Atherosclerosis 205 (2009) 458–465
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/atherosclerosis
The negative effects of hydrogenated trans fats and what to do about them
Fred A. Kummerow∗
Department of Bioscience, College of Veterinary Medicine, The Burnsides Research Laboratory, University of Illinois, Urbana, IL 61801, United States
a r t i c l e i n f o
Received 14 July 2008
Received in revised form 23 February 2009
Accepted 7 March 2009
Available online 19 March 2009
Coronary heart disease
Trans fatty acids
a b s t r a c t
Partially hydrogenated vegetable oils have been in the American diet since 1900. More than 50 years ago
they were found to contain trans fatty acids that were different from natural fatty acids in plant oils and
in animal fat. There was growing evidence that the consumption of trans fats have negative health effects,
including increasing plasma lipid levels. In 2003, the Food and Drug Administration (FDA) ruled that the
amount of trans fat in a food item must be stated on the label after January 1, 2006; food items could be
labeled 0% trans if they contain less than 0.5g/serving.
Since the initial ruling, it is now known that the fatty acids in partially hydrogenated vegetable oil are
14 cis and trans isomers of octadecenoic and octadecadienoic acids that are formed during hydrogena-
tion. They cause inflammation and calcification of arterial cells: known risk factors for coronary heart
disease (CHD). They inhibit cyclooxygenase, an enzyme required for the conversion of arachidonic acid
to prostacyclin, necessary for the regulation of blood flow.
There have been several reformulations of hydrogenated fat containing varying amounts of trans fatty
acids and linoleic acid, an essential fatty acid that is converted to arachidonic acid. Epidemiological data
suggest that when trans fat percentages go up and linoleic acid percentages go down, death rates rise;
when trans goes down, death rates go down. In spite of the harmful effects of trans fats, the FDA allows
it in the food supply as long as the amount in a food item is declared on the label. Trans fat should be
banned from the food supply.
© 2009 Elsevier Ireland Ltd. All rights reserved.
This paper will review the history of hydrogenated trans fat
including the identification of their chemical composition and
properties leading to its use. It will compare natural trans fat found
in ruminant fats, e.g. butter, to those from hydrogenated fat. Stud-
ies showing the negative effects of hydrogenated trans fats will be
reviewed and epidemiological data presented to further illustrate a
trans fat will be explained, and data presented on the limitations of
the current ruling. Courses of action such as banning hydrogenated
trans fats in its current form and reformulating its composition are
∗Correspondence address: 205 Burnsides Research Laboratory, 1208 West Penn-
sylvania Ave, Urbana, IL 61801, United States. Tel.: +1 217 333 1806;
fax: +1 217 333 7370.
E-mail address: email@example.com.
2. Fats and oils background
Geography first determined which fats and oils were included
in the diet: butter, lard and beef tallow in Northern Europe and
North and South America, and olive, sesame, sunflower seed and
soybean oils in Southern Europe and the rest of the world . No
matter the geography or the form, all fats and oils are composed
of triglycerides, which is glycerol attached to three fatty acids. If
these fatty acids are largely saturated fatty acids, such as stearic
acid, they are a solid fat (like butter) at room temperature . If
they are attached to an unsaturated fatty acid, such as linoleic or
linolenic acid, known as polyunsaturated fatty acids (PUFA), they
are an oil (like soybean oil) at room temperature . In the late
1800s, a French chemist  discovered that an unsaturated fatty
acid can be converted to a saturated fatty acid by bubbling hydro-
gen through a heated vegetable oil in a closed vessel. If completely
hydrogenated, they become stearic acid .
The exact fatty acid composition of the hydrogenated oil was
essentially unknown until the development of gas chromatogra-
phy (GC) by James and Martin in 1952 . The FDA, using the AOCS
method , labeled the isomers in partially hydrogenated fat as
only one peak (elaidic acid) . It is only with a GC equipped with
a 200m column that it is possible to further separate the fatty
acid isomers of partially hydrogenated fat into at least 14 separate
isomeric fatty acids .
0021-9150/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved.
F.A. Kummerow / Atherosclerosis 205 (2009) 458–465
Fig. 1. The geometric structure of linoleic and vaccenic acid and oleic and elaidic
Using soybean oil as an example, differences between the nat-
ural oil and the result of the hydrogenation process is explained
below. Soybean oil in its natural form  contains 52.5% linoleic
(18:2 ?9,12) acid, which is also known as 18:2n6or omega-6. It
contains 7.5% linolenic (18:3 ?9,12,15) acid also known as 18:3n3
or omega-3. The designation 18:2 ?9,12, and 18:3 ?9,12,15means
that these two fatty acids have double bonds at position 9 and 12 or
9,12 and 15 at which hydrogen can be added. During hydrogenation
the double bond at any of these 9,12 or 9, 12, 15 positions can be
shifted to form new cis and trans unsaturated fatty acid isomers
not present in vegetable oil. The double bond of the cis-natural
linoleic and linolenic fatty acids can also change the configuration
from cis to trans, creating a geometric isomer like trans ?11-18:1
vaccenic acid (Fig. 1). Oleic acid, the largest percentage of the nat-
ural fatty acid in the human body, is cis ?9-18:1 (the number after
delta indicates the position of the double bond at the carbon atom
counting from the carboxyl group). Oleic acid goes through geo-
metrical isomerisation during hydrogenation to trans ?9-18:1 acid
known as elaidic acid; thus the “natural” oleic acid is turned into
elaidic acid during the hydrogenation process, and becomes an
“unnatural” fatty acid (Fig. 1). It twists into a new form and can
be both a cis and/or a trans fatty acid. In addition to geometrical
isomerisation, the double bond of either cis or trans fatty acids can
linolenic acid changing their position from ?9or ?9,12?9,12,15cre-
ating 5 monoene cis positional isomers, 6 trans monoene isomers
and 3 trans diene positional isomers (9). Thus hydrogenated soy-
bean oil contains 24.1% trans monoenes, 6.2% trans dienes and 9.4%
cis monoene isomers or a total of 39.7% isomeric fatty acids. They
were identified as cis and trans octadecenoic and octadecadienoic
isomers on a GC equipped with a 200m column by their mixed
melting points  with authentic octadecenoic and octadeca-
these fatty acids are present in natural soybean oil. For simplicity,
the isomers will be referred to as trans fat in this paper whenever
Fig. 2. Synthesis of prostacyclins and thromboxanes.
3. The need for essential fatty acids (EFA) in the diet
It was unknown until 1930 that linoleic (18:2n6) and linolenic
and the vitamins , cannot be synthesized in the human body;
they must come from a diet that includes natural fats and oils. The
14 isomers in hydrogenated fat can be used as a source of energy
but they cannot substitute for EFA because they do not have the
required double bond structure.
is synthesized into arachidonic acid and linolenic acid (n−3) is syn-
thesized into eicosapentaenoic acid (Fig. 2). Both in turn are made
into prostacyclin or thromboxane. Prostacyclin and thromboxane
have to be continually made from the EFA because they last only
about 10s in the blood and thus must be constantly replaced .
Prostacyclins are synthesized in the endothelial cells that line the
blood vessel wall. Thromboxanes are synthesized in the platelets
in the blood . Fish have already converted the linolenic acid
they get from seaweed into eicosapentaenoic acid. Hence fish oil is
often recommended as a dietary supplement, although as (Fig. 2)
indicates, prostacyclin and thromboxane can be made from linoleic
acid as well. The least expensive source of omega-3 and omega-6 is
soybean oil, which is sold as vegetable oil.
The balance between prostacyclin for flow and thromboxane for
clotting is a very delicate one and can be changed by different diets
farin) may be prescribed for those who have heart disease in order
to keep their blood from clotting. However, Coumadin plus the nat-
ural production of prostacyclin may cause too much bleeding .
This can lead to macular degeneration, an eye disease in which the
ing. Vitamin K may be recommended when the blood is too fluid,
although it is often in the diet, especially in greens. Vitamin K in
caused by cerebral (brain) artery blockages . Vioxx, a medica-
tion to alleviate the pain of arthritis, was recently withdrawn from
the market because of its effect on heart attacks and strokes; it led
to too little production of prostacyclin .
EFA are also needed for reproduction. Since the 1930s, it was
known that reproduction always failed on fat-free diets . In
studies on rats, reproduction continued under low fat conditions
because the rats had enough linoleic acid stored in their bodies.
They synthesized arachidonic acid from the linoleic acid in their
F.A. Kummerow / Atherosclerosis 205 (2009) 458–465
ies (such as rats born to mothers on fat-free diets), they could not
make enough of the arachidonic acid needed for healthy reproduc-
tion, and their young died. Women need the EFA for reproduction,
and the easiest way to supply them is from plant oils . EFA are
tions, such as brain activity and vision . Brain cells contain 70%
fat including 24% omega-3 and 28% omega-6 fatty acids . Veins
and arteries also contain these fatty acids, with the veins of adults
containing 5% omega-3 and 6% omega-6 fatty acids .
3.1. Differences between natural and hydrogenated trans fats and
Butterfat from dairy cows contains 2–4% trans fatty acid,
known as trans vaccenic acid (t?11-18:1). It is produced from the
linolenic (18:3n3) and linoleic (18:2n6) acids in the grass fat by
the microorganisms’ enzymes in the stomach of dairy cows. Nat-
ural trans fats are metabolized differently from hydrogenated trans
For example, a study with piglets  from mothers fed hydro-
genated soybean oil showed that their arteries contained less
linoleic acid converted to arachidonic acid than the arteries of
piglets from mothers fed butterfat or corn oil. This indicated that
the trans fat in hydrogenated soybean oil inhibited the metabolic
conversion of linoleic to arachidonic acid. Furthermore, an analysis
of the fat embedded in the arteries of the piglets from mothers fed
partially hydrogenated soybean oil showed that they contained 3%
trans fat incorporated into their phospholipids by 48 days of age.
tained 30.3% of trans fat . The butterfat contained only 2–4% of
trans present as vaccenic acid (t?11-18:1) which was metabolized
into conjugated linoleic acid . Vaccenic acid did not inhibit the
metabolic conversion of linoleic to arachidonic acid. Epidemiolog-
ical studies of intake of ruminant trans fat and risk of coronary
heart disease (CHD) indicated that the intake of ruminant trans
fatty acid was innocuous or even protective against coronary heart
Pilgeram has discussed in two reviews the use of fat in the
human body [28,29]. The mitochondria in heart smooth mus-
cle cells use fatty acids as a source of energy through oxidative
phosphorylation, a process that involves many steps before the
mitochondria can use that energy . The trans fatty acid (elaidic
acid in unhydrogenated vegetable oil [31,32]. During a heart attack,
it is likely that more energy is needed quickly than is provided by
the slower metabolizing elaidic acid.
4. Health effects of trans fatty acids in hydrogenated fat
This section discusses several types of studies regarding the
health effects of hydrogenated trans fats.
4.1. The negative effect on plasma lipids
There are thousands of papers documenting the effects of trans
fat on plasma lipid levels in the blood. The best known are the clin-
ical studies by Katan and others [33–42] in the 1990s that indicated
high-density lipoprotein (HDL) plasma levels. They focused on the
level of LDL and HDL plasma levels in healthy subjects and found
that the replacement of 10% of energy from saturated fatty acids by
vasodilatation as an endpoint in dietary intervention. An increase
in LDL plasma concentrations was believed to be a risk factor for
Studies on CHD during the 1950s and 1960s typically did
not consider the percentage of trans fat and the percentage of
linoleic acid in the diet as factors in plasma cholesterol levels.
One of the most comprehensive studies on the possible role of
hydrogenated fat (The National Diet-Heart Study)  in heart
disease was carried out in 1968. In this study, persons consum-
ing margarine C (with 12% trans fat and 62% linoleic acid) had
plasma cholesterol levels 20mg% lower than those consuming
margarine D (with 38% trans fat and only 12% linoleic acid). At
the time, this study was interpreted to mean that certain for-
mulations of margarine were healthy since LDL cholesterol levels
were lower; however in retrospect, it appears that it was the
presence of the linoleic acid that led to these lower cholesterol
4.2. Effect on increasing systematic inflammation
trans fats increase the inflammation in the arteries. According to
Sun et al. , higher levels of trans fat of red blood cells are
associated with systematic inflammation and an increased risk
of CHD in women. Basu et al.  studied dietary factors and
their role in inflammation; they found that trans fat promoted
low grade inflammation. Lopez-Garcia et al.  also believed that
consumption of trans fat is related to plasma biomarkers of inflam-
mation and endothelial dysfunction. Their study suggested that the
higher intake of trans fat could adversely affect endothelial func-
Several researchers have studied the effects of other dietary fac-
tors and inflammation, often through the presence of C-reactive
proteins (CRP), which are associated with inflammation. For exam-
ple, Massaro et al.  believed that atherosclerosis was a dynamic
process with inflammatory changes in the endothelium of conduit
arteries. Furthermore they showed that the presence of omega-
3 fatty acids decreased the amount of inflammation. Giugliano
et al.  researched several dietary strategies included ade-
quate omega-3 fatty acids intake, reduction of saturated and
trans fats, and consumption of a diet high in fruits, vegetables,
nuts, and whole grains and low in refined grains. Each of these
strategies was associated with lower generation of inflamma-
tion. Most of the studies using fish oil or pure omega-3 fatty
acids supplementation failed to show any effect on CRP lev-
els unless the fish oil supplement was given at a high dose
Harvey et al.  concluded that the presence of inflammation
was an independent risk factor for atherosclerosis; sudden death
from cardiac causes like diabetes and heart failure may result. They
further stated that effects of trans fats may account in part for
inflammatory effects on cardiovascular health. Increased levels of
the inflammatory biomarker, high-sensitivity CRP, predicted car-
as well as cholesterol, Ridker et al.  hypothesized that people
with elevated high-sensitivity CRP levels but without hyperlipi-
This randomized trial of apparently healthy men and women
who did not have hyperlipidemia but did have elevated levels
of high-sensitivity CRP, indicated that the rates of a first major
cardiovascular event and death from any cause was apparently
reduced among the participants who received rosuvastatin as
compared with those who received a placebo . These studies
looked at inflammation from a variety of perspectives and pro-
vided a link between consumption of trans fats and inflammatory
F.A. Kummerow / Atherosclerosis 205 (2009) 458–465
4.3. Effect on Cyclooxygenase-2 (COX-2) expression
COX-2 is the enzyme that is necessary to make prostacy-
clin to keep the blood flowing, thus lowering the potential for
a heart attack. Mozaffarian et al.  calculated the potential
effect of reducing the intake of industrially produced trans fatty
acids on the incidence of CHD in the United States. They pre-
dicted on the basis of changes in total and HDL cholesterol levels
alone, a meaningful proportion of CHD events (3–6%) would be
averted. However, they believed that this reduction was under-
estimated, since trans fats may also influence the risk of CHD
through other mechanisms, such as inflammatory or endothe-
lial effects. It has also been shown that trans fat inhibited the
conversion of linoleic acid to arachidonic acid and inhibited the
secretion of prostacyclin . Vane et al.  have shown that COX,
an enzyme that converts arachidonic acid to prostaglandin H2, is
further metabolized to prostanoids. Vane et al.  stated two
isoforms of COX existed, a constitutive (COX-1) and an inducible
(COX-2) enzyme. COX-2 may be the enzyme that recognizes the
isomers produced during hydrogenation as a foreign substrate
and reacts to them by causing inflammation and inhibition of
prostacyclin. COX-2 is the inducible isoform of COX. COX-1 is
present constitutively while COX-2 is expressed primarily after
the inflammatory insult. The activity of COX-1 and -2 results in
the production of a variety of potent biological mediators (the
prostaglandins) that regulate homeostatic and disease processes
4.4. Negative impact on prostacyclin synthesis
The biochemical studies of Holman et al. [56–58] indicated that
trans fat inhibited the conversion of linoleic to arachidonic acid.
Both the cis and trans fatty acid isomers in hydrogenated fat com-
petitively inhibited the synthesis of arachidonic acid from linoleic
acid and eicosapentaenoic acid from linolenic acid. Thus, it may
not be only the trans fatty acid isomers, but the cis fatty acid iso-
showed how the liver microsomes desaturated the unsaturated 18
(18:2n6) to arachidonic acid (20:4n6).
Kummerow et al.  carried this a step further with endothe-
lial cells, those cells which are the first layer in the arteries. They
cultured endothelial cells in a medium that contained 100?M of
the fatty acids of hydrogenated soybean oil. The cells contained
less prostacyclin than endothelial cells that had been cultured with
100?M of the fatty acids from unhydrogenated soybean oil. These
data showed that the incorporation of trans fat from hydrogenated
soybean oil into endothelial cell membrane phospholipid inhibited
the synthesis of linoleic acid to arachidonic acid and depressed the
secretion of prostacyclin (Table 1). They also showed that incorpo-
cells that line human coronary arteries may depress the secre-
tion of prostacyclin that keep the blood from clotting. Cheng et al.
 have shown that prostacyclin had a role in the cardiovascu-
lar response to thromboxane. The addition of an excess amount
of linoleic acid to this hydrogenated soybean oil fatty acids did
not increase the secretion of prostacyclin in endothelial cells. The
concentration of trans fatty acid rather than the concentration of
linoleic acid was therefore responsible for regulating the synthe-
sis and secretion of prostacyclin in endothelial cells. The trans fat
in hydrogenated fat not only inhibited the synthesis of prostacy-
clin that regulated the clotting of blood but also, could not serve
as precursors for prostacyclin synthesis. The trans fat “incorpo-
Prostacyclin synthesis from endogenous arachidonic acid by endothelial cells which
had incorporated fatty acids in soybean oil or hydrogenated soybean oil.
Fatty acid fraction Amount of prostacyclin as pmol/mg
Total fatty acid of soybean oil
Total fatty acid of
hydrogenated soybean oil
Monoene fraction of soybean
Monoene fraction of partially
38.9 ± 3.1a
2.4 ± 0.5a
142.6 ± 11.9a
70.0 ± 7.7a
14.6 ± 2.0a
222.1 ± 27.5a
9.4 ± 0.4a
110.1 ± 27.8a
Results are given as means ± standard deviation of three experiments.
aStatistical difference at a level of p<0.05, comparing with control group (total
fatty acid of soybean oil) in the same column. Experimental detail reference Kum-
merow et al. .
and displaced the essential linoleic, linolenic and arachidonic
4.5. The association of trans fat with CHD
CHD is due to either atherosclerosis severe enough to block
blood flow or to a blood clot due to a lack of prostacyclin secre-
tion in the endothelial cells that line the coronary arteries. Both
result in a lack of nutrients to the muscle cells in the heart and
they stop functioning. Consumption of trans fat is considered a
risk in CHD [33,52]. There is a belief, however, that the negative
effects of consuming trans fats can be overcome with consumption
of polyunsaturated fats. Oh et al.  found an inverse associa-
tion between polyunsaturated fat intake and CHD risk, and it was
strongest among overweight women. In addition, trans fat intake
was associated with increased risk of CHD, particularly for younger
women . In patients who died from primary cardiac arrest,
Lemaitre et al.  showed an increase of trans fat in their red cell
membrane was also accompanied by a decrease of total n−3 fatty
Several researchers have documented the effects of foods with-
et al.  showed that n−3 PUFAs from both seafood and plant
sources may reduce CHD risk, with little apparent influence from
background n−6 PUFA intake. They found lower death rates among
those with high seafood and plant-based diets. Plant-based n−3
PUFAs may particularly reduce CHD risk when seafood-based n−3
PUFA intake was low, which has implications for populations with
low consumption or availability of fatty fish . Kris-Etherton et
al.  found that nuts and peanuts routinely incorporated in a
healthy diet with a composite of numerous cardioprotective nutri-
partially explain why the positive relationship between trans fat
and cardiovascular risk is greater than one would predict based
solely on its adverse effects on plasma lipids.
4.6. Suggested mechanisms that are involved in CHD
Two mechanisms may be involved in CHD: (1) the oxidation of
the fatty acids and oxidation of the cholesterol in the LDL; (2) the
deposition of trans fat in the cardiovascular system of the veins and
arteries. These two mechanisms are outlined in Fig. 3.
When sufficient biological antioxidants are not present [68–76]
in the plasma, the LDL is oxidized to oxLDL and cholesterol is
oxidized to oxysterol [23,71,72]. Oxysterols incorporated into the
endothelial layer of the arteries and veins can change the phos-
pholipid cell membrane composition so that more sphingomyelin
F.A. Kummerow / Atherosclerosis 205 (2009) 458–465
Fig. 3. Mechanisms according to references involved in the plasma and cells that
may lead to coronary heart disease.
infiltration . Oxysterols were present at higher concentrations
in the plasma of patients who had coronary artery bypass graft-
ing (CABG) surgery . These patients had 40 times more calcium
in their bypassed veins than normal veins in the same patient
. When oxysterol purchased from Sigma–Aldrich were added
to plasma from patients who did not need CABG surgery, endothe-
the incorporation of radioactive calcium did not differ from that
of plasma from CABG patients . This indicates that oxysterols
oxysterols in a standard culture media, the cells became calcified
in a similar way to those of the CABG patient . The oxidation of
cholesterol and deposition of calcium is the primary cause for the
development of atherosclerosis in the arteries and veins [71–76].
The second mechanism that may be involved in CHD is trans fat.
As discussed earlier [9,51–54], trans fat inhibits COX-2, an enzyme
which converts arachidonic acid to prostacyclin that is needed to
clot in any of the coronary arteries can result in sudden death
[77,78]. The American Heart Association has stated that 42% of vic-
tims of a sudden heart attack do not reach a hospital still alive
tured under two conditions showed that trans fatty acid calcify
arterial cells. One with a trans fatty acid added as the “unnatu-
ral” elaidic acid (t18:1n9) and the other with a cis fatty acid added
as the “natural” oleic acid (cis 18:1n9) and testing with radioac-
An autopsy of 24 human specimens showed that human subjects
that had died of heart disease contained up to 12.2% trans fat in
their adipose tissue, 14.4% in liver, 9.3% in heart tissue, and 8.8% in
aortic tissue and in atheroma .
5. Epidemiological data collected by the Center for Disease
Epidemiological data collected by the CDC further illustrate the
potential harmful effects of trans fat . These data showed that,
death from CHD in the USA increased from 265.4/100,000 in 1900
to 581/100,000 population by 1950. During this time period, both
margarine and shortening had a high percentage of trans fat (rang-
ing from 39 to 50%) and a low percentage of linoleic acid (ranging
from 6 to 11%) according to the technical director of the Institute of
Shortening and Edible Oils . In 1968, the President of the Insti-
tute persuaded its members to lower the trans fat and increase the
Fig. 4. Comparison of fat sources and consumption .
linoleic acid content of margarine and shortening. The composition
of margarine and shortening was changed in 1968 with trans fats
ranging from 20 to 27% and the linoleic acid ranging 24–25%. The
decades even though the consumption of hydrogenated fat kept
increasing and animal fat was decreasing  as shown in Fig. 4.
Lower trans fat and increased linoleic acid are possible explana-
tions for this change. The death rate from CHD declined  after
1968 from 588.8/100,000 to 217/100,000 in 2004. CHD deaths in
the USA, according to American Heart Association data , were
total deaths would have been 1,840,000 in 2008, had the 1950 rate
of deaths from CHD continued . Unfortunately, this downward
men , the CHD rate has been increasing since 2004. The recent
reformulation of partially hydrogenated fat raises the trans fatty
acid levels from 20% to almost 40%. Whether the increase in the
fat needs further epidemiology study.
6. The FDA response to trans fat in the diet
6.1. The FDA trans fat labeling ruling did not consider other
potential mechanisms leading to heart disease
by January 1, 2006 of foods that contain trans fat [85,86]. The FDA
based this directive on peer-reviewed articles [33–42]. The FDA’s
major concern was the role of trans fat in increasing the plasma
lier in the paper in the plasma lipid level section. The FDA did
not consider other factors involved in the development of heart
disease and the impact of trans fat in that development. As we pre-
viously discussed, these include the effect on prostacyclin, Cox-2,
CRP, inflammation and changes in cell structure.
6.2. Failure to differentiate between effects of hydrogenated and
naturally occurring trans fats
In 2003, the metabolism of the trans fat in hydrogenated oil was
assumed [85,86] to follow the same pathway as the natural rumi-
nant trans fat in butterfat. The FDA has stated  that the main
reason for the trans fat in partially hydrogenated oil to remain in
the diet in the USA rested on the generally held belief that trans fat
is metabolized the same way as the natural trans fat in butterfat. A
study described earlier comparing the metabolic uses of butterfat
versus hydrogenated trans fat showed this not to be true . The
F.A. Kummerow / Atherosclerosis 205 (2009) 458–465
Summary of percentage fatty acid composition in soybean oil, hydrogenated soybean oil and in seven food products purchased from a grocery store.
Fatty acidSoybean oil Hydrogenated Soybean oilCookies Biscuitsa
Total trans Monoene (18:1)
Total trans diene (18:2)
Trans 18:1 represents a sum of isomers with double bonds at the trans 8, 9, 10, 11, 12 or 13 positions, 18:1 cis isomers represent a sum of isomers with double bonds at cis 9,
10, 11, 12, 13 or 14 positions, total diene represents a sum of trans, tran; trans, cis; and cis, trans 18:2 isomers, margarine 4 represents a margarine that claimed to have no
trans fat, but in fat did.
aProducts labeled as containing no trans fat.
bCis isomers other than oleic acid.
trans may be from the natural vaccenic acid that had no harmful
effects. Their figures suggested that approximately 2.6% of the total
daily fat intake is from trans fat and that 50% of the trans may be
from vaccenic acid (18:1n11). Trans fats were seen as a health con-
cern to the point that the FDA mandated its labeling in food items;
items with less than 0.5g/serving are exempt . There was a fail-
ure to differentiate between the compositions of hydrogenated and
naturally occurring trans fat.
6.3. Use of an assay that underestimates the trans fat content of
Under the current mandate in the USA , food items with any
amount of isomeric fatty acids were still allowed as long as they
were labeled. Products containing less than 0.5g/serving can be
labeled as trans free. There was also no limit on how much hydro-
genated fat a food product can contain. In 2003, the daily intake
of trans fat for men was estimated by the FDA to be nearly 7g/day
and for women almost 5g/day . The FDA admitted the presence
of hydrogenated fat in the diet would cause the deaths from heart
disease of 500–1000 Americans/year at a cost of 1 billion dollars in
medical costs .
To further illustrate the point consider that two cookies repre-
the cookies could be listed as trans free or 0% trans fat. However,
two servings (4 cookies) could provide more than 0.5g trans fat. On
the other hand, as long as the amount per serving was listed, a two-
cookies serving could contain 2g or more/serving of trans fat. On
the basis of weight/person, two cookies with 2g of trans fat eaten
by a 30-pound toddler, compared to a 180-pound man eating those
same cookies, would be equivalent to eating 12g of trans fat for the
6.4. Criteria to classify food as trans fat and its potential effects
The USA FDA defines trans fat chemically as “all unsaturated
fatty acids that contain one or more isolated (i.e., unconjugated)
double bonds in a trans configuration” . To check the labeling
process, common food products labeled to contain hydrogenated
fat were analysed . Fatty acid analysis, on a GC 200m column of
the fat in those food products, is shown in Table 2. A summary of
for comparison purposes alongside the partially hydrogenated soy-
bean oil. The cis and trans 18:1 and 18:2 fatty acid isomers were
present in the partially hydrogenated soybean oil and also were
present in every food product, even those labeled as trans free. All
contained both the cis and trans 18:1 fatty acid isomers with one
double bond (the cis and trans monoene) and the trans 18:2 with
two double bonds (c,t, t,t or t,c: 18:2). Three of these products, the
biscuits, one of the margarines and the vegetable shortening, were
labeled to contain less than 0.5g/serving or zero or no trans fat,
suggesting they contained no trans fat as allowed by the FDA. This
to contain no trans fat, yet it contained trans fat.
If a mother was breast-feeding her child and was also eating
foods containing trans fat, she would have a substantial amount
of trans fat in her milk supply and pass those to her infant .
The piglet study described earlier  showed that the plasma of
the lactating mothers contained 11.3% trans fat at the birth of their
piglets and decreased during lactation to 4% in 21 days. The plasma
6 weeks of age. Transferring this result to humans, a human mother
would also transfer the trans fat in her milk supply to her infant.
The infant would incorporate the trans fat into its arterial cells and
inhibit arachidonic acid synthesis and prostacyclin secretion. Fur-
thermore calcium deposition into the endothelial cells could be
enhanced. To date, the FDA has not considered the daily intake of
trans fat relevant to the health of small children since they do not
exhibit overt heart disease. This can be shortsighted thinking. In
cases where children have died of unknown causes and had been
autopsied, 99% of them showed the beginning stages of hardening
(calcifications) of the arteries, which ultimately can lead to heart
7. Reasons for the industry to still use trans fat
The fat industry uses hydrogenated fats for several reasons. It
provides some special features to margarines, which unlike but-
ter, allowed margarine to be taken out of the refrigerator and
immediately spread on a slice of bread. Adding 5–10% mono- and
diglycerides to hydrogenated fat provided superior baking proper-
fat is its “mouth feel.” It melts in the mouth and leaves no waxy
after taste due to the melting points of 13–44◦C of the cis and trans
octadecenoic and octadecadienoic isomers .
The first was a solid fat, similar to lard or beef tallow that was used
as a frying and baking fat. This fat was used until 2004. It con-
tained 45% “trans” fatty acids and 0% essential fatty acids (linoleic
and linolenic acid) according to its producer . A second type
of hydrogenated fat  was used from 1968 to 2004. It contained
20–27% trans fatty acid with approximately 24% linoleic acid .
tains 39.7% isomeric cis and trans fat, 16.6% linoleic acid and 0.7%
linolenic acid . A recent conference on hydrogenated fat indi-
cated 16 billion pounds of soybean oil were produced in the USA in
2006 of which 8 billion pounds were hydrogenated . According
to the president of the Institute of Shortening and Edible Oils there
are 33 plants making hydrogenated fat in the United States .
According to the director of research of the largest company in the
world that was hydrogenating plant oils, they could have provided
a trans fat free product 40 years ago, but at a higher cost, and the
F.A. Kummerow / Atherosclerosis 205 (2009) 458–465
company would not have been able to remain competitive. At least
one company is already doing so.
It is evident that partially hydrogenated fats have excellent
culinary properties but have detrimental health effects. Partially
hydrogenated fats change plasma lipid levels in negative ways.
They calcify cells and cause inflammation of the arteries, which
are known risk factors in heart disease. They are not metabolized
the same way as the trans vaccenic acid in ruminant fat and are
not harmless. Trans fats inhibit cyclooxygenase (COX-2) an enzyme
which converts arachidonic acid to an eicosanoid that is necessary
to prevent blood clots in the arteries and veins. A blood clot in the
not be completely prevented by adding more linoleic acid to the
partially hydrogenated fat. The FDA practice of assigning a label
of 0% trans fat when it is below 0.5g/serving is misleading. The
only course to protect the health of consumers is to eliminate the
production of partially hydrogenated trans fats.
I would like to acknowledge the helpful suggestions of Dr. M.
Mahfouz, Dr. Q. Zhou and Dr. Jean Kummerow and the financial
support of the University of Illinois Foundation and the Hildebrand
 Kummerow FA. Improving hydrogenated fat for the world population. Preven-
tion Control 2005;1:157–64.
 Bailey AE. Industrial oil and fat products. New York: Interscience Publisher Inc.;
 Deuel H. The lipids—their chemistry and biochemistry. New York: Interscience
Publisher Inc.; 1955.
 Kritchevsky D. Cholesterol. New York: John Wiley & Sons, Inc.; 1958.
 Zalewski S, Kummerow FA. Rapeseed oil in a two-component margarine base
stock. JAOCS 1968;45:87–92.
 James AT, Martin AJ. Gas-liquid partition chromatography: the separa-
tion and micro-estimation of ammonia and the methylamines. Biochem J
 Satchithanandam A, Rader JI. Trans, saturated, and unsaturated fat in foods in
the United States prior to mandatory trans-fat labeling. Lipids 2005;39:11–3.
 Firestone D. Official methods and recommended practices of the AOCS. 5th ed.
Champaign: The American Oil Chemists’s Society; 1999.
 Kummerow FA, Mahfouz MM, Zhou Q. Trans fatty acids in partially hydro-
genated soybean oil inhibit prostacyclin release by endothelial cells in
presence of high level of linoleic acid. Prostaglandins Other Lipid Mediat
 Sober H. Handbook of biochemistry: selected data for molecular biology. 2nd
ed. Cleveland, OH: The Chemical Rubber Co.; 1970.
J Biol Chem 1930;86:587–620.
 Rose WC, Wixom RL, Lockhart HB, Lambert GF. The amino acid requirements of
man XV. The valine requirement; summary and final observations. J Biol Chem
 Kunau WH, Holman RT. Polyunsaturated fatty acids. 3rd ed. Champaign: The
American Oil Chemists’ Society; 1977.
 Ramwell PW. The prostaglandins. New York: Plenum; 1973.
 Prostaglandins and perinatal medicine. New York: Raven; 1978.
 Schwartz JI, Agrawal NG, Hartford AH, et al. The effect of etoricoxib on
the pharmacodynamics and pharmacokinetics of warfarin. J Clin Pharmacol
 Ratageri VH, Shepur TA, Kiran G. Vitreous hemorrhage secondary to vitamin K
deficiency bleeding. Ind J Pediatr 2007;74:314.
 Kummerow FA, Pan HP, Hickman H. The effect of dietary fat on the reproductive
performance and the mixed fatty acid composition of fat-deficient rats. J Nutr
 Innis SM. Essential fatty acids in growth and development. Prog Lipid Res
 Uauy R, Hoffman DR, Peirano P, Birch DG, Birch EE. Essential fatty acids in visual
and brain development. Lipids 2001;36:885–95.
 Siegel G, et al. Basic neurochemistry. 4th ed. New York: Raven Press, Ltd.; 1989.
 Kummerow FA, Mahfouz MM, Zhou Q, Cook LS. 27-Hydroxycholesterol causes
remodeling in endothelial cell membrane lipid composition comparable to
remodeling in the failed vein grafts of CABG patients. Life Sci 2006;78:958–63.
 Kummerow FA, Zhou Q, Mahfouz MM, Smiricky MR, Grieshop CM, Schaeffer DJ.
Trans fatty acids in hydrogenated fat inhibited the synthesis of the polyunsatu-
rated fatty acids in the phospholipid of arterial cells. Life Sci 2004;74:2707–23.
 Bunge Foods Corp. Tem Cote IEO/U. Kankakee, IL.
 Jakobsen MU, Bysted A, Anderson NL. Intake of ruminant trans fatty acids and
risk of coronary heart disease—an overview. Atheroscler Suppl 2006;7:9–11.
 Stender S, Dyerberg J, Hansen HS.First international symposium on trans fatty
acids and health. 2005;
Stender S, Dyerberg J, Hansen HS. Atherosclerosis 2006;7:2–10.
 Pilgeram L. Atherogenesis and fibrinogen: historical perspective and current
status. Naturwissenschaften 1993;80:547–55.
 Pilgeram L. Atherogenesis: historical perspective, biochemical mechanism, and
current status. Cardio Eng 2003;2:111–28.
 Crofts AR. The cytochrome bc1 complex: function in the context of structure.
Annu Rev Physiol 2004;66:689–733.
 Lawson LD, Kummerow FA. beta-Oxidation of the coenzyme A esters of elaidic,
dria. Biochim Biophys Acta 1979;573:245–54.
 Ascherio A, Katan MB, Zock PL. Trans fatty acids and coronary heart disease. N
Engl J Med 1999;340:1994–8.
 Judd JT, Clevidence BA, Muesing RA. Dietary trans fatty acids: effects on
plasma lipids and lipoproteins of healthy men and women. Am J Clin Nutr
 Lichtenstein AH. Effects of difference forms of dietary hydrogenated fats on
plasma lipoprotein cholesterol levels. N Engl J Med 1999;340:1933–40.
 Mensink RP, Katan MB. Effect of dietary trans fatty acids on high-density and
low-density lipoprotein cholesterol levels in healthy subjects. N Engl J Med
 deRoos NM, Schouten EG, Katan MB. Consumption of a solid fat rich in lauric
acid results in a more favorable plasma lipid profile in healthy men and women
than consumption of a solid fat rich in trans fatty acids. J Nutr 2001:131.
 Katan MB. Trans fatty acids and plasma lipoproteins. Nutr Rev 2000;58:188–91.
in humans. Annu Rev Nutr 1995;15:473–93.
 Mensink RP, Zock PL, Kester AM, Katan MB. Effects of dietary fatty acids and
carbohydrates on the ratio of plasma total to HDL cholesterol and on plasma
lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin
 Zock PL, Katan MB. Hydrogenation alternatives: effects of trans fatty acids and
stearic acid versus linoleic acid on plasma lipids and lipoprotein in humans. J
Lipid Res 1992;33:399–410.
 Zock PL, Katan MB. Linoleic acid intake and cancer risk: a review and meta-
analysis. Am J Clin Nutr 1998;68:142–53.
 The National Diet-Heart Study Final Report. Circulation 1968;37:I1–428.
 Sun Q, Ma J, Campos H, Hu FB. Plasma and erythrocyte biomarkers of dairy fat
intake and risk of ischemic heart disease. Am J Clin Nutr 2007;86:929–37.
 Basu A, Devaraj S, Jialal I. Dietary factors that promote or retard inflammation.
Arterioscler Thromb Vasc Biol 2006;26:995–1001.
 Lopez-Garcia E, Schulze MB, Meigs JB, et al. Consumption of trans fatty acids
is related to plasma biomarkers of inflammation and endothelial dysfunction.
J Nutr 2005;135:562–6.
 Massaro M, Scoditti E, Carluccio MA, Montinari MR, De Caterina R. Omega-3
fatty acids inflammation and angiogenesis: nutrigenomic effects as an expla-
nation for anti-atherogenic and anti-inflammatory effects of fish and fish oils.
J Nutrigenet Nutrigenomics 2008;1:4–23.
 Giugliano D, Ceriello A, Esposito K. The effects of diet on inflammation. J Am
Coll Cardiol 2006;48:677–85.
 Harvey KA, Arnold T, Rasool T, Antalis C, Miller SJ, Siddiqui RA. Trans-fatty acids
induce pro-inflammatory responses and endothelial cell dysfunction. Br J Nutr
 Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes
after statin therapy. N Engl J Med 2005;352:20–8.
 Ridker P. Rosuvastatin to prevent vascular events in men and women with
elevated C-reactive protein. N Engl J Med 2008.
and cardiovascular disease. N Engl J Med 2006;354:1601–13.
 Vane JR, Bakhle YS, Botting RM. Cyclooxygenase 1 and 2. Annu Rev Pharmacol
 Vane JR, Mitchell JA, Appleton I, et al. Inducible isoforms of cyclooxyge-
nase and nitric-oxide synthase in inflammation. Proc Natl Acad Sci USA
 Mitchell JA, Warner TD. Cyclo-oxygenase-2: pharmacology, physiology, bio-
chemistry and relevance to NSAID therapy. Br J Pharmacol 1999;128:1121–32.
 Holman R, Mahfouz M. Cis- and transpolyunsaturated fatty acids. Prog Lipid
 Holman R, Pusch F, Svingen B, Dutton HJ. Unusual isomeric polyunsaturated
fatty acids in liver phospholipids of rats fed hydrogenated oil. Proc Natl Acad
Sci USA 1991;88:4830–4.
 Holman R, Johnson S, Ogburn P. Deficiency of essential fatty acids and
membrane fluidity during pregnancy and lactation. Proc Natl Acad Sci USA
F.A. Kummerow / Atherosclerosis 205 (2009) 458–465
 Mahfouz MM, Valicenti A, Holman R. Desaturation of isomeric trans-
octadecenoic acids by rat liver microsomes. Biochim Biophys Acta 1980;
 Mohrhauer H, Christiansen K, Gan M, Deubig M, Holman R. Chain elongation
of linoleic acid and its inhibition by other fatty acids in vitro. J Biol Chem
 Hill EG, Johnson SB, Lawson LD, Mahfouz MM, Holman R. Perturbation of the
metabolism of essential fatty acids by dietary partially hydrogenated vegetable
oil. Proc Natl Acad Sci USA 1982;79:953–7.
 Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular
response to thromboxane A2. Science 2002;296:539–41.
 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 J Epidemiol 2005;161:672–9.
 Mozaffarian D, Pischon T, Hankinson SE, et al. Dietary intake of trans
fatty acids and systemic inflammation in women. Am J Clin Nutr 2004;79:
 Lemaitre RN, King IB, Raghunathan TE, Pearce RM, Weinmann S, Knopp RH. Cell
membrane trans-fatty acids and the risk of primary cardiac arrest. Circulation
 Mozaffarian D, Ascherio A, Hu FB, et al. Interplay between different polyun-
saturated fatty acids and risk of coronary heart disease in men. Circulation
 Kris-Etherton PM, Hu FB, Ros E, Sabate J. The role of tree nuts and peanuts in
 Navab M, Berliner JA, Watson AD, et al. The Yin and Yang of oxida-
tion in the development of the fatty streak. A review based on the 1994
George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 1996;16:
 Heinecke JW. Oxidants and antioxidants in the pathogenesis of atherosclerosis:
implications for the oxidized low density lipoprotein hypothesis. Atherosclero-
 Kummerow FA. Nutrition imbalance and angiotoxins as dietary risk factors in
coronary heart disease. Am J Clin Nutr 1979;32:55–83.
 Zhou Q, Smith TL, Kummerow FA. Cytotoxicity of oxysterols on cultured
smooth muscle cells from human umbilical arteries. Proc Soc Exp Biol Med
 Hessler JR, Morel DW, Lewis LJ, Chisolm GM. Lipoprotein oxidation and
lipoprotein-induced cytotoxicity. Arteriosclerosis 1983;3:215–22.
 Zhou Q, Jimi S, Smith TL, Kummerow FA. The effect of 25-hydroxycholesterol
on accumulation of intracellular calcium. Cell Calcium 1991;12:467–76.
 Kummerow FA, Cook LS, Wasowicz E, Jelen H. Changes in the phospholipid
composition of the arterial cell can result in severe atherosclerotic lesions. J
Nutr Biochem 2001;12:602–7.
 Zhou Q, Wasowicz E, Handler B, Fleischer L, Kummerow FA. An excess concen-
tration of oxysterols in the plasma is cytotoxic to cultured endothelial cells.
 Kummerow FA, Olinescu RM, Fleischer L, Handler B, Shinkareva SV. The
relationship of oxidized lipids to coronary artery stenosis. Atherosclerosis
 Kummerow FA, Zhou Q, Mahfouz MM. Effect of trans fatty acids on calcium
influx into human arterial endothelial cells. Am J Clin Nutr 1999;70:832–8.
 Johnston PV, Johnson OC, Kummerow FA. Occurrence of trans fatty acids in
human tissue. Science 1957;126:698–9.
 National Center for Health Statistics, U.S. Department of Health and Human
Services. Health, United States, 2007 with Chartbook on Trends in the Health
of Americans. Washington,D.C.: U.S. Government Printing Office; 2007.
 Meyer W. Technical Director of the Institute of Shortening and Edible Oils.
 Kummerow FA. Viewpoint on the report of the National Cholesterol Educa-
tion Program Expert Panel on detection evaluation and treatment of high blood
cholesterol in adults. J Am Coll Nutr 1993;12:2–13.
 American Heart Association. About sudden death and cardiac arrest.
2007 [cited; available from: http://www.americanheart.org/presenter.jhtml?
 Vital Statistics of the United States, NCHS. Age-Adjusted Death Rates for Coro-
nary Heart Disease, U.S. 1950–2005 [cited; available from: http://www.nhlbi.
 Nemetz PN, Roger VL, Ransom JE, Bailey KR, Edwards WD, Leibson CL. Recent
of nonnatural deaths. Arch Intern Med 2008;168:264–70.
 FDA. Food labeling: trans fatty acids in nutrition labeling, nutrient content
claims, and health claims. Final rule. Fed Regist 2003;68:41433–506.
 FDA. Questions and answers about trans fat nutrition labeling. 2006 [cited;
available from: http://www.cfsan.fda.gov].
 Mosley EE, Wright AL, McGuire MK, McGuire MA. Trans fatty acids in milk
produced by women in the United States. Am J Clin Nutr 2005;82:1292–
regression. Z Kardiol 2000;89(Suppl. 2):28–35.
 Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types
of atherosclerotic lesions and a histological classification of atherosclero-
sis. A report from the Committee on Vascular Lesions of the Council on
Arteriosclerosis, American Heart Association. Arterioscler Thromb Vasc Biol
 Eckels RH, Borra S, Shirley Y. Understanding the complexity of trans fatty acid
reduction in the American diet. Circulation 2007;115:2231–46.
 Personal communication: President of the Institute of Shortening and Edible