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Because of their large sample sizes, epidemiologic studies can provide important data on the relation between diet, specifically dietary fat and fatty acids, and lipid and lipoprotein concentrations as well as the incidence of coronary artery disease. Although correlation coefficients vary widely (from 0.84 to 0.01) and are frequently low between dietary variables and coronary artery disease or lipids and lipoprotein fractions in the studies reviewed here, intakes of saturated fatty acids and dietary cholesterol are generally positively correlated with blood cholesterol in men and women. Associations between other fatty acids are less consistent and may be related to the considerable differences in these studies in dietary methodologies used, databases used for analyses, and homogeneity of intakes within populations. Relatively few data are available for women, cultural minorities within the United States, or young or elderly populations. However, the trends observed in the United States, ie, lower rates of coronary artery disease as well as lower reported intakes of both total and saturated fats, support the relations observed in the epidemiologic studies.

Studies with animal models suggest that saturated fatty acids raise low density lipoprotein (LDL)-cholesterol levels by reducing LDL receptor-mediated clearance. To examine this directly in humans, we studied the effects of lowering dietary saturated fat on LDL-receptor abundance in peripheral mononuclear cells which reflects hepatic LDL-receptor status. Healthy males and females (n = 25) participating in the DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activity) Study consumed three experimental diets in a randomized cross-over design. Diets provided 34% fat, 15% saturated fatty acids (Average American Diet); 29% fat, 9% saturated fatty acids (Step-One Diet); and 25% fat, 6% saturated fatty acids (Low SAT Diet). Peripheral mononuclear cells were isolated from blood samples collected after 6 and 8 wk. An ELISA was used to quantify LDL-receptor protein in total cell membranes. LDL-receptor abundance increased by 10.5% after the Low SAT Diet (P < 0.05). This was associated with an 11.8% decrease in serum LDL-cholesterol (P < 0.05). A linear inverse relationship was observed between the percentage change in LDL-cholesterol and the percentage change in LDL-receptor abundance (r = -0.59; P < 0.01). In addition, LDL-receptor abundance also was correlated inversely (P < 0.001) with serum levels of LDL-cholesterol (r = -0.747) and apoB (r = -0.593). In summary, reducing dietary saturated fat is associated with an increase in LDL-receptor abundance of magnitude similar to the decrease in serum LDL-cholesterol. Thus, an important mechanism by which reductions in dietary saturated fatty acids decrease LDL-cholesterol in humans is through an increase in LDL-receptor number.

The present study was conducted to determine the effects of dietary fatty acids on hepatic LDL receptor (LDLr) protein abundance and mRNA levels. Sixty pigs were randomized into 10 groups and fed corn-soybean meal diets containing three cholesterol levels (0.25%, 0.5%, and 1.0%, w/w) with no added fat, or fats rich (30% of calories) in palmitic acid or linoleic acid. A control group was fed the base diet with no added fat. After 30 days, plasma LDL-cholesterol (LDL-C) levels increased as the dietary cholesterol increased (P < 0.05); however, there was no significant effect of either fatty acid. Dietary fatty acids, however, had distinctly different effects on hepatic LDLr protein (analyzed by ELISA) and mRNA (analyzed by Northern blot) abundance. When pigs consumed diets containing 0.25% cholesterol, linoleic acid increased hepatic LDLr protein 40% whereas palmitic acid reduced it 40% (P < 0.05). These changes in LDLr protein abundance were accompanied by parallel changes in hepatic LDLr mRNA; linoleic acid increased LDLr mRNA 2-fold (P < 0.01), whereas palmitic acid decreased it 60% (P < 0.01). The differential effects of fatty acids on LDLr expression were only observed at 0.25% cholesterol, suggesting that higher intakes of cholesterol have a dominant and repressive effect on regulation of LDLr expression. Cholesterol intake increased hepatic total cholesterol levels (P < 0.01) while dietary fatty acids had no effect on hepatic sterols. In summary, our results indicate that dietary linoleic acid and palmitic acid have markedly different effects on hepatic LDLr protein abundance that are mediated by differential effects on LDLr mRNA and protein levels. Further studies are needed to fully elucidate the molecular mechanisms by which fatty acids regulate LDLr mRNA and protein levels.

Milk chocolate does not adversely affect plasma lipids and lipoproteins despite its relatively high content of saturated fatty acids (SFAs). Evidence from well-controlled feeding studies indicates that this unique response is due to the high proportion of stearic acid in milk chocolate. In experimental diets containing very high amounts (eg, 280 g/d, or 10 oz/d) and more typical amounts (46.2 g, or 1.65 oz) of milk chocolate, plasma total- and low-density-lipoprotein-cholesterol concentrations are not elevated. Furthermore, isoenergetic substitution of one milk chocolate bar per day for a high-carbohydrate snack in a National Cholesterol Education Program/American Heart Association Step 1 Diet does not adversely affect the cholesterol-lowering response. These findings indicate that stearic acid is not hypercholesterolemic as are the other long-chain SFAs. Thus, as illustrated by the different results generated from the predictive equations that group all long-chain SFAs vs those that consider stearic acid separately, grouping stearic acid with other SFAs appears to misrepresent the actual blood cholesterol response.

The present study compared the effects of diets rich in stearic acid (C18:0) versus one high in lauric and myristic acid (C12:0, C14:0) on platelet phospholipid fatty acid levels and concentrations of urinary thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, which are stable metabolites of thromboxane A2 (TXA2) and PGI2 and indicators of cardiovascular hemostasis. A diet high in dairy butter (B) was the source of C12:0 and C14:0; C18:0 was provided by diets high in cocoa butter (CB), milk chocolate (CHOC) or CB+B in a 4:1 ratio (MIX). A randomized, crossover double-blind experimental design was used. Experimental subjects (n = 15) consumed each diet for 26 days, with a 1-month washout period between each experimental period. Urine and blood were collected from each subject at the beginning and end of each dietary period. Urinary TXB2 and 6-keto-PGF1 alpha were analyzed by radioimmunoassay (RIA). There were no effects of diet on the 24-hour excretion of either metabolite or on the ratio of 6-keto-PGF1 alpha/TXB2, even though there were significant changes in the eicosanoid precursor, arachidonic acid (C20:4n-6), in platelet phospholipids. C20:4n-6 levels increased (44.8% +/- 1.0% to 47.1% +/- 1.3%; P < .05) in the phosphatidylethanolamine phospholipid subclass in subjects on the B diet and decreased in the phosphatidylcholine subclass on the CB diet (16.5% +/- 1.0% to 14.2% +/- 1.1%; P < .05) compared with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

The present studies were conducted to evaluate the cholesterolemic effects of whole-food diets high in stearic acid. In study no. 1, normocholesterolemic young men were fed diets high in stearic acid provided by cocoa butter (CB); oleic acid provided by olive oil (OO); linoleic acid provided by soybean oil (SO); and myristic acid (and lauric acid) provided by dairy butter (B). In study no. 2, different subjects with similar baseline characteristics were fed diets high in stearic acid provided by milk chocolate (C), CB, CB+B (4:1, MIX), and myristic (and lauric) acid provided by B. Both studies used a randomized, crossover, double-blind experimental design, and experimental subjects (n = 18 for study no. 1 and n = 15 for study no. 2) in each study consumed every diet for 26 days with a 1-month wash-out period between each experimental period. The diets provided 37% of calories from fat, of which 81% was provided by the test fat. Ten ounces (280 g) C was provided daily by the C diet. In study no. 1, the B diet was hypercholesterolemic, whereas the SO diet was hypocholesterolemic, compared with the other diets. The OO and SO diets were hypocholesterolemic compared with the CB diet. Low-density lipoprotein (LDL) cholesterol levels, in general, paralleled the changes in plasma total cholesterol levels. SO significantly decreased apolipoprotein (apo) B levels compared with the other diets. Plasma very-low density lipoprotein (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apo A-I levels were unaffected by the experimental diets.(ABSTRACT TRUNCATED AT 250 WORDS)