Health Effects of Saturated Fatty Acids

RP Mensink, Maastricht University, The Netherlands

r 2013 Elsevier Ltd. All rights reserved.

This article is a revision of the previous edition article by R. P.

Mensink and E. H. M. Temme, volume 2, pp 225–230, r 2005,
Elsevier Ltd.

Glossary Fibrinolysis The process of dissolving a thrombus by lysis

Apoprotein The protein part of lipoproteins.
Coagulation The formation of a stable thrombus through
the formation of fibrin.
Eicosanoids Bioactive molecules made from fatty acids
with 20 carbon atoms.
of fibrin.
Lipoproteins Lipid–protein complexes that carry fats
(e.g., triacylglycerol and cholesterol) in the blood stream.
Platelet aggregation The formation of a loose aggregate
of platelets (thrombus) in the blood.

Fats and oils always consist of a mixture of fatty acids, al-
though one or two fatty acids are usually predominant.
Table 1 shows the fatty acid composition of some edible fats
rich in saturated fatty acids. In the Western diet, palmitic acid
(C16:0) is the major saturated fatty acid. A smaller proportion
comes from stearic acid (C18:0), followed by myristic acid
(C14:0), lauric acid (C12:0), and short-chain and medium-chain
fatty acids (MCFA) (C10:0 or less).
When discussing the health effects of the total saturated
fat content of diets, this class of fatty acids has to be com-
pared with some other component of the diet that provides a
similar amount of energy (isoenergetic). Otherwise, two vari-
ables are being introduced: changes in total dietary energy
intake and as a consequence, changes in body weight. Nor-
mally, an isoenergetic amount from carbohydrates is used for
comparisons.
Cholesterol Metabolism
Lipoproteins and their associated apoproteins are strong
predictors of the risk of coronary heart disease (CHD). Con-
centrations of total cholesterol, low-density lipoproteins
(LDL) and apoprotein B are positively correlated with CHD
risk; high-density lipoprotein (HDL) and apoprotein AI con-
centrations are negatively correlated. Controlled dietary trials
have now demonstrated that the total saturated fat content
and the type of saturated fatty acid in the diet affect serum
lipid and lipoprotein levels.
Total Saturated Fat Content of Diets
Using statistical techniques, results from independent experi-
ments have been combined to develop equations that estimate
the mean change in serum lipoprotein levels for a group of
subjects when carbohydrates are replaced by an isoenergetic
amount of a mixture of saturated fatty acids. The predicted
changes for total LDL and HDL cholesterol, and triacylgly-
cerols are shown in Figure 1. Each bar represents the predicted
change in the concentration of that particular lipid or lipo-
protein when a particular fatty acid class replaces 10% of the
daily energy intake from carbohydrates. For a group of adults
with an energy intake of 10 MJ daily, 10% of energy is pro-
vided by about 60 g of carbohydrates or 27 g of fatty acids.
A mixture of saturated fatty acids strongly elevates serum
total cholesterol concentrations. It was predicted that when
10% of dietary energy provided by carbohydrates was ex-
changed for a mixture of saturated fatty acids, serum total
cholesterol concentrations would increase by 0.36 mmol l1.
This increase in total cholesterol will result from a rise in both
LDL and HDL cholesterol concentrations. Saturated fatty acids
will also lower fasting triacylglycerol concentrations compared
with carbohydrates. Besides affecting LDL and HDL choles-
terol concentrations, a mixture of saturated fatty acids also

Table 1 Composition of fats rich in saturated fatty acids

Weight per 100 g of total fatty acids (g)

oC10:0 C12:0 C14:0 C16:0 C18:0 C18:1 C18:2 C18:3 Other

Butter fat 9 3 17 25 13 27 3 1 2
Palm kernel fat 8 50 16 8 2 14 2
Coconut fat 15 48 17 8 3 7 2
Palm oil 1 45 5 39 9 1
Beef fat 3 26 22 38 2 1 8
Pork fat (lard) 2 25 12 44 10 1 6
Cocoa butter 26 35 35 3 1

Encyclopedia of Human Nutrition, Volume 2 http://dx.doi.org/10.1016/B978-0-12-375083-9.00101-X 215

216 Fatty Acids: Health Effects of Saturated Fatty Acids

0.40
Saturates
Cis-monounsaturates
0.20 Cis-polyunsaturates

mmol l−1
0.00

−0.20

−0.40
Total LDL HDL Triacylglycerol
cholesterol cholesterol cholesterol
Figure 1 Predicted changes in serum lipids and lipoproteins when 10% of energy from dietary carbohydrates is replaced by an isoenergetic
amount of saturated fatty acids. Adapted from Mensink RP, Zock PL, Kester AD, and Katan MB (2003) 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.
American Journal of Clinical Nutrition 77: 1146–1155, with permission from ASN.

0.80
Lauric acid (C12:0)
0.60 Myristic acid (C14:0)

Palmitic acid (C16:0)

0.40
mmol l−1

Stearic acid (C18:0)

0.20

0.00

−0.20
Total LDL HDL Triacylglycerol
cholesterol cholesterol cholesterol
Figure 2 Overview of the effects of particular fatty acids on serum total, LDL, and HDL cholesterol concentrations when 10% of energy from
dietary carbohydrates is replaced by an isoenergetic amount of a particular saturated fatty acid. Adapted from Mensink RP, Zock PL, Kester AD,
and Katan MB (2003) 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. American Journal of Clinical Nutrition 77: 1146–1155, with permission from ASN.

changes the concentrations of their associated apoproteins. In
general, strong associations are observed between changes in
LDL cholesterol and changes in apo-B, and between changes
in HDL cholesterol and apo-AI.
The figure also shows that total and LDL cholesterol con-
centrations decrease when saturated fatty acids are replaced by
unsaturated fatty acids. In addition, slight decreases of HDL
cholesterol concentrations are then predicted.
Effects of Specific Saturated Fatty Acids
Cocoa butter raises total cholesterol concentrations to a lesser
extent than palm oil does. This difference in the serum chol-
esterol-raising potency of two fats high in saturated fatty acids
(see Table 1) shows that not all saturated fatty acids have
equal effects on cholesterol concentrations. Figure 2 illustrates
the effects of lauric, myristic, palmitic, and stearic acids on
LDL and HDL cholesterol concentrations. Compared with
other saturated fatty acids, lauric and myristic acids have the
strongest potency to increase serum total and LDL cholesterol
concentrations, and also HDL cholesterol concentrations.
Effects of lauric acid on HDL cholesterol are stronger than
those of myristic acid.
Stearic acid, a major fatty acid in cocoa butter, does not
raise total, LDL and HDL cholesterol levels compared with
carbohydrates. Also, MCFA have been reported not to raise
LDL and HDL cholesterol concentrations compared with
carbohydrates, but data are limited. Like carbohydrates, diets
containing large amounts of MCFA increase fasting triacylgly-
cerol concentrations compared with the other saturated fatty
acids. However, such diets are the sole energy source only in

parenteral or enteral nutrition, or in sports drinks. Other sat-
urated fatty acids have not been reported to raise triacylgly-
cerol concentrations compared with each other, but lower
triacylglycerol concentrations compared with carbohydrates.
Platelet Aggregation
Increased platelet aggregation may be an important risk
marker for the occurrence of cardiovascular disease, and dif-
ferent types of fatty acids can modify platelet aggregation
in vitro. However, reports of research on this topic are con-
fusing. All measurements have their limitations, and it is not
known whether measurement in vitro of platelet aggregation
reflects the reality of platelet reactivity in vivo.
Many methods are available to measure platelet aggregation
in vitro. Firstly, the blood sample is treated with an anti-
coagulant to avoid clotting of the blood in the test tube or in
the aggregometer; many different anticoagulants are used,
which all differ in their mechanism of action. Secondly, platelet
aggregation can be measured in whole-blood, in platelet-rich
plasma or (to remove the influence of the plasma constituents)
in a washed platelet sample. Finally, the platelet aggregation
reaction in the aggregometer can be initiated with many dif-
ferent compounds, such as collagen, Adenosine diphosphate
(ADP), arachidonic acid, and thrombin. Platelet aggregation
can also be studied by measuring the stable metabolites of the
proaggregatory thromboxane A2 (TxA2), thromboxane B2
(TxB2), the stable metabolite of the antiaggregatory prosta-
glandin (prostacyclin: PGI2), or 6-keto-PGF1a.
Total Saturated Fat Content of Diets
Platelet aggregation and clotting activity of plasma were
studied in British and French farmers, who were classified
according to their intake of saturated fatty acids. A positive
correlation was observed between thrombin-induced aggre-
gation of platelet-rich plasma and the intake of saturated fatty
acids. Aggregation induced by ADP or collagen, however, did
not correlate with dietary saturated fat intake. In a follow-up
study, a group of farmers consuming high-fat diets were asked
to replace dairy fat in their diets with a special margarine rich
in polyunsaturated fatty acids. Besides lowering the intake of
saturated fatty acids, this intervention also resulted in a lower
intake of total fat. A control group of farmers did not change
their diets. After this intervention the thrombin-induced ag-
gregation of platelet-rich plasma decreased when saturated fat
intake decreased. Aggregation induced by ADP, however, in-
creased in the intervention group. From these studies, it is not
clear whether the fatty acid composition of the diets or the
total fatty acid content is responsible for the changes in
platelet aggregation. Furthermore, it is not clear if one should
favor increased or decreased platelet aggregation after de-
creasing the saturated fat content of diets as effects did depend
on the agonist used to induce platelet aggregation. Saturated
fatty acids from milk fat have also been compared with un-
saturated fatty acids from sunflower and rapeseed oils. Ag-
gregation induced by ADP or collagen in platelet-rich plasma
was lower with the milk fat diet than with either oil.
Fatty Acids: Health Effects of Saturated Fatty Acids 217
One of the mechanisms affecting platelet aggregation is
alteration of the proportion of arachidonic acid in the platelet
phospholipids. Arachidonic acid is a substrate for the pro-
duction of the proaggregatory TxA2 and the antiaggregatory
PGI2, and the balance between these two eicosanoids affects
the degree of platelet activation. The proportion of arachi-
donic acid in membranes can be modified through changes in
dietary fatty acid composition. Diets rich in saturated fatty
acids increase the arachidonic acid content of the platelet
phospholipids, but this is also dependent on the particular
saturated fatty acid consumed (see below).
Diets rich in saturated fatty acids have also been associated
with a lower ratio of cholesterol to phospholipids in platelet
membranes, which may affect receptor activity and platelet
aggregation. However, these mechanisms have been described
from studies in vitro and on animals and have not adequately
been confirmed in human studies.
Effects of Specific Saturated Fatty Acids
Diets rich in coconut fat have been reported to raise TxB2 and
lower 6-keto-PGF1a concentrations in collagen-activated
plasma compared with diets rich in palm or olive oils, indi-
cating a less favorable eicosanoid profile. The main saturated
fatty acids of coconut fat – lauric and myristic acids – did not,
however, change collagen-induced aggregation in whole-
blood samples compared with a diet rich in oleic acid. Also,
diets rich in MCFA or palmitic acid did not change collagen-
induced aggregation in whole-blood samples. Compared with
a diet rich in a mixture of saturated fatty acids, a stearic acid
diet increased collagen-induced aggregation in platelet-rich
plasma. In addition, a decreased proportion of arachidonic
acid in platelet phospholipids was demonstrated after a cocoa
butter diet compared with a diet rich in butter fat. Changes in
eicosanoid metabolite concentrations in urine, however, were
not observed after either diet. These results are conflicting and
it is debatable whether measurement in vitro of platelet
aggregation truly reflects the situation in vivo.
Coagulation and Fibrinolysis
Processes involved in thrombus formation include not only
those required for the formation of a stable thrombus (platelet
aggregation and blood clotting), but also a mechanism to
dissolve the thrombus (fibrinolysis). Long-term prospective
epidemiological studies have reported that in healthy men
factor VII coagulant activity (factor VIIc) and fibrinogen con-
centrations were higher in subjects who developed cardio-
vascular diseases at a later stage of the study. Factor VIIc in
particular was associated with an increased risk of dying from
cardiovascular disease. A high concentration of plasminogen
activator inhibitor type 1 (PAI-1) indicates impaired fibrino-
lytic capacity of the plasma and is associated with increased
risk of occurrence of coronary events.
Saturated fatty acids can affect the plasma activity of some
of these coagulation and fibrinolytic factors and thus the
prethrombotic state of the blood. However, the effects of sat-
urated fatty acids on coagulation and fibrinolytic factors in
humans, unlike effects on cholesterol concentrations, have
218 Fatty Acids: Health Effects of Saturated Fatty Acids
received little attention, and few well-controlled human
studies have been reported. Also, regression equations derived
from a meta-analysis, which predict the effects on coagulation
and fibrinolytic factors of different fatty acid classes compared
with those of carbohydrates, do not exist. Therefore, the ref-
erence fatty acid is dependent on the experiment discussed. In
the epidemiological studies that have found associations be-
tween CHD risk and factors involved in thrombogenesis or
atherogenesis, subjects were mostly fasted. Also, the effects of
saturated fatty acids on cholesterol metabolism, platelet ag-
gregation, and coagulation and fibrinolysis have been studied
mainly in fasted subjects. It should be noted, however, that
concentrations of some coagulation factors (e.g., factor VIIc)
and fibrinolytic factors change after a meal.
Total Saturated Fat Content of Diets
Coagulation
Results of studies on the effects of low-fat diets compared with
high-fat diets provide some insight into the effects of de-
creasing the saturated fat content of diets. However, in these
studies multiple changes are introduced which makes inter-
pretation of results difficult.
Figure 3 demonstrates that decreased factor VIIc levels were
demonstrated in subjects on low-fat diets compared with
those on high-saturated fat diets. In many of these studies, the
low-fat diet provided smaller quantities of both saturated and
unsaturated fatty acids and more fiber than the high-saturated
fat diets. The combined results, however, suggest that, apart
from a possible effect of dietary fiber, saturates increase factor
VII levels compared with carbohydrates. Effects on other
clotting factors are less clear. Measurements of markers of
in vivo coagulation (e.g., prothrombin fragment 1 þ 2) might
have provided more information on the effect of saturates on
blood coagulation, but were unfortunately not measured in
most experiments.
Fibrinolysis
Effects of low- and high-fat diets on the fibrinolytic capacity of
the blood have also been studied. A similar problem, as stated
100
Factor VIIc (% of standard)
95
90
High-saturated fat diet
85 Low-fat, high-carbohydrate diet
80
75
70
Fasting
Figure 3 Effects of a high-saturated fat diet on fasting and
postprandial factor VIIc activity. Adapted from Mensink RP, Zock PL,
Kester AD, and Katan MB (2003) 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. American Journal of Clinical Nutrition 77: 1146–1155, with
permission from ASN.
before, is that multiple changes were introduced within
a single experiment. Results of longer and shorter-term
studies with dietary changes of total fat (decrease of saturated
and unsaturated fatty acids contents) and increased
fiber content indicate beneficially increased euglobulin fibri-
nolytic capacity of the blood. However, when the saturated
fatty acid and fiber content of two diets were almost
identical and only the unsaturated fatty acid content was
changed, no significant differences of fibrinolytic capacity
were observed.
Little is known about the relative effects on fibrinolytic
capacity of saturated fatty acids compared with unsaturated fatty
acids. It has been reported, however, that diets rich in butter fat
decreased plasminogen activator inhibitor (PAI)-1 activity
compared with a diet rich in partially hydrogenated soybean oil,
but whether this is because of changes in the saturated acid or
the trans fatty acid content is not clear from this study.
As for coagulation factors, the findings on the fibrinolytic
effects of saturates are still inconclusive and need to be
examined by more specific assays, measuring the activities of
the separate fibrinolytic factors such as tPA and PAI-1.
Effects of Specific Saturated Fatty Acids
Coagulation
The interest in the effects of particular fatty acids on coagu-
lation and fibrinolytic factors has increased because the ob-
servation that different saturated fatty acids raise serum lipids
and lipoproteins in different ways (see Cholesterol metabol-
ism). Although results are conflicting, some studies indicate
that the most potent cholesterol-raising saturated fatty acids
also increase factor VII activity.
Diets rich in lauric plus myristic acids compared with a
diet rich in stearic acid also increase concentrations of
other vitamin K-dependent coagulation proteins. In addition,
this mixture of saturated fatty acids raised F1 þ 2 concen-
trations, indicating increased in vivo turnover of prothrombin
to thrombin. This agreed with a study in rabbits where
increased F1 þ 2 concentrations were associated with in-
creased hepatic synthesis of vitamin K-dependent clotting
factors.
Diets rich in certain saturated fatty acids (lauric acid
and palmitic acid) and also diets rich in butter fat have been
reported to raise fibrinogen concentrations, but increases were
small.
Postprandially, increased factor VIIc concentrations
have been demonstrated after consumption of diets rich in
fat compared with fat-free meals (Figure 3). The response
is stronger when more fat is consumed, but this occurs re-
gardless of whether the fat is high in saturated or unsaturated
fatty acids. Only meals with unrealistically high amounts of
MCFA have been reported not to change factor VIIc levels in
Non-fasting comparison with a meal providing a similar amount of olive
oil.
Fibrinolysis
Increased PAI-1 activity of a palmitic acid-rich diet has been
observed compared with diets enriched with oleic acid, indi-
cating impaired fibrinolytic capacity of the plasma. However,

this was not confirmed by other experiments on the effects of
particular saturated fatty acids (including palmitic acid),
which did not indicate changes in fibrinolytic capacity of the
blood, measured as tPA, PAI-1 activity, or antigen concen-
trations of tPA and PAI-1.
Conclusion
Saturated fatty acids as a group affect factors involved
in cholesterol metabolism. Relative to the carbohydrate
content of the diet, a decrease in saturated fat content induces
a favorable decrease in serum total and LDL cholesterol
concentrations, but unfavorably reduces HDL cholesterol
concentrations. Both increasing and decreasing effects of sat-
urates on platelet aggregation have been observed, as well as
absence of effect, so results are inconsistent and difficult to
interpret. Whether the beneficial effect of a diet low in satur-
ated fat on the prethrombotic state of blood depends on the
dietary fiber content is still unclear.
Of the saturated fatty acids, lauric and myristic acids
have the strongest potency to raise total and LDL cholesterol
concentrations. In addition, both of these saturated fatty
acids raise HDL cholesterol levels. Palmitic acid raises
total and LDL cholesterol levels compared with carbohy
drates but is less potent than lauric and myristic acids.
Stearic acid does not raise LDL and HDL cholesterol concen-
trations compared with carbohydrates. Lauric, myristic,
and palmitic acids increase factor VII activity in a similar
way, whereas the effects of MCFA and stearic acid seem
limited.
See also: Cholesterol: Factors Determining Blood Levels; Sources,
Absorption, Function, and Metabolism. Coronary Heart Disease:
Lipid Theory; Prevention. Fatty Acids: Metabolism
Fatty Acids: Health Effects of Saturated Fatty Acids 219
Further Reading
Delgado-Lista J, Lopez-Miranda J, Cortés B, et al. (2008) Chronic dietary fat intake
modifies the postprandial response of hemostatic markers to a single fatty test
meal. American Journal of Clinical Nutrition 87: 317–322.
Hornstra G and Kester ADM (1997) Effect of the dietary fat type on arterial
thrombosis tendency: Systematic studies with a rat model. Atherosclerosis 131:
25–33.
Kris-Etherton PM, Binkoski AE, Zhao G, et al. (2002) Dietary fat: Assessing the
evidence in support of a moderate-fat diet; the benchmark based on lipoprotein
metabolism. Proceedings of the Nutrition Society 61: 287–298.
Lefevre M, Kris-Etherton PM, Zhao G, and Tracy RP (2004) Dietary fatty acids,
hemostasis, and cardiovascular disease risk. Journal of the American Dietetic
Association 104: 410–419.
Mensink RP, Zock PL, Kester AD, and Katan MB (2003) 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. American
Journal of Clinical Nutrition 77: 1146–1155.
Miller GJ (2005) Dietary fatty acids and the hemostatic system. Atherosclerosis 179:
213–227.
Mutanen M and Freese R (2001) Fats, lipids and blood coagulation. Current
Opinion in Lipidology 12: 25–29.
Sacks FM and Katan M (2002) Randomized clinical trials on the effects of dietary
fat and carbohydrate on plasma lipoproteins and cardiovascular disease.
American Journal of Medicine 113 (Supplement 9B): 13S–24S.
Sanders TA and Berry SE (2005) Influence of stearic acid on postprandial lipemia
and hemostatic function. Lipids 40: 1221–1227.
Sanders TA (2009) Fat and fatty acid intake and metabolic effects in the human
body. Annals of Nutrition and Metabolism 55: 162–172.
Temme EHM, Mensink RP, and Hornstra G (1998) Saturated fatty acids and effects
on whole blood aggregation in vitro. European Journal of Clinical Nutrition 52:
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Temme EHM, Mensink RP, and Hornstra G (1999) Effects of diets enriched in
lauric, palmitic or oleic acids on blood coagulation and fibrinolysis. Thrombosis
and Haemostasis 81: 259–263.
Thijssen MA, Hornstra G, and Mensink RP (2005) Stearic, oleic, and linoleic acids
have comparable effects on markers of thrombotic tendency in healthy human
subjects. Journal of Nutrition 135: 2805–2811.
Tholstrup T, Miller GJ, Bysted A, and Sandström B (2003) Effect of individual
dietary fatty acids on postprandial activation of blood coagulation factor VII and
fibrinolysis in healthy young men. American Journal of Clinical Nutrition 77:
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Tholstrup T (2005) Influence of stearic acid on hemostatic risk factors in humans.
Lipids 40: 1229–1235.