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Exchanging Carbohydrate or Protein for Fat Improves Lipid-Related Cardiovascular Risk Profile in Overweight Men and Women When Consumed Ad Libitum
  1. Mario Kratz, PhD*†,
  2. David S. Weigle, MD,
  3. Patricia A. Breen, BSc, RN,
  4. Kaatje E. Meeuws, BSc,
  5. Verna R. Burden, MS, RD,
  6. Holly S. Callahan, MSc, RD§,
  7. Colleen C. Matthys, BSc, RD§,
  8. Jonathan Q. Purnell, MD
  1. From the *Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Cancer Prevention Program; †University of Washington, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, Seattle, WA; ‡Oregon Health & Science University, Center for the Study of Weight Regulation, Division of Endocrinology, Diabetes and Clinical Nutrition, Portland, OR; and §University of Washington General Clinical Research Center, Seattle, WA.
  1. Received December 14, 2009, and in revised form February 19, 2010.
  2. Accepted for publication February 20, 2010.
  3. Reprints: Mario Kratz, PhD, Fred Hutchinson Cancer Research Center, Public Health Sciences, Cancer Prevention Program, Mail Stop M4-B402, 1100 Fairview Ave N, Seattle, WA 98109. E-mail: mkratz{at}
  4. Supported by the Oregon Clinical and Translational Research Institute (grant UL1-RR024140), the University of Washington General Clinical Research Center (M01-RR-00037), and the University of Washington Clinical Nutrition Research Unit (DK35816), all funded by the National Institutes of Health (NIH). Additional funding came from NIH (grants DK-55460 [to D.S.W.], DK-02860 [to D.S.W.], and DK-02689 [to J.Q.P.]). M.K. was supported by a Dick & Julia McAbee Fellowship in Diabetes Research from the University of Washington Diabetes Endocrinology Research Center (NIH grant DK-17047).
  5. None of the authors has any conflict of interest to declare.
  6. M.K. was responsible for statistical analyses and interpretation of the data and for writing the first draft of the manuscript. D.S.W. and J.Q.P. designed the research, supervised the collection of the data, and were involved in analyzing and interpreting the data. J.Q.P. also had final responsibility for the final content. P.A.B. was the study coordinator for both studies and was involved in designing the experiments and the collection of the data. H.S.C., C.C.M., K.E.M., and V.R.B. were responsible for designing the experimental diets and for supervising the production, distribution, and weigh-backs of the diets. All authors read and approved the final manuscript.


Background The impact of low-fat diets on the plasma lipoprotein profile is incompletely understood.

Methods We conducted two 16-week dietary studies to compare the effects of a moderate-fat (mod-FAT) baseline diet with isocaloric and ad libitum low-fat diets rich in either carbohydrates (high-CHO, n = 16) or protein (high-PRO, n = 19) on plasma lipids, post-heparin lipase activities, cholesteryl ester transfer protein, and phospholipid transfer protein.

Results Switching from the mod-FAT to the isocaloric high-CHO diet lowered plasma high-density lipoprotein cholesterol concentrations (P < 0.001) and tended to increase triglyceride levels (P = 0.087). Cholesterol content in the larger, buoyant low-density lipoprotein (LDL) fractions decreased, whereas those of the very-low-density lipoprotein, intermediate-density lipoprotein, and smaller, denser LDL fractions tended to increase. These changes were largely reversed when subjects lost weight by consuming this high-CHO diet ad libitum. Switching from the mod-FAT diet to the isocaloric high-PRO diet did not increase cholesterol content in the small-dense LDL fraction and led to decreases in both LDL and high-density lipoprotein cholesterol in plasma (P < 0.001 for both).

Consumption of the high-protein ad libitum diet accompanied by weight loss did not change plasma lipids further, except for a shift of cholesterol from dense low-density lipoprotein fractions to more buoyant low-density lipoprotein fractions. Cholesteryl ester transfer protein concentrations decreased with high-cholesterol feeding, whereas cholesteryl ester transfer protein concentrations and hepatic lipase and phospholipid transfer protein activities all decreased during high-protein feeding.

Conclusions Both high-CHO and high-PRO diets improve plasma lipid-related risk of cardiovascular disease when consumed ad libitum.

Key Words
  • fat
  • carbohydrate
  • protein
  • lipoproteins
  • lipids
  • cardiovascular disease

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