Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men. The Dietary Alternatives Study

R. H. Knopp, C. E. Walden, B. M. Retzlaff, B. S. McCann, A. A. Dowdy, J. J. Albers, G. O. Gey and M. N. Cooper
Northwest Lipid Research Clinic, Department of Medicine, University of Washington, Seattle 98104, USA. rhknopp@u.washington.edu

CONTEXT: The long-term effect of aggressively vs moderately fat-restricted diets has not been studied extensively in free-living subjects with different types of hyperlipidemia. OBJECTIVE: To compare the cholesterol-lowering effects of 4 levels of dietary fat intake restriction after 1 year. DESIGN: Randomized, parallel, comparison trial. SETTING: Male employees of a large industry. PARTICIPANTS: A total of 444 men had low-density lipoprotein cholesterol (LDL-C) levels above the 75th age-specific percentile. Subjects with triglyceride (TG) levels less than the 75th age-specific percentile were defined as hypercholesterolemic (HC) and those with TG levels at or above the 75th age-specific percentile were defined as combined hyperlipidemic (CHL). INTERVENTIONS: Hypercholesterolemic subjects were randomized to diets 1, 2, 3, and 4 taught to contain 30%, 26%, 22%, and 18% fat, and the CHL subjects were randomized to diets 1, 2, and 3. All 4 diets were taught to subjects and spouses or partners in 8 weekly 2-hour classes. MAIN OUTCOME MEASURES: Plasma lipoprotein levels after 1 year. RESULTS: Fat intake after 1 year declined from a mean of 34% to 36% of energy to 27%, 26%, 25%, and 22% in the 4 HC diet groups and 28%, 26%, and 25% in the 3 CHL diet groups. Mean+/-SD percent LDL-C reductions were 5.3%+/-16.2%, 13.4%+/-12.6%, 8.4%+/-11.2%, and 13.0%+/-15.7% in the HC diet groups and 7.0%+/-16.2%, 2.8%+/-15.8%, and 4.6%+/-13.5% in the CHL diet groups (P<.01 in all but 1 instance). Apoprotein B levels decreased 8.6%, 10.7%, 4.3%, and 5.3% in the HC groups and 14.6%, 11.4%, and 9.9% in the CHL groups (P<.05-.01 in each instance). Triglyceride levels increased significantly in subjects following HC diets 3 and 4, 21.7% and 38.7% (P<.05 and .01), but not in any CHL subjects. High-density lipoprotein cholesterol decreased 2.8% and 3.2% in subjects on HC diets 3 and 4, respectively (P<.05 in both cases). CONCLUSIONS: After 1 year, moderate restriction of dietary fat intake attains meaningful and sustained LDL-C reductions in HC subjects and apoprotein B reductions in both HC and CHL subjects. More extreme restriction of fat intake offers little further advantage in HC or CHL subjects and potentially undesirable effects in HC subjects.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Pleiotropic Effects of Statins: Benefit Beyond Cholesterol Reduction?: A Meta-Regression Analysis
Robinson et al.
J Am Coll Cardiol 2005;46:1855-1862.
ABSTRACT | FULL TEXT  

Cholesterol Feeding Increases C-Reactive Protein and Serum Amyloid A Levels in Lean Insulin-Sensitive Subjects
Tannock et al.
Circulation 2005;111:3058-3062.
ABSTRACT | FULL TEXT  

Pathophysiology of dyslipidaemia in the metabolic syndrome
Kolovou et al.
Postgrad. Med. J. 2005;81:358-366.
ABSTRACT | FULL TEXT  

Saturated fat prevents coronary artery disease? An American paradox
Knopp and Retzlaff
Am. J. Clin. Nutr. 2004;80:1102-1103.
FULL TEXT  

Management of Hypertriglyceridemia in Patients Receiving Interferon for Malignant Melanoma
Wong et al.
The Annals of Pharmacotherapy 2004;38:1655-1659.
ABSTRACT | FULL TEXT  

Dietary and antismoking advice and ischemic heart disease mortality in men with normal or high fasting triacylglycerol concentrations: a 23-y follow-up study
Ellingsen et al.
Am. J. Clin. Nutr. 2003;78:935-940.
ABSTRACT | FULL TEXT  

Cholesterol Absorption and the Metabolic Syndrome: A New Look at an Old Area
Berglund and Hyson
Arterioscler. Thromb. Vasc. Bio. 2003;23:1314-1316.
FULL TEXT  

Effects of Insulin Resistance and Obesity on Lipoproteins and Sensitivity to Egg Feeding
Knopp et al.
Arterioscler. Thromb. Vasc. Bio. 2003;23:1437-1443.
ABSTRACT | FULL TEXT  

Carbohydrate Intake Is Associated with Diet Quality and Risk Factors for Cardiovascular Disease in U.S. Adults: NHANES III
Yang et al.
J. Am. Coll. Nutr. 2003;22:71-79.
ABSTRACT | FULL TEXT  

Randomized Controlled Community-Based Nutrition and Exercise Intervention Improves Glycemia and Cardiovascular Risk Factors in Type 2 Diabetic Patients in Rural Costa Rica
Goldhaber-Fiebert et al.
Diabetes Care 2003;26:24-29.
ABSTRACT | FULL TEXT  

References
Circulation 2002;106:3373-3421.
FULL TEXT  

Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women
Liu et al.
Am. J. Clin. Nutr. 2002;75:492-498.
ABSTRACT | FULL TEXT  

Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects
Lichtenstein et al.
J. Lipid Res. 2002;43:264-273.
ABSTRACT | FULL TEXT  

Lipoproteins, nutrition, and heart disease
Schaefer
Am. J. Clin. Nutr. 2002;75:191-212.
ABSTRACT | FULL TEXT  

Evidence-Based Nutrition Principles and Recommendations for the Treatment and Prevention of Diabetes and Related Complications
Franz et al.
Diabetes Care 2002;25:148-198.
FULL TEXT  

Assessment of Questionnaire Validity for Measuring Total Fat Intake using Plasma Lipid Levels as Criteria
Willett et al.
Am J Epidemiol 2001;154:1107-1112.
ABSTRACT | FULL TEXT  

Dietary glycemic load assessed by food-frequency questionnaire in relation to plasma high-density-lipoprotein cholesterol and fasting plasma triacylglycerols in postmenopausal women
Liu et al.
Am. J. Clin. Nutr. 2001;73:560-566.
ABSTRACT | FULL TEXT  

Introduction: Low-Saturated Fat, High-Carbohydrate Diets: Effects on Triglyceride and LDL Synthesis, the LDL Receptor, and Cardiovascular Disease Risk
Knopp
Exp. Biol. Med. 2000;225:175-177.
FULL TEXT  

Will High-Carbohydrate/Low-Fat Diets Reduce the Risk of Coronary Heart Disease?
Willett
Exp. Biol. Med. 2000;225:187-190.
FULL TEXT  

One-Year Effects of Increasingly Fat-Restricted, Carbohydrate-Enriched Diets on Lipoprotein Levels in Free-Living Subjects
Knopp et al.
Exp. Biol. Med. 2000;225:191-199.
ABSTRACT | FULL TEXT  

Dietary Fat Intake and Endogenous Sex Steroid Hormone Levels in Postmenopausal Women
Holmes et al.
JCO 2000;18:3668-3676.
ABSTRACT | FULL TEXT  

Treatment of Dyslipidemia : Room for Improvement?
Crouse and Furberg
Arterioscler. Thromb. Vasc. Bio. 2000;20:2333-2335.
FULL TEXT  

Reply to R Sichieri
Bray and Popkin
Am. J. Clin. Nutr. 2000;72:204-205.
FULL TEXT  

A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women
Liu et al.
Am. J. Clin. Nutr. 2000;71:1455-1461.
ABSTRACT | FULL TEXT  

Differential Effect of National Cholesterol Education Program (NCEP) Step II Diet on HDL Cholesterol, Its Subfractions, and Apoprotein A-I Levels in Hypercholesterolemic Women and Men After 1 Year : The beFIT Study
Walden et al.
Arterioscler. Thromb. Vasc. Bio. 2000;20:1580-1587.
ABSTRACT | FULL TEXT  

The Lipid-Lowering Effect of Lean Meat Diets Falls Far Short of That of Vegetarian Diets
Barnard et al.
Arch Intern Med 2000;160:395-396.
FULL TEXT  

Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms1
Parks and Hellerstein
Am. J. Clin. Nutr. 2000;71:412-433.
ABSTRACT | FULL TEXT  

Dietary Fat Intake and Regulation of Energy Balance: Implications for Obesity
Hill et al.
J. Nutr. 2000;130:284-284.
ABSTRACT | FULL TEXT  

Dietary fat affects obesity rate
Bray and Popkin
Am. J. Clin. Nutr. 1999;70:572-573.
FULL TEXT  

Reply to GA Bray and BM Popkin
Willett
Am. J. Clin. Nutr. 1999;70:573-573.
FULL TEXT  

A Randomized Trial Comparing the Effect of Casein With That of Soy Protein Containing Varying Amounts of Isoflavones on Plasma Concentrations of Lipids and Lipoproteins
Crouse III et al.
Arch Intern Med 1999;159:2070-2076.
ABSTRACT | FULL TEXT  

Drug Treatment of Lipid Disorders
Knopp
NEJM 1999;341:498-511.
FULL TEXT  

Dietary fat and obesity
Purnell et al.
Am. J. Clin. Nutr. 1999;70:108-108.
FULL TEXT  

Reply to JQ Purnell, RH Knopp, and JD Brunzell
Willett
Am. J. Clin. Nutr. 1999;70:108a-109.
FULL TEXT  

Other Articles Noted
Evid. Based Nurs. 1998;1:100-104.
FULL TEXT  

Very Low Fat Diets
Lichtenstein and Van Horn
Circulation 1998;98:935-939.
FULL TEXT  

Effects of Diet and Exercise in Men and Postmenopausal Women with Low Levels of HDL Cholesterol and High Levels of LDL Cholesterol
Stefanick et al.
NEJM 1998;339:12-20.
ABSTRACT | FULL TEXT  

Serum Lipids After a Low-Fat Diet
Ornish and Knopp
JAMA 1998;279:1345-1346.
FULL TEXT  

Dietary Fat Intake and the Risk of Coronary Heart Disease in Women
Ockene et al.
NEJM 1998;338:917-919.
FULL TEXT  

Low-Fat Diets
Ornish et al.
NEJM 1998;338:127-129.
FULL TEXT  

Extremely-Low-Fat Diet Challenged
Journal Watch Cardiology 1997;1997:2-2.
FULL TEXT  

CASE FOR VERY LOW-FAT DIET WEAKENS
JWatch General 1997;1997:2-2.
FULL TEXT