Effects of the National Cholesterol Education Program s Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis 1,2 Shaomei Yu-Poth, Guixiang Zhao, Terry Etherton, Mary Naglak, Satya Jonnalagadda, and Penny M Kris-Etherton ABSTRACT Background: Plasma lipid and lipoprotein responses have been variable in dietary intervention studies. Objective: The objective of this study was to evaluate the effects of the National Cholesterol Education Program s Step I and Step II dietary interventions on major cardiovascular disease risk factors using meta-analysis. Design: MEDLINE was used to select 37 dietary intervention studies in free-living subjects published from 1981 to1997. Results: Step I and Step II dietary interventions significantly decreased plasma lipids and lipoproteins. Plasma total cholesterol (TC), LDL cholesterol, triacylglycerol, and TC:HDL cholesterol decreased by 0.63 mmol/l (10%), 0.49 mmol/l (12%), 0.17 mmol/l (8%), and 0.50 (10%), respectively, in Step I intervention studies, and by 0.81 mmol/l (13%), 0.65 mmol/l (16%), 0.19 mmol/l (8%), and 0.34 (7%), respectively, in Step II intervention studies (P < 0.01 for all). HDL cholesterol decreased by 7% (P = 0.05) in response to Step II but not to Step I dietary interventions. Positive correlations between changes in dietary total and saturated fatty acids and changes in TC and LDL and HDL cholesterol were observed (r = 0.59, 0.61, and 0.46, respectively; P < 0.001). Multiple regression analyses showed that for every 1% decrease in energy consumed as dietary saturated fatty acid, TC decreased by 0.056 mmol/l and LDL cholesterol by 0.05 mmol/l. Moreover, for every 1-kg decrease in body weight, triacylglycerol decreased by 0.011 mmol/l and HDL cholesterol increased by 0.011 mmol/l. Exercise resulted in greater decreases in TC, LDL cholesterol, and triacylglycerol and prevented the decrease in HDL cholesterol associated with low-fat diets. Conclusion: Step I and Step II dietary interventions have multiple beneficial effects on important cardiovascular disease risk factors. Am J Clin Nutr 1999;69:632 46. KEY WORDS National Cholesterol Education Program, NCEP Step I diet, NCEP Step II diet, total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerol, body weight, risk factors, cardiovascular disease, exercise, meta-analysis, humans INTRODUCTION Diet is the first line of therapy for the management of plasma lipids in the prevention and treatment of cardiovascular disease See corresponding editorial on page 581. (CVD). The goal of dietary therapy is to reduce elevated total cholesterol and LDL-cholesterol concentrations and thereby reduce CVD morbidity and mortality. The National Cholesterol Education Program (NCEP) recommends that dietary therapy be implemented in a stepwise manner. Step I and Step II diets are designed to progressively reduce dietary saturated fatty acids (SFA) and cholesterol and to promote weight loss, if indicated, through diet and exercise. In addition, individuals are encouraged to adopt a healthy lifestyle that includes regular physical activity. Controlled feeding studies have consistently found that a reduction in dietary SFA decreases plasma total and LDL-cholesterol concentrations. In general, a Step I diet decreases plasma total cholesterol and LDL cholesterol by 7 9% compared with the average American diet. A Step II diet has been shown to decrease total cholesterol and LDL cholesterol by 10 20% (1, 2). In controlled feeding studies in which body weight was maintained, low-fat diets often were associated with decreases in HDL cholesterol and increases in triacylglycerol (2 4). A low HDL-cholesterol concentration and an elevated triacylglycerol concentration are both risk factors for CVD (4). In contrast with these potentially adverse effects of low-fat diets on HDL-cholesterol and triacylglycerol concentrations, which have been reported in well-controlled clinical feeding studies, a body of evidence from dietary intervention studies conducted in free-living populations has shown that low-fat diets are typically accompanied by weight loss, and often other risk-factor modifications result in a decrease in plasma total cholesterol, LDL cholesterol, and triacylglycerol, and no change in HDL cholesterol (5 15). Likewise, many free-living populations worldwide consume very-low-fat diets and have a favorable lipid profile, which likely is due to their lifestyle practices, including regular physical activity and maintenance of an ideal body weight (16, 17). 1 From the Graduate Program in Nutrition, The Pennsylvania State University, University Park. 2 Address reprint requests to PM Kris-Etherton, S-126 Henderson Building, Nutrition Department, University Park, PA 16802. E-mail: pmk3@psu.edu. Received May 21, 1998. Accepted for publication November 3, 1998. 632 Am J Clin Nutr 1999;69:632 46. Printed in USA. 1999 American Society for Clinical Nutrition
DIETARY INTERVENTION AND CVD RISK 633 Many primary and secondary intervention studies have evaluated how different intervention strategies to reduce the risk of CVD, including diet modification, affect various CVD risk factors in free-living subjects. In general, the responses in these intervention studies have been quite variable. For example, some studies have shown that dietary intervention and other risk-factor modifications often accompanied by weight loss reduce plasma total cholesterol, LDL cholesterol, as well as triacylglycerol, but increase or have no significant effects on HDL cholesterol (5 15). Other intervention studies, however, found that low-fat diets resulted in an increase in plasma triacylglycerol and a decrease in HDL cholesterol (18 22). Thus, the purpose of the present study was to evaluate the effects of different dietary interventions on major CVD risk factors in healthy and high-risk subjects by conducting a meta-analysis. METHODS Selection of studies MEDLINE (National Library of Medicine, Bethesda, MD) and the references in the papers we identified were used to search all published dietary intervention studies related to cholesterol lowering or reduction of other CVD risk factors in freeliving subjects. Thirty-seven (5 15, 18 43) intervention studies published between 1981 and 1997 were selected for the present meta-analysis. The following criteria were used for inclusion of a dietary intervention trial: 1) the study was designed to lower blood cholesterol concentrations or to decrease body weight for the primary purpose of preventing CVD; 2) the investigators used a randomized design; 3) a Step I diet (in all intervention groups: 30% of total energy as fat, 10% of energy as SFA, and 300 mg dietary cholesterol/d), a Step II diet ( 7% of energy as SFA and 200 mg dietary cholesterol/d), or both were part of the dietary intervention; 4) the subjects were free-living, prepared their own food, and were counseled by dietitians or other professionals about implementing low-fat diets; and 5) the intervention lasted 3 wk to stabilize plasma cholesterol concentrations. Statistical analysis Changes in plasma total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol after Step I and Step II dietary interventions were assessed. Effects of exercise and body weight were evaluated. In addition, effects of baseline plasma total cholesterol, LDL-cholesterol, HDL-cholesterol, and triacylglycerol concentrations on lipid responses were also analyzed. We also examined the relation between changes in body weight and changes in dietary fat and energy consumption. All analyses were done by using the SAS statistical package (44). In each study, plasma lipid concentrations after dietary intervention were compared with lipid concentrations in the control groups as well as with baseline lipid concentrations. Changes in plasma lipid concentrations and in dietary fat or cholesterol were calculated by using the difference between a treatment group and a control group or differences between intervention and baseline values in the intervention groups. Analysis of variance was used to compare the effects of Step I with those of Step II dietary interventions and the effects of interventions including exercise with those not including exercise. Correlations between changes in plasma lipid concentrations (both absolute and percentage changes) and changes in total fat and SFA intakes (as a percentage of total daily energy intake) and changes in dietary cholesterol (mg/d) and changes in body weight (kg) were evaluated by Pearson correlation analysis. Changes in plasma total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol in response to changes in body weight and in dietary total fat, SFA, and cholesterol were evaluated by regression analysis. In each study, the differences in plasma lipid concentrations between intervention and control groups (or between baseline and intervention values) were used as dependent variables and the differences in dietary total fat, SFA, and cholesterol as independent variables. Changes in body weight in the intervention groups were used as a covariable in the regression analysis. Both bivariate and multiple regression analyses were conducted. Bivariate regression analysis included the change ( )in 1 independent variable ( TF, SFA, or cholesterol) and 1 covariable ( BW); multiple regression analysis included the change in 2 independent variables ( TF and cholesterol or SFA and cholesterol) and 1 covariable ( BW). The equations are as follows: Total cholesterol ( LDL cholesterol, HDL cholesterol, or triacylglycerol) = 1 TF ( SFA, or cholesterol) + 2 BW for bivariate regression analysis (Model 1) Total cholesterol ( LDL cholesterol, HDL cholesterol, or triacylglycerol) = 1 TF ( SFA) + 2 cholesterol + 3 BW for multiple regression analysis (Model 2) where BW is body weight and TF is total fat. The coefficients ( 1, 2, and 3 ) were estimated by least-squares regression. Changes in body weight in response to changes in dietary total fat intake were tested by regression analysis and Pearson correlation analysis. In the regression analysis, the change in body weight after intervention was used as a dependent variable and the change in total fat intake was used as an independent variable. The regression equation is as follows: BW = 1 TF (1) Correlation between change in body weight and change in fat was evaluated using the Pearson correlation analysis conducted with and without using subject number as a weight factor from each study. RESULTS The present meta-analysis included 37 intervention studies (5 15, 18 43) in which there were 9276 subjects in intervention groups and 2310 subjects in control groups. The study designs varied remarkably; some were sequential studies but most were randomized, parallel-arm studies. The dietary interventions ranged from vegetarian diets providing <10% of energy as fat, <6% of energy as SFA, and <100 mg cholesterol/d to a Step I diet providing 30% of energy as fat, <10% of energy as SFA, and 300 mg cholesterol/d. The diet compositions and study designs of the interventions are summarized in Table 1; 8 studies evaluated the effects of diet on body weight. Despite the differences in experimental design and populations studied, total cholesterol decreased by 2 25% as a result of dietary and other risk-factor interventions. Lipid concentration data from 30 studies before and after intervention are summarized in Table 2.
634 YU-POTH ET AL TABLE 1 Summary of study designs and diet composition in 37 intervention studies 1 Duration Baseline diet Experimental diet Weight Reference and group of study Energy TF SFA Cholesterol Energy TF SFA Cholesterol Exercise change kj % of % of mg/d kj % of % of mg/d kg energy energy energy energy Step I intervention Hjermann et al (5) I (n = 604M) 4 y ND ND ND ND 9406 28 8 289 No 3.6 C (n = 628M) 4 y ND ND ND ND 9753 44 18 527 No 0.6 Nikolaus et al (6) I (n = 18M) 1 y 9615 44 17 403 6703 29 8 161 Yes 4.5 C (n = 27M) 1 y 9150 38 15 377 7971 37 14 322 No 0.6 Wood et al (7) I (n = 31F) 1 y 8104 37 14 296 5925 29 10 173 No 4.1 I (n = 42F) 1 y 8104 37 14 296 6046 28 10 183 Yes 5.1 C (n = 39F) 1 y 8104 37 14 296 8163 36 13 291 No 1.3 I (n = 40M) 1 y 10945 38 14 400 8033 32 11 241 No 5.1 I (n = 39M) 1 y 10945 38 14 400 8577 28 10 215 Yes 8.7 C (n = 40M) 1 y 10945 38 14 400 11100 39 14 407 No 1.7 Schuler et al (8) I (n = 56M) 1 y 8858 40 ND 355 6443 26 ND 135 Yes 4.8 C (n = 57M) 1 y 8427 37 ND 357 6853 34 ND 232 No 0.6 Singh et al (9) I (n = 204M+F) 1 y 8828 26 10 300 7581 24 7 147 No 7.6 C (n = 202M+F) 1 y 9008 24 10 310 8117 28 11 287 No 1.1 Singh et al (10) I (n = 231M) 12 wk ND ND ND ND 7665 28 6 229 Yes 3.7 C (n = 232M) 12 wk ND ND ND ND 8075 29 12 317 No 1.5 Singh et al (11) I (n = 310M+F) 16 wk 9037 27 12 303 7807 25 8 105 No 1.7 I (n = 310M+F) 24 wk 9037 27 12 303 7929 24 7 186 Yes 3.6 C (n = 311M+F) 16 wk 9129 29 12 317 8933 28 10 291 No 1.1 C (n = 311M+F) 24 wk 9129 29 12 317 8527 27 11 307 No 1.4 Baer (12) I (n = 31M) 1 y 10652 38 ND 444 9397 31 ND 304 No 5.0 C (n = 33M) 1 y 11088 37 ND 425 10 795 36 ND 430 No 1.0 Katzel et al (13) I (n = 14M) 3 mo 10837 36 ND 330 9330 28 ND 220 No 1.0 I (n = 14M) 12 mo 10837 36 ND 330 8452 29 ND 190 Yes 11.0 McCarron et al (14) I (n = 277M+F) 10 wk 8874 35 12 284 6899 25 8 179 No 3.2 Ehnholm et al (18) I (n = 30M) 6 wk 12155 39 22 537 10 226 24 9 302 No 1.1 I (n = 24F) 6 wk 12155 39 22 537 10 226 24 9 302 No 1.0 Kuusi et al (19) I (n = 19M) 6 wk 10694 38 20 466 9075 24 9 277 No ND I (n = 19M) 12 wk 10694 38 20 466 9632 22 8 283 No 1.5 C (n = 19M) 6 wk 11125 38 20 533 9414 25 11 368 No ND C (n = 19M) 12 wk 11125 38 20 533 9745 23 10 351 No 1.6 I (n = 20F) 6 wk 10694 38 20 466 9075 24 9 277 No ND I (n = 20F) 12 wk 10694 38 20 466 9632 22 8 283 No 1.5 C (n = 20F) 6 wk 11125 38 20 533 9414 25 11 368 No ND C (n = 20F) 12 wk 11125 38 20 533 9745 23 10 351 No 1.6 de Lorgeril et al (20) I (n = 219M+F) 2 y 8627 31 11 333 8067 31 8 217 No 1.4 C (n = 192M+F) 2 y 8627 31 11 333 8954 33 12 318 No 2.3 Knopp et al (21) I (n = 78M) 1 y 10234 36 12 347 8950 27 8 238 No 3.0 I (n = 62M) 1 y 9351 36 13 325 8648 26 7 164 No 3.0 I (n = 71M) 1 y 9652 35 12 301 8385 25 7 137 No 2.0 I (n = 59M) 1 y 9205 35 12 314 8226 22 6 136 No 2.0 I (n = 57M) 1 y 9941 36 12 321 8452 28 8 244 No 2.0 I (n = 55M) 1 y 9602 36 12 319 8351 26 7 170 No 2.0 I (n = 62M) 1 y 9548 34 12 323 8021 25 7 136 No 6.0 (Continued)
DIETARY INTERVENTION AND CVD RISK 635 TABLE 1 (Continued) Duration Baseline diet Experimental diet Weight Reference and group of study Energy TF SFA Cholesterol Energy TF SFA Cholesterol Exercise change kj % of % of mg/d kj % of % of mg/d kg energy energy energy energy Step I intervention cont. Ehnholm et al (23) I (n = 38M+F) 6 wk ND 39 20 475 ND 23 7 282 No 0.7 C (n = 36M+F) 6 wk ND 39 20 475 ND 39 20 475 No ND Boyd et al (24) I (n = 100F) 1 y 7335 37 15 333 6456 21 7 244 No 1.0 C (n = 106F) 1 y 7289 37 14 369 7289 35 14 344 No 0.1 Denke and Grundy (25) I (n = 44M) 4 mo ND 37 14 415 7084 30 10 192 No 0.9 C (n = 39M) 1 mo ND 37 14 415 9966 40 15 415 No 0.1 Geil et al (26) I (n = 63F) 8 wk ND ND ND ND 5899 30 10 167 No 0.83 I (n = 99M) 8 wk ND ND ND ND 8745 31 10 231 No 0.89 Dengel et al (27) I (n = 28M) 3 mo 10878 35 11 381 10029 30 8 231 No 1.0 I (n = 14M) 3 mo 9590 35 12 441 9134 30 8 210 No 1.0 I (n = 28M) 9 mo 10878 35 11 381 9263 30 8 213 No 11.0 I (n = 14M) 9 mo 9590 35 12 441 9238 30 8 203 No 0 Davidson et al (28) I (n = 44M+F) 4 wk 10247 37 13 348 7556 28 9 231 No 1.5 I (n = 44M+F) 8 wk 10247 37 13 348 7719 28 10 218 No 1.8 Bae et al (29) I (n = 87M+F) 6 wk 8263 32 11 232 7732 29 9 213 No 0.6 I (n = 87M+F) 12 wk 8263 32 11 232 7636 30 9 186 No 1.1 I (n = 87M+F) 18 wk 8263 32 11 232 7247 29 9 181 No 2.4 Step II intervention McCarron et al (14) I (n = 282M+F) 10 wk 8360 33 11 263 6866 18 6 109 No 4.6 Haskell et al (15) I (n = 118M+F) 4 y 8142 32 10 237 7837 24 7 143 Yes 3.0 C (n = 127M + F) 4 y 8858 33 10 284 8941 33 11 271 No 0.9 Kasim et al (22) I (n = 34F) 1 y 8063 36 12 290 6577 18 6 146 No 3.4 C (n = 38F) 1 y 7100 36 13 295 6272 34 12 266 No 0.8 Arntzenius et al (30) I (n = 39M+F) 2 y 8376 ND 12 178 8381 ND 7 59 No 1.2 Ornish et al (31) I (n = 22M+F) 1 y 8201 32 ND 213 7598 7 ND 12 Yes 10.1 C (n = 19M+F) 1 y 7201 30 ND 205 7100 30 ND 190 No 1.4 Barnard (32) I (n = 4587M+F) 3 wk ND AAD ND ND ND <10 ND <25 Yes 4.3 Barnard et al (33) I (n = 72M+F) 3 wk ND AAD ND ND ND <10 ND <25 Yes 4.0 Seim et al (34) I (n = 41M+F) 6 wk ND 36 ND ND 5268 18 ND ND Yes 4.7 Walden et al (35) I (n = 84F) 6 mo 7657 33 12 222 6523 25 8 154 No 1.6 I (n = 94F) 6 mo 7707 34 12 222 6389 25 7 146 No 2.2 I (n = 123M) 6 mo 9975 34 12 280 8920 24 7 188 No 3.4 I (n = 108M) 6 mo 10330 34 12 281 9004 26 8 189 No 2.9 Diet + weight-loss intervention 2 Fox et al (36) I (n = 16F) 24 wk ND 43 ND ND 2929 3 30 ND ND Yes 7.1 I (n = 13F) 24 wk ND 43 ND ND 2092 3 30 ND ND No 6.6 I (n = 12F) 24 wk ND 41 ND ND 2929 3 30 ND ND No 5.8 Sheppard et al (37) I (n = 171F) 6 mo 7293 39 ND ND 5535 21 ND ND No 3.2 I (n = 171F) 1 y 7293 39 ND ND 5448 22 ND ND No 3.0 I (n = 158F) 2 y 7293 39 ND ND 5640 23 ND ND No 1.9 C (n = 105F) 6 mo 7196 39 ND ND 6548 38 ND ND No 0.4 (Continued)
636 YU-POTH ET AL TABLE 1 (Continued) Duration Baseline diet Experimental diet Weight Reference and group of study Energy TF SFA Cholesterol Energy TF SFA Cholesterol Exercise change kj % of % of mg/d kj % of % of mg/d kg energy energy energy energy Diet + weight-loss intervention cont. 2 C (n = 105F) 1 y 7196 39 ND ND 6602 38 ND ND No 0.4 C (n = 105F) 2 y 7196 39 ND ND 6749 37 ND ND No 0.1 Tremblay et al (38) I (n = 4F) 14 mo 8958 36 ND ND 7703 30 ND ND Yes 4.6 Schlundt et al (39) I (n = 25M+F) 16 20 wk 9205 38 ND ND 5966 19 ND ND No 4.6 I (n = 24M+F) 16 20 wk 8364 39 ND ND 5293 20 ND ND No 8.3 Shah et al (40) I (n = 47F) 6 mo 7920 34 ND ND 6611 21 ND ND No 4.4 I (n = 42F) 6 mo 8866 34 ND ND 6489 30 ND ND No 3.8 Siggaard et al (41) I (n = 50M+F) 12 wk 8201 39 ND ND 7699 28 ND ND No 4.2 C (n = 16M+F) 12 wk 8301 38 ND ND 8401 37 ND ND No 0.8 Jeffery et al (42) I (n = 39F) 6 mo 8222 35 ND ND 6703 22 ND ND No 4.6 I (n = 35F) 6 mo 9305 35 ND ND 6335 30 ND ND No 2.1 I (n = 39F) 12 mo 8222 35 ND ND 6611 25 ND ND No 3.7 I (n = 35F) 12 mo 9305 35 ND ND 7222 31 ND ND No 0.5 Raben et al (43) I (n = 24M+F) 11 wk 12799 37 ND ND 13401 26 ND ND No 1.3 C (n = 24M+F) 11 wk 11498 35 ND ND 11498 35 ND ND No 0 1 I, intervention diet group; C, control group (consumed habitual diet); ND, no data; TF, total fat; SFA, saturated fatty acids. 2 Dietary SFA were not reported in these studies. 3 Change in total energy. Twenty-one intervention studies included both men and women, 9 studies included only men, and 7 studies included only women. Nineteen studies included a control group in which subjects maintained their habitual lifestyle and food consumption throughout the study. Dietary information was estimated by using either a 24-h food recall or 3 7-d food records; a food-frequency questionnaire was also used in some studies. Some studies did not report complete dietary information. For example, 3 Step I (5, 10, 26) and 2 Step II (32, 33) dietary interventions did not report baseline energy, total fat, SFA, and cholesterol intakes (Table 1). The length of intervention ranged from 3 wk to 4 y. Intervention intensity was moderate to high and 13 studies included an exercise intervention. Mean baseline total cholesterol and LDL-cholesterol concentrations were between 4.84 and 6.88 mmol/l (x ± SE: 6.04 ± 0.53 mmol/l) and 3.05 and 4.55 mmol/l (4.01 ± 0.46 mmol/l), respectively, except in the study of Hjermann et al (5) in which subjects had higher baseline concentrations of total cholesterol (8.47 mmol/l) and LDL cholesterol (6.78 mmol/l). Mean baseline HDL-cholesterol concentrations were between 0.72 and 1.72 mmol/l (1.24 ± 0.23 mmol/l) and triacylglycerol concentrations were between 0.85 and 2.51 mmol/l (1.67 ± 0.46 mmol/l). Most studies had more than one endpoint blood collection. Some studies (24, 25, 30, 34) did not have complete plasma lipid data. For example, 2 studies (24, 30) did not report plasma LDL-cholesterol, HDL-cholesterol, and triacylglycerol concentrations and 1 study (25) did not report baseline plasma lipid concentrations (Table 2). A total of 59 dietary intervention groups yielded 59 data points for the regression and correlation analyses. Comparison of the effects of Step I and Step II dietary interventions on plasma lipids Plasma total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerol, and total cholesterol:hdl cholesterol all decreased after both Step I and Step II dietary interventions, by 0.63 ± 0.06 mmol/l (10%), 0.49 ± 0.05 mmol/l (12%), 0.04 ± 0.02 mmol/l (1.5%), 0.17 ± 0.04 mmol/l (8%), and 0.50 ± 0.11 (10%), respectively, after the Step I dietary interventions (P < 0.01 for all, except for HDL cholesterol ) and by 0.81 ± 0.12 mmol/l (13%), 0.65 ± 0.09 mmol/l (16%), 0.09 ± 0.03 mmol/l (7%), 0.19 ± 0.14 mmol/l (8%), and 0.34 ± 0.12 (7%), respectively, after the Step II dietary intervention studies (P < 0.01 for all). The Step II dietary intervention resulted in greater decreases in plasma total cholesterol (P < 0.05), LDL cholesterol (P < 0.05), HDL cholesterol (P = 0.13), triacylglycerol (P = 0.37), and total cholesterol:hdl cholesterol (data not shown) than did the Step I dietary intervention (Figure 1). When analyses were weighted by the number of subjects in each study, plasma total cholesterol, LDL-cholesterol, HDL-cholesterol, and triacylglycerol concentrations decreased by 21%, 21%, 13%, and 33%, respectively, after Step II dietary interventions. Plasma total cholesterol, LDL-cholesterol, and triacylglycerol concentrations decreased by 8%, 8%, and 10%, respectively, after Step I dietary interventions; HDL cholesterol increased by 2%. Decreases in plasma lipids and lipoproteins were much greater after the Step II dietary interventions than after Step I dietary interventions (P < 0.001).
DIETARY INTERVENTION AND CVD RISK 637 FIGURE 1. Changes ( ) in plasma lipids and lipoproteins after National Cholesterol Education Program Step I and Step II dietary interventions. * Significantly different from Step I, P < 0.05. TC, total cholesterol; TG, triacylglycerol. Interestingly, plasma lipid and lipoprotein responses of males and females were comparable after both Step I and Step II dietary interventions (data not shown), with one notable exception. The decrease in HDL cholesterol was greater in women (0.10 mmol/l, 6.8%) than in men (0.03 mmol/l, 2.2%) (P < 0.05) after the Step II intervention. In addition, triacylglycerol concentrations tended to increase in women by 0.01 mmol/l (2.4%) and 0.07 mmol/l (5.4%) and decrease in men by 0.21 mmol/l (10.4%) and 0.03 mmol/l (1.5%), respectively, after Step I and Step II dietary interventions. In addition, most lipid responses were comparable after interventions lasting <6 mo and those after interventions lasting >6 mo (data not shown). The only exception was that HDL-cholesterol FIGURE 2. Correlation between change ( ) in dietary total fat and change in plasma lipids and lipoproteins. Pearson correlation coefficients are significant for plasma total cholesterol (TC, ; r = 0.61, P < 0.0001), LDL cholesterol ( ; r = 0.63, P < 0.0001), and HDL cholesterol ( ; r = 0.41, P < 0.001), but not for triacylglycerol ( ; r = 0.19, P = 0.47). concentrations decreased by 0.09 mmol/l (6.4%) and by 0.13 mmol/l (9.7%), respectively, after Step I and Step II interventions lasting <6 mo and increased by 0.03 mmol/l (4.7%) after Step I interventions and decreased by only 0.01 mmol/l (0.5%) after Step II interventions lasting >6 mo (P < 0.05). Effects of dietary fat and SFAs and body weight on plasma lipids Changes in plasma total cholesterol, LDL cholesterol, and HDL cholesterol were significantly correlated (by Pearson correlation analyses) with changes in dietary total fat (Figure 2) and SFA (Figu re 3). The correlation between the change in plasma triacylglycerol and the change in dietary fat and SFA was not significant. Changes in total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol (both absolute and percentage changes) were significantly correlated with changes in dietary cholesterol (Table 3). When Pearson correlation analyses were weighted by the number of subjects in each study, all correlation coefficients were significant. The regression coefficients of dietary fat, SFA, and cholesterol were significant for changes in total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol by bivariate regression analysis with the change in body weight as a covariable (Table 4). For example, every 1% decrease in energy from dietary total fat decreased total cholesterol by 0.06 mmol/l (0.9%), LDL cholesterol by 0.042 mmol/l (1.04%), and HDL cholesterol by 0.01 mmol/l (0.79%). The regression analysis showed that changes in body weight significantly affected plasma HDL-cholesterol and triacylglycerol concentrations. For example, with dietary total fat as a variable and body weight as a covariable, every 1-kg increase in body weight increased plasma triacylglycerol by 0.041 mmol/l (1.14%) and decreased HDL cholesterol by 0.01 mmol/l (0.83%). The regression coefficients of body weight for changes in total cholesterol and LDL cholesterol were not significant (data not shown). Multiple regression analyses have shown that dietary total fat and SFA had significant effects on plasma total cholesterol, LDL cholesterol, and HDL cholesterol (Table 5). For example, every 1% decrease in energy from dietary SFA resulted in a decrease in
638 YU-POTH ET AL FIGURE 3. Correlation between change ( ) in dietary saturated fatty acids and change in plasma lipids and lipoproteins. Pearson correlation coefficients are significant for plasma total cholesterol ( ; r = 0.70, P < 0.0001), LDL cholesterol ( ; r = 0.70, P < 0.0001), and HDL cholesterol ( ; r = 0.41, P < 0.001), but not for triacylglycerol ( ; r = 0.36, P = 0.06). total cholesterol by 0.056 mmol/l (0.77%), LDL cholesterol by 0.05 mmol/l (1.07%), and HDL cholesterol by 0.012 mmol/l (0.6%). Dietary cholesterol had significant effects on total cholesterol, LDL cholesterol, and possibly triacylglycerol, but not on HDL cholesterol. The regression coefficients of dietary total fat and SFA for triacylglycerol were not significant. Body weight change was shown again to have significant effects on HDL cholesterol and triacylglycerol. With every 1-kg decrease in body weight, plasma triacylglycerol concentrations decreased by 0.011 0.012 mmol/l (0.77 0.87%), whereas HDL-cholesterol concentrations increased by 0.011 mmol/l ( 1%) (Table 5). The regression coefficients for body weight change and changes in total cholesterol and LDL cholesterol were not significant (data not shown). Pearson correlation analyses showed that body weight change was positively correlated with changes in plasma triacylglycerol concentrations (r = 0.35, P < 0.01) and negatively correlated with HDL-cholesterol concentrations (r = 0.38, P < 0.02) in Step I and Step II dietary intervention studies. The correlations between body weight change and changes in total cholesterol and LDL cholesterol were significant only when the analyses were weighted by the number of subjects in each study: r = 0.49 (P = 0.001) and r = 0.49 (P = 0.002), respectively. Effects of exercise on plasma lipids In the present study, we included 14 intervention groups with exercise and 45 intervention groups without exercise. Analysis of variance showed that exercise had significant effects on plasma lipids and lipoproteins. Plasma total cholesterol, LDL-cholesterol, HDL-cholesterol, and triacylglycerol concentrations decreased by 0.60 ± 0.06, 0.47 ± 0.05, 0.06 ± 0.02, and 0.11 ± 0.04 mmol/l, respectively, in intervention groups without exercise and decreased by 0.78± 0.13, 0.56 ± 0.12, 0.01 ± 0.04, and 0.35 ± 0.12 mmol/l in intervention groups with exercise (Figure 4). Exercise groups had a greater decrease than nonexercise groups in plasma total cholesterol (13% compared with 10%), LDL cholesterol (15% compared with 11%), and triacylglycerol (17% compared with 5.2%), but no significant change in HDL cholesterol was observed between exercise and nonexercise groups. When the analyses were weighted by a subject number from each study, the exercise groups had as much as a 3-fold greater decrease in total cholesterol (by 1.27 compared with 0.43 mmol/l, 21% compared with 7%) and LDL cholesterol (by 0.83 compared with 0.29 mmol/l, 21% compared with 7%), a 5-fold greater decrease in triacylglycerol (by 0.77 compared with 0.11 mmol/l, 33% compared with 6%), and a 10-fold smaller decrease in HDL-cholesterol concentrations (by 0.015 compared with 0.145 mmol/l, 0.02% compared with 5.1%) (P < 0.0001 for all comparisons) than the nonexercise groups. Correlation between baseline lipids and lipoproteins and responses to intervention Pearson correlation coefficients showed that the changes in LDL cholesterol, HDL cholesterol, and triacylglycerol were significantly correlated with the baseline concentrations of these lipids (Figure 5). The change in total cholesterol was not correlated with the baseline concentration (Figure 5). However, if baseline total cholesterol concentrations were <6.2 mmol/l, the change in total cholesterol was significantly correlated with baseline concentrations (r = 0.591, P < 0.001). In contrast, no relation was observed in subjects with an initial total cholesterol concentration >6.2 mmol/l (data not shown). A similar relation was observed for LDL cholesterol (data not shown). Thus, it appears that individuals with marked elevations in total cholesterol and LDL cholesterol were less responsive to dietary interventions than were mildly to moderately hypercholesterolemic individuals. Effects of dietary fat and energy intake and exercise on body weight Dietary fat had a significant effect on body weight. The change in body weight after intervention was highly correlated
DIETARY INTERVENTION AND CVD RISK 639 TABLE 2 Lipid concentrations before and after interventions in 30 studies 1 Baseline lipids Endpoint lipids Percentage change Reference and group TC LDL-C HDL-C TG TC LDL-C HDL-C TG TC LDL-C HDL-C TG mmol/l mmol/l % Step I intervention Hjermann et al (5) I 8.47 6.78 0.74 2.15 6.81 4.84 1.30 1.46 19.6 28.6 75.7 32.1 C 8.48 6.72 0.74 2.27 8.82 6.70 1.09 2.26 4.0 0.30 47.3 0.4 Nikolaus et al (6) I 6.28 4.25 0.92 2.28 5.95 4.29 1.04 1.59 5.3 0.9 13.0 30.3 C 6.15 4.23 0.92 2.22 6.06 4.31 0.93 1.83 1.5 1.9 1.1 17.6 Wood et al (7) I 4.98 3.09 1.50 0.85 4.59 2.81 1.35 0.94 7.8 9.1 10.0 10.6 I 4.98 3.09 1.50 0.85 4.70 2.80 1.48 0.83 5.6 9.4 1.3 2.4 C 4.98 3.09 1.50 0.85 4.95 3.06 1.45 0.98 0.6 1.0 3.3 15.3 I 5.41 3.63 1.10 1.44 4.99 3.24 1.12 1.32 7.8 10.7 1.8 8.3 I 5.41 3.63 1.10 1.44 5.03 3.36 1.24 0.96 7.0 7.4 12.7 33.3 C 5.41 3.63 1.10 1.44 5.27 3.43 1.05 1.62 2.6 5.5 4.6 12.5 Schuler et al (8) I 6.05 4.24 0.92 1.97 5.74 4.07 1.01 1.64 5.1 4.0 9.8 16.8 C 6.09 4.25 0.91 2.16 6.08 4.37 0.94 1.79 0.2 2.8 3.3 17.1 Singh et al (9) I 5.83 4.39 1.15 1.94 5.09 3.85 1.22 1.65 12.7 12.3 6.1 14.9 C 5.91 4.31 1.10 1.97 5.59 4.07 1.06 1.85 5.4 5.6 3.6 6.1 Singh et al (10) I 6.29 4.31 1.21 1.79 5.72 3.88 1.25 1.59 9.1 10.0 3.3 11.2 C 6.28 4.26 1.17 1.81 6.09 4.10 1.11 1.71 3.0 3.8 5.1 5.5 Singh et al (11) I 6.31 4.35 1.20 1.79 5.71 3.88 1.25 1.57 9.5 10.8 4.2 12.3 I 6.31 4.35 1.20 1.79 5.46 3.62 1.28 1.45 13.5 16.8 6.7 19.0 C 6.37 4.29 1.71 1.81 6.23 4.17 1.14 1.73 2.2 2.8 33.3 4.4 C 6.37 4.29 1.71 1.81 6.14 4.13 1.14 1.71 3.6 3.7 33.3 5.5 Baer (12) I 6.15 4.30 1.09 1.68 5.43 4.00 1.07 1.49 11.7 7.0 1.8 11.3 C 6.08 4.11 1.09 1.75 6.12 4.16 1.08 1.79 0.7 1.2 0.9 2.3 Katzel et al (13) I 5.24 3.40 0.85 2.25 4.62 3.05 0.79 1.67 11.8 10.3 7.1 25.8 I 5.24 3.40 0.85 2.25 4.17 2.73 0.85 1.27 20.4 19.7 0.0 43.6 McCarron et al (14) I 5.66 3.49 1.16 2.14 5.38 3.33 1.14 1.99 5.0 4.6 1.7 7.0 Ehnholm et al (18) I 5.77 3.59 1.32 1.37 4.99 2.92 1.19 1.30 13.5 18.7 9.9 5.1 I 5.74 ND 1.32 1.23 6.10 ND 1.40 1.26 6.3 ND 6.1 2.4 Kuusi et al (19) I 6.46 4.22 1.45 1.34 5.30 3.44 1.22 1.41 18.0 18.5 15.9 5.2 I 6.46 4.22 1.45 1.34 5.43 3.49 1.19 1.35 15.9 17.3 17.9 0.8 C 6.80 4.52 1.45 1.49 5.92 3.88 1.29 1.51 12.9 14.2 11.0 1.3 C 6.80 4.52 1.45 1.49 6.15 4.03 1.29 1.51 9.6 10.8 11.0 1.3 I 5.92 3.67 1.73 0.86 4.84 2.87 1.40 1.03 18.2 21.8 19.1 19.8 I 5.92 3.67 1.73 0.86 5.02 3.05 1.45 0.82 15.2 16.9 16.2 4.7 C 6.00 3.75 1.71 0.96 5.07 3.15 1.45 1.06 15.5 16.0 15.2 10.4 C 6.00 3.75 1.71 0.96 5.22 3.18 1.45 1.05 13.0 15.2 15.2 9.4 de Lorgeril et al (20) I 6.50 4.52 1.16 2.15 6.17 4.18 1.28 1.85 5.1 7.5 10.3 14.0 C 6.47 4.54 1.17 2.00 6.16 4.11 1.32 1.92 4.8 9.5 12.8 4.0 Knopp et al (21) I 6.22 4.42 1.28 1.11 5.98 4.14 1.29 1.14 3.9 6.3 0.8 2.7 I 6.43 4.61 1.27 1.19 5.76 3.96 1.28 1.16 10.4 14.1 0.8 2.5 I 6.42 4.57 1.27 1.17 5.96 4.13 1.23 1.31 7.2 9.6 3.2 12.0 (Continued)
640 YU-POTH ET AL TABLE 2 (Continued) Baseline lipids Endpoint lipids Percentage change Reference and group TC LDL-C HDL-C TG TC LDL-C HDL-C TG TC LDL-C HDL-C TG mmol/l mmol/l % I 6.55 4.68 1.35 1.09 5.96 4.03 1.29 1.40 9.0 13.9 4.4 28.4 I 6.89 4.69 1.14 2.03 6.51 4.33 1.12 2.32 5.5 7.7 1.8 14.3 I 6.68 4.58 1.09 2.06 6.38 4.41 1.11 1.92 4.5 3.7 1.8 6.8 I 6.72 4.50 1.11 2.18 6.38 4.24 1.14 2.14 5.1 5.8 2.7 1.8 Ehnholm et al (23) I 6.80 4.78 1.40 1.40 5.20 3.54 1.14 1.08 23.5 25.9 18.6 22.9 C 6.18 4.24 1.45 1.03 4.86 3.23 1.22 0.86 21.4 23.8 15.9 16.5 Boyd et al (24) I 4.83 ND ND ND 4.63 ND ND ND 4.1 ND ND ND C 4.88 ND ND ND 4.88 ND ND ND 0.00 ND ND ND Denke and Grundy (25) I ND ND ND ND 6.23 4.58 0.98 1.72 ND ND ND ND C ND ND ND ND 6.78 4.97 0.98 2.01 ND ND ND ND Geil et al (26) I 6.74 4.45 1.37 1.77 6.12 4.04 1.32 1.57 9.2 9.2 3.7 11.3 I 6.41 4.50 1.06 1.86 5.95 4.06 1.03 1.82 7.2 9.8 2.8 2.2 Dengel et al (27) I 5.41 3.42 1.11 1.91 4.56 2.98 0.93 1.45 15.7 12.9 16.2 24.1 I 5.39 3.57 1.04 1.68 4.56 3.03 0.83 1.53 15.4 15.1 20.2 8.9 I 5.41 3.42 1.11 1.91 4.33 2.72 1.06 1.18 20.0 20.5 4.5 38.2 I 5.39 3.57 1.04 1.68 4.82 3.19 0.88 1.64 10.6 10.6 15.4 2.4 Davidson et al (28) I 6.34 4.27 1.32 1.64 5.61 3.71 1.27 1.59 11.5 13.1 3.8 3.1 I 6.34 4.27 1.32 1.64 5.83 3.86 1.25 1.57 8.0 9.6 5.3 4.3 Bae et al (29) I 6.28 4.37 1.27 1.45 6.12 4.22 1.29 1.49 2.6 3.4 1.6 2.8 I 6.28 4.37 1.27 1.45 6.24 4.30 1.28 1.51 0.6 1.6 0.8 4.1 I 6.28 4.37 1.27 1.45 6.35 4.41 1.30 1.50 1.1 0.9 2.4 3.5 Step II intervention McCarron et al (14) I 5.69 3.54 1.14 2.18 5.38 3.31 1.11 2.08 5.5 6.5 2.6 4.6 Haskell et al (15) I 6.03 4.07 1.19 1.77 5.03 3.12 1.33 1.42 16.6 23.3 11.8 19.8 C 5.87 4.04 1.10 1.75 5.79 3.89 1.16 1.76 1.4 3.7 5.5 0.6 Kasim et al (22) I 5.21 3.20 1.56 1.15 4.87 2.79 1.44 1.35 6.5 12.8 7.7 17.4 C 5.29 3.42 1.47 1.02 5.21 3.09 1.56 1.25 1.5 9.7 6.1 22.6 Arntzenius et al (30) I 6.90 ND 1.01 ND 6.20 ND 0.98 ND 10.1 ND 3.0 ND Ornish et al (31) I 5.88 3.92 1.00 2.38 4.45 2.46 0.97 2.91 24.3 37.2 3.0 22.3 C 6.34 4.32 1.35 2.45 6.00 4.07 1.31 2.24 5.4 5.8 3.0 8.6 Barnard (32) I 5.99 3.90 1.03 2.51 4.53 2.92 0.91 1.56 24.4 25.1 11.7 37.9 I 6.15 3.97 1.39 1.90 4.87 3.15 1.12 1.14 20.8 20.7 19.4 40.0 Barnard et al (33) I 5.90 3.70 1.22 2.31 4.60 2.84 0.98 1.70 22.0 23.2 19.7 26.4 Seim and Holtmeier (34) I 6.05 3.54 1.47 ND 5.07 3.13 1.22 ND 16.2 11.6 17.0 ND Walden et al (35) I 6.36 4.41 1.49 1.13 5.93 4.04 1.38 1.10 6.8 8.4 7.4 2.7 I 6.60 4.48 1.29 1.99 6.23 4.07 1.22 2.02 5.6 9.2 5.4 1.5 I 6.31 4.54 1.19 1.27 5.84 4.09 1.17 1.27 7.5 9.9 1.7 0.0 I 6.60 4.55 1.07 2.10 6.14 4.16 1.04 2.04 7.0 8.6 2.8 2.9 1 I, intervention diet group; C, control group (consumed habitual diet); ND, no data; TC, total cholesterol; TG, triacylglycerol; LDL-C, LDL cholesterol; HDL-C, HDL cholesterol.
DIETARY INTERVENTION AND CVD RISK 641 FIGURE 4. Effects of exercise on plasma total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triacylglycerol (TG). * Significantly different from no exercise, P < 0.05. with the change in dietary total fat (Figure 6) as well as with the change in energy intake. The change in dietary fat was related to the change in energy intake. Regression analysis showed that the change in dietary fat had a significant effect on the change in body weight. BW = 0.28 TF (R 2 = 0.57, P < 0.0001) (4) The regression equation revealed that for every 1% decrease in energy as total fat, there was a 0.28-kg decrease in body weight. The effect of change in total fat on weight loss explained 57% of the total variance. Diet intervention with exercise resulted in significantly greater weight loss than diet intervention without exercise. Body weight decreased by 5.66 ± 0.77 kg in intervention groups with exercise and by 2.79 ± 0.31 kg in intervention groups without exercise (Figure 7). Furthermore, there was no significant difference in the change in dietary fat between intervention groups with and without exercise ( 11.6 ± 1.9% compared with 10.0 ± 0.7% of FIGURE 5. Correlation between changes ( ) in plasma total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triacylglycerol (TG) and their baseline values. r = Pearson correlation coefficient.
642 YU-POTH ET AL TABLE 3 Correlation between changes in dietary total fat (TF), saturated fatty acids (SFA), and cholesterol and changes in plasma lipids and lipoproteins 1 total energy, P > 0.05). Thus, the effect of change in dietary fat on body weight was independent of the effect of exercise. DISCUSSION Short-term controlled-feeding studies have shown that Step I and Step II diets typically decrease total cholesterol and LDL cholesterol by 7 9% and 10 20%, respectively (1). In addition, these diets decrease HDL-cholesterol and increase triacylglycerol concentrations (2, 4, 45, 46). Many intervention studies conducted in free-living populations have not observed these potentially adverse effects on HDL cholesterol and triacylglycerol (5, 8 11, 14, 20, 21). Results of the present meta-analysis of dietary interventions in free living populations (n = >9000) showed that consumption of Step I and Step II diets, respectively, significantly (P < 0.001) decreased plasma total cholesterol (by 10% and 13%), LDL cholesterol (by 12% and 16%), and triacylglycerol (by 8% and 8%). Plasma HDL-cholesterol concentrations did not decrease significantly (by 1.5%) after Step I dietary intervention studies but did decrease significantly (by 7%) after Step II dietary interventions; total cholesterol:hdl cholesterol decreased significantly after both Step I and Step II dietary interventions. Average plasma lipid and Intervention versus control group TF SFA Cholesterol r P r P r P Absolute change (mmol/l) TC 0.59 (0.89) <0.0001 0.71 (0.91) <0.0001 0.65 (0.89) <0.0001 LDL-C 0.61 (0.86) <0.0001 0.72 (0.89) <0.0001 0.56 (0.84) <0.001 HDL-C 0.46 (0.81) <0.001 0.55 (0.78) <0.001 0.47 (0.73) 0.002 TG 0.15 (0.88) 0.37 0.32 (0.89) 0.06 0.31 (0.86) 0.053 Percentage change (%) TC 0.57 (0.88) <0.0001 0.67 (0.90) <0.0001 0.65 (0.89) <0.0001 LDL-C 0.61 (0.87) <0.0001 0.69 (0.89) <0.0001 0.58 (0.84) <0.001 HDL-C 0.43 (0.85) 0.002 0.49 (0.82) 0.002 0.47 (0.78) 0.002 TG 0.07 (0.85) 0.69 0.26 (0.88) 0.14 0.43 (0.86) 0.009 1 r, Pearson correlation coefficient; TC, total cholesterol; LDL-C, LDL cholesterol; HDL-C, HDL cholesterol; TG, triacylglycerol. Values in parentheses are weighted by the number of subjects in each study; P < 0.0001 for all values. lipoprotein responses were comparable with those observed in controlled feeding studies. However, there was an appreciable range in the response to the dietary interventions with the maximal effect being more than twice the average response reported in controlled feeding studies with Step I dietary interventions (total cholesterol concentrations decreased by 23.5% compared with 9%). Moreover, the maximal response of total cholesterol ( 24.4%) to the Step II dietary intervention programs implemented was marked. The marked hypocholesterolemic response to Step I and Step II dietary interventions in some free-living subjects likely reflected the effects of diet, weight loss, and exercise. The attenuated cholesterol lowering response in individuals with pronounced hypercholesterolemia raises important questions about the biological basis of hypercholesterolemia as well as what the ideal interventions should be. Thus, overall, Step I and Step II dietary interventions have beneficial effects on plasma lipid profiles in free-living populations, especially in individuals who are not markedly hypercholesterolemic. These findings support current dietary guidelines and recommendations to exercise regularly to reduce the risk of CVD. Although the results of the present meta-analysis clearly indicate the benefits of a low-fat diet on CVD risk factors, especially those of Step I dietary interventions (because they did not decrease HDL TABLE 4 Bivariate regression analysis: plasma lipids and lipoproteins in response to changes ( ) in dietary total fat (TF), saturated fatty acids (SFA), or cholesterol, with the change in body weight (BW) as a covariable 1 Coefficient P Coefficient P Coefficient P TF, BW TF, BW R 2 SFA, BW TF, BW R 2 Cholesterol, BW Cholesterol, BW R 2 Absolute change (mmol/l) TC (0.060, NS) (0.0001, NS) 0.77 (0.107, NS) (0.0001, NS) 0.84 (0.049, NS) (0.0001, NS) 0.84 LDL-C (0.042, NS) (0.0001, NS) 0.57 (0.078, NS) (0.0001, NS) 0.84 (0.033, NS) (0.0001, NS) 0.78 HDL-C (0.010, 0.010) (0.0001, 0.001) 0.50 (0.018, 0.009) (0.0001, 0.005) 0.50 (0.008, 0.011) (0.0001, 0.001) 0.46 TG (0.012, 0.018) (0.04, 0.05) 0.49 (0.027, 0.019) (0.001, 0.001) 0.60 (0.013, 0.011) (0.004, 0.24) 0.46 Percentage change (%) TC (0.90, NS) (0.0001, NS) 0.77 (1.73, NS) (0.0001, NS) 0.82 (0.79, NS) (0.0001, NS) 0.84 LDL-C (1.04, NS) (0.0001, NS) 0.78 (1.89, NS) (0.0001, NS) 0.82 (0.85, NS) (0.0001, NS) 0.78 HDL-C (0.79, 0.83) (0.0001, 0.001) 0.46 (1.36, 0.78) (0.0001, 0.005) 0.43 (0.60, 0.96) (0.0001, 0.001) 0.44 TG (0.50, 1.14) (0.07, 0.008) 0.45 (1.32, 1.22) (0.001, 0.001) 0.66 (0.70, 0.75) (0.002, 0.08) 0.54 1 TF and SFA, change in percentage of energy per day from TF and SFA; BW, change in BW in kilograms; cholesterol, change in dietary cholesterol per day divided by 10; TC, total cholesterol; LDL-C, LDL cholesterol; HDL-C, HDL cholesterol; TG, triacylglycerol.
DIETARY INTERVENTION AND CVD RISK 643 FIGURE 6. Correlation between changes ( ) in body weight and changes in dietary total fat and energy intake and between changes in energy intake and dietary total fat. Pearson correlation coefficients (r) are significant for all correlations. FIGURE 7. Effects of diet and diet plus exercise interventions on weight loss. * Significantly different from diet alone, P < 0.0001. cholesterol ), there is compelling emerging data that a diet high in monounsaturated fatty acids but low in SFA and cholesterol may result in a more favorable lipid profile (ie, higher HDLcholesterol and lower triacylglycerol concentrations) (47). An alternative dietary intervention may be most appropriate for women because they had lower HDL-cholesterol and higher triacylglycerol concentrations than did men who were following a Step II diet. Because of this provocative evidence, there is a need to conduct intervention studies with diets high in monounsaturated fatty acids to evaluate their efficacy in free-living subjects and to establish which dietary intervention is superior for reducing CVD risk. Another beneficial effect of low-fat diets on CVD risk was that these diets often result in weight loss. Obesity, defined as a body weight 20% above ideal, is also a risk factor for CVD (3). Mild-to-moderate overweight has been associated with an increased risk of CVD (4). Decreases in body weight and body fat are associated with numerous favorable changes in CVD risk factors, including increased HDL-cholesterol concentrations; decreased total cholesterol, LDL-cholesterol, VLDLcholesterol, and triacylglycerol concentrations; and decreased factor VII and plasminogen activator inhibitor 1 concentrations (14, 48 51). In these studies, for every 1-kg decrease in body weight, plasma HDL-cholesterol concentrations increased by 0.007 0.009 mmol/l (48 51) and triacylglycerol concentrations decreased by 0.015 mmol/l (49). In agreement with earlier reports (49 51), results of the present meta-analysis showed that every 1-kg decrease in body weight resulted in a 0.011-mmol/L increase in HDL cholesterol (P < 0.001) and a 0.011-mmol/L decrease in plasma triacylglycerol. A metaanalysis conducted by Dattilo and Kris-Etherton (48) also showed that every 1-kg decrease in body weight was associated with a 0.05-mmol/L decrease in plasma total cholesterol and a 0.02-mmol/L decrease in LDL cholesterol. The present metaanalysis showed a significant correlation between weight loss and a decrease in total cholesterol and LDL cholesterol when analyses were weighted by the number of subjects in each study. Diet in combination with exercise can effectively reduce multiple risk factors for CVD (eg, high plasma LDL, VLDL, and triacylglycerol concentrations; low plasma HDL concentrations; high blood pressure; and excess body weight). Epidemiologic studies have shown that some populations who consume very-low-fat diets have a very low incidence of CVD; this may be because these populations have a very low incidence of overweight and obesity and a high level of physical
644 YU-POTH ET AL TABLE 5 Multiple regression analysis: plasma lipids and lipoproteins in response to changes in dietary total fat (TF), saturated fatty acids (SFA), and cholesterol with the change in body weight (BW) as a covariable 1 Variables Coefficient P R 2 Model 1 Absolute change (mmol/l) TC 0.86 TF 0.020 0.037 Cholesterol 0.036 0.0001 LDL-C 0.83 TF 0.023 0.003 Cholesterol 0.018 0.002 HDL-C 0.51 TF 0.006 0.02 Cholesterol 0.004 0.19 BW 0.011 0.0004 TG 0.46 TF 0.004 0.64 Cholesterol 0.016 0.037 BW 0.011 0.238 Percentage change (%) TC 0.86 TF 0.30 0.06 Cholesterol 0.60 0.0001 LDL-C 0.83 TF 0.59 0.003 Cholesterol 0.47 0.003 HDL-C 0.49 TF 0.41 0.11 Cholesterol 0.34 0.09 BW 0.97 0.0004 TG 0.56 TF 0.48 0.26 Cholesterol 0.94 0.07 BW 0.77 0.007 Model 2 Absolute change (mmol/l) TC 0.88 SFA 0.056 0.004 Cholesterol 0.026 0.003 LDL-C 0.86 SFA 0.050 0.002 Cholesterol 0.013 0.036 HDL-C 0.51 SFA 0.012 0.11 Cholesterol 0.003 0.32 BW 0.011 0.004 TG 0.64 SFA 0.002 0.87 Cholesterol 0.012 0.07 BW 0.012 0.101 Percentage change (%) TC 0.88 SFA 0.77 0.018 Cholesterol 0.48 0.001 LDL-C 0.85 SFA 1.07 0.007 Cholesterol 0.41 0.017 HDL-C 0.47 SFA 0.60 0.33 Cholesterol 0.38 0.002 BW 0.99 0.16 TG 0.70 SFA 0.02 0.998 Cholesterol 0.65 0.019 BW 0.87 0.046 1 TF and SFA, change in percentage of energy per day from TF and SFA; BW, change in BW in kilograms; cholesterol, change in dietary cholesterol per day divided by 10; LDL-C, LDL cholesterol; HDL-C, HDL cholesterol. activity (16, 17). In dietary intervention studies conducted in free-living populations, subjects are encouraged to adopt a healthy lifestyle that includes exercise. The present metaanalysis found that exercise had significant effects on plasma lipids and lipoproteins that were independent of the effects of diet. Both dietary modification and body weight loss had independent beneficial effects on plasma lipid profiles and the effects were additive. Diet in combination with exercise resulted in a further significant decrease in plasma total cholesterol, LDL cholesterol, and triacylglycerol compared with diet alone. Furthermore, exercise offset the adverse effects of low-fat diets on plasma HDL-cholesterol concentrations. The effects of exercise on plasma HDL-cholesterol concentrations may have been due to weight loss. Wood et al (7) showed that a Step I dietary intervention with exercise resulted in a greater decrease in body weight and less of a decrease (in females) or an increase (in males) in HDL-cholesterol than did the intervention with no exercise. An earlier meta-analysis (48) found that plasma HDL cholesterol significantly increased only when weight reduction was maintained. In the present meta-analysis, exercise resulted in significant weight loss additional to that of decreased dietary fat and energy intake alone, which prevented a decrease in HDL-cholesterol concentrations. Both intervention and within-population epidemiologic studies have shown that a high fat intake plays a role in weight gain (16, 17, 52, 53). A significant positive correlation between the change in body weight and the change in dietary fat was found in the present meta-analysis (r = 0.46, P < 0.001). A reduction in dietary fat results in weight loss (54, 55), likely because of a decrease in energy intake. Some studies have reported that a high fat intake is related to high energy consumption (54 57). Free-living subjects consuming high-fat diets tend to consume more energy than those consuming highcarbohydrate diets, which results in weight gain (54 58). The present meta-analysis showed that weight loss after dietary intervention was significantly correlated with the change in energy intake (r = 0.54, P < 0.001), which was related to the change in dietary fat (r = 0.47, P < 0.001). Thus, a decrease in dietary fat facilitates a reduction in energy intake, thereby promoting weight loss. In summary, an exhaustive survey of the literature of dietary interventions showed that a reduction in dietary fat and SFA has beneficial effects on CVD risk factors in free-living subjects. Plasma total cholesterol, LDL-cholesterol, and triacylglycerol concentrations and the ratio of total cholesterol to HDL cholesterol significantly decreased after both Step I (by 10%, 12%, 8%, and 10%, respectively) and Step II (by 13%, 16%, 8%, and 7%, respectively) dietary interventions. In many of these interventions, subjects lost weight (0.5 11 kg, x : 3.38 kg). Weight loss and exercise resulted in a decrease in plasma triacylglycerol and an increase in HDL-cholesterol concentrations. Both exercise and a reduction in dietary fat (related to a decrease in energy intake) increased weight loss (2.8 kg weight loss from exercise and 0.28 kg weight loss for every 1% decrease in energy from total fat, respectively) and the effects were additive. The results of this study provide a good benchmark of the extent to which Step I and Step II intervention programs can affect CVD risk status. In addition, it is clear that exercise as well as weight loss can markedly potentiate the effects of diet. Thus, effective intervention programs should target healthy lifestyle practices that include diet modification, exercise, and