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relationships, it has been necessary to pursue other experimental paradigms to evaluate the effects of individual fatty acids. Controlled Clinical Studies

The Seven Countries Study laid the groundwork for the remarkably productive era of clinical investigation that followed. Many well-controlled feeding studies have been conducted over the past 45 years that have advanced our understanding of the effects different fats, fat classes and individual fatty acids have on plasma lipids, lipoproteins and, in more recent years, measures of thrombogenesis. These studies have culminated in analyses that have summarized primarily the effects of fat classes and, to a lesser extent, individual fatty acids on plasma lipids and lipoproteins.

Most notable are the blood cholesterol predictive equations reported in 1965 by Keys et al. (19) and Hegsted et al. (20). More recently, blood cholesterol predictive equations have been developed to assess the effects of fat quality on plasma total and lipoprotein cholesterol levels (Table 6.1) (21, 22).

In addition, other modeling approaches have been used to summarize the literature and characterize the effects of individual fatty acids on plasma lipids and lipoproteins (Fig. 6.1).

Table 6.1 Predictive equations for estimating the changes in plasma cholesterol in response to changes in dietary fatty acids and cholesterol*.

Equation Author

Original equations

DTC = 1.2 (2D(C12:0 C16:0)) DP) + 1.52DZ Keys et al. (19)

DTC = 2.16DS 1.65DP = 0.067 DC 0.53 Hegsted et al. (20)

Recent equations

DTC = 1.51DS 0.12DM 0.60DP Mensink and Katan (21)

DLDL-C = 1.28DS 0.12DM 0.60DP DHDL-C = 0.47DS + 0.34DM + 0.28DP

DTC = 2.02D(C12:0 C16:0) 0.03DC18:0 0.48DM 0.96DP Yu et al. (22)

DLDL-C = 1.46D(C12:0 C16:0) + 0.07DC18:0 0.69DM 0.96DP DHDL-C = 0.62D(C12:0 C16:0) 0.06DC18:0 + 0.39DM + 0.24DP

* Where DTC = change in plasma total cholesterol in mg/dl; DLDL-C and DHDL-C = change in plasma LDL and HDL cholesterol in mg/ dl; DC12:0, DC14:0, DC16:0, DC18:0 = change in percentage of daily calories from C12:0, C14:0, C16:0; DS, DM, DP = change in percentage of daily calories from SFA, MUFA and PUFA; DZ = change in the square root of daily dietary cholesterol in mg/1000 calories; and DC = change in dietary cholesterol in mg/day.

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Effects of individual fatty acids on serum total, LDL and HDL cholesterol when 1% of energy from carbohydrates in the diet is replaced by 1% of energy from the fatty acid in question.

Effects of individual fatty acids on serum total, LDL and HDL cholesterol when 1% of energy from carbohydrates in the diet is replaced by 1% of energy from the fatty acid in question.

The blood cholesterol predictive equations consistently show that SFAs raise blood cholesterol levels approximately twice as much as PUFAs lower them. MUFAs are either neutral or mildly hypocholesterolemic. In this paper, neutral is used to convey that blood cholesterol levels are neither increased nor decreased. As shown in the Yu et al. (22) equations, stearic acid is a unique SFA in that it elicits a neutral blood cholesterol response. In fact, both Keys et al. (19) and Hegsted et al. (20) did not include stearic acid in the grouping of SFA for the development of their predictive equations. Both investigators classified stearic acid as a neutral fatty acid (like oleic acid) with respect to its effect on plasma cholesterol level. (Of note is that Keys et al. (19) reported that the predictive equations 'failed' when they were used to estimate the plasma cholesterol response to diets high in stearic acid (e.g. cocoa butter)). Interestingly, the LDL cholesterol response parallels the total cholesterol response. Also of interest is that the regression equations demonstrate that all fatty acid classes raise HDL cholesterol levels. Stearic acid, however, has a neutral effect on HDL cholesterol. Thus, all other fatty acid classes raise HDL cholesterol compared with stearic acid.

Interest in the cholesterolemic effects of stearic acid was renewed in 1988 when Bonanome and Grundy (24) demonstrated that stearic acid was hypocholesterolemic compared to palmitic acid. This study raised important questions about the relative hypocholesterolemic effects of stearic acid compared to the other

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