona, Spain.
Supplemental material for this article can be accessed here.
FOOD REVIEWS INTERNATIONAL
https://doi.org/10.1080/87559129.2020.1867565
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://
creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the
original work is properly cited, and is not altered, transformed, or built upon in any way.

population .
[6]
Precisely, in the majority of European countries the prevalence of T2D is between
10–20% in people aged 60–80 years and the prevalence of preDM is between 15 and 20% for
people older than 60 years of age .
[7]
T2D prevention
As preDM is a reversible condition, many therapies have been developed to reduce the conversion
ratio to T2D. Most of them aim to reduce body weight due to studies in which it was observed that
intentional weight loss in overweight participants were associated with a lower rate of T2D develop-
ment .
[8]
This is due to increasing adiposity could be responsible for insulin resistance (IR) that drives
in T2D .
[9]
Specifically, with a weight loss goal intervention, the incidence of converting from preDM to T2D
reduced. In particular, the percentage conversion to T2D was approximately 9% for subjects who lost
at least 5% of their body weight .
[10]
Also, it has been reported by losing about a 7% of body weight,
a reduction of 58% to the risk of manifesting T2D can be achieved .
[11,12]
According to previous
studies, nutrition interventions have significant effects on weight loss .
[13–15]
Weight loss by regulating
lifestyle interventions, including nutrition interventions, has been associated with a lower incidence of
diabetes .
[16]
Precisely, studies reveal that intensive lifestyle modification has a higher effect on T2D
prevention than common used hypoglycemic drugs,
[17]
which together with gastric surgery are only
recommended to those with high risk of developing T2D and a BMI ≥ 25 kg/m2 or BMI ≥ 35 kg/m2,
respectively .
[18]
Despite that, overweight and obesity account for 44% of the T2D cases
[19]
and the connotation
“diabesity” was created as the modern epidemic,
[20]
there are non-obese people that develop T2D in
which weight loss should not be a proposed intervention. This becomes especially sensitive in the
highest prevalence age group, the elderly where weight loss in ≥65 year old individuals has been
reported to cause loss of lean body mass, bone mineral density, and fat mass, leading to different health
problems,
[21]
despite its usual beneficial effects in physical function and metabolic parameters .
[22]
Even so, some epidemiological studies have shown that it leads to increased mortality,
[23,24]
con-
cretely, the crude mortality rate for ≥65 years old in those who lost weight was 6%, compared with
2.6% in the stable weight and 2.4% in the weight gain group .
[25]
Generally, nutritional interventions used for weight loss are based on hypocaloric diets that and,
even in the presence of obesity, caloric restriction in this group is not always advised because can lead
to malnutrition .
[26]
A more interesting intervention, for this age group but also for all the people
without weight problems but with T2D risk, would be one based on changing dietary patterns instead
of focused on restricting caloric intake .
[27]
According to ADA, there is not a recommended diet to treat T2D or to prevent it, although it
advises following a diet rich in whole grain, fruits, vegetables, seafood omega-3 fats and poultry.
A dietary pattern similar to the Mediterranean diet has been seen to reduce mortality due to diabetes
condition or cardiovascular disease (CVD) in a 50% in an aging population with normal weight but
also with a BMI above 25 .
[28]
Many dietary treatments have been tested in which they demonstrate
that caloric restriction is not the only way to achieve preDM control.
On one hand, studies based on the association of micronutrients intake and T2D risk have been
demonstrated protective associations especially for calcium and vitamin D with odds ratio (OR) 0.82,
[29]
vitamin E
[30]
with OR 0.80, and magnesium with OR 0.66 .
[31]
Moreover, recent review has been
published where dietary polyphenols showed antidiabetic activity in human study promoting the
prevention and management of T2D. Especially resveratrol, curcumin, and anthocyanins, despite the
structure–activity relationship are still not clear .
[32]
On the other hand, the largest number of investigations focuses especially on the study of
macronutrients. Because of its direct involvement with glycemia, carbohydrates have been among
the most studied and, in general, have shown: low carbohydrates diet has demonstrated a reduction of
HbA1c and an improvement of glycemic control
[33]
; a positive association with a diet based on low
2D. A. DÍAZ-RIZZOLO ET AL.

dietary glycemic index and/or glycemic load and protective effects against T2D
[34]
; a high-fiber diet,
translates into ≥30gr/day, showed no weight loss but an improvement in blood glucose levels .
[35]
Related to fats, different studies have shown clear associations. In an observational study, recently-
diagnosed diabetics had both higher relative intake of total fat and concretely saturated fatty acids
from animal fat sources compared with healthy controls .
[36]
Also, it has been demonstrated, with
a clear dose–response connection, an inverse relation between polyunsaturated fatty acids (PUFA)
consumption and risk to develop T2D with the highest quintile of intake 0.87 of relative risk .
[37]
Especially, this opposite relation is observed in omega-6 fatty acid (FA) consumption
[38,39]
and an
inverse association between the amount of omega-3 FA and insulin resistance was studied .
[40]
Regarding proteins, a study made in 2004 demonstrated that a high-protein but also low-
carbohydrate diet improves HbA1c in an obese population but the protein role was not clear .
[41]
On
the contrary, some years after, it was observed that a high-protein intake may be associated with
increased risk
[42]
. The source of the protein consumed could be responsible for the difference in both
results. Therefore, the risk of developing T2D was observed according to the consumption of food
groups. The association between high meat intake, especially processed meat, and an increased risk of
T2D, was especially clear. But, for fish consumption, observational studies showed confusing results .
[43]
Fish consumption
The observation that communities consuming a diet rich in fish present a low grade of chronic
diseases
[44–47]
promotes the investigation to understand what is the role of this food on health. Fish has
been seen to have many potential beneficial effects on metabolism although its physiological mechan-
isms are not well known yet. This assumption comes from different epidemiological studies in which
an inverse relation between fish consumption and the incidence of CVD, T2D, and cognitive decline
have been observed .
[44,48,49]
Fish consumption could also play a role in preventing metabolic
syndrome and it has been seen that the effect might be stronger in men than women .
[50]
Particularly, the first population-based prospective study to investigate the effect of fish intake
in the development of T2D reported that people who weekly consume fish were correlated with
a 25% decrease of T2D risk in comparison with who consume less than one portion per week .
[44]
A study on the Japanese population revealed that only small and medium-sized fish (horse mackerel,
sardine, saury, mackerel, and eel) are associated with the decrease of T2D incidence with 0,68 OR
whereas big-sized fish (salmon, skipjack tuna, cod, flatfish, and sea bream) have no relation with it .
[46]
Evidence from other studies show that a higher fish or fish oil consumption lowers the risk of CVD
and sudden death .
[50]
Therefore, it makes sense that the Japanese population present lower rates of
CVD death compared to Western population, as their fish intake is much higher .
[51,52]
Similar results
were found in an epidemiological study among the Dutch population, in which those who ate fish once
or twice per week had a 50% less CVD mortality risk compared to those who ate fewer .
[53]
More
specifically, in different meta-analyzes and reviews, the intake of between 2 and 4 servings of fish per
week was associated with a 4% reduction in the risk of suffering cerebrovascular disease
[54]
and 18% of
having a stroke .
[55]
In the same line, a consumption of 4 servings of fish per week reduced acute
coronary syndrome by 21% .
[56]
On the other hand, with a minimum consumption of 1 time per week
of fish, a reduction of around 50% due to sudden death has been observed
[57]
and with the consump-
tion of small amounts of fish a 17% reduction in death due to coronary illness .
[58]
Finally, fish
consumption has been associated with a lower prevalence of atherosclerosis .
[59–61]
However, some cohort studies reveal a positive association between fish consumption and T2D risk
.
[62,63]
It is thought that this positive association could be due to environmental contaminants in fish
such as persistent organic pollutants (POPs), dioxins or other contaminants like methyl-mercury. It is
believed that some POPs could induce abdominal obesity, impair insulin sensitivity, and reduce
glucose intake
[64,65]
and it has been observed a positive association of some POPs with T2D,
[66]
concretely, a dose-response relation between serum concentrations and T2D prevalence with 25th,
50th, 75th, and 90
th
percentiles of POPS and OR 1.0, 14.0, 14.7, 38.3, and 37.7 .
[67]
FOOD REVIEWS INTERNATIONAL 3

Despite that, data were not sufficient to establish causality and, especially with fish consumption,
there are no studies that show a higher incidence of T2D due to POPs intake through fish in diet.
Therefore, there are gaps on experimental data to confirm the chemical exposure in the pathogenesis
of T2D
[66]
and there is much work in limiting contaminants level in fish so this should not take
relevance to the beneficial effect of its intake .
[45]
The way that fish reduces T2D risk is controversial, but it has been discussed that insulin sensitivity is
positively associated with the content of omega-3 FA in cell membranes as PUFA are capable of increasing
membrane fluidity, the amount of insulin receptors, and the action of insulin .
[68]
Moreover, the beneficial
action of fish could be also led by its huge content of proteins and amino acids, as fish proteins play a role in
increasing satiety which explains its involvement in weight loss,
[69]
and also have many essential amino
acids. Therefore, the anti-inflammatory effect of fish consumption, which is generally attributed to omega-
3 FA intake, could also be due to the consumption of fish proteins .
[70]
Nevertheless, higher fish intake is usually linked to healthier diets and physical activity which could
mean the protective effect against T2D and other diseases may be due to the synergistic action of all these
parameters. According to that, a review about the effect of the Mediterranean diet on prevention of CVD
suggests that this kind of diet which is rich in fish, has a protective effect on some risk factors considering
that it is capable of reducing total cholesterol and blood pressure .
[71]
Because of all these beneficial effects
of fish, dietary guidelines recommend the intake of this food, preferentially oily fish, at least twice a week .
[2]
Oily sh
Due to the controversial results obtained in different observational but also interventional studies
between fish consumption and T2D risk, a meta-analyses was realized dividing lean and oily fish due
to its composition .
[72]
Lean fish store lipid in the liver while oily fish store lipid in the flesh, which
leads to a higher fat intake when consuming oily fish. In this meta-analyses, a significant effect of oily
fish intake on risk of T2D was shown. Concretely, dose-response analysis suggested that 80 g intake of
oily fish per day may reduce the risk of T2D by 20% .
[72]
Changes in lipid profile have been observed when a diet rich in oily fish is followed. Exactly, oily fish is
rich in PUFA omega-3 FA, both of α-linolenic acid (ALA) as well as eicosanoid acid (EPA) and
docosahexaenoic acid (DHA) which have been the primary seafood components with proven health
benefits. Therefore, nutritional recommendations are made to ensure their consumption in the prevention
of CVD including 400–500 mg/day of EPA and DHA or at least 2 servings/week of oily fish .
[73]
But, EPA
and DHA are not the only ones, most lipids present in oily fish are found to be involved in insulin signaling
and inflammation,
[74]
especially ceramides, sphingolipids which are thought to be the junction between
excess of nutrients, proinflammatory cytokines, and insulin resistance .
[75]
An oily fish intake 100–150 gr/
meal at least four time a week for 8 weeks produced a decrease of plasma lipids (ceramides, lysopho-
sphatidylcholines, diacyglycerols, lysophosphatidylethanolamines and phosphatidylcolines) with an aver-
age reduction of −0.5 fold change .
[74]
Moreover, oily fish consumption in 150gr/meal for 5 meals/week
during 4 weeks demonstrated a decreased in serum triglycerides (TAG) whereas it increases HDL
cholesterol .
[76]
Both parameters were widely observed in various studies and a meta-analysis concluded
that oily fish consumption (ranging 20–150g/day for 4–24 weeks) in healthy or with CV risk (hyperlipi-
demia, hypertriacylglycerolaemia or obese) adults, leads to a moderately significant reduction in plasma
TAG levels (−9.73 mg/dL) and an increase in HDL cholesterol levels (2.32 mg/dL)
[77]
which is associated
with reducing CVD risk factors
[78]
strongly associated with T2D pathogenesis .
[79]
Despite the fact that PUFA blood profile has been shown to be modified in patients with T2D as
a diminished (EPA+DHA)/arachidonic acid ratio has been seen,
[80]
it has been observed that people with
higher plasma phospholipid omega-3 FA have lower risk of T2D progression .
[81]
It has been described that
higher protective effect of oily fish compared to lean fish against T2D is due to its huge content in omega-3
FA, which improves insulin-stimulated oxidative and non-oxidative glucose disposal through the reduc-
tion in the inhibitory effect of excessive β-oxidation in humans
[82]
and prevent diet-induced insulin
resistance through the insulin-sensitizing action of omega-3 FA in a nonhuman primate model .
[83]
4D. A. DÍAZ-RIZZOLO ET AL.

Interventions with omega-3 mix supplementation did not show the same effect (Fig. 1). Even the omega-3s
called EPA and DHA, proposed as responsible for those benefits,
[44,45,51]
could not demonstrate their
benefits in isolated supplementation .
[84]
All of this, leads us to think about the whole food as the developer
of this beneficial effect against T2D progression. Therefore, the type of fish, cooking methods or environ-
mental contaminants could have an impact on results .
[72]
Although the effect of omega-3 FA, this action may also be assisted by fish proteins and vitamins,
which are thought to improve insulin sensitivity and have antihypertensive, antioxidant, antiproli-
ferative and anticoagulant capacities .
[76,85–88]
Different bioactive motifs have been found which are
thought to have antidiabetic and hypocholesterolemic properties .
[88]
Moreover, in a model of high-fat
-fed rats supplemented with different fish proteins a reduction of proinflammatory cytokines was seen,
[87]
although only salmon proteins promotes an improvement in adipose tissue composition .
[86]
So, according to the previous statements, oily fish would be capable of improving endothelial
dysfunction, and arrhythmia, reducing microvascular complications, and improving other mechan-
isms present in both T2D and CVD .
[89]
On the differences between lean and oily fish, apart from fat content in the flesh, increased presence of
fat-soluble vitamins such as vitamin D in oily fish .
[90]
There are no major differences in overall protein
content between white and blue fish, but there are specific differences with some amino acids .
[91]
Taurine
One of the amino acids highly present in seafood and specially in oily fish is taurine (2-aminoetha-
nesulfonic acid), a semi-essential amino acid which is normally found in high concentrations in β
pancreatic islets .
[92]
Taurine is normally assimilated through diet but it can also be synthesized in
small proportions in the pancreas with the presence of cysteine. Its main functions involve oxidative
stress, Ca
+2
transport regulation, osmoregulation, and anti-inflammation .
[93,94]
Taurine levels have been found decreased in subjects with preDM or T2D, which is thought to be
due to the overactivity of the polyol pathway coming from the increased glucose levels .
[95,96]
This fact
suggests a lack of taurine as a role in T2D development and further complications which have been
demonstrated in T2D animal models where taurine supplementation among T2D rats has been
observed to decrease glucose levels and increase plasma insulin,
[97]
but clinical trials have not been
able to demonstrate this fact on human
[98,99]
(Table 1).
Taurine has been described to have hypoglycemic effects (improving hepatic insulin sensitivity,
stimulating glycogen synthesis in the liver and glucose uptake in peripheral tissues such as the
Figure 1. Justification for the choice of sardines in relation to possible preventive effects in humans against the risk of developing
T2D.
FOOD REVIEWS INTERNATIONAL 5

Table 1. Studies with taurine supplementation.
Compound Dose Model Sample size Effect Reference
Taurine 0,3 mM
taurine
3T3-L1 preadipocyte
In vitro
- Promotion of autophagosome formation and
autophagic flux. Antioxidant activity
through ROS.
[100]
Taurine 1% taurine per day
21 days
Adult male Wistar rats 45 total.
Taurine groups: 6 non-diabetic and 10
diabetic
Restores GLUT4 expression. Antioxidant,
antihyperlipidemic and antiinflammatory
action.
Decreases circulating damage cardiac
markers, proinflammatory cytokines and
NFkB translocation.
[101]
Taurine 2% taurine
30 days
Male Swiss mice 76 total.
36 in group of taurine supplemented
Higher nuclear expression of PDX-1 and
peripheral insulin sensitivity. No effect on
body weight nor basal blood glucose.
[92]
Taurine 5% taurine
supplement
19 weeks
Female and male Swiss mice Total not reported.
7–30 in each 2 groups of taurine
supplemented
Improves plasma glucose levels (117 ± 7 and
142 ± 7 mg/dL taurine supplemented and
control respectively), glucose tolerance
(ipGTT around −100 mg/dL at 120 and
180 min compared to control), insulin
sensitivity (AUC for ipGTT around
−1000 mg/dL.min
−1
compared to control)
and activates Akt in liver (30% higher than
control) in high fat diet fed ones.
[95]
Taurine 2% taurine, high fat
diet
10 weeks
Male mice C57BL/6 40 total.
8–10 in each 2 groups of taurine
supplemented
Improves in high fat diet mice body weight
(8.7 ± 0.8 and 14.5 ± 0.9 gr taurine
supplemented and control respectively) and
visceral fat (1229.8 ± 214.7 and
1866.3 ± 183.5 mg taurine supplemented
and control respectively). Improves plasma
glucose levels (around −20 mg/dL in all
timepoint compared to control) disturbance
plasma insulin (between −4 and −10 ng/ml
in different timepoint compared to control)
and leptin (between −5 and −50 ng/ml in
different timepoint compared to control)
and Per1 expression in pancreatic islets.
[102]
(Continued)
6D. A. DÍAZ-RIZZOLO ET AL.

Table 1. (Continued).
Compound Dose Model Sample size Effect Reference
Taurine 2% taurine,
12 weeks
OLETF diabetic rats 14 total.
7 in taurine-supplemented group
Ameliorates hyperglycemia (200 mg/dL and
>300 mg/dL fasted glucose taurine
supplemented and control respectively) and
dyslipidemia by reducing insulin resistance
(HOMA-IR was half in the group
supplemented with taurine) and leptin level
(serum leptin levels was half in the group
supplemented with taurine)
[103]
Taurine 750 mg/kg taurine
71 days
Alloxan-treated diabetic rats 75 total.
25 in taurine-supplemented group
Improves hyperglycemia by glucose plasma
reduction (3.69 ± 0.12 and
10.34 ± 0.92 mmol/L taurine supplemented
and control respectively) and insulin plasma
increase (56.03 ± 2.78 and 21.23 ± 0.74
pmol/L taurine supplemented and control
respectively)
[97]
Taurine 1,5 g/day
8 weeks
Overweight men with a genetic predisposition
for T2D
20 total.
10 in taurine-supplemented group
No effect of taurine on body weight, blood
pressure, insulin secretion and sensitivity
nor glucose homeostasis and HbA1c.
[98]
Taurine 3 g/day
4 months
T2D participants without DM-medication 45 total.
30 in taurine-supplemented group
No effects in glucose, HbA1c, lipids or insulin.
[99]
FOOD REVIEWS INTERNATIONAL 7

liver and skeletal muscle) and is also capable of decreasing serum cholesterol in different ways .
[93]
It
plays a role in bile acids and its transporters,
[104]
and also enhances the expression of 7α-hydroxylase,
which is involved in biliary acid synthesis .
[105]
At the glycemic level, taurine has been seen to promote
nuclear expression of PDX-1 factor, which is required for the expression of insulin, and various genes
involved in the same pathways such as Glut-2, GK, Sur-1, Pcsk-1 .
[92]
Moreover, a function as an
antioxidant has been reported as well as promoting autophagy by interacting with taurine-induced
nuclear translocation of transcription factor EB (TFEB) .
[92]
In other way, taurine has been shown to participate in the modulation of circadian rhythm. The
circadian clock maintains alignment of peripheral tissue clocks present in nearly all cells and circadian
rhythms are controlled by oscillators, which depend on specific clock genes .
[106]
Peripheral clocks
regulating local metabolic rhythms are determined by feeding and fasting cycles. Moreover, nutrients
reset peripheral circadian clocks and the local clock genes control downstream metabolic
processes
[107]
and, specially, the circadian system which has been shown to regulate glucose metabo-
lism .
[108]
Concretely, taurine supplementation in mice model demonstrated the modulation of clock
genes expression in β cells in those consuming a diet rich in high fat diet
[102]
which is linked to an
improvement with sleep quality
[109]
and negatively associated with obesity and T2D development .
[110]
Furthermore, the supplementation through the combination between omega-3 + taurine in
humans has shown a cardioprotective and anti-inflammatory effect greater than both elements
separately .
[111]
Also, in mice with T2D the combination of fish oil + taurine showed a decrease in
glucose and insulin levels and improved the leptin resistance contributing to the suppression of weight
gain
[112]
(Table 2).
Sardines
Among the oily fish (Supplementary Table 1), sardines are the richest in lipids. Specifically, it is the oily
fish with the most PUFA content. Moreover, as one of the oily fishes richest in omega-3 FA and due to
its whole nutritional composition, sardines are believed to have many potential beneficial effects on
health (Table 3). As already mentioned, its high omega-3 FA content contributes in reducing CVD and
T2D risk. Moreover, sardines are the richest oily fish in proteins and most of amino acids
(Supplementary Table 1), of which, taurine described is one of the highest among oily fish
[114]
and
contains between 122 mg/100 gr of product
[115]
and 147 mg/100 gr of product
[116]
in fresh weight,
depending on the specie. Its take on relevance in the prevention of CVD and T2D as it is thought to
have hypoglycemic, antioxidant, and anti-inflammatory actions. Sardines are also a source of calcium
Table 2. Studies with taurine and omega-3/oily fish supplementation.
Compound Dose Model Sample size Effect Reference
Soybean or fish oil
± taurine
Soybean, soybean +
taurine, fish oil, fish oil
+ taurine
4 weeks
Type 2
Diabetic/
Obese KK-Ay
Mice
36 total.
6–7 in each 3 groups of
fish oil + taurine
supplemented
Taurine supplemented
fish oil, compared to
supplemented
soybean oil,
decreases blood
glucose (around
−200 mg/dL) and
insulin (around
−0.5 ng/mL).
[112]
Omega-3 + taurine 1 g/day EPA/DHA +
425 mg/d taurine
7 weeks
Healthy adult
human
80 total.
41 in group of omega-3
+ taurine
supplemented
Decrease of total
cholesterol (−5%),
LDL cholesterol
(−8%) and Apo
B (−4%) and
increase HDL
cholesterol (6%).
[111]
8D. A. DÍAZ-RIZZOLO ET AL.

and vitamin D (Supplementary Table 1), which is already known to play a role in reducing T2D
risk .
[29]
Apart from its favorable nutritional composition, sardines are also one of the fish with lower
contaminants content and the results indicated that sardines are safe for consumption based on the
toxicologically relevant parameters regulated by European Commission .
[117]
This can be explained
because the concentrations of POPs increase their concentration through the trophic chain. This
is because large predatory fish accumulate more pollutants because they have a longer life since
they cannot be caught by other medium and small fish .
[118,119]
Sardines can also be caught year round and are economically affordable by the public. With
these reasons, they are proposed to be the best option to prevent T2D progression and diminish
CVD risk (Fig. 1).
Table 3. Sardines composition by United States Department of Agriculture (USDA) .
[113].
Nutrient Unit
Value
Nutrient Unit
Value
(per 100 g) (per 100 g)
Water g 59.61 Vitamins
Energy kcal 208 Vitamin C, total ascorbic acid mg 0.00
Energy kJ 871 Thiamin mg 0.08
Protein g 24.62 Riboflavin mg 0.23
Total lipid (fat) g 11.45 Niacin mg 5.25
Carbohydrate g 0.00 Pantothenic acid mg 0.64
Fiber, total dietary g 0.00 Vitamin B-6 mg 0.17
Minerals Folate. total µg 10
Calcium, Ca mg 382 Folic acid µg 0
Iron, Fe mg 2.92 Choline, total mg 75
Magnesium, Mg mg 39 Vitamin B-12 µg 8.94
Phosphorus, P mg 490 Vitamin A, RAE µg 32
Potassium, K mg 397 Retinol µg 32
Sodium, Na mg 307 Vitamin A, IU IU 108
Zinc, Zn mg 1.31 Vitamin D (D2 + D3) µg 4.80
Copper, Cu mg 0.19 Vitamin D IU 193
Manganese, Mn mg 0.11 Vitamin E mg 2.04
Selenium, Se µg 52.70 Vitamin K µg 2.60
Nutrient Unit Value Nutrient Unit Value
(per 100 g) (per 100 g)
Fatty acids Fatty acids
Fatty acids, total saturated g 1.53 Fatty acids. total polyunsaturated g 5.15
12:0 g 0.00 18:2 undifferentiated g 3.54
14:0 g 0.19 18:3 undifferentiated g 0.50
16:0 g 0.99 18:4 g 0.13
18:0 g 0.34 20:4 undifferentiated g 0.00
Fatty acids. total monounsaturated g 3.87 20:5 n-3 (EPA) g 0.47
16:1 undifferentiated g 0.22 22:5 n-3 (DPA) g 0.00
18:1 undifferentiated g 2.15 22:6 n-3 (DHA) g 0.51
20:1 g 0.42 Cholesterol mg 149
22:1 undifferentiated g 1.08
Nutrient Unit Value Nutrient Unit Value
(per 100 g) (per 100g)
Amino acids Amino acids
Tryptophan g 0.28 Valine g 1.27
Threonine g 1.08 Arginine g 1.47
Isoleucine g 1.13 Histidine g 0.73
Leucine g 2 Alanine g 1.49
Lysine g 2.26 Aspartic acid g 2.52
Methionine g 0.73 Glutamic acid g 3.67
Cystine g 0.27 Glycine g 1.81
Phenylalanine g 0.96 Proline g 0.87
Tyrosine g 0.83 Serine g 1
FOOD REVIEWS INTERNATIONAL 9

There have not been many studies where sardine was given as an intervention (Table 4). Human
studies in which this fish has been supplemented, ensuring at least double weekly fish consumption
from sardine-based, reveal a positive effect in overweight or obese non-treated T2D patients with
HbA1c between 6.0 and 8.0% and aged between 40 and 70 years old. Participants increased of
adiponectin from 2.1 ± 0.3 μg/mL at baseline to 3.0 ± 0.3 μg/mL after 6 months intervention,
a biomarker related to an improvement of insulin sensitivity and the decreased of CVD risk index .
[122]
Moreover, in diabetic humans receiving hemodialysis, sardines consumption 3 times/week during
8 weeks have promoted a significant reduction −1.01 ± 1.11 mg/L of C-reactive protein which is
known for its role in inflammation and considered as a T2D and CVD-progression marker .
[123]
Also, animal model studies have reported the beneficial actions of this fish. Reduction of systolic
and diastolic pressure, reduction of glycemia and HbA1c, reduction of 137 and total cholesterol and
Table 4. Studies with sardine supplementation.
Compound Dose Model Sample size Effect Reference
Sardine by-
products
30%
30 days
Wistar rats
(In vivo)
12 total.
6 in group of sardine by-
products supplemented
Reduction of glycemia
(7.23 ± 0.28 and
8.93 ± 0.75 mmol/L
sardine supplemented
and control respectively)
and HbA1c (3.14 ± 0.70
and 5.51 ± 1.51%
sardine supplemented
and control
respectively).
Moreover, reduction of
SBP, DBP, TAG, total
cholesterol, LDL
cholesterol and VLDL.
Increase of HDL cholesterol
and LCAT enzyme.
[120]
Canned sardines 11% or 22% of
the total
diet.
10 weeks
Wistar rats
(In vivo)
27 total.
9 in each 2 groups of
canned sardines
supplemented
22% of sardines group had
higher % of EPA+DHA
and MUFA. Increase
omega-3 FA:omega-6
FA ratio. Higher EPA
deposition in liver and
erythrocytes. Decrease
total cholesterol
decrease LDL
cholesteroland increase
adiponectin in both
groups (21.8–24.5 and
18.7 µg/ml sardine and
control group
respectively).
[121]
Sardine 100g sardine
5d/week.
6 months
T2D subjects without
antidiabetic drugs
35 total.
19 in group of sardine
supplemented
Increased adiponectin
(40.7%), omega-3 FA
index (2.6%) and
Prevotella
concentrations.
Decreased Firmicutes/
Bacteroidetes ratio
[122]
Sardine canned
sandwich
3 times per
week.
8 weeks.
Human subjects
receiving
hemodialysis
63 total.
31 in group of sardine
sandwich supplemented
Reduction of CRP in
patients with higher
baseline concentrations
(−1.01 ± 1.11 and
−0.079 ± 0.85 the
higher and lower CRP at
baseline respectively).
[123]
10 D. A. DÍAZ-RIZZOLO ET AL.

increases of adiponectin, HDL cholesterol, and EPA+DHA have been observed after administering
sardines .
[120,121]
Furthermore, studies report an improvement of insulin resistance, increased activity
of PI3K/Akt pathway, and translocation of GLUT4 transporters which all together contribute to the
improvement of insulin action and glucose homeostasis .
[124]
Although studies with sardine supplementation are not very common, research with its main
components has been performed more regularly (Table 5). In the case of sardine oil supplementation,
it has been seen to reduce TAG as well as total and LDL cholesterol. However, the effects of sardine on
glycemia have not been as clearly described as different controversial results have been published.
On the other hand, studies with animal models in which sardine protein was supplemented have
reported a reduction of white adipose tissue, improvements on insulin sensitivity and glycemia
[124,129]
(Table 6).
Conclusions
Non-communicable diseases, especially T2D, are becoming widespread. Researchers must investi-
gate the best strategies to prevent its development and weight loss is one of the most studied areas.
However, in elderly people, who are at greater risk of developing T2D, we know that it may be more
interesting to focus on the quality of the food they eat.
Table 5. Studies with sardine oil supplementation.
Compound Dose Model Sample size Effect Reference
Sardine oil 20%
30 days or
60 days
Male Wistar
rats
(In vivo)
24 total.
12 in group of sardine oil
supplemented.
And 6 from control group
started with sardine oil at
middle of study.
Lowers hypertriglyceridemia (−68%)
and hypercholesterolemia (−50%)
replacing margarine. No effects on
glycemia but improves HbA1c
(−36%) and insulinemia (−65%)
when sardine oil replaces
margarine.
[125]
Sardine oil 20% 4 weeks Obese male
Wistar rats
(in vivo)
16 total.
8 in group of sardine oil
supplemented
No effect on glycemia.
Reduces cholesterol (−8%), TAG
(−36%) and apolipoproteins.
Increased lecithin (35%) and
paraoxonase-1 activity (25%).
[89]
Sardine oil 0,5 mL/rat
3 weeks
Alloxan-
induced
diabetic rats
32 total.
8 in group of sardine oil
supplemented
Decreases glycemia (−54%).
Inhibition of α-amylase activity
(−27%).
Improve ALT, AST and ALP
enzymes (−66, 26 and 69%
respectively).
[126]
Sardine oil 7,5%
6 weeks
Sucrose-
induced
metabolic
syndrome
male Wistar
rats.
44 total.
10 in group of sardine oil
supplemented
Serum glucose remained similar to
no metabolic syndrome rats.
Moreover, other metabolic
parameters returns to control
level (reduces serum insulin by
−150%, BP by −60%,, TAG by
−98%, total cholesterol by −106%
and LDL cholesterol by −40%)
[127]
Sardine oil Oil capsules:
180 mg EPA
and 120 mg
DHA during
90 days
Human with
metabolic
syndrome.
102 in total.
21 in group of sardine oil
supplemented and 26 in
group with control
supplementation +
sardine oil.
Reduction of prooxidant state
(hydroperoxide, AOPP, AOPP/
TRAP index and TRAP/AOPP
index).
No effects on glycemia, insulin
levels or HOMA-IR.
Decreases total cholesterol
(around −20 mg/dL compared to
control) and LDL cholesterol
(around −27 mg/dL post-
intervention).
[128]
FOOD REVIEWS INTERNATIONAL 11

Fish consumption has been studied on various occasions, with some contradictory results due to
the differences between the species consumed. The fish with the least amount of toxic compounds as
well as the highest amount of PUFA, especially omega-3 FA, could be the most interesting due to the
subject’s improvement in insulin sensitivity.
Fish also contain other interesting nutrients that can stop or delay progression to T2D. Among
them, protein content and more specifically some amino acids. Taurine is one of the most present,
especially in oily fish, and has been related to a hypoglycemic effect but without being able to
demonstrate it in the supplementing trials in isolation.
The fish with the lowest concentration of POPs and the highest content of PUFA as well as
taurine is sardine. An in vivo study in rats concluded that sardine consumption reduced glycemia
and HbA1c, but the few clinical trials investigating the effect of sardine consumption with diabetes
were unable to link it. Instead, they observed a decrease in CRP and an increase in circulating
adiponectin.
On the other hand, some in vitro studies in rats, not carried out in humans to reproduce effects,
with sardine-derived products such as oil or proteins, produced an improvement in glycemia as well as
an improvement in sensitivity to insulin or in the absorption of glucose.
More interventional studies need to be carried out to know discover the impact of sardine
consumption in metabolic diseases is. Specially, it could be interesting to promote clinical trials in
order to evaluate the preventive effects that a sardine-enriched diet could have against T2D. This
would be especially interesting in a high-risk population with preDM but also with a high level of
fragility for example an old-age population.
We consider that is very important to know the mechanisms by which sardine consumption,
through its nutrients acts on glucose homeostasis as well as insulin secretion or sensibility. Therefore,
mechanistic studies involving the composition of the gut microbiota, transcriptomic, or metabolomics
could be of great interest in the scientific community.
Table 6. Studies of sardine protein supplementation.
Compound Dose Model Sample size Effect Reference
Sardine
protein
200 g/kg
2 months
Wistar rats
(in vivo)
24 in total.
6 in each 2 groups
sardine-protein
supplemented.
Decrease of glycemia and insulin levels (glucose
6.54 ± 0.47 and 8.31 ± 1.06 mmol/l, insulin
43.22 ± 12.25 and 66.65 ± 5.97 µU/ml sardine
protein supplemented and control in high-
fructose diets respectively). Likewise, in same
diet, reduces HOMA-IR (12.70 ± 4.46 and
21.94 ± 5.43) and HbA1c (10.39 ± 1.29 and
16.42 ± 1.74%) sardine protein supplemented
and control respectively.
Reduces index of adiposity (2.05 ± 0.29 and
2.68 ± 0.14) and TAG (0.92 ± 0.09 and 1.21 ± 0.08)
sardine protein supplemented and control
respectively.
Decrease inflammatory markers (leptin between
−15 and −19% and TNF-α between −16 and
−31%).
[124]
Sardine
protein
20%
28 days
High-fat
diet-
induced
T2D rats.
24 in total.
6 in each 2 groups
of sardine-protein
supplemented
Lowers glycemia (14.49 ± 2.07 and
23.15 ± 1.71 mM), HbA1c (8.32 ± 0.84 and
11.70 ± 1.51%) and insulin levels (292.10 ± 21.91
and 331.77 ± 24.89 pmol/l) likewise HOMA-IR
(24.90 ± 1.50 and 50.54 ± 4.14) sardine protein
supplemented and control respectively.
Reduce serum total cholesterol (2.51 ± 0.44 and
4.71 ± 0.73 mM) and TAG (1.97 ± 0.58 and
3.51 ± 0.43 mM) sardine protein supplemented
and control respectively. Enhances LCAT activity
(16.74 ± 5.81 and 27.55 ± 2.09 nol/h per ml).
[129]
12 D. A. DÍAZ-RIZZOLO ET AL.

To summaries, it may be both timely and appropriate to suggest that the elderly tailor their dietary
intake to increase the consumption of sardine as all studies carried out to date prove that its
consumption is safe. Moreover, it could lead to a health benefit by promoting the consumption of
healthy fats, as well as vitamins and minerals potentially at risk in this population group such as
calcium or vitamin D and reducing the risk of protein-energy malnutrition. In conclusion, after all the
scientific evidence presented in this review, sardine consumption could have a protective effect against
the development of metabolic diseases such as T2D with such a high prevalence and incidence in this
group.
ORCID
Diana A. Díaz-Rizzolo http://orcid.org/0000-0003-1327-1937
References
[1] World Health Organization. International Encyclopedia of Public Health. http://www.who.int/diabetes/en/
(accessed Aug 11, 2019).
[2] American Diabetes Association. Standards of Medical Care in Diabetes 2018. Diabetes Care. 2018, 41(Supplement
1), S1. DOI: 10.2337/dc18-Sint01.
[3] Forouhi, N. G.; Luan, J.; Hennings, S.; Wareham, N. J. Incidence of Type 2 Diabetes in England and Its
Association with Baseline Impaired Fasting Glucose: The Ely Study 1990–2000. Diabet. Med. 2007, 24(2),
200–207. DOI: 10.1111/j.1464-5491.2007.02068.x.
[4] Nathan, D. M.; Davidson, M. B.; DeFronzo, R. A.; Heine, R. J.; Henry, R. R.; Pratley, R.; Zinman, B. Impaired
Fasting Glucose and Impaired Glucose Tolerance: Implications for Care. Diabetes Care. 2007, 30(3), 753–759.
DOI: 10.2337/dc07-9920.
[5] Soriguer, F.; Goday, A.; Bosch-Comas, A.; Bordiú, E.; Calle-Pascual, A.; Carmena, R.; Casamitjana, R.;
Castaño, L.; Castell, C.; Catalá, M.; et al. Prevalence of Diabetes Mellitus and Impaired Glucose Regulation in
Spain: The Di@bet.es Study. Diabetologia. 2012, 55(1), 88–93.
[6] Narayan, K. M. V.; Boyle, J. P.; Geiss, L. S.; Saaddine, J. B.; Thompson, T. Impact of Recent Increase in
Incidence on Future Diabetes Burden: U.S., 2005–2050. Diabetes Care. 2006, 29(9), 2114–2116. DOI: 10.2337/
dc06-1136.
[7] DECODE study group. Diabetes and Impaired Glucose Regulation in 13 European Cohorts. Diabetes Care. 2003,
26(1), 61–69. DOI: 10.2337/diacare.26.1.61.
[8] Will, J. C.; Williamson, D. F.; Ford, E. S.; Calle, E. E.; Thun, M. J. Intentional Weight Loss and 13-year Diabetes
Incidence in Overweight Adults. Am. J. Public Health. 2002, 92(8), 1245–1248. DOI: 10.2105/AJPH.92.8.1245.
[9] DeFronzo, R. A.; Ferrannini, E.; Groop, L.; Henry, R. R.; Herman, W. H.; Holst, J. J.; Hu, F. B.; Kahn, C. R.; Raz, I.;
Shulman, G. I.; et al. Type 2 Diabetes Mellitus. Nat Rev Dis Primers. 2015, 1, 15019.
[10] Lindström, J.; Louheranta, A.; Mannelin, M.; Rastas, M.; Salminen, V.; Eriksson, J.; Uusitupa, M.; Tuomilehto, J.
Finnish Diabetes Study. Diabetes Care. 2003, 26(12), 3230–3236.
[11] Schellenberg, E. S.; Dryden, D. M.; Vandermeer, B.; Ha, C.; Korownyk, C. Lifestyle Interventions for Patients with
and at Risk for Type 2 Diabetes. Ann. Intern. Med. 2013, 159(8), 543–551. DOI: 10.7326/0003-4819-159-
8-201310150-00007.
[12] Fox, C. S.; Golden, S. H.; Anderson, C.; Bray, G. A.; Burke, L. E.; de Boer, I. H.; Deedwania, P.; Eckel, R. H.;
Ershow, A. G.; Fradkin, J.; et al. Update on Prevention of Cardiovascular Disease in Adults with Type 2 Diabetes
Mellitus in Light of Recent Evidence. Circulation. 2015, 132(8), 691–718.
[13] Curioni, C. C.; Lourenço, P. M. Long-term Weight Loss after Diet and Exercise: A Systematic Review. Int. J. Obes.
2005, 29(10), 1168–1174. DOI: 10.1038/sj.ijo.0803015.
[14] Ditschuneit, H. H.; Flechtner-mors, M.; Johnson, T. D.; Adler, G. Metabolic and Weight-loss Effects of a
Long-term Dietary Intervention in Obese Patients. Am. J. Clin. Nutr. 1999, 69(2), 198–204. DOI: 10.1093/ajcn/
69.2.198.
[15] Goodpaster, B. H.; Delany, J. P.; Otto, A. D.; Kuller, L.; Vockley, J.; South-Paul, J. E.; Thomas, S. B.; Brown, J.;
McTigue, K.; Hames, K. C.; et al. Effects of Diet and Physical Activity Interventions on Weight Loss and
Cardiometabolic Risk Factors in Severely Obese Adults: A Randomized Trial. JAMA. 2010, 304(16),
1795–1802.
[16] Hamman, R. F.; Wing, R. R.; Edelstein, S. L.; Lachin, J. M.; Bray, G. A.; Delahanty, L.; Hoskin, M.; Kriska, A. M.;
Mayer-David, E. J.; Pi-Sunyer, X.; et al. Effect of Weight Loss with Lifestyle Intervention on Risk of Diabetes.
Diabetes Care. 2006, 29(9), 2102–2107.
FOOD REVIEWS INTERNATIONAL 13

[17] The Diabetes Prevention Program Research Group. Reduction in the Incidence of Type 2 Diabetes with Lifestyle
Intervention or Metformin. N. Engl. J. Med. 2002, 346(6), 393–403. DOI: 10.1056/NEJMoa012512.
[18] Sjöström, L.; Peltonen, M.; Jacobson, P.; Sjöström, C. D.; Karason, K.; Wedel, H.; Ahlin, S.; Anveden, Å.;
Bengtsson, C.; Bergmark, G.; et al. Bariatric Surgery and Long-term Cardiovascular Events. JAMA. 2012, 307
(1), 56–65.
[19] Fried, M.; Yumuk, V.; Oppert, J. M.; Scopinaro, N.; Torres, A. J.; Weiner, R.; Yashkov, Y.; Frühbeck, G. European
Association for the Study of Obesity, International Federation for the Surgery of Obesity - European Chapter:
Interdisciplinary European Guidelines on Metabolic and Bariatric Surgery. Obes. Facts. 2013, 6(5), 449–468. DOI:
10.1159/000355480.
[20] Farag, Y. M. K.; Gaballa, M. R. Diabesity: An Overview of a Rising Epidemic. Neprol. Dial. Transplant. 2011, 26
(1), 28–35. DOI: 10.1093/ndt/gfq576.
[21] Waters, D. L.; Ward, A. L.; Villareal, D. T. Weight Loss in Obese Adults 65 Years and Older: A Review of the
Controversy. Exp. Gerontol. 2013, 48(10), 1054–1061. DOI: 10.1016/j.exger.2013.02.005.
[22] Forsythe, L. K.; Wallace, J. M.; Livingstone, M. B. Obesity and Inflammation: The Effects of Weight Loss. Nutr.
Res. Rev. 2008, 21(2), 117–133. DOI: 10.1017/S0954422408138732.
[23] Ler, L.; Odell, P. M.; DAgostino, R. B.; Stokes, J., 3rd; Kreger, B. E.; Belanger, A. J.; Brownell, K. D. Variability of
Body Weight and Health Outcomes in the Framingham Population. N. Engl. J. Med. 1991, 324(26), 1839–1844.
DOI: 10.1056/NEJM199106273242602.
[24] Blair, S. N.;. Evidence for Success of Exercise in Weight Loss and Control. Ann. Intern. Med. 1993, 119(7),
702–706. Pt 2. DOI: 10.7326/0003-4819-119-7_Part_2-199310011-00015.
[25] Newman, A. B.; Yanez, D.; Harris, T.; Duxbury, A.; Enright, P. L.; Fried, L. P. Weight Change in Old Age and
Its Association with Mortality. J. Am. Geriatr. Soc. 2001, 49(10), 1309–1318. DOI: 10.1046/j.1532-
5415.2001.49258.x.
[26] Darmon, P.; Kaiser, M. J.; Bauer, J. M.; Sieber, C. C.; Pichard, C. Restrictive Diets in the Elderly: Never Say Never
Again? Clin. Nutr. 2010, 29(2), 170–174. DOI: 10.1016/j.clnu.2009.11.002.
[27] Díaz-Rizzolo, D. A.; Kostov, B.; López-Siles, M.; Serra, A.; Colungo, C.; González-de-Paz, L.; Martínez-Medina,
M.; Sisó-Almirall, A.; Gomis, R. Healthy Dietary Pattern and Their Corresponding Gut Micrbiota Profile are
Linked to a Lower Risk of Type 2 Diabetes, Independent of the Presence of Obesity. Clin. Nutr. 2020, 39(2),
524–532. DOI: 10.1016/j.clnu.2019.02.035.
[28] Knoops, K. T.; de Groot, L. C.; Kromhout, D.; Perrin, A. E.; Moreiras-Varela, O.; Menotti, A.; van Staveren, W. A.
Mediterranean Diet, Lifestyle Factors, and 10-Year Mortality in Elderly the HALE Project. JAMA. 2004, 292(12),
1433–1439. DOI: 10.1001/jama.292.12.1433.
[29] Pittas, A. G.; Lau, J.; Hu, F.; Dawson-Hughes, B. The Role of Vitamin D and Calcium in Type 2 Diabetes.
A Systematic Review and Meta-Analysis. J. Clin. Endocrinol. Metab. 2007, 92(6), 2017–2029. DOI: 10.1210/
jc.2007-0298.
[30] Mayer-Davis, E. J.; Costacou, T.; King, I.; Zaccaro, D. J.; Bell, R. A. Plasma and Dietary Vitamin E in Relation to
Incidence of Type 2 Diabetes. Diabetes Care. 2002, 25(12), 2172–2177. DOI: 10.2337/diacare.25.12.2172.
[31] Lopez-Riadura, R.; Willett, W. C.; Rimm, E. B.; Liu, S.; Stampfer, M. J.; Manson, J. E.; Hu, F. B. Magnesium Intake
and Risk of Type 2 Diabetes in Men and Women. Diabetes Care. 2004, 27(1), 134–140. DOI: 10.2337/
diacare.27.1.134.
[32] Sun, C.; Zhao, C.; Guven, E. C.; Paoli, P.; Simal-Gandara, J.; Ramkumar, K. M.; Wang, S.; Buleu, F.; Pah, A.;
Turi, V.; et al. Dietary Polyphenols as Antidiabtic Agents: Advances and Opporunities. Food Frontiers. 2020, 1(1),
18–44. DOI: 10.1002/fft2.15.
[33] Saslow, L. R.; Kim, S.; Daubenmier, J. J.; Moskowitz, J. T.; Phinney, S. D.; Goldman, V.; Murphy, E.; Cox, R. M.;
Moran, P.; Hecht, F. M. A Randomized Pilot Trial of A Moderate Carbohydrate Diet Compared to A Very Low
Carbohydrate Diet in Overweight or Obese Individuals with Type 2 Diabetes Mellitus or Prediabetes. PLoS One.
2014, 9(4), e91027. DOI: 10.1371/journal.pone.0091027.
[34] Greenwood, D. C.; Threapleton, D. E.; Evans, C. E.; Cleghorn, C. L.; Nykjaer, C.; Woodhead, C.; Burley, V. J.
Glycemic Index, Glycemic Load, Carbohydrates, and Type 2 Diabetes: Systematic Review and Dose-response
Meta-analysis of Prospective Studies. Diabetes Care. 2013, 36(12), 4166–4171. DOI: 10.2337/dc13-0325.
[35] Rendell, M.;. Dietary Treatment of Diabetes Mellitus. New Engl. J. Med. Ed. 2000, 342(19), 1440–1441. DOI:
10.1056/NEJM200005113421910.
[36] Thanopoulou, A. C.; Karamanos, B. G.; Angelico, F. V.; Assaad-Khalil, S. H.; Barbato, A. F.; Del Ben, M. P.;
Djordjevic, P. B.; Dimitrijevic-Sreckovic, V. S.; Galloti, C. A.; Katsilambros, N. L.; et al. Dietary Fat Intake as Risk
Factor for the Development of Diabetes: Multinational, Multicenter Study of the Mediterranean Group for the
Study of Diabetes (MGSD). Diabetes Care. 2003, 26(2), 302–307.
[37] Meyer, K. A.; Kushi, L. H.; Jacobs, D. R.; Folsom, A. R. Dietary Fat and Incidence of Type 2. Diabetes Care. 2001,
24(9), 1528–1535. June 2000. DOI: 10.2337/diacare.24.9.1528.
[38] Hu, F. B.; van Dam, R. M.; Liu, S. Diet and Risk of Type II Diabetes: The Role of Types of Fats and Carbohydrates.
Diabetologia. 2001, 44(7), 805–817. DOI: 10.1007/s001250100547.
14 D. A. DÍAZ-RIZZOLO ET AL.

[39] Lichtenstein, A. H.; Schwab, U. S. Relationship of Dietary Fat to Glucose Metabolism. Atherosclerosis. 2000, 150
(2), 227–243. DOI: 10.1016/S0021-9150(99)00504-3.
[40] Pan, D. A.; Lillioja, S.; Milner, M. R.; Kriketos, A. D.; Baur, L. A.; Bogardus, C.; Storlien, L. H. Skeletal Muscle
Membrane Lipid Composition Is Related to Adiposity and Insulin Action. J. Clin. Invest. 1995, 96(6), 2802–2808.
DOI: 10.1172/JCI118350.
[41] Brinkworth, G. D.; Noakes, M.; Parker, B.; Foster, P.; Clifton, P. M. Long-term Effects of Advice to Consume a
High-protein, Low-fat Diet, Rather than a Conventional Weight-loss Diet, in Obese Adults with Type 2 Diabetes:
One-year Follow-up of a Randomised Trial. Diabetologia. 2004, 47(10), 1677–1686. DOI: 10.1007/s00125-004-
1511-7.
[42] van Nielen, M.; Feskens, E. J. M.; Mensink, M.; Sluijs, I.; Molina, E.; Amiano, P.; Ardanaz, E.; Balkau, B.;
Beulens, J. W. L.; Boeing, H.; et al. Dietary Protein Intake and Incidence of Type 2 Diabetes in Europe: The
EPIC-InterAct Case-Cohort Study. Diabetes Care. 2014, 37(7), 1854–1862.
[43] Tian, S.; Xu, Q.; Jiang, R.; Han, T.; Sun, C.; Na, L. Dietary Protein Consumption and the Risk of Type 2 Diabetes:
A Systematic Review and Meta-analysis of Cohort Studies. Nutrients. 2017, 9(9), 1–17. DOI: 10.3390/nu9090982.
[44] Patel, P. S.; Sharp, S. J.; Luben, R. N.; Khaw, K. T.; Bingham, S. A.; Wareham, N. J.; Forouhi, N. G. Association
between Type of Dietary Fish and Seafood Intake and the Risk of Incident Type 2 Diabetes: The European
Prospective Investigation of Cancer (Epic)-norfolk Cohort Study. Diabetes Care. 2009, 32(10), 1857–1863. DOI:
10.2337/dc09-0116.
[45] Mozaffarian, D.; Rimm, E. B.; Intake, F. Contaminants, and Human Health. JAMA. 2006, 296(15), 1885. DOI:
10.1001/jama.296.15.1885.
[46] Nanri, A.; Mizoue, T.; Noda, M.; Takahashi, Y.; Matsushita, Y.; Poudel-Tandukar, K.; Kato, M.; Oba, S.;
Inoue, M.; Tsugane, S.; et al. Fish Intake and Type 2 Diabetes in Japanese Men and Women: The Japan Public
Health Center-based Prospective Study. Am. J. Clin. Nutr. 2011, 94(3), 884–891.
[47] Kromann, N.; Green, A. Epidemiological Studies in the Upernavik District, Greenland. Incidence of Some
Chronic Diseases 1950–1974. Acta. Med. Scand. 1980, 208(401), 401–406.
[48] Zheng, J.; Huang, T.; Yu, Y.; Hu, X.; Yang, B.; Li, D. Fish Consumption and CHD Mortality: An Updated
Meta-analysis of Seventeen Cohort Studies. Public Health Nutr. 2012, 15(4), 725–737. DOI: 10.1017/
S1368980011002254.
[49] Qin, B.; Plassman, B. L.; Edwards, L. J.; Popkin, B. M.; Adair, L. S.; Mendez, M. A. Fish Intake Is Associated with
Slower Cognitive Decline in Chinese Older Adults1–3. J. Nutr. 2014, 144(10), 1579–1585. DOI: 10.3945/
jn.114.193854.
[50] Esmailzadehha, N.; Ziaee, A.; Kazemifar, A. M.; Ghorbani, A.; Oveisi, S. Prevalence of Metabolic Syndrome in
Qazvin Metabolic Diseases Study (QMDS), Iran: A Comparative Analysis of Six Definitions. Endocr. Regul. 2013,
47(3), 111–120. DOI: 10.4149/endo_2013_03_111.
[51] Yokoyama, M.; Origasa, H.; Matsuzaki, M.; Matsuzawa, Y.; Saito, Y.; Ishikawa, Y.; Oikawa, S.; Sasaki, J.;
Hishida, H.; Itakura, H.; et al. Effects of Eicosapentaenoic Acid on Major Coronary Events in
Hypercholesterolaemic Patients (JELIS): A Randomised Open-label, Blinded Endpoint Analysis. Lancet. 2007,
369(9567), 1090–1098.
[52] Iso, H.; Kobayashi, M.; Ishihara, J.; Sasaki, S.; Okada, K.; Kita, Y.; Kokubo, I.; Tsugane, S. Intake of Fish and N3
Fatty Acids and Risk of Coronary Heart Disease among Japanese: The Japan Public Health Center-Based (JPHC)
Study Cohort I. Circulation. 2006, 113(2), 195–202. DOI: 10.1161/CIRCULATIONAHA.105.581355.
[53] de Goede, J.; Geleijnse, J. M.; Boer, J. M. A.; Kromhout, D.; Verschuren, W. M. M. Marine (N-3) Fatty Acids, Fish
Consumption, and the 10-Year Risk of Fatal and Nonfatal Coronary Heart Disease in a Large Population of
Dutch Adults with Low Fish Intake. J. Nutr. 2010, 140(5), 1023–1028. DOI: 10.3945/jn.109.119271.
[54] Chowdhury, R.; Stevens, S.; Gorman, D.; Pan, A.; Warnakula, S.; Chowdhury, S.; Ward, H.; Johnson, L.;
Crowe, F.; Hu, F. B.; et al. Association between Fish Consumption, Long Chain Omega 3 Fatty Acids, and Risk
of Cerebrovascular Disease: Systematic Review and Meta-analysis. BMJ. 2012, 345(7881), 1–9. DOI: 10.1136/bmj.
e6698.
[55] He, K.; Song, Y.; Daviglus, M. L.; Liu, K.; Van Horn, L.; Dyer, A. R.; Goldbourt, U.; Greenland, P. Fish
Consumption and Incidence of Stroke: A Meta-analysis of Cohort Studies. Stroke. 2004, 35(7), 1538–1542.
DOI: 10.1161/01.STR.0000130856.31468.47.
[56] Leung Yinko, S. L. L.; Stark, K. D.; Thanassoulis, G.; Pilote, L. Fish Consumption and Acute Coronary Syndrome:
A Meta-analysis. Am. J. Med. 2014, 127(9), 848–857. DOI: 10.1016/j.amjmed.2014.04.016.
[57] Mozaffarian, D.; Prineas, R. J.; Stein, P. K.; Siscovick, D. S. Dietary Fish and N-3 Fatty Acid Intake and Cardiac
Electrocardiographic Parameters in Humans. J. Am. Coll. Cardiol. 2006, 48(3), 478–484. DOI: 10.1016/j.
jacc.2006.03.048.
[58] König, A.; Bouzan, C.; Cohen, J. T.; Connor, W. E.; Kris-Etherton, P. M.; Gray, G. M.; Lawrence, R. S.;
Savitz, D. A.; Teutsche, S. M. A Quantitative Analysis of Fish Consumption and Coronary Heart Disease
Mortality. Am. J. Prev. Med. 2005, 29(4), 335–346. DOI: 10.1016/j.amepre.2005.07.001.
FOOD REVIEWS INTERNATIONAL 15

[59] Buscemi, S.; Nicolucci, A.; Lucsiano, G.; Galvano, F.; Grosso, G.; Belmonte, S.; Sprini, D.; Migliaccio, S.;
Cianferotti, L.; Brandi, M. L.; et al. Habitual Fish Intake and Clinically Silent Carotid Atherosclerosis. Nutr. J.
2014, 13(1). DOI: 10.1186/1475-2891-13-2.
[60] He, K.; Liu, K.; Daviglus, M. L.; Mayer-Davis, E.; Jenny, N. S.; Jiang, R.; Ouyang, P.; Steffen, L. M.; Siscovick, D.;
Wu, C.; et al. Intakes of Long-chain N-3 Polyunsaturated Fatty Acids and Fish in Relation to Measurements of
Subclinical Atherosclerosis. Am. J. Clin. Nutr. 2008, 88(4), 1111–1118.
[61] Erkkila, A. T.; Lichtenstein, A. H.; Mozaffarian, D.; Herrington, D. M. Fish Intake Is Associated with a Reduced
Progression of Coronary Artery Atherosclerosis in Postmenopausal Women with Coronary Artery Disease. Am.
J. Clin. Nutr. 2004, 80(3), 626–632. DOI: 10.1093/ajcn/80.3.626.
[62] Lee, C.; Liese, A.; Wagenknecht, L.; Lorenzo, C.; Haffner, S.; Hanley, A. Fish Consumption, Insulin Sensitivity
and Beta-cell Function in the Insulin Resistance Atherosclerosis Study (IRAS). Nutr. Metab. Cardiovasc Dis. 2013,
23(9), 829–835. DOI: 10.1016/j.numecd.2012.06.001.
[63] Kaushik, M.; Mozaffarian, D.; Spiegelman, D.; Manson, J. E.; Willett, W. C.; Hu, F. B. Long-chain Omega-3 Fatty
Acids, Fish Intake, and the Risk of Type 2 Diabetes Mellitus. Am. J. Clin. Nutr. 2009, 90(3), 613–620. DOI:
10.3945/ajcn.2008.27424.
[64] Wu, H.; Bertrand, K. A.; Choi, A. L.; Hu, F. B.; Laden, F.; Grandjean, P.; Sun, Q. Persistent Organic Pollutants and
Type 2 Diabetes: A Prospective Analysis in the Nurses Health Study and Meta-analysis. Environ. Health Perspect.
2013, 121(2), 153–161. DOI: 10.1289/ehp.1205248.
[65] Ruzzin, J.; Petersen, R.; Meugnier, E.; Madsen, L.; Lock, E. J.; Lillefosse, H.; Ma, T.; Pesenti, S.; Sonne, S. B.;
Marstrand, T. T.; et al. Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome. Environ.
Health Perspect. 2010, 118(4), 465–471.
[66] Taylor, K. W.; Novak, R. F.; Anderson, H. A.; Birnbaum, L. S.; Blystone, C.; DeVito, M.; Jacobs, D.; Kohrle, J.;
Lee, D.-H.; Rylander, L.; et al. Evaluation of the Association between Persistent Organic Pollutants (Pops) and
Diabetes in Epidemiological Studies: A National Toxicology Program Workshop Review. Environ. Health
Perspect. 2013, 121(7), 774–783.
[67] Lee, D. H.; Lee, I. K.; Song, K.; Steffes, M.; Toscano, W.; Baker, B. A.; Jacobs, D. R., Jr. A Strong Dose-response
Relation between Serum Concentrations of Persistent Organic Pollutants and Diabetes: Results from the National
Health and Examination Survey 1999–2002. Diabetes Care. 2006, 29(7), 1638–1644.
[68] Borkman, M.; Storlien, L. H.; Pan, D. A.; Jenkins, A. B.; Chisholm, D. J.; Campbell, L. V. The Relation between
Insulin Sensitivity and the Fatty-Acid Composition of Skeletal-Muscle Phospholipids. N. Engl. J. Med. 1993, 328
(4), 238–244. DOI: 10.1056/NEJM199301283280404.
[69] Uhe, A. M.; Collier, G. R.; ODea, K. A Comparison of the Effects of Beef, Chicken and Fish Protein on Satiety and
Amino Acid Profiles in Lean Male Subjects. J. Nutr. 1992, 122(3), 467–472. DOI: 10.1093/jn/122.3.467.
[70] Pilon, G.; Ruzzin, J.; Rioux, L. E.; Lavigne, C.; White, P. J.; Frøyland, L.; Jacqes, H.; Bryl, P.; Beaulieu, L.;
Marette, A. Differential Effects of Various Fish Proteins in Altering Body Weight, Adiposity, Inflammatory
Status, and Insulin Sensitivity in High-fat-fed Rats. Metabolism. 2011, 60(8), 1122–1130.
[71] Rees, K.; Hartley, L.; Flowers, N.; Clarke, A.; Hooper, L.; Thorogood, M.; Stranges, S. Mediterranean Dietary
Pattern for the Primary Prevention of Cardiovascular Disease (Review). Cochrane Database Syst. Rev. 2016, 12(8),
CD009825.
[72] Zhang, M.; Picard-deland, E.; Marette, A. Fish and Marine Omega-3 Polyunsatured Fatty Acid Consumption and
Incidence of Type 2 Diabetes : A Systematic Review and Meta-Analysis. Int. J. Endocrinol. 2013, 2013, 501015.
DOI: 10.1155/2013/501015.
[73] Lichtenstein, A. H.; Appel, L. J.; Brands, M.; Carnethon, M.; Daniels, S.; Franch, H. A.; Franklin, B.; Kris-
Etherton, P.; Harris, W. S.; Howard, B.; et al. Diet and Lifestyle Recommendations Revision 2006 A Scientific
Statement from the American Heart Association Nutrition Committee. Ciruculation. 2006, 114(1), 82–96.
[74] Lankinen, M.; Schwab, U.; Erkkilä, A.; Seppänen-Laakso, T.; Hannila, M. L.; Mussalo, H.; Lehto, S.;
Uusituupa, M.; Gylling, H.; Oresic, M. Fatty Fish Intake Decreases Lipids Related to Inflammation and Insulin
Signaling — A Lipidomics Approach. Plos One. 2009, 4(4), 1–9. DOI: 10.1371/journal.pone.0005258.
[75] Summers, S. A.;. Progress in Lipid Research Ceramides in Insulin Resistance and Lipotoxicity. Prog. Lipid Res.
2006, 45(1), 42–72. DOI: 10.1016/j.plipres.2005.11.002.
[76] Hagen, I. V.; Helland, A.; Bratlie, M.; Brokstad, K. A.; Rosenlund, G.; Sveier, H.; Mellgren, G.;
Gudbrandsen, O. A. High Intake of Fatty Fish, but Not of Lean Fish, Affects Serum Concentrations of TAG
and HDL-cholesterol in Healthy, Normal-weight Adults : A Randomised Trial. Br. J. Nutr. 2016, 116(4), 648–657.
DOI: 10.1017/S0007114516002555.
[77] Alhassan, A.; Young, J.; Lean, M. E. J.; Lara, J. Consumption of Fi Sh and Vascular Risk Factors : A Systematic
Review and Meta-analysis of Intervention Studies. Atherosclerosis. 2017, 266, 87–94. DOI: 10.1016/j.
atherosclerosis.2017.09.028.
[78] Manninen, V.; Tenkanen, L.; Koskinen, P.; Huttunen, J. K.; Manttari, M.; Heinonen, O. P.; Frick, M. H. Joint
Effects of Serum Triglyceride and LDL Cholesterol and HDL Cholesterol Concentrations on Coronary Heart
Disease Risk in the Helsinki Heart Study. Implications for Treatment. Circulation. 1992, 85(1), 37–45. DOI:
10.1161/01.CIR.85.1.37.
16 D. A. DÍAZ-RIZZOLO ET AL.

[79] Kim, J.; Koh, K. K.; Quon, M. J. The Union of Vascular and Metabolic Actions of Insulin in Sickness and in
Health. Arterioscler Thromb. Vasc. Biol. 2005, 46, 1978–1985.
[80] Imamura, S.; Morioka, T.; Yamazaki, Y.; Numaguchi, R.; Urata, H.; Motoyama, K.; Mori, K.; Fukumoto, S.;
Shoji, T.; Emoto, M.; et al. Plasma Polyunsaturated Fatty Acid Profile and Delta-5 Desaturase Activity are Altered
in Patients with Type 2 Diabetes. Metabolism. 2014, 63(11), 1432–1438.
[81] Djoussé, L.; Biggs, M. L.; Lemaitre, R. N.; King, I. B.; Song, X.; Ix, J. H.; Mukamal, K. J.; Siscovick, D. S.;
Mozaffarian, D. Plasma Omega-3 Fatty Acids and Incident Diabetes in Older Adults. Am. J. Clin. Nutr. 2011, 94
(2), 527–533.
[82] Stephens, F. B.; Mendis, B.; Shannon, C. E.; Cooper, S.; Ortori, C. A.; Barrett, D. A.; Mansell, P.; Tsintzas, K. Fish
Oil Omega-3 Fatty Acids Partially Prevent Lipid Induced Insulin Resistance in Human Skeletal Muscle without
Limiting Acylcarnitine Accumulation. Clin. Sci. (Lond). 2014, 127(5), 315–322. DOI: 10.1042/CS20140031.
[83] Bremer, A. A.; Stanhope, K. L.; Graham, J. L.; Cummings, B. P.; Ampah, S. B.; Saville, B. R.; Havel, P. J. Fish Oil
Supplementation Ameliorates Fructose- Induced Hypertriglyceridemia and Insulin Resistance in Adult Male
Rhesus Macaques. J. Nutr. 2014, 144(1), 5–11. DOI: 10.3945/jn.113.178061.
[84] Chen, C.; Yu, X.; Shao, S. Effects of Omega-3 Fatty Acid Supplementation on Glucose Control and Lipid Levels in
Type 2 Diabetes: A Meta-analysis. PLoS One. 2015, 10(10), 1–14.
[85] Ouellet, V.; Marois, J.; Weisnagel, S. J.; Jacques, H. Dietary Cod Protein Improves Insulin Sensitivity in
Insulin-Resistant Men and Women. Diabetes Care. 2007, 30(11), 2816–2821. DOI: 10.2337/dc07-0273.
[86] Drotningsvik, A.; Mjøs, S. A.; Pampanin, D. M.; Slizyte, R.; Carvajal, A.; Remman, T.; Høgøy, I.;
Gudbrandsen, O. A. Dietary Fish Protein Hydrolysates Containing Bioactive Motifs Affect Serum and Adipose
Tissue Fatty Acid Compositions, Serum Lipids, Postprandial Glucose Regulation and Growth in Obese Zucker
Fa/fa Rats. Br. J. Nutr. 2016, 116(8), 1336–1345. DOI: 10.1017/S0007114516003548.
[87] Ryan, J. T.; Ross, R. P.; Bolton, D.; Fitzgerald, G. F.; Stanton, C. Bioactive Peptides from Muscle Sources : Meat
and Fish. Nutrients. 2011, 3(9), 765–791. DOI: 10.3390/nu3090765.
[88] Kim, S. K.; Wijesekara, I. Development and Biological Activities of Marine-derived Bioactive Peptides : A Review.
J. Funct. Foods. 2010, 2(1), 1–9. DOI: 10.1016/j.jff.2010.01.003.
[89] Boukhari, N.; Taleb-Senouci, D.; Chabane, F. Z.; Besbes, M.; Lamri-Senhadji, M. Y. Fish By-products Oil Corrects
Dyslipidemia, Improves Reverse Cholesterol Transport and Stimulates Paraoxonase-1 Activity in Obese Rat.
Ann. Cardiol. Angeiol. (Paris). 2013, 62(3), 149–154. DOI: 10.1016/j.ancard.2013.04.007.
[90] Lu, Z.; Chen, T. C.; Zhang, A.; Persons, K. S.; Kohn, N.; Berkowitz, R.; Martinello, S.; Holick, M. F. An Evaluation
of the Vitamin D3 Content in Fish: Is the Vitamin D Content Adequate to Satisfy the Dietary Requirement for
Vitamin D? J. Steroid. Biochem. Mol. Biol. 2007, 103,(3–5), 642–644.
[91] Tratado de nutrición; Hernández M., Sastre, A. Ediciones Días de Santos S.A.: Madrid, Spain, 1999.
[92] Carneiro, E. M.; Latorraca, M. Q.; Araujo, E.; Beltrá, M.; Oliveras, M. J.; Navarro, M.; Berná, G.; Bedoya, F. J.;
Velloso, A.; Soria, B.; et al. Taurine Supplementation Modulates Glucose Homeostasis and Islet Function. J. Nutr.
Biochem. 2009, 20(7), 503–511.
[93] Imae, M.; Asano, T.; Murakami, S. Potential Role of Taurine in the Prevention of Diabetes and Metabolic
Syndrome. Amino Acids. 2014, 46(1), 81–88. DOI: 10.1007/s00726-012-1434-4.
[94] Schaffer, S. W.; Jong, C. J.; Ramila, K. C.; Azuma, J. Physiological Roles of Taurine in Heart and Muscle.
J. Biomed. Sci. 2010, 17(Suppl 1), 1–8. DOI: 10.1186/1423-0127-17-S1-S2.
[95] Ribeiro, R. A.; Santos-Silv, J. C.; Vettorazzi, J. F.; Cotrim, B. B.; Mobiolli, D. D. M.; Boschero, A. C.;
CArneiro, E. M. Taurine Supplementation Prevents Morpho-physiological Alterations in High- Fat Diet Mice
Pancreatic B-cells. Amino Acids. 2012, 43(4), 1791–1801. DOI: 10.1007/s00726-012-1263-5.
[96] Hansen, S. H.;. The Role of Taurine in Diabetes and the Development of Diabetic Complications. Diabetes Metab.
Res. Rev. 2001, 17(5), 330–346. DOI: 10.1002/dmrr.229.
[97] Gavrovskaya, L. K.; Ryzhova, O. V.; Safonova, A. F.; Matveev, A. K.; Sapronov, N. S. Protective Effect of Taurine
on Rats with Experimental Insulin-dependent Diabetes Mellitus. Bull. Exp. Biol. Med. 2008, 146(2), 226–228.
DOI: 10.1007/s10517-008-0258-4.
[98] Brøns, C.; Spohr, C.; Storgaard, H.; Dyerberg, J.; Vaag, A. Effect of Taurine Treatment on Insulin Secretion and
Action, and on Serum Lipid Levels in Overweight Men with a Genetic Predisposition for Type II Diabetes
Mellitus. Eur. J. Clin. Nutr. 2004, 58(9), 1239–1247. DOI: 10.1038/sj.ejcn.1601955.
[99] Chauncey, K. B.; Tenner, T. E.; Lombardini, J. B.; Jones, B. G.; Brooks, M. L.; Warner, R. D.; David, R. L.;
Ragain, R. M. The Effect of Taurine Supplementation on Patients with Type 2 Diabetes Mellitus. Taur. 5. Adv.
Exp. Med. Biol. 2003, 526, 91–96.
[100] Kaneko, H.; Kobayashi, M.; Mizunoe, Y.; Yoshida, M.; Yasukawa, H.; Hoshino, S.; Itagawa, R.; Furuichi, T.;
Okita, N.; Sudo, Y.; et al. Taurine Is an Amino Acid with the Ability to Activate Autophagy in Adipocytes. Amino
Acids. 2018, 50(5), 527–535.
[101] Das, J.; Vasan, V.; Sil, P. C. Taurine Exerts Hypoglycemic Effect in Alloxan-induced Diabetic Rats, Improves
Insulin-mediated Glucose Transport Signaling Pathway in Heart and Ameliorates Cardiac Oxidative Stress and
Apoptosis. Toxicol. Appl. Pharmacol. 2012, 258(2), 296–308. DOI: 10.1016/j.taap.2011.11.009.
FOOD REVIEWS INTERNATIONAL 17

[102] Figueroa, A. L.; Figueiredo, H.; Rebuffat, S.; Vieira, E.; Gomis, R. Taurine Treatment Modulates Circadian
Rhythms in Mice Fed A High Fat Diet. Sci. Rep. 2016, 6(November), 1–13. DOI: 10.1038/srep36801.
[103] Kim, K. S.; Oh, D. H.; Kim, J. Y.; Lee, B. G.; You, J. S.; Chang, K. J.; Chung, H. J.; Yoo, M. C.; Yang, H. I.;
Kang, J. H.; et al. Taurine Ameliorates Hyperglycemia and Dyslipidemia by Reducing Insulin Resistance and
Leptin Level in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats with Long-term Diabetes. Exp. Mol. Med.
2012, 44(11), 665–673.
[104] Miyazaki, T.; Sasaki, S.; Toyoda, A.; Shirai, M.; Ikehami, T.; Matsuzaki, Y.; Honda, A. The Effects of Taurine
Depletion on Bile Acid Composition and Its Amino Acid-conjugation in the Bile of Cats. Faseb J. 2019, 33(S1).
[105] Nakamura-Yamanaka, Y.; Tsuji, K.; Ichikawa, T. Effect of Dietary Taurine on Cholesterol 7 Alpha-hydroxylase
Activity in the Liver of Mice Fed a Lithogenic Diet. J. Nutr. Sci. Vitaminol. (Tokyo). 1987, 33(3), 239–243. DOI:
10.3177/jnsv.33.239.
[106] Bass, J.; Takahashi, J. S. Circadian Integration of Metabolism and Energetics. Science. 2010, 330(6009),
1349–1354. DOI: 10.1126/science.1195027.
[107] Oike, H.; Oishi, K.; Kobori, M. Nutrients, Clock Genes, and Chrononutrition. Curr. Nutr. Rep. 2014, 3(3),
204–212. DOI: 10.1007/s13668-014-0082-6.
[108] Qian, J.; Scheer, F. Circadian System and Glucose Metabolism: Implications for Physiology and Disease. Trens.
Endocrinol. Metab. 2016, 27(5), 282–293. DOI: 10.1016/j.tem.2016.03.005.
[109] Parsons, M. J.; Lester, K. J.; Barclay, N. L.; Archer, S. N.; Nolan, P. M.; Eley, T. C.; Gregory, A. M. Polymorphisms
in the Circadian Expressed Genes PER3 and ARNTL2 are Associated with Diurnal Preference and GNβ3 with
Sleep Measures. J. Sleep Res. 2014, 23(5), 595–604. DOI: 10.1111/jsr.12144.
[110] Laermans, J.; Depoortere, I. Chronobesity: Role of the Circadian System in the Obesity Epidemic. Obes. Rev. 2016,
17(2), 108–125. DOI: 10.1111/obr.12351.
[111] Elvevoll, E. O.; Eilertsen, K. E.; Brox, J.; Dragnes, B. T.; Falkenberg, P.; Olsen, J. O.; Kirkhus, B.; Lamglait, A.;
Osternud, B. Seafood Diets: Hypolipidemic and Antiatherogenic Effects of Taurine and N-3 Fatty Acids.
Atherosclerosis. 2008, 200(2), 396–402. DOI: 10.1016/j.atherosclerosis.2007.12.021.
[112] Mikami, N.; Hosokawa, M.; Miyashita, K. Dietary Combination of Fish Oil and Taurine Decreases Fat
Accumulation and Ameliorates Blood Glucose Levels in Type 2 Diabetic/Obese KK-A Y Mice. J. Food Sci.
2012, 77(6), 114–120. DOI: 10.1111/j.1750-3841.2012.02687.x.
[113] United States Department of Agriculture. Agricultural Research Service; National Nutrient Database for Standard
Reference Legacy Release. https://www.usda.gov/(accessed July 24, 2019).
[114] Gormley, T. R.; Neumann, T.; Fagan, J. D.; Brunton, N. P. Taurine Content of Raw and Processed Fish Fillets/
portions. Eur. Food Res. Technol. 2007, 225(5–6), 837–842. DOI: 10.1007/s00217-006-0489-4.
[115] Connell, J. J.; saff of Torry Research Station. Advances in Fish Science and Technology; Press: United Kingdom,
1980.
[116] Balfegó, M. Diabetis mellitus tipus 2: Impacte metabòlic duna dieta rica en sardina. Ph.D. Biomedicine thesis,
Universitat de Barcelona, Barceona, Spain, 2016.
[117] Vuković, G.; Romanić, S. H.; Babić, Z.; Mustać, B.; Štrbac, M.; Deljanin, I.; Antanasijević, D. Persistent Organic
Pollutants (Pops) in Edible Fish Species from Different Fishing Zones of Croatian Adriatic. Mar. Pollut. Bull.
2018, 137, 71–80. DOI: 10.1016/j.marpolbul.2018.10.014.
[118] Kljaković-Gašpić, Z.; Romanić, S. H.; Klinčić, D.; Tičina, V. Chlorinated Compounds in the Muscle Tissue of Fish
from the Croatian Adriatic: Preliminary Data on Contamination and the Associated Health Risks. Arch. Ind. Hyg.
Toxicol. 2015, 66(4), 299–308.
[119] Bocio, A.; Domingo, J. L.; Falcó, G.; Llobet, J. M. Concentrations of PCDD/PCDFs and PCBs in Fish and Seafood
from the Catalan (Spain) Market: Estimated Human Intake. Environ. Int. 2007, 33(2), 170–175. DOI: 10.1016/j.
envint.2006.09.005.
[120] Affane, F.; Benahmed Daidj, N. B.; Louala, S.; Munezero, A. N.; Lamri-Senhadji, M. Y. Effects of an Obesogenic
Diet Enriched in Sardine By-products on Pro-atherogenic Markers in Wistar Rats. Ann. Cardiol. Angeiol. 2016,
65(3), 214–218. DOI: 10.1016/j.ancard.2016.04.011.
[121] Rodrigues, P. O.; Martins, S. V.; Lopes, P. A.; Ramos, C.; Miguéis, S.; Alfaia, C. M.; Pinto, R. M.; Rolo, E. A.;
Bispo, P.; Batista, I.; et al. Influence of Feeding Graded Levels of Canned Sardines on the Inflammatory Markers
and Tissue Fatty Acid Composition of Wistar Rats. Br. J. Nutr. 2014, 112(3), 309–319.
[122] Balfegò, M.; Canivell, S.; Hanzu, F. A.; Sala-Vila, A.; Martínez-Medina, M.; Murillo, S.; Mur, T.; Ruano, E.;
Linares, F.; Porras, N.; et al. Effects of Sardine-enriched Diet on Metabolic Control, Inflammation and Gut
Microbiota in Drug-naïve Patients with Type 2 Diabetes: A Pilot Randomized. Lipids Health Dis. 2016, 15(1),
DOI: 10.1186/s12944-016-0245-0.
[123] Moreira, A. C.; Gaspar, A.; Serra, M. A.; Simões, J.; Lopes da Cruz, J.; Amaral, T. F. Effect of a Sardine Supplement
on C-reactive Protein in Patients Receiving Hemodialysis. J. Ren. Nutr. 2007, 17(3), 205–213. DOI: 10.1053/j.
jrn.2007.02.005.
[124] Madani, Z.; Louchami, K.; Sener, A.; Malaisse, W. J.; Ait Yahia, D. Dietary Sardine Protein Lowers Insulin
Resistance, Leptin and TNF- α and Beneficially Affects Adipose Tissue Oxidative Stress in Rats with Fructose-
induced Metabolic Syndrome. Int. J. Mol. Med. 2012, 29(2), 311–318. DOI: 10.3892/ijmm.2011.836.
18 D. A. DÍAZ-RIZZOLO ET AL.

[125] Hamza-Reguig, S.; Benahmed Daidj, N. B.; Louala, S.; Boualga, A.; Lamri-Senhadji, M. Effect of Replacing Sardine
Oil with Margarine on Dyslipidemia, Dysglycemia and Redox Status of Adipose Tissue in High-fat Diet-induced
Obesity in Wistar Rats. Nutr. Food Sci. 2017, 47(1), 2–17. DOI: 10.1108/NFS-04-2016-0041.
[126] BelHadj, S.; Hentati, O.; Baccouch, N.; Ben Salah, H.; Boudaouara, T.; Ben Hadj, A.; Allouch, N.; El Feki, A. F.
Effect of Sardina Pilchardus Oil on Alloxan-induced Diabetic Rats. J. Metab. Dis. 2016, 122(1), 27–35.
[127] Aguilera, A. A.; Díaz, G. H.; Barcelata, M. L.; Guerrero, O. A.; Ros, R. M. Effects of Fish Oil on Hypertension,
Plasma Lipids, and Tumor Necrosis factor-α in Rats with Sucrose-induced Metabolic Syndrome. J. Nutr.
Biochem. 2004, 15(6), 350–357. DOI: 10.1016/j.jnutbio.2003.12.008.
[128] Venturini, D.; Simão, A. N.; Urbano, M. R.; Dichi, I. Effects of Extra Virgin Olive Oil and Fish Oil on Lipid Profile
and Oxidative Stress in Patients with Metabolic Syndrome. Nutrition. 2015, 31(6), 834–840. DOI: 10.1016/j.
nut.2014.12.016.
[129] Benaicheta, N.; Labbaci, F. Z.; Bouchenak, M.; Boukortt, F. O. Effect of Sardine Proteins on Hyperglycaemia,
Hyperlipidaemia and Lecithin:cholesterol Acyltransferase Activity, in High-fat Diet-induced Type 2 Diabetic
Rats. Br. J. Nutr. 2016, 115(1), 6–13. DOI: 10.1017/S0007114515004195.
FOOD REVIEWS INTERNATIONAL 19