Saturated Fatty Acids

The Seven Countries Study (7) was a landmark epidemiologic investigation that played a seminal role in establishing a relationship between diet and the incidence of coronary heart disease (CHD). Moreover, this study also provided evidence that diet affected serum cholesterol levels and that an elevation in cholesterol increased risk of coronary disease. This marked the beginning of the dietheart hypothesis era, a time during which numerous studies were conducted to examine the effects of different dietary factors on risk factors for coronary disease. Many of these studies evaluated the relationship between the type of fat in the diet and serum cholesterol levels.

An important finding of the Seven Countries Study was that saturated fat intake (as a percentage of calories) was significantly correlated with serum cholesterol levels; 80% of the variability was due to differences in dietary SFA among the populations. Moreover, SFA intake was also correlated with five-year incidence of CHD. This finding has been confirmed in numerous subsequent studies. This epidemiologic evidence provided the impetus for an era in which carefully controlled clinical studies were conducted initially to evaluate the effects of fat classes and then to assess the impact of individual fatty acids on plasma lipids and lipoproteins. The results from many of the well-controlled clinical studies were used to develop blood cholesterol predictive equations for estimating the changes in total cholesterol (TC) in response to changes in type of fat and amount of dietary cholesterol. The original equations developed by Keys et al. (8) and Hegsted et al. (9) demonstrated that saturated fat was markedly hypercholestero-lemic, whereas PUFA lowered blood cholesterol levels. Saturated fat was found to be twice as potent in raising blood cholesterol levels as PUFA were in lowering them. Both groups of investigators reported that MUFA had a neutral effect and that dietary cholesterol raised the blood cholesterol level but less so than saturated fat. More recently, predictive equations have been developed for low-density lipoprotein (LDL) and HDL cholesterol. The LDL cholesterol response mimics that for total cholesterol. All fatty acid classes and dietary cholesterol increase HDL cholesterol.

These studies have been followed by investigations that evaluated the effects of individual fatty acids on plasma lipids and lipoproteins. A recent summary of the literature evaluating the effects of individual fatty acids is shown in Figure 1 (10). It is evident that the effects observed are quite divergent when comparisons are made among the different fatty acids and even within a fatty acid class. For example, when comparisons are made among the long-chain SFAs, it is apparent that there are pronounced differences in potency. Specifically, myristic acid (C14:0) is twice as potent as lauric acid (C12:0) in raising total and LDL cholesterol. However, stearic acid (C18:0) is uniquely different; it has either a neutral or slight cholesterol-lowering effect. The most potent cholesterol-lowering fatty acid is linoleic acid (C18:2). Oleic acid has effects that are intermediate to those of linoleic acid and the cholesterol-raising SFA. The trans isomer of oleic acid has effects that are quite different from the cis isomer; trans 18:1 raises serum total and LDL cholesterol and may decrease HDL cholesterol.

In contrast to the extensive literature on fat classes and individual fatty acids on blood lipid/lipoprotein responses, much less is known about the effects of dietary fat on thrombosis. Some epidemiologic evidence from the Atherosclerosis Risk in Communities (ARIC) Study indicates that a high intake of total fat, SFA, and cholesterol is associated with higher levels of Factor VII and fibrinogen, two hemostatic factors that play a role in blood clot formation. Likewise, in the Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA) Study, a well-controlled multicenter feeding study, a reduction in saturated fat decreased Factor VII. However, a reduction in total fat increased fibrinogen levels. It is important to note that the magnitude of response for both was modest (ie, 2-3%).

There has been great debate about the association between fat intake and breast cancer. However, a pooled analysis of seven major cohort studies from four countries did not find any association between total fat intake and incidence of breast cancer (11). Population studies have shown a relationship between SFA intake, especially from animal products, and risk of colorectal adenomas. In addition, there is some evidence that SFA increases risk of ovarian cancer (12) and prostate cancer (13).

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