Food Wave, Vol. 2, 2014, pp.

29-44

SATURATED FAT AND CARDIOVASCULAR DISEASE

D. B. Khadka1*, B. Pokhrel2 and S. Pokhrel3

1

Nutrition and Dietetic Department, Central Campus of Technology, TU, Dharan, Nepal
2
Nepal Bereau of Standard and Metrology, Birgunj, Nepal
3
Birat Medical College Teaching Hospital, Biratnagar, Nepal
*
Corresponding author: khadkadambarb@gmail.com

ABSTRACT
This article highlights the relationship between saturated fat intake and its association with
cardiovascular diseases through available literature. Saturated fat intake has been believed to be one
of the causable factors of cardiovascular disease due its association with the increase level of the
blood cholesterol and other lipoproteins. But available case control studies, systematic reviews and
Meta-analysis of prospective cohort studies, and randomised trail studies are still not sufficient to
provide strong evidence on direct relationship of saturated fat intake and cardiovascular disease and
death rate. The lack of strong association and fully depicted mechanism of the cholesterol and
lipoprotein such LDL, total to HDL cholesterol to cause

cardiovascular disease still generate

uncertainty to support recommendation of reduction of dietary saturated fat has beneficial effect on
prevention and reduction of cardiovascular disease risk.
Keywords: Saturated fat, cardiovascular disease, Cholesterol, Low density lipoprotein, high density
lipoprotein

INTRODUCTION
Cardiovascular disease is a major cause of

of CVDs. CVDs due to atherosclerosis includes

disability and premature death throughout the

Ischaemic heart disease or coronary heart disease

world, and contributes substantially to the

(CHD or heart attacks), cerebrovascular disease

escalating costs of health care. Cardiovascular

(e.g. stroke), and disease of aorta and arteries

disease (CVD) is a non-communicable disease

including raised blood pressure (hypertension)

includes disease of the heart vascular disease of

and peripheral vascular disease. Other forms of

the brain and disease of the blood vessels. CVD

CVDs

has been reported as one of the leading cause of

congenital heart disease, cardiomyopathies and

the death representing 31% of the global deaths

cardio arrhythmias (WHO, 2011a). Worldwide

(WHO 2011a). CVD is caused by disorders of

17.3 million people died from the CVDs

the heart and blood vessels. CVD can be divided

accounting 31% of the global deaths (Figure 1).

into CVD due to atherosclerosis and other forms

Among them, 7.3 million due to Ischaemic heart

include

rheumatic

heart

disease,

Saturated fat and cardiovascular disease

disease or CHD (heart attack) and 6.2 are due to

disposition, psychological factor such as stress,

cerebrovascular disease (e.g. stroke) (WHO

and excess homocysteine (WHO, 2011a)

2011b).
While comparing the death due to CVDs in
WHO regions, Europe (4.6 million), Souh East
Asia (4.6 million) and Western pacific regions
(4.73 million) death are estimated due to CVDs.
As compare to these regions, the estimated
numbers of death in America, Africa and Eastern
Mediterranean regions are low (Figure 1). In
men and women, mortality due to CVD is
equally distributed worldwide (Figure 2). The
most affected age group are elder and older
population of age 30 years and above (WHO
2011a). It has also been reported that the rate of
disability and mortality due CVD is increasing in

Fig1. Death due to CVD per year by WHO

low and middle income countries affecting

regions (WHO, 2011b)

almost equally in men and women. The

percentage of premature death from CVDs
ranges from 4% in high income countries to 42%
in low income countries, leading to growing
inequalities in the occurrence and outcomes of
CVDs between countries and populations (WHO
20011a). It has been estimated that by 2030, the
death due to CVDs is going to be 23.6 million
and are mainly due to CHD and strokes (WHO,
20011a).

Risk factors of CVD

The common risk factors associated with the

Fig 2. Distribution of CVD deaths due to heart

CVD is generally categorized as behaviour risk

attacks, strokes and other types of CVD (in

factor

males and female) (WHO, 2011c)

(tobacco

use,

physical

inactivity,

unhealthy diet e.g. high in saturated fat, salt, fat

and calorie, metabolic risk factor (hypertension.

CVD disability and mortality in Nepal

diabetes, blood lipid e.g. high cholesterol,

In south East Asia, including Nepal, are

overweight and obesity), and other risk factor

witnessing an epidemic of CVD, diabetes and

(poverty,

other non communicable disease. CVD accounts

education,

gender

and

genetic

27 % of all the death in this region. The

B. Pokhrel, S. Pokhrel and D. B. Khadka/Food Wave 2, 2014

magnitude of problem varies with country to

been linked with increase level of low-density

country, and in urban and in rural areas. The

lipoprotein (LDL) cholesterol, Increase level of

incidence of the CVDs is higher in urban area as

the total cholesterol.

compared to rural area because of several risk

cholesterol mainly low density cholesterol has

factor including sedentary lifestyles, obesity and

been consider as a one of CVD risk and as used

smoking (NHRC, 2010).

in number of study as biomarker for the

Elevated level of

prediction of CVDs (Mensinki et al., 2003;

According to WHO data published in April 2011

Siri-Tarino et al., 2010b). The link between

(WHO, 2011c), CVD death in Nepal reached

dietary fat, SFAs, serum cholesterol and

45,000 of death accounting 24.6% of the total

coronary heart disease has been referred to as the

death; the age adjusted death rate is 152.62 per

100,000

populations.

The

more

Diet Heart or lipid hypothesis since long

affected

time. This hypothesis was not universally

mortality group due CVD in Nepal are the age

accepted

group of over 60 year of age and having almost

due

to

ongoing

arguments

and

cholesterol controversy (Steinberg, 2006). It is

equal distribution in male and female. While in

believed that SFAs are hypercholesterolemic

population group of 15-59 years of age, the

effects while unsaturated fatty acids have a

mortality almost double in male than female

hypocholesterolemic effects (Kris-Etherton and

(Figure 3).

Yu, 1997).
The association of the SFAs and CVD led the
word wide recommendation on decrease in
consumption of the saturated fat. Several Public
health organizations straightly introduced the
strategies to decrease the dietary fat especially
SFAs to reduce the CHD and CVDs (Parodi,
2009).

The Advisory Committee of U.S.

Department of the Agriculture (USDA) and U.S.

Fig 3. Death due to CVD by sex and age group
in Nepal (WHO, 2011c, with conversion of data
in number to the % of total death)

Department of Health and Human services

Saturated fat and CVDs

less than 7% of calories from saturated fat and

(USDHSS)

(USDA/UDHHS,2010)

recommended to reduce the dietary reduction

European Food safety Authority (EFSA, 2010)

CVD is the leading cause of the death and

recommended to consume dietary saturated fat

disability in the worlds. Diets high in saturated

as low as possible.

fats (SFAs), cholesterols and sedentary life style

However despites a half

century of intensive research, dietary advice

predispose one of the developments of risk factor

primarily to reduce SFAs and production of

associated with premature CVDs (Schaefer,

healthy food items by the food industry, CVDs

1997). Dietary intake of the saturated fat has

31

Saturated fat and cardiovascular disease

is still a leading cause of the death in developed

plasma lipid and lipoprotein level have also been

country. The dietary guideline published by the

reported

USDA and USDHSS in 2010, have been

Predominantly SFAs with C12-C16 tends to

criticized for being based on a incomplete body

increase plasma total cholesterol levels whereas

of

inaccurately

stearic acid (C18:0) does not have cholesterol

representing the science on saturated fat in

raising effects in comparison with the oleic

relation to CVD (Hite, 2010).

acids. Among the cholesterol raising SFAs,

relevant

science

and

for

(Kris-Etherton

and

Yu,

1997).

myristic acids (C14:0) appears to be more potent

Saturated fat intake and serum cholesterol

and lipoprotein levels

than lauric acid (C12:0) or palmitic acids (C16:0)

(Figure 6)( Kris-Etherton & Yu, 1997).

It

Ahrens et al. (1954) showed that when animal fat

contrasts that even in the SFAs, the potent ability

are replaced by the plant fat iso-calorically, there

of elevating cholesterol levels differ with fatty

was

significant

reduction

of

the

serum

acids.

cholesterol. Same group again showed lower

serum cholesterol when corn oil, safflower oil or

In 2003, A meta analysis of 60 controlled trials

cottonseed oils is a sole source dietary fat

(34 from US; 8 from Netherlands; 4 from

whereas all other sole dietary fat with coconut oil

Denmark; 3 from Canada; 2 of each from

and butterfat provide rise in cholesterol level

Finland, Israel, Malaysia, Norway; 1 of each

(Keys et al., 1957).

from Germany, Italy and UK) was published

relating to dietary intake of fat and serum

Mensiki and Katan (1992) carried out meta-

cholesterol and lipo-protein levels (Melsinki et

analysis regarding the effect of dietary fatty acids

al., 2003).The analysis showed saturated fat

on serum lipids and lipoproteins considering data

from 27 trials study. All three classes of fatty
acid

(SFA,

monounsaturated

and

increase the levels of LDL cholesterol, HDL

cholesterol compared with carbohydrate without

poly

changing the ratio of total to HDL cholesterol

unsaturated fatty acids) have been found to affect

(Figure 7). However the replacement of saturated

plasma lipoprotein levels.

All three types of

fat and carbohydrate by Cis-unsaturated fatty

fatty acids elevate serum high density lipoprotein

acids and polyunsaturated fatty acids (PUFA)

(HDL) levels. However SFAs when replaced the

significantly

energy of carbohydrates found to increase the

cholesterol level by decreasing the LDL

serum low density lipoprotein (LDL) and total

cholesterol and increasing the HDL cholesterol.

cholesterol, whereas Poly and monounsaturated

In other side, trans monosaturated fatty acid has

acid had LDL lowering effects (Minsinki and

reduced

the

total

to

HDL

more profound effect on increasing the LDL

Katan 1992)

cholesterol (bad cholesterol) and lowering the

It shows the association of the saturated fat can

HDL cholesterol (good cholesterol) and elevated

raise the cholesterol levels or lipoprotein and acts

the level of Total to HDL cholesterol (Milsinki et

as risk factor for CVDs. Furthermore different

al., 2003).

classes of fatty acids have different effects on

B. Pokhrel, S. Pokhrel and D. B. Khadka/Food Wave 2, 2014

Dietary Saturated Fat and LDL and HDL

particle size

intake of saturated fat at base line and inversely

There are number of studies that had shown

(Keys et al., 1986).The study also found that

some association with the dietary fat and the

intake of high saturated fat is linked with the

particle size of the LDL and HDL. Data from

serum lipoprotein and cholesterol level (Keys et

Framingham Offspring study showed that Low

al., 1980).

SFA and cholesterol intake has been associated

shown the strong relationship between sugar,

with smaller dense LDL particles (Campos et al.,

eggs, protein and total calories with CHDs

1992). In the other cross-sectional study no

(Stamler, 1978).

associated with monounsaturated fatty acids

strong relationship has been found between

But ecological studies have also

It shows that the association obtained from the

SFAs intakes and size of dense LDL particles.

ecological studies have large number of chance

However individual fatty acid typically found in

to produce false association and these types of

milk fat ( C5:0-C10:0 and C14:0) and C15:0 and

the association can always representative at the

C17:0 in serum phospholipids were found

individual group and a community, these types

negatively associated with Level of small dens

of study only generate the hypothesis. Therefore

LDL Particles (Sjogren et al., 2004). In healthy

for actual causal relationship, the ecological

men, intake of SFAs as well as C14: and C16:0

study could not be prime useful (Parodi, 2009)

were found to be associated with increase in

and other random control or prospective studies

larger particle size of LDL and decrease in

could be stronger to show relation between SFAs

smaller LDL Particles (Doren et al., 1998).

and CVD risk (Skeaff, 2009).

Saturated fat Intake and association with

CVDs

Case control studies

In facts, case control are simple, rapid, low cost

Ecological studies

design for the determination of differences in

The ecological studies could be important to

previous dietary exposure in individuals with

compare the difference in CVDs rate between

CHD and those free of disease. But very a few

mean intakes of the fatty acids in different

case control studies that have investigated to

population. The one of the ecological studies is a

show the association between SFAs intake and

seven country study consisted of 16 cohorts in 7

the risk of CHD (Parodi, 2009). Most of the early

different countries involving a total of 12,763

case control studies did not find the difference in

middle aged men that were examined between

the % calorie intake of SFAs between cases and

1958 and 1964 .This is one of the best known

control subjects, therefore later case control

ecological study which support the diet heart

studies found to be use multiple regression

hypothesis. The study showed that death rates

analysis to measure the risks (Table 1) (Parodi,

from CHDs during 10-15 yr follow up across 16

2009).Among the case control studies presented

cohorts were positively related with dietary

in Table 1, only a study of men and women from

33

Saturated fat and cardiovascular disease

that was from Costarica (Kabagambe et al.,

subjects to represent the population under the

2003) has shown statistically significant positive

study, error in recall of past history of diets, so it

association between SFA intakes and risks of

might not be effective to draw the strict

CHDs. On other hand, case control studies prone

conclusions

(Parodi,

2009).

to bias. Bias can result from failure of control of

Table 1. Summary of some case control studies that used regression analysis for risk measurement
Studies

Relative Risk (RR), RR

ranges

Greek study
comparison of the highest
quintile of SFA in take
with lowest quintile of
the intake
Korean men study

1.02 CI 95%, 0.41-2.54

No strong association

Tzonou et al., 1993

1.00 95% CI , 0.81-1.25

No strong association

Suh et al., 2001

Costarica
men
women study

3.00 CI 95% , 1.54-5.84

Strong
association

Kabagambe et al., 2003

and

Outcomes

Reference

positive

available. Most of the systematic review of

Prospective Cohort studies

cohort studies and their Meta-analysis have

The prospective cohort studies provide the most

shown no association and /or weak association

reliable design for determining the association

between dietary saturated fat intake and risk of

between dietary intake and disease risk. These

CVDs in term of CHD or stroke. For examples

study largely overcome the biases introduced in

the overall results of Meta analysis of dietary fat

case control studies, thus the diets is assessed

intake and risk of CHD that showed a consistent

before disease is diagnosed and at a more

lack of an association between saturated fat

etiologically relevant time, while case

intake and CHDs except some individual cases

and

control subjects are from the same cohort

are presented in Table 2.

negative aspects include high cost associated

with the large number of participants required to

Parodi (2009) also investigated the 24 report of

ensure adequate CHD events. A large cohort can

cohort studies with 33 data set regarding absolute

made it difficult to obtain accurate information

saturated fat intake and/or percentage of energy

on diet and potential puzzling factors. Because of

from SFAs and risk of CHD. A comparison of

the length of time the study runs, it may be

daily intake for energy total fat, SFAs and

advisable to identify individuals who changed

PUFAs in individual and in those free of disease

their dietary patterns due to awareness of health

in 15 reports from 11 cohorts and other studies

risks irrespective of format, the accuracy of the

that reported CHD, RR, odd ratio (OR) or hazard

epidemiological studies is dependent on the

ratio with 95% CIs for the highest compared

quality of dietary assessment and the nutrient

with the lowest reported intake level of total,

database (Parodi, 2009).

saturated fats, mono-saturated fats and poly-

The number of systematic review of prospective

studies that has examinined the direct relation
between saturated fat intake and CVDs were

unsaturated fats from nine report have been

investigated. But only four studies (Yano et al.,
1978; Mcgee et al., 1984; khushi et al., 1985)

B. Pokhrel, S. Pokhrel and D. B. Khadka/Food Wave 2, 2014

have been found to be associated positively. The

Randomized Control Trial Studies

Honolulu Heart study (McGee et al., 1984; yano

Clinical randomised control Trial (RCT) is

et al., 1984) and the Ireland Boston Diet Heart

important to establish causal relationship if

study (Khushi et al., 1985) both found positive

dietary SFA requires these acids to be replaced

association between % energy from SFAs but not

or substituted by unsaturated fatty acids or other

from absolute intake. In an small Canadian study

energy source iso-calorically. Most of available

(52 events) the significant association with

RCT studies have shown no strong relationship

increasing intake of the SFAs for CHD mortality

on iso-calorical replacement of saturated fat by

were found only in 30-49 yrs old men ( RR 1.11,

other dietary components because of either poor

1.04-1.18) but not for those of 60-79-years old

design, or insufficient intervention time and

men(RR 0.96, 0.88-1.05).

The other positive

population size (Table 3). In these types of trial

association was found in a small British study

the life style and dietary item and total fat

with only 57 events, found 100g per week

associated with CHD must be similar for

increase in saturated fat intake correspond to an

intervention and control subjects and along with

RR of 1.40(1.09-1.79) in women but not

dietary changes remains in operation for many

evidence was found in corresponding to men

years. But in practice these condition are difficult

(Boniface and Tefft, 2002). Two studies (Farchi

to manage and it can be effective to establish the

et al., 1989; Fehily et al., 1993) have been found

relationship

to be negatively associated in both cases. Rest of

adequately designed (Parodi, 2009).

between

SFA

and

CVDs,

if

the studies in this investigation have shown null

association between the dietary saturated fat
intake and risk of CHDs.
Table 2. Some systematic review and Meta analysis of cohort studies outcome for the dietary intake of
SFAs and risk of the coronary heart diseases (CHDs)
Prospective study
Systematic review and
Meta analysis

Study
Saturated fat intake
and CHD death

Output
RR 1.14(0.82,1.60)

SFA intakes & CHD

event

RR 0.93, 95% CI
0.831.05, p = 0.269

RR 1.11, 95% CI
0.751.65, p = 0.593

Results
No significant
associate for those in
the highest compared
with the lowest
category of SFA
intake
SFA intake was not
significantly
associated with CHD
events for high versus
low categories
no significant
association with CHD
death per 5% total
energy increment in
SFA intake

References
Skeaff et al., 2009

Skeaff et al., 2009

Skeaff et al., 2009

Systematic review and

Meta analysis

SFA intake and

coronary outcome

1.06(0.96-1.15)

No significant even in
term of dietary intake,
sex and by regions.

Mente et al., 2009

Systematic review and

Meta analysis

SFA and CHD

Stroke,

1.07 (0.96,1.19)
0.81(0.62,1.05)

For CHD
For stroke

Siri-Tarino et al.,
2010a

35

Saturated fat and cardiovascular disease

Table 3. Summary of some Randomized Control Studies

Name
of
Trial
The
Minnesota
Coronary
Survey

Population

The Finnish
Mental
Hospitals
Study

A
primary
prevention
study,
conducted
with middleaged men in
two
mental
hospitals

1 yr

The
Los
Angeles
Veterans
Administrat
ion Study

846 veterans
with
and without
previously
diagnosed
CHD

about 8
years of
intervention

The Oslo
Diet-Heart
Study

412 men aged

3064
years. They
were

9057
institutionalis
ed men and
women

Intervention
period
1 year

Study design

Results

References

The study compared a normal

diet (39% fat calories, 18%
SFA, 16% MUFA, 5%
PUFA) with a treatment diet
(38% fat calories, 9% SFA,
14% MUFA, 15% PUFA)
One of the hospitals received
a serum cholesterol-lowering
diet by replacing butter with
PUFA margarine and whole
milk with soybean oil lled
milk. The other hospital
served its normal diet.
After 6 years
intervention the diets at the
two hospitals were reversed
and the
trial was continued for
another
6
years.
The
intervention diet
decreased serum cholesterol
levels by about 15%
Randomised to a conventional
diet, which contained 40% of
energy mainly from animal
fat, or a test diet where about
two-thirds of the animal fat
were replaced by vegetable
oils.

Serum cholesterol levels fell by 14% during the intervention period of a

little over 1 year. For the study population no differences between
treatment and control groups were observed for cardiovascular (CV)
events, CV deaths or total mortality.

Frantz et al.,
1989

The intervention diet decreased serum cholesterol levels by about 15%.

However, as a randomised control trial this study was seriously awed.
The institutions were randomised not the individuals and thus was a
cluster randomised trial with only two clusters; the inmates in the
institutions changed during the trial and there were differences between
groups in BP, cigarette smoking and use of psychotropic drugs. A
characteristic of the cholesterol-lowering diet was the removal of
common margarine which during the time of this study would have
contained considerable quantities of trans fatty acids that are now
known to be more atherogenic than SFAs (Ascherio, 1999). Thus
reduction in CHD events was probably in part due to reduction in
trans fat.

Turpeinen et al.,
1979

Serum cholesterol levels were reduced by about 13% in the treatment

group. But there was no statistically signicant difference in the
primary end point of the study sudden death or (myocardial Infarction
(between the groups. However, when these data were pooled with that
for cerebral infarction and other secondary end points signicance was
obtained. Deaths due to non-atherosclerotic causes were higher in the
intervention group so that overall total mortality was similar in both
groups
After 5 years of intervention serum cholesterol was 14%
lower in the treatment group and there were signicantly fewer major
CHD relapses, but fatal MI, CV mortality and total mortality while
lower than in the control group did not attain statistical signicance.
Intervention was more successful in patients under age 60 years and in

Dayton
1969

Randomised 12 years after a

rst myocardial infarction to
a
control
group
who
consumed their normal diet or
an
intervention
group

et

Leren, 1966

al.,

B. Pokhrel, S. Pokhrel and D. B. Khadka/Food Wave 2, 2014

London
Hospitals
Study

a small trial
of 80 patients
of average
age 55 years
with CHD

Medical
Research
Council
Soybean
Oil Study

393 men aged

under 60
years
recovering
from a rst
MI
d of a control
group of 237
men with
average
age around 49
years
recovering
from CHD

Sydney
Diet-Heart
Study

MRC LowFat diet trial

involved 252
men less than
65 years of
age
who were
recovering
from a rst
MI.

consuming 39% of total

calories from fat with 8.5%
from SFA, 20.7% from PUFA
and 10.2% from MUFA to
give a P/S ratio of 2.4.
Randomised
to either their normal diet
(control) or to two treatment
groups with a restriction of
animal
fat
and
supplementation of
about 60 g per day of either
olive or corn oil.
Randomly allocated to their
normal diet or
a diet that was low in
saturated fat and contained
about 80 g
soybean oil daily.
A
similarly
matched
intervention group substituted
PUFA margarine for butter
resulting in a dietary intake of
9.8% of calories from SFA
and 15.1% as PUFA. After 5
years of intervention 16.7%
of the PUFA group had died
compared with only 11.8% in
the control group
They were randomised to
receive their normal diet,
which contained from 110 g
to 130 g of fat per day or a
low-fat diet with the same
type of fats as the controls but
at a level of about 45 g per
day.

this study CHD mortality was correlated with

age, cholesterol levels, BP, body weight, smoking habits and
a combination of these risk factors.

After 2 years of
intervention serum cholesterol levels fell signicantly in the corn
oil group but not in the olive oil group. Both vegetable oil groups
fared worse than the control group with the percentage of patients
remaining alive being 75%, 57% and 52% for the control, olive and
corn oil groups, respectively.

Rose et al., 1965

Participants were in the trial for 2 to nearly 7

years and the test diet lowered serum cholesterol levels by a mean
of 22%. Fatal CHD events and major rst relapses were the same in
both groups, but non-major relapses were non-signicantly lower
in the soybean group. Relapses were not related to initial serum
cholesterol levels.
During follow-up serum cholesterol had no predictive value for
outcome and dietary factors were not signicantly related to
survival

Research
Committee to the
Medical
Research
Council, 1968)

Despite a lowering of serum cholesterol levels and greater loss of body

weight in the treatment group there was not a signicant difference in
reinfarction and
death in the two groups.

Research
Committee to the
Medical
Research
Council, 1965

37

Woodhill et al.,
1978

Saturated fat and cardiovascular disease

DISCUSSION
The association between saturated fat and

fat contains the SFA as well as the unsaturated

elevation in plasma cholesterol has been reported

fatty acid and the later has been associated with

by several investigators. During the past several

lowering the Total to HDL ratio by decreasing

decades, reduction of fat specifically saturated

the LDL and increasing the HDL cholesterol

fat has been emphasizing focus for the national

and mask the effects of replacing saturated fat

dietary recommendation to reduce the risk of

by the carbohydrates. It postulated that SFA and

CVDs (Parodi 2009) and the world dietary fat

development of the CVDs might be weakly

has become synonymous with obesity and heart

associated. However the recommendation to

disease in general public (Hu, 2001). But it has

lower the fat by replacing the carbohydrate has

been seen that not all saturated fat are

been practiced and mentioned in WHO guideline

responsible for the increment of the LDL level

and other bodies for the reduction of the CHDs.

and serum cholesterol level. Consumption of

But if we consider the newer marker of CVDs

saturated fat especially C12-16 have reflective

such as ratio of apo B: apo A, the replacement of

positive effect in the cholesterol and LDL level,

carbohydrate might not be good option. The low

which are generally taken as the marker for the

fat, low saturate fat diet and high carbohydrate

atherosclerosis or CVDs. Even in those SFAs the

rich diet intake has been associated with the

myristic acid (C14:0) has been associated to

decrease the apo B and apo A level but ratio of

mark increase in LDL, Cholesterol and marked

apo-B: apo-A has been dramatically found to be

decrease in HDL i.e. beneficial cholesterol (Kris-

increased (Shin et al., 2007) .The higher level of

Etherton and Yu, 1997). These finding induce

serum apo-B considered as the high risk factor

several difficulties not only for the choice of

CHDs or atherosclerosis (Pischon et al., 2005).

appropriate fat sources but also for planning,

developing of guideline and development of
dietary prevention strategy for public health
perspectives and in a community intervention
levels. It has been clear that intake of saturated
fat not only brought changes in the LDL and
Total cholesterol but also some changes in HDL
level have further been reported. The ratio of
Total to HDL cholesterol is widely accepted to
predict of chances of CVDS in individual
population.

Surprisingly Meta-analysis by

Mensinki et al. (2003) found no significant

association between the Total to HDL ratio and
intake of SFAs when 1% of energy from
saturated

fat

has

been

replaced

by

the

carbohydrate. It might be due to that all natural

An early ecological studies showed dietary

intake of the saturated fat has been associated
with the CVDs disease and death; support the
lipid or diet heart hypothesis. The other
behaviour and dietary factor has also been
associated with the increase risk of the CVDs
(Stamler, 1978) and hence for the causal relation
ecological studies might not be good support. In
other hand, Parodi et al. (2009) pointed very low
availability of the case control study, and even
the most of them have shown no positive
association except the study carried out in
Costarica by Kabagambe et al. (2003). Apart
from availability case control study; these types
of studies consist number of biases such as
failure of control of subjects to represent the

B. Pokhrel, S. Pokhrel and D. B. Khadka/Food Wave 2, 2014

population under the study, error in recall of past

the trial are too small to have strength to

diet history and could not be fit for drawing

determine certain CHDs.

good association (Parodi, 2009). In addition

Till now the association based on the elevated

prospective cohort study to establish the relation

level of the cholesterol, LDL and lowering of

between saturate fat intake and risk of CVD is

HDL due to intake of SFA are only supporting

pointed out by several investigators as an

base that shows the possible relation between

effective epidemiological design to draw a solid

FAs intake and risk of CVD. But controversy

association. But most of the prospective studies

still

have shown very weak association between the

regarding

mechanism

of

the

cholesterol and other lipoprotein and their

saturated fat intake and CHD death and

mortality.

exists

contribution to CVDs. High level of LDL is

A few studies (Yano et al., 1978;

considered as leading cause of initiation of

Mcgee et al., 1984; khushi et al., 1985) have

atherosclerosis (Libby et al., 2000). However

been found the positive association and some

various hypotheses have been projected to

studies also found the negative association

describe the initiation of atherosclerosis but

(Farchi et al., 1989; Fehily et al., 1993). In

response to retention model is more preferred

contrast, most of systematic review of large

one (Tabas et al., 2007). This model explain that

number of cohort study and their meta analysis

apo-B lipoprotein frequently penetrate the

has shown no statistically significant relation

arterial wall by upregulating transcytosis and

between SFAs intake and CVDs risks (Seaff,

entered into the intimal subdendothelial space.

2009; Mente, 20009; and Siri-Tarino et al.,

Some

2010a).

of

these

particles

adhere

to

subendotheliam matrix molecules mainly with

Several randomised control trial that involved

the range of proteoglycans synthesized by

reduction in saturated fat in the context of

endothelial cell and macrophage. Accessory

reduced total fat and increased carbohydrate

molecules like lipoprotein lipase, phospholipase

intake showed no significant CVD risk benefit

A2 and sphingomylinase secreted by endothelial

but these study may have been limited by small

cells and macrophage for instance, can cleave

sample size and or limited duration of follow up

sphingomyline on the surface of lipoprotein

(Siri-Tarino et al., 2010b). Random control

leading to fusion and aggregation of lipoprotein

Trials ( Annex1) that had been conducted to

particles. These types of aggregation lead to an

observe the reduced saturated fat and relation to

increase in size that prohibits their exit from

CHD and CVDs produce no convincing evident

artery

that removal of SFA from the diet will assist to

lipoprotein. Biological response to retained apoB

prevent CHD. There was only one primary

containing lipoprotein is considered as initiating

prevention study and other was secondary

event in antherosceloresis. Prolonged retention

prevention studies conducted within the men

of the lipoprotein complexes can result in

recovering from the premature CHDs which does

chemical

not reflect the total population. The numbers in

(Tabas et al., 2007).

39

wall

compared

modification

with

especially

monomeric

oxidation

Saturated fat and cardiovascular disease

There is low rate of uptake of native LDl by

disease. Furthermore to what extent elevated

macarophages, which is not considered as

LDL cholesterol impair in or more innumerable

antherogenic.

LDL

process may involved in lipoprotein processing

components, apo-B and lipid moieties like the

and metabolism. What are the dysfunctional

phospholipids

are

processes within the arterial wall that lead

immunogenic and proinflammatory. Oxidised

aggregation and retention of apo-B containing

LDL does not bind to LD l receptor, but bind

lipoprotein and their subsequent oxidation that

devotedly to scavenger receptor on macrophage

leads to cholesterol enriched foam cell formation

leading to foam cell formation and secretion of

much is still to be learnt? It emphasize that there

an array of proinflammatory cytokines that drive

is still a lot of uncertainty exist between

atherosclerosis process (Glass and Witzum,

saturated fat its effect on cholesterol and

2001; Witzum & steinberg, 2001)

lipoprotein and their mechanism of causing

However

contain

oxidised

epitopes

that

CVDs.
Cholesterol

has

been

concerned

in

atherosclerosis for more than a century due to its

In an overall, independent association and

accumulation in atherosclerotic plaques, because

plausible is still lacking in spite of the

this cholesterol originates from the major

conventional

circulating lipoprotein LDL and LDL cholesterol

dietary SFAs is beneficial for cardiovascular

are considered as major risk factor for CHD .

health.

understanding

about

reduced

However it is well cited that individuals with

normal or low serum LDL cholesterol levels, as

CONCLUSION

currently defined by national guideline, can yield

From the above discussion, it can be realized that

to CHD, whereas some individuals with high

there is still no strong evidence about saturated

LDL cholesterol can manage a normal life span.

fat intake and its direct association with the

In addition, major statin trials showed substantial

CVD. Although there is relationship that intake

lowering LDL cholesterol but statin drug does

of saturated fat

not prevent most events in patients at risk of

increase in serum cholesterol and LDL level but

CHDs. Obviously other risk factor must be

the lack of plausible mechanism between these

involved. It is interesting to note that LDL is

lipid and elevated lipoprotein level on instigation

ligand for the other antherogenic molecules such

of atherosclerosis and other CVDs.

could be associated with

as homocysteine and C-reactive protein (CRP).

Olszewiski & McCully (1991) found that the
homocysteine level was 4:1 times higher per
gram of protein in LDl hypercholesterolemic
men than from normocholesterolmic men, CRP
binds to its phospholipids, but not native LDL
(Chang et al., 2002).Therefore it is still unclear
that LDL cholesterol is a causative factor for
CHD or it is just a correlate or consequence of

However some of the advisory committee and

public

health

organization

(for

e.g.

UDHHS/USDA, 2010 and EFSA, 2010) on their

report recommended for reduction of saturated
fat to improve the health status of the CVD in the
population.

These

recommendations

has

probably excluded the systematically evaluated

results from the prospective studies that shown

B. Pokhrel, S. Pokhrel and D. B. Khadka/Food Wave 2, 2014

weak relationship between saturated fat intake

lack of strong scientific evidence and association

and CVD (Hoenselaar, 2011).

between saturated fat intake and CVD, It will not

be convenient to draw conclusion that the

In conclusion, in spite some conventional

reduction of dietary saturated fat could be best

understanding, still there is lack of strong

independent

association

and

intervention to reduce the public health burden of

plausible

the CVD. Further study and research on this area

mechanism between saturated fat intakes and/or

is still needed to clarify the effect of saturated

increasing level of the plasma lipid and

fatty acid intake to establish a strong association

lipoproteins like LDL causing the CVD. In the

and mechanism causing the CVD.

REFERENCES
Ahrens, E. H., Blankenhorn, D. H. & Tsaltas,
T. T. (1954). Effect on human serum lipids
of substituting plant for animal fat in diet.
Proceedings
of
the
Society
for
Experimental and Biological Medicine, 86,
872878.

cells through recognition of common

ligand: phosphorylcholine of oxidised
phospholipids. Proceeding of the national
academy of science of United States of
America, 99, 13043-13048. Available at
http://www.pnas.org/content/99/20/13043

Ahrens, E. H., Hirst, J., Insull, W., Tsaltas, T.

T., Blomstrand, R. & Peterson, M. L.
(1957). The inuence of dietary fats on
serum-lipid levels in man. Lancet, 272
(6976), 943953

Dayton, S., Pearce, M. L., Hashimoto, S.,

Dixon, W. J. & Tomiyasu, U., (1969). A
controlled clinical trial of a diet high in
unsaturated fat in preventing complications
of atherosclerosis. Circulation 40 (Suppl.
II), II-1II-63.

Ascherio, A. (1999). Trans fatty acids and

coronary heart disease. The New England
Journal of Medicine 340, 19941998.

Dreon, D. M., Fernstorm, H. A., Campos, H.,

Blanche, P., Williams, P. T. & Krauss, R.
M. (1998). Change in dietary saturated fat
intake is correlated with change in mass of
large low density lipoprotein particles in
men. American Journal of Clinical
Nutrition, 67,828-36.

Boniface, D. R. & Tefft M. E. (2002 ).

Dietary fats and 16-year coronary heart
disease mortality in a cohort of men and
women in Great Britain. European Journal
of Clinical Nutrition 56, 786792.

EFSA (2010). Panel on Dietetic Products,

Nutrition, and Allergies (NDA), Scientific
opinion on dietary reference value for fats,
including SFAs, polyunsaturated fatty
acids, monounsaturated fatty acids, trans
fatty acids and cholesterol, EFSA Journal,
8,1461.
Available
at
http://www.efsa.europa.eu/en/efsajournal/d
oc/1461.pdf.

Campos, H., Blijlevens, E., McNamara, J. R.,

Ordovas, J. M., Posner, B. M., Wilson, P.
W. F., Castelli, W.P. & Schaefer, E J.
(1992). LDL particle size distribution,
Results from Framingham Offspring Study.
Arteriosclerosis and Thrombogenesis, 12,
1410-1419.
Chang M. K., Binder C. J., Torzewski M. &
Witzum J. L. (2002). C-creative protein
binds to both oxidised LDL and apoptic

Farchi, G., Mariotti, S., Menotti, A.,

Seccareccia, F., Torsello, S. & Fidanza, F.
41

Saturated fat and cardiovascular disease

(1989). Diet and 20-yr mortality in two

rural population groups of middle-aged
men in Italy. The American Journal of
Clinical Nutrition, 50, 10951103.
Fehily, A. M., Yarnell, J. W. G., Sweetnam,
P. M. & Elwood, P. C. (1993) Diet and
incident ischemic heart disease: The
Caerphilly Study. British Journal of
Nutrition, 69, 303314.
Frantz, I. D., Dawson, E. A., Ashman, P. L.,
Gatewood, L. C., Bartsch, G. E., Kuba, K.,
Brewer, E.R. (1989). Test of effect of lipid
lowering by diet on cardiovascular risk.
Arteriosclerosis, 9, 129135.
Glass C. K. & Witzum J. L. (2001.)
Atherosclerosis: the road ahead. Cell, 104,
503-516.
Hite, A. H.,Feinman, R. D., Guzman, G. E.,
Datin, M., Schoenfield, P.A. & Wood ,R. J.
(2010). In the face of contradictory
evidence report of the dietary guideline for
Americans Committee, Nutrition,26,915924.
Hoenselaar R. (2012). Saturated fat and
cardiovascular disease: The discrepancy
between the scientific literature and dietary
advice. Nutrition, 28, 118-123.
Hu F. B. (2001). Types of dietary fat and risk
of coronary heart disease: A critical review.
Journal of American College of Nutrition,
20 (1), 5-19.
Kabagambe, E. K., Baylin, A., Siles, X. &
Campos, H. (2003) Individual saturated
fatty acids and non fatal acute myocardial
infarction in Costa Rica. European Journal
of Clinical Nutrition, 57, 1447-1457.
Keys, A. (1980). Coronary heart disease in
seven countries. circulation, 41, 1-211.
Keys, A., Menotti, A., Karvinen, M. J.,
Aravanis, C., Blackburn, H, Buzina, R,
Djordjevic, B. S., Dontas, A. S., Fidanza, F.
& Key, M. H. (1986). The diet and 15years death rate in the seven countries
study. Am J Epidemiol, 124, 903-915.

Kris-Etherton, P. M. & YU, S. (1997).

Individual fatty acid effects on plasma
lipids and lipoprotein: human studies.
American Journal of Clinical Nutrition, 65
(5 Suppl),1628S-1644S.
Kushi, L. H., Lew, R. A., Stare, F. J., Ellison,
C. R., el-Lozy, M., Bourke, G., Daly, L.,
Graham, I., Hickey, N., Mulcahy, R. &
Kevaney, J. ( 1985). Diet and 20-year
mortality from coronary heart disease. The
New England Journal of Medicine, 312,
811818.
Leren, P. (1966). The effect of plasma
cholesterol lowering diet in male survivors
of myocardial infarction. Acta Medica
Scandinavica, Supplement 466, 192.
Libby, P., Aikawa, M. & Schonbeck, U.
(2000). Cholesterol and atherosclerosis.
Biochimica et Biophysica Acta,1529, 299
309.
McGee, D. L., Reed, D. W., Yano, K., Kagan
A. & Tillotson, J. (1984). Ten-Year
Incidence of coronary heart disease in the
Honolulu Heart Program. American
Journal of Epidemiology, 119, 667-676.
Mensinki, R. P. & Katan, M. B. (1992).
Effect of dietary fatty acids on serum lipid
and lipoprotein. A meta-analysis of 27
trials. Arteriosclerosis Thrombosis and
Vascular Biology, 12, 911-919.
Mensinki, R. P., Zock, P. L. Kester, A. D. M.
& Katan, M. B. (2003). Effects of dietary
fatty acids and carbohydrate on the ratio of
serum totak to HDL cholesterol and serum
lipid and apolipoproteins: a metaanalysis of
60 controlled trials. Am Journal of Clinical
Nutrition, 77, 1146-55.
Mente, A. (2009). A systematic review of the
evidence supporting a causal link between
dietary factors and coronary heart disease.
Arch Intern Med, 169(7), 659-669.
Olszewski, A .J. & McCully, K. S.(1991).
Homocysteine content of lipoproteins in
hypercholesterolemia. Atherosclerosis, 88,
6168

B. Pokhrel, S. Pokhrel and D. B. Khadka/Food Wave 2, 2014

Parodi, P. W. (2009) Has the association

between saturated fatty acidsm serum
cholesterol and coronary heart disease been
over emphasized?. International dairy
Journal, 19,345-361

Siri-Tarino, P. W., Sun Q., HU F. B. &

Krauss R. M. (2010b).Saturated Fat,
carbohydrate ,and cardiovascular disease,
American Journal of Clinical Nutrition, 91,
502-529.

Pischon, T., Girman, C. J., Sacks, F. M., Rifai,

N., Stampfer, M. J. & Rimm, E. B. (2005).
Non high-density lipoprotein cholesterol
and apolipoprotein B in the prediction of
coronary heart disease in men. Circulation,
112, 33753383.

Sjogren, P., Rosell, M., Skoglund-Andersson,

C., Zdravkovic, S., Vessby, B., DeFaire,
U., Hamsten, A., Hellenius, M. & Fischer,
R. M.(2004). Milk-derived fatty acids are
associated with a more favourable LDL
Particle size distribution in healthy men.
Human Nutrition & Metabolism, 134,
1729-1735.

Research Committee to the Medical Research

Council ( 1968). Controlled trial of
soyabean oil in myocardial infarction.
Lancet, 2 (7570), 693700

Skeaff, C. M & Miller, J. (2009). Dietary Fat

and coronary heart disease summary of
evidence from prospective cohort and
randomised controlled trials. Ann Nutr
Metab, 55,173-201.

Research Committee to the Medical Research

Council (1965). Low-fat diet in myocardial
infarction. Lancet, 2 (7411), 501504.

Stamler, J., Wentworth, D. & Neaton, J. D.

(1986). Is the relationship between serum
cholesterol and risk of premature death
from coronary heart disease continuous and
graded? Journal of Americation Medical
Association, 256, 2823-2828.

Rose, G. A., Thomson, W. B. & Williams, R.

T. (1965). Corn oil in treatment of
ischaemic heart disease. British Medical
Journal, 1 (5449), 15311533
Schaefer, E. J. (1997). Effects of dietary
fattyacids on lipoprotein and cardiovascular
disease risk: summary. Clin Nutr, 65
(Suppl) 165S-6S.

Suh, I., Oh, K. W., Lee, K. H., Psaty, B. M.,

Nam, C. M., Kim, S. I., Kang, H. G., Cho,
S. Y. & Shim, W. H. (2001). Moderate
dietary fat consumption as a risk factor for
Ischemic heart disease in a population with
a low fat intake: a case control study in
Korean men. The American Journal of
Nutrition, 73, 722-727.

Shin, M. J., Blanche, P. J., Rawlings, R. S.,

Fernstrom, H. S. & Krause, R. M. ( 2007).
Increased plasma concentrations of
lipoprotein(a) during a low-fat, highcarbohydrate diet are associated with
increased plasma concentrations of
apolipoprotein
C-III
bound
to
apolipoprotein B-containing lipoproteins.
The American Journal of Clinical
Nutrition, 85, 15271532.

Tabas I., Williams K. I. & Boren J. (2007).

Sub endothelial lipoprotein retention as the
initiating process in atherosclerosis.
Circulation, 116, 18321844.
Turpeinen, O., Karvonen, M. J., Pekkarinen,
M., Miettinen, M., Elosuo, R. &
Paavilainen, E. (1979) Dietary prevention
of coronary heart disease: The Finnish
Mental Hospital Study. International
Journal of Epidemiology 8, 99118.

Siri-Tarino, P. W., Sun Q., HU F. B. &

Krauss R. M. (2010a). Meta-analysis of
prospective cohort studies evaluating the
association of saturated fat with
cardiovascular disease. American Journal
of Clinical Nutrition, 91, 535-546.

Tzonou, A., Kalandidi, A., Trichopoulou, A.,

Hsieh, C. C., Toupadaki, N., Willet, W. &
43

Saturated fat and cardiovascular disease

Trichopoulos, D. (1993). Diet and coronary

heart disease: a case control study in
Athens, Greece. Epidemiology, 4, 511-516.
USDA & UDHHS (2010) Report of the
Dietary Guideline Advisory Committee on
the dietary guidelines for Americans.
Aavailable at
http://www.cnpp.usda.gov/Publications/Die
taryGuidelines/2010/DGAC/Report/QandA
-DGACReport.pdf
WHO (2011a). Global Atlas on cardiovascular
Disease prevention and Control. WHO
(World Health Organization/WHF (World
Heart Federation) & World Stroke
Organization. Mendis S, Puska P, Norving
B editors, World Health organization.
WHO (2011b). Cause of death 2008 summary
table. Health
Static and Informatics
Department, World Health Organization,
May
2011.
Available
at
http://apps.who.int/ghodata
WHO (2011c). Mortality and Global Burden
of Disease, Disease and Injury country

estimates, 2008; by sex and age. World

Health
Organization,
Organisation
Mondiale de la sant, Department of
Measurement and Health Information,
April
2011.
Available
at
http://www.who.int/gho/mortality_burden_
disease/countries/en/index.html
WItzum J. L. & Stenberg D. (2001). The
oxidative modification hypothesis of
atherosclerosis: does it hold for human?
Trends in Cardiovascular Medicine, 11,
93-102.
Woodhill, J. M., Palmer, A. J., Leelarthaepin,
B., McGilchrist, C. & Blacket, R. B.
(1978). Low fat, low cholesterol diet in
secondary prevention of coronary heart
disease. Advances in Experimental
Medicine and Biology, 109, 317330.
Yano K., Rhoades G. G., Kagan A. &
Tillotson J. (1978). Dietary Intake and the
risk of coronary heart disease in Japanese
men living in Hawai. The American
Journal of clinical Nutrition, 31, 12701279.