TABLE 1. Composition of the Study Diets As Determined by Chemical Analysis Diet Variable Baseline Reduced Fat Low Fat Protein, % Carbohydrate, % Fat, % SFA,% 12:0 <strong>14</strong>:0 16:0 18:0 MUFA, % 16:1 18:1 PUFA,% 18:2 n6 18:3 n3 20:4 n6 Cholesterol, mg/1000 kcaJ 16.5±0.5 48.1 ±2.9 35.6+2.4 12.90±1.97 0.37±0.03 1.45±0.22 6.86±0.96 3.29±0.67 12.17±1.60 0.05±0.10 11.16±1.29 7.94±0.75 6.95±0.66 0.82±0.06 0.06±0.01 128±21 17.4 t0.9 53.3 t2.4 29.4 t1.5 6.90 t0.60 0.09 t0.01 0.04 t0.04 4.33: t0.30 1.60 t0.21 8.98: t0.64 0.30 fcO.08 8.40 t0.55 11.21 t0.52 10.67 t0.53 0.40 t0.06 0.05: t0.01 <strong>Lichtenstein</strong> et al Low-Fat Diet, Weight Loss, and Plasma Lipids 1753 16.9±0.6 68.0: 15.1: :2.6 5.01: :0.93 0.12d :0.02 0.47: :0.09 2.77d:0.46 1.36d:0.31 4.86d:0.657 0.24: :0.02 4.46: :0.64 2.54: :0.50 2.20: :0.42 0.26; :0.06 0.04: :0.01 85±4 73±3 SFA indicates saturated fatty acids; MUFA, monounsaturated tatty acids; and PUFA, polyunsaturated fatty acids. See "Methods" for definitions of diets. Values are mean±SD; n=3. tein determinations. On one day during the final week of the first three phases or during weeks 5 and 10 of the low-fat (J, energy) phase subjects consumed their three meals plus one snack at standardized intervals, and blood was sampled at 0, 5, 8, 10, and 24 hours. Biochemical Analysis Fasting (12-hour) blood was collected in tubes containing 0.1% EDTA, and very-low-density lipoprotein (VLDL) was isolated from plasma by a single ultracentrifugational spin at density 1.006 g/mL (39 000 rpm for 18 hours at 4°C). Plasma and the 1.006-g/mL infranate were assayed for total cholesterol and/or triglyceride with an Abbott Diagnostics ABA-200 bichromatic analyzer using enzymatic reagents. 33 HDL-C was measured as described, 54 and non-HDL-C (total cholesterol minus HDL-C) was determined in nonfasting plasma after HDL-C precipitation. Lipid assays were standardized through the Lipid Standardization Program of the Centers for Disease Control and Prevention, Atlanta, Ga. Within-run and between-run coefficients of variation of these assays were less than 5%. Apolipoprotein (apo) B was assayed with a noncompetitive, enzyme-linked assay by using immunopurified polyclonal antibodies 53 in plasma after VLDL had been removed. Plasma apoA-I was assayed in the same manner by using apoA-I polyclonal antibodies. 56 Coefficients of variation for both assays were less than 5% within runs and less than 10% between runs. Assays were standardized with LDL containing only apoB and purified apoA-I with the protein content determined by amino add analysis. Lipoprotein(a) [Lp(a)] was quantified by using an enzyme-linked assay with a monoclonal antibody that did not cross-react with plasminogen as the first antibody and a polyclonal antibody as the second antibody that was directed against the apo(a) portion of the Lp(a) particle (Terumo Medical Corp). Lp(a) concentrations are expressed as total Lp(a) mass in milligrams per deciliter. 57 TABLE 2. Baseline Characteristics of the Study Subjects Variable Women (n=6) Men (n=5) Mean Age, y 66±12 54±12 60±13 Body weight, kg 69+18 82±<strong>14</strong> 75+17 Height, cm 159±3 175±10 166±10 Body mass index, kg/m 2 27.2+6 0 26.8±2.4 27.0±4.5 Total cholesterol, mg/dl 243+32 244±11 243±23 VLDL cholesterol, mg/dL 27+7 29±12 28±9 LDL-C, mg/dL 167±28 173±15 169±22 HDL-C, mg/dL 50+9 42±12 46±10 Triglycerides, mg/dL 135±35 <strong>14</strong>4±61 139±46 TC/HDL-C 5.03±1.13 6.16±1.79 5.55±1.51 VLDL indicates very-low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; and TC, total cholesterol. Values are mean±SD. Statistical Analysis The data were analyzed by using SAS (STATISTICAL ANALYSIS SYSTEM; SAS Institute Inc) both for the IBM-compatible personal computer using version 6.04 and as run on a VAX mainframe (Digital Equipment Corp), PROC GLM was used for ANOVA procedures for repeated measures followed by Tukey's t test performed at the ^=.05, .01, and .001 levels of comparison. Results The mean age of the study subjects was 60 ±13 years (Table 2); all subjects had somewhat elevated body mass indexes. At the time of screening they had a mean LDL-C concentration of 169±22 mg/dL. The women tended to have higher HDL-C and lower LDL-C concentrations than the men. The consumption of the reduced-fat diet (29% of calories as fat) resulted in 13%, 18%, and 10% decreases in total cholesterol, LDL-C, and HDL-C concentrations, respectively, relative to the baseline diet (36% of calories as fat) (Table 3 and Fig 1). Changes in LDL apoB concentrations mirrored those of LDL-C. In contrast, despite a decrease in HDL-C concentrations, there was little change in the concentration of apoA-I. These changes resulted in similar total cholesterol/ HDL-C ratios but significantly lower LDL apoB/apoA-I ratios. No significant effects of consuming the reducedfat diet on the concentrations of triglyceride and Lp(a) relative to the baseline diet were observed. When the fat content of the diet was decreased to 15% of calories and consumed at isocaloric levels (low fat [-> energy]), there was a less favorable effect on plasma lipid levels than when the fat content of the diet was reduced to only 29% of calories. Relative to the baseline diet, there were 7%, <strong>14</strong>%, and 25% decreases in total cholesterol, LDL-C, and HDL-C concentrations during the low-fat (-» energy) period (Table 3 and Fig 1). These changes were accompanied by dramatic increases in VLDL cholesterol (95%) and triglyceride (75%) concentrations. Relative to the baseline diet the decrease in LDL apoB concentrations (-17%) was similar to that observed for LDL-C concentrations (-<strong>14</strong>%); however, as Downloaded from http://atvb.ahajournals.org/ by guest on December 7, 2012
1754 <strong>Arterioscler</strong>osis and <strong>Thromb</strong>osis Vol <strong>14</strong>, No 11 November <strong>1994</strong> TABLE 3. Effects of Dietary Fat Reduction and Weight Loss on Plasma Upld and Upoproteln Concentrations Upld or Upoproteln Total cholesterol VLDL cholesterol LDL-C HDL-C Triglycerides TC/HDL LDLapoB ApoA-l Lp(a)§ LDL apoB/apoA-l Baseline 226±33* 21 ±6* 158±28* 48±11* 110±32t 4.99±1.30t 105±23* 131 ±23* 16±21* 0.82±0.21* Reduced Fat 195±19tt (-13+7) 25±3t* (33±48) 128 + 16+* (-18 ±9) 42±9t (-10±6) 115+311" (8 ±25) 4.78±0.97t 82±18t (-20 + 16) 129+20*t (-1+9) 17±23* (7±<strong>14</strong>) 0.65+0.19+ Diet Low Fat (—Energy) 208±22t (-7±10) 39±15* (95±69) 134±17t (-<strong>14</strong>±12) 35±7t (-25±10) 188±76* (75±51) 6.13±1.43* 85±13t (-17±13) 116±<strong>14</strong>t+ (-10+10) 15±21* (-2±25) 0.74±0.13*t Low Fat (i Energy) 190±19+ (-15±8) 32±9*t (64 ±62) 119±15+ (-23±9) 38±8t* (-18±10) 130±32f (22 ±25) 5.13±1.09t 74±18t (-23±24) 111 =t 15t* (-12±10) 13±24t (-27±33) 0.68±0.19*t VLDL indicates very-low-density lipoproteln; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TC, total cholesterol; apo, apolipoprotein; and Lp(a), lipoprotein(a). Values are in milligrams per deciliter (mean percent difference from baseline). See "Methods" for definitions of diets. Values without a common symbol were significantly different at P
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