Fact Sheet 1
In recent years new clinical recommendations for the assessment and treatment of lipid risk for coronary heart disease (CHD) have been developed by national and international expert and consensus groups as a consequence of a rapidly expanding knowledge basis. Lipid risk factors included in current clinical guidelines are total or low density lipids (LDL) cholesterol, high density lipids (HDL) cholesterol, and plasma triglycerides (12,34,39).
There is no doubt that elevated cholesterol levels due to high levels of LDL cholesterol play a causal role in atherosclerotic heart disease. Extensive observational epidemiological data from both between- and within-population studies relate elevations of total cholesterol or LDL cholesterol to increased CHD incidence. These data are corroborated by genetic and experimental evidence. Furthermore, a large body of interventional epidemiological data, from both primary and secondary prevention trials show a reduction in CHD events with a reduction in total or LDL cholesterol. In general, a 1% reduction in total cholesterol yields a 2-3 % reduction in CHD risk (12,14,24,28).
Numerous epidemiological studies have also established that HDL cholesterol is an independent and powerful predictor of CHD incidence. Until now, information on the effects of increasing HDL cholesterol levels in humans is limited, but suggests favourable effects on CHD risk (12,24,39).
The findings regarding a relation between plasma triglyceride level and CHD incidence are mixed. There is a consistent, strong association in case-control studies. The relation is confirmed in most prospective studies on univariate analysis, but on multivariate analysis of their data it weakens or disappears, in particular when HDL cholesterol, coagulation factors or indicators of abnormal glucose metabolism are taken into account (40).
In the last years evidence has emerged
that elevated triglyceride levels confer a high risk for CHD if they occur in
conjunction with low HDL cholesterol and elevated LDL cholesterol (so-called
lipid triad) or if the LDL/HDL cholesterol ratio is high and triglyceride
concentration is elevated. In addition, it has been shown that the conjunction
of elevated triglycerides and low HDL cholesterol is often associated with
increased insulin resistance, hyperinsulinaemia, higher glucose levels,
hypertension, and central obesity. This constellation of risk factors
constitutes a syndrome predisposing to atherosclerosis (24,40).
As a general rule, there is the
finding that one single or isolated lipid value can not be classified as
normal or elevated. The lipid cutpoints shown in
Table 1 are not absolute. They should only be
regarded as general advice for risk evaluation and therapy. All other risk
factors (Table 2) should be also taken into account when
assessing the cardiovascular risk. All therapeutic decisions should generally
be based on the patient's overall risk profile. Furthermore, treatment goals
for hyperlipidaemia also strongly depend on the global risk (Table 3) (12,24,39).
Decades of research work have clearly demonstrated that diet has a strong influence on serum levels of lipids and lipoproteins. Thus, diet is a cornerstone both in the prevention and treatment of lipid metabolism disorders and CHD.
The action of dietary saturated fatty acids (SFA) as a lipid class to raise total cholesterol levels is well established. The increase in total cholesterol induced by SFA is due mostly to an increase in LDL cholesterol. This increase in LDL cholesterol is accompanied by an elevation of LDL apolipoprotein (apo) B-100, without changes in the ratio between LDL cholesterol and apo B-100. Thus, the increase in LDL cholesterol is due to an increase in the number of LDL particles and not to changes in the cholesterol content of LDL particles. Diets high in fat and SFA also lead to an increase in HDL cholesterol and apo A-I.
This elevation in HDL cholesterol deserves some attention because it is said to antagonise the adverse effects of high LDL concentrations. However, low HDL cholesterol associated with low LDL cholesterol in populations consuming high-carbohydrate, low-fat diets does not increase the coronary risk, whereas populations with high LDL due to high saturated fatty acids (SFA) diets undoubtedly have a high coronary risk in spite of their higher HDL levels. Obviously the magnitude of LDL elevation outweighs the smaller relative increase in HDL cholesterol. Furthermore, the LDL/HDL cholesterol ratio was found to be higher on diets high in total fat and SFA than on low-fat or polyunsaturated fatty acid (PUFA)rich diets in nearly all studies (5,10,20,26,32,33).
Saturated dietary fat usually contains a mixture of SFA of different chain lengths. It has been demonstrated that the different SFA are not equally hypercholesterolaemic. The principal SFA in Western diets is palmitic acid (C16:0), followed by stearic acid (C18:0), myristic acid (C14:0) and lauric acid (C12:0). In a mixed Western diet lauric, myristic and palmitic acids together usually make up about 60-70% of all SFA. These three fatty acids are responsible for the cholesterol-raising effect of saturated fat.
Palmitic acid is the main SFA of animal fat, while myristic acid is abundant in butter fat, palm kernel oil and coconut oil. The latter two also contain very high proportions of lauric acid. It is still a matter of discussion which of the three fatty acids has the highest cholesterol-raising potential, but as a result from several well-controlled studies, the differences among lauric, myristic and palmitic acids appear modest. All three clearly raise LDL cholesterol (8,9,43,48).
The cholesterol-elevating effect of stearic acid, of which the highest content is found in cacoa butter, is much less than that of lauric, myristic and palmitic acids, and more closely approximates the effect of oleic acid. Recent trials, however, have reported a modest fall in HDL cholesterol in response to dietary stearic acid relative to dietary unsaturated fatty acids. Thus, stearic acid and oleic acid are equivalent in their effects on LDL cholesterol but might be somewhat different in their effects on HDL cholesterol concentrations (6,27).
Despite the recent findings about differences in the cholesterol-raising potential of the different SFA, the general recommendation to reduce the amount of SFA consumed in the Western diet is still valid, especially in practice. Most foods contain a mixture of different fatty acids, and, in addition, the cholesterol-elevating SFA are the major fatty acids of a typical Western diet.
In individuals who are not overweight, foods rich in SFA would have to be replaced with other types of food in order to maintain the energy balance in equilibrium. In the past, carbohydrate-rich foods were generally considered to be an ideal candidate for replacing SFA-rich foods. The second alternative as a replacement for saturated fat were polyunsaturated fatty acids (PUFA).
PUFA naturally occur in two major groups with distinct metabolic properties: -3 and -6 fatty acids. These terms indicate the position of the first double bond counting from the methyl end of the fatty acids. The major dietary PUFA is linoleic acid (C18:2, -6) which is predominant in most vegetable oils and in products derived from them. The dietary intake of the other -6-PUFA, -linolenic acid (C18:3,-6) and arachidonic acid (C20:4,-6), represents less than 2% of the total dietary fatty acids.
The -3 fatty acid -linolenic acid (C18:3,-3) is found in very small amounts in many vegetable oils, in higher proportions only in soybean oil, rapeseed oil and linseed oil, whereas the long-chain -3 fatty acids eicosapentaenoic acid (C20:5,-3) and docosahexaenoic acid (C22:6,-3) are contained in fats and oils of marine origin. Marine cold-water fish (herring, mackerel, salmon, tuna) and their products are the major dietary source of these fatty acids. With regard to their effects on lipid metabolism, -3 fatty acids primarily lower serum triglyceride. They have only minor effects on total, LDL and HDL cholesterol (5).
As a cholesterol-lowering alternative
to SFA, only -6 PUFA are of importance. The substitution of SFA with linoleic
acid leads to a marked fall in total cholesterol. This reduction is mainly due
to a decrease in LDL cholesterol which is caused by a reduction in the number
of LDL particles. Diets with high amounts of PUFA (>12-15% of energy) and a
high P/S ratio (> 2) have been shown to also lower HDL cholesterol (2,11,21,32,35).
In the majority of naturally occurring unsaturated fatty acids the double bonds are in cis configuration. Trans fatty acids, mainly the trans isomers of oleic acid (elaidic acid (C18:1,-9,trans) and vaccenic acid (C18:1,-7,trans)), are produced during hydrogenation, either in the rumen of cows or in oil-hardening factories. The change from cis to trans configuration of the double bond leads to a straightening of the molecule and to changes in the physical and biochemical properties of the fatty acid. Trans fatty acids have a higher melting point, leading to increased solidity of hydrogenated fats.
The effects of trans fatty acids on
serum lipoproteins markedly differ from those of the natural cis isomers. Trans
fatty acids have been shown to raise LDL cholesterol concentrations and to
decrease HDL cholesterol. Furthermore, they elevate plasma concentrations of
lipoprotein (a), an atherogenic lipoprotein that was hitherto thought
impervious to dietary changes. However, many people eat no more than a few
grams of trans fatty acids per day, and these quantities produce only small
effects on serum lipoprotein concentration (1,25,36,38,46,47).
For many years, monounsaturated fatty acids (MUFA) were not given much attention. More recently, however, a large body of evidence has accumulated showing that MUFA might have some advantages over carbohydrate and PUFA as a substitute for SFA in Western diets.
The major MUFA in the diet is oleic acid (C18:1,-9). Oleic acid is the predominant fatty acid of olive oil (Table 4). Thus, in recent years scientific attention has been focused on the so-called Mediterranean diet and on olive oil as one of its most characteristic components. In the Mediterranean area MUFA usually provide more than 15% of energy (up to 27% in Crete), and they are primarily derived from olive oil. Simultaneously, coronary heart disease incidence, as well as hypercholesterolaemia are by far lower than in other European countries and in the U.S.
Many studies have compared the effects of MUFA and PUFA on plasma lipoproteins under different experimental conditions (2-4,7,11,22,23,29,30,35, 41-46). Well designed and controlled studies are characterised by the following criteria: The dietary intervention trials were conducted with human subjects randomised to a high PUFA-diet and a high MUFA-diet. They consisted of at least two intervention periods which were similar in all respects except for the contents of MUFA and PUFA. Total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were analysed as end-point data from the dietary intervention periods, and the studies included more than 10 participants on each of the diets to obtain a reasonable accurate estimate of the within-group variance.
The majority of studies conducted under such strict conditions consistently shows that serum total and LDL cholesterol are reduced to a similar extent when MUFA or PUFA were substituted for SFA. Most of these studies used olive oil as the MUFA-rich oil, whereas sunflower or safflower oil was used as PUFA-rich oil. Some experimental diets with a very high PUFA content (> 12% of energy) also showed a decrease in HDL cholesterol. This reduction, however, was not observed after diets with a lower PUFA content (< 12% of energy). The substitution of MUFA for SFA did not lead to any significant changes in HDL cholesterol, even if they were consumed in larger amounts (> 15% of energy).
Two recent meta-analyses confirmed that there is no significant difference in total, LDL and HDL cholesterol between diets relatively high in MUFA versus PUFA when fat intake is primarily derived from common vegetable oils, especially when the fatty acid contents are in a range practicable for a long-term diet. The reductions in total and LDL cholesterol are highly significant, and the LDL/HDL cholesterol ratio is also lowered significantly.
On the basis of these results it no longer seems justifiable to recommend the preferential use of PUFA over MUFA. In addition, there is increasing concern about the long-term safety of high intakes of PUFA: First, there is no country world-wide with a long-term intake of PUFA of 10% of energy or even more that could provide the epidemiological evidence that such high intakes indeed will not cause any harmful health effects. Secondly, PUFA easily undergo peroxidation, yielding free oxygen radicals which could cause serious cellular damage. In some animal experiments very large intakes of PUFA were associated with carcinogenesis. High PUFA intake could induce disbalance among different prostaglandins, leading to coagulation disturbances. It has been further discussed if PUFA are associated with a higher risk of cholelithiasis. Taken together, all these aspects have led to a certain caution regarding the recommendations of PUFA intake.
On the other hand, a high MUFA intake has been proved by the mass-experiment of the Mediterranean countries, where olive oil has been used for centuries. In these countries with low CHD mortality the incidence of cancer, gallstones, and other fat-related diseases is not higher than in other countries. Thus, MUFA can be generally regarded as safe.
Carbohydrates, which have been recommended as a substitute for SFA in cholesterol-lowering diets just as PUFA already for many years, can also be regarded as safe. Low-fat, high-carbohydrate diets significantly lower total and LDL cholesterol concentrations, but they also clearly reduce HDL cholesterol levels (16,17). In addition, those diets may have untoward effects on plasma triglycerides, glucose and insulin. These adverse metabolic effects may be more pronounced in individuals with pre-existing underlying disorders, such as diabetes mellitus. They also depend on the fibre content of the diets. If a carbohydrate-rich diet does not contain only starch and sugar but has a high fibre content, i.e. if the diet contains a lot of whole-grain cereals, vegetables, legumes and fruit, the untoward metabolic effects can be prevented to a large degree.
In summary, the various dietary approaches which can replace SFA in the diet of individuals and populations at high risk for CHD do not differ substantially in terms of their ability to reduce plasma cholesterol and LDL cholesterol which is the major target of a diet for prevention of atherosclerosis. However, their influence on other lipid parameters, non-lipid cardiovascular risk factors and other diseases are not identical. Taking this into account, MUFA seem to have some advantages over both PUFA and carbohydrates (5,13,15,18,19,31,34,37).
From the clinical point of view the best diet in terms of both effectiveness and compliance combines the two dietary approaches of both fat reduction and fat modification. A diet, moderately high in carbohydrates and fibre, not too restricted in total fat, but strictly restricted in SFA, with a moderately high MUFA content seems to be the most feasible approach both to preventing and treating dyslipidaemia.
These scientific findings were of great importance in the formulation of the lipid-lowering diet guidelines of both the European Atherosclerosis Society and the American Heart Association: The total fat intake should be reduced to 30% of the total energy intake, SFA should be reduced below 10% of energy. The intake of PUFA should be not more than 10% of energy (7-10%), whereas the remaining fat proportion should be provided by MUFA (10-15% of energy). The dietary cholesterol content should be below 300 mg/day. Furthermore, the intake of complex carbohydrates and dietary fibre should be increased (12,39).
The traditional Mediterranean diet provides an excellent example how these guidelines could be converted into a tasty and appetising diet. It is characterised by an abundance of plant foods such as bread, pasta, vegetables, salad, legumes, fruit; olive oil as the principal source of fat; low to moderate amounts of dairy products; and also only low to moderate amounts of meat, poultry, fish, and eggs. This diet is low in SFA, rich in carbohydrate and fibre, and, as already discussed, has a high MUFA content. The MUFA are primarily derived from olive oil.
In the most Northern and Western European countries the MUFA intake is also relatively high (15% of energy or more), but the MUFA are mainly taken up with foods simultaneously rich in cholesterol-raising SFA, especially with high-fat animal products. So, if the intake of these SFA-rich foods would be reduced to reach the desirable reduction of the SFA intake from 16-20% at present below 10% of energy as recommended, the MUFA intake as well would fall to 10% of energy or less. Thus, to reach the recommended fat content and composition of the diet, clear changes in the food intake must be made in the Western diets. The intake of vegetable foods has to be greatly increased while the consumption of animal foods, primarily high-fat products such as animal fat, high-fat cheese, fatty meats and sausages, as well as of SFA-rich vegetable fats and oils such as palm and coconut oil, and hydrogenated fat should be clearly decreased.
As a substitute for solid (animal and vegetable) fat, vegetable oils are recommended. Due to its high MUFA content olive oil stands out as a vegetable oil with excellent benefits for human health. The consumption of olive oil increases the MUFA intake without any significant elevation of SFA, and ensures an appropriate intake of the essential PUFA. Thus, olive oil can make a valuable contribution to a healthy lipid-lowering and anti-atherogenic diet.