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Review
Trans fatty acids and lipid profile: A serious risk factor to
cardiovascular disease, cancer and diabetes
Md. Ashraful Islam
a
, Mohammad Nurul Amin
b
,
*
, Shafayet Ahmed Siddiqui
b
,
Md. Parvez Hossain
a
, Farhana Sultana
b
, Md. Ruhul Kabir
a
a
Department of Food Technology and Nutrition Science, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
b
Department of Pharmacy, Atish Dipankar University of Science and Technology, Dhaka, 1230, Bangladesh
article info
Article history:
Received 26 February 2019
Accepted 14 March 2019
Keywords:
Trans fatty acid
Atherosclerosis
Diabetes
abstract
Trans Fatty acids (TFAs) have long been used in food manufacturing due in part to their melting point at
room temperature between saturated and unsaturated fats. However, increasing epidemiologic and
biochemical evidence suggests that excessive trans fats in the diet are a significant risk factor for car-
diovascular events as well as a risk factor for cancer and diabetes. A 2% absolute increase in energy intake
from trans-fat has been associated with a 23% increase in cardiovascular risk. They increase the levels of
low-density lipoprotein which is bad for health. Moreover, several epidemiological studies have been
demonstrated that a high intake of TFAs increases the incidence of cancer and diabetes. On the other
hand, total elimination of TFAs is not possible in a balanced diet due to their natural presence in dairy and
meat products. Many products with almost 0.5 g trans-fat, if consumed over the course of a day, may
approximate or exceed the 2 g maximum as recommended by the American Heart Association. The
objective of the review to demonstrate the causal association between trans fatty acid intake and in-
crease the risk of coronary heart disease through their influence on lipoprotein, association with
atherosclerosis, stroke, diabetes and cancer.
©2019 Published by Elsevier Ltd on behalf of Diabetes India.
1. Introduction
Trans-fatty acids (TFAs) are unsaturated fatty acids which
contain leastwise one double bond in the trans configuration. TFAs
are manufactured through industrial processes referred as indus-
trial trans fatty acids (iTFA) by partial hydrogenation and deodor-
ization of vegetable oils, and heating oil at very high temperature
[1]. Elaidic acid is the prime TFA often found in partially hydroge-
nated vegetable oil [2]. Low levels of naturally occurring TFAs are
obtained from the milk and meat of ruminant animals those are
referred as ruminant trans fatty acid (rTFA) e.g., cattle and sheep
[3]. The most predominant trans-isomer in ruminant TFA is vac-
cenic acid. Another TFA namely conjugated linoleic acid can be
formed from vaccenic acid [4]. In general, there is wide evidence
that all isomeric cis and trans fatty acids in ruminant fats and
partially hydrogenated vegetables oils are efficiently absorbed and
incorporated into chylomicrons with the possible exceptions of
fatty acids with double bonds in the 2 to 7 positions. Once they
reach the liver, chylomicron remnant triacylglycerol is taken up,
repackaged and exported into the circulation in the form of low
density lipoproteins [5]. Following incorporation into lipoprotein
fractions, triacylglycerol is transported to the peripheral tissues,
where they are hydrolyzed by enzyme lipoprotein lipase and taken
up into cells. Though trans fats are edible, consumption of trans fats
has been showed to increase the risk of Coronary heart disease
(CHD) in part by increasing the level of low-density lipoprotein
(LDL) referred as “bad cholesterol”and decreases the level of high-
density lipoprotein (HDL) referred as “good cholesterol”and raising
Triglycerides (TG) in the bloodstream thus promoting systemic
inflammation [6] (see Table 1).
Trans fatty acids are needed generally for commercial motives in
the food industries to yield semi fat foods and increase the shelf life
of products like margarine, crackers, deep-fried fast foods, pan-
cakes, omelets, etc. and can also be found in restaurants [7]. The
contents of TFAs differ from one food item to another, it is tough to
account their consumption in different countries. In USA it is
calculated to be 2e3 energy percent, whereas some countries in
Middle East and South Asia, it can be as aerial as 7 energy percent
*Corresponding author.
E-mail addresses: amin.pharma07@gmail.com (M.N. Amin), research.noory@
gmail.com (Md.R. Kabir).
Contents lists available at ScienceDirect
Diabetes &Metabolic Syndrome: Clinical Research &Reviews
journal homepage: www.elsevier.com/locate/dsx
https://doi.org/10.1016/j.dsx.2019.03.033
1871-4021/©2019 Published by Elsevier Ltd on behalf of Diabetes India.
Diabetes &Metabolic Syndrome: Clinical Research &Reviews 13 (2019) 1643e1647
[8]. In South Asian region, Vanaspati ghee is the principal source of
TFA. For instance, in India, Vanaspati ghee used to contain as high as
40e50% TFA [9]. In Iran, 33% fatty acids in partially hydrogenated oil
were TFA [10]. Around the world, different levels of TFA intake have
been accomplished due to dietary habit and varying quantities of
iTFA in processed foods [1].
High intake of dietary trans fatty acids (TFA) have a strong as-
sociation in increasing the risk of coronary heart disease [11 ].
Coronary heart disease (CHD) is commenced as a procurement of
atheromatous plaque in the arteries which inflict oxygen and blood
to the working heart. Development of plaque in the arteries is a
consequence of abundant risk factors including infection, diabetes,
smoking, physical activity, increased BMI, and high triglyceride
levels [12]. Various epidemiological studies have demonstrated a
potent definitive adherence between the consumption of TFA and
risk of CHD [13]. It has been estimated that a 2% raise in energy
consumption from TFA is linked with a 23% increase risk of CHD [7].
Due to the adverse health effects, the WHO recommends less than
1% TFA intake of total energy percent [14]. In Europe, trans fat are
“nearly banned”in Denmark (less than 2%), Australia, Austria,
Hungary, Iceland, Norway and Switzerland [15].
The objective of this paper is to review the causal association
between trans fatty acid intake and increase risk of coronary heart
disease through their influence on lipoprotein, association with
atherosclerosis, stroke, diabetes and cancer. This review aims to
provide a critical and up-to-date overview of current information
on existing condition on trans-fat intake and risk of cardiovascular
disease, blood lipid profile, diabetes and cancer.
2. Potential mechanism of trans fats metabolism
Trans fats seem to affect lipid metabolism by diverse pathways.
In vitro, trans fatty acids alter the secretion, lipid composition, and
size of Apo lipoprotein B-100 (apoB-100) particles produced by
hepatic cells [16]. This alteration is assimilated in studies in humans
by reduced rates of LDL apoB-100 catabolism [17], losses in the size
of LDL cholesterol particles [18], increased rates of apoA-I catabo-
lism [17], and alter in serum lipid levels [19 ]. In humans, the
structure of trans fat increases plasma mobility of cholesteryl ester
transfer protein [20], the key enzyme for the transfer of cholesterol
esters from HDL to LDL and very low-density lipoprotein (VLDL)
cholesterol. Such increased mobility may set out reduces in the
levels of HDL and rises in the levels of LDL and VLDL cholesterol
noticed with consumption of trans fatty acids [19].
The cellular mechanisms uttering trans fats to inflammatory
pathways and other non-lipid pathways are not well recognized.
Monocytes and macrophages, endothelial cells, and adipocytes may
each perform a role. Trans fatty acids accord monocyte and
macrophage reactions in humans, rising the production through
monocytes of tumor necrosis factor-
a
(TNF-
a
) and interleukin-6
(ILd6) [21] and probably also levels of monocyte chemo-
attractant protein (MCP) [22]. Trans fats also interfere in vascular
function. Trans fats have been demonstrated to raise circulating
biomarkers of endothelial dysfunction [23] and to weak nitric
oxideedependent arterial dilatation [24]. Trans fatty acids also
affect fatty acid metabolism of adipocytes, resulting in decreased
triglyceride elevation, decreased esterification of recently synthe-
sized cholesterol, and increased formulation of free fatty acids [25].
The effects of adiposity on the connection between consumption of
trans fat and circulating interleukin-6 and C-reactive protein levels
suspect that the inflammatory effects of trans fats may be partly
negotiated by adipose tissue [22].
The contents of TFAs differ from one food item to another; it is
tough to account their health effects and mechanism of metabolism
and consumption in different countries. Trans fat content in various
foods, ordered in g per 100g.
3. Trans fat, inflammation and atherosclerosis
There is competing evidence about the effect of trans fats on
systemic inflammation: in an interventional study, trans fat raised
markers of inflammation [27] but in other one did not [28]. There is
another conflict in observational studies in two reviews of the
Nurses’Health Study; two different groups of researchers have
found different markers of inflammation [23].
One considerable reason of atherosclerosis is disorders of lipid
metabolism and positive interrelation between plasma cholesterol
and atherosclerosis is now amply certified. So, the potential for
dietary TFAs to promote this.
Concern was a feasible mechanism for harmful effects of TFAs on
the cardiovascular system [29]. Bassett and colleagues demon-
strated that supplementation of the diet of LDL receptor deleted
mice with an industrial trans-fat, elaidic acid, resulted in the
distinct and definite incitement of atherosclerosis. Moreover, they
also exhibited that coupling of elaidic acid to a cholesterol-
supplemented diet did not persuade an additive payoff [30].
Abruptly, in the study conducted in the same model of empirical
atherosclerosis an amazing anti-atherogenic act by the ruminant
TFA, the vaccenic acid was unrolled. A momentous reduction in the
area of the atherosclerotic plaques veiled in the aortas from LDL
receptor deleted mice was observed, when diets were supple-
mented with cholesterol and vaccenic acid in comparison to diets
supplemented with both cholesterol and elaidic acid, or just
cholesterol alone [31].
4. Trans fatty acids increasing risk of coronary heart disease
and stroke
Individuals with higher dietary TFA intake possess increased
low-density lipoprotein (LDL) levels and lowering high-density li-
poprotein (HDL) levels [17]. Replacing just 2% of energy with un-
hydrogenated unsaturated fat instead of TFA reduce the risk of
CHD by 53% [32]. Leth and colleagues found a 60% decrease in CVD
risk in Denmark after the Danish Government implemented the
legislation to reduce the iTFA intake (Depending on calorie basis,
risk of CHD increases about 1e3% with TFA intake) [33]. A more
crucial proof found from Nurses’Health Study in which CHD risk
roughly doubled for each 2% increase in trans-fat calories consumed
Table 1
Contents of TFAs in different food types.
Food type TFA content Food type TFA content
Shortenings 10e33g Salty snacks 0e4g
Margarine/spreads 0.2e26g Cake frostings and sweets 0.1e7g
Butter 2e7g Animal fat 0e5g
Whole milk 0.07e0.1g Ground beef 1g
Breads/cake products 0.1e10g Vanaspati ghee (vegetable ghee) 3.5e28g
Source: [26], American Nutrition Association, The Heart Foundation.
Md.A. Islam et al. / Diabetes &Metabolic Syndrome: Clinical Research &Reviews 13 (2019) 1643e1647164 4
[32]. Epidemiological data have provided believing proof that the
inclusion of TFAs in our diet is related with an adoption of cardio-
vascular disease. Dietary TFAs have been associated with CHD and
an increased incidence of myocardial infarction [34]. According to
systemic review in 2009, there is convincing proof that intake of
trans fats increases the risk of CHD [35].
Regarding South Asia, it has been concluded that about 39% of
CHD cases in Iran can be reduced by replacing TFA with cis-unsat-
urated fats [10]. Indian Government has taken an attempt to pre-
vent TFA related health problems plans to reduce TFA content in
Vanaspati oil to 5% in 2013 [36]. In Pakistan there is no such
legislation in reducing TFAs intake. Therefore, an alarming rise of
CVD risk in Pakistan [37].
5. Trans fats adversely affect lipid profile &lipoproteins
There is a positive correlation between plasma LDL and
atherosclerosis and/or CHD [38]. Although epidemiological evi-
dence suggests that there is a positive association between TFA
intake and elevated plasma LDL [17] [as well as triglycerides [39], a
clear mechanism has not been established. In the human hepato-
blastoma (HepG2) cell line, TFAs have been associated with
increased LDL: high-density lipoprotein (HDL) ratios, increased Apo
lipoprotein B: Apo lipoprotein A (apoB: apoA) ratio and increased
cholesterol content in both LDL and HDL particles in comparison to
saturated fats [16]. All of these outcomes have been associated with
a higher risk of atherosclerosis and CHD. Similar outcomes reported
by Mitmesser et al. who suggested that TFAs altered the size and
composition of apoB-100 containing lipoproteins. These studies
provide a basic mechanism whereby TFAs deposit cholesterol in
arteries. However, itis important to recognize that these studies are
primarily correlative and more concrete evidence is necessary.
Furthermore, there is no distinction in these studies between rTFAs
and iTFAs. These two types of TFAs are structurally different and
therefore, their biological effects may also be very different [16].
Epidemiological evidence has generated conflicting results with
respect to an association of TFAs with serum lipid levels. In an ev-
idence based analysis observing the effects of isocaloric replace-
ment of polyunsaturated fatty acids (PUFAs), saturated fatty acids
(SFAs) or monounsaturated fatty acids (MUFAs) with TFAs, a sig-
nificant increase in low-density lipoprotein cholesterol (LDL-C)
levels, total cholesterol: high-density lipoprotein cholesterol (HDL-
C) ratio and the ratio of Apo B: Apo A was observed as well as a
decrease in HDL-C levels [33]. Others have shown a decrease in
LDL-C particle size with consumption of TFAs as opposed to un-
saturated fatty acids [18]. It is important to recognize that these
studies investigated a particular isomer of TFAs associated with the
hydrogenation of vegetable oils (such as the trans isomer of oleic
acid); therefore, more investigation with a wider variety of TFAs
may be necessary to fully understand the effect of TFAs on
lipoproteins.
6. Can trans fatty acids effect on cancer?
There are very few epidemiological studies that have investi-
gated the association of intake of vaccenic acid (VA) [40] and
conjugated linolenic acid (CLA) [41] and risk of cancer. A prospec-
tive study on women (1989e2002) revealed that trans-fat intake
supposedly associated with increased risk of breast cancer [42].
Some of the epidemiological studies that have been reported a
direct association with VA concentrations in serum or erythrocytes
and risk of breast cancer [40,43] or prostate cancer [44]. In
Netherlands a Cohort Study, energy-adjusted intake of VA was
associated with an increased risk of breast cancer [45]. There have
been 4 case-control studies that have investigated CLA intake and
cancer. Of these, one study has reported an inverse association with
dietary intake of CLA and risk of colorectal cancer [41], and one
study found significantly lower dietary intake and serum concen-
trations of CLA in individuals with breast cancer compared to those
without breast cancer among postmenopausal women [46]. In
women in the highest quartile of CLA intake, there was a 29%
reduction in the risk of colorectal cancer compared to those in the
lowest [41]. In the other 2 case-control studies, there was no sig-
nificant association of CLA [either as dietary intake [47] or con-
centration of CLA incorporated into adipose tissue [48] and the risk
of breast cancer]. However, in one of the studies, there was a
diminished risk of having an estrogen receptor (ER)-negative tu-
mor, in premenopausal women, when comparing the maximum
quartile of CLA intake and the minimum [47]. A prospective cohort
study has been demonstrated that intake of CLA is weakly related
with breast cancer incidence when comparing the maximum and
minimum quintiles of consumption [45].
7. Even trans fatty acid associates with diabetes
Three prospective studies have investigated the relationship
between the consumption of trans fatty acids and the occurrence of
diabetes. Consumption of trans fat was not significantly associated
with the risk of diabetes in two of these studies - among male
health professionals [49] and among women in Iowa [50]. However,
the ingestion of trans fatty acids significantly related to the risk of
diabetes among 84,941 female nurses who were observed for 16
years and in whom self-reported diabetes was affirmed and report
on dietary intake was periodically updated [51]. After adjustment
for other risk factors, trans fat consumption was positively linked
with the incidence of diabetes with a risk 39% points greater in the
upper quintile than in the lower quintile [13]. In the Iowa cohort, a
validation study supposed that the self-reported diagnosis of dia-
betes was incorrect in 36% of subjects, and diet was assessed onlyat
baseline and may have changed over time [50]. Molecular mecha-
nisms that might account for an effect of trans fatty acids on the
incidence of diabetes are not well established, but evidence of ef-
fects of trans fatty acids on metabolism in adipocytes [52].
8. Discussion
Trans fats are suspected to be nutritionally unnecessary.
Epidemiologic evidence has demonstrated that they are a signifi-
cant risk factor for cardiovascular disease; several studies demon-
strated that a 2% increase in daily energy intake from TFAs is
associated with a 23% increase in cardiovascular disease risk [53].
Trans fats have also been exhibited to have an adverse impact on
serum lipids and lipoproteins, increasing cardiovascular disease
risk to a greater extent [19]. A number of mechanisms for the effects
of trans fats have been proposed, including increased activity of
cholesteryl-ester transfer protein and increased levels of inflam-
matory marker [27], positive correlation with atherosclerosis [30],
increased risk of CHD [33], and positive association between TFAs
and elevated level of plasma LDL [17]. In case of diabetes there are
both inverse [49] and positive [51] association whereas epidemio-
logical studies demonstrated significant association between TFAs
intake and risk of cancer [40,48]. In review of Nurses’Health Study,
researchers have found different markers of inflammation [23].
Specific epidemiological studies demonstrated that 2% increase
intake of TFAs causes two times more risk of CHD [32]. Excess
intake vaccenic acid and conjugated linoleic acid the risk of cancer
[41]. TFA intake is positively linked with the incidence of diabetes
with a risk 39% points greater the upper quintile than in the lower
quintile [13]. It is clear from several trans-fat related studies that
dietary trans fats should be minimized. However, the presence of
Md.A. Islam et al. / Diabetes &Metabolic Syndrome: Clinical Research &Reviews 13 (2019) 1643e1647 16 45
trans fats in dairy and meat products will make complete elimi-
nation from a balanced diet impossible.
Food manufacturers and the food industry want alternatives to
trans fats but barriers comprise supply of ingredients and unknown
health sequel of new processes. Trans fats gained popularity as a
means of replacing saturated fats in the diet. Nevertheless, we now
know that trans fats have greater adverse health implications than
the saturated fats they wanted to replace. Eradicating trans fats by
returning to a high-saturated-fat diet is inappropriate. Consumers
are not fully conscious of the well-established health complications
of trans fats. Actually, many are disconcerted as to what fats they
should or should not be eating. Many are likely consuming trans
fats in excess of the maximum intake recommended by the
American Heart Association [54]. The present FDA labeling re-
quirements are a better first step in giving consumers with infor-
mation on trans fats. However, given the recommendation that
trans-fat intake be as low as possible, allowing all products with
<0.5 g trans fats to claim 0 g trans fats can be misleading to many
consumers. Eating four or five daily servings of foods with close to
0.5 g trans-fat can mean an individual who believes he/she is
consuming a healthful, balanced diet is actually exceeding 1% total
energy from trans fats. Greater transparency is required to allow
consumers to restrict dietary trans fats more effectively. Average
consumers do not understand the Nutrition Facts label, or its
relation to actual portion size [55,56]. Consumer education is
extremely important. In the interim, educational programs targeted
at these consumers must be developed to help them determine
which foods likely contain trans fats based on the presence of hy-
drogenated or partially hydrogenated oils in the ingredient list, as
well as to more accurately estimate their portion size relative to
standardized values on the Nutrition Facts panel.
9. Recommendations
Public awareness about the adverse health effects of TFAs should
be increased. More study and survey should be implemented about
the health hazards of TFAs, especially in South Asian countries and
developing countries because of the high prevalence of CVD. Na-
tional and international agencies can perform vital role in this
perspective. Media can also be focusing the bad health effects of
TFAs to the root level. Several plan and policies can be implemented
to eliminate the available use of TFAs. The legislations of FDA and
World Health Organization on TFAs consumption should be fol-
lowed. Daily consumption of TFAs should be less than 1% of total
energy intake. Industrial manufacturers should take measures to
use alternatives of TFA in their produce food products. They should
label the contents of TFAs in the packet of their products.
In South Asian countries, there should be conducted epidemi-
ological studies on TFAs consumption and health hazards. Rules and
legislations should be implemented based on the findings of the
study. In Bangladesh, people are less concern about the health
hazards of TFAs. So epidemiological studies should be implemented
and public awareness should be increased on adverse effect of high
intake of TFAs.
10. Conclusion
There is now overwhelming evidence based upon several
studies, TFAs have deleterious effects on our cardiovascular health,
cancer and diabetes when included in the diet in high amounts. The
synergistic effect of TFAs and other dietary components, drugs and
environmental factors also still needs to be investigated in order to
better understand TFAs and CHD and other health hazards. The
direct action of TFAs on cardio myocyte function is also unclear and
may represent yet another important mechanism for the
deleterious effects of TFAs. Due to the impressive preliminary
outcome documented in Denmark, many other countries across the
world are following their lead and creating legislation to limit the
amount of iTFAs available for public consumption. However,
restricting all TFA consumption may not be realistic or possible.
Finding novel ways to block the atherogenic action of TFAs may be a
more reasonable approach. Supplementation of the diet with flax
seed, for example, can prevent the atherogenic effects of dietary
iTFAs in animal models. Other dietary approaches remain to be
discovered. It is also important to recognize that many of our
concepts regarding TFAs do not consider other TFA isomers beyond
iTFAs. Because of the intriguing positive effects of vaccenic acid
consumption, the picture of the effects of TFAs as risk factors for
atherosclerosis may require further study to fully reveal the effects
of trans fats on cardiovascular disease. Ultimately, this may result in
some changes in the enacted public legislation.
Conflicts of interest
None of the authors declare a conflict of interest.
Sources of financial support
There is no funding to be disclosed.
Acknowledgements
The authors Md. Ashraful Islama, and Mohammad Nurul Aminb
contributed equally to this work.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.dsx.2019.03.033.
Abbreviations
TFAs Trans fatty acids
iTFA industrial Trans fatty acids
rTFA ruminant Trans fatty acid
CHD Coronary heart disease
TG Triglycerides
LDL Low-density lipoprotein
HDL High-density lipoprotein
VLDL Very low-density lipoprotein
TNF-
a
Tumor necrosis factor-
a
ILd6 Interleukin-6
MCP Monocyte chemoattractant protein
PUFAs Polyunsaturated fatty acids
SFAs Saturated fatty acids
MUFAs Monounsaturated fatty acids
LDL-C Low-density lipoprotein cholesterol
HDL-C High-density lipoprotein cholesterol
VA Vaccenic acid
CLA Conjugated linolenic acid
ER Estrogen receptor
References
[1] Downs SM, Loeh S, Wu JH. Trans fatty acids: a summary of the evidence
relating consumption to cardiovascular outcomes and the efficacy of pre-
vention policy to reduce levels in the food supply. In: Bendich A,
Deckelbaum R, editors. Preventive nutrition 5th edition: the comprehensive
guide for health professionals. Cham, Switzerland: Springer; 2016.
[2] Alonso L, Fontecha J, Lozada L, Fraga MJ, Juarez M. Fatty acid composition of
caprine milk: major, branched-chain, and trans fatty acids. J Dairy Sci
Md.A. Islam et al. / Diabetes &Metabolic Syndrome: Clinical Research &Reviews 13 (2019) 1643e1647164 6
1999;82(5):878e84.
[3] Stender S, Astrup A, Dyerberg J. Ruminant and industrially produced trans
fatty acids: health aspects. Food Nutr Res 2008;52.
[4] Lock AL, Corl BA, Barbano DM, Bauman DE, Ip C. The anti-carcinogenic effect of
trans-11 18:1 is dependent on its conversion to cis-9, trans-11 CLA by delta 9-
desaturase in rats. J Nutr 2004;134:2698e704.
[5] Sebedo JL, Christie WW. Metabolism of trans fatty acids in Human Nutrition.
second ed. 2009. p. 163e94.
[6] Food, Board Nutrition. Institute of medicine of the national academies. Na-
tional Academies Press; 2005. p. 423.
[7] Mozaffarian D, Martijn BK, Alberto A, Stampfer MJ, Walter CW. Trans fatty
acids and cardiovascular disease. N Engl J Med 2006;354:1601e13.
[8] Sundram K, Basiron Y. Trans fatty acids - nutritional considerations and la-
beling: an update and implications for oils and fats industry. In: Seminar on
food and micro nutritional aspects of red pal oil; 2003.
[9] Ghafoorunissa G. Role of trans fatty acids in health and challenges to their
reduction in Indian foods. Asia Pac J Clin Nutr 2008;17(1):212e5.
[10] Mozaffarian D, Abdollahi M, Campose H, Houshiarrad A, Willett WC. Con-
sumption of trans fats and estimated effects on coronary heart disease in Iran.
Eur J Clin Nutr 2007;61(8):1004e10.
[11] Willett WC, Stampfer MJ, Manson JE, Colditz GA, Speizer FE, Rosner BA. Intake
of trans fatty acids and risk of coronary heart disease among women. Lancet
1993;341(8845):581e5.
[12] Wilson PW, D'Agostino RB, Levy D, Belanger AM, et al. Prediction of coronary
heart disease using risk factor categories. Circulation 1998;97:1837e47.
[13] Oh K, Hu FB, Manson JE, Stampfer MJ, Willett WC. Dietary fat intake and risk of
coronary heart disease in women: 20 years of follow-up of the Nurses' Health
Study. Am JEpidemiol 2005;161:672e9.
[14] World Health Organization. Scientific update on trans fatty acids. TFA; 2016.
[15] World Health Organization. Europe leads the world in eliminating trans fats.
2014.
[16] Mitmesser SH, Carr TP. Trans fatty acids alter the lipid composition and size of
apoB-100-containing lipoproteins secreted by HepG2 cells. J Nutr Biochem
2005;16:178e83.
[17] Matthan NR, Welty FK, Barrett PH, Harausz C, Dolnikowski GG, Parks JS, et al.
Dietary hydrogenated fat increases high-density lipoprotein apoA-I catabo-
lism and decreases low-density lipoprotein apoB-100 catabolism in hyper-
cholesterolemic women. Arterioscler Thromb Vasc Biol 2004;24(6):1092e7.
[18] Mauger JF, Lichtenstein AH, Ausman LM, Jalbert SM, Jauhiainen M, Ehnholm C,
et al. Effect of different forms of dietary hydrogenated fats on LDL particle size.
Am J Clin Nutr 2003;78(3):370e5.
[19] Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and
carbohydrates on the ratio of serum total to HDL cholesterol and on serum
lipids and Apo lipoproteins: a meta-analysis of 60 controlled trials. Am J Clin
Nutr 2003;77:1146e55.
[20] van Tol A, Zock PL, van Gent T, Scheek LM, Katan MB. Dietary trans fatty acids
increase serum cholesteryl ester transfer protein activity in man. Athero-
sclerosis 1995;115:129e34.
[21] Han SN, Leka LS, Lichtenstein AH, Ausman LM, Schaefer EJ, Meydani SN. Effect
of hydrogenated and saturated, relative to polyunsaturated, fat on immune
and inflammatory responses of adults with moderate hypercholesterolemia.
J Lipid Res 2002;43:445e52.
[22] Mozaffarian D, Pischon T, Hankinson SE, Rifai N, Joshipura K, Willett WC, et al.
Dietary intake of trans fatty acids and systemic inflammation in women. Am J
Clin Nutr 2004;79(4):606e12.
[23] Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N. Consumption of
trans fatty acids is related to plasma biomarkers of inflammation and endo-
thelial dysfunction. J Nutr 2005;135:562e6.
[24] De Roos NM, Bots ML, Katan MB. Replacement of dietary saturated fatty acids
by trans fatty acids lowers serum HDL cholesterol and impairs endothelial
function in healthy men and women. Arterioscler Thromb Vasc Biol 2001;21:
1233e7.
[25] Matthan NR, Cianflone K, Lichtenstein AH, Ausman LM, Jauhiainen M, Jones PJ.
Hydrogenated fat consumption affects acylation-stimulating protein levels
and cholesterol esterification rates in moderately hypercholesterolemic
women. J Lipid Res 2001;42:1841e8.
[26] Tarrago-Trani MT, Phillips KM, Lemar LE, Holden JM. New and existing oils
and fats used in products with reduced trans-fatty acid content. J Am Diet
Assoc 2006;106(6):867e80.
[27] Bendsen NT, Christensen R, Bartels EM, Astrup A. Consumption of industrial
and ruminant trans fatty acids and risk of coronary heart disease: a systematic
review and meta-analysis of cohort studies. Eur J Clin Nutr 2011 Jul;65(7):
773e83.
[28] Smit LA, Katan MB, Wanders AJ, Basu S, Brouwer IA. A high intake of trans
fatty acids has little effect on markers of inflammation and oxidative stress in
humans. J Nutr 2011 Sep;141(9):1673e8.
[29] Nestel P. Trans fatty acids: are its cardiovascular risk fully appreciated? Clin
Ther 2014;36:315e21.
[30] Bassett CM, McCullough RS, Edel AL, Maddaford TG, Dibrov E, Blackwood DP,
et al. Trans-fatty acids in the diet stimulate atherosclerosis. Metabolism 2009
Dec;58(12):1802e8.
[31] Bassett CM, Edel AL, Patenaude AF, McCullough RS, Blackwood DP,
Chouinard PY, et al. Dietary vaccenic acid has antiatherogenic effects in
LDLr-/- mice. J Nutr 2010;140(1):18e24.
[32] Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Rosner BA, et al. Dietary
fat intake and the risk of coronary heart disease in women. N Engl J Med 1997
Nov 20;337(21):1491e9.
[33] Micha R, Mozaffarian D. Trans fatty acids: effects on cardio metabolic health
and implications for policy. Prostaglandins Leukot Essent Fatty Acids 2008;79:
147e52.
[34] Erkkil€
a AT, Booth SL, Hu FB, Jacques PF, Manson JE, Rexrode KM, et al. Phyl-
loquinone intake as a marker for coronary heart disease risk but not stroke in
women. Eur J Clin Nutr 2005;59(2):196e204.
[35] Teegala SM, Willett WC, Mozaffarian D. Consumption and health effects of
trans fatty acids: a review. J AOAC Int 2009;92:1250e7.
[36] Chibber A. India to reduce trans fats in Vanaspati oils. 2012. 19 January, www.
foodnavigator-asia.com.
[37] Ahmad K. Facing up to Pakistan's cardiovascular challenge. Lancet
2002;359(9309):859.
[38] Mureddu GF, Brandimarte F, De Luca L. High-density lipoprotein levels and
risk of cardiovascular events: a review. J Cardiovasc Med (Hagerstown) 2012
Sep;13(9):575e86.
[39] Adams TH, Walzem RL, Smith DR, Tseng S, Smith SB. Hamburger high in total,
saturated and trans-fatty acids decreases HDL cholesterol and LDL particle
diameter, and increases TAG, in mildly hypercholesterolaemic men. Br J Nutr
2010;103(1):91e8.
[40] Shannon J, King IB, Moshofsky R, Lampe JW, Gao DL, Ray RM. Erythrocyte fatty
acids and breast cancer risk: a case-control study in Shanghai, China. Am J Clin
Nutr 2007;85:1090e7.
[41] Larsson SC, Bergkvist L, Wolk A. High-fat dairy food and conjugated linoleic
acid intakes in relation to colorectal cancer incidence in the Swedish
Mammography Cohort. Am J Clin Nutr 2005;82:894e900.
[42] Chaj
es V, Thi
ebaut AC, Rotival M, Gauthier E, Maillard V, Boutron-Ruault MC,
et al. Association between serum trans-monounsaturated fatty acids and
breast cancer risk. Am J Epidemiol 2008;167(11):1312e20.
[43] Rissanen H, Knekt P, Jarvinen R, Salminen I, Hakulinen T. Serum fatty acids
and breast cancer incidence. Nutr Canc 2003;45:168e75.
[44] King IB, Kristal AR, Schaffer S, Thornquist M, Goodman GE. Serum trans-fatty
acids are associated with risk of prostate cancer in beta Carotene and Retinol
Efficacy Trial. Cancer Epidemiol Biomark Prev 2005;14:988e92.
[45] Voorrips LE, Brants HA, Kardinaal AF, Hiddink GJ, van den Brandt PA,
Goldbohm RA. Intake of conjugated linoleic acid, fat, and other fatty acids in
relation to postmenopausal breast cancer: The Netherlands Cohort Study on
Diet and Cancer. Am J Clin Nutr 2002;76(4):873e82.
[46] Aro A, Mannisto S, Salminen I, Ovaskainen ML, Kataja V, Uusitupa M. Inverse
association between dietary and serum conjugated linoleic acid and risk of
breast cancer in postmenopausal women. Nutr Canc 2000;38:151e7.
[47] McCann SE, Ip C, Ip MM, McGuire MK, Muti P, Edge SB. Dietary intake of
conjugated linoleic acids and risk of premenopausal and postmenopausal
breast cancer, Western New York Exposures and Breast Cancer Study (WEB
Study). Cancer Epidemiol Biomark Prev 2004;13:1480e4.
[48] Chajes V, Lavillonniere F, Ferrari P, Jourdan ML, Pinault M, Maillard V, et al.
Conjugated linoleic acid content in breast adipose tissue is not associated with
the relative risk of breast cancer in a population of French patients. Cancer
Epidemiol Biomark Prev 2002;11:672e3.
[49] van Dam RM, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Dietary patterns and
risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med 2002;136:201e9.
[50] Meyer KA, Kushi LH, Jacobs Jr DR, Folsom AR. Dietary fat and incidence of type
2 diabetes in older Iowa women. Diabetes Care 2001;24:1528e35.
[51] Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG. Diet, lifestyle,
and the risk of type 2 diabetes mellitus in women. N Engl J Med 2001;345(11):
790e7. 13.
[52] Saravanan N, Haseeb A, Ehtesham NZ, Ghafoorunissa X. Differential effects of
dietary saturated and trans-fatty acids on expression of genes associated with
insulin sensitivity in rat adipose tissue. Eur J Endocrinol 2005;153:159e65.
[53] Ascherio A, Katan MB, Zock PL, Stampfer MJ, Willett WC. Trans fatty acids and
coronary heart disease. N Engl J Med 1999;340:1994e8.
[54] American Heart Association Nutrition Committee, Lichtenstein AH, Appel LJ,
Brands M, Carnethon M, Daniels S, et al. Diet and lifestyle recommendations
revision 2006: a scientific statement from the American Heart Association
Nutrition Committee. Circulation 2006;114:82e96.
[55] Borra S. Consumer perspectives on food labels. Am J Clin Nutr 2006;83(suppl):
1235S.
[56] Rolls BJ, Morris EL, Roe LS. Portion size of food affects energy intake in normal-
weight and overweight men and women. Am J Clin Nutr 2002;76:1207e13.
Md.A. Islam et al. / Diabetes &Metabolic Syndrome: Clinical Research &Reviews 13 (2019) 1643e1647 16 47
