European Journal of Clinical Nutrition (2007) 61, 1004–1010
& 2007 Nature Publishing Group All rights reserved 0954-3007/07 $30.00
www.nature.com/ejcn
ORIGINAL ARTICLE
Consumption of trans fats and estimated effects on
coronary heart disease in Iran
D Mozaffarian1,2,3, M Abdollahi4, H Campos1,2, A HoushiarRad4 and WC Willett1,2,3
1
The Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Harvard School of
Public Health, Boston, MA, USA; 2Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; 3Department of
Epidemiology, Harvard School of Public Health, Boston, MA, USA and 4The National Nutrition & Food Technology Research Institute,
Shaheed Beheshti University of Medical Science, Tehran, Iran
Objective: To investigate the consumption of industrial trans-fatty acids (TFAs) in Iranian homes and the proportion of coronary
heart disease (CHD) events in Iran attributable to such intake.
Design, setting and participants: The consumption of industrial TFAs was determined using (1) detailed in-home assessments
of dietary intake among 7158 urban and rural households containing 35 924 individuals and (2) gas chromatography to
determine TFA contents of the most commonly consumed partially hydrogenated oils. The population-attributable risk for CHD
owing to TFA consumption was calculated on the basis of (1) documented effects of TFAs on total:high-density lipoprotein
(HDL) cholesterol in randomized controlled dietary trials and (2) relationships of TFA intake with incidence of CHD in prospective
observational studies.
Results: Partially hydrogenated oils were used extensively for cooking in Iranian homes with average per-person intake of 14 g/
1000 kcal. TFAs accounted for 33% of fatty acids in these products, or 4.2% of all calories consumed (12.3 g/day). On the basis
of total:HDL cholesterol effects alone, 9% of CHD events would be prevented by replacement of TFA in Iranian homes with
cis-unsaturated fats (8% by replacement with saturated fats). On the basis of relationships of TFA intake with CHD incidence in
prospective studies, 39% of CHD events would be prevented by replacement of TFA with cis-unsaturated fats (31% by
replacement with saturated fats). These population-attributable risks may be overestimates owing to competing risks and
because not all the fat used for cooking might actually be consumed. If actual TFA consumption were only half as large, the
estimated proportion of CHD events prevented by TFA elimination would be 5% on the basis of total:HDL cholesterol effects and
replacement with cis-unsaturated (4% for replacement with saturated fats), and 22% on the basis of prospective studies and
replacement with cis-unsaturated fats (17% for replacement with saturated fats). These estimates do not include possible
additional benefits derived from replacing TFAs with vegetable oils containing n-3 fatty acids.
Conclusions: Intake of TFAs is high in Iranian homes and contributes to a sizeable proportion of CHD events. Replacement of
partially hydrogenated oils with unhydrogenated oils would likely produce substantial reductions in CHD incidence.
Sponsorship: National Heart, Lung and Blood Institute, National Institutes of Health, USA. National Nutrition & Food
Technology Research Institute, Tehran, Iran.
European Journal of Clinical Nutrition (2007) 61, 1004–1010; doi:10.1038/sj.ejcn.1602608; published online 31 January 2007
Keywords: trans-fatty acids; coronary heart disease; diet
Correspondence: Dr D Mozaffarian, 665 Huntington Ave, Building 2 Room 315, Boston, MA 02115, USA.
E-mail: [email protected]
Guarantor: D Mozaffarian.
Contributors: DM participated in the conception and design, statistical analysis and data interpretation, manuscript drafting, critical revision of the manuscript for
important intellectual content and approval of the final manuscript for submission.MA participated in the collection of data, critical revision of the manuscript for
important intellectual content, and approval of the final manuscript for submission.HC participated in the collection of data, critical revision of the manuscript
for important intellectual content, and approval of the final manuscript for submission.AH participated in the collection of data, critical revision of the manuscript for
important intellectual content, and approval of the final manuscript for submission.WW participated in the conception and design, data collection and
interpretation, critical revision of the manuscript for important intellectual content, and approval of the final manuscript for submission.
Received 18 November 2005; revised 14 November 2006; accepted 14 November 2006; published online 31 January 2007
Estimated effects on coronary heart disease in Iran
D Mozaffarian et al
1005
Introduction
Trans-fatty acids (TFAs), unsaturated fats with at least one
double bond in the trans configuration, are formed during
the partial hydrogenation of vegetable oils. This process
facilitates conversion of vegetable oils to solid or semi-solid
products for use in margarines, deep frying and food
manufacturing. Partially hydrogenated oils may contain
up to 30–50% TFAs, resulting in significant TFA intake in
many populations (Allison et al., 1999; Hulshof et al., 1999).
Substantial evidence indicates that consumption of TFAs
increases the risk of coronary heart disease (CHD) (Willett
et al., 1993; Mozaffarian et al., 2006), which may be related
to adverse effects on serum lipids and lipoproteins (Ascherio
et al., 1999; Mauger et al., 2003; Mensink et al., 2003;
Mozaffarian et al., 2006), systemic inflammation (Han et al.,
2002; Baer et al., 2004; Mozaffarian et al., 2004a, b; LopezGarcia et al., 2005) and endothelial function (Kummerow
et al., 1999; de Roos et al., 2001; Baer et al., 2004; LopezGarcia et al., 2005). TFA consumption may also increase
the incidence of sudden death (Lemaitre et al., 2002, 2005)
and diabetes mellitus (Hu et al., 2001). Consumption of
TFAs may therefore contribute to a substantial burden of
cardiovascular disease.
The intake and potential adverse health effects of TFAs in
Western countries have received considerable attention
(Allison et al., 1999; Hulshof et al., 1999; Dietary Guidelines
Advisory Committee, 2005; New York City Department of
Health and Mental Hygiene, 2005), with resulting legislation
to increase awareness of and/or limit TFA consumption in
these populations (Health Canada, 2005; Leth et al., 2005;
US Food and Drug Administration, 2005). However, little
is known regarding TFA intake in many other regions. Data
are particularly sparse for countries in the Middle East, a
populous region that generally receives less attention in
CHD research. We determined the consumption of TFAs
from partially hydrogenated oils in Iran and calculated the
health impact of this TFA intake on CHD risk in Iran.
Materials and methods
Assessment of dietary intake in Iran
A national Food Consumption Survey was used to determine
dietary intakes in Iran. A systematic stratified sampling
design was used to select a nationally representative sample
of urban and rural households from the 28 Iranian
provinces. Between March 2001 and November 2003, inhome interviews were performed by trained nutritionists of
the member of each household most responsible for food
preparation and cooking. Dietary habits of the household
were assessed using three consecutive 24-h dietary recalls,
including information on types, quantities and sources of
food items; cooking methods; recipes and ingredients.
Quantities were reported in units of foods as they were
brought into the household from the store, garden or farm.
To increase the accuracy of the reported quantities, a Soehnle
kitchen weighing scale (with accuracy of 5 g) was used to
weigh regularly used foods. Consumption of foods representing major contributors to energy intake (breads, fats and oils,
and sugars) was further evaluated using 2 days of weighed
diet records. To account for seasonal variation in food
intake, one-quarter of the households in each province were
interviewed in each season. A major food purchase list for
the past year was also completed for each household. All data
were computerized, and a food composition table modified
for Iranian diets was used to determine the average nutrient
intakes of the individuals in the household.
Assessment of TFA intake
The dietary data were used to determine the average
consumption of partially hydrogenated oils in Iranian
homes. We determined the national market share of brands
of partially hydrogenated oils consumed in Iran (Zandi, 2004)
and analyzed the fatty acid content of the most commonly
consumed partially hydrogenated oils. Fatty acid contents
were determined by gas chromatography with a nonbonded,
biscyanopropyl polysiloxane column as described previously
(Baylin et al., 2002). Peak retention times and area percentages of total fatty acids were identified by injecting known
standards (NuCheck Prep, Elysium, MN, USA), and analyzed
with computer software (Agilent Technologies ChemStation
A.08.03, Santa Clara, CA, USA). The TFA contents of the
most commonly consumed partially hydrogenated oils were
averaged, weighted by market share and multiplied by the
mean per-person intake of partially hydrogenated oils to
determine the average TFA consumption.
Estimation of impact on CHD risk
We calculated the proportion of CHD events in Iran
attributable to intake of TFAs in partially hydrogenated oils.
The population-attributable risk percent was calculated
as Pe(RR1)/(Pe(RR1) þ 1), where Pe is the prevalence of
exposure to TFAs in the population and RR is the relative
risk of CHD associated with TFA intake. TFA intake was
assumed to be equally distributed in the population; other
distributions resulted in similar or higher populationattributable risk percents (if some individuals were less
exposed, others would be more exposed to produce the
observed per capita TFA intake). Two estimates of the health
impact were calculated. The first estimate was on the basis
of documented effects of TFAs on the total:high-density
lipoprotein (HDL) cholesterol ratio in a meta-analysis of
randomized controlled dietary trials (Mozaffarian et al.,
2006), coupled with established relationships of this ratio
to CHD risk (Stampfer et al., 1991). Because TFAs affect many
other risk factors beyond total and HDL cholesterol concentrations (Mozaffarian et al., 2006), this would likely
underestimate the full health impact. The second estimate
was on the basis of associations of TFA intake with incidence
European Journal of Clinical Nutrition
Estimated effects on coronary heart disease in Iran
D Mozaffarian et al
1006
of CHD events in a meta-analysis of prospective cohort
studies (Mozaffarian et al., 2006). For each estimate, effects
were calculated for the replacement of TFAs with (1) cis
monounsaturated and n-6 polyunsaturated fats (the averaged effect) and (2) saturated fats. In practice, partially
hydrogenated oils are most commonly replaced with a
combination of cis monounsaturated and polyunsaturated
fats from unhydrogenated sunflower, canola and soybean
oils, with the relative proportions depending on market
prices and specific product reformulations. Because population-attributable risks may be overestimates owing to
competing risks and because not all the fat used for cooking
might actually be consumed, we also repeated the estimates
of health impact assuming that actual TFA consumption
were only half as large as observed.
Results
Participant characteristics
A total of 7158 urban and rural households, representing
35 924 individuals, were evaluated (Table 1). Consistent with
the demographics of modern Iran, 41% of the population
were at or below 18 years of age and 88% were at or below 50
years of age. Educational attainment was highly variable
with nearly one-quarter of the heads of households having
no formal education and an additional one-quarter having
graduated from high school or attended college.
Dietary intakes
The overall dietary results are shown in Table 2. Total energy
intake was consistent with estimated energy requirements
on the basis of weight and occupation of adults and
predicted basal metabolic rate and age- and sex-specific
estimated physical activity in children (Schofield, 1985;
James and Schofield, 1990). Partially hydrogenated oils were
commonly used for cooking in Iranian homes, with average
per-person intake of 14 g/1000 kcal, representing 12.5% of
all calories. On the basis of total market sales of partially
hydrogenated fats (retail and commercial), the per capita
intake would be 19 g/1000 kcal (Nowrouzi and Samimi,
2002). This latter value is likely the result of additional
intake of partially hydrogenated oils outside the home, such
as in restaurants, universities, ministries, prisons, military
bases, etc. We used the more conservative value (14 g/
1000 kcal) for these analyses.
The TFA content of the most commonly consumed
partially hydrogenated oils in Iran ranged from 23 to 36%
(Table 3). Weighted by their market share, TFAs accounted
for 33% of all fatty acids in these partially hydrogenated oils.
This can be compared to 5% TFAs in sunflower oil (likely
owing to deodorization) and o1% TFAs in unhydrogenated
soybean or olive oil. Thus, with partially hydrogenated oils
accounting for 12.5% of all calories consumed and TFAs
representing 33% of all fatty acids in these oils, TFAs
European Journal of Clinical Nutrition
Table 1 Characterisitics of participants in the Food Consumption
Survey, Iran 2001–2003
Households, n
Urban (%)
Rural (%)
Individuals, n
7158
65
35
35 924
Age (%)
p18 years
19–50 years
450 years
Sex, % male
41
47
12
50
Education attained by head of household (%)
None
Some primary school
Primary school completed
Some high school
High school graduate
College
22
14
25
15
17
6
Participants selected using a systematic stratified sampling design to identify
households representing each of the 28 provinces in Iran.
Table 2
Dietary consumption in the home, Iran 2001–2003
Total energy (kcal)
Macronutrients (% energy)
Total fat
Carbohydrates
Protein
Foods (g/1000 kcal)
Bread and cereals
Dairy products
Meats
Refined (simple) sugars
Partially hydrogenated cooking oils
Fish
2636
25
64
11
170
53
24
22
14
2.7
Average daily consumption per person, based on a national Food Consumption Survey of 7158 households representing 35 924 individuals in each of the
28 provinces in Iran.
accounted for 4.2% of all calories consumed per capita in
the home (12.3 g/day for the average diet). This is approximately double the per capita TFA intake from partially
hydrogenated oils in the United States (Allison et al., 1999),
and does not account for additional TFAs that might be
consumed outside the home in Iran.
Impact of TFA intake on CHD incidence in Iran
We calculated the proportion of CHD events in Iran that
might be prevented by eliminating TFA consumption from
partially hydrogenated oils in Iranian homes (Figure 1). On
the basis of changes in the total:HDL cholesterol ratio alone,
9% of CHD events would be prevented if TFAs were replaced
with cis-unsaturated fats (8% if TFAs were replaced with
saturated fats). This likely underestimates the full health
Estimated effects on coronary heart disease in Iran
D Mozaffarian et al
1007
Table 3 Fatty acid composition of the most commonly consumed partially hydrogenated oils in Iran and, for comparison, of unhydrogenated soybean
and olive oils
Percentage composition of different fats
Saturated cis-monounsaturated cis-n-6 polyunsaturated cis-n-3 polyunsaturated trans 18:1 trans 18:2 Total trans
Partially hydrogenated oil no. 1
Partially hydrogenated oil no. 2
Partially hydrogenated oil no. 3
Soybean oil
Sunflower oil
Olive oil
23.5
22.6
24.6
13.9
11.5
15.2
30.2
33.9
31.6
19.9
22.5
70.6
10.8
6.2
19.9
56.9
60.6
12.7
0.7
0.8
0.5
8.3
0.4
0.8
31.2
31.1
21.6
0.2
0.7
0.3
3.2
5.1
1.6
0.7
4.0
0.1
34.4
36.2
23.2
0.9
4.7
0.4
Partially hydrogenated oils, selected based on national market share (Zandi, 2004), and fatty acid compositions determined by gas chromatography using previously
described methods (Baylin et al., 2002). Nearly all of the partially hydrogenated oils used in Iran are imported and subsidized by the government for distribution as
rationed oils. The three oils evaluated were blends of partially hydrogenated soybean (B90% content), sunflower, cottonseed and palm oils. Values may not sum to
100% due to rounding.
Baylin et al. (2002).
Zandi (2004).
Proportion of CHD Events
Preventable in Iran (%)
0
-5
-10
-15
-20
-25
-30
-35
-40
Based on ∆ total:HDL-C ratio, replacement with cis unsaturated fats (clinical trials)
Based on ∆ total:HDL-C ratio, replacement with saturated fat (clinical trials)
Based on relations with CHD events, replacement with cis unsaturated fats (prospective studies)
Based on relations with CHD events, replacement with saturated fat (prospective studies)
Figure 1 Estimated impact of TFA consumption on CHD events in Iran. The proportion of CHD events that would be prevented by eliminating
TFA consumption from partially hydrogenated oils in Iranian homes was calculated based on (1) the effects of isocaloric replacement of TFAs with
cis-unsaturated fats or saturated fats on the total cholesterol (TC):HDL ratio in a meta-analysis of randomized controlled dietary trials (Mozaffarian
et al., 2006) and the relationships of this ratio with CHD incidence (Stampfer et al., 1991) and (2) the relationships of TFA intake with CHD
incidence in a meta-analysis of prospective observational studies (Mozaffarian et al., 2006).
impact as TFAs influence other cardiovascular risk factors
beyond total and HDL cholesterol levels, including triglyceride concentrations (Mensink et al., 2003), lipoprotein(a)
levels (Ascherio et al., 1999), low-density lipoprotein (LDL)
particle size (Mauger et al., 2003), systemic inflammation
(Han et al., 2002; Baer et al., 2004; Mozaffarian et al.,
2004a, b; Lopez-Garcia et al., 2005), endothelial function (de
Roos et al., 2001; Baer et al., 2004; Lopez-Garcia et al., 2005),
and possibly abdominal adiposity and insulin resistance
(Koh-Banerjee et al., 2003; Kavanagh et al., 2006). On the
basis of relationships of TFA intake with CHD incidence seen
in prospective studies, which may better account for the
total effects, 39% of CHD events would be prevented by
replacement of TFAs with cis-unsaturated fats (31% by
replacement with saturated fats).
Population-attributable risks may overestimate the true
effect of eliminating a risk factor owing to the principle of
competing risks: when one risk factor is removed from the
environment, a proportion of the events that would have
been caused by that risk factor may still occur as a result of
other unrelated (competing) risk factors. Additionally, most
TFA intake in Iranian homes were owing to use of cooking
oils, and not all the fat used for cooking might actually be
consumed. To account for such potential uncertainties, we
performed sensitivity analyses assuming that actual TFA
consumption were only half as large as observed. In this case,
the proportion of CHD events prevented by TFA elimination
would be 5% on the basis of total and HDL cholesterol effects
alone and replacement with cis-unsaturated fats (4% for
replacement with saturated fats), and 22% on the basis of
European Journal of Clinical Nutrition
Estimated effects on coronary heart disease in Iran
D Mozaffarian et al
1008
prospective studies and replacement with cis-unsaturated
fats (17% for replacement with saturated fats).
We did not consider the potential effects of naturally
occurring ruminant TFAs from dairy or meat sources. We
estimated that TFA intake from these sources totaled B0.5%
energy, considerably less than the consumption of industrially produced TFAs from partially hydrogenated oils.
Consumption of naturally occurring TFAs has not been
associated with higher CHD risk, which may be related to the
much lower levels of intake, possible different biologic
effects of ruminant vs industrial TFAs (which share some
but not all isomers), or the presence of other factors in dairy
and meat products which balance any effects of the small
amount of TFAs (Mozaffarian et al., 2006).
Nearly 350 000 deaths occur annually in Iran (Unicef,
2005), and B70 000 of these (20.5%) are owing to CHD (on
the basis of death rate statistics from 18 provinces; Dr M
Janghorbani, personal communication, 24 October 2004).
On the basis of health impact of TFAs (Figure 1), the near
elimination of TFA consumption from partially hydrogenated oils in Iranian homes would prevent between
5600 (8%) and 27 300 (39%) CHD deaths annually. These
estimated benefits do not include corresponding reductions
in other CHD events, which would likely be reduced by
decreased TFA consumption, including nonfatal myocardial
infarctions, acute coronary syndromes and coronary revascularization procedures. These estimates also do not include
possible additional benefits of replacing TFAs with vegetable
oils containing n-3 fatty acids.
Discussion
TFA intake from partially hydrogenated oils in Iranian
homes is very high, approximately twice as high as in the
United States and much higher than many European
countries. This intake likely contributes to a significant
proportion of CHD events in Iran: between 8 and 39% of
CHD events might be due to consumption of TFAs. The
upper range may be an overestimate if the observed
associations between TFA intake and CHD risk in prospective
studies were partly due to residual confounding from
unmeasured lifestyle or dietary habits. Conversely, the lower
range likely underestimates the health impact because it is
based only on total and HDL cholesterol effects, and TFAs
affect many other risk factors (Mozaffarian et al., 2006).
Nevertheless, even this lower estimate represents a substantial proportion of CHD events in Iran.
We did not account for potential additional benefits of
using replacement oils containing a-linolenic acid (ALA, 18:3
n-3), the plant-derived n-3 fatty acid. In Iran, consumption
of fish, and therefore seafood-derived n-3 fatty acids, is very
low (Table 2). Thus, plant sources (vegetable oils) represent
the major potential source of n-3 fatty acid intake. ALA is
destroyed by partial hydrogenation, so that partially hydrogenated oils contain o1% ALA, compared with 7–9% ALA in
European Journal of Clinical Nutrition
unhydrogenated soybean or canola oil (Table 3). Although
cardiovascular benefits of ALA are not conclusively established (Mozaffarian, 2005), the replacement of partially
hydrogenated oils with unhydrogenated oils containing
ALA (such as soybean or canola oil) would possibly reduce
the risk further. Because intake of n-3 fatty acids is already
low in Iran, the destruction of ALA in vegetable oils by
partial hydrogenation may be as significant a problem as the
creation of TFAs. Rapid reductions in CHD mortality – within
months – were seen with a dietary intervention that
included increased ALA intake in the Lyon Heart Study trial
(de Lorgeril et al., 1999) and also in Poland after increases in
vegetable oil consumption, mainly as canola oil, in the early
1990s (Zatonski et al., 1998). Thus, replacement of partially
hydrogenated oils with unhydrogenated oils that include
ALA might reduce CHD incidence in Iran within months,
with additional benefits in ensuing years.
Experiences in several European countries demonstrate
that the use of partially hydrogenated oils can be reduced
without increases in food cost or reductions in availability
or palatability (Jensen, 2005; Aro, 2006; Leth et al., 2006;
Nielsen, 2006). TFA consumption in Iran could be reduced
by recognition and avoidance of partially hydrogenated oils
by consumers, voluntary reductions in their use by restaurants and food manufacturers, or governmental intervention
to limit use. In Iran, each individual is entitled to an annual
ration of inexpensive (i.e., heavily subsidized) cooking oil,
currently fulfilled by sales of partially hydrogenated oils.
Nonhydrogenated oils are also available, but are unsubsidized and thus much more expensive. Thus, governmental
legislation to subsidize unhydrogenated rather than partially
hydrogenated oils would likely produce rapid and substantial reductions in TFA consumption.
Several limitations are worth noting. The well-defined
effects of TFA intake on LDL and HDL cholesterol have not
been proven to affect CHD risk; however, other interventions that affect LDL or HDL cholesterol result in changes in
CHD risk as large or larger than predicted (Robins et al., 2001;
Baigent et al., 2005). Our estimates were confined to in-home
consumption of TFAs, which likely underestimates total TFA
intake in the population; estimated benefits would be greater
if consumption of TFAs outside the home was also reduced.
The estimates of benefit also did not account for potential
effects of TFAs on risk of sudden death (Lemaitre et al., 2002;
Lemaitre et al., 2005) or diabetes mellitus (Hu et al., 2001),
the incidence of which may also be lowered by reductions in
TFA intake.
Reducing the intake of partially hydrogenated oils in Iran
through governmental intervention is feasible and would
likely result in substantial health benefits, and little
justification exists for not doing so. The incidence of CHD
in Iran has been increasing, and such increases are likely to
continue unless other underlying causes are also addressed,
including smoking, overweight, low levels of physical
activity and other unhealthy dietary habits in addition to
intake of partially hydrogenated oils. If ongoing increases in
Estimated effects on coronary heart disease in Iran
D Mozaffarian et al
1009
these other causes of heart disease are not addressed, the
reductions in rates of CHD over time may be less than
estimated. Thus, the importance of reducing TFA intake
should not, and need not, distract from other CHD
prevention efforts. Nevertheless, we believe that a comprehensive strategy to replace partially hydrogenated oils with
unhydrogenated oils in Iran would have dramatic health
benefits, substantially reducing the incidence of CHD.
Acknowledgements
Dr Mozaffarian was supported by funding from the National
Heart, Lung and Blood Institute, National Institutes of
Health (K08-HL-075628). We thank Dr Mohsen Janghorbani
for providing cause-specific mortality data from Iran and
the investigators of the Nutrition Research Department,
National Nutrition & Food Technology Research Institute,
who collaborated in the conduction of the Iranian Food
Consumption Survey.
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