Lipid-lowering drugs and essential omega-6 and omega-3 fatty acids in patients with coronary heart disease.
OBJECTIVE
There are only little data about the effects of lipid-lowering drugs (LLDs) on the metabolism of essential n-6 and n-3 fatty acids in patients with established coronary heart disease (CHD).


RESULTS
Male patients with CHD and high cholesterol levels (>6.2 mmol/L) were randomized (double-blind protocol) to receive either simvastatin 20mg (S) or fenofibrate 200mg daily (F) for 3 months. Dietary habits and plasma fatty acids were not different in the two groups at baseline. After treatment, there were significant changes in both the groups for the main n-6 fatty acids, with an increase in arachidonate (from 6.5+/-1.7% of total fatty acids to 7.5+/-2.1, p<0.001 in S and from 6.2+/-1.4 to 6.8+/-1.4, p<0.005 in F) and a decrease in linoleate (from 26.9+/-3.9 to 24.2+/-3.6, p<0.001, and from 27.8+/-3.4 to 26.1+/-4.2, p<0.05, in S and F, respectively). In addition, there was a decrease in two major n-3 fatty acids (alpha-linolenate and docosahexanoate, both p<0.05), but only in F.


CONCLUSIONS
For the first time in a double-blind randomized study in CHD patients, we report that LLDs significantly alter the metabolism of essential fatty acids that are critically important for the pathogenesis and prevention of CHD. Further studies are urgently needed to examine the effects of higher dosages of statins (as currently proposed to reduce more cholesterol) on these essential fatty acids in the clinical setting and the crucial questions of whether specific dietary intervention (combining low intake of n-6 fatty acids and high intake of n-3 fatty acids) may improve the effectiveness of these drugs.
de Lorgeril
Michel
M
Laboratoire Nutrition, Vieillissement et Maladies Cardiovasculaires (NVMCV), UFR de Médecine, Université Joseph Fourier, Grenoble, France. michel.delorgeril@ujf-grenoble.fr
Salen
Patricia
P
Guiraud
Annabelle
A
Zeghichi
Sabrina
S
Boucher
François
F
de Leiris
Joël
J
D000704:Analysis of Variance; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D038441:Diet, Mediterranean; D004311:Double-Blind Method; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D000960:Hypolipidemic Agents; D019821:Simvastatin; D011345:Fenofibrate