Vitamin E blocks the CETP-lowering effect of pravastatin and raises CETP concentration on its own (Coron Artery Dis 1998)

Original title: Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia

Coron Artery Dis · 1 January 1998 · 8

Napoli C, Leccese M, Palumbo G, de Nigris F, Chiariello P, Zuliani P, Somma P, Di Loreto M, De Matteis C, Cacciatore F, Abete P, Liguori A et al.

In a placebo-diet-controlled multicenter trial, 220 hypercholesterolemic patients were randomized to diet plus 20-40 mg pravastatin (n=52), diet plus alpha-tocopherol (n=60), or diet plus placebo (n=52), with plasma CETP and LCAT activity measured to test whether combining pravastatin with vitamin E has greater effects than pravastatin alone. Pravastatin significantly decreased plasma CETP activity (P < 0.05), but this effect was less evident when vitamin E was co-administered, and for the first time it was shown that vitamin E alone significantly increased CETP concentration (P < 0.05). No significant differences in LCAT activity were observed among the groups. The authors conclude that pravastatin reduces CETP activity but not LCAT activity, that vitamin E prevents the pravastatin-induced CETP decrease and independently raises CETP, and that this may reflect vitamin E preventing radical-induced damage to CETP.

Original abstract

Background: The enzyme lecithin-cholesterol acyl transferase (LCAT) esterifies free cholesterol on high-density lipoprotein (HDL) and the cholesteryl ester transfer protein (CETP) transfers cholesteryl ester to very-low-density lipoprotein (VLDL) and low-density lipoproteins (LDL). Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia. In contrast, LCAT activity appears to be unaffected by simvastatin. Antioxidants have also been proposed for the use of anti-atherosclerotic treatment, because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis.

Objective: To investigate, in hypercholesterolemic patients, whether a combination of pravastatin with the antioxidant, vitamin E, has greater effects on the activity of CETP and of LCAT than does pravastatin alone.

Methods: This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned randomly to groups to receive: diet and 20-40 mg pravastatin (n = 52), diet and alpha-tocopherol (n = 60), or diet associated with placebo (n = 52). Plasma LCAT activity was determined using excess exogenous substrate, containing [3H]cholesterol. Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2+. The exchange of cholesteryl esters between [14C]cholesteryl ester-labeled LDL and unlabeled HDL was measured during a 16-h incubation, while LCAT was inhibited.

Results: The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity (P < 0.05); this effect was less evident in the group cotreated with vitamin E. For the first time, it was shown that CETP concentrations increased significantly after vitamin E alone (P < 0.05). No significant differences in the plasma activity of LCAT were observed among the groups.

Conclusions: Pravastatin reduced CETP activity, but not that of LCAT. Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity. The mechanism responsible for these effects is unknown, but could involve the prevention of radical-induced damage to CETP by vitamin E.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.