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Differential Metabolic Effects of Saturated Versus Polyunsaturated Fats in Ketogenic Diets

Department of Medicine (Divisions of Endocrinology and Metabolism and Pulmonary Medicine) (M.L.B.) and General Clinical Research Center (B.S.F., M.S.R., J.N.S., M.W.W., D.W.T., P.W.S.), College of Medicine, University of Florida, Gainesville, Florida 32610; and Department of Epidemiology (G.E.D.), Nutritional Sciences Program, University of Washington, Seattle, Washington 98103

Address all correspondence and requests for reprints to: Dr. Mark L. Brantly, P.O. Box 100255, Gainesville, FL 32610-0255. E-mail: warren{at}ufl.edu.

Ketogenic diets (KDs) are used for treatment of refractory epilepsy and metabolic disorders. The classic saturated fatty acid-enriched (SAT) KD has a fat:carbohydrate plus protein ratio of 4:1, in which the predominant fats are saturated. We hypothesized that a polyunsaturated fat-enriched (POLY) KD would induce a similar degree of ketosis with less detrimental effects on carbohydrate and lipid metabolism. Twenty healthy adults were randomized to two different weight-maintaining KDs for 5 d. Diets were 70% fat, 15% carbohydrate, and 15% protein. The fat contents were 60 or 15% saturated, 15 or 60% polyunsaturated, and 25% monounsaturated for SAT and POLY, respectively. Changes in serum ß-hydroxybutyrate, insulin sensitivity (S_I), and lipid profiles were measured. Mean circulating ß-hydroxybutyrate levels increased 8.4 mg/dl in the POLY group (P = 0.0004), compared with 3.1 mg/dl in the SAT group (P = 0.07). S_I increased significantly in the POLY group (P = 0.02), whereas total and low-density lipoprotein cholesterol increased significantly in the SAT group (both P = 0.002). These data demonstrate that a short-term POLY KD induces a greater level of ketosis and improves S_I, without adversely affecting total and low-density lipoprotein cholesterol, compared with a traditional SAT KD. Thus, a POLY KD may be superior to a classical SAT KD for chronic administration.

This study was supported by National Institutes of Health Grant M01-RR00082-41 to the GCRC.

B.S.F., M.S.R., J.N.S., and M.W.W. contributed equally to this work.

Abbreviations: BOHB, ß-Hydroxybutyrate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; POLY, polyunsaturated fat-enriched; SAT, saturated fatty acid-enriched; S_I, insulin sensitivity.

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