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Trans-fatty acids and mortality in patients referred for coronary angiography: The Ludwigshafen Risk and Cardiovascular Health Study


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Aims: Trans fatty acids (TFAs) are generated by the food industry and also occur naturally in trace amounts in dairy products. For the latter, beneficial health effects have been claimed, while there are numerous reports about TFA of industrial origin being hazardous to human health. Therefore, we aimed to investigate the association of TFA with mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Methods and results: The fatty acid composition of erythrocyte membranes was analysed using the HS-Omega-3 Index(®) methodology in 3259 participants of the LURIC study at baseline. During a median of 10.0 years of follow-up, a total of 975 (29.9%) study participants died, 614 (18.8%) from cardiovascular causes including 254 (7.8%) sudden cardiac deaths (SCDs). Association of TFA with clinical outcome was investigated with Cox proportional hazards regression. Total TFAs were inversely associated with mortality due to cardiovascular causes or SCD. This was mainly driven by the naturally occurring TFA C16:1n-7t (trans-palmitoleic acid). The reduced risk of SCD associated with C16:1n-7t persisted after multivariate adjustment with a hazard ratio of 0.63 (0.46-0.86) for the third tertile compared with the first tertile. There was no association of any TFA subgroup with an increased risk of adverse outcomes. Conclusions: In contrast to previous findings, the low concentrations of total TFAs found in LURIC were inversely associated with adverse cardiac outcomes. While the naturally occurring TFA C16:1n-7t was associated with reduced risk, no increased risk was found for industrially produced TFAs.
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Trans fatty acids and mortality in patients referred
for coronary angiography: the Ludwigshafen Risk
and Cardiovascular Health Study
Marcus E. Kleber1, 2*, Graciela E. Delgado1, Stefan Lorkowski2, 3, Winfried Ma
¨rz1, 4, 5,
and Clemens von Schacky6,7
Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany;
Competence Cluster of Nutrition and
Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany;
Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany;
Clinical Institute of Medical and Chemical
Laboratory Diagnostics, Medical University of Graz, Graz, Austria;
Synlab Academy, Synlab Services GmbH, Mannheim, Germany;
Omegametrix, Martinsried, Germany; and
Department of Preventive Cardiology, Medizinische Klinik und Poliklinik I, Munich University, Munich, Germany
Received 10 November 2014; revised 6 July 2015; accepted 17 August 2015
Aims Trans fatty acids (TFAs) are generated by the food industry and also occur naturally in trace amounts in dairy products.
For the latter, beneficial health effects have been claimed, while there are numerous reports about TFA of industrial
origin being hazardous to human health. Therefore, we aimed to investigate the association of TFAwith mortality in the
Ludwigshafen Risk and Cardiovascular Health (LURIC) study.
and results
The fatty acid composition of erythrocyte membranes was analysed using the HS-Omega-3 Index
methodology in
3259 participants of the LURIC study at baseline. During a median of 10.0 years of follow-up, a total of 975 (29.9%)
study participants died, 614 (18.8%) from cardiovascular causes including 254 (7.8%) sudden cardiac deaths (SCDs).
Association of TFA with clinical outcome was investigated with Cox proportional hazards regression. Total TFAs
were inversely associated with mortality due to cardiovascular causes or SCD. This was mainly driven by the naturally
occurring TFA C16:1n-7t (trans-palmitoleic acid). The reduced risk of SCD associated with C16:1n-7t persisted after
multivariate adjustment with a hazard ratio of 0.63 (0.46 0.86) for the third tertile compared with the first tertile.
There was no association of any TFA subgroup with an increased risk of adverse outcomes.
Conclusions In contrast to previous findings, the low concentrations of total TFAs found in LURIC were inversely associated with
adverse cardiac outcomes. While the naturally occurring TFA C16:1n-7t was associated with reduced risk, no increased
risk was found for industrially produced TFAs.
Keywords Trans fatty acids Trans-palmitoleic acid Mortality Cardiovascular mortality Sudden cardiac death
Trans fatty acids (TFAs) are unsaturated fatty acids containing double
bonds in trans configuration. In animals and plants, fatty acids usually
occur in cis configuration. However, in milk, dairy products, and
meat, some trans-isomers occur naturally in small quantities. Other
TFAs are ‘man-made’ by industrial hardening of unsaturated fats. If
oils are only partially hydrogenated, a portion of cis-isomers is con-
verted into trans-isomers (industrially produced TFAs, IP-TFAs).
While beneficial health effects have been claimed for the naturally
occurring TFA vaccenic acid or trans-palmitoleic acid in some
there are numerous reports suggesting that IP-TFA may
be hazardous to human health.
Industrially produced trans fatty
acids have been linked to increased risks for a number of diseases
that are associated with modern Western lifestyle, such as cardio-
vascular disease (CVD), stroke, diabetes, infertility, Alzheimer’s dis-
ease, or certain cancers. Therefore, a range of actions has been
taken to reduce the intake of IP-TFA on a population level. These
measures are effective as demonstrated by decreasing levels of
IP-TFAs in the USA.
In Europe, intake of IP-TFA has traditionally
been lower compared with the USA where major sources for
TFAs have been cakes, cookies, pies and pastries.
*Corresponding author. Tel: +49 621 383 3019, Fax: +49 621 383 3804, Email: marcus.kleber@medma.uni-heidelb
Published on behalf of the European Society of Cardiology. All rights reserved. &The Author 2015. For permissions please email:
European Heart Journal
European Heart Journal Advance Access published September 22, 2015
by guest on November 7, 2015 from
It is unclear whether variations of TFAs at low concentrations are
associated with CVD risk and how the highest concentration of TFA
that may be harmless should be defined.
Equally open today is the
question whether the same thresholds should be applied to both
IP-TFA and ruminant TFA. Therefore, it has been the aim of our
study to investigate the association of total TFA concentrations
and individual TFA species measured in the membrane of red blood
cells with CVD and mortality in a large and well-characterized
clinical cohort, the Ludwigshafen Risk and Cardiovascular Health
(LURIC) study.
Study populations
The LURIC study included 3316 Caucasians hospitalized for coronary
angiography between 1997 and 2000 at a tertiary care centre in south-
western Germany.
Clinical indications for angiography were chest
pain or a positive non-invasive stress test suggestive of myocardial is-
chaemia. To limit clinical heterogeneity, individuals suffering from acute
illnesses other than acute coronary syndrome, chronic non-cardiac dis-
eases, and a history of malignancy within the past 5 years were excluded.
The study was approved by the ethics committee at the ‘Landesa¨rzte-
kammer Rheinland-Pfalz’ and was conducted in accordance with the
‘Declaration of Helsinki’. Informed written consent was obtained from
all participants.
Laboratory procedures
Fasting blood samples were obtained by venipuncture in the early morn-
ing. Cholesterol and triglycerides (TG) were measured with enzymatic
reagents from WAKO (Neuss, Germany) on an Olympus AU640 ana-
lyser (Centre Valley, PA). Lipoproteins were separated by a combined
ultracentrifugation– precipitation method (b-quantification) as de-
scribed previously.
Erythrocyte fatty acid composition was analysed
according to the HS-Omega-3 Index
methodology as described previ-
Fatty acid methyl esters were generated from erythrocytes by
acid transesterification and analysed by gas chromatography using a
GC2010 gas chromatograph (Shimadzu, Duisburg, Germany) equipped
with a 100-m SP2560 column (Supelco, Bellefonte, PA) using hydrogen
as carrier gas. Fatty acids were identified by comparison with a standard
mixture of fatty acids characteristic of erythrocytes. Results are given as
a percentage of total identified fatty acids after response factor correc-
tion. The chromatographic conditions allowed to separate the C16:1
trans-isomers and three trans-isomers of C18:2n6 (C18:2n6tt,
C18:2n6ct, and C18:2n6tc). The individual trans-isomers of C18:1 (i.e.
6 through C18:1
13) could not be separated, but appeared as
two blended peaks, eluting just ahead of oleic acid. The areas of these
two peaks were added and referred to as C18:1t. The sum of the five
TFAs had a coefficient of variation of 7%. The sum of C18:2n6tt,
C18:2n6ct, and C18:2n6tc is referred to as ‘C18:2t’, whereas the sum
of all measured TFAs is referred to as total TFAs.
Clinical definitions
Coronary artery disease (CAD) was defined as the presence of a visible
luminal narrowing (.20% stenosis) in at least one of the 15 coronary
segments according to the classification of the American Heart Associ-
ation. Diabetes mellitus was defined according to 2010 guidelines of the
American Diabetes Association as increased fasting (126 mg/dL) and/
or post-challenge (2 h after the 75 g glucose load 200 mg/dL) glucose
and/or elevated glycated haemoglobin (6.5%) and/or history of dia-
betes. Blood pressure was measured with an automated oscillometric
device (Omron MX4, Omron Healthcare GmbH, Hamburg, Germany)
while supine for at least 10 min. At least three consecutive measure-
ments of systolic and diastolic blood pressures were taken 30 s apart.
Hypertension was defined as a systolic and/or diastolic blood pressure
.140 and/or .90 mmHg or a significant history of hypertension. The
glomerular filtration rate was estimated by using the 2012 CKD-EPI
eGFRcreat-cys equation.
Self-reported physical exercise was mea-
sured on a scale ranging from 25 (extremely low) to +5 (extremely
high, athlete).
Definition of clinical endpoints
Information on vital status was obtained from local registries. Death cer-
tificates and medical records of local hospitals and autopsy data were
reviewed independently by two experienced clinicians who were
blinded to patient characteristics and who classified the causes of death.
In cases of disagreement or uncertainty concerning the coding of a spe-
cific cause of death, the decision was made by a principal investigator
(W.M.). During a median follow-up of 10.0 years (range: 0.111.9
years), 995 (30%) participants died. Cardiovascular mortality (CVM) in-
cluded the following categories: sudden cardiac death [SCD; n¼259
(12.8%)], fatal myocardial infarction [n¼106 (3.20%)], death due to
congestive heart failure [n¼148 (4.46%)], death immediately after
intervention to treat CAD [n¼26 (0.78%)], fatal stroke [n¼61
(1.84%)], and other causes of death due to CAD [n¼19 (0.57%)]. Infor-
mation for mortality is complete for all participants. The cause of death
of 23 individuals was unknown and these patients were included in cal-
culations of all-cause mortality but not in calculations considering differ-
ent causes of death. Trans fatty acid measurements were available for
3259 study participants.
Statistical analyses
The primary aim of our study was to examine the association of TFA
with fatal endpoints, namely all-cause mortality, CVM, and SCD, which
we did by building Cox proportional hazard models. As the distribution
of individual TFA was slightly skewed to the left, wechose to stratify our
patients into tertiles of TFAs. The first tertile of total TFAs included all
values 0.83% of all fatty acids in the membrane of erythrocytes, the
second tertile encompassed all values from 0.84 to 1.08%, and the third
tertile included all values 1.09%. The functional form of covariates was
analysed by calculating Martingale residuals and the proportional hazard
assumption was checked by examination of scaled Schoenfeld residuals.
Adjustments were carried out including known confounding variables
for CVM.
We also adjusted the data distribution by inverse probability weight-
ing so that each tertile’s weighted distribution matched that of the whole
cohort, thereby balancing the subgroups for the confounding variables.
We plotted the reweighted distribution of confounding variables for
each C16:1n7t tertile to check whether the balancing worked. A
weighted Cox model was calculated and we report the result of the ro-
bust score test as implemented in the coxph function in R that corre-
sponds to a log-rank test corrected for weighting.
The distribution of all variables was examined visually by viewing his-
tograms and by comparing mean and median values. Continuous data
are presented as the mean +standard deviation when normally distrib-
uted or as the median and 25th and 75th percentile for non-normally
distributed variables. Categorical data are presented as percentages.
Statistical differences between groups and continuous variables were
determined using analysis of variance. Non-normally distributed vari-
ables were log-transformed before entering analysis in order to achieve
an approximately normal distribution. The x
test was used for categor-
ical variables. Correlation and partial correlation adjusted for age and
M.E. Kleber et al.Page 2 of 7
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sex between TFAs and biomarkers were analysed by Spearman’s r. All
tests were two sided and Bonferroni-adjusted thresholds for signifi-
cance were calculated as indicated for the respective tables to correct
for multiple testing. All analyses were carried out using the SPSS 21.0
statistical package (IBM SPSS, USA) and R v3.1.1 (http://www.r-project.
Trans fatty acids were measured in 3259 participants of the LURIC
study who all underwent coronary angiography. They ranged from
0.27 to 2.40% of total fatty acids in erythrocyte membranes with a
mean of 0.96 +0.26%. Total TFAs were composed of 61.8 +0.1%
C18:1t isomers, 22.4 +0.1% C18:2t isomers, and 15.8 +0.1%
C16:1n-7t isomers. Study demographics are shown in Table 1.
Correlation of total trans fatty acids with
biomarkers at study baseline
Study characteristics according to tertiles of total TFAs as well as
specific subgroups of TFAs are shown in Supplementary material
online, Tables S1 S4. Partial correlation coefficients adjusted for
age and gender are shown in Table 2.
Percentages of total TFAs were directly correlated with LDL-C
and inversely correlated with body mass index (BMI), waist-to-hip
ratio, physical exercise, blood pressure, TG, and markers of glucose
metabolism (fasting glucose, fasting insulin, HbA1c, and homeostasis
model assessment (HOMA) index). These correlations were largely
similar for the subgroups of C16:1n-7 and C18:1t isomers, but not
for the subgroup of C18:2t isomers (Supplementary material online,
Table S5). About 50% of the LURIC participants were receiving
lipid-lowering therapy (mostly statins) at baseline with a lower per-
centage in the higher tertiles of total TFAs. We, therefore, repeated
the analyses restricted to those patients not receiving lipid-lowering
therapy (Supplementary material online, Table S6). Several associa-
tions then turned insignificant, which is likely due to the reduced
power following the approximate bisection of the sample. Most
notably, however, the strong associations of TFAs with BMI, TG,
blood pressure, markers of glucose metabolism, and diabetes melli-
tus remained almost unchanged.
Trans fatty acids and mortality
We examined the association of TFA with all-cause mortality, CVM,
and SCD by means of Cox regression adjusted for age and gender
(Model 1) or additionally adjusted for traditional risk factors and
markers significantly associated with TFA, namely BMI, LDL-C,
HDL-C, TG, fibrinogen, smoking, hypertension, diabetes, estimated
glomerular filtration rate, and lipid-lowering therapy (Model 2). In-
creasing total TFAs were associated with lower CVM and SCD in
Model 1 (Table 3). C16:1n-7t was associated with reduced all-cause
mortality, CVM as well as SCD in Model 1.
In Model 2, only the association of the highest tertile with de-
creased risk of SCD remained statistically significant at a hazard ratio
(HR; 95% confidence interval) of 0.63 (0.46 0.86), and Pfor trend
across tertiles was also significant (Table 3). Adjusted survival curves
are shown in Figure 1. The distribution of confounding variables was
balanced by inverse variance weighting. Resulting HRs were similar
to the ones obtained by simple adjustment with HR of 0.82 (0.61–
1.12) and 0.67 (0.48 0.93) for the second and the third tertile, re-
spectively. The C18:1t and C18:2t isomers did not show any associ-
ation with endpoints except for an association of the middle tertile
of C18:1t with SCD. Of note, we did not observe any increased risk
for any of the investigated endpoints for any of the TFAs. This was
also true for the individual C18:2t isomers C18:2n6tt, C18:2n6ct,
and C18:2n6tc (Supplementary material online, Table S7).
Table 1 Study demographics
Age ( years) 62.7 +10.6
Male sex (%) 69.7
BMI (kg/m
) 27.5 +4.07
Waist-to-hip ratio 0.96 +0.08
Systolic BP (mmHg) 141 +23.6
Diastolic BP (mmHg) 81.0 +11.5
LDL-C (mg/dL) 116 +34.3
HDL-C (mg/dL) 38.8 +10.8
TG (mg/dL) 147 (109 201)
Fasting glucose (mg/dL) 102 (93.6–118)
Coronary artery disease (%) 77.9
Hypertension (%) 72.9
Diabetes (%) 39.8
Lipid-lowering therapy (%) 48.6
Shown are mean +standard deviation or median (25th –75th percentile).
BMI, body mass index; BP, blood pressure.
Table 2 Partial correlation of total trans fatty acids
with biomarkers adjusted for age and sex
Total TFAs
BMI (kg/m
)20.137 ,0.001
Waist-to-hip ratio 20.042 0.018
Physical exercise 20.057 0.001
Systolic BP (mmHg) 20.065 ,0.001
Diastolic BP (mmHg) 20.075 ,0.001
LDL-C (mg/dL) 0.042 0.016
HDL-C (mg/dL) 20.012 0.507
TG (mg/dL) 20.132 ,0.001
Fasting glucose (mg/dL) 20.147 ,0.001
Fasting insulin (mmol) 20.052 0.003
HbA1c (%) 20.192 ,0.001
HOMA index 20.083 ,0.001
High-sensitivity C-reactive protein (mg/dL) 20.004 0.839
Fibrinogen (mg/dL) 20.069 ,0.001
SAA (mg/L) 0.009 0.589
NT-proBNP (ng/mL) 0.027 0.129
BMI, body mass index; BP, blood pressure; TFAs, trans fatty acids; SAA, serum
amyloid A; NT-proBNP, N-terminal of the prohormone brain natriuretic peptide.
*After Bonferroni adjustment for 16 tests, a Pvalue of 0.0031 could be regarded as
Trans fatty acids and mortality in patients Page 3 of 7
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Table 3 Association of tertiles of trans fatty acids with mortality, cardiovascular mortality, and sudden cardiac death
Total TFAs C16:1n-7t C18:1t C18:2t
Model 1 Model 2 Model 1 Model 2 Model 1 Model 2 Model 1 Model 2
HR (95% CI) PHR (95% CI) PHR (95% CI) PHR (95% CI) PHR (95% CI) PHR (95% CI) PHR (95% CI) PHR (95% CI) P
All-cause mortality
First 292 1
Second 399 0.87 (0.74
0.065 0.91 (0.78
0.241 0.85 (0.73
0.037 0.89 (0.76
0.130 0.87 (0.74
0.073 0.88 (0.75
0.106 0.89 (0.76
0.139 0.92 (0.79
Third 284 0.86 (0.73
0.072 0.92 (0.78
0.345 0.81 (0.69
0.005 0.88 (0.76
0.116 0.90 (0.77
0.186 0.94 (0.81
0.476 0.96 (0.81
0.630 1.00 (0.84
0.117 0.473 0.012 0.189 0.176 0.269 0.300 0.463
Cardiovascular mortality
First 196 1
Second 240 0.77 (0.64
0.008 0.82 (0.68
0.051 0.87 (0.71
0.140 0.92 (0.76
0.398 0.82 (0.67
0.042 0.83 (0.68
0.069 0.86 (0.71
0.139 0.91 (0.75
Third 178 0.79 (0.64
0.029 0.87 (0.70
0.194 0.75 (0.62
0.003 0.85 (0.70
0.106 0.89 (0.74
0.257 0.95 (0.78
0.603 0.88 (0.71
0.222 0.93 (0.75
0.019 0.142 0.013 0.268 0.125 0.174 0.301 0.631
Sudden cardiac death
First 100 1
Second 80 0.52 (0.39
,0.001 0.56 (0.42
,0.001 0.74 (0.55
0.050 0.81 (0.60
0.157 0.70 (0.51
0.027 0.71 (0.52
0.034 0.85 (0.63
0.270 0.90 (0.67
Third 74 0.68 (0.50
0.013 0.74 (0.54
0.063 0.55 (0.41
,0.001 0.63 (0.46
0.004 0.92 (0.70
0.594 1.00 (0.74
0.981 0.87 (0.63
0.426 0.94 (0.67
,0.001 0.001 0.001 0.015 0.075 0.055 0.532 0.788
Model 1: adjusted for age and gender. Model 2: additionally adjusted for body mass index, LDL-C, HDL-C, logTG, log-fibrinogen, smoking, hypertension, diabetes, lipid-lowering therapy, and estimated glomerular filtration rate. A P-value of
,0.004 would be regarded as significant after Bonferroni correction for 12 tests (three outcomes and four TFA metrics).
HR, hazard ratio; TFAs, trans fatty acids; CI, confidence interval.
M.E. Kleber et al.Page 4 of 7
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We repeated the analyses for only those patients not on
lipid-lowering therapy. While the inverse association of total TFAs
with CVM became insignificant, the association of C16:1n-7t with
a reduced risk of all-cause mortality and SCD remained statistically
significant in Model 2 (Supplementary material online, Table S8).
Additional adjustment for antihypertensive medication, glycaemic
status, and alcohol intake only slightly attenuated the association
(Supplementary material online, Table S9).
Main findings
We analysed the association of the TFA content in erythrocyte
membranes with total mortality and a number of biomarkers for
cardiovascular risk in the well-characterized LURIC cohort including
patients of Caucasian origin scheduled for coronary angiography.
Our main findings are as follows: First, the concentrations of TFAs
in erythrocyte membranes were low compared with concentrations
reported for the USA at a similar time period (e.g. mean 0.96 +
0.3% in LURIC vs. 2.68 +0.8inHarriset al.
). Second, none of
the TFAs showed any association to adverse outcome. Finally, there
were statistically significant inverse associations with the risk of
CVM and SCD, especially for trans-palmitoleic acid.
Trans fatty acids, coronary heart disease,
and mortality
Initially, TFAs were considered as a safe replacement for saturated
fat. However, it has soon been noted that TFA increase LDL-C while
decreasing HDL-C.
Many studies consistently reported
associations between TFA consumption and coronary heart disease
A recent meta-analysis confirmed the direct association
of dietary TFA intake with coronary outcomes while there was no
association for circulating TFA.
Consequently, organizations like
the World Health Organization recommended reducing TFA diet-
ary intake to ,4% and several countries like Denmark introduced
legal bans. The German Society for Nutrition went even further by
recommending a daily TFA intake of ,1% of energy.
the FDA has concluded in June 2015 that partially hydrogenated oils
are no longer ‘Generally Recognized As Safe’.
While TFA concentrations in food products have declined mark-
edly in most industrialized countries over the last decades,
the decline was smaller in Eastern Europe
and concentrations re-
main high in several developing countries.
Furthermore, many
food products labelled as free of TFA still contain significant
amounts of TFAs.
Most studies suggesting increased risks associated with TFAs have
recruited patients decades ago when TFA concentrations were
higher than today.
26 28
Furthermore, most studies were conducted
in the USA, where TFA concentrations have traditionally been high-
er compared with Europe,
and used questionnaires to assess TFA
intake. These estimates may not be accurate because of incomplete
or inaccurate nutrient databases and the common under-reporting
of unhealthy foods like sugar or fat.
We, therefore, investigated
the association of TFA with all-cause mortality, CVM, and SCD in
the German LURIC cohort. Trans fatty acids were measured in
erythrocyte membranes using the Omega-3 Index technology that
allows a more objective way to estimate individual nutrient intake.
We observed rather low concentrations of TFA in our patients
and found no association with mortality. On the contrary, we found
that total TFAs were inversely associated with CVM and SCD in
age- and gender-adjusted models. After adjustment for other car-
diovascular risk factors, only the association with SCD remained
statistically significant.
Individual trans fatty acid and mortality
Looking at specific subgroups of TFAs, we did not find an association
with mortality for any of the TFA species that we were able to sep-
arate. For the mostly ruminant-derived C16:1n7t, there was a strong
inverse association with CVM and SCD with significant Pfor trend
values. For the C18:1t isomers, which are a mixture of ruminant-
derived and industrially produced TFA, Pvalues for trend were
almost nominally significant, while for the exclusively industrially
produced C18:2t isomers, there was no significant trend. This could
point towards an inverse association of ruminant-derived TFA only,
with industrially produced TFA showing no association (at least at
the concentrations found here).
C16:1n-7t, or trans-palmitoleic acid, is relatively specific for dairy
products, although it can be produced by the partial hydrogenation
of vegetable oils as well. Mozaffarian et al.
have recently reported
an inverse association of C16:1n-7t with incident diabetes, which is
consistent with our findings for prevalent diabetes (Supplementary
material online, Table S2), and animal models showed that the
cis-isomer C16:1n-7c is a major signalling lipid associated with im-
proved insulin sensitivity.
Similarly, the trans-isomer may act as a
signalling molecule, but so far no physiologic function has been
shown for C16:1n-7t.
Figure 1 Adjusted survival curves for sudden cardiac death.
Tertiles of C16:1n7t were balanced for body mass index, LDL-C,
HDL-C, logTG, log-fibrinogen, smoking, hypertension, diabetes,
lipid-lowering therapy, and estimated glomerular filtration rate
by inverse variance weighting. The inset shows the same data on
atruncatedyaxis. Hazard ratios (95% confidence interval) for
the second and third tertile compared with the first tertile were
0.82 (0.61 1.12) and 0.67 (0.48 0.93), respectively. The P-value
of the robust score test was 0.043.
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A number of reports examined the effect of dairy fats on CHD
(reviewed in 33). Animal studies have shown beneficial effects of
trans-vaccenic acid (C18:1n-11t), which constitutes 50– 80% of
TFAs in ruminant-derived fats,
on post-prandial lipid metabolism
and dyslipidaemia.
Interestingly, a recent report has shown that
C16:1n-7t may be synthesized in humans from C18:1n-11t with
conversion rates of 17%.
This conversion may explain the simi-
lar albeit mostly weaker associations for the C18:1t isomers com-
pared with C16:1n-7t because C18:1n-11t constitutes one of the
major TFA summarized in this variable. Alternatively, these associa-
tions could be due to direct effects of C18:1n-11t or another
A recent study has shown that circulating C18:2n-t/t was asso-
ciated with higher total mortality, CVM, and total CHD, whereas
C18:2n-t/c was positively related to total mortality, and nonfatal
CHD only after mutual adjustment.
Another study showed each
1 SD increase of plasma trans 18:2 to be associated with a 22% lower
risk of heart failure.
The differing results for TFA subspecies were
exploited by Liu et al.
to calculate a TFA index by dividing the sum
of industrially derived TFA by the sum of ruminant-derived TFA.
This TFA index was associated with 10-year CHD risk, but only
when the TFAs were measured in erythrocyte membranes.
Implications for public health
The TRANSFAIR study reported that the average TFA intake is
2.4 g/d for Germany, which is below 1% of total energy intake,
and that 79% of TFA intake was derived from milk and ruminant
The data had been collected in the 1990s and might, therefore,
be comparable with our LURIC patients, although the methodology
used in this study has been questioned.
Nevertheless, we also ob-
serve rather low TFA levels of only 0.96% of total fatty acids of
erythrocyte membranes. Our results are also in line with findings
by Kro¨ger et al.
who reported very similar erythrocyte concentra-
tions of C16:1n-7t and C18:1t isomers in the EPIC-Potsdam study. A
large percentage of total TFAs seems to be of natural origin and is
likely not derived from industrial processes. We observe no direct
association with mortality or CVM for any of the investigated TFA,
suggesting no need for efforts to further decreasing TFA in food in
Germany. Based on our data, it seems that an upper limit for the sum
of the trans-isomers of 18:1 and 18:2 of the mean of the upper ter-
tile, i.e. 1.04%, might be regarded as safe. However, while well within
the framework of our data, this concept also needs to be substan-
tiated by more research.
In contrast, the beneficial associations of C16:1n-7t with biomar-
kers and long-term cardiovascular outcome in our patients might al-
low speculating about the potential benefit of interventions to
increase the C16:1n-7t content of milk products or perhaps direct
supplementation. Of course, this concept has to be investigated in
more detail.
Strengths and limitations
All LURIC participants were of German origin and were recruited at
a tertiary referral centre. Therefore, our findings may not be repre-
sentative for a random population sample or applicable to other
ethnicities. Furthermore, TFAs were only measured once in baseline
samples and concentrations may vary over time due to dietary
changes, lifestyle changes, or diseases. As TFA concentrations in
our study were rather low, we could not examine the effect of high-
er concentrations (like they have been reported by previous stud-
ies) on mortality. Data on the dietary intake of fatty acids were
not available; we, therefore, cannot exclude that low TFA concen-
trations are caused by changed dietary patterns on physician advice
in patients with severe disease. Some potential confounding vari-
ables like socio-economic status, lifestyle, or drug treatment during
follow-up were also not available. The major strengthsof the LURIC
cohort are, however, the precise clinical and metabolic character-
ization of the participants including the availability of coronary
angiograms and its cross-sectional and prospective design.
Furthermore, fatty acids were measured in erythrocyte cell mem-
branes that represent fatty acid intake over the last months, as
erythrocytes have a lifespan of 120 days.
We examined the association of TFA measured in erythrocyte
membranes with plasma biomarkers and long-term outcome in
the LURIC cohort. In contrast to previous findings, we observed
that at generally low concentrations,TFAs were inversely associated
with adverse cardiac outcomes. Especially ruminant-derived TFAs
were associated with a reduced risk of CVM and SCD. Furthermore,
high TFA concentrations in our study (which are low relative to
other populations) were associated with mostly favourable meta-
bolic profiles with lower TG, lower fasting glucose, and lower blood
Authors’ contributions
M.E.K. and G.E.D. performed statistical analysis; C.v.S. and W.M.
handled funding and supervision; C.v.S. acquired the data; C.v.S.
and W.M. conceived and designed the research; M.E.K. drafted the
manuscript; and G.E.D., S.L., W.M., and C.v.S. made critical revision
of the manuscript for key intellectual content.
Supplementary material
Supplementary material is available at European Heart Journal online.
We extend our appreciation to the participants of the LURIC study
and thank the LURIC study team who were either temporarily or
permanently involved in patient recruitment as well as sample and
data handling, in addition to the laboratory staff at the Ludwigshafen
General Hospital and the Universities of Freiburg and Ulm,
This work was supported by the 7th Framework Program (Athero-
Remo, grant agreement number 201668 and RiskyCAD, grant
agreement number 305739) of the EU and by the INTERREG-IV-
Oberrhein-Program (Project A28, Genetic mechanisms of cardiovascu-
lar diseases) with support from the European Regional Development
Fund (ERDF) and the Wissenschaftsoffensive TMO. M.E.K., S.L., and
W.M. are supported by the German Federal Ministry of Education and
M.E. Kleber et al.Page 6 of 7
by guest on November 7, 2015 from
Research as part of the Competence Cluster of Nutrition and Cardio-
vascular Health (nutriCARD).
Conflict of interest: C.v.S. has founded Omegametrix, a laboratory
performing fatty acid analysis, which analysed LURIC samples free of
charge. W.M. is employed with synlab Services GmbH and holds shares
of synlab Holding GmbH. The other authors declare no conflict of
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Trans fatty acids and mortality in patients Page 7 of 7
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... Higher circulating tPA levels were associated in three of these studies with elevated LDL-cholesterol and HDL-cholesterol concentrations, but lower TAG and biomarkers of T2D risk (i.e. fasting glucose, fasting insulin and insulin resistance index) (49,53,78) . In contrast, a more recent prospective cohort study observed direct cross-sectional relationships between higher circulating tPA and tVA and markers of glycaemic control (i.e. ...
... Since then, two prospective cohort studies observed inverse associations between circulating tVA and risk of strokes (75) , or between tPA and sudden cardiac mortality (78) , but other studies failed to observe associations between tPA and CVD risk (74) or between tVA and tPA and risk of T2D (79) (Table 2). ...
In epidemiological studies, dairy food consumption has been associated with minimal effect or decreased risk of some cardiometabolic diseases (CMD). However, current methods of dietary assessment do not provide objective and accurate measures of food intakes. Thus, the identification of valid and reliable biomarkers of dairy intake is an important challenge to best determine the relationship between dairy consumption and health status. This review investigated potential biomarkers of dairy fat consumption, such as odd-chain, trans - and branched-chain fatty acids, which may improve the assessment of full-fat dairy product consumption. Overall, the current use of serum/plasma fatty acids as biomarkers of dairy fat consumption is mostly based on observational evidence, with a lack of well-controlled, dose response intervention studies to accurately assess the strength of the relationship. Circulating odd-chain saturated fatty acids and trans -palmitoleic acid are increasingly studied in relation to CMD risk and seem to be consistently associated with a reduced risk of type 2 diabetes in prospective cohort studies. However, associations with cardiovascular diseases are less clear. Overall, adding less studied fatty acids such as vaccenic and phytanic acids to the current available evidence may provide a more complete assessment of dairy fat intake and minimise potential confounding from endogenous synthesis. Finally, the current evidence base on the direct effect of dairy fatty acids on established biomarkers of CMD risk (e.g. fasting lipid profiles and markers of glycaemic control) mostly derives from cross-sectional, animal, and in vitro studies, and should be strengthened by well-controlled human intervention studies.
... In fact, there could even be a positive effect. A study carried out in patients with chest pain or symptoms of possible myocardial ischemia [research framed within the Ludwigshafen Risk and Cardiovascular Health (LURIC) study] found that the highest concentrations of TFAs detected in the membrane of red blood cells (low compared to other population groups) corresponded to lower cholesterol and TG levels, lower fasting glucose, and lower blood pressure (Kleber, Delgado, Lorkowski, März, & Von Schacky, 2016). In addition, these authors have suggested that the consumption of trans fats of ruminants might be associated with a decrease in the risk of cardiovascular mortality and sudden cardiac death. ...
... Milk is the most complete liquid food of animal origin in nature, and milk and dairy products are among the most important human food [1][2][3]. Although for decades, ruminant's milk had a negative image due to its high content in saturated fatty acid (SFA) and the relationship of these with cardiovascular diseases [4][5][6][7], milk fatty acids are still important nutritional elements. Besides, it has also been reported that milk fat would have beneficial effects on health [8][9][10]. ...
Full-text available
This study is aimed at comparing the milk fatty acid profile (FAP) of cows that changed from a mixed system (MS) of double grazing plus total mixed ration (TMR) to a total confinement system (TCS, 100% TMR) with cows that changed to another MS with one overnight grazing plus TMR and compare with cows that were kept unchanged in TCS. The diet change was made in the second month of lactation. The milk samples were collected at one (M1-spring) and three months of lactation (M3-summer). Three treatments are as follows (each n = 10 ): confined cows fed with TMR throughout the period (GTMR), cows that changed from MS with double grazing plus TMR in M1 to TCS in M3 (GCHD), and cows that changed from a MS with double grazing plus TMR in M1 to a MS with overnight grazing plus TMR in M3 (GTMR+P). Unlike GTMR+P, GCHD improved milk production after change (increased 14% from M1 to M3), but milk FAP was impaired. In M3, conjugated linoleic acid (C18 : 2-CLA) in GTMR and GCHD was lower than GTMR+P ( p < 0.05 ), and linolenic (C18 : 3-n-3) was lower in GCHD than GTMR+P. Maintaining grazing in summer overnight sustained milk fat quality, evidenced by higher C18 : 3 (n-3); C18 : 2 (CLA); and n-6/n-3 ratio than cows that changed to TCS.
... Partially hydrogenated vegetable oil is the source of trans fatty acids that are related to health disorders when consumed for a long time [54,55]. In addition, even though a coffee creamer is labelled as non-dairy, it may still contain milk-derived proteins such as casein and sodium-caseinate as stated on the label of a commercial non-dairy creamer. ...
... Some clinical trials indicated no significant correlation between plasma, serum, WAT or erythrocyte membrane levels of C16:1n7 and increased cardiovascular mortality in patients suffering from ischemic heart disease or HF [20][21][22], as reviewed by [23], whereas other studies identified a positive correlation [24,25], as reviewed by [23]. Other clinical trials implicated a cardioprotective effect of palmitoleic acid [26]. In addition, C16:1n7plasma levels have been linked to the development of metabolic syndrome and obesity [27]. ...
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Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 (Angptl4) and Pyruvate Dehydrogenase Kinase 4 (Pdk4). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage.
... A systematic review of the literature identified 18 studies, including the 60YO, that met the inclusion criteria (Fig 3) [ [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. The characteristics of the studies and their quality assessment based on NOS are presented in Tables F and G in S1 File. ...
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Background We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality. Methods and findings We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose–response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case–cohort, or nested case–control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. Conclusions In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.
... Administration 2013), which makes keeping up-to-date values of TFA in foods a virtually impossible task. Third, recent evidence support that the effect of TFA on health could by source-specific with natural ruminant TFA, and especially conjugated linoleic acids and trans-palmitoleic acid, compensating for some of the adverse effects of other TFA(Astrup et al. 2016;Kleber et al. 2016;Kuhnt et al. 2016).mean sugar content of the sweetened beverages in WWEIA/NHANES(Table A2.6)We investigate the contribution of TFA on HENI for all food items by food category (Figure A2.29). ...
Suboptimal diet is a major public health concern, responsible for ~10 million death/year globally associated with nutrition, plus additional deaths associated with environmental emissions from food production. Informing consumer choices is crucial and would require to consistently combine latest epidemiological evidence on the impact of diet and pollution, with life cycle assessment (LCA) of food systems to analyze relevant trade-offs. This dissertation aims to address four critical challenges for assessing the life cycle impact and benefits of food systems on human health: (1) The failure to capture both environmental impacts and nutritional effects of foods consistently. (2) The lack of nutritional assessment metrics that evaluate the performance of individual food items based on health burden. (3) The overly simplified assessment of impacts of particulate matter (PM2.5) on human health, which do not consider spatial variation in exposure, nor evidence for non-linear exposure-response. (4) The need for a consistent approach to evaluate multi-ingredient mixed dishes, a central component in modern diets. Chapter 2 developed a novel Combined Nutritional and Environmental Life Cycle Assessment (CONE-LCA) framework that evaluates and compares in parallel the environmental and nutritional effects of foods or diets in a common metric, disability adjusted life years (DALYs). A proof-of-concept case study indicated that nutritional health net benefits of adding a serving of milk to the average U.S. diet exceeded environmental impacts and highlighted the need for considering nutrition as a new LCA impact category. Chapter 3 operationalized the nutritional approach by establishing the Health Nutritional Index (HENI). This health burden-based nutritional index quantifies the health burden of one food serving in minutes of healthy life lost or gained, using epidemiological evidence for a comprehensive set of 16 dietary risks. Application to ~7,000 food items in the U.S. diet revealed substantial variability in HENI scores between and within food categories, thus the importance of informed choices at the level of individual food items. In Chapter 4, we developed spatially-explicit intake fractions for ground-level PM2.5, NH3, SO2, and NOx emissions in the contiguous U.S. for agriculture and other relevant sectors. Using a non-linear exposure-response function and state-specific burden data, we developed the corresponding characterization factors considering a marginal and an average slope. Spatial estimates varied by three orders of magnitude, sector-specific estimates by a factor of four, and the average slope doubled estimates compared to marginal. This work stressed the importance of spatially-explicit and sector-specific estimates in LCA. Finally, in Chapter 5 we established a new nutritional impact category for LCA, providing both inventory flows and nutritional characterization factors, and a systematic approach to decompose mixed dishes into individual components for which environmental life cycle inventory is available. Using a case study of pizzas, we quantified and compared environmental and nutritional impacts on health and found that nutrition dominates health damages. Nutritional and environmental impacts were correlated with red meat pizzas generating the highest and vegetable pizzas the lowest health damages. This dissertation provides the foundation for evaluating nutritional and environmental impacts of foods and diets comprehensively and systematically in food sustainability assessments and LCAs. It introduces a new nutritional LCA impact category, pioneers a powerful nutritional health based index that can inform healthier dietary choices and substitutions, and improves PM2.5 impact assessment. Findings can inform sustainable decision making for foods and diets within and beyond LCA.
... Apesar de promissores, poucos estudos estão disponíveis sobre a expressão gênica e a suplementação de ômega 3. (PETIT, 2009). Além disso, estudos demonstraram que a metabolização dos compostos bioativos da linhaça pelos microrganismos colonizadores do rúmen é capaz de produzir compostos com efeitos ainda maiores à saúde humana (CÔRTES, et al., 2008 (KLEBER et al., 2016;LIANG, et al., 2018) e até indicam que o consumo de laticínios dentro dos padrões dietéticos normais está inversamente associado a esse risco (KRATZ, et al., 2013;) (THORNING et al., 2017). ...
Full-text available
1 | INTRODUÇÃO A linhaça é a semente da planta do linho (Linum usitatissimum L.) pertencente à família Lineaceae (BEKHIT et al., 2018). Esta cultura apresenta-se em duas variedades nutricionalmente idênticas: a semente de coloração amarelo dourado e a marrom avermelhado (SONI et al., 2016). O uso da linhaça pelo ser humano remonta desde os tempos antigos (5000 a.C.) na mesopotâmia, por onde se espalhou ao redor do mundo, sendo hoje comercialmente explorada pelas indústrias de tecidos, papéis, tintas e alimentícia, esta última impulsionada por suas propriedades nutricionais e medicinais (SONI et al., 2016). Nas últimas décadas, a linhaça despontou no cenário alimentício como um alimento com propriedades funcionais, ou seja, além das suas propriedades nutricionais básicas, a semente apresenta numerosos compostos biologicamente ativos e benéficos à saúde. A semente de linhaça, além de ser uma das fontes alimentícias com maior teor de ômega-3, tornando-a uma excelente alternativa para a incorporação dos ácidos graxos na dieta, também é fonte de fibras dietéticas, proteínas de alta qualidade, peptídeos bioativos, fitoesteróis e compostos fenólicos (WU et al., 2019; KANIKOWSKA et al., 2020). O excelente perfil nutricional da semente de linhaça reflete nos seus efeitos benéficos à saúde humana. Estudos demonstram que a semente de linhaça pode ajudar na prevenção e tratamento de várias doenças, tais como: minimizar os distúrbios da obesidade, reduzir o risco de câncer de mama, controlar a diabetes, além de apresentar propriedades antiinflamatórias, antioxidantes e de regulação da função intestinal (CHISTHY & BISSU, 2016; WU et al., 2019). Deste modo, a linhaça é de grande interesse para o mercado consumidor, sendo amplamente recomendada por nutricionistas, pesquisadores e médicos como um alimento funcional, seguro e barato para o tratamento de doenças (SHEKHARA et al., 2020). O alimento pode ser incorporado nas dietas em suas diferentes formas, incluindo a semente inteira, ou os subprodutos da semente: farinha, goma, óleo, extrato/isolado fenólico, hidrolisado proteico, uma vez que há relatos de suas atividades anti-inflamatória, antioxidante e prebiótica (PARIKH et al., 2019). Portanto, este capítulo busca fornecer uma revisão robusta e atualizada das atividades biológicas da semente de linhaça como recurso terapêutico à saúde humana.
... Apesar de promissores, poucos estudos estão disponíveis sobre a expressão gênica e a suplementação de ômega 3. (PETIT, 2009). Além disso, estudos demonstraram que a metabolização dos compostos bioativos da linhaça pelos microrganismos colonizadores do rúmen é capaz de produzir compostos com efeitos ainda maiores à saúde humana (CÔRTES, et al., 2008 (KLEBER et al., 2016;LIANG, et al., 2018) e até indicam que o consumo de laticínios dentro dos padrões dietéticos normais está inversamente associado a esse risco (KRATZ, et al., 2013;) (THORNING et al., 2017). ...
Atherosclerosis (AS) is the most common cardiovascular disease (CVD). Currently, it is widely believed that R-TFA and I-TFA may cause different biological effects. In the present study, we aim to elucidate the effect of mixed R-TFA derived from butter on the development of AS in high-fat diet-fed ApoE-/- mice and find the possible mechanism. It was shown that butter-derived R-TFA promoted dyslipidemia, reduced thoracic and abdominal aorta diameters, and induced aortic lipid deposition and atherosclerotic lesions in high-fat diet-fed ApoE-/- mice. Meanwhile, butter-derived R-TFA affected the serum lipid profile of high-fat diet-fed ApoE-/- mice and the lipid metabolism of human umbilical vein endothelial cells (HUVECs). Through lipidomic techniques, we found that butter-derived R-TFA had a significant effect on the glycerophospholipid metabolic pathway. In conclusion, our results demonstrated that butter-derived R-TFA does not alleviate but promotes atherosclerotic lesions in high-fat diet-fed ApoE-/- mice and that the glycerophospholipid metabolic pathway plays a major role in this pro-atherosclerotic effect.
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Although there is evidence that consumption of trans fat has declined in the United States, limited documentation exists on current levels of industrial trans fat in foods. We estimated the prevalence of partially hydrogenated oils in 4,340 top-selling US packaged foods. Nine percent of products in the sample contained partially hydrogenated oils; 84% of these products listed "0 grams" of trans fat per serving, potentially leading consumers to underestimate their trans fat consumption. Government efforts to eliminate partially hydrogenated oils from packaged foods will substantially reduce exposure to this known cardiovascular disease risk factor.
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Background While self‐reported trans–fatty acid (TFA) consumption is linked to coronary heart disease (CHD), relationships between objective biomarkers of TFA subtypes (t‐16:1n9, total t‐18:1, and cis/trans‐(c/t‐), t/c‐ and t/t‐18:2) and cardiovascular disease (CVD) or total mortality are not well established. Methods and Results We evaluated 2742 adults in the Cardiovascular Health Study, aged 74±5 years and free of prevalent CVD, with plasma phospholipid TFA measures in 1992. Incident fatal and nonfatal CHD events, CVD and non‐CVD mortality, and total mortality were centrally adjudicated through 2010. Risks were assessed using Cox proportional hazards. During 31 494 person‐years, 1735 total deaths and 639 total CHD events occurred. In the multivariate model including mutual adjustment for the 5 TFA subtypes, circulating t/t‐18:2 was associated with higher total mortality (extreme quintile hazard ratio (HR)=1.23, 95% CI=1.04 to 1.44, P‐trend=0.01), CVD mortality (HR=1.40, 95% CI=1.05 to 1.86, P‐trend=0.02), and total CHD (HR=1.39, 95% CI=1.06 to 1.83, P‐trend=0.01). t/c‐18:2 was positively related to total mortality (HR=1.19, P‐trend=0.05), total CHD (HR=1.67, P‐trend=0.002), and nonfatal CHD (HR=2.06, P‐trend=0.002) after mutual adjustment; these associations were insignificant without mutual adjustment. Neither t‐16:1n9 nor t‐18:1 was significantly associated with total mortality or CVD, nor was c/t‐18:2 if we excluded early cases. Conclusions Among circulating TFAs, t/t‐18:2 was most adversely associated with total mortality, mainly due to the increased risk of CVD. t/c‐18:2 was also positively associated with total mortality and CHD, but only after adjustment for other TFAs. These results highlight the need for further investigation of dietary sources, nondietary determinants, and health effects of specific TFA subtypes, especially t‐18:2 isomers.
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Objective To minimise the intake of industrial artificial trans fat (I-TF), nearly all European countries rely on food producers to voluntarily reduce the I-TF content in food. The objective of this study was to investigate the effect of this strategy on I-TF content in prepackaged biscuits/cakes/wafers in 2012–2013 in 20 European countries. Design The I-TF content was assessed in a market basket investigation. Three large supermarkets were visited in each capital, and in some countries, three additional ethnic shops were included. Results A total of 598 samples of biscuits/cakes/wafers with ‘partially hydrogenated vegetable fat’ or a similar term high on the list of ingredients were analysed, 312 products had more than 2% of fat as I-TF, exceeding the legislatively determined I-TF limit in Austria and Denmark; the mean (SD) was 19 (7)%. In seven countries, no I-TF was found, whereas nine predominantly Eastern European countries had products with very high I-TF content, and the remaining four countries had intermediate levels. Of the five countries that were examined using the same procedure as in 2006, three had unchanged I-TF levels in 2013, and two had lower levels. The 18 small ethnic shops examined in six Western European countries sold 83 products. The mean (SD) was 23 (12)% of the fat as I-TF, all imported from countries in Balkan. In Sweden, this type of food imported from Balkan was also available in large supermarkets. Conclusions The findings suggest that subgroups of the population in many countries in Europe still consume I-TF in amounts that increase their risk of coronary heart disease. Under current European Union (EU) legislation, the sale of products containing I-TF is legal but conflicts with the WHO recommendation to minimise the intake of I-TF. An EU-legislative limit on I-TF content in foods is expected to be an effective strategy to achieve this goal.
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trans Palmitoleic acid (t-16:1n-7, or 16:1t9 in the δ nomenclature usually applied to trans fatty acids and used herein) arouses great scientific interest because it has been suggested to serve as a biomarker for lower risks of type 2 diabetes and coronary artery disease. Although 16:1t9 has been assumed to derive from dietary sources, we examined the hypothesis that 16:1t9 might also be endogenously produced from its metabolic precursor vaccenic acid (t-18:1n-7 or 18:1t11). We reevaluated fatty acid data obtained from one human intervention study and one cellular model in both of which 18:1t11 was supplemented. Both studies have already been published, but to our knowledge, 16:1t9 has not yet been considered. This reanalysis of the datasets was reasonable because a new methodology for identifying 16:1 cis and trans isomers allowed us to address the subject presented in this article. Data showed that the systemic or intracellular increase in 16:1t9 was strongly correlated with the increase in 18:1t11 after the dietary intake or cellular uptake of 18:1t11. The conversion rate in humans was, on average, 17%. Our findings suggest that endogenous 16:1t9 is not, as has been assumed, exclusively diet derived but may also be produced by the partial β oxidation of dietary 18:1t11.
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Methodological limitations compromise the validity of U.S. nutritional surveillance data and the empirical foundation for formulating dietary guidelines and public health policies. Evaluate the validity of the National Health and Nutrition Examination Survey (NHANES) caloric intake data throughout its history, and examine trends in the validity of caloric intake estimates as the NHANES dietary measurement protocols evolved. Validity of data from 28,993 men and 34,369 women, aged 20 to 74 years from NHANES I (1971-1974) through NHANES 2009-2010 was assessed by: calculating physiologically credible energy intake values as the ratio of reported energy intake (rEI) to estimated basal metabolic rate (BMR), and subtracting estimated total energy expenditure (TEE) from NHANES rEI to create 'disparity values'. 1) Physiologically credible values expressed as the ratio rEI/BMR and 2) disparity values (rEI-TEE). The historical rEI/BMR values for men and women were 1.31 and 1.19, (95% CI: 1.30-1.32 and 1.18-1.20), respectively. The historical disparity values for men and women were -281 and -365 kilocalorie-per-day, (95% CI: -299, -264 and -378, -351), respectively. These results are indicative of significant under-reporting. The greatest mean disparity values were -716 kcal/day and -856 kcal/day for obese (i.e., ≥30 kg/m2) men and women, respectively. Across the 39-year history of the NHANES, EI data on the majority of respondents (67.3% of women and 58.7% of men) were not physiologically plausible. Improvements in measurement protocols after NHANES II led to small decreases in underreporting, artifactual increases in rEI, but only trivial increases in validity in subsequent surveys. The confluence of these results and other methodological limitations suggest that the ability to estimate population trends in caloric intake and generate empirically supported public policy relevant to diet-health relationships from U.S. nutritional surveillance is extremely limited.
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To systematically review evidence for the effectiveness of policies, including self-regulation, aimed at reducing industrially produced trans fatty acids (TFAs) in food. The Medline, Embase and Cinahl databases were searched to identify peer-reviewed articles examining the effect of TFA policies. In addition, the first 20 pages of Google searches were examined for articles from the grey literature. A study was included if: (i) it was empirical and conducted in a "real-world" setting (i.e. modelling studies were excluded); (ii) it examined a TFA policy involving, for example, labelling, voluntary limits or bans; and (iii) it examined a policy's effect on TFA levels in food, people's diets, blood or breast milk. Twenty-six articles met the inclusion criteria: 5 involved voluntary self-regulation; 8, labelling alone; 4, labelling and voluntary limits; 5, local bans and 4, national bans. Overall, the TFA content of food decreased with all types of policy intervention. In general, saturated fat levels increased or decreased, depending on the product type, and total fat content remained stable. National and local bans were most effective at eliminating TFAs from the food supply, whereas mandatory TFA labelling and voluntary TFA limits had a varying degree of success, which largely depended on food category. Policies aimed at restricting the TFA content of food were associated with significant reductions in TFA levels, without increasing total fat content. Such policies are feasible, achievable and likely to have an effect on public health.
Objective The goal of this article was to review the causal link between trans fatty acids (TFA) produced from partially hydrogenated vegetable oil (PHVO) and cardiovascular disease (CVD) risk and its likely mechanisms. The potential risk of TFA from ruminant dairy and meats, which are currently the major sources of dietary TFA, is also discussed. Methods Evidence was derived from observational studies of large cohorts followed up prospectively; from randomized controlled trials of clinical interventions; and from specific case-control studies that investigated biomarkers in tissues. Searches included PubMed and Medline from 1990 to 2013. Results Despite TFA from PHVO being associated more strongly with CVD risk than even saturated fats, it may prove difficult to totally eliminate PHVO from all foods. This raises the issue of the lower limit of TFA consumption below which CVD risk is not increased. Limits of <1% of total energy have been suggested. The major mechanism underlying the increased CVD risk from TFA is an increase in LDL-C and Lp(a) lipoproteins and a decrease in HDL-C; increased inflammation and adverse effects on vascular function have also been shown. Both PHVO and ruminant TFA comprise a range of isomers, some specific to each source but including a substantial commonality that supports findings of similar adverse effects at equivalent intakes of TFA. However, the amount of TFA in ruminant fat is relatively small; this limits the CVD risk from eating ruminant products, an inference supported by analysis of prospective cohort studies. Conclusions Two key challenges to the health industry arise from this evidence. They must first determine whether a small intake of TFA from PHVO is safe and what constitutes a safe amount. They must also determine whether TFA from ruminant fat in currently consumed amounts represent limited cardiovascular risk that is balanced by the nutritional benefits of dairy products.
Background: The issue of whether saturated fats and trans fats are superior predictors of all-cause death and cardiovascular disease than n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), remains a matter of contention. Furthermore, few studies have examined the relationship between fatty acids and the outcomes of cardiovascular disease (CVD) in Asian populations. The aim of this study was to compare the effectiveness of various plasma fatty acids as predictors for all-cause death and CVD events in an ethnic Chinese population. Methods: This study assembled a community-based prospective cohort, comprising 1833 participants (60.6 ± 10.5 yrs, 44.5% women) who underwent a comprehensive evaluation of fatty acids in blood using gas chromatography. None of the subjects had a history of CVD at the time of recruitment. Results: A total of 568 individuals died and 275 individuals developed CVD during the follow-up period (median of 9.6 years; interquartile range of 8.9-10.5 years). Following adjustment for established cardiovascular risk factors, the relative risk of all-cause death in the highest quartile, compared with the lowest quartile, was 1.33 for saturated fats (95% confidence interval [CI], 1.01-1.75, test for trend, P = 0.015), 1.71 for trans fats (95% CI, 1.27-2.31, test for trend, P = 0.0003), 0.77 for EPA (95% CI, 0.59-1.00, test for trend, P = 0.048), and 0.89 for DHA (95% CI, 0.68-1.18, test for trend, P = 0.354). Similar patterns were observed for CVD events. Trans fats presented the largest area under the receiver operator characteristic curve (0.740, 95% CI, 0.716-0.766) for the prediction of all-cause death. A mutually adjusted two-marker model indicated that saturated fats and trans fats were significant predictors of all-cause death and CVD; however, the other fatty acids were not. In addition, trans fats presented the greatest improvement in net reclassification for all-cause death (7.7%, P = 0.003), followed by EPA (3.8%, P = 0.033). Saturated fats presented the greatest improvement in net reclassification for CVD events (5.6%, P = 0.039). Conclusions: Our data provides strong evidence to support that plasma saturated fats and trans fats can predict all-cause death and CVD more effectively than other fatty acid markers.