TRANS-FATTY ACIDS

Health Effects, Recommendations, and Regulations

SK Gebauer and DJ Baer, US Department of Agriculture, Beltsville, MD, USA
r 2013 Elsevier Ltd. All rights reserved.

Glossary Interleukin-6 Cytokine derived from activated T

C-reactive protein An acute-phase protein synthesized by lymphocytes involved with induction of hepatocyte
the liver whose concentrations in blood increase during secretion of acute-phase inflammatory proteins.
inflammation. Tumor necrosis factor-alpha Cytokine that stimulates the
E-selectin Cell adhesion molecule that mediates adhesion acute-phase reaction and is involved in systemic
of immune cells to cytokine-activated endothelial cells. inflammation.
ICAM-1 Intercellular adhesion molecule-1; glycoprotein VCAM-1 Vascular cell adhesion molecule-1; cytokine-
that is expressed on a variety of cells and involved in induced cell adhesion molecule present on a variety of cells
cytokine-stimulated cell adhesion. and important for the recruitment of leukocytes to the sites
Interesterification A process in which fatty acids are of inflammation.
rearranged on a triacylglycerol molecule.

Introduction
Canada ranges from 3 to 4 g day1. In northern European
countries, dietary intake ranges from 2 to 4 g day1, whereas in
Trans-fatty acids are a class of fatty acids that contain one or
Mediterranean and eastern Asian countries intake ranges from
more double bonds in the trans configuration. The two pri-
1 to 3 g day1 and less than 1 g day1, respectively.
mary sources of trans-fatty acids are those that are produced
The proportion of trans fat intake derived from ruminant
through the partial hydrogenation of vegetable oils (industri-
sources varies across countries. In a study assessing the dietary
ally produced), and those that are produced by ruminant
intake of trans-fatty acids in 14 Western European countries,
animals (naturally occurring). Historically, vegetable oils were
trans fat from milk and ruminant fat ranged from 28% to 79%
partially hydrogenated for use in margarines, commercial
of the total trans-fatty acid intake. In Mediterranean countries,
cooking and frying, and food manufacturing. The presence of
450% of trans fat intake came from ruminant sources. In the
trans-fatty acids results in solid fats at room temperature,
US, intake of ruminant trans-fatty acids represents approxi-
longer shelf-life of commercial products, and stability of oils
mately 20% of the total trans-fatty acid intake, with more than
at very high temperatures. The majority of trans-fatty acids in
85% of ruminant trans-fatty acids coming from milk fat. In
foods are C18:1 isomers. Elaidic acid, which is derived from
European and Australian populations, ruminant trans-fatty
oleic acid, typically is the major isomer in industrial sources of
acids intake represents approximately 63–75% of the total
trans-fatty acids. Ruminant trans-fatty acids are synthesized via
trans-fatty intake.
bacterial metabolism of C18 unsaturated fatty acids in ru-
minant animals, and found in ruminant-derived products,
such as beef, lamb, and dairy. Vaccenic acid, the predominant
trans-monoene isomer in ruminant fats, comprises 50–80% of
Health Effects
the total trans-fatty acids in ruminant fat. Vaccenic acid is the
precursor for the c9,t11 isomer of conjugated linoleic acid
There are distinct differences in the isomeric distribution of
(CLA). CLA is a group of positional and geometric conjugated
trans-fatty acids from industrial sources and ruminant animals,
isomers of linoleic acid. The two predominant isomers of CLA
which may translate to differential effects on health outcomes.
with known bioactive properties are c9,t11 and t10,c12.
There is a vast literature that demonstrates the deleterious ef-
fects of industrially produced trans-fatty acids on the risk of
chronic diseases, including cardiovascular disease, cancer, and
Dietary Intake diabetes; however, the health effects of ruminant trans-fatty
acids in humans have not been well studied. More recently,
Owing to increased public awareness of the adverse health ef- epidemiological studies have begun to differentiate between
fects of trans fat, as well as government regulations worldwide, industrially produced and ruminant trans-fatty acids. Clinical
recent intake data suggest that trans fat consumption has sig- studies comparing the two sources of trans-fatty acids are
nificantly declined. Dietary intake of trans fat in the US and limited.

288 Encyclopedia of Human Nutrition, Volume 4 [Link]

 Trans-Fatty Acids: Health Effects, Recommendations, and Regulations 289

Cardiovascular Disease higher concentrations of IL-6. Results from clinical studies

have been mixed, with some demonstrating a proin-
Coronary Heart Disease
flammatory effect of trans-fatty acids, and others reporting no
Numerous epidemiological studies have demonstrated an as-
effect. In a study in hypercholesterolemic individuals, the ef-
sociation between intake of trans-fatty acids and risk of cor-
fects of trans-fatty acids (consumed as margarine) on markers
onary heart disease. In the early 1990s, results from the
of inflammation did not differ from those of saturated fatty
Nurses’ Health Study, a prospective study, demonstrated that
acids (consumed as butter). In a study in men, consumption
intake of trans-fatty acid isomers was directly related to risk of
of a diet rich in trans fat (8% energy) for 5 weeks led to higher
coronary heart disease (RR ¼ 1.5, 95% CI 1.12–2.00, p for
concentrations of IL-6 when compared with a carbohydrate
trend ¼ 0.001). In contrast, there was a nonsignificant inverse
diet (po0.05), and higher concentrations of CRP when
association with intake of trans-fatty acids from ruminant
compared with a carbohydrate diet or monounsaturated fat
sources and risk of coronary heart disease. In a recent meta-
diet. In contrast, in two other studies, neither industrial trans-
analysis of six prospective cohort studies, the total trans-fatty
fatty acids nor ruminant trans-fatty acids had an effect on
acid intake was associated with an increased risk of coronary
concentrations of CRP, following 4 weeks of intervention.
heart disease (RR ¼ 1.22, 95% CI 1.08–1.38; p ¼ 0.002); there
Overall, results from these studies suggest that trans-fatty acids
was a trend for a positive association with intake of industri-
increase markers of inflammation when compared with
ally produced trans-fatty acids and coronary heart disease
carbohydrate and unsaturated fatty acids; their effects when
(RR ¼ 1.21, 95% CI 0.97–1.5; p ¼ 0.09), whereas there was no
compared with saturated fatty acids remain unclear.
association with intake of ruminant trans-fatty acids. One case-
The effects of ruminant trans-fatty acids on inflammation
control study and three prospective studies reported no asso-
are not well studied. Observational studies have not reported
ciation with intake of ruminant trans-fatty acids and risk of
an association with ruminant trans-fatty acids and markers of
coronary heart disease, whereas one study found similar as-
inflammation, whereas few clinical studies have evaluated
sociations between ruminant and industrial trans-fatty acids.
their effects. In some studies, mixtures of c9,t11 and t10,c12-
Overall, data suggest that intake of ruminant trans-fatty acids
CLA caused an increase in CRP in both healthy individuals
may have differential effects compared with those of in-
and those with metabolic syndrome. In contrast, other studies
dustrially produced trans-fatty acids; however, more research is
have found no effect of CLA on markers of inflammation in
needed to determine the effects of ruminant trans-fatty acids
diabetics and individuals at risk for coronary heart disease.
on cardiovascular disease risk factors.
Owing to the discrepancies in results from current studies,
more research is needed to clarify the effects of industrial and
Lipids and Lipoproteins ruminant trans-fatty acids on markers of inflammation.
Clinical trials consistently demonstrate that consumption of
trans fat adversely affects lipids and lipoproteins. Studies have
demonstrated that these effects are greater than those of satur- Endothelial Function
ated fatty acids. Compared with saturated fatty acids, trans-fatty Some epidemiological studies have shown an association with
acids decrease high-density lipoprotein (HDL)-cholesterol and trans fat intake and plasma markers of endothelial dysfunction,
increase low-density lipoprotein (LDL)-cholesterol (specifically specifically adhesion molecules (intercellular adhesion mol-
small dense LDL particles), triglycerides, and Lp(a). ecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1),
There have been few clinical studies that have investigated and E-selectin). Results from randomized controlled trials in-
the effects of ruminant trans-fatty acids on lipids and lipo- dicate that long-term consumption of trans-fatty acids impairs
proteins. In a study in healthy men and women, ruminant endothelial function to a greater extent than saturated fatty
trans-fatty acids increased HDL-cholesterol, but this effect was acids. In a postprandial study, consumption of a meal rich in
only observed in women. In addition, LDL-cholesterol and trans fat or saturated fat did not impair postprandial flow
triglycerides were also increased. Results from another study mediated dilation of the brachial artery in healthy men.
suggest that at lower doses ruminant trans-fatty acids may not However, in a chronic feeding study in healthy men and
affect lipids and lipoproteins, but at higher doses (i.e., higher women (4 weeks), the trans fat diet (9.2% energy as trans
amounts than typically consumed) they may have similar ef- fat) significantly impaired flow mediated dilation of the bra-
fects as industrially produced trans-fatty acids. Owing to the chial artery (decreased by 29%) compared with a diet rich in
inconsistencies in the data, additional highly controlled clin- saturated fat.
ical studies are warranted.

Cancer
Inflammation
Some epidemiological studies have demonstrated an associ- Epidemiological Studies
ation with total or industrial trans-fatty acids and plasma The association of intake of trans-fatty acids and risk of cancer is
markers of inflammation, including tumor necrosis factor- not well understood. Results from epidemiological studies have
alpha, interleukin-6 (IL-6), and C-reactive protein (CRP). In a been inconsistent, particularly with ruminant trans-fatty acids.
study in overweight women, CRP was significantly higher in Three studies have demonstrated a direct association with
individuals in the highest quintiles of intake versus the lowest concentration of vaccenic acid in serum or erythrocytes and risk
quintiles of intake, after multivariate adjustment (p for of breast or prostate cancer, whereas one study demonstrated
trend ¼ 0.009). In a study in individuals with established heart an inverse association of serum concentration of vaccenic acid
disease, membrane trans-fatty acids levels were associated with and breast cancer (among postmenopausal women). Studies
290 Trans-Fatty Acids: Health Effects, Recommendations, and Regulations

with CLA have been mixed; one case-control study reported an diabetes. Results from this study suggest that replacement of
inverse association with dietary intake of CLA and risk of col- 2% of energy from trans-fatty acids with polyunsaturated fatty
orectal cancer, and one case-control study found significantly acids would result in a 39% increase in risk of type 2 diabetes.
lower CLA (dietary intake and serum concentrations) in indi- However, in two other prospective studies, the Health Pro-
viduals with breast cancer compared to those without breast fessionals Follow-Up Study and Iowa Women’s Health Study,
cancer (among postmenopausal women). In two other case- there was no association with trans fat intake and risk of
control studies, there was no significant association of CLA and diabetes.
breast cancer risk. Interestingly, in one of these studies, intake
of CLA was associated with a reduced risk of having an estrogen Insulin Sensitivity
receptor (ER)-negative tumor in premenopausal women Studies in healthy individuals have found no effect of trans fats
(OR ¼ 0.40, 95% CI 0.16–1.01). In a prospective cohort study, on insulin sensitivity. In a study in hypercholesterolemic
intake of CLA was weakly associated with breast cancer inci- overweight adults, both fasting insulin levels and insulin re-
dence (RR ¼ 1.24, 95% CI 0.91 1.69; p for trend ¼ 0.02). The sistance (homeostatic model assessment) were higher in those
relationship of CLA and metastasis has been investigated in one following a partially hydrogenated soybean oil diet (4% of
study; there was no significant association between the con- energy as trans fat), compared with a soybean oil or canola oil
centration of CLA in breast adipose tissue at the time of diag- diet. In a study in insulin-resistant individuals with type 2
nosis and risk of metastasis or death. diabetes, a high trans-monounsaturated fat diet (20% of en-
Some epidemiological studies have shown a direct associ- ergy) resulted in a 59% higher postprandial insulin response
ation between intakes of industrially produced trans fat or total (po0.05) when compared to a cis-monounsaturated fat diet
trans fat and risk of colorectal, prostate, and breast cancers. In (20% total energy); however, this response was not signifi-
studies with prostate cancer, results have varied depending on cantly different when compared to the saturated fat diet. In a
the methodological approaches that have been utilized. Studies recent study in healthy women with abdominal obesity, nei-
using food frequency questionnaires to assess dietary intake ther a diet rich in industrial trans-fatty acids (5.58 g day1;
have not found associations with prostate cancer risk; in con- 4 weeks) nor a diet rich in ruminant trans-fatty acids
trast, other studies have found direct associations with serum (4.86 g day1; 4 weeks) had an effect on insulin sensitivity, as
and adipose tissue concentrations of trans-fatty acids. Most assessed by hyperinsulinemic–euglycemic clamp, when com-
studies with colon cancer suggest a direct association with intake pared to a low trans fat diet (0.54 g day1; 4 weeks each).
of trans-fatty acids and colon cancer risk, although one pro- Results from these studies suggest that trans-fatty acids may
spective study found no association. In studies of breast cancer have little or no effect on insulin sensitivity in healthy indi-
risk, direct associations have been reported with concentrations viduals, but may have adverse effects in individuals with dia-
of trans-fatty acids in adipose tissue; however, studies using food betes or those who are overweight.
frequency questionnaires to assess dietary intake or serum Studies with ruminant trans-fatty acids are limited, but suggest
concentrations of trans-fatty acids have not found an association that vaccenic acid does not have an effect on fasting glucose and
with trans fat intake and risk of breast cancer. Some studies have insulin. Some studies in obese, insulin-resistant men suggest that
demonstrated that both genetic factors and hormone levels can supplementation with CLA (purified t10,c12-CLA, purified
influence the association of trans fat and cancer risk; thus, c9,t11-CLA, or 50:50 mixture) increases insulin resistance and
additional studies are needed that account for these types of fasting glucose, compared to placebo. In a study in individuals
variables. Overall, results of case-control studies suggest that with type 2 diabetes, CLA supplementation (50:50 mixture of
intake of trans-fatty acids is associated with increased risk of c9,t11 and t10,c12 isomers) increased fasting glucose and
cancer; however, results from prospective studies, which are reduced insulin sensitivity. However, other studies have found no
stronger study designs, do not consistently support the results of effect of trans fat on measures of insulin sensitivity.
case-control studies. Thus, further studies are warranted to in-
vestigate the relationship of trans-fatty acids, particularly specific
isomers of trans-fatty acids, and risk of cancer. Dietary Recommendations and Regulations

In 2002, the panel on Macronutrients of the US National

Clinical Trials
Academies, Institute of Medicine, recommended that trans-
Although some cell culture and animal studies have suggested
fatty acid consumption should be as low as possible in a
an anticarcinogenic effect of CLA on various forms of cancer,
nutritionally adequate diet. In 2003, the World Health Or-
including breast, colon, and prostate, human intervention
ganization recommended that trans-fatty acid intake should be
studies are lacking. There are two ongoing studies designed to
limited to less than 1% of overall energy consumption. Nu-
investigate the effects of CLA consumption in patients with
merous other national and international organizations rec-
newly diagnosed and advanced cancers. Results from these
ommend that trans fat consumption should be as low as
studies will provide valuable information regarding the effects
possible, including the Institute of Medicine, the US Dietary
of CLA and the progression of various cancers.
Guidelines, the National Cholesterol Education Program, and
the American Dietetic Association.
Owing to the adverse health effects of trans-fatty acids,
Diabetes
numerous countries and cities have started to regulate trans fat
In the Nurses’ Health Study, high intake of trans-fatty acids in the food supply. In 2003, Denmark became the first country
(3% of energy) was associated with an increased risk of type 2 to regulate trans fats by mandating that only 2% of fats and
 Trans-Fatty Acids: Health Effects, Recommendations, and Regulations 291

oils could be trans fats. Switzerland also imposed federal kernel oil, and coconut oil), as well as oils developed by ma-
regulations to restrict the amount of trans fats in the food nipulating the fatty acid composition of oil seeds (low-linoleic,
supply, whereas Canada has requested that manufacturers midoleic, or high-oleic oils) to create products that exhibit in-
voluntarily reduce trans fats. In 2008, the state of California creased oxidative stability during deep-frying, and increased
implemented a state-wide ban on trans fats in food service shelf-life by increasing relatively stable fatty acids (i.e., oleic
establishments (excluding prepackaged goods). In addition, acid) and decreasing relatively unstable fatty acids (i.e., lino-
multiple US cities have banned trans fat in food service es- lenic acid). The choice in alternatives for trans fats depends on
tablishments, including Philadelphia and Boston. In New the application. For frying applications, oils such as soybean,
York City, restaurant food must contain less than 0.5 g of trans canola, cottonseed, and high-oleic sunflower oil can be used;
fat. Most bans were implemented in two phases: (1) elimin- however, for baking applications, where solid or semisolid fats
ation in frying, grilling, and spreads and (2) complete elim- are needed for consistency and feel, alternatives such as tropical
ination including baking. oils, fully hydrogenated vegetable oil, and interesterified fats are
There are no federal regulations in the US limiting trans fats; more useful. Although these alternatives have been useful in
however in 2003, the US Food and Drug Administration ruled manufacturing foods without trans fats, their health effects are
that trans fat, defined as all unsaturated fatty acids that contain not yet well understood; more research is needed to compare
one or more isolated double bonds in the trans configuration, the health effects of different trans fats alternatives.
must be listed on the Nutrition Facts Panel of the food label (as
of 2006). CLA, which contains conjugated double bonds in the
trans configuration, is excluded from being listed on the food Conclusions
label, because the ruling specifies isolated double bonds in the
definition of trans fat; however, other ruminant trans-fatty acids, Overall, data from epidemiological and clinical studies con-
such as vaccenic acid, are included under the definition and sistently demonstrate the adverse effects of industrial trans-
would be accounted for on the food label. In the US, the fatty acids on coronary heart disease risk and lipids and
amount of trans fats in a product can be listed as 0 g if the lipoproteins; their effects on other chronic disease risk factors,
product contains less than 0.5 g per serving. Many food such as inflammation, endothelial function, and insulin re-
manufacturers have responded by lowering the trans fat content sistance, as well as risk of type 2 diabetes, are less consistent.
of many of their products to less than 0.5 g per serving. A listing The effects of industrial and ruminant trans-fatty acids on risk
of 0 g of trans fats on a food label when the product does of cancer remain unclear. Although some animal studies
indeed contain trans fats may be misleading to consumers, suggest that industrial and ruminant trans-fatty acids may
particularly if multiple servings of that product are typically differ in their biological effects, further research is needed to
consumed. In other countries such as Canada trans fat content elucidate whether they exhibit differential effects on chronic
of a given product must be less than 0.2 g per serving to be disease risk factors. As various trans fats alternatives are used in
listed as 0 g on the label. the food supply, it is important to adequately study their ef-
fects on health outcomes, so as to avoid increasing the use of
ingredients that are more harmful than the ingredient for
Trans Fat Alternatives which they replaced.

Trans fats became a prevalent ingredient in food products as a

means for replacing saturated fats in the diet, as the adverse Disclaimer
effects of saturated fats were well known. It is now understood
that the effects of industrial trans-fatty acids on numerous dis- Mention of trade names or commercial products in this
ease risk factors are more deleterious than those of saturated publication is solely for the purpose of providing specific in-
fatty acids. Increased pressure in the last decade to remove or formation and does not imply recommendation or endorse-
significantly reduce trans-fatty acids in the food supply has ment by the US Department of Agriculture.
prompted the question: What alternatives should be used as The US Department of Agriculture (USDA) prohibits dis-
food manufacturers are reformulating products to remove crimination in all its programs and activities on the basis of
partially hydrogenated oils? There are multiple considerations race, color, national origin, age, disability, and where applic-
when choosing an alternative for trans fats, including taste and able, sex, marital status, familial status, parental status, re-
texture, as well as cost and availability. Moreover, the potential ligion, sexual orientation, genetic information, political
health effects of the alternative should be considered, so as to beliefs, reprisal, or because all or part of an individual’s in-
avoid introducing a harmful ingredient into the food supply. come is derived from any public assistance program. (Not all
A common technique that is utilized for preparation of trans prohibited bases apply to all programs.) Persons with dis-
fats alternatives is interesterification – a process in which fatty abilities who require alternative means for communication of
acids are rearranged on a triacylglycerol molecule. This techni- program information (Braille, large print, audiotape, etc.)
que is useful because the position of fatty acids on the glycerol should contact USDA’s TARGET Center at (202) 720-2600
molecule is critical in creating a fat with the proper physical (voice and TDD). To file a complaint of discrimination, write
properties required for a trans fats alternative. Stearic acid and to USDA, Director, Office of Civil Rights, 1400 Independence
palmitic acid, both saturated fatty acids, typically are used in Avenue, S.W., Washington, DC 20250-9410, or call (800) 795-
interesterification. Other alternatives are oils that require little 3272 (voice) or (202) 720-6382 (TDD). USDA is an equal
or no hydrogenation, such as tropical oils (palm oil, palm opportunity provider and employer.
292 Trans-Fatty Acids: Health Effects, Recommendations, and Regulations

Further Reading Mozaffarian D, Aro A, and Willett WC (2009) Health effects of trans-fatty aicds:
Experimental and observational evidence. European Journal of Clinical Nutrition
Bendsen NT, Christensen R, Bartels EM, and Astrup A (2011) Consumption of 63: S5–S21.
industrial and ruminant trans fatty acids and risk of coronary heart disease: A Remig V, Franklin B, Margolis S, Kostas G, Nece T, and Street JC (2010) Trans fats
systematic review and meta-analysis of cohort studies. European Journal of in America: A review of their use, consumption, health implications, and
Clinical Nutrition [Epub ahead of print]. regulation. Journal of the American Dietetic Association 110: 585–592.
Berry SE (2009) Triacylglycerol structure and interesterification of palmitic and Smith BK, Robinson LE, Nam R, and Ma D (2009) Trans-fatty acids and cancer: A
stearic acid-rich fats: An overview and implications for cardiovascular disease. mini-review. British Journal of Nutrition 102: 1254–1266.
Nutrition Research Reviews 22: 3–17. Tardy A, Morio B, Chardigny J, and Malpuech-Brugere C (2011) Ruminant and
Micha R and Mozaffarian D (2008) Trans fatty acids: Effects on cardiometabolic industrial sources of trans-fat and cardiovascular and diabetic diseases. Nutrition
health and implications for policy. Prostaglandins Leukotrienes and Essential Research Reviews 24: 111–117.
Fatty Acids 79: 147–152.