Critical Reviews in Food Science and Nutrition

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Ruminant and industrial trans-fatty acids

consumption and cardiometabolic risk markers: A
systematic review

Bárbara Júlia Fonseca Verneque, Adriane Moreira Machado, Luciana de

Abreu Silva, Aline Cristine Souza Lopes & Camila Kümmel Duarte

To cite this article: Bárbara Júlia Fonseca Verneque, Adriane Moreira Machado, Luciana de Abreu
Silva, Aline Cristine Souza Lopes & Camila Kümmel Duarte (2022) Ruminant and industrial trans-
fatty acids consumption and cardiometabolic risk markers: A systematic review, Critical Reviews in
Food Science and Nutrition, 62:8, 2050-2060, DOI: 10.1080/10408398.2020.1836471

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CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
2022, VOL. 62, NO. 8, 2050–2060
https://doi.org/10.1080/10408398.2020.1836471

REVIEW

Ruminant and industrial trans-fatty acids consumption and cardiometabolic risk

markers: A systematic review
B
arbara Ju

lia Fonseca Verneque, Adriane Moreira Machado, Luciana de Abreu Silva, Aline Cristine Souza Lopes,
and Camila Ku €mmel Duarte
Departament of Nutrition, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

ABSTRACT KEYWORDS
The development of cardiometabolic diseases is related to conditions such as obesity, abdominal Fatty acids; dietary fats;
fat, insulin resistance, diabetes mellitus, elevated blood pressure and changes in lipid profile. The metabolic syndrome;
whole of Trans Fatty Acid (TFA) intake is associated with the increase of cardiometabolic risk fac- cardiovascular disease
tors. There are two main sources of TFA, the ruminant TFA (rTFA) which are produced by biohy-
drogenation in animal’s rumen, and the industrial TFA (iTFA), produced by hydrogenation of
vegetable oils, the individual effect of each group is still controversial. The aim of this study was
to analyze the effect of industrially and ruminants TFA intake on cardiometabolic risk in adults. It
was carried out a systematic search of the literature in October 2019 and two independent
authors selected and extracted data from articles. After the selection process, nine clinical trials
were included, and summary tables were constructed to present data for all outcomes. The results
showed that both sources of TFA can increase cardiometabolic risk parameters, especially lipid
profile. At levels up to 1.5%–7% of energy, the effect of rTFA seems to be greater than iTFA and it
seems to be greater in women. However, rTFA seems to be less harmful than iTFA for High
Density Lipoprotein cholesterol, although for total cholesterol and Low density Lipoprotein choles-
terol it may be worse. In summary, both sources of TFA can increase cardiometabolic risk parame-
ters, especially lipid profile. However, the dose of TFA and the whole composition of the food
must be considered.

Introduction The source of iTFA is ultra-processed food and it also

contains lots of food additives, sugar, and salt (i.e., cookies,
Cardiovascular diseases (CVD) are the leading cause of
margarine, etc), which are known to have deleterious health
death in the world (Naghavi et al. 2017; OPAS 2017). The
effects (Schnabel et al. 2019). The food sources rTFA are
development of a cardiovascular disease is related to condi- milk, dairy products, and meat, provide a considerably
tions such as obesity, abdominal fat, insulin resistance, dia- greater amount of saturated fatty acids, when compared
betes mellitus, changes in lipid profile, and elevated blood with the food sources of iTFA. In addition, saturated fatty
pressure (Brassard et al. 2019; Fleming and Kris-Etherton acids in meat are commonly linked to hypercholesterolemic
2016) According to the Global Burden and Disease Study effects (Bergeron et al. 2019). However, these rTFA source
(GBD), dietary risks ranks second for mortality causes, and foods receive a lower degree of processing, having a better
more than 50% of those deaths are due to CVD (Gakidou nutritional profile, when compared to ultra-processed foods
et al. 2017). (Schnabel et al. 2019).
The consumption of total trans fatty acids (TFA) in The TFA food source also presents different composi-
human feeding has been largely related to the development tions, mainly due to the differences in the TFAs’s formation
of CVD (Mozaffarian et al. 2006). However, TFAs have two process on each source. iTFA is formed in greater quantity
sources: industrially produced trans fatty acids and naturally by elaidic acid (trans 18:1n-9), while rTFA consists mainly
occurring trans fatty acids. The ruminant TFA (rTFA) are of vaccenic acid (C18:1 trans-11) and conjugated linoleic
produced by biohydrogenation of unsaturated fatty acids in acid (CLA or 9-cis, 11-trans-C18:2) (Micha and Mozaffarian
the rumen of animals like cattle and goats, by means of the 2008; Guillocheau et al. 2020).
bacterial metabolism. On the other hand, Industrial TFA Experimental and epidemiological studies showed that
(iTFA) are produced industrially by partial hydrogenation of iTFA intake is associated with the increase in low-density
vegetable or fish oils, resulting in commercial solid edible lipoprotein (LDL) cholesterol, triglycerides, and the reduc-
fats which increases shelf life of foods (Dhaka et al. 2011). tion of high-density lipoprotein (HDL) cholesterol. All of

CONTACT Camila K€ummel Duarte [email protected] Departament of Nutrition, Universidade Federal de Minas Gerais, Belo Horizonte 31270-
901, Brazil.
Supplemental data for this article can be accessed at https://doi.org/10.1080/10408398.2020.1836471.
ß 2020 Taylor & Francis Group, LLC
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 2051

those circumstances are related to cardiometabolic risk Products")))). The search strategy for the other databases are
(Stender, Astrup, and Dyerberg 2008; Ganguly and Pierce available at Table S1 (Supplementary material).
2012). Thus, efforts have been made in the past decade to
remove iTFA from food. Consequently, rTFAs have become
Eligibility criteria
a more significant food source of TFA (Hansen et al. 2012)
and it seems to be not as harmful as iTFA. In the Scottish RCT was included to make it possible to compare the effect
Heart Health Study (Bolton-Smith et al. 1996) the intake of of iTFA versus TFA eliminating confusion bias can be pre-
rTFA, in men was inversely associated with cardiometabolic sent in observational studies.
risk. Results from a meta-analysis of prospective cohort Trials were included if cardiometabolic risk markers
studies suggest that iTFA may increase the risk of CVD, (weight, Body Mass Index (BMI), body fat percentage, total
whereas rTFA does not (Bendsen et al. 2011). Thus, the aim cholesterol (TC), low density lipoprotein (LDL) cholesterol,
of this study was to analyze the effect of consumption of high density lipoprotein (HDL) cholesterol, triglycerides
trans fatty acids from industry and ruminants on cardiome- (TG), glycemia, insulin resistance, systolic and diastolic
tabolic risk in adults, gathering more consistent and conclu- blood pressures, including postprandial result) were eval-
sive information that can help to clarify the relationship uated in adults after intervention with rTFA compared with
between TFA, its sources, and CVD. iTFA products or capsule. Studies that compared only
Ruminant Trans Fatty acids intake, in different doses, were
not included. A priori, case-control studies, cohort or eco-
Methods logical studies, commentaries, general reviews, case reports,
A systematic review of randomized clinical trials (RCT) that animal studies, or studies conducted on subjects other than
evaluated the consumption of rTFA versus iTFA on cardio- adults without any CVD were excluded. Addition, studies
metabolic risk markers in adults was carried out. This sys- with no outcomes of interest and with no comparison
between the intake of different sources of TFA were
tematic review was conducted following the
also excluded.
recommendations of the Cochrane Handbook for Systematic
Reviews of Interventions (Higgins et al. 2019). In October
2019, RCT was selected if they met all the eligibility criteria Study selection, data-collection process, and data items
for this paper. This review was registered in the inter-
national prospective register of systematic reviews The titles and abstracts were read in duplicate by two inves-
tigators (BJF and AMM) to check for eligibility criteria, with
PROSPERO network (registration no. CRD42020151216).
differences resolved by consensus. The software ENDNOTE
X9 was used to read titles and abstracts. For abstracts from
Search strategy congress and symposia, authors were contacted for informa-
tion about recent publications or information about
Searches were performed with the use of MEDLINE (via
those data.
PubMed), Embase, Web of Science, CENTRAL Cochrane, Data was extracted independently and in duplicate by
SCOPUS and related articles, hand-searching of reference two investigators (BJF and AMM), including the year when
lists, and direct author contact. Besides, bases of unpub- the study was performed and reported, study design, sample
lished articles and thesis were also used as sources of size, type of population studied, cardiometabolic risk
articles. No period or language restrictions were used in the markers outcomes (weight, BMI, body fat percentage, TC,
search strategy. Key words were “Trans Fatty Acids,” “Fatty LDL, HDL, TG, glycemia, insulin resistance, systolic and
Acids,” “Ruminants,” and “industrially.” The following diastolic blood pressures) duration of follow-up, median,
search strategy was used in PubMed: (((((“rTFA” OR “trans- mean, interquartile range, standard deviation, standard error
vaccenic acid” OR “transvaccenic” OR “rumenic acid” OR and confidence intervals or mean and standard deviation in
“vaccenic acid” OR conjugated linoleic acid” OR “ruminant all doses of day intake.
trans fatty acids” OR “ruminant trans fatty acid” OR
“ruminant trans fat))) AND ((“industrial trans fatty acids”
OR “industrial trans fatty acid” OR “industrial trans fat” OR Risk of bias within and across studies
“Elaidic acid” OR “Trans oleic acid” OR “Trans linoleic The Cochrane Collaboration’s revised tool (Higgins et al.
acid” OR “iTFA”)))) OR ((((((“industrial” OR “Partially 2019) to assess the risk of bias in randomized trials, Risk of
Hydrogenated Oils” OR “industrially”))) AND (("Trans Fatty Bias 2.0 (RoB 2.0), was used for the quality assessment
Acids"[Mesh] OR “Trans Fatty Acids” OR “Acids, Trans of studies. Two authors (BJF and AMM) evaluated the risk
Fatty” OR “TFA” OR “trans” OR “Fatty Acids, Trans” OR of bias. The RoB 2.0 contains assessment for individually
“Trans-Fatty Acids” OR “Acids, Trans-Fatty”)))) AND randomized trials in five domains: randomization process,
(((("Trans Fatty Acids"[Mesh] OR “Trans Fatty Acids” OR deviations from intended interventions, missing outcome
“Acids, Trans Fatty” OR “TFA” OR “trans” OR “Fatty data, and measurement of the outcome and selection of the
Acids, Trans” OR “Trans-Fatty Acids” OR “Acids, Trans- reported result. Differences in quality assessment scores
Fatty”))) AND ((“Ruminants"[Mesh] OR “Ruminants” OR between investigators were unusual and were solved by con-
“ruminant” OR “Dairy Products” [Mesh] OR “Dairy sensus or by a third investigator.
2052 B. J. F. VERNEQUE ET AL.

Figure 1. Flowchart showing the process of article selection.

Results et al. 2012; Gebauer et al. 2015) both, men and women; in
In systematic search of the literature was found 1123 cita- all cases the participants were healthy. All studies were per-
tions. Of these 159 were duplicates and 964 were abstracts, formed in Europe (n ¼ 6) or North America (n ¼ 3). The
leaving 58 full-text citations. Out of these, 9 (Wanders et al. delivery vehicle for TFAs of all studies was food, namely
2010; Radtke et al. 2017; De Roos et al. 2011; Motard- mostly margarine, butter, and yogurts. The studies’ charac-
B
elanger et al. 2008; Desgagn
e et al. 2016; Engberink et al. teristics are presented in Table 1.
2012; Tardy et al. 2009; Gebauer et al. 2015; Chardigny et al. The amount of TFA varied from 1.5 to 7% of energy and
2008) RCT meeting our eligibility criteria were included in in some studies this proportion represented 4.2 to 20 grams
the systematic review (Figure 1). of TFA. Four articles (Wanders et al. 2010; Engberink et al.
The studies included from 9 to 124 participants, who 2012; Tardy et al. 2009; Gebauer et al. 2015) brought data on
were followed for periods ranging from 3 to 4 weeks. Three TFA intake after the intervention. The total TFA intake on
studies included only men (De Roos et al. 2011; Motard- the rTFA diet was 0.6 to 1.6% of energy (or 1 to 5 g/day),
B
elanger et al. 2008; Desgagn
e et al. 2016), one study (Tardy higher than the iTFA diet in three studies (Wanders et al.
et al. 2009) only women, and five studies (Wanders et al. 2010; Engberink et al. 2012; Gebauer et al. 2015); and 0.55%
2010; Chardigny et al. 2008; Radtke et al. 2017; Engberink of energy (or 1 g/day) lower than the iTFA diet in one (22).
Table 1. Characteristics of the studies in which the response of cardiometabolic risk markers to ruminant and industrial trans-fatty acids consumption was assessed.
Interventions2
Control group/ Evaluated
Study, Year Country Study design Population (n) Male (%) Age1 (years) Delivery vehicle dose/duration rTFA/dose/duration iTFA/dose/duration variables
Chardigny France Crossover Healthy men and 47.5 27.6 ± 7.1 Butter, cheese – Mixed isomers/ Mixed isomers/ TG; TC; HDL-c;
et al., 2008 women (40) and cookies 5.4%E/3w 5.4%E/3w LDL-c
De Roos Netherlands Crossover Health men (12) 100 33.4 ± 13.5 Margarines and Oleic acid/7%E/3w 80 % cis-9, trans- trans-C 18:1/ TG; TC; HDL-c;
et al. 2011 yoghurt drinks 11 CLA þ 20% 7%E/3w LDL-c; Insulin;
enriched with % trans-10, cis- Glucose;
the special oils 12 CLA/7%E/3w HOMA-IR
and fats
Desgagn
e Canada Crossover Healthy men (9) 100 36.6 ± 16.9 TFA-enriched Mixed fatty acids/ Mixed isomers/ Mixed isomers/ Body weight;
et al. 2016 butter, control rTFA 0.8%E/4w 3.7%E/4w 3.7%E/4w Waist; TG; TC;
butter HDL-c; LDL-
and shortening c; BP
Engberink Netherlands Crossover Healthy men and 41 30.9 ± 13.7 Margarines and Oleic acid/7%E/3w 80 % cis-9, trans- trans-C 18:1/ BP
et al. 2012 women (61) yoghurt drinks 11 CLA þ 20% 7%E/3w
enriched with % trans-10, cis-
the special oils 12 CLA/7%E/3w
and fats.
Gebauer United States Crossover Healthy men and 44.3 47.6 ± 10.8 Various food items Mixed TFA Vaccenic acid/ Mixed isomers/ TG; TC; HDL-c;
et al. 2015 women (106) (baked goods, isomers/0.1%E/ 3.3%E/3.5 w 3.3%E/3.5w LDL-c; Insulin;
sauces and 3.5 w Glucose;
spreads, and HOMA-IR
mashed
potatoes)
Motard-B
elanger Canada Crossover Healthy men (38) 100 32.8 ± 15.0 TFA-enriched Mixed fatty acids/ 1) Mixed isomers/ Mixed isomers/ Body weight;
et al. 2008 butter, control rTFA 0.8%E/4w 1.5%E/4w 3.7%E/4w Waist; TG; TC;
butter 2) Mixed HDL-c; LDL-c
and shortening isomers/
3.7%E/4w
Radtke et al. 2017 Switzerland Clinical trial Healthy men and 44.3 45 to 69 Alpine butter, NI/NI/4w NI/2%E/4w NI/2%E/4w TG; TC; HDL-c;
women (124) margarine and LDL-c
a control
margarine
without
TFAs
Tardy et al. 2009 France Clinical trial Healthy 0 18 to 50 Butter, dessert NI/NI/4w Mixed isomers/ Mixed isomers/ Body weight;
women (58) cream 2,04 ± 0,27 2,59 ± 0,48 Waist; TG; TC;
and biscuits %E/4w %E/4w HDL-c; LDL-c;
Insulin; Glucose;
HOMA-IR
Wanders Netherlands Crossover Healthy men and 41 30.9 ± 13.7 Margarines and Oleic acid/7%E/3w 80 % cis-9, trans- trans-C 18:1/ Body weight;
et al. 2010 women (61) yoghurt drinks 11 CLA þ 20% 7%E/3w Waist; TG; TC;
enriched with % trans-10, cis- HDL-c; LDL-c
the special oils 12 CLA/7%E/3w
and fats
1
Mean ± SD or age group.
2
Fatty acid type/isomer.
NI: not informed.
BP: Blood Pressure; CLA: Conjugated Linoleic Acid; HDL-c: High-density lipoprotein cholesterol; iTFA: industrial trans fatty acids; LDL-c: Low-density lipoprotein cholesterol; rTFA: ruminant trans fatty acids; TC: Total
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION

Cholesterol; TFA: Trans fatty acids TG: Triglycerides.

2053
2054 B. J. F. VERNEQUE ET AL.

Macronutrient composition in rTFA and iTFA interven- reduction of HDL with both diets, but the effect of iTFA
tion diets varied from 45 to 55% for carbohydrates, 10–20% was greater compared to rTFA. In contrast, Gebauer et al.,
for protein, and 33–43.5% for fat. The proportion of each observed a significant increase in HDL with the rTFA diet
macronutrient was balanced between diets (Wanders et al. and no effect was observed with the iTFA diet. The evalua-
2010; Chardignyet al., 2008; Radtke et al. 2017; Motard- tions of TG were controversial: three studies found no effect
B
elanger et al. 2008; Engberink et al. 2012; Tardy et al. of TFA on TG (Motard-B
elanger et al. 2008; Tardy et al.
2009; Gebauer et al. 2015). Tardy et al. and Radtke et al. 2009; Radtke et al. 2017) and three trials observed an
provided lipid composition from foods were TFA were vehi- increase on TG with any of the TFA diets (Wanders et al.
culated. Only six studies provided data of lipids distribution 2010; Chardigny et al., 2008; Gebauer et al. 2015). The
on diets (Wanders et al. 2010; Chardigny et al., 2008; De intake of rTFA seems to have a greater impact on the TG
Roos et al. 2011; Motard-B
elanger et al. 2008; Engberink increase, although a significant effect was also observed with
et al. 2012; Gebauer et al. 2015) and differences in saturated iTFA intake (Wanders et al. 2010).
and/or unsaturated fatty acids consumption between inter- Two other selected trials had data for lipid profile (De
vention arms were observed in five studies (Wanders et al. Roos et al. 2011; Desgagn
e et al. 2016). However, the results
2010; Chardigny et al; Motard-B
elanger et al. 2008; De Roos were not shown because they were part of the same popula-
et al. 2011; Engberink et al. 2012). In four studies (Wanders tion sample evaluated in other included studies (Wanders
et al. 2010; Chardigny et al. 2008; De Roos et al. 2011; et al. 2010; Motard-B
elanger et al. 2008).
Engberink et al. 2012) the percentage of energy from satu-
rated fatty acids in the iTFA was higher than the percentage
Anthropometry
in the rTFA. No difference was observed regarding saturated
fatty acids in two studies (Motard-B
elanger et al. 2008; Three studies evaluated the relationship between body
Gebauer et al. 2015). On the specific study of Motard- weight and the consumption of the two sources of TFA
B
elanger et al., minor differences were observed in the (Wanders et al. 2010; Motard-B
elanger et al. 2008; Tardy
intake of monounsaturated fatty acids (MUFA) and polyun- et al. 2009) In a crossover study by Motard-B
elanger et al.,
saturated fatty acids (PUFA) between diets. In the higher subjects weight had no significant change between rTFA and
dose intervention with rTFA, the consumption of MUFA iTFA diets and a significant difference in waist circumfer-
and PUFA was similar to the iTFA diet, but lower than the ence was observed between diets, but it was no longer sig-
one registered in a moderate rTFA diet. nificant when baseline values were not included in the
analysis. Nevertheless, in Tardy et al. study, body weight
decreased in all intervention diets as well as waist circumfer-
Lipid profile
ence and BMI, but these changes were not significant. In
Six studies (Wanders et al. 2010; Chardigny et al., 2008; Wanders et al. trial, body weight reduced with all interven-
Motard-B
elanger et al. 2008; Gebauer et al. 2015; Tardy tion arms, and no difference was observed between iTFA
et al. 2009; Radtke et al. 2017) evaluated the association of and rTFA diets.
the consumption of different sources of TFA and the lipid One of the selected trials also had data for anthropometry
profile, as shown in Table 2. Four trials (Wanders et al. (Desgagn
e et al. 2016). However, the results were not pre-
2010; Motard-B
elanger et al. 2008; Radtke et al. 2017; sented because it was part of the same sample population
Gebauer et al. 2015) showed that TFA, independent of the evaluated in other included study (Motard-B
elanger
source, increased TC. One study found a most favorable TC et al. 2008).
profile with rTFA (Wanders et al. 2010) and three
(Chardigny et al., 2008, Radtke et al. 2017; Gebauer et al.
Metabolic control
2015) with iTFA. In one study (Motard-B
elanger et al.
2008), although at the same dose of rTFA and iTFA, no sig- Five trials (Tardy et al. 2009; Gebauer et al. 2015; Engberink
nificant difference was observed—the increase of TC and et al. 2012; Desgagn
e et al. 2016; De Roos et al. 2011) pro-
LDL was dependent of the rTFA dose. vided data to evaluate the metabolic control as shown in
Regarding cholesterol fractions, LDL cholesterol levels Table 3. Three studies (Tardy et al. 2009; Gebauer et al.
increased after any TFA diets in five studies (Wanders et al. 2015; De Roos et al. 2011) investigated the effect of different
2010; Chardigny et al., 2008; Motard-B
elanger et al. 2008; sources of TFA on insulin levels and sensitivity, measured
Gebauer et al. 2015; Radtke et al. 2017) and had no effect in by HOMA, and fasting blood glucose. No changes through
one (Tardy et al. 2009). Three studies observed a greater intervention with the different sources of TFA were found.
increase in LDL with rTFA compared to iTFA (Chardigny Blood pressure was assessed by two studies (Tardy et al.
et al., 2008; Gebauer et al. 2015; Radtke et al. 2017). In 2009; Gebauer et al. 2015; Engberink et al. 2012; Desgagn
e
Gebauer’s study, a clinical reduction (data not analyzed) was et al. 2016). Both trials observed no difference effect on sys-
observed in all three arms compared to baseline LDL. tolic and diastolic BP between the iTFA or rTFA intake. On
According to Motard-B
elanger et al., an inverse dose- the other hand, systolic and diastolic BP reduced when com-
response may be observed with the rTFA intake and the pared to the baseline values (greater reduction on systolic
decrease in HDL. No difference appears between iTFA and BP with the rTFA diet; slightly greater decrease on diastolic
rTFA at the same dose. Chardigny et al. also observed a BP with the iTFA) (Engberink et al. 2012).
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 2055

Table 2. Main results on lipid profile according to the intervention.

Systematic
Author, year Effect of ruminant TFA (delta) Effect of industrial TFA (delta) Main study result review conclusion
Total cholesterol
Chardigny et al., 2008 0.30 mmol/l 12.20 mmol/l TC was significantly higher in TFA could increases TC
women (p < 0.001) consuming rTFA seems to present
rTFAs than in those consuming a greater effect than
iTFAs, but not in men (p ¼ 0.642) iTFA
Motard-B
elanger et al. 2008 Moderate: þ 0.40 mmol/l þ0.56 mmol/l TC increased after the consumption Women had a different
High: þ0.60 mmol/l of the iTFA (p < 0.05) and hrTFA effect than men
(p < 0.05) in comparison with
mrTFA, although, in comparison
with the control diet, none of the
differences reached significance
Gebauer et al. 2015 þ0.08 nmol/l 0.05 nmol/l TC was higher after the
consumption of the iTFA
(p ¼ 0.023) and rTFA (p < 0.0001)
in comparison with the control
diet, with a greater effect with
the rTFA diet (p ¼ 0.0004).
Radtke et al. 2017 þ0.5 mmol/l þ0.06 mmol/l TC increased after the consumption
of the rTFA in comparison with
the control (p < 0.05) and iTFA
(p < 0.05) diets
Tardy et al. 2009 þ0.06 mmol/l 0.01 mmol/l TC tend to increase with rTFA diet,
although no difference effect on
TC was observed between diets
Wanders et al. 2010 þ0.08 mmol/l þ0.18 mmol/l TC increased in both rTFA
(p < 0.001) and iTFA (p < 0.001)
diets, in comparison with control
diet, with a greater increase with
the iTFA diet (p < 0.05)
LDL cholesterol
Chardigny et al., 2008 þ0.40 mmol/l 7.60 mmol/l LDL was significantly higher in TFA could increase LDL
women consuming rTFAs cholesterol
(p ¼ 0.001) than in those rTFA seems to present
consuming iTFAs, but not in greater effect than iTFA
men (p ¼ 0.99) Women had a different
Gebauer et al. 2015 0.12 nmol/l 0.02 nmol/l LDL-c was greater with the iTFA effect than men
(p ¼ 0.0028) and rTFA
(p < 0.0001) diets in comparison
with the value after the control
diet, although a clinical decrease
is observed in all arms compared
to the baseline. A greater value
of LDL was observed with the
rTFA diet (p ¼ 0.0114) compared
to iTFA
Motard-B
elanger et al. 2008; Moderate: þ0.66 mmol/l þ0.86 mmol/l LDL-c increased after the
High: consumption of the iTFA (p ¼ 0.02)
þ 0.91 mmol/l and h-rTFA (p ¼ 0.002) in
comparison with m-rTFA. h-rTFA
was also higher than control
diet (p ¼ 0.03)
Radtke et al. 2017 þ0.51 mmol/l þ0.1 LDL-c increased after the
consumption of the rTFA in
comparison with the control
(p < 0.05) and iTFA (p < 0.05)
diets. Comparing to baseline, a
tend increase in LDL was
observed for control and for rTFA
Tardy et al. 2009 þ0.09 mmol/l þ0.03 mmol/l LDL tend to increase with both
types of TFA intervention, but no
difference between interventions
was observed
Wanders et al. 2010 þ0.05 mmol/l þ0.13 mmol/l LDL-c increased in both rTFA
(p < 0.001) and iTFA (p < 0,001)
diets, in comparison with control
diet, with a greater increase with
the iTFA diet (p < 0.05)
HDL cholesterol
Chardigny et al., 2008 2.60 mmol/l 4.50 mmol/l HDL concentrations were TFA could lower HDL
significantly (p ¼ 0.012) lower in cholesterol
women with consumption of iTFA seems to present
iTFAs than with consumption of a greater effect than
rTFAs, but not in men (p ¼ 0.743) rTFA
(continued)
2056 B. J. F. VERNEQUE ET AL.

Table 2. Continued.
Systematic
Author, year Effect of ruminant TFA (delta) Effect of industrial TFA (delta) Main study result review conclusion
Gebauer et al. 2015 þ0.19 nmol/l þ0.16 nmol/l HDL was higher after the Women had a different
consumption of rTFA (p < 0.011) effect than men
in comparison with control and
iTFA (p ¼ 0.003) diets, although a
clinical increase is observed in all
arms compared to the baseline
Motard-B
elanger et al. 2008 Moderate: þ0.03 mmol/l 0.02 mmol/l HDL-c decrease after the h-rTFA
High: 0.03 mmol/l (p ¼ 0.02) in comparison with m-
rTFA diet. No difference was
observed between iTFA and rTFA at
the same dose
Radtke et al. 2017 0.12 mmol/l 0.01 mmol/l The experimental diets had no
effect on HDL-c
Tardy et al. 2009 0.02 mmol/l 0.02 mmol/l HDL-c decreased in all groups,
independently of dietary
intervention (p < 0.0001)
Wanders et al. 2010 0.06 mmol/l 0.05 mmol/l HDL-c was lower after the
consumption of the rTFA
(p < 0.001) and iTFA (p < 0.001),
in comparison with control diet.
Without difference between rTFA
and iTFA diets
Triglycerides
Chardigny et al., 2008 þ9.50 mmol/l 0.60 mmol/l TG was significantly (p ¼ 0.001) TFA could increase TG
higher in women consuming rTFA seems to have a
rTFAs than in those consuming greater impact,
iTFAs, but not in although significant
men (p ¼ 0.994). effect was observed
Gebauer et al. 2015 þ0.04 nmol/l 0.01 nmol/l TG was higher after the rTFA diet, with iTFA
in comparison with iTFA Women had a different
(p ¼ 0.029). Without difference effect than men
between other groups
Motard-B
elanger et al. 2008 Moderate: 0.19 mmol/l 0.17 mmol/l No significant difference was
High: 0.15 mmol/l observed between diets, although a
trend reduction was observed in
three arms compared to baseline
Radtke et al. 2017 þ0.13mmol/l þ0.03mmol/l The rTFA tend to increase TG
compared to iTFA and control
diet, although a statistical
difference was not reached
Tardy et al. 2009 0.03 mmol/l 0.01 mmol/l The experimental diets had no
effect on TG
Wanders et al. 2010 þ0.01 mmol/l þ0.10 mmol/l TG was higher after the iTFA diet
(p < 0.001) in comparison with
control (p < 0.001) and rTFA
(p < 0.015) diets. Without
difference between final values
observed on groups
¼ p < 0.05 compared with baseline values.
¼ Data presented in median.
h-rTFA ¼ High Ruminant Trans Fatty Acid; m-rTFA ¼ Moderate Ruminant Trans Fatty Acid; rTFA ¼ Ruminant Trans Fatty Acid; iTFA ¼ Industrial Trans Fatty Acid.

Risk of bias was the lack of time to minimize any carry-over effect. In
the study of Gebauer et al., the deviations from the intended
The overall risk of bias of the RCT varied from low to high
interventions were the main source of bias, therefore it was
(Wanders et al. 2010; Radtke et al. 2017; De Roos et al.
rated as a high risk of bias. The risk of bias assessment of
2011; Motard-B
elanger et al. 2008; Desgagn
e et al. 2016;
included studies is summarized in Table S2
Engberink et al. 2012; Tardy et al. 2009; Gebauer et al. 2015;
Chardigny et al.,2008). Only four trials (Wanders et al. 2010; (Supplementary material).
Motard-B
elanger et al. 2008; Desgagn
e et al. 2016;
Chardigny et al.,2008) presented a low risk of bias. Most tri- Discussion
als presented concerns about the randomization process,
especially due to the lack of information on randomization The present systematic review addresses the difference
sequence concealment and lack of comparison between base- between the consumption of distinct sources of TFA and
line characteristics of the participants. the cardiometabolic risk. While the deleterious effect of
Deviations from the intended interventions and selection the iTFA intake is unanimously accepted (Stender, Astrup,
of the reported result were also steps with concerns on the and Dyerberg 2012), the question remains unclear regard-
primary studies. Among crossover trials, the major concern ing the intake of rTFA. However, the results showed that
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 2057

Table 3. Main results on metabolic parameters according to the intervention.

Author, year Effect of ruminant TFA (delta) Effect of industrial TFA (delta) Main study result Systematic review conclusion
Glycemia
De Roos et al. 2011 NA The experimental diets had no No effect
effect on fasting glycemia
Gebauer et al. 2015 þ0.11 mmol/l þ0.09 mmol/l The experimental diets had no
effect on fasting glycemia
Tardy et al. 2009 0.10 mmol/l 0.10 mmol/l The experimental diets had no
effect on fasting glycemia
HOMA
De Roos et al. 2011 NA The experimental diets had no
effect on insulin sensitivity
Gebauer et al. 2015 NA The experimental diets had no No effect
effect on insulin sensitivity
Tardy et al. 2009 0.47 þ0.14 The experimental diets had no
effect on insulin sensitivity
Insulin
De Roos et al. 2011 NA The experimental diets had no No effect
effect on insulinemia
Gebauer et al. 2015 NA The experimental diets had no
effect on insulinemia
Tardy et al. 2009 1.20 mIU/mL þ0.90 mIU/mL The experimental diets had no
effect on insulinemia
Blood pressure systolic
Desgagn
e et al. 2016 NA The experimental diets had no No effect
effect on systolic BP
Engberink et al. 2012 1.70 mmHg 0.50 mmHg The experimental diets had no
effect on systolic BP
Blood pressure diastolic
Desgagn
e et al. 2016 NA Diastolic BP increased in both Controversial effect
TFA diets compared to control
diet, although after
adjustments it was no longer
significant
Engberink et al. 2012 0.60 mmHg 0.90 mmHg No significant differences in
diastolic BP among the diets.
¼ p < 0.05 compared with baseline values.
NA ¼ No baseline data available; h-rTFA ¼ High Ruminat Trans Fatty Acid; m-rTFA ¼ Moderate Ruminat Trans Fatty Acid; rTFA ¼ Ruminant Trans Fatty Acid;
iTFA ¼ Industrial Trans Fatty Acid.

both sources of TFA can increase cardiometabolic In all included studies TFA delivery vehicles were mainly
risk parameters. butter, margarine, and cheese. It is known it’s important to
At levels up to 1.5%–7% of energy, the effect of rTFA consider the whole food matrix and not just the isolated
seems to be greater than iTFA and it seems to be different nutrients. The source of iTFA is ultra-processed food and it
according to gender, being greater in women. Our analysis also contains lots of food additives, sugar, and salt, which
suggests that the intake of rTFA can increase TC and LDL are known to have deleterious health effects (Schnabel et al.
at higher levels than the iTFA, apparently with dose-depend- 2019). On the other hand, the food sources of rTFA, milk,
ent effect. Also, both sources seem to lower HDL, but iTFA dairy products, and meat, provide a considerably greater
seems to present a greater effect than rTFA. amount of saturated fatty acids when compared with the
The results suggested a more hypercholesterolemic food sources of iTFA. Saturated fatty acids in meat are com-
effect with rTFA than iTFA and these associations were monly linked to hypercholesterolemic effects (Bergeron et al.
stronger in high doses of rTFA. Contrary, in observational 2019). However, the literature suggests that the unique com-
studies with rTFA in a more similar amount to the con- bination of nutrients and bioactive components may be
sumed TFA intake by the adult population, the effect of responsible for a neutral or beneficial impact on cardiovas-
rTFA was not as harmful as iTFA for coronary heart dis- cular health (Zhong et al. 2019).
ease (Bendsen et al. 2011). Ruminant TFA are generally Despite this, for some risk markers, rTFA seems to be
present in food at low levels (up to 8% of total fatty acids less harmful than iTFA, such as for HDL, or even present a
in milk fat), whereas iTFA may reach up to 61% of total neutral effect, like for TG, glycemia, insulin resistance, and
fatty acids in pastries and shortenings (Gayet-Boyer et al. blood pressure. In the Gebauer et al., study vaccenic acid
2014; Mozaffarian et al. 2006). The daily average intake of intake, the main rTFA, increased HDL cholesterol and apoli-
rTFA by the adult population is normally low (around poprotein AI. Previous quantitative review concluded that
1.2 g/day or  0.5% of energy intake (Doell et al. 2012). the effect of rTFA on the LDL to HDL ratio was less than
Thus, it is important to emphasize that, despite the bad the effect of iTFA although the difference was not significant
results on the lipid profile observed in this systematic (Brouwer, Wanders, and Katan2010; Wanders et al. 2010).
review, the amounts of rTFA consumed by the subjects Regarding the composition of the diets, the results
were higher than the actual amount consumed routinely showed differences in the consumption of saturated and
by adults. unsaturated fatty acids between the intervention arms in
2058 B. J. F. VERNEQUE ET AL.

relation to most studies (Wanders et al. 2010; Chardigny intervention periods were short than 3 to 4 weeks. Most tri-
et al., 2008; De Roos et al. 2011; Motard-B
elanger et al. als presented some risk of bias; therefore, the certainty of
2008; Engberink et al. 2012). The Motard-B
elanger et al. the overall evidence is influenced. All trials evaluating rTFA
study presented differences in the amounts of unsaturated used dairy products as the source of TFA, any of the studies
fatty acids between the iTFA diet and rTFA (moderate and made adjusted analysis with total lipids or its fractions. Also,
high) diets. In this study, the levels of HDL increased after the amount of rTFA provided was higher than the daily
the consumption of moderate rTFA (data not assessed in average intake of the adult population and the proportion of
the study). The MUFA have been related to higher levels of saturated and unsaturated fatty acids were different in
HDL, an important factor to reduce CVD (Panth et al. 2018; some studies.
Tholstrup et al. 2006). Regarding macronutrient composition The present study has several strengths. The review as
of the intervention diet, although it varied between studies, conducted following a rigorous methodology based on
the proportion of each macronutrient was balanced between Cochrane Handbook for Systematic Reviews of Interventions
diets. However, since total lipids and carbohydrate can dir- (Higgins et al. 2019); a comprehensive literature search,
ectly effect some cardiometabolic risk factors (Liu et al. including four electronic databases (PubMed, Embase, Web
2019), authors should have performed multivariable analysis of Science, Central Cochrane); a well-defined eligibility crite-
aiming to minimize its effects. ria which prioritize only studies focused on the sources of
The total intake of TFA in the rTFA diet was higher in TFA, minimizing any differences resulting from other
three studies (Wanders et al. 2010; Engberink et al. 2012; nutrients. All this methodological care showed the weakness
Gebauer et al. 2015), and lower in one (Tardy et al. 2009) in of the available studies and the need to make efforts to
which more TFA was offered in the iTFA diet. The main investigate the atherogenic effects of rTFA on cardiometa-
differences occurred when adjustments in energy intake bolic risk factors. Additionally, considering the divergence of
were necessary to maintain body weight. Thus, the portion the TFA doses used in interventions and the estimated
sizes were adjusted, so the nutrient content of the diets amounts on population, more long and parallel RCT are
remained the same for all participants, regardless of the needed to say if the TFA may present a different effect
energy intake. Therefore, the real amount of TFA and other according to their food source.
nutrients varied. This is a study limitation. Once choosing In summary, this systematic review showed that both
the caloric restriction, it was not possible to achieve a simi- sources of TFA can increase cardiometabolic risk parame-
lar amount on TFA in all compared diets, which suggests an ters, especially lipid profile. rTFA seems to be less harmful
impact and influence on the results obtained. The influence than iTFA for HDL cholesterol, although for TC and LDL it
on the results may be related to a possible dose-response may be worse. It is recommend evaluating the whole com-
effect of TFA. A meta-analysis of cohort studies indicates position of the food as well since other nutrients such as
that the dietary TFA intake had a direct dose-response asso- saturated fatty acids have an important effect on cardiometa-
ciation with CVDs risk (Zhu, Bo, and Liu 2019). bolic risks. The implementation of political policies to avoid
Although any significant difference between groups was iTFA would improve the quality of the dietary patterns and,
found in Chardigny’s study, when all sample data were ana- probably, the amount of rTFA in natural sources would be
lyzed, an association between rTFA diet and higher levels of low and would probably not result in negative outcomes,
TC, LDL, HDL, and TG in comparison with iTFA diet was contributing to health promoting of the population.
found only in women. The literature demonstrates that the
intake of TFA can affect men and women differently Declaration of interest
(Jakobsen et al. 2008). The strong differences found between
genders suggest that the regulation of lipid metabolism by No potential conflict of interest was reported by the authors.
TFA can be mediated by sex hormones (Knop 2018). Stusy
suggests that the hormones estrogens and androgens affect Funding
in opposite ways fat metabolism (Palmisano et al. 2018).
More research on the subject is needed. This paper received support from Universidade Federal de Minas
Gerais/Portuguese: Este trabalho recebeu apoio da Universidade
Seven studies included in our review were cross-over tri- Federal de Minas Gerais.
als and washout periods were absent in most of them, there-
fore the carry-over effect could be present and influenced
the results (Shen, 2006). In addition, most of included trials
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