Possible Interaction: Linoleic Acid and Simvastatin

“HepG2 cells also converted LA and alpha-LNA, but simvastatin increased significantly only the conversion of LA (9.5+/-1.9% versus 23.8+/-5.1%, p<0.02).”

“ Simvastatin …), linoleic acid (C18:2n-6) by 5.3% (P<0.001), and &agr;-linolenic acid by 6.8% (P<0.05), and increased proportions of &…) by 14.2% (P<0.001), and the sum of long-chain polyunsaturated fatty acids (C20-22) by 9.0% (P<0.001).”

“In THP-1 cells, simvastatin decreases, in a concentration-dependent manner, cholesterol synthesis and increases linoleic acid (LA) conversion to its long-chain derivatives, in particular to arachidonic acid, activating Δ6 and Δ5 fatty acid (FA) desaturases.”

“In fact, simvastatin decreased cholesterol synthesis and enhanced LA conversion (mainly Δ5 desaturation), whereas curcumin and nicardipin decreased Δ5 desaturation, with a limited effect on cholesterol synthesis.”

“ Simvastatin enhances the conversion of linoleic acid to their long chain polyunsaturated fatty acid derivatives, e.g. arachidonic acid, in addition to typically inhibiting the de novo cholesterol synthesis, in cultured cells.”

“The dose-response relationships for the above effects show that simvastatin , atorvastatin and fluvastatin affect linoleic acid conversion and the delta5 desaturase step more potently than the synthesis of cholesterol, simvastatin being the most effective in inhibiting sterol synthesis, whereas atorvastatin in stimulating the conversion of linoleic acid.”

“In the monocytic THP-1 cells, the …-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor simvastatin (5 microM) … of exogenous linoleic (18:2 n-6) and eicosapentaenoic (20:5 n-3) acids to their long-chain … (LC-PUFA) derivatives, and this effect is associated with changes in the desaturation steps.”