Effects of fish oil on VLDL triglyceride kinetics in humans1

Dietary n-3 fatty acids (FAs) found in fish oils markedly lower plasma triglyceride (TG) and very low density lipoprotein (VLDL) levels in both normal and hypertriglyceridemic subjects. The present study examined the mechanism of this effect. Ten subjects with widely different plasma triglyceride levels (82 to 1002 mg/dl) were fed metabolically controlled diets containing 20% fat. The control diet contained a blend of cocoa butter and peanut oil (P/S = 0.8). The test diet contained fish oil (P/S = 1.1) and provided 10-17 g of n-3 FAs per day (depending on calorie intake). After 3 to 5 weeks of each diet, the kinetics of VLDL-TG were determined over a 48-h period after the injection of [3H]glycerol. The fish oil diet reduced the VLDLTG synthetic rate from 23 * 14.3 (mean * SD) to 12.6 f 7.5 mg/h per kg ideal weight (P<O.O05) and increased the fractional catabolic rate (FCR) for VLDL-TG from 0.23 * 0.12 to 0.38 * 0.16 h 1 (PC0.005). At the same time, there was a 66 % reduction of plasma triglyceride levels, resulting largely from a 78% decrease in VLDL-TG levels (398 * 317 to 87 + 77 mg/dl; PC0.005). There was a strong correlation (Y = 0.83; P<O.Ol) between the change in synthetic rates and pool sizes, but there was no correlation (r = 0.24; NS) between changes in FCRs and pool sizes. The VLDL cholesterol: triglyceride ratio increased during the n-3 diet suggesting that smaller VLDL particles were present. These particles would be expected to leave the VLDL fraction more rapidly than larger particles producing a higher FCR. m We conclude that the hypotriglyceridemic effect of fish oil appears to be caused primarily by an inhibition of very low density lipoprotein-triglyceride synthesis, but an additional, independent effect upon VLDL catabolsim cannot be ruled out.-Harris, W. S., W. E. Connor, D. R. Illingworth, D. W. Rothrock, and D. M. Foster. Effects of fish oil on VLDL triglyceride kinetics in humans. J Lipid Res. 1990. 31: 1549-1558. Supplementary key words fractional catabolic rate n-3 fatty acids in cultured cells (512) have supported the hypothesis that n-3 fatty acids inhibit the synthesis of triglyceride, thereby reducing the rate of secretion of VLDL triglyceride from the liver. The kinetics of VLDL triglyceride in humans given n-3 fatty acids have been reported in three earlier trials (13-15). However, these studies were limited by either the failure to give n-3 fatty acids during the actual kinetic studies, the lack of a control period, dietary inconsistencies among subjects, or by examining very small numbers of patients with rare types of secondary hyperlipidemia. The purpose of the current study was to examine the effects of dietary n-3 fatty acids on VLDL triglyceride kinetics in a relatively larger number of individuals who were given fish oil during the turnover study. Subjects with widely varying baseline triglyceride levels were purposely chosen in order to determine whether the mechanism(s) of triglyceride lowering by fish oil was influenced by the magnitude of the hypertriglyceridemia.