Fatty acids in cardiovascular health and disease: A comprehensive update
Miller School of Medicine, University of Miami, Miami, FL 33136, USA.Journal of Clinical Lipidology (Impact Factor: 3.9). 05/2012; 6(3):216-34. DOI: 10.1016/j.jacl.2012.04.077
Research dating back to the 1950s reported an association between the consumption of saturated fatty acids (SFAs) and risk of coronary heart disease. Recent epidemiological evidence, however, challenges these findings. It is well accepted that the consumption of SFAs increases low-density lipoprotein cholesterol (LDL-C), whereas carbohydrates, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) do not. High-density lipoprotein (HDL)-C increases with SFA intake. Among individuals who are insulin resistant, a low-fat, high-carbohydrate diet typically has an adverse effect on lipid profiles (in addition to decreasing HDL-C, it also increases triglyceride and LDL particle concentrations). Consequently, a moderate fat diet in which unsaturated fatty acids replace SFAs and carbohydrates are not augmented is advised to lower LDL-C; compared with a low-fat diet, a moderate-fat diet will lower triglycerides and increase HDL-C. Now, there is some new evidence that is questioning the health benefits of even MUFAs and PUFAs. In addition, in a few recent studies investigators have also failed to demonstrate expected cardiovascular benefits of marine-derived omega-3 fatty acids. To clarify the clinical pros and cons of dietary fats, the National Lipid Association held a fatty acid symposium at the 2011 National Lipid Association Scientific Sessions. During these sessions, the science regarding the effects of different fatty acid classes on coronary heart disease risk was reviewed.
Get notified about updates to this publicationFollow publication
Fatty acids in cardiovascular health and disease:
A comprehensive update
Seth J. Baum, MD, FNLA, Co-Chair
, Penny M. Kris-Etherton, PhD, RD, Co-Chair,
Walter C. Willett, MD, DrPH, Alice H. Lichtenstein, DSc, Lawrence L. Rudel, PhD,
Kevin C. Maki, PhD, Jay Whelan, PhD, MPH, Christopher E. Ramsden, MD, USPHS,
Robert C. Block, MD, MPH
Miller School of Medicine, University of Miami, Miami, FL 33136, USA (Dr. Baum); Penn State University, University
Park, PA, USA (Dr. Kris-Etherton); Harvard School of Public Health, Boston, MA, USA (Dr. Willett); Tufts University,
Medford, MA, USA (Dr. Lichtenstein); Wake Forest University School of Medicine, Winston–Salem, NC, USA (Dr. Rudel);
Biofortis–Provident Clinical Research, Addison, IL, USA (Dr. Maki); University of Tennessee, Knoxville, TN, USA
(Dr. Whelan); NIH, Bethesda, MD, USA (Dr. Ramsden); and University of Rochester Medical Center, Rochester, NY, USA
Coronary heart disease;
Abstract: Research dating back to the 1950s reported an association between the consumption of
saturated fatty acids (SFAs) and risk of coronary heart disease. Recent epidemiological evidence, how-
ever, challenges these ﬁndings. It is well accepted that the consumption of SFAs increases low-density
lipoprotein cholesterol (LDL-C), whereas carbohydrates, monounsaturated fatty acids (MUFAs), and
polyunsaturated fatty acids (PUFAs) do not. High-density lipoprotein (HDL)-C increases with SFA in-
take. Among individuals who are insulin resistant, a low-fat, high-carbohydrate diet typically has an
adverse effect on lipid proﬁles (in addition to decreasing HDL-C, it also increases triglyceride and
LDL particle concentrations). Consequently, a moderate fat diet in which unsaturated fatty acids re-
place SFAs and carbohydrates are not augmented is advised to lower LDL-C; compared with a low-
fat diet, a moderate-fat diet will lower triglycerides and increase HDL-C. Now, there is some new ev-
idence that is questioning the health beneﬁts of even MUFAs and PUFAs. In addition, in a few recent
studies investigators have also failed to demonstrate expected cardiovascular beneﬁts of marine-derived
omega-3 fatty acids. To clarify the clinical pros and cons of dietary fats, the National Lipid Association
held a fatty acid symposium at the 2011 National Lipid Association Scientiﬁc Sessions. During these
sessions, the science regarding the effects of different fatty acid classes on coronary heart disease risk
Ó 2012 National Lipid Association. All rights reserved.
Fatty acids are biologically active molecules with a wide
array of effects. For decades, fatty acids have been a focus
of dietary recommendations for heart health. Historically,
saturated fatty acids (SFAs) have been a target for reduc-
tion. More recently, this dietary restriction has been
extended to trans-fatty acids. In contrast, unsaturated fatty
acids have been considered to be heart healthy. Thus, in re-
cent years, dietary recommendations have been made to
decrease saturated and trans-fatty acids and to emphasize
unsaturated fatty acids (both monounsaturated [MUFAs]
* Corresponding author.
E-mail address: firstname.lastname@example.org
Submitted February 1, 2012. Accepted for publication April 11, 2012.
1933-2874/$ - see front matter Ó 2012 National Lipid Association. All rights reserved.
Journal of Clinical Lipidology (2012) 6, 216–234
and polyunsaturated fatty acids [PUFAs]). Since the early
1970s and thereafter, long-chain omega (n)-3 PUFA (nota-
bly eicosapentaenoi c acid [EPA] and docosahexaenoic acid
[DHA]) have been associated with cardiovascular health
As the science has evolved, new evidence is challenging
these time-honored beliefs. Recent epidemiologic research
is showing that SFAs and reﬁned carbohydrates are simi-
larly associated with coronary disease risk. There is some
evidence from studies in monkeys that suggests similar
atherogenic effects of MUFA and SFA, and reanalysis of
the n-6 PUFA clinical studies has raised questions about
their health beneﬁts, suggesting that they too may have
adverse effects. Finally, although the cardiovascular bene-
ﬁts of marin e-derived n-3 fatty acids have been demon-
strated previously, in new studies investigators have failed
to show some of the expected beneﬁts.
The 2011 National Lipid Association’s Fatty Acid Sum-
mit provided an opportunity for experts from across the
nation to explore confusing, and oftentimes contradictory,
aspects of the dietary fatty acid literature and to inform
clinicians and scientists about the controversies. The main
question addressed by each speaker was, ‘‘How does each
fatty acid class impact cardiovascular health and disease?’’
The conference was organized into examinations of SFAs,
MUFAs—oleic acid in particular, n-6 fatty acids—l inoleic
acid (LA) in particular, and n-3 fatty acids—EPA and
DHA in particular. The summaries that follow from the pro-
gram present opposing v iewpoints about the cardiovascular
health effects of the different fatty acid classes. The intent
of the chairs was for the speakers to engage in a dialetic, ie,
a forum for discussing opposing views, rather than a debate.
Thus, the goal of the summit was to raise awareness of con-
cepts and controversies regarding fatty acid classes and risk
of cardiovascular disease (CVD) and to identify topics for
future research to answer questions that have been raised
by recent research ﬁndings.
The fundamentals of fatty acids
Seth J. Baum, MD, FNLA
University of Miami, Miami, FL, USA
Triglycerides (TG), also known as triacylglycerols, are
the primary constituents of vegetable oil and animal fats.
Glycerol, a polyalcohol, is esteriﬁed with one, two, or three
fatty acids, resulting in monoglycerides, diglycerides, or
TG, respectively. During the intestinal absorption of TG,
bile acids emulsify fat to very small fat-containing
The interaction of lipases with TG results in
the formation of monoglycerides and free fatty acids
(FFAs). These can then be transported into the enterocyte
via micelles. Chylomicrons, TG-containing lipoproteins,
are formed within the enterocyte. A key aspect of chylomi-
cron synthesis is the formation of TG from monoglycerides,
diglycerides, and FFA.
Fatty acids are classiﬁed as saturated or unsaturated on
the basis of the absence or presence of double bonds. Fatty
acids that have no double bonds are ‘‘saturated’’ with
hydrogen atoms, hence the name. MUFAs have one double
bond; PUFAs have more than one double bond. Oleic acid is
the major dietary MUFA. Also important is the cis- versus
trans-conﬁguration of the double bonds because it impacts
physical and chem ical properties. All double bonds in fatty
acids are assumed to be in the cis-conﬁguration unless oth-
erwise noted to be trans-. Natural trans fatty acids occur
in limited amounts in beef, lamb, and dairy products, which
are the predominant dietary sources. Most are produced dur-
ing chemical hydrogenation of unsaturated fats when some
of the cis-isomers are converted to the trans-conﬁguration
instead of undergoing complete hydrogenation.
The nomenclature of n-3, n-6, and n-9 PUFA is deter-
mined by the location of the ﬁrst double bond by counting
carbons from the terminal (nth or omega) methyl group.
Alpha-linolenic acid (ALA; 18:3 n-3) is an 18-carbon n-3
essential fatty acid. The 18 refers to the number of carbon
atoms, three refers to the number of double bonds, and n-3
refers to the position on the carbon backbone where the ﬁrst
double bond is located. LA (18:2 n-6) is an 18-carbon n-6
essential fatty acid with two double bonds, and oleic acid
(18:1 n-9) is an n-9 fatty acid with just one double bond.
The science regarding the biological effects of fatty
acids is complex and constantly evolving (Fig. 1). The
long-chain PUFAs most often studied include LA, ALA,
arachidonic acid (AA; 20:4 n-6), EPA (20:5 n-3), and
DHA (22:6 n-3).
An important point in Figure 1 is that
with dietary conditions typical of developed countries, the
conversions of LA to AA and ALA to EPA occur to mini-
mal extents in humans. Previously, it was believed that the
conversion of LA to AA and ALA to EPA represented pro-
cesses wherein there was intense competition for the
enzymes of elongation and desaturation.
However, it is
now believed that there is minimal forward conversion of
Figure 1 Relationships among the PUFA. EFAs, essential fatty
acids; PG, prostaglandin.
Baum et al Fatty acids in cardiovascular health and disease 217
these PUFAs to longer and more unsaturated fats. Instead,
retroconversion, ie, the small increase in EPA when DHA
is fed, may be more consequential. This retroconversion
may or may not be attributable to actual enzymatic produc-
tion of EPA from DHA.
It is possible that DH A feeding
liberates, or otherwise facil itates, the transfer of EPA
from noncirculating depots into the blood. Tracer studies
are needed to test the retroconversion hypothesis.
AA and EPA are precursors for the eicosanoids, ie,
20-carbon chain com pounds, including leukotrienes, pros-
taglandins, prostacyclins, thromboxanes, and lipoxins.
DHA and EPA are the predominant long chain n-3 fatty
acids in ﬁsh oil. They are taken up by cell membranes,
where they increase membrane ﬂuidity, regulate gene ex-
pression, modulate ion channels, and enhance pinocytosis.
EPA is involved in eicosanoid formation, and DHA is in-
volved in the formation of docosanoids.
There are a variety of EPA and DHA pharmaceutical
and dietary supplement products, including those in ethyl
ester, TG, FFA, and phospholipid forms. The manufactur-
ing of ﬁsh oils initially results in an unpuriﬁed oil, which
must be cleansed and concentrated.
The maximum quan-
tity of n-3s that can be obtained in unconcentrated oil is
w30% because, at most, only one of the positions on the
glycerol backbone is occupied by an n-3 fatty acid. To
achieve EPA 1 DHA concentrations greater than 30%,
some manufacturers add alcohol and potassium hydroxide
to cleave the fatty acids and form ethyl esters of DHA
and EPA, which can then be separated and concentrated.
The only pharmaceutical n-3 product currently approved
by the Food and Drug Administration contain s n-3 acid
ethyl esters and is indicated for the treatment of TG
$500 mg/dL. The TG form of n-3 fatty acids can also
be concentrated through a lengthy process that requires
re-esterifying the concentrated EPA and DHA ethyl esters
back to a glycerol backbone. A FFA form may soon be
available as an enteric-coated pharmaceutical product,
and the phospholipid form of n-3 fatty acids found in krill
oil is also available in dietary supplements.
The saturated fat and dietary carbohydrate
debate: are they ‘‘one and the same’’ relative
to cardiovascular risk?
Walter C. Willett, MD, DrPH
Harvard School of Public Health, Boston, MA, USA
This presentation provides an overview of the available
evidence on the topic of SFA and carbohydrates in relation to
CVD risk. Fifteen years ago, this debate would have been
considered impossible because it was believed that SFA
intake was the primary determinant of the high rates of CVD
in Western countries. However, in recent years, that question
has been reexamined, or, more accurately, seriously examined
for the ﬁrst time. In truth, there was not very good epidemi-
ological evidence for this relationship from the beginning.
At a recent meeting in Copenhagen addressing the topic
of SFA versus carbohydrate intake in relation to CVD,
following issues were discussed: (1) To what is SFA being
compared? (2) Do speciﬁc fatty acids have different effects
on heart disease risk, and should the focus be more on food
sources of SFA, recognizing that pure saturated fats or pure
unsaturated fats are never consumed? (3) Have the effects
of SFA versus carbohydrate changed as obesity has in-
creased, and should the effects of SFA on stroke, cancer,
and other health outcomes be considered in recommenda-
tions? (4) What types of evidence are sufﬁcient to guide
Although randomized controlled trials with clinical end
points would be ideal to answer all, or even one, of these
questions, such trials are difﬁcult to conduct and often are
not feasible. The best-available evidence wi ll likely come
from a combination of controlled feeding studies with
intermediate end points such as blood lipids, blood pres-
sure, inﬂammation, and platelet aggregation, in combina-
tion with large prospective, observational studies in which
investigators examine the relationship between intakes and
Several large cohort studies examining diet and health
outcomes have been conducted. The Nurses’ Health Study
enrolled 121,000 women in 1976 and dietary data collection
started in 1980.
The database on diet is continually up-
dated, now every 4 years, because the food supply and com-
position are always changing, particularly for manufactured
products like margarines and shortenings, and people’s die-
tary preferences are continually evolving. Intakes of differ-
ent types of fatty acids were examined in relation to risk of
coronary h eart disease (CHD), speciﬁcally acute myocardial
infarction (MI) or fatal CHD. After 14 years, w1000 such
incident events had occurred. When carbohydrates were
used for comparison and the changes in risk with increasing
percentages of energy from different types of fatty acids
were examined, we found that trans-fat was most strongly
related to a greater risk of CHD. SFA intake was nonsignif-
icantly related when compared calorie-for-calorie with car-
bohydrate. MUFAs, and more so, PUFAs (n-6, LA), were
associated with a lower risk of CHD. Thus, the tradeoff of
SFA versus carbohydrates appeared to be a wash in this
study. The best option to reduce risk appears to be the re-
placement of trans-fat and some SFA with a combination
of MUFAs and PUFAs. Again, as far as SFAs are concerned,
after 20 years of follow-up in the Nurses’ Health Study, there
was a ﬂat dose-response relationship between SFA and CHD
Results from a recent pooled analysis of large cohort
studies indicated that, when compared calorie-for-calorie,
there was a statistically signiﬁcant greater relative risk for
CHD with carbohydrate versus SFA (Fig. 2).
comparison was made between n-6 PUFA and SFA,
PUFA intake was associated with a statistically signiﬁcant
lower CHD risk. This result was similar to the original
Nurses’ Health Study, ie, that the relation of SFA intake
to CHD risk depended on the comparator.
218 Journal of Clinical Lipidology, Vol 6, No 3, June 2012
To brieﬂy summarize the metabolic evidence, a seminal
study conducted by Mensink and Katan
showed that re-
ducing SFA and replacing it with carbohydrate resulted in
decreased high-density lipoprotein (HDL)-C and increased
fasting TG, raising concerns about an increased risk of
CHD. Later, they conducted a meta-analysis of controlled
feeding studies in which they compared SFAs, MUFAs,
and PUFAs versus carbohydrates.
For HDL-C, all types
of fat compared with carbohydrate elev ated HDL-C, and, as
expected, SFA increased low-density lipoprotein (LDL)-C.
However, because SFA intake also increased HDL-C, it
had little effect on the LDL-C/HDL-C ratio (a metric that
is considered to be a better predictor of CHD risk than
LDL-C alone). This ﬁnding was consistent with the epide-
miologic evidence showing that the exchange of SFA for
carbohydrate is a wash in relation to CHD risk. However,
replacement of carbohydrate with either MUFA or PUFA,
or replacement of SFA with either MUFA or PUFA, sub-
stantially improved the LDL-C/HDL-C ratio. For TG, all
types of fat, except trans fat, produced about the same re-
sponse—a reduction compared with carbohydrate.
Because pure SFAs, MUFAs, or PUFAs are never
consumed in the real world, Mensink and Katan
ducted another meta-analysis in which they evaluated the
impact on the total C/HDL-C ratio of oils in the forms
we typically consume. The best types of fat, in terms of im-
proving the lipid ratio, were canola (rapeseed) oil, soybean
oil, and olive oil, whereas the worst types were butter and
stick margarine. Not surprisingly, all types of fat were bet-
ter than pure SFA because even the worst of them do con-
tain some unsaturated fats. There is limited epidemiological
evidence on CHD as a function of speciﬁc types of SFA, in
part, because the different types of SFA are highly corre-
lated and it is difﬁcult to assess independent relationships.
It should be noted that although the aforementioned
comparisons were with carbohydrates, not all carbohydrates
are the same in terms of composition and relationship with
clinical end points. Approximately one-half of the calories in
the United States diet are from carbohydrates; the majority in
the forms of sugar, reﬁned starch, and starch from potatoes.
Therefore, any comparisons with carbohydrates in epidemi-
ologic studies are inherently comparisons with unhealthful
choices. In a recent study by Jakobsen et al
in which they
compared different forms of carbohydrates with SFAs, high
glycemic index carbohydrates were more strongly associated
with risk of CHD than was SFA intake. However, low- or
medium-glycemic index carbohydrates, compared with
SFAs, were not associated with increased risk.
Thus, the relationship of SFA intake to CVD risk is
complex and depends to a great degree on the comparator.
The available evidence suggests that replacing SFA with
MUFA and PUFA may be beneﬁcial while replacing SFA
with carbohydrate may not lower risk or may increase risk
if the replacement is with high glycemic index forms of
An argument for displacing saturated fat
from the diet: beneﬁts depend on what
Alice H. Lichtenstein, DSc
Tufts University, Medford, MA, USA
The objectives of this presentation are to address issues
related to the temporal association between dietary fat and
CVD rates, dietary fat type and CVD outcomes, and the
translation of scientiﬁc ﬁndings to messages for patients
and the general public. Since approximately 1970, the
incidence of CVD has decreased dramatically. It is of
interest to parse what contributed to this decline, ie, more
sophisticated medical modalities, or improved risk factors
contributed to by changes in lifestyle. Focusing on the
United States, and following the trends in three time frames
Figure 2 Coronary deaths in the Pooling Project of Cohort Stud-
ies on Diet and Coronary Disease. The model included intake of
MUFA, PUFA, trans-fatty acids, carbohydrates, and protein ex-
pressed as percentages of total energy, ﬁber, alcohol, and choles-
terol intakes; smoking; body mass index; physical activity and
educational levels; history of hypertension; and ages at baseline
and when questionnaire was returned. Within each study, hazard
ratios with 95% CIs for the incidence of coronary events from
CHD were calculated by the use of Cox proportional hazards
regression with time in study as the time metric. The study-
speciﬁc logs of hazard ratios were weighted by the inverse of their
variances, and a combined estimate of the hazard ratios was com-
puted by using a random effects model. The squares and horizon-
tal lines represent the study-speciﬁc hazard ratios and 95% CIs,
respectively. The area of the squares reﬂects the study-speciﬁc
weight (inverse of the variance). The diamonds represent the com-
bined hazard ratios and 95% CI. AHS, Adventis Health Study;
ARIC, Atherosclerosis Risk in Communities Study; ATBC,
Alpha-Tocopherol and Beta-Carotene Cancer Prevention Study;
CH, carbohydrate; FMC, Finnish Mobile Clinic Health Study;
GPS, Glostrup Population Study; HPFS, Health Professionals
Follow-Up Study; NHSa, Nurses’ Health Study 1980; NHSb,
Nurses’ Health Study 1986; VIP, V
asterbotten Intervention Pro-
gram; WHS, Women’s Health Study. Permission to reuse ﬁgure
granted by American Society for Nutrition.
Baum et al Fatty acids in cardiovascular health and disease 219
(196821976, 198021990, and recent years), one can see
that lifestyle modiﬁcation has had a large effect.
ing lifestyle changes, dietary fat type, and speciﬁcally the
balance between SFAs and unsaturated fatty acids, is an
area that has received substantial attention.
One of the ﬁrst publications that advised a decrease in SFA
intake was published in 1961 by the American Heart Asso-
At that time, there was also a recommendation to
decrease total fat intake; the latter recommendation was
dropped in the year 2000. Why was there a recommendation
to decrease SFA intake 50 years ago? Some of the support
came from observational studies, including the iconic
Seven-Countries Study of Keys et al, which suggested a
positive relationship between SFA intake and CHD death, al-
though there were other differences among the populations.
One way to examine observational data regarding diet and
CHD is to calculate dietary PUFA to SFA (P/S) ratios, thus si-
multaneously accounting for both dietary components. In the
Nurses’ Health Study, a greater P/S ratio was associated with
lower relative risk of CHD.
It is also possible to calculate the
expected change in total-C from a change in dietary SFA and
PUFA using the predictive equations generated by Keys et al
and Hegsted et al.
Both concluded that decreasing SFA in-
take had about twice the effect to lower total-C as increasing
PUFA, and that MUFA was relatively neutral.
A limited number of intervention studies have examined
dietary SFA intake and CHD outcomes. It is prohibitively
expensive to carry out such studies, and it is unlikely we
will see new ones in the near future. Hence, it is important
to carefully consider the historical data while acknowledg-
ing that some of the methodology is not consistent with
current standards. Of note, a common thread among these
studies is that not only was SFA intake reduced but PUFA
intake was increased. One of the ﬁrst studies was the
Medical Research Council soybean oil study, a secondary
CHD prevention study in which SFA were displaced with
soybean oil, high in PUFA.
Among those surviving free
of relapse, subjects in the soybean oil group fared better
than those in the control (SFA) group. The primary and sec-
ondary prevention Los Angeles Veterans Diet Study admin-
istered a diet relatively high in total fat (40% of energy)
with unsaturated fat, predominately PUFA, tripled at the
expense of SFA. Again, fewer events were reported with
the intervention diet.
The secondary prevention Oslo
Diet Heart Study also demonstrated that a diet lower in
SFA and greater in PUFA resulted in better outcomes.
However, it should be noted that the increase in PUFA in-
take was attributable not only to LA but also n-3 fatty acids
as described in detail by Dr. Ramsden later in this report.
Investigators from the primary prevention Finnish Men-
tal Hospital Study reported fewer deaths from CHD and
lower rates of MI in a hospital that administered dairy
products in which SFAs were replaced with PUFA (soybean
oil) compared with regular SFA-containing dairy products.
With 6 years per treatme nt phase and the use of a crossover
study design, this was probably the longest dietary cross-
over trial that ever has been conducted.
secondary prevention Leiden Intervention Trial, less nar-
rowing in coronary artery vessel diameter was demon-
strated in individuals who were compliant with dietary
instructions to increase the P/S ratio to greater than two.
The investigators for the intervention component of the
primary prevention Minnesota Coronary Survey reported
that increasing the relative amount of PUFA at the expense
of SFA did not result in a difference between the control
(39% total fat; 18% SFA, 5% PUFA, 16% MUFA, 446 mg
cholesterol/d) and intervention groups (38% total fat; 9%
SFA, 15% PUFA, 14% MUFA, 166 mg cholesterol/d) with
respect to CHD events at 4.5 years follow-up.
however, is that 62% of the study subjects were younger
than 60 years of age, and the study authors indicated that
they suspected a signiﬁcant reduction might have been ev-
ident if the treatment period had been longer in persons in
the age range most likely to beneﬁt. The St. Thomas’ Ath-
erosclerosis Regression Study assessed the impact of diet
on reversing atherosclerosis, by displacing SFA with
Individuals with the greatest regression were those
who reported consuming the least amount of SFA.
Why have questions re-emerged about whether dietary
SFA is or is not related to CHD? Starting in 2009, a number
of reports have concluded that there is a weak association
between either SFA or major foods that contain SFA—meat
and milk—and CHD risk.
Strong inverse associations
between the incidence of CHD and the Mediterranean
diet, a high-quality diet, and a Prudent Heart diet have
also been reporte d, as well as a positive relationship be-
tween a Western diet and CHD,
suggesting that dietary
patterns should be the focus rather than individual compo-
nents of the diet.
As an example of the confusing reports, in one article
the authors stated there was no signiﬁcant association of
CHD risk with SFA intake
; however, in a separate article
in the same journal issue, the same authors stated ‘‘. in
summary, although subst itution of dietary polyunsaturated
fat for saturated fat has been shown to lower CVD risk,
there are few epidemiologic or clinical trial data to support
the beneﬁt of replacing saturated fat with carbohydrate.’’
In another report, investigators, using pooled data, came to
a similar conclusion.
These ﬁndings were corroborated in
a separate analysis of the same data (Fig. 3).
these reports emphasize the importance of accounting for
not only what is decreased in the diet but also other compo-
nents of the diet that are altered and even augmented as a
consequence of the primary change.
This brings the discussion to the last point—message
translation. On the basis of available data, the clear message
medical professionals should be communicating for both
primary and secondary prevention is to displace SFA with
unsaturated fats, primarily PUFAs. Although that was the
intended message before the 1990s, the message became
mutated to ‘‘eat a low-fat diet.’’ This is an appropriate
message for major dietary sources of SFA such as meat and
milk. Switching from full-fat milk to nonfat milk eliminates
the SFA and cuts the calories in half. However, changes such
220 Journal of Clinical Lipidology, Vol 6, No 3, June 2012
as exchanging butter with sugar in baked products may
decrease the SFA, but the price associated with this variation
is an increased carbohydrate content of the diet as well as a
potentially neutral impact on calories.
A further mut ation of the low-fat message is that ‘‘low-
fat’’ became synonymous with ‘‘low-calorie,’’ giving the
false impression that a product labeled low-fat is automat-
ically also low in calories. As a result, in the Unite d States,
there was a proliferation of fat-free and low-fat cookies,
brownies, ice creams, and cakes. And even worse, there was
a proliferation of products in which PUFA was removed
from the food, as often occurs in salad dressings, and
replaced with reﬁned carbohydrate, frequently sugar. What
was the result of these changes? The carbohydrate content of
the diet increased at the expense of the unsaturated fats. Such
changes can promote dyslipidemia (low HDL-C, high TG,
high LDL particle concentration), especially in overweight
and obese individuals. Therefore, it is important to remem-
ber that all messages must be embedded within the over-
arching dictum—to achieve and maintain energy balance.
MUFA—Mediterraneans love olive oil,
but is it our friend or foe?
Lawrence L. Rudel, PhD
Wake Forest University School of Medicine,
Winston-Salem, NC, USA
According to the lipid hypothesis for atherogenesis,
apolipoprotein (apo) B-containing lipoproteins enter the
artery wall, accumulate, are oxidized, and become ligands
for scavenger receptors on macroph ages. They are taken up
by and accumulate within macrophages, converting them
into foam cells. In this way, the process of atherogenesis
begins. HDLs are the cholesterol efﬂux promoters. When
an imbalance between inﬂux and efﬂux occurs, more foam
cells form and atherosclerosis progresses. Not only is the
concentration of apo B-containing lipoproteins dramati-
cally affected by the types of fat consumed, but their
composition also is affected, and these changes can affect
the atherogenicity of the particles.
An old assumption regarding fatty acids and their effects
on atherosclerosis was that MUFAs were neutral, SFAs
were bad, and PUFAs were good. However, a study
conducted by Scott Grundy and Fred Mattson in 1985
turned the ‘‘world of MUFA’’ around.
that diets rich in SFAs caused a high LDL- C/HDL-C ratio,
and that substitution of MUFA for SFA reduced LDL-C but
did not reduce HDL-C. Consequently the LDL-C/HDL-C
ratio was the lowest with MU FA, given that PUFA reduced
HDL-C as well as LDL-C.
Starting with the Seven Countries Study, other authors
have shown that in Mediterranean countries versus the
United States, CHD mortality rates are appreciably lower,
even correcting for plasma cholesterol.
Many assume that
this difference is because of MUFA, speciﬁcally olive oil,
in the Mediterranean diet. However, the Mediterranean
diet differs from the United States diet in many ways.
When diets rich in MUFA versus PUFA are consumed,
even for only a few weeks, plasma LDL cholesterol ester
fatty acid composition changes dramatically. On a MUFA-
rich diet, cholesteryl oleate can become up to 32% of the
cholesterol esters, and cholesteryl linoleate comprises
roughly 45%. When LA-rich fats are consumed, cholesteryl
linoleate increases from 45% to 64%, and cholesteryl oleate
Figure 3 Meta-analysis of randomized controlled trials evaluating effects on CHD events of increasing polyunsaturated fat in place of
saturated fat. CS, Coronary Survey; DART, Diet And Reinfarction Trial; LA, Los Angeles; MRC, Medical Research Council; RR, relative
risk; Rx, treatment; STARS, St. Thomas’ Atherosclerosis Regression Study. Permission to reuse ﬁgure granted by PLoS Medicine.
Baum et al Fatty acids in cardiovascular health and disease 221
decreases from 32% to 13.8%. Why is the effect on
cholesterol ester composition important? Data from the
Atherosclerosis Risk in Communities study showed that
greater carotid artery intimal medial thickness was associ-
ated with the highest quartile of the percentage of circu-
lating saturated cholesterol esters.
The same was also true
for cholesteryl oleate; the greatest quartile was associated
with greater intimal medial thickness. The inverse was
true for cholesteryl linoleate. Data from the Uppsala Longi-
tudinal Study of Adult Men showed a pattern of circulating
cholesterol ester percentages similar to those in the afore-
mentioned study: greater mortality was associated with
cholesteryl oleate and lower mortality was associated
with cholesteryl linoleate (Table 1).
data suggest that enrichment of plasma lipoproteins with
cholesteryl oleate, as promoted by dietary MUFA, may off-
set the beneﬁt of an improved LDL-C/HDL-C ratio.
The following is a discussion of studies conducted in
animal models to examine the lipid hypothesis for athero-
genesis, with particular focus on fatty acid intakes. The lipid
and coronary artery atherosclerosis responses to diets pro-
viding 35% of energy as fat (predominantly SFA [palm oil],
MUFA [high in oleinate from genetically modiﬁed safﬂower
oil], or PUFA [high in LA]) plus cholesterol to boost the
amount of atherosclerosis, were examined in male African
green monkeys (n 5 15 per group) studied for 5 years.
lipid effects in the monkeys were the same as those reported
by Mattson and Grundy in their study of San Diego veterans.
In the monkey studies, average HDL-C was 50 mg/dL in the
PUFA group versus 86 and 81 mg/dL in the SFA and MUFA
Average plasma LDL-C concentra-
tions in the PUFA and MUFA-fed monkeys were 157 and
167 mg/dL, respectively (no signiﬁcant difference between
them) versus 257 mg/dL in the SFA-fed animals.
The largest effects of these diets were in the LDL
cholesterol ester fatty acid composition.
With PUFA feed-
ing, 70% of cholesterol ester was cholesteryl linoleate;
when MUFA oleic acid was fed, 70% of the cholesterol es-
ter was cholesteryl oleate; and the SFA diet resulted in pre-
dominantly cholesteryl oleate with a greater percentage of
cholesteryl palmitate as well. Because only shorter trials
in humans have been conducted to date, it is unknown
whether such dramatic changes as those shown in the mon-
keys would also occur in humans.
Atherosclerotic lesions were circumferential in the SFA-
and MUFA-fed monkeys, but were rarely so in the PUFA-
The average intimal area for all coronary
arteries in each monkey (measured from 16 serial cross
sections of heart) showed similar extents of coronary artery
atherosclerosis in the SFA- and MUFA-fed animals, whereas
monkeys fed PUFA had less atherosclerosis. The choles-
terol oleate conce ntration in the right coronary artery of
the MUFA- and SFA-fed monkeys was essentially the
same, whereas PUFA-fed monkeys had less accumulation.
Table 1 Proportional hazard ratios for fatty acids in serum cholesteryl esters in relation to CVD and total mortality
Fatty acid and estimated
desaturase activities Scrum proportion
Cardiovascular disease mortality
(n 5 461 events) Total mortality
(n 5 1012 events)
% of total FAs
Myristic acid (14:0) 1.1 6 0.3 1.16 (1.06, 1.27) 1.12 (1.02, 1.23) 1.09 (1.03, 1.16) 1.06 (0.99, 1.13)
Palmitic acid (16:0) 11.7 6 0.99 1.25 (1.14, 1.37) 1.15 (1.04, 1.26) 1.16 (1.09, 1.24) 1.09 (1.02, 1.17)
Palmitoleic acid (16:1) 3.5 (3.0–4.4) 1.32 (1.21, 1.44) 1.18 (1.07, 1.30) 1.28 (1.21, 1.36) 1.19 (1.11, 1.27)
Stearic acid (18:0) 1.1 (0.97–1.3) 1.07 (0.97, 1.17) 1.04 (0.94, 1.15) 1.01 (0.95, 1.08) 0.98 (0.91, 1.04)
Oleic acid (18:1) 19.4 6 2.7 1.29 (1.18, 1.41) 1.18 (1.07, 1.30) 1.25 (1.18, 1 33) 1.17 (1.10, 1.25)
Linoleic acid (18:2n–6) 53.9 6 5.2 0.76 (0.70, 0.83) 0.85 (0.78, 0.94) 0.80 (0.76, 0.85) 0.87 (0.81, 0.93)
g-Linolenic acid (18:3n–6) 0.71 6 0.30 1.15 (1.05, 1.27) 1.09 (0.98, 1.21) 1.08 (1.01, 1.15) 1.04 (0.97, 1.11)
a-Linolenic acid (18:3n–3) 0.66 6 0.16 1.08 (0.99, 1.18) 1.10 (1.0, 1.21) 1.03 (0.97, 1.09) 1.03 (0.97, 1.10)
0.57 1 0.13 1.16 (1.07, 1.27) 1.06 (0.96, 1.18) 1.07 (1.01, 1.14) 1.0 (0.94, 1.08)
Arachidonic acid (20:4n–6) 4.8 6 0.93 1.00 (0.92, 1.10) 0.95 (0.86, 1.05) 0.98 (0.92, 1.04) 0.96 (0.90, 1.02)
1.3 (0.9–1.6) 1.07 (0.98, 1.17) 0.99 (0.90, 1.09) 1.04 (0.98, 1.11) 1.0 (0.94, 1.08)
0.68 (0.56–0.81) 0.97 (0.89, 1.07) 0.92 (0.84, 1.02) 0.96 (0.90, 1.02) 0.95 (0.89, 1.02)
SCD (16:1/16:0) 0.30 (0.26–0.37) 1.27 (1.16, 1.39) 1.15 (1.04, 1.27) 1.26 (1.18, 1.34) 1.18 (1.10, 1.26)
D6D (18:3n–6 /18:2n–6) 0.012 (0.009–0.017) 1.20 (1.10, 1.32) 1.12 (1.0, 1.24) 1.12 (1.06, 1.19) 1.07 (1.0, 1.14)
D5D (20:4n–6/20:3n–6) 8.6 6 2.0 0.84 (0.76, 0.93) 0.88 (0.80, 0.98) 0.92 (0.86, 0.98) 0.96 (0.89, 1.02)
CVD, cardiovascular disease; FAs, fatty acids; SCD, steroyl-CoA-desaturated; D6D, D
-desaturase; D5D, D
*Values are means 6 SD or means (interquartile ranges).
†Values are hazard ratios (95% conﬁdence intervals).
‡The adjusted model included total-C, body mass index, smoking, physical activity, and hypertension.
Permission to reuse table granted by American Society for Nutrition.
222 Journal of Clinical Lipidology, Vol 6, No 3, June 2012
Collectively these data showed that despite MUFA-fed
monkeys having a lower LDL-C/HDL-C ratio, there was no
difference in the amount of atherosclerosis between the
SFA- and MUFA-fed monkeys, and only the monkeys fed
PUFA were protected against coronary art ery atherosclero-
sis. It was suspected that the high cholesteryl oleate
composition of plasma LDL may have inﬂuenced this
outcome. An examination of the livers of these animals
poststudy indicated that the MUFA-fed animals had twice
as much cholesteryl ester accumulation compare d with
monkey livers from the other two groups.
perfusion yielded a strong correlation (r 5 0.8) between
the extent of coronary artery atherosclerosis and perfusate
cholesterol ester secretion rate.
Acetyl-coenzyme A acetyltransferase 2 (ACAT2) ester-
iﬁes hepatic cholesterol and is responsible for secretion of
cholesterol esters, primarily cholesteryl oleate. In view of
the data on hepatic perfusion, it can be hypothesized that
dietary MUFA promoted hepatic ACAT2-catalyzed choles-
teryl oleate secretion into lipoproteins, leading to enhanced
atherogenicity. The aortic cholesterol est er concentration in
LDL receptor null, apo-B1002only mice with and without
ACAT2 was similar to that seen in the African green
The percentage of cholesterol ester as choles-
teryl oleate in mice without ACAT2 was dramatically re-
duced and replaced by cholesterol esters with PUFA.
Furthermore, ACAT2 gene deletion limited the severity of
aortic atherosclerosis independent of the type of fat that
was fed. These data from two animal models are consistent
with the hypothesis that stimulation of hepatic ACAT2-
mediated cholesteryl oleate secretion by dietary MUFA
can promote atherosclerosis.
In conclusion, the results from the animal studies
described herein suggest that the kind of fat consumed
impacts the amount of atherosclerosis that develops. Stud-
ies in nonhuman primates and mice have shown that dietary
MUFA does not protect any better than SFA against the
development of coronary artery atherosclerosis. Instead, it
is dietary PUFA that offers protection. ACAT2 is the
presumed mediator of these fatty acid effects, a point that
remains to be proven in humans. Finally, the protect ion
offered by the Mediterranean diet is likely attributable to
the many differences in the diet other than olive oil.
Monounsaturated fatty acid intake and
atherosclerotic cardiovascular disease risk
Kevin C. Maki, PhD
Biofortis-Provident Clinical Research, Addison,
The National Cholesterol Education Program Third Adult
Treatm ent Panel introduced the Therapeutic Lifestyle
Changes (TLC) diet, which was more restrictive regarding
SFA and cholesterol than the previous Step I diet.
ever, total fat intake was liberalized from ,30% to up to
35% of calories, with an emphasis on unsaturated fats,
primarily from MUFA (up to 20% total calories) and second-
arily PUFA (up to 10% total calories). There are several
sources of MUFA in the diet, including nuts and nutlike
foods (eg, macadamia, almonds, pistachios, peanuts, and ha-
zelnuts), seeds, and vegetable oils (Table 2).
sometimes underappreciated, foods containing animal fats
such as cheddar cheese, whole eggs, and ground beef also
contain a high percentage of MUFA (28%269% of the fatty
acids per serving).
Decades of clinical studies in humans have demon-
strated that modiﬁcation of the fatty acid cont ent of the
diet can affect the lipoprotein/lipid proﬁle. For example,
LDL-C increases when carbohydrate in the diet is replaced
with either trans-fatty acids or SFAs (Fig. 4).
LDL-C is reduced when carbohydrates are replaced with
MUFAs or PUFAs, although the effect is more pronounced
HDL-C is reduced by the addition of trans-
fatty acids to the diet, but replacement of carbohydrate
with SFAs, MUFAs, or PUFAs will increase HDL-C, with
MUFA having an intermediate effect between those of
SFA and PUFA. The total-C/HDL-C ratio is raised by
trans-fatty acid intake but there is a relatively neutral effect
with SFAs because they increase both total-C and HDL-C.
Reductions in the total-C/HDL-C ratio occur with both
PUFAs and MUFAs.
It is therefore critical to take into ac-
count the nutrient being replaced when considering the
lipid effects of fatty acids.
Data from diet intervention trials have demonstrated
relationships between shifts in dietary fatty acid intakes and
Table 2 Fatty acid content of selected foods and oils
Total SFA MUFA PUFA
Nuts and Nutlike Foods
Macadamia 1 oz 21.6 3.4 16.8 0.4
Almonds 1 oz 15.7 1.2 9.9 3.8
Pistachios 1 oz 12.9 1.6 6.8 3.9
Peanuts 1 oz 14.0 1.9 6.9 4.4
Walnuts 1 oz 18.5 1.7 2.5 13.4
Hazelnuts 1 oz 17.0 1.3 12.8 2.2
Avocado 1 19.9 2.9 13.3 2.5
Cheddar cheese 1 oz 9.3 5.9 2.6 0.3
Whole egg 1 medium 5.0 1.6 1.9 0.7
95% lean ground
0.25 lb 5.4 2.4 2.2 0.3
fatty acid content
High oleic safﬂower 6.2 74.6 14.4
Olive 13.8 73.0 10.5
Canola 7.0 61.0 32.0
Peanut 16.9 46.2 32.0
Corn 12.9 27.6 54.7
MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty
acids; SFA, saturated fatty acids.
Baum et al Fatty acids in cardiovascular health and disease 223
changes in card iovascular risk markers. Jenkins et al
placed subjects with hypercholesterolemia on a 1-month
TLC diet lead-in followed by one of two dietary portfolios
for 1 month, both of which were high in soy protein and
viscous ﬁber and designed to be either high (26% energy)
or low (13% energy) in MUFA. At the conclusion of the
lead-in period, the HDL-C concentrations declined; and
when subjects were switched to the high MUFA diet, there
was a 12.5% increase in HDL-C that was not present with
the low MUFA diet. This was accompanied by an increase
in apo A1 concentrations, suggesting a possible increase in
the number of HDL particles. LDL-C was reduced follow-
ing the TLC lead-in diet and continued to decline following
both the high- and low-MUFA diets. There were no differ-
ences between the two diets in LDL-C or apo B concentra-
tions, indicating no difference in the number of atherogenic
particles. Interestingly, high sensitivity C-reactive protein
was signiﬁcantly reduced by the high MUFA diet relative
to the lower MUFA diet, a ﬁnding that merits additional
The results from this and other dietary intervention trials
suggest that reductions in LDL-C, non-HDL-C, and apo B
occured when MUFAs replaced SFAs in the diet.
When MUFAs replace carbohydrates in the diet, TG, very
low-density lipoprotein-C, high-sensitivity C-reactive pro-
tein, and blood pressure decrease , while HDL-C and apo
These changes suggest that increased
MUFA intake should reduce the risk of cardiovascular
events. However, caution is warranted because results
from studies in nonhuman primates and mice, as reviewed
by Dr. Rudel, have suggested that dietary MUFA compared
to SFA intake may not protect against the development of
coronary artery atherosclerosis, despite favorable changes
in serum lipoprotein lipids.
There is little clinical trial evidence available regarding
MUFA intake and CHD ou tcomes, but in epidemiological
studies researchers have examined this relationship. In the
Nurses’ Health Study, modeling an isocaloric replacement
of 5% of energy from SFA with carbohydrate was associated
with a nonsigniﬁcant reducti on in CHD risk (Fig. 5).
carbohydrates were substituted for MUFAs, CHD risk was
increased, whereas when MUFAs were substituted for
SFAs there was an apparent reduction in risk. However,
such results are challenging to interpret because MUFA in-
take is highly correlated with SFA intake (correlation
Figure 4 Changes in blood lipid levels following replacement of
carbohydrate with various fats. b reﬂects the change for each 1%
energy isocaloric replacement. *P , .05. CHO, carbohydrate; TC,
total cholesterol; TFA, trans-saturated fatty acids. Permission to
reuse ﬁgure granted by Springer.
Figure 5 Estimated percent changes in CHD risk with isocaloric substitutions of dietary components: The Nurses’ Health Study. Permis-
sion to reuse ﬁgure granted by New England Journal of Medicine, Massachusetts Medical Society.
224 Journal of Clinical Lipidology, Vol 6, No 3, June 2012
coefﬁcient of 0.81 in the Nurses’ Health Study data) and is
moderately correlated with intakes of PUFA (correlation co-
efﬁcient 0.30) and trans-fatty acids (correlation coefﬁcient
Tanasescu et al
evaluated the relationships between
speciﬁc dietary fatty acids, cholesterol, and CHD risk in
5672 women with type 2 diabetes in the Nurses’ Health
Study. The age-adjusted relative risk (RR) between the
greatest (.19.9% total energy) and lowest (,13.4% tot al
energy) quintiles of MUFA intakes was 1.22 (95% conﬁ-
dence interval [95% CI] 0.9521.56). In the multivariate
analysis (adjusted for age; smoking; postmenopausal hor-
mone use; parental history of MI before age 60 years; mod-
erate/vigorous activities; body mass index; total caloric,
protein, ﬁber, and alcohol intakes; and multivitamin, vita-
min E supplement, and medication use), the association
was attenuated (RR 1.10, 95% CI 0.8221.46), and further
adjustments (for intakes of SFA, PUFA, and trans unsatu-
rated fats and cholesterol) led to a reversal in the direction
of the association (RR 0.84, 95% CI 0.5321.34). Although
these relationships were not signiﬁcantly different from
unity, the pattern illustrates the difﬁculties encountered
when modeling highly correlated dietary exposures to as-
sess their associations with dise ase risk.
Mente et al
evaluated the relationships between vari-
ous dietary factors and CHD risk and found that a Mediter-
ranean diet was associated with a lower incidence of
coronary outcomes, as were diets consisting of a high in-
take of nuts and MUFA. There are several potential protec-
tive components of the Mediterranean diet, and this diet, as
well as diets rich in nuts, are typically greater in MUFAs.
Other investigations on nut intake have demonstrated ben-
eﬁts on the lipid proﬁle. An analysis of 25 intervention
trials including 583 men and women with normal or ele-
vated lipids showed that a mean intake of 67 g/d nuts led
to reductions in total-C, LDL-C, and the total-C/HDL-C
Pooled data from four cohort studies also reported
a signiﬁcantly lower risk for CHD mortality associated
with higher nut intake.
Mozaffarian et al’s
review and meta-analysis of ran-
domized controlled trials showed that replacement of SFA
with PUFA was associated with lower predicted CHD risk
(RR 0.91, 95% CI 0.8720.95), based on changes in the
total-C/HDL-C ratio; (Fig. 6). This ﬁnding was consistent
with the protective effect observed in a pooled analysis of
data from 11 observational cohort studies (RR 0.87, 95%
When MUFAs were substituted for SFAs
in clinical trials, there was also a predicted beneﬁt based
on changes in the total-C/HDL-C ratio (0.93, 95% CI
0.8920.96). The pooled analysis of observational cohort
data suggested a trend in the opposite direction (RR 1.19,
95% CI 1.0021.42),
although, as illustrated by the previ-
ous example, the point estimates can be markedly inﬂue nced
by adjustment for other correlated dietary components, so
caution in interpretation of such results is warranted.
Other factors should also be taken into account when
considering the relationship between MUFA intake and
atherosclerotic CVD risk. For example, MUFAs coexist with
SFAs in many foods. In addition, cis- and trans-isomers of
MUFAs were sometimes categorized together in
Figure 6 Effects on CHD risk of consuming PUFA, carbohydrate, or MUFA in place of SFA. Predicted effects were determined by
changes in the TC/HDL-C ratio in short-term trials (eg, each 5% energy of PUFA replacing SFA lowers TC/HDL-C ratio by 0.16) coupled
with observed associations between the TC/HDL-C ratio and CHD outcomes in middle-aged adults. Evidence for effects of dietary changes
on actual CHD events came from the meta-analysis of eight randomized controlled trials for PUFA replacing SFA and from the Women’s
Health Initiative randomized controlled trial for carbohydrate replacing SFA. Evidence for observed relationships of usual dietary habits
with CHD events was from a pooled analysis of 11 prospective cohort studies. RCT, randomized controlled trials; RR, relative risk;
TC, total cholesterol; WHI, Women’s Health Initiative. Permission to reuse ﬁgure granted by PLoS Medicine.
Baum et al Fatty acids in cardiovascular health and disease 225
epidemiological studies. Studies that speciﬁcally assessed
trans-fatty acid intake sometimes characterize d them poorly,
which may have led to residual confounding. Possible ef-
fects of the other nutrients in foods being replaced and
what is substituted for the displaced foods also have to be
considered. Furthermore, the speciﬁc food sources of
MUFA may inﬂuence the results. For example, relatively un-
reﬁned olive oil retains several lipophilic components,
whereas highly reﬁned olive oil has a low level of some of
these potentially bioactive compounds. The net effect of a
particular dietary change may also be modiﬁed by character-
istics of the population being studied. Individuals with insu-
lin resistance, metabolic syndrome, diabetes, or
dyslipidemia may respond differently from those who do
not have these conditions. Therefore, in light of the uncer-
tainty regarding the relationship between consumption of
speciﬁc fatty acids and CVD risk, the most prudent recom-
mendation in the author’s view is a dietary pattern that em-
phasizes whole grains, legumes, nuts and oils, fruits,
vegetables, ﬁsh, lean meats, and low-fat dairy products,
with sparing consumption of reﬁned grains, white rice, pota-
toes, stick margarines, shortenings, sugar-sweetened sodas,
confectionary products, desserts, high-fat meat and high-
fat dairy products.
Dietary n-6 PUFA and CVD risk
Jay Whelan, PhD, MPH
University of Tennessee, Knoxville, TN, USA
LA is the parent compound for all n-6 PUFAs. When
consumed, LA can be theoretically converted to and enrich
tissues with AA via the rate limiting D
AA subsequently can be converted to bioactive eicosanoids,
which have been linked to processes involved in the devel-
opment of cancer, CVD, and inﬂammation.
Elevated LDL-C and LDL particle concentrations con-
tribute to the atherosclerotic process by injuring the vascu-
lar endothelium resulting in lipid deposition and necrosis. It
is well established that LDL-C is a risk factor for CVD, and
reducing LDL-C decreases CVD risk.
In a stud y of 1098 United States white, Japanese
American, Japanese, and Korean men, greater serum LA
concentrations were signiﬁcantly associated with lower
concentrations of LDL particles.
An inverse relationship
between dietary PUFA and CVD was recently conﬁrmed
in a review by Astrup et al,
who summarized the evidence
from epidemiologic, clinical, and mechanistic studies in
which authors consistently reported that replacement of
SFA with PUFA reduced the risk of CHD. In a 15-year
study of 1551 white men, energy-adjusted dietary intakes
of PUFA and LA in the upper tertil e were associated with
more than a 50% lower risk for CVD mortality.
30-year Uppsala Longitudinal Study, the authors reported
that CVD mortality was lower for individuals with choles-
terol ester LA levels above versus below the median.
ilarly, investigators from the Nur ses’ Health Study reported
that increasing intakes of LA corresponded with a gradual
reduction in CHD risk, and risk for MI declined with higher
levels of LA in serum lipids.
The American Heart Association Scientiﬁc Advisor y
recommends an n-6 fatty acid or LA intake of 5% to 10%
of calories, based primarily on a review of four ecological,
two case control, 18 prospective cohort, and 10 randomized
controlled trials in which authors concluded that consump-
tion of 5% to 10% of energy from LA or n-6 fatty acids
reduced the risk of CHD relative to intakes below 5%.
review of 12 prospective cohorts and 9 randomized con-
trolled trials, Czernichow et al
concluded that the body of
evidence supports the recommendation of n-6 PUFA intake
greater than 5%, and ideally near 10% of energy, for reducing
risk. Furthermore, consumpt ion below the current lowest
values of LA in France, 4% of energy, was not recommended.
At intakes of 12 to 17 g/d, LA is the major PUFA in the
United States diet. ALA intake is typically in the range of
1.1 to 1.6 g/d, resulting in an n-6/n-3 ratio of approximately
10:1. When LA consumption increas es, consumption of
ALA also increases.
Soybean oil is the main contributor
of dietary LA in the United States; 88% of PUFA in soy-
bean oil is LA. The intake of soybean oil (n-6/n-3 ratio
of approximately 8:1) dramatically increased beginning
Interestingly, with this huge inﬂux of LA,
the mortality rates of CHD precipitously declined.
One criticism of the aforementioned observational stud-
ies is that people do not eat LA in isolation. Typically, n-3
PUFAs, including ALA, accompany LA in the diet. There-
fore, a more controlled study to evaluate the effects of LA,
separate from n-3, on CHD risk was needed. In an evaluation
of previous data, studies were divided into an n-6-only
group, and an n-3/n-6 mix in which the LA content of the
diet was between 5- and 20-fold greater than the n-3
There was no signiﬁca nt increase in nonfatal MI
risk observed in the n-6-only group, and some reduced risk
occurred in the n-3/n-6 group. With regard to relative risk
for CHD death, there was no signiﬁcant risk reduction re-
ported in either of the groups.
A major concern with dietary LA consumption is that it
theoretically enriches tissues with AA with subsequent
generation of excessive amounts of pro-inﬂammat ory eico-
To further address the potential adverse mech-
anism associated with increased LA intake, conversion of
LA to AA and subsequent increased eicosanoid production,
Rett and Whelan examined 36 papers, identiﬁed from more
than 4300, and asked: If intakes of LA were increased or
decreased from typical dietary intakes, would AA in tissue
It was observed that increasing di-
etary LA levels by up to six-fold, or decreasing them by up
to 90%, did not change plasma/serum AA content
(Fig. 7 ).
These data were consistent with those published
by Liou and Innis
in a randomized crossover study of men
consuming a 1% ALA diet containing either 4% or 10%
LA. Changing LA content had little or no effect on AA
content in plasma phospholipids. In fact, if anything, an in-
verse relat ionship was detected; as LA increas ed, AA levels
226 Journal of Clinical Lipidology, Vol 6, No 3, June 2012
decreased. In earlier studies, Lands
also showed little
change in AA content between 4% and 10% LA consump-
tion in the United States.
Despite these ﬁndings, it has been suggeste d that LA
intakes should be reduced to less than 2% of energy to
change the tissue AA levels. However, if LA were reduced
or eliminated, there is no guarantee that dietary gamma-
linolenic acid or AA would not replenish tissue AA levels
and maintain those levels in tissues. Because LA is a major
constituent in most common foods consumed, it is difﬁcult
to determine how to decrease LA intake from 14.5 g/d (6%
of energy) to 4.5 g/d (2% of energy). Selective elimination
from the diet of foods with high LA content could also be
undesirable. For example, as discussed previously, the
advent of increasing soybean oil (88% of PUFA is LA) in
the food supply was associated with reductions in the risk
Even so, the elimination of soybean oil, a ma-
jor source of LA in the diet, would require changing the en-
tire food supply infrastructure in the United States, which is
a difﬁcul t proposition. Similarly, targeting foods that con-
tribute to a balanced diet, such as walnuts, which have an
LA content of 81% of PUFA, would also be undesirable be-
cause walnut consumption decreases total-C and LDL-C
and has been associated with lower CVD risk.
ducing LA does not appear to be the best way to decrease
AA in tissue phospholipids. If it were desirable to do so, the
best strategy for reducing AA would be to increase the in-
take of long chain n-3 PUFA. The American Heart Associ-
ation recommends an EPA 1 DHA intake of 500 mg/d in
patients without coronary artery disease (ie, 400 mg/d in
addition to the w100 mg/d that is typically consumed)
which would result in a 20% to 25% reduction in tissue
AA content, and has been associated with a signiﬁcantly re-
duced risk of sudden death compared with lower n-3 blood
The 2010 Dietary Guidelines for Americans rec-
ommends 250 mg/day, which is twice current intake.
In conclusion, available evidence suggests that increas-
ing intake of LA correlates with reduced CHD risk.
However, because of the theoretical potential for LA to
be converted to AA leading to putative increased produc-
tion of potentially damaging eicosanoids, additional re-
search that suppor ts current dietary recommendations for
PUFA would resolve the lingering controversy about their
Are All PUFA created equal? LA-speciﬁc
PUFA interventions show no beneﬁt and a
signal toward harm in randomized controlled
Christopher E. Ramsden, MD, USPHS
NIH, Bethesda, MD, USA
Are all PUFAs created equal? The main objective of this
presentation is to evaluate whether n-6 LA is cardiopro-
tective, on the basis of the best-available evidence from
clinical trials that selectively increased LA in place of SFA
and trans-fatty acids. Key questions addressed are: (1) Are
all PUFAs equivalent? Use of the general term PUFA im-
plies that all PUFAs are a single molecular species with
shared metabolic and health effects when, in reality, the
situation is more complex; and (2) Is the speciﬁc PUFA
composition of a given dietary intervention a critical deter-
minant of its effect on CHD risk?
The pooled analysis of 11 prospective cohorts by
Jakobsen et al
demonstrated that for every 5% increase
in energy as PUFA, in place of SFA, there was a 13% re-
duction in CHD risk. It should be noted that although the
most abundant PUFA was LA, all PUFAs, including n-3
and n-6 fatty acids, deﬁned the exposure variable(s). It is
not necessarily a valid assumption to attribute effects of
PUFA in general to LA. Similarly, it is not a valid assump-
tion that because 88% of PUFA content of soybean oil is
LA (ratio of LA to ALA of 8:1), that, soybean oil is equiv-
alent to LA.
A pooled analysis of randomized controlled trials of
dietary PUFA and clinical CHD outcomes reported a 10%
CHD risk reduction for every 5% of energy substitution of
PUFA in place of SFA.
However, again, the independent
Figure 7 Effects of decreasing and increasing dietary LA in-
takes on changes in blood phospholipid AA content. Signiﬁcant
(P , .05) changes in AA as reported in the original papers desig-
nated as triangles; nonsigniﬁcant (P . .05) AA changes as re-
ported in the original papers designated as diamonds. PL,
phospholipid. Permission to reuse ﬁgure granted by BioMed
Baum et al Fatty acids in cardiovascular health and disease 227
variable was total PUFA including not only n-6 LA, but
also n-3 ALA, EPA, and DHA. In the American Heart As-
sociation advisory, the reviewed data similarly evaluated
the CHD effects of PUFA in general but the advice was
more speciﬁc, in advising Americans to maintain or in-
crease consumption of n-6 PUFA.
One extreme example of confounding resulting from a
lack of clarity in deﬁning the independent variable(s) is
from the Oslo Diet Heart Study.
According to Leren,
men from Oslo had a 7-fold increased incidence of ﬁrst
MI in the two decades before the trial, indicating that the
normal diet was likely atherogenic, perhaps as the result
of the high trans-fatty acid content. The cont rol d iet con-
tained massive amounts of partially hydrogenated ﬁsh oil
and vegetable oil margarines (w65 g/d), with w9% to
10% of calories from trans fatty acids, including some 20
and 22-carbon trans-PUFA. The control diet was very
low in LA and ALA, as well as EPA and DHA. In the in-
tervention group, margarines were replaced with a large
amount of soybean oil, which markedly increased LA to
nearly 16% of calories, but, importantly, also substantially
increased ALA to about 4.5 times average United States in-
take. Perhaps most importantly, the investi gators provided
Norwegian sardines canned in cod liver oil and advised
the substitution of ﬁsh, shellﬁsh, and whale in place of
meats and eggs. The intervention group consumed w5g/
d of EPA and DHA, which is equivalent to approximatel y
16 ﬁsh oil capsules per day. Despite this dominant con-
founder, the Oslo trial has previously been considered
strong evidence for the beneﬁts of n-6 LA.
Interestingly, ALA and/or EPA and DHA were also
increased substant ially in all but one of the randomized
controlled trials pooled by Mozaffarian et al.
trial included which selectively increased LA (in place of
SFAs and trans fatty acids) showed a slight signal in the op-
Controlled trials that substituted LA for SFAs and trans-
fatty acids are arguably the best available evidence for
evaluating the effects of LA, without the potentially con-
founding role of n-3 EPA 1 DHA and/or ALA. In an effort
to more speciﬁcally evaluate the effects of LA separate from
other PUFAs, a detailed evaluation of the dietary interven-
tions and oils provided in studies described in cited random-
ized controlled trial manuscripts, other obscure manuscripts
from these trials, R01 and other grant materials, and data
from interim analyses were included.
From the database
constructed using this information, it was apparent that there
were three trials (four datasets) with 9569 participants, that
increased LA selectively. Four other datasets with 1706 par-
ticipants substantially increased n-3 ALA and/or EPA 1
DHA in addition to n-6 LA, thereby preventing a speciﬁc
evaluation of the effects of LA. These datasets are described
The Rose Corn Oil Trial, a study with 54 participants,
was the ﬁrst LA-selective PUFA trial.
Corn oil was
substituted for typical fat sources, including hydrogenated
oils, and was also taken as a supplement. There was more
than a four-fold increased risk of CHD death and death
from all causes in the corn oil group. Rose concluded
that ‘‘corn oil cannot be recommended in the treatment of
ischemic heart disease’’ because it is ‘‘most unlikely to be
beneﬁcial and possibly harmful.’’
The next LA selective PUFA trial, the Sydney Diet Heart
Study (n 5 458), has received little attention.
publication identiﬁed the oil provided as w2 tablespoons/d
of liquid safﬂower oil as well as a safﬂower polyunsatu-
rated margarine (Miracle Margarine, Marrickville Marga-
rine Party Limited). After intervention, there was a 49%
increased risk of death from all causes in the LA selective
PUFA group, which approached statistical signiﬁcance de-
spite the replacement of animal fats and common marga-
rines. Because most of these deaths were caused by CHD
(91% of total deaths were CHD deaths; 96% were CVD
deaths in the two groups combined), omission of the Syd-
ney data from previous analyses likely led to an overestima-
tion of the apparent beneﬁts of PUFA on CHD risk
reduction in general and an underestimation of possible
harm of n-6 LA.
The ﬁnal n-6 LA-selective PUFA randomized controlled
trial was the Minnesota Coronary Survey, in which corn oil
and corn oil polyunsaturated margarine, providing w14.5%
of calories from LA, were the intervention oils provided for
an average of slightly longer than 1 year.
This is the only
randomized controlled trial that included women (.4600).
There was no alteration in the risk for CHD or death asso-
ciated with the LA intervention in the 4500 male partici-
pants. However, in women in the experimental group
there were statistically insigniﬁcant increased risks for non-
fatal MI (147%), composite CHD and CVD events
(130%), and death (116%).
Analyses of individual trials and a meta-analysis of
pooled data from the aforementioned three studies (four
datasets) resulted in a relatively consistent increased risk
associated with LA consumption (Fig. 8).
Sydney Study was included in the pooled analysis, with
the assumption that 91% of all deaths in each group were
caused by CHD, it increased the risk for CHD death
(128%), CHD events (125%), and death from all causes
(116%) associated with LA. Exclusion of the Sydney data
from the meta-analysis resulted in a statistically insigniﬁcant
risk ratio for CHD events of 1.13. Thus, there was no indica-
tion of beneﬁt and a nonsigniﬁcant signal toward harm from
LA-speciﬁc PUFA interventions as a replacement for SFAs
and trans-fatty acids. Important limitations of this analysis
included the small number of datasets, moderate number
of participants with LA-speciﬁc interventions (fewer than
10,000), limited generalizability to other patient popula-
tions, and high LA dose (14%215% of calories as LA, com-
pared with the average American consumption of 6%27%).
Evaluation of the studies that substantially increased n-3
and n-6 intakes indicated a different result. When catego-
rized into three groups: (1) LA 1 EPA 1 DHA interventions
showed a signiﬁcant beneﬁt; (2) LA 1 ALA without EPA 1
DHA showed a signal toward beneﬁt; and (3) LA-selective
228 Journal of Clinical Lipidology, Vol 6, No 3, June 2012
PUFA interventions showed a signal in the opposite direction
As is apparent, the results for LA were not in the
right direction. Mechanisms through which EPA and DHA
may have cardioprotective effects are well-documented.
Some have also speculated that ALA may reduce risk for ar-
rhythmias, enhance arterial compliance, and lower levels of
One might therefore speculate that
n-3s in general, and especially EPA 1 DHA, were cardiopro-
tective in these trials, and that these beneﬁts were attenuated
by the concomitant increase in LA.
There are two major gaps in the critical evidence. First,
there are no randomized controlled trial data evaluating effects
on CHD of diets with LA intakes between 2% and 5% of
calories, the advised cutoff. To put this into context, it is
estimated that the range of LA intake in historical (evolution-
ary) diets was w2-3%. At the beginning of the 20
LA intake in the United States was w2% of calories. Because
it is difﬁcult to consume more than 5% of calories from LA
without added seed oils, a reduction in LA to 2% to 3% of cal-
ories would not create an atypical scenario. In fact, that is the
amount of LA provided by virtually any whole food-based
diet, whether it is meat-based, or it is predominantly
vegetable-based. The second gap in the critical evidence is
that there have been no studies assessing the effect on CHD
of selectively increasing n-3 ALA, without increasing LA.
n-3 PUFA: Does new research debunk old
truths? The omega-3 debate
Robert C. Block, MD, MPH
University of Rochester Medical Center, Rochester,
This presentation reviews recent marine-derived n-3
fatty acid clinical trials that evaluated pote ntial beneﬁts
for reducing CVD. Also considered are evidence-based
dietary guidelines for n-3 fatty acids, as well as the
potential safety, and multi-organ effects of EPA and DHA.
The Gruppo Italiano per lo Studio della Sopravvivenza
nell’Infarto (GISSI) Miocardico Prevenzione Trial random-
ized w11,000 subjects (85% men) soon after they had an
Figure 8 Forest plots of CHD death and death from all causes from a meta-analysis of randomized controlled trials in which dietary
interventions increased n-6 PUFA speciﬁcally, or increased both n-3 and n-6 PUFA. (A) indicates mixed n-3/n-6 randomized controlled
trial datasets providing substantial quantities of n-3 EPA 1 DHA and n-6 LA; (B) indicates mixed n-3/n-6 datasets providing substantial
quantities of n-3 ALA and n-6 LA; (C) indicates n-6 speciﬁc datasets selectively increasing n-6 LA. Permission to reuse ﬁgure granted by
Cambridge University Press.
Baum et al Fatty acids in cardiovascular health and disease 229
MI (within 3 months) to 1 g/d ﬁsh oil concentrate, which
provided w840 mg combined EPA and DHA, similar to
the prescription ﬁsh oil product available in the United
The authors found that there was a signiﬁcant re-
duction in sudden cardiac death and cardiovascular events
that was evident after approximately 3 months of treatment.
A subsequent randomized double-blind controlled trial by
the same group studied patients with congestive heart fail-
ure. Participants were given either 1 g/d ﬁsh oil concentrate
(840 mg of EPA 1 DHA) or placebo and followed for 3.9
The investigators reported a signiﬁcant difference
between ﬁsh oil and placebo treatments in those who died
from any cause (27% and 29%, respectively) and those
who died from or were admitted to hospital for cardiovas-
cular reasons (57% and 59%, respectively). The authors es-
timated that 56 patients needed to be treated for a median
duration of w4 year s to avoid one death, and in the same
timeframe 44 patients needed to be treated to avoid one
event of admission to hospital for cardiovascular reasons.
In both groups, gastrointestinal disorders, although infre-
quent, were the most common adverse reactions, which
has been the case in nearly every n-3 fatty acid study.
The rates of other adverse events tended not to differ signif-
icantly from placebo.
In a more recent randomized controlled, prospective
double-blind parallel study, 663 United States outpatients
with symptomatic paroxysmal or persistent atrial ﬁbrilla-
tion received 6720 mg/d of EPA 1 DHA for 7 days and
then 3360 mg/d of EPA 1 DHA for 24 weeks in the FDA-
approved prescription ﬁsh oil product.
There was no
beneﬁt of prescription n-3 in reducing the ﬁrst episode of
recurrent symptomatic atrial ﬁbrillation among all subjects,
nor were there any signiﬁcant effects detected in subgroups
on the basis of age, sex, race, smoking status, or diabetes.
Limitations of this study included that the population was
primarily persons with paroxysmal atrial ﬁbrillation, with-
out o ther signiﬁcant cardiac issues, such as reduced left
ventricular ejection fraction or other mechanical problems.
Furthermore, this trial was not powered to investigate epi-
sodes of stroke or CVD, so it was not possible to evaluate
other clinically important events such as mortality, and it
was not designed to evaluate a dose effect. Another weak-
ness of this trial could be that ﬁsh intake was not deter-
mined; however, it is not practical to obtain 3.6 g/d of
EPA 1 DHA by consuming ﬁsh, so this design ﬂaw prob-
ably had little impact on the ﬁndings.
In the Alpha Omega trial, a randomized double-blind
placebo-controlled multicenter study, investigators assessed
whether EPA and DHA, given for 40 months to individuals
w3.5 to 4 years after MI, would improve cardiovascular
N-3 fatty acids were provided as one of four trial
margarines supplemented with: 400 mg of combine d
EPA 1 DHA, 2 g of ALA, 400 mg of EPA 1 DHA 1 2g
of ALA, or placebo. The dose of ALA was signiﬁcantly
more than what is typically consumed in the United States,
and the dose of EPA 1 DHA was relatively low. However,
if the amount of EPA 1 DHA already present in the diet
(w130 mg/d) was considered, subjects in the EPA and
DHA treatment group consumed w500 mg/d, which meets
current recommendations from various organizations.
In the Alpha Omega trial, there were no signiﬁcant
differences between groups in the primary outcome, major
cardiovascular events, or other end points (Table 3).
though the EPA 1 DHA arm had fewer fatal cardiovascular
events early in the study, Kaplan-Me ier curves showed no
signiﬁcant beneﬁt with regard to either fatal CHD or major
cardiovascular events. This study was considered to show a
neutral effect; however, subgrou p analyses conduc ted post
hoc showed that patients with diabetes receiving EPA 1
DHA had signiﬁcantly reduced risk of incident CVD and
death from CHD.
Differences between the Alpha Omega trial
GISSI heart failure study
were that patients in Alpha
Omega had received optimal treatment for a period of
time, and the study intervention occurred signiﬁcantly
past their incident MI. Also, in the Alpha Omega trial, sub-
jects received state-of-the-art antihypertensive, lipid-
lowering (up to 90% for statins), and antithrombotic drugs
at much greater proportions than subjects in the GISSI
study. Limitations of the Alpha Omega trial included low
doses of EPA and DHA, and the fact that subjects were en-
rolled years after their MI, thereby missing opportunities
for evaluating effects of EPA and DHA on myocardial heal-
ing, arrhythmias, and ischemia in the acute and post-MI set-
ting. Furthermore, the number of subjects with diabetes was
relatively low, hindering statistical power for evaluations in
this high-risk population.
The OMEGA trial was a randomized double-blind
multicenter trial that evaluated 840 mg of EPA 1 DHA—
the same dose that was used in the GISSI study—versus an
olive oil control.
Subjects included 3851 survivors of an
acute MI (ST elevation or non-ST elevation) who were ran-
domized soon after the MI, similar to the GISSI study. The
primary outcome of sudden cardiac death, which was re-
duced in the GISSI study, was not beneﬁtted with treatment
in the OME GA trial (Fig. 9).
Furthermore, there were no
reductions in cardiovascular events, or sta tistically signiﬁ-
cant differences in total mortality or revascularization. Es-
sentially, this was a neutral study, although the guidelines
for treatment of acute cardiovascular events have improved
since the time of the GISSI study, which may explain why
the percentage of patients with sudden cardiac death was
signiﬁcantly lower in the OMEGA trial com pared with
the GISSI trial.
A major problem with the OMEGA trial was that the
investigators changed the inclusion criteria after the trial
had started becau se they realized that the study lacked
statistical power. In a statistical power calculation per-
formed before the study had been completed, it was
determined that w20,000 patients would have been re-
quired to demonstrate signiﬁcant differences in the out-
comes. Other limitations are that ﬁsh consumption
increased by nearly a factor of two in both groups, and
the OMEGA follow up period of w1 year is quite short.
230 Journal of Clinical Lipidology, Vol 6, No 3, June 2012
According to the 2010 Dieta ry Guidelines for Ameri-
cans, the amount and vari ety of seafood consumed should
be increased by choosing seafood in place of some meat
This is the ﬁrst time that such a recommen-
dation has been issued in the Dietary Guidelines. The
median in take of seafood in the United States is approxi-
mately 3.5 oz/week. Sea food varieties commonly con-
sumed in the United States that are greater in EPA and
DHA and tend to be lower in mercury, include salmon, an-
chovies, a nd h erring. The Dietary Guidelines also sugges t
that women who are pregnant o r breastfeeding consume 8
to 12 oz of seafood/week from a variety of seafood types.
This recommendation is based on improved infant visual
and cognitive development, even in the presence of great er
mercury levels. Because of its greater methyl mercury
content, white albacore tuna should be limited to 6 oz
per week, and ﬁsh that accumulate mercury, such as
tileﬁsh, shark, swordﬁsh, and king mackerel, should be
avoided, especially by p regnant an d breast feeding
Beyond the effects of EPA and DHA on CVD events,
these fatty acids have pleiotropic effects and very few side
effects, as well as few interactions with other drugs.
Areas of ongoing EPA and DHA research include the ﬁelds
of macular degeneration, corneal healing, neural health and
regeneration, anti-inﬂammation, inﬂammation-resolving,
antiapoptotic, attention deﬁcit hyperactivity disorder, and
other psychiatric disorders. When patients with major de-
pressive disorder and bipol ar disorder were given n-3,
they had reduced symptoms of depression,
gests that EPA and DHA may prove to be a viable option
for treating MI patients who have a high risk of depression
after being hospita lized.
However, other evidence has not
been supportive of this beneﬁt.
Results from some studies
suggest that n-3 fatty acids beneﬁt inﬂammation/autoim-
mune diseases, such as asthma and rheumatoid arthritis,
and lower the need to use anti-inﬂammatory drugs.
is also interest in the potential use of intravenous EPA and
DHA infusions for people who are injured badly on the bat-
tleﬁeld, due to the purported beneﬁts on inﬂammation and
Table 3 Primary and secondary outcomes according to n-3 supplementation in the Alpha Omega trial
EPA-DHA (N 5 2404)
Placebo or ALA Only
(N 5 2433)
P Valueno. (%)
patient-yr no. (%)
Primary outcome: major cardiovascular
336 (14.0) 46.0 335 (13.8) 45.7 1.01 (0.87–1.17) .93
Incident cardiovascular disease 170 (7.1) 22.4 185 (7.6) 24.3 0.92 (0.75–1.13) .43
Death from cardiovascular disease 80 (3.3) 10.3 82 (3.4) 10.5 0.98 (0.72–1.33) .89
Death from coronary heart disease 67 (2.8) 8.7 71 (2.9) 9.1 0.95 (0.68–1.32) .75
67 (2.8) 8.7 74 (3.0) 9.6 0.90 (0.65–1.26) .55
Death from any cause 186 (7.7) 24.0 184 (7.6) 23.7 1.01 (0.82–1.24) .92
ALA (N 5 2409)
Placebo or EPA–DHA
Only (N 5 2428)
P Valueno. (%)
patient-yr no. (%)
Primary outcome: major cardiovascular
319 (13.2) 43.6 352 (14.5) 48.1 0.91 (0.78–1.05) .20
Incident cardiovascular disease 168 (7.0) 22.1 187 (7.7) 24.5 0.90 (0.73–1.11) .34
Death from cardiovascular disease 78 (3.2) 10.1 84 (3.5) 10.8 0.94 (0.69–127) .67
Death from coronary heart disease 66 (2.7) 8.6 72 (3.0) 9.2 0.92 (0.66–1.29) .64
62 (2.6) 8.1 79 (3.3) 10.2 0.79 (0.57–1.10) .16
Death from any cause 182 (7.6) 23.5 188 (7.7) 24.1 0.97 (0.79–1.19) .80
ALA, alpha-linolenic acid; CI, conﬁdence interval; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid.
*The two groups that received EPA 1 DHA were combined and compared with the two groups that did not receive EPA 1 DHA (ie, the groups that
received either placebo or only ALA). Similarly, the two groups that received ALA were combined and compared with the two groups that did not receive
ALA (ie, the groups that received either placebo or only EPA 1 DHA).
†The hazard ratios and 95% conﬁdence intervals were calculated with the use of Cox proportional-hazards models.
‡Major cardiovascular events comprised fatal and nonfatal cardiovascular events and the cardiac interventions percutaneous coronary intervention
and coronary-artery bypass grafting.
xVentricular-arrhythmia-related events comprised sudden death, fatal and nonfatal cardiac arrest, and placement of implantable cardioverter
Permission to reuse table granted by New England Journal of Medicine, Massachusetts Medical Society.
Baum et al Fatty acids in cardiovascular health and disease 231
neural protection. Resolvins and protectins are metabolites
of EPA and DHA with anti-inﬂammatory and neuroprotec-
tive effects up to about 1000 times greater than EPA and
There could be great interest in the clinical beneﬁts
of these EPA and DHA metabolites in the future.
In conclusion, the beneﬁts of EPA 1 DHA supplemen-
tation for CVD prevention via supplements are supported if
ﬁsh intake is low, particularly in individuals with elevated
TG. Nonetheless, pleiotropic effects and possible beneﬁts
for depression and inﬂammatory diseases, issues that affect
many patients, are supportive of the use of these n-3 fatty
acids. Additional research is needed to more clearly deﬁne
the groups that would beneﬁt from supplemental n-3 fatty
acid intake and the mechanisms responsible for the beneﬁts
observed in observational studies and some clini cal trials.
The National Lipi d Association 2011 Fatty Acid Summit
included presentations that summarized current controver-
sies in fatty acid science relative to CVD risk. Food is
extraordinarily complex; thus, it is unlikely that randomized
controlled trials assessing dietary interventions will be able
to determine deﬁnitively the effects of altering intakes of
various fatty acids on CVD risk. To make dietary recom-
mendations, we will have to rely on epidemiologic evidence
coupled with controlled clinical trials on surrogate markers,
along with an evolving understanding of the pathophysiol-
ogy of CVD. Messages conveyed at the summit were that
SFAs have unfavorable effects on LDL-C and are probably
equivalent to reﬁned and high glycemic index carbohydrates
with respect to CVD risk (based on epidemiological studies).
Furthermore, the presentations underscored that, when
evaluating diet studies one must carefully consider which
foods and nutrients are substituted for those that are
displaced. With regard to MUFA, speciﬁcally oleic acid—
one element of a Mediterranean diet, substantial evidence
was presented for favorable effects on CVD risk markers
and a suggestion of beneﬁt from some observational
studies. However, a MUFA-rich diet has also been shown
to increase the percentage of cholesteryl oleate in choles-
terol esters, which has been found to correlate with
increased arterial intima-media thickness, greater mortality
in observational studies, and with coronary artery athero-
sclerosis in intervention studies conducted in mice and
non-human primates. More information on the relationship
between oleic acid intake and CVD risk is needed.
Although cardioprotective effects of n-6 PUFA, speciﬁcally
LA, have been promoted based, in part, on results from
several clinical trials, a detailed evaluation of the dietary
interventions provided in those studies suggested possible
confounding in some by inclusion of signiﬁcant amounts of
ALA, EPA, and DHA. Thus, it was concluded that LA is
essential and may be beneﬁcial for cardiovascular health,
although there are limitations in the available literature.
Finally, with respect to n-3 fatty acids and CVD risk, the
message conveyed at this summit was a reafﬁrmation of
current recommendations regarding consumption of EPA
and DHA for CVD prevention, and particularly for sec-
1. Mu H, Hoy CE. The digestion of dietary triacylglycerols. Prog Lipid
2. IUPAC-IUB Commission on Biochemical Nomenclature (CBN). The
nomenclature of lipids (recommendations 1976). Eur J Biochem.
3. Russo GL. Dietary n-6 and n-3 polyunsaturated fatty acids: from
biochemistry to clinical implications in cardiovascular prevention.
Biochem Pharmacol. 2009;77:937–946.
4. Gregory MK, Gibson RA, Cook-Johnson RJ, et al. Elongase reactions
as control points in long-chain polyunsaturated fatty acid synthesis.
PLoS One. 2011;6:e29662.
5. Brenna JT, Salem N Jr., Sinclair AJ, Cunnane SC. International
Society for the Study of Fatty Acids and Lipids (ISSFAL). Alpha-
linolenic acid supplementation and conversion to n-3 long-chain poly-
unsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty
6. Calder PC. Polyunsaturated fatty acids, inﬂammatory processes and
inﬂammatory bowel diseases. Mol Nutr Food Res. 2008;52:885–897.
7. McKenney JM, Sica D. Prescription omega-3 fatty acids for the treat-
ment of hypertriglyceridemia. Am J Health Syst Pharm. 2007;64:
Figure 9 Kaplan-Meier diagrams from the OMEGA study in
which 1 g/d n-3-acid ethyl esters were administered after acute
MI. P-values are from the univariate analysis. A, Survival without
sudden cardiac death during 1-year follow-up (red line, omega
group; blue line, olive oil control group). B, total survival during
one-year follow-up (red line, omega group; blue line, olive oil
control group). Permission to reuse ﬁgure granted by the
American Heart Association.
232 Journal of Clinical Lipidology, Vol 6, No 3, June 2012
8. Schuchardt JP, Schneider I, Meyer H, et al. Incorporation of EPA and
DHA into plasma phospholipids in response to different omega-3 fatty
acid formulations—a comparative bioavailability study of ﬁsh oil vs.
krill oil. Lipids Health Dis. 2011;10:145.
9. Astrup A, Dyerberg J, Elwood P, et al. The role of reducing intakes of
saturated fat in the prevention of cardiovascular disease: where does
the evidence stand in 2010? Am J Clin Nutr. 2011;93:684–688.
10. Hu FB, Stampfer MJ, Manson JE, et al. Dietary fat intake and the risk
of coronary heart disease in women. N Engl J Med. 1997;337:
11. Oh K, Hu FB, Manson JE, et al. Dietary fat intake and risk of coronary
heart disease in women: 20 years of follow-up of the nurses’ health
study. Am J Epidemiol. 2005;161:672–679.
12. Jakobsen MU, O’Reilly EJ, Heitmann BL, et al. Major types of dietary
fat and risk of coronary heart disease: a pooled analysis of 11 cohort
studies. Am J Clin Nutr. 2009;89:1425–1432.
13. Mensink RP, Katan MB. Effect of monounsaturated fatty acids versus
complex carbohydrates on high-density lipoproteins in healthy men
and women. Lancet. 1987;1:122–125.
14. Mensink RP, Katan MB. Effect of dietary fatty acids on serum lipids
and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb.
15. Mensink RP, Zock PL, Kester AD, et al. Effects of dietary fatty acids
and carbohydrates on the ratio of serum total to HDL cholesterol and
on serum lipids and apolipoproteins: a meta-analysis of 60 controlled
trials. Am J Clin Nutr. 2003;77:1146–1155.
16. Jakobsen MU, Dethlefsen C, Joensen AM, et al. Intake of carbohy-
drates compared with intake of saturated fatty acids and risk of myo-
cardial infarction: importance of the glycemic index. Am J Clin Nutr.
17. Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S.
deaths from coronary disease, 1980–2000. N Engl J Med. 2007;356:
18. American Heart Association. Dietary fat and its relation to heart
attacks and strokes. JAMA. 1961;175:135–137.
19. Keys A. Coronary heart disease in seven countries. 1970. Nutrition.
20. Hu FB, Stampfer MJ, Manson JE, et al. Dietary intake of alpha-
linolenic acid and risk of fatal ischemic heart disease among women.
Am J Clin Nutr. 1999;69:890–897.
21. Keys A, Anderson JT, Grande F. Serum-cholesterol response to dietary
fat. Lancet. 1957;1:787–795.
22. Hegsted DM, McGandy RB, Myers ML, et al. Quantitative effects of
dietary fat on serum cholesterol in man. Am J Clin Nutr. 1965;17:
23. Medical Research Council. Controlled trial of soya-bean oil in myo-
cardial infarction. Lancet. 1968;2:693–699.
24. Dayton S, Pearce ML. Prevention of coronary heart disease and other
complications of arteriosclerosis by modiﬁed diet. Am J Med. 1969;
25. Leren P. The Oslo Diet-Heart Study: eleven-year report. Circulation.
26. Miettinen M, Turpeinen O, Karvonen MJ, et al. Cholesterol-lowering
diet and mortality from coronary heart-disease. Lancet. 1972;2:
27. Turpeinen O. Effect of cholesterol-lowering diet on mortality from
coronary heart disease and other causes. Circulation. 1979;59:1–7.
28. Arntzenius AC, Kromhout D, Barth JD, et al. Diet, lipoproteins, and
the progression of coronary atherosclerosis. The Leiden Intervention
Trial. N Engl J Med. 1985;312:805–811.
29. Frantz ID Jr., Dawson EA, Ashman PL, et al. Test of effect of lipid
lowering by diet on cardiovascular risk: The Minnesota Coronary Sur-
vey. Arteriosclerosis. 1989;9:129–135.
30. Watts GF, Jackson P, Mandalia S, et al. Nutrient intake and progres-
sion of coronary artery disease.
Am J Cardiol. 1994;73:328–332.
31. Mente A, de Koning L, Shannon HS, et al. A systematic review of the
evidence supporting a causal link between dietary factors and coro-
nary heart disease. Arch Intern Med. 2009;169:659–669.
32. Skeaff CM, Miller J. Dietary fat and coronary heart disease: a sum-
mary of evidence from prospective cohort and randomised controlled
trials. Ann Nutr Metab. 2009;55:173–201.
33. Siri-Tarino PW, Sun Q, Hu F, et al. Meta-analysis of prospective co-
hort studies evaluating the association of saturated fat with cardiovas-
cular disease. Am J Clin Nutr. 2010;91:535–546.
34. Siri-Tarino PW, Sun Q, Hu FB, et al. Saturated fat, carbohydrate, and
cardiovascular disease. Am J Clin Nutr. 2010;91:502–509.
35. Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease
of increasing polyunsaturated fat in place of saturated fat: a systematic
review and meta-analysis of randomized controlled trials. PLoS Med.
36. Mattson FH, Grundy SM. Comparison of effects of dietary saturated,
monounsaturated, and polyunsaturated fatty acids on plasma lipids and
lipoproteins in man. J Lipid Res. 1985;26:194–202.
37. Keys A, Menotti A, Karvonen MJ, et al. The diet and 15-year death
rate in the seven countries study. Am J Epidemiol. 1986;124:
38. Ma J, Folsom AR, Lewis L, et al. Relation of plasma phospholipid and
cholesterol ester fatty acid composition to carotid artery intima-media
thickness: the Atherosclerosis Risk in Communities (ARIC) Study.Am
J Clin Nutr. 1997;65:551–559.
o E, Sundstr
om J, Vessby B, et al. Markers of dietary fat qual-
ity and fatty acid desaturation as predictors of total and cardiovascular
mortality: a population-based prospective study. Am J Clin Nutr. 2008;
40. Rudel LL, Parks KS, Sawyer JK. Compared with dietary monounsat-
urated and saturated fat, polyunsaturated fat protects African green
monkeys from coronary artery atherosclerosis. Arterioscler Thromb
Vasc Biol. 1995;15:2101–2110.
41. Rudel LL, Haines J, Sawyer JK, et al. Hepatic origin of cholesteryl
oleate in coronary artery atherosclerosis in African green monkeys.
Enrichment by dietary monounsaturated fat. J Clin Invest. 1997;100:
42. Rudel LL, Kelley K, Sawyer JK, et al. Dietary monounsaturated fatty
acids promote aortic atherosclerosis in LDL receptor-null, human Apo
B100-overexpressing transgenic mice. Arterioscler Thromb Vasc Biol.
43. Expert Panel on Detection, Evaluation and Treatment of High Blood
Cholesterol in Adults. Executive summary of the third report of the
National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation and Treatment of High Blood Cholesterol in
Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–2497.
44. U.S. Department of Agriculture. What’s in the foods you eat. Search
Tool, 4.1 Available at: http://www.ars.usda.gov/Services/docs .htm?docid5
17032. Accessed April 16, 2012.
45. Micha R, Mozaffarian D. Saturated fat and cardiometabolic risk fac-
tors, coronary heart disease, stroke, and diabetes: a fresh look at the
evidence. Lipids. 2010;45:893–905.
46. Jenkins DJA, Chiavaroli L, Wong JMW, et al. Adding monounsatu-
rated fatty acids to a dietary portfolio of cholesterol lowering foods
in hypercholesterolemia. CMAJ. 2010;182:1961–1967.
47. Allman-Farinelli MA, Gomes K, Favaloro EJ, et al. A diet rich in
high-oleic sunﬂower oil favorably alters low-density lipoprotein cho-
lesterol, triglycerides, and factor VII coagulant activity. J Am Diet
48. Appel LJ, Sacks FM, Carey VJ, et al. Effects of protein, monounsat-
urated fat, and carbohydrate on blood pressure and serum lipids.
49. Berglund L, Lefevre M, Ginsberg HN, et al, DELTA Investigators. Com-
parison of monounsaturated fat with carbohydrates as a replacement for
saturated fat in subjects with a high metabolic risk proﬁle: studies in
fasting and postprandial states. Am J Clin Nutr. 2007;86:1611–1620.
50. Tanasescu M, Cho E, Manson JE, et al. Dietary fat and cholesterol and
the risk of cardiovascular disease among women with type 2 diabetes
J Clin Nutr. 2004;79:999–1005.
e J, Oda K, Ros E. Nut consumption and blood lipid levels.Arch
Intern Med. 2010;170:821–827.
Baum et al Fatty acids in cardiovascular health and disease 233
52. Hu FB. Dietary pattern analysis: a new direction in nutritional epide-
miology. Curr Opin Lipidol. 2002;13:3–9.
53. Maki KC. Dietary factors in the prevention of diabetes mellitus and
coronary artery disease associated with the metabolic syndrome.Am
J Cardiol. 2004;93(suppl):12C–7C.
54. Choo J, Ueshima H, Curb JD, et al, ERA-JUMP Study Group. Serum
n-6 fatty acids and lipoprotein subclasses in middle-aged men: the
population-based cross-sectional ERA-JUMP study. Am J Clin Nutr.
55. Laaksonen DE, Nyyss
onen K, Niskanen L, et al. Prediction of cardi-
ovascular mortality in middle-aged men by dietary and serum linoleic
and polyunsaturated fatty acids. Arch Intern Med. 2005;165:193–199.
56. Harris WS, Mozaffarian D, Rimm E, et al. Omega-6 fatty acids and risk
for cardiovascular disease: a science advisory from the American Heart
Association Nutrition Subcommittee of the Council on Nutrition, Physical
Activity, and Metabolism; Councilon Cardiovascular Nursing; and Coun-
cil on Epidemiology and Prevention. Circulation. 2009;119:902–907.
57. Czernichow S, Thomas D, Bruckert E. n-6 fatty acids and cardiovas-
cular health: a review of the evidence for dietary intake recommenda-
tions. Br J Nutr. 2010;104:788–796.
58. Friesen RW, Innis SM. Linoleic acid is associated with lower long-
chain n-6 and n-3 fatty acids in red blood cell lipids of Canadian preg-
nant women. Am J Clin Nutr. 2010;91:23–31.
59. Blasbalg TL, Hibbeln JR, Ramsden CE, et al. Changes in consumption
of omega-3 and omega-6 fatty acids in the United States during the
20th century. Am J Clin Nutr. 2011;93:950–962.
60. Roberts DC. Dietary factors in the fall in coronary heart disease mor-
tality. Prostaglandins Leukot Essent Fatty Acids. 1991;44:97–101.
61. Ramsden CE, Hibbeln JR, Majchrzak SF, et al. N-6 fatty acid-speciﬁc
and mixed polyunsaturated dietary interventions have different effects
on CHD risk: a meta-analysis of randomised controlled trials.BrJ
62. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid
ratio in cardiovascular disease and other chronic diseases. Exp Biol
Med (Maywood). 2008;233:674–688.
63. Lagarde M, Chen P, V
ericel E, et al. Fatty acid-derived lipid mediators
and blood platelet aggregation. Prostaglandins Leukot Essent Fatty
64. Wall R, Ross RP, Fitzgerald GF, et al. Fatty acids from ﬁsh: the anti-
inﬂammatory potential of long-chain omega-3 fatty acids. Nutr Rev.
65. Rett BS, Whelan J. Increasing dietary linoleic acid does not increase
tissue arachidonic acid content in adults consuming Western-type
diets: a systematic review. Nutr Metab (Lond). 2011;8:36.
66. Liou YA, Innis SM. Dietary linoleic acid has no effect on arachidonic
acid, but increases n-6 eicosadienoic acid, and lowers dihomo-gamma-
linolenic and eicosapentaenoic acid in plasma of adult men. Prosta-
glandins Leukot Essent Fatty Acids. 2009;80:201–206.
67. Lands WE. Biochemistry and physiology of n-3 fatty acids. FASEB J.
68. Mukuddem-Petersen J, Oosthuizen W, Jerling JC. A systematic review
of the effects of nuts on blood lipid proﬁles in humans. J Nutr. 2005;
69. Von Schacky C, Harris WS. Cardiovascular beneﬁts of omega-3 fatty
acids. Cardiovasc Res. 2007;73:310–315.
70. U.S. Department of Agriculture. Dietary Guidelines for Americans,
2010. Available at: http://www.cnpp.usda.gov/dietaryguidelines.htm.
Accessed April 16, 2012.
71. Leren P. The effect of plasma cholesterol lowering diet in male survi-
vors of myocardial infarction. A controlled clinical trial. Acta Med
Scand Suppl. 1966;466:1–92.
72. Rose GA, Thompson WB, Williams RT. Corn oil in treatment of is-
heart disease. Br Med J. 1965;1:1531–1533.
73. Woodhill JM, Palmer AJ, Blacket RB. Dietary habits and their modi-
ﬁcation in a coronary prevention programme for Australians. Food
Technol Aust. 1969;21:264–271.
74. Anderson BM, Ma DL. Are all n-3 polyunsaturated fatty acids created
equal? Lipids Health Dis. 2009;8:33.
75. Dietary supplementation with n-3 polyunsaturated fatty acids and
vitamin E after myocardial infarction results of the GISSI-
Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza
nell’Infarto miocardico. Lancet. 1999;354:447–455.
76. GISSI-HF Investigators; Tavazzi L, Maggioni AP, Marchioli R, et al.
Effects of n-3 polyunsaturated fatty acids in patients with chronic
heart failure (the GISSI-HF trial): a randomised, double-blind,
placebo-controlled trial. Lancet. 2008;372:1223–1230.
77. Harris WS, Ginsberg HN, Arunkakul N, et al. Safety and efﬁcacy of
Omacor in severe hypertriglyceridemia. Cardiovasc Risk. 1997;4:
78. Kowey PR, Reiffel JA, Ellenbogen KA, et al. Efﬁcacy and safety of
prescription omega-3 fatty acids for the prevention of recurrent symp-
tomatic atrial ﬁbrillation: a randomized controlled trial. JAMA. 2010;
79. Kromhout D, Giltay EJ, Geleijnse JM; Alpha Omega Trial Group. N-3
fatty acids and cardiovascular events after myocardial infarction.
N Engl J Med. 2010;363:2015–2026.
80. Kromhout D, Geleijnse JM, de Goede J, et al. N-3 fatty acids, ventric-
ular arrhythmia-related events, and fatal myocardial infarction in post-
myocardial infarction patients with diabetes. Diabetes Care. 2011;34:
81. Rauch B, Schiele R, Schneider S, et al, OMEGA Study Group. OMEGA,
a randomized, placebo-controlled trial to test the effect of highly
puriﬁed omega-3 fatty acids on top of modern guideline-adjusted ther-
apy after myocardial infarction. Circulation. 2010;122:2152–2159.
82. Kar S. Omacor and omega-3 fatty acids for treatment of coronary ar-
tery disease and the pleiotropic effects. Am J Ther. 2011;Oct 4 [Epub
ahead of print].
83. Ross BM, Seguin J, Sieswerda LE. Omega-3 fatty acids as treatments
for mental illness: which disorder and which fatty acid? Lipids Health
84. Thombs BD, Bass EB, Ford DE, et al. Prevalence of depression in sur-
vivors of acute myocardial infarction. J Gen Intern Med. 2006;21:
85. Carney RM, Freedland KE, Rubin EH, et al. Omega-3 augmentation
of sertraline in treatment of depression in patients with coronary heart
disease: a randomized controlled trial. JAMA. 2009;301:1651–1657.
86. Simopoulos AP. Omega-3 fatty acids in inﬂammation and autoimmune
diseases. J Am Coll Nutr. 2002;21:495–505.
87. Serhan CN, Petasis NA. Resolvins and protectins in inﬂammation res-
olution. Chem Rev. 2011;111:5922–5943.
234 Journal of Clinical Lipidology, Vol 6, No 3, June 2012
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
[Show abstract] [Hide abstract] ABSTRACT: Purpose – This study aims to quantify the dietary intake of different fat classes in Lebanese adults, compare the intakes between adult age groups and gender and compare the intakes to the World Health Organization (WHO) recommendations. Despite the health benefits of the Mediterranean diet, the diet of Lebanese adults may be altered away from the typical dietary lipid profile, possibly by the increased consumption of trans fatty acids (TFAs) and the ratio of omega 6 (n-6) to omega 3 (n-3) fatty acids. Design/methodology/approach – This is a cross-sectional survey conducted on 657 Lebanese adults (19-70 years) who completed the USA National Institute of Health diet history questionnaire. Findings – Mean daily energy intake was estimated at 2,900 ± 1,466 kcal in men and 1,977 ± 902 kcal in women. Mean TFA consumption was significantly higher in men than in women (7.2 ± 1.9 and 6.8 ± 2.0 per cent of total fat, p < 0.001) and was at least double the WHO recommendations of 1 per cent of total energy, particularly among younger adults. The n-6 to n-3 fatty acid intake ratio, fluctuated around 9:1 in both genders and in all age groups and is higher than the maximum 5-to-1 ratio recommended by WHO. The mean intake of eicosapentaenoic acid and docosahexaenoic acid was significantly lower than the latest recommendations (147 ± 182 mg/day for men and 100 ± 155 mg/day for women). Originality/value – Limited data exists on the quantity and quality of fat consumed among Lebanese adults. In conclusion, this descriptive study estimated the quantity of different fat classes consumed and compared the intakes of critical fatty acids to the WHO recommendations. Future studies need to address the implications of the high intakes of TFA and n-6 to n-3 ratio on health outcomes, including cardiometabolic diseases in our population.
- "The protective cardiometabolic effect of the Med-D, when related to dietary fat quality, may be linked to the effect of the " inter-play " between individual fat classes on improving insulin sensitivity and shifting the balance of both inflammatory mediators and plasma lipoprotein and lipid particles toward a less potentially atherogenic metabolic profile, including lower concentrations of plasma pro-inflammatory interleukin 6 and higher concentrations of plasma high-density lipoproteins. The proposed whole-body and cellular mechanisms of these and other cardioprotective effects of the Med-D-involved lipids were recently reviewed (Baum et al., 2012; Bergouignan et al., 2009). In recent years, countries of the Middle East and North Africa (MENA) region are facing a " nutrition transition " away from the traditional Med-D (FAO, 2015; Sibai et al., 2010), adhering more to a " westernized " diet, with a reduction in the consumption of fruits and vegetables and an increase in the intake of animal products (Karamanos et al., 2002; Tur et al., 2004). "
[Show abstract] [Hide abstract] ABSTRACT: Background: Scientific workers play an important role in the development of science and technology. However, evidence is lacking with regard to the associations between their dietary factors and their health-related quality of life (HRQOL). Methods: A cross-sectional survey was conducted among 775 scientific workers from multiple universities and institutes in the Southwest region of China. A self-administered food-frequency questionnaire was used to collect the food consumption information, and the 36-item Short-Form Health Survey was used to assess physical HRQOL. Hierarchical multiple regression analysis was used to identify the factors associated with scientific workers' HRQOL. Results: Physical HRQOL was negatively associated with age and intake of fresh pork (fat) and animal viscera, whereas consumption of vegetables, fruits, refined cereals and dairy products were positively correlated with physical HRQOL. Participants with daily intake of vegetable oils or mixed oils showed higher physical HRQOL scores than those with intake of animal oils. Conclusions: Dietary habits are closely associated with the physical HRQOL of scientific workers. The dietary patterns that had more vegetables and fruits, less fresh pork (fat) and animal viscera, and used vegetable oils during cooking corresponded to higher physical HRQOL scores. These findings are important for planning dietary strategies to improve physical health in scientific workers.
- "Antioxidants and polyphenols, which are largely present in vegetables and fruits, have been reported to have anti-inflammatory properties and have also been found to play a protective role against cardiovascular diseases and cancer . Moreover, intake of monounsaturated fatty acids, which is the major component in vegetable oil, has been found to be associated with a reduced prevalence of risk factors for major chronic disease [27,28]. Therefore, the higher physical HRQOL scores found in scientific workers who frequently consumed vegetables, fruits and vegetable oil in this study may be attributed to the role of antioxidants and monounsaturated fatty acids in their dietary intake. "
[Show abstract] [Hide abstract] ABSTRACT: Northern shrimp (Pandalus borealis) oil, which is rich in omega-3 fatty acids, was recovered from the cooking water of shrimp processing facilities. The oil contains significant amounts of omega-3 fatty acids in triglyceride form, along with substantial long-chain monounsaturated fatty acids (MUFAs). It also features natural isomeric forms of astaxanthin, a nutritional carotenoid, which gives the oil a brilliant red color. As part of our efforts in developing value added products from waste streams of the seafood processing industry, we present in this paper a comprehensive characterization of the triacylglycerols (TAGs) and astaxanthin esters that predominate in the shrimp oil by using HPLC-HRMS and MS/MS, as well as 13C-NMR. This approach, in combination with FAME analysis, offers direct characterization of fatty acid molecules in their intact forms, including the distribution of regioisomers in TAGs. The information is important for the standardization and quality control, as well as for differentiation of composition features of shrimp oil, which could be sold as an ingredient in health supplements and functional foods.
- "This result is in a similar trend with the report by Dahl et al.' , fish oil (27%)  and cod liver oil (24%) . Potential health benefits of PUFAs and MUFAs derived from marine oils are reported to reduce body weight , promote lipid metabolism [38,39], control hyperlipidemia , prevent cardiovascular diseases [41,42], circulate lipids and reduce chronic inflammation434445. The American Heart Association suggested that MUFAs have a favorable effect on cardiovascular disease risks [39,46] and may have benefit in preventing type-2 diabetes [47,48]. "